All in One Day Seminar, Clinical Evidence Based Practice of Chiropractic: Ethics & Law, Basic Science (Nutrition), & Advanced Chiropractic Adjustive Technique.
California Approval Numbers: CA-A-21-06-06138 Advanced Adjustive Technique CA-A-21-06-06136 Basic Science (Nutrition) CA-A-21-06-06139 Ethics & Law
Arizona Approval Number: AZCE15016 All In One Day, Clinical Evidence Based Practice of Chiropractic: Ethics, Nutrition and Advanced Chiropractic Adjustive Technique
Online Distance Learning Triad Seminars | Mark Cymerint, D.C. Nutrition
Inflammation a.Definition, literature review b.Natural inflammation reduction treatment options, including nutritional supplements and special dietary recommendations for an anti-inflammatory protocol.
Metabolic Questionnaire Causes of Inflammation[1]
■ Pathogens (germs) like bacteria, viruses ■ External injuries like scrapes or foreign objects ■ Effects of chemicals or radiation ■ Any “-itis.”
What is an inflammation?. Institute for Quality and Efficiency in Health Care (IQWiG). 2015. Available at: https://www.ncbi.nlm.nih.gov/pubmedhealth/ PMH0072482/. Accessed October 12, 2016. Body’s Response to Inflammation[1]
Signs & Symptoms: ■ Feeling sick, exhaustion, or fever – The immune defense is very active and needs a lot of energy ■ Changes in blood counts ■ Release of tissue hormones- causing narrowing of blood vessels in the tissues to expand allowing more blood to reach the injured tissue.
What is an inflammation?. Institute for Quality and Efficiency in Health Care (IQWiG). 2015. Available at: https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0072482/. Accessed October 12, 2016. Inflammation & Autoimmune Disease [1]
Autoimmune Disease = immune system attacks itself causing harmful inflammatory responses:
■ Rheumatoid arthritis - joints inflamed ■ Psoriasis ■ Inflammation of the bowel- Crohn’s disease or ulcerative colitis
What is an inflammation?. Institute for Quality and Efficiency in Health Care (IQWiG). 2015. Available at: https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0072482/. Accessed October 12, 2016. Inflammation
■ Underlying root cause of every disease! ■ Biggest problem in a chiropractic practice today! ■ NSAIDs = damage to kidneys & stomach problems. ■ Natural options: turmeric (curcumin), black pepper, ginger, bromelain, saffron – See Organiccs Absolutely Pure Supplements Turmeric that is Non GMO, Organic, Gluten Free, Kosher, & Vegan ■ Increase Omega 3s, antioxidant rich food, & add probiotics Sources
■ Maple C, McLaren M, Bancroft A, Ho M, Belch JJF. Dietary supplementation with omega 3 and omega 6 fatty acids reduces induced white blood cell aggregation in healthy volunteers. Prostaglandins, Leukotrienes and Essential Fatty Acids (PLEFA). 1998;58:365-368. ■ Calder PC. Omega-3 polyunsaturated fatty acids and inflammatory processes: nutrition or pharmacology? British Journal of Clinical Pharmacology. 2013;75:645-662. ■ Tilg H. Cruciferous vegetables: prototypic anti-inflammatory food components. Clinical Phytoscience. 2015;1:1-6. ■ Kocabas H, Kocabas V, Buyukbas S, Salli A, Ugurlu H. Relationship of Cellular Oxidant and Antioxidant Status with Disease Activity in Patients with Rheumatoid Arthritis. Turkish Journal of Rheumatology. 2010;25:141-146. ■ Al-Okbi SY. Nutraceuticals of anti-inflammatory activity as complementary therapy for rheumatoid arthritis. Toxicology and Industrial Health. 2014;30:738-749. ■ Disease-modifying potential of Cinnamon extract in inflammation and arthritis. Australian Journal of Herbal Medicine. 2014;26:36. Curcumin, Curcuminoids, & Turmeric Research Article Title: Curcumin Releasing Eggshell Derived Carbonated Apatite Nanocarriers for Combined Anti-Cancer, Anti-Inflammatory and Bone Regenerative Therapy.
Date & Journal: J Nanosci Nanotechnol. 2019 Nov 1
• Bone cancer or osteosarcoma is an aggressive cancer affecting the long bones and is treated by a combination of surgery and chemotherapy. Local drug delivery directly to the site of bone cancer and the use of plant-based drugs has been explored towards improving the efficacy and decreasing the toxicity of the anti-cancer drugs. Curcumin, derived from turmeric is highly effective against cancer cells and shows very low toxicity against normal cells. Bone repair is facilitated by use of bone substitutes such as bioceramics, amongst which the carbonated apatite (CA) nanocarriers closely mimic the natural bone mineral. In the current work, we have developed CA nanocarriers based local delivery of curcumin as an adjunct treatment for bone cancer. CA nanocarriers with 6 wt. % carbonate were prepared by wet chemical synthesis using synthetic derived (6SWCA) and eggshell derived (6EWCA) precursors along with hydroxyapatite (WHA) as a control. The X-ray diffraction (XRD) patterns showed the CAs to be phase pure with a mean crystallite size of 17 nm. The Fouriertransform infrared spectroscopy (FTIR) analysis of both CAs indicated the carbonate substitution as B-Type. The amount of carbonate substitution was observed to be around 6 wt.% using FTIR and CHNO elemental analyzer. The 6EWCA showed a greater loading (36%) and release (66%) of curcumin than 6SWCA and WHA nanocarriers. The bovine serum albumin (BSA) protein denaturation assay showed the curcumin loaded CAs to be highly anti-inflammatory while their anti- cancer activity was confirmed by the high cytotoxic activity against MG-63 human osteosarcoma cells. Conclusively, an eggshell derived apatite drug delivery system was found to be very suitable to cure osteosarcoma, prevent post-cancer inflammation and modulate bone repair and regeneration. Article Title: Curcumin: New Insights into an Ancient Ingredient against Cancer.
Date & Journal: Int J Mol Sci. 2019 Apr 12
• Cancer patients frequently use complementary medicine. Curcumin (CUR) and its derivates (from the extract of Curcuma longa L.) represent some of the most frequently used ones, having a long history in traditional Asian medicine. CUR was demonstrated, both in vitro and in vivo, to have significant anti-inflammatory effects, thus potentially counteracting cancer-promoting inflammation, which is a hallmark of cancer. CUR modulate a plethora of signaling pathways in cancer cells, comprising the NF-κB (nuclear factor k-light-chain-enhancer of activated B cells), the JAK/STAT (Janus-Kinase/Signal Transducers and Activators of Transcription), and the TGF-β (transforming growth factor-β) pathways. Furthermore, CUR confers properties of electron receptors, which destabilize radical oxygen species (ROS), explaining its antioxidant and anti-apopototic effects. Although CUR has a low bioavailability, its role in advanced cancer treatment and supportive care was addressed in numerous clinical trials. After promising results in phase I⁻II trials, multiple phase III trials in different indications are currently under way to test for direct anti-cancer effects. In addition, CUR exerts beneficial effects on cancer treatment-related neurotoxcity, cardiotoxicity, nephrotoxicity, hemato-toxicity, and others. More efficient galenic formulations are tested to optimze CUR's usability in cancer treatment. This review should provide a comprehensive overview of basic science, and pre-clinical and clinical data on CUR in the field of oncology. Article Title: The impact of curcumin and its modified formulations on Alzheimer's disease.
Date & Journal: J Cell Physiol. 2019 Mar 7
• Alzheimer's disease (AD) is a major health problem worldwide, with no effective treatment approach. Curcumin is the main ingredient of turmeric traditionally used in Asian medicine. Several experimental studies have indicated the protective effect of curcumin and its novel formulations in AD. Curcumin has antioxidant, anti-inflammatory and neurotrophic activities, proposing a strong potential to prevent neurodegenerative diseases. However, there are no sufficient clinical trials to confirm curcumin use in AD patients. Low bioavailability following oral administration of curcumin limits its usage in human. The present study was designed to gather the effects of curcumin and its modified formulations in human and experimental models of AD. Article Title: The Influence of Curcumin on the Downregulation of MYC, Insulin and IGF-1 Receptors: A possible Mechanism Underlying the Anti-Growth and Anti-Migration in Chemoresistant Colorectal Cancer Cells.
Date & Journal: Medicina (Kaunas). 2019 Apr 3
• Background and objectives: Mounting evidence shows that curcumin, a bioactive substance originating from turmeric root, has anticancer properties. Additionally, curcumin prevents the migration and metastasis of tumor cells. However, the molecular mechanism involved in the anti-metastatic action of curcumin is not clear. Most studies have suggested that migration inhibition is related to curcumin's anti- inflammatory properties. Curcumin possesses a regulatory effect on insulin and insulin-like growth factor-1 (IGF-1) receptors and signaling. Insulin signaling is one of the important pathways involved in tumor initiation and progression; therefore, we proposed that the anti-metastatic effect of curcumin may mediate the downregulation of insulin and insulin-like growth factor-1 receptors. Materials and Methods: Viable resistant cells resulting from treating SW480 cells with 5-fluorouracil (5-FU) were subjected to curcumin treatment to analyze the proliferation and migration capacity in comparison to the untreated counterparts. To test the proliferation and migration potential, MTT, colony formation, and wound healing assays were performed. Real-time polymerase chain reaction (RT-PCR) was performed to measure the mRNA expression of insulin-like growth factor-1R (IGF-1R), insulin receptor (IR), and avian myelocytomatosis virus oncogene cellular homolog (MYC). Results: Our findings showed that curcumin significantly decreased insulin and IGF-1 receptors in addition to MYC expression. Additionally, the downregulation of the insulin and insulin-like growth factor-1 receptors was correlated to a greater decrease in the proliferation and migration of chemoresistant colorectal cancer cells. Conclusions: These results suggest the possible therapeutic effectiveness of curcumin in adjuvant therapy in metastatic colorectal cancer. Article Title: Curcuma longa L. ameliorates asthma control in children and adolescents: A randomized, double-blind, controlled trial.
Date & Journal: J Ethnopharmacol. 2019 Apr 13
• ETHNOPHARMACOLOGICAL RELEVANCE: Roots of Curcuma longa L. are used as medicine for millennia. They possess several pharmacological properties, including anti-inflammatory action, and can be suitable for asthma treatment.
• AIM OF THE STUDY: We aimed to test the hypothesis that, in children and adolescents with persistent asthma, the administration of powdered roots of C. longa for 6 months, in addition to standard treatment, compared to placebo, will result in better disease control.
• PATIENTS AND METHODS: We conducted a randomized, double-blind, placebo-controlled, phase II clinical trial. Patients were randomly assigned to receive 30mg/kg/day of C. longa for 6 months, or placebo. Data were collected prospectively. All patients were categorized for asthma severity and control according to GINA-2016 and underwent pulmonary function tests.
• RESULTS:Overall, both groups experienced amelioration of their frequency of symptoms and interference with normal activity, but no differences were found between the two treatment groups. However, patients receiving C. longa experienced less frequent nighttime awakenings, less frequent use of short-acting β-adrenergic agonists, and better disease control after 3 and 6 months.
• CONCLUSION: The powdered roots of C. longa led to less frequent nighttime awakenings, less frequent use of short-acting β-adrenergic agonists, and better disease control after 3 and 6 months, when compared to placebo. Mem Inst Oswaldo Cruz. 2018 Jul 16;113(9):e180171. doi: 10.1590/0074-02760180171.
CURCUMIN EXERTS ANTI-INFLAMMATORY AND VASOPROTECTIVE EFFECTS THROUGH AMELIORATION OF NFAT- DEPENDENT ENDOTHELIN-1 PRODUCTION IN MICE WITH ACUTE CHAGAS CARDIOMYOPATHY
■METHODS: Inflammation of heart vessels from Cur-treated and untreated infected mice were analysed by histology, with benznidazole (Bz) as the reference compound. Parasitaemia was monitored by the direct method. Capillary permeability was visualised by Evans-blue assay. Myocardial ET-1, IL-6, and TNF-α mRNA expressions were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Microvascular endothelial HMEC-1 cells were infected in vitro with or without addition of Cur or Bz. Induction of the Ca2+/NFAT pathway was assessed by fluorometry, immunoblotting, and reporter assay. ■FINDINGS: Oral Cur therapy of recently infected mice reduced inflammatory cell infiltration of myocardial arteries without lowering parasite levels. Compared to that of the phosphate-buffered saline-receiving group, hearts from Cur-treated mice showed significantly decreased vessel inflammation scores (p < 0.001), vascular permeabilities (p < 0.001), and levels of IL-6/TNF-α (p < 0.01) and ET-1 (p < 0.05) mRNA. Moreover, Cur significantly (p < 0.05 for transcript; p < 0.01 for peptide) downregulated ET-1 secretion from infected HMEC-1 cells. Remarkably, Cur addition significantly (p < 0.05 at 27.0 μM) interfered with T. cruzi-dependent activation of the Ca2+/NFATc1 signalling pathway that promotes generation of inflammatory agents in HMEC-1 cells. ■CONCLUSIONS: Oral treatment with Cur dampens cardiovasculopathy in acute Chagas mice. Cur impairs the Ca2+/NFATc1-regulated release of ET-1 from T. cruzi-infected vascular endothelium. These findings identify new perspectives for exploring the potential of Cur-based interventions to ameliorate Chagas heart disease. Evid Based Complement Alternat Med. 2018 Jun 19;2018:9041309. doi: 10.1155/2018/9041309. eCollection 2018. SYSTEMIC ADMINISTRATION OF CURCUMIN AFFECT ANXIETY- RELATED BEHAVIORS IN A RAT MODEL OF POST TRAUMATIC STRESS DISORDER VIA ACTIVATION OF SEROTONERGIC SYSTEMS
■Posttraumatic stress disorder (PTSD) is a trauma-induced psychiatric disease characterized by impaired hyperarousal, fear extermination, depression, anxiety, and amnesic symptoms that may include the release of monoamines in the dread circuit. Curcumin (CUR), a major diarylheptanoid and polyphenolic component of Curcuma longa, reportedly possesses several pharmacological features, including antidiabetic, antiatherosclerotic, anticancer, and neuropsychiatric actions. But the anxiolytic-like effects of CUR and its mechanism of action in PTSD are unclear. The current research measured some anxiety-related behavioral responses to examine the effects of CUR on symptoms of anxiety in rats after single prolonged stress (SPS) exposure by reversing the serotonin (5-HT) dysfunction. Rats received CUR (20, 50, or 100 mg/kg, i.p., once daily) for 14 days after SPS exposure. Administration of CUR significantly increased the number of central zone crossings in the open field test and reduced grooming behavior in the elevated plus maze (EPM) test and increased the number of open-arm visits on the EPM test. CUR administration significantly reduced freezing response to contextual fear conditioning. CUR recovered neurochemical abnormalities and SPS-induced decreased 5-HT tissue levels in the hippocampus, amygdala, and striatum. These results suggested that CUR has anxiolytic-like effects on biochemical and behavioral symptoms associated with anxiety. Thus, CUR may be a useful agent to alleviate or treat psychiatric disorders similar to those observed in patients with PTSD. Phytother Res. 2018 Jun 19. doi: 10.1002/ptr.6125. CURCUMIN IN EPILEPSY
■Curcumin, a principal curcuminoidDISORDERS present in turmeric, has an antioxidant, anti-inflammatory and neuroprotective properties. Preclinical studies have indicated its beneficial effect for the treatment of epilepsy disorders. The molecule has an anti-seizure potential in preclinical studies, including chemical and electrical models of acute and chronic epilepsy. Curcumin also possesses an anti-epileptogenic activity as it reduces spontaneous recurrent seizures severity in a kainate model of temporal lobe epilepsy. The antioxidant and anti-inflammatory nature of curcumin might be responsible for its observed anti-seizure effects; nevertheless, the exact mechanism is not yet clear. The poor availability of curcumin to the brain limits its use in clinics. The application of nanoliposome and liposome technologies has been tested to enhance its brain availability and penetrability. Unfortunately, there are no randomized, double-blinded controlled clinical trials validating the use of curcumin in epilepsy. The present article analyzes different preclinical evidence illustrating the effect of curcumin in seizure models. The review encourages carrying out clinical trials in this important area of research. In conclusion, curcumin might be beneficial in patients with epilepsy disorders, if its bioavailability issues are resolved. J Med Food. 2018 Jun 29. doi: 10.1089/jmf.2017.0146 IS CURCUMIN A POSSIBILITY TO TREAT INFLAMMATORY BOWEL DISEASE?
■The inflammatory bowel diseases (IBDs) are mainly represented by Crohn's disease and Ulcerative colitis that are characterized by chronic and relapsing inflammatory processes of the gastrointestinal system. Curcuma longa L. is a plant with several medicinal properties, including anti-inflammatory effects, and curcumin is the most important compound derived from its rhizomes. As curcumin has remarkable anti-inflammatory actions, the aim of this work is to review the potential use of this compound in IBD patients. We consulted MEDLINE (PubMed/PMC), and the literature search was performed with the following combinations of terms "Inflammatory Bowel Diseases" and "Curcumin," "Crohn's Disease" and "Curcumin," "Ulcerative colitis" and "Curcumin." The inclusion criteria were articles that showed original studies with human models and the exclusion criteria were not full-text articles, articles not in English, poster presentations, letters, editorials, and articles not available. Curcumin interacts with receptors, growth and transcription factors, cytokines, enzymes, and genes leading to inhibitory effects on cyclooxygenase-1, tumor necrosis factor-α, interferon-γ, inducible nitric oxide synthase, transcriptional nuclear factor kappa B, and many other molecules associated with inflammatory processes. These molecules are critical factors in the positive regulation of inflammatory cytokines in inflammatory diseases, suggesting that curcumin may be considered as a new therapeutic agent for patients with IBD. Curcumin is a natural anti-inflammatory agent that represents an attractive, safe and inexpensive alternative for the treatment of IBD. Nevertheless, it is necessary to know the efficient and safe dose and consider its poor absorption. Arch Ital Urol Androl. 2018 Jun 30;90(2):107-111. doi: 10.4081/aiua.2018.2.107.
EFFECT ON PROSTATIC SPECIFIC ANTIGEN BY A SHORT TIME TREATMENT WITH A CURCUMA EXTRACT: A REAL LIFE EXPERIENCE AND IMPLICATIONS FOR PROSTATE BIOPSY.
■INTRODUCTION AND OBJECTIVES: PSA elevation is associated with prostate cancer and it is used in screening programs for its diagnosis. It is one of the most common indications for referral to an urologist. There's no consensus about what to do in PSA elevation management. Antibiotics, nutraceuticals or anti- inflammatories are commonly prescribed in daily practice. Our objective was to verify the effect on the PSA value of a short 30-day trial of a curcuma extract, than to discuss the implications in terms of reducing the number of prostate biopsies performed. ■RESULTS: Mean age of the patients was 64.56 ± 8.88 (range, 42- 81 years). Prostate volume was 48.34 ± 15,77 ml (range, 18-80 ml). At visit 1, PSA value was in mean 6,84 ± 3.79 ng/ml (range 2.93-21ng/ml). Consequently, mean PSA density value was 0.16 ± 0.16 (range 0.05-1.11). PSA free and PSA total ratio at baseline was 16.85 ± 3.9% (range 8-26%). At visit 2, the prostate volume did not change. Total PSA was 4.65 ± 2,67 ng/ml (range 1-16.82 ng/ml). PSA free and PSA total ratio (PSAF/T) after treatment was 19.68 ± 5.35 % (range 7.8-29%). The differences of total PSA and PSAF/T between visit 1 and visit 2 were < 0.0001 and p < 0.0036, respectively. We performed 26 TRUSbx. Prostate cancer was diagnosed in 6 cases, PIN HG in 2 cases and non neoplastic findings in the remnants 18 patients. ■CONCLUSIONS:Use of the Curcuma extract is able to lower the PSA value after a 30-day intake period. We are not able to state that the reduction of PSA after intake of this Curcuma extract may exclude a prostate cancer. We need further studies to evaluate that. Altern Med Rev. 2009 Jun;14(2):141-53. ANTI-INFLAMMATORY PROPERTIES OF CURCUMIN, A MAJOR CONSTITUENT OF CURCUMA LONGA: A REVIEW OF PRECLINICAL AND CLINICAL RESEARCH.
■ Curcuma longa (turmeric) has a long history of use in Ayurvedic medicine as a treatment for inflammatory conditions. Turmeric constituents include the three curcuminoids: curcumin (diferuloylmethane; the primary constituent and the one responsible for its vibrant yellow color), demethoxycurcumin, and bisdemethoxycurcumin, as well as volatile oils (tumerone, atlantone, and zingiberone), sugars, proteins, and resins. While numerous pharmacological activities, including antioxidant and antimicrobial properties, have been attributed to curcumin, this article focuses on curcumin's anti-inflammatory properties and its use for inflammatory conditions. Curcumin's effect on cancer (from an anti-inflammatory perspective) will also be discussed; however, an exhaustive review of its many anticancer mechanisms is outside the scope of this article. Research has shown curcumin to be a highly pleiotropic molecule capable of interacting with numerous molecular targets involved in inflammation. Based on early cell culture and animal research, clinical trials indicate curcumin may have potential as a therapeutic agent in diseases such as inflammatory bowel disease, pancreatitis, arthritis, and chronic anterior uveitis, as well as certain types of cancer. Because of curcumin's rapid plasma clearance and conjugation, its therapeutic usefulness has been somewhat limited, leading researchers to investigate the benefits of complexing curcumin with other substances to increase systemic bioavailability. Numerous in-progress clinical trials should provide an even deeper understanding of the mechanisms and therapeutic potential of curcumin. RESEARCH ON PIPERINE (BLACK PEPPER) Article Title: A systematic review on black pepper (Piper nigrum L.): from folk uses to pharmacological applications.
Date & Journal: Crit Rev Food Sci Nutr. 2019 Feb 11
• Considered as the "King of spices", black pepper (Piper nigrum L.) is a widely used spice which adds flavor of its own to dishes, and also enhances the taste of other ingredients. Piper nigrum has also been extensively explored for its biological properties and its bioactive phyto-compounds. There is, however, no updated compilation of these available data to provide a complete profile of the medicinal aspects of P. nigrum. This study endeavors to systematically review scientific data on the traditional uses, phytochemical composition, and pharmacological properties of P. nigrum. Information was obtained using a combination of keywords via recognized electronic databases (e.g., Science Direct and Google Scholar). Google search was also used. Books and online materials were also considered, and the literature search was restricted to the English language. The country with the highest number of traditional reports of P. nigrum for both human and veterinary medicine was India, mostly for menstrual and ear-nose-throat disorders in human and gastrointestinal disorders in livestock. The seeds and fruits were mostly used, and the preferred mode of preparation was in powdered form, pills or tablets, and paste. Piper nigrum and its bioactive compounds were also found to possess important pharmacological properties. Antimicrobial activity was recorded against a wide range of pathogens via inhibition of biofilm, bacterial efflux pumps, bacterial swarming, and swimming motilities. Studies also reported its antioxidant effects against a series of reactive oxygen and nitrogen species including the scavenging of superoxide anion, hydrogen peroxide, nitric oxide, DPPH, ABTS, and reducing effect against ferric and molybdenum (VI). Improvement of antioxidant enzymes in vivo has also been reported. Piper nigrum also exhibited anticancer effect against a number of cell lines from breast, colon, cervical, and prostate through different mechanisms including cytotoxicity, apoptosis, autophagy, and interference with signaling pathways. Its antidiabetic property has also been confirmed in vivo as well as hypolipidemic activity as evidenced by decrease in the level of cholesterol, triglycerides, and low-density lipoprotein and increase in high-density lipoprotein. Piper nigrum also has anti-inflammatory, analgesic, anticonvulsant, and neuroprotective effects. The major bioactive compound identified in P. nigrum is piperine although other compounds are also present including piperic acid, piperlonguminine, pellitorine, piperolein B, piperamide, piperettine, and (-)-kusunokinin, which also showed biological potency. Most pharmacological studies were conducted in vitro (n = 60) while only 21 in vivo and 1 clinical trial were performed. Hence, more in vivo experiments using a pharmacokinetic and pharmacokinetic approach would be beneficial. As a conclusive remark, P. nigrum should not only be regarded as "King of spices" but can also be considered as part of the kingdom of medicinal agents, comprising a panoply of bioactive compounds with potential nutraceutical and pharmaceutical applications. Article Title: Alkaloids from Piper nigrum Synergistically Enhanced the Effect of Paclitaxel against Paclitaxel-Resistant Cervical Cancer Cells through the Downregulation of Mcl-1.
Date & Journal: J Agric Food Chem. 2019 May 8
• In the current study, nine amide alkaloids, including two new dimeric amides and a new natural product, were identified from Piper nigrum. Among them, seven compounds sensitized paclitaxel-resistant cervical cancer cells HeLa/ PTX to paclitaxel. Piperine was a major component obtained from Piper nigrum, and its sensitization mechanism was investigated. Combination treatment enhanced cell apoptosis, which was mediated by downregulation of phospho-Akt and Mcl-1. Piperine (50 μM) combined with paclitaxel (200 nM) downregulated Mcl-1 protein expression with a decrease of 35.9 ± 9.5% ( P < 0.05). Moreover, overexpression of Mcl-1 attenuated the inhibitory effect of this combination. Furthermore, combination treatments of six dimeric amide alkaloids and paclitaxel all downregulated Mcl-1 protein expression with a decrease ranging from 23.5 ± 9.7% to 41.7 ± 7.2% ( P < 0.05). We reveal, for the first time, that dimeric amide alkaloids from plants possess a remarkable sensitization effect on cancer cells to paclitaxel. Crit Rev Food Sci Nutr. 2007;47(8):735-48. BLACK PEPPER AND ITS PUNGENT PRINCIPLE-PIPERINE: A REVIEW OF DIVERSE PHYSIOLOGICAL EFFECTS.
■ Black pepper (Piper nigrum) is one of the most widely used among spices. It is valued for its distinct biting quality attributed to the alkaloid, piperine. Black pepper is used not only in human dietaries but also for a variety of other purposes such as medicinal, as a preservative, and in perfumery. Many physiological effects of black pepper, its extracts, or its major active principle, piperine, have been reported in recent decades. Dietary piperine, by favorably stimulating the digestive enzymes of pancreas, enhances the digestive capacity and significantly reduces the gastrointestinal food transit time. Piperine has been demonstrated in in vitro studies to protect against oxidative damage by inhibiting or quenching free radicals and reactive oxygen species. Black pepper or piperine treatment has also been evidenced to lower lipid peroxidation in vivo and beneficially influence cellular thiol status, antioxidant molecules and antioxidant enzymes in a number of experimental situations of oxidative stress. The most far-reaching attribute of piperine has been its inhibitory influence on enzymatic drug biotransforming reactions in the liver. It strongly inhibits hepatic and intestinal aryl hydrocarbon hydroxylase and UDP-glucuronyl transferase. Piperine has been documented to enhance the bioavailability of a number of therapeutic drugs as well as phytochemicals by this very property. Piperine's bioavailability enhancing property is also partly attributed to increased absorption as a result of its effect on the ultrastructure of intestinal brush border. Although initially there were a few controversial reports regarding its safety as a food additive, such evidence has been questionable, and later studies have established the safety of black pepper or its active principle, piperine, in several animal studies. Piperine, while it is non-genotoxic, has in fact been found to possess anti-mutagenic and anti-tumor influences. Med Chem. 2018;14(3):269-280. doi: 10.2174/1573406413666170623083810. BIOLOGY-ORIENTED SYNTHESIS (BIOS) OF PIPERINE DERIVATIVES AND THEIR COMPARATIVE ANALGESIC AND ANTI-INFLAMMATORY ACTIVITIES.
■METHOD: Based on "biology-oriented synthesis approach", piperine alkaloid was isolated from Piper nigrum L. and some derivatives of piperine having azomethine, sulfamoyl, propanoyl, acetamoyl and heterocyclic oxadiazole were synthesized. The structures of synthetic derivatives were confirmed by using different spectroscopic techniques such as 1H-, 13C-NMR, EI-MS, and IR. Melting points were also determined for all compounds. Piperine and its all the synthetic derivatives were subjected to comparative in vivo evaluation of analgesic and antiinflammatory activities at the oral dose of 6 mg/kg/day. Analgesic activity was evaluated by tail immersion, hot plate and acetic acid writhing methods. While, antiinflammatory activity was evaluated by carrageenan-induced paw inflammation. In silico studies of all synthetic compounds was also conducted on COX-2 and adenosine kinase enzymes. ■RESULTS: A number of derivatives showed enhanced antiinflammatory and analgesic activities as compared to piperine and standard drug diclofenac. ■CONCLUSION:The newly identified molecules may serve as lead for the future research in connection of potent and safer antiinflammatory and analgesic drug candidate. RESEARCH ON GINGER Title: Ginger Extract Enhances Antioxidant Ability and Immunity of Layers
Abstract
This experiment was to investigate ginger extract on production performance, antioxidant ability and immunity of laying hens. A total of 600 Hy-Line brown laying hens aged at 25 wk old were randomly divided into 2 treatments, 4 replicates per treatment, 75 layers each replicate. The control group hens were fed a basal diet; the experimental group hens were fed basal diets with 0.1% ginger extract. The results were shown as follows: 1) ginger extract significantly enhanced laying rates (P < 0.05) and daily egg weight (P < 0.05), substantially reduced the ratio of feed to egg (P < 0.05) of the hens; 2) ginger extract did not change the activities of glutathione peroxidase (GSH-PX) and total antioxidant capacity (TAOC) but significantly improved plasma superoxide dismutase (SOD) activity (P < 0.05), reduced malondialdehyde (MDA) content (P < 0.05) of the birds; 3) ginger extract did not affect the contents of serum total protein (TP), albumin (ALB), globulin (GLB), but significantly increased lysozyme (LZM) activity (P < 0.05); 4) ginger extract also significantly reduced plasma prostaglandin E2 (PGE2) content (P < 0.05). This study shows that ginger extract not only can improve the birds' antioxidant capacity, enhance immune function, but also has a potential of reducing inflammatory response.
An S, Liu G, Guo X, An Y, Wang R. Ginger extract enhances antioxidant ability and immunity of layers. Anim Nutr. 2019;5(4):407‐409. doi:10.1016/j.aninu.2019.05.003 Article Title: Chemopreventive efficacy zingerone (4-[4-hydroxy-3-methylphenyl] butan-2-one) in experimental colon carcinogenesis in Wistar rats.
Date & Journal: Environ Toxicol. 2019 May
• Colorectal cancer is one of the most common cancers worldwide. Development of naturally occurring inexpensive and safe alternatives can be effective in suppressing colon related proliferations. Zingerone (4-[4- hydroxy-3-methylphenyl] butan-2-one), a polyphenolic alkanone of ginger, has massive pharmacological properties and thus can be used as promising candidate against various ailments. In the current study, we aimed at demonstrating the protective effect of zingerone against experimental colon carcinogenesis and elucidating its possible mechanism by studying inflammatory and Nrf-2 signaling cascade. Four groups of animals (I-IV) were made with six animals each. Group I (control) was given normal saline orally. Group II was given 1,2-dimethylhydrazine (DMH) at the dose rate of 20 mg/kg body weight. Group III and IV were treated with DMH at the dose rate of 20 mg/kg body weight and also received oral treatment of zingerone at a dose rate of 50 and 100 mg/kg body weight, respectively, for first 5 weeks and animals were euthanized after 16 weeks. Our results reveal that DMH treated rats exhibited elevated ROS and MDA levels, increased activity of cytochrome P450 2E1 and serum marker enzyme carcinoembreyonic antigen (CEA), increased no of aberrant crypts of foci (ACF), and elevated expression of inflammatory and proliferative proteins. Nrf-2 was downregulated by DMH treatment. Treatment with zingerone to DMH treated rats, resulted in alterations in the activity of the cytochrome P450 2E1 and CEA. In addition, immunostaining of NF-kB-p65, COX-2, iNOS, and PCNA, Ki-67 was suppressed by zingerone. Furthermore, zingerone administration also attenuated the level of IL-6 and TNF-α and it also helps in preserving mucous layer. Thus, zingerone could be considered as a good chemopreventive agent in experimental model of colon carcinogenesis. Further studies are required to study other pathways involved in colon carcinogenesis and their modulation buy zingerone. Article Title: Dietary Ingredients as an Alternative Approach for Mitigating Chronic Musculoskeletal Pain: Evidence-Based Recommendations for Practice and Research in the Military.
Date & Journal: Pain Med. 2019 Apr 15
• OBJECTIVE: Approximately 55-76% of Service members use dietary supplements for various reasons, including pain and related outcomes. This work evaluates current research on dietary ingredients for chronic musculoskeletal pain to inform decisions for practice and self-care, specifically for Special Operations Forces personnel. • METHODS: A steering committee convened to develop research questions and factors required for decision- making. Key databases were searched through August 2016. Eligible systematic reviews and randomized controlled trials were assessed for methodological quality. Meta-analysis was applied where feasible. GRADE was used to determine confidence in the effect estimates. The committee made evidence-informed judgments and recommendations for practice and self-care use. • RESULTS: Nineteen eligible dietary ingredients were assessed for quality, efficacy, and safety. Avocado soybean unsaponifiables, capsaicin, curcuma, ginger (as a food source), glucosamine, melatonin, polyunsaturated fatty acids, and vitamin D were conditionally recommended as their benefits outweighed risks, but there was still some uncertainty about the trade-offs. No recommendations were made for boswellia, ginger (as a dietary supplement), rose hip, or s-adenosyl-L-methionine. Recommendations were made against the use of collagen, creatine, devil's claw, l-carnitine, methylsulfonylmethane, pycnogenol, willow bark extract, and vitamin E. Research priorities were developed to address gaps precluding stronger recommendations. • CONCLUSIONS: Currently the scientific evidence is insufficiently robust to establish definitive clinical practice guidelines, but processes could be established to track the impact of these ingredients. Until then, providers have the evidence needed to make informed decisions about the safe use of these dietary ingredients, and future research can address existing gaps. Heliyon. 2016 May 24;2(5):e00115. doi: 10.1016/j.heliyon.2016.e00115. eCollection 2016 May.
BLACK GINGER EXTRACT INCREASES PHYSICAL FITNESS PERFORMANCE AND MUSCULAR ENDURANCE BY IMPROVING INFLAMMATION AND ENERGY METABOLISM.
■ We previously reported that polymethoxyflavones (PMFs) in black ginger (Kaempferia parviflora) extract (KPE) increased energy production by activating AMP-activated protein kinase (AMPK) in C2C12 myoblasts. We herein evaluated the effects of KPE on physical fitness performance and muscular endurance in mice. Male mice were orally administered KPE for 4 weeks, and then forced swimming test, open-field test, inclined plane test, and wire hanging test were performed. KPE significantly increased the swimming time, motility after swimming, and grip strength. IL-6 and TNF-α mRNA expression levels were decreased in the soleus muscle, whereas peroxisome proliferator-activated receptor γ coactivator (PGC)-1α and glycogen synthase mRNA expression levels, mitochondrial number, and glycogen content were increased. These results were in agreement with those obtained for KPE and PMFs in C2C12. Therefore, the activation of AMPK by PMFs may be one of the mechanisms by which KPE improves physical fitness performance and muscular endurance. Biomed Pharmacother. 2018 Jun 29;106:381-389. doi: 10.1016/j.biopha.2018.06.148.
GINGER ALLEVIATES HYPERGLYCEMIA-INDUCED OXIDATIVE STRESS, INFLAMMATION AND APOPTOSIS AND PROTECTS RATS AGAINST DIABETIC NEPHROPATHY
■Oxidative stress plays a major role in the development and progression of diabetic nephropathy (DN). In this study, the potential protective effect of ginger (Zingiber officinale) rhizome extract on hyperglycemia-induced oxidative stress, inflammation and apoptosis was investigated. An experimental diabetic rat model was induced by intraperitoneal injection of streptozotocin. Diabetic rats were treated orally with 400 or 800 mg/kg/day Z. officinale extract for six weeks. Diabetic animals exhibited elevated blood glucose levels and glycated hemoglobin (HbA1c) with altered lipid profile. Blood urea nitrogen, serum creatinine and urea, and urine albumin levels were significantly increased in diabetic rats. Treatment with Z. officinale ameliorated hyperglycemia, hyperlipidemia and kidney function. In addition, Z. officinale minimized the histological alterations in the kidney of diabetic rats. Chronic hyperglycemia resulted in a significant increase in malondialdehyde, protein carbonyl, pro- inflammatory cytokines, cytochrome c and caspase-3 in the kidney of rats. Z. officinale extract significantly attenuated oxidative stress, inflammation and apoptosis, and enhanced antioxidant defenses in the diabetic kidney. In conclusion, this study strongly suggests that Z. officinale rhizome extract exerts a protective role against diabetes-induced renal injury by ameliorating oxidative stress, inflammation and apoptosis. Med J Islam Repub Iran. 2015 Sep 12;29:261. eCollection 2015.
ACUTE EFFECTS OF GINGER EXTRACT ON BIOCHEMICAL AND FUNCTIONAL SYMPTOMS OF DELAYED ONSET MUSCLE SORENESS.
■ BACKGROUND: Inflammation and pain induced by delayed onset muscle soreness (DOMS) as a result of eccentric exercise (EE) or unaccustomed activity cause some difficulties in exercise for athletes. The purpose of this study was to survey the effect of ginger extract on biochemical and functional symptom of delayed onset muscle soreness.
■ METHODS: In a quasi-experimental study, 36 healthy female subjects, who were recruited by intra dormitory calls, randomly divided into 3 groups, including: ginger intake 1 hour before exercise (GIBE), ginger intake immediately after exercise (GIAE) and placebo group (PL). Subjects consumed capsules contain 60 mg of ginger extract (equivalent of 2 g dried ginger powder) or placebo before and after exercise. The exercise protocol consisted of a 20 minute step test using a 46cm step at a rate of 15 steps per minute. The blood samples were taken before, 1, 24 and 48 hour after exercise to assay creatine kinase (CK) and interleukin-6 (IL-6). Muscle pain scores, isometric strength and circumference of thigh muscle, and hip range of motion were recorded at mentioned times. The analysis of variance (ANOVA) with repeated measure was used to determine the differences between groups.
■ RESULTS: The results showed a significant reduction of pain in GIBE compared to GIAE after 24 and 48h of EE and GIAE compared to PL (p<0.05). IL-6 changed significantly in GIBE compared to PL (p<0.05) after 1, 24, and 48h after EE. The other factors didn't change meaningfully.
■ CONCLUSION: The finding of this study suggests that 2 grams of ginger may have anti-inflammation and analgesic effect on DOMS Phytother Res. 2015 Jun;29(6):887-93. doi: 10.1002/ptr.5328. Epub 2015 Mar 18. THE EFFECTS OF PRE-EXERCISE GINGER SUPPLEMENTATION ON MUSCLE DAMAGE AND DELAYED ONSET MUSCLE SORENESS.
■ Ginger possesses analgesic and pharmacological properties mimicking non-steroidal antiinflammatory drugs. We aimed to determine if ginger supplementation is efficacious for attenuating muscle damage and delayed onset muscle soreness (DOMS) following high-intensity resistance exercise. Following a 5-day supplementation period of placebo or 4 g ginger (randomized groups), 20 non-weight trained participants performed a high-intensity elbow flexor eccentric exercise protocol to induce muscle damage. Markers associated with muscle damage and DOMS were repeatedly measured before supplementation and for 4 days following the exercise protocol. Repeated measures analysis of variance revealed one repetition maximum lift decreased significantly 24 h post-exercise in both groups (p < 0.005), improved 48 h post-exercise only in the ginger group (p = 0.002), and improved at 72 (p = 0.021) and 96 h (p = 0.044) only in the placebo group. Blood creatine kinase significantly increased for both groups (p = 0.015) but continued to increase only in the ginger group 72 (p = 0.006) and 96 h (p = 0.027) post-exercise. Visual analog scale of pain was significantly elevated following eccentric exercise (p < 0.001) and was not influenced by ginger. In conclusion, 4 g of ginger supplementation may be used to accelerate recovery of muscle strength following intense exercise but does not influence indicators of muscle damage or DOMS. SAFFRON, BROMELAIN, & EDTA RESEARCH Article Title: Bromelain inhibits the ability of colorectal cancer cells to proliferate via activation of ROS production and autophagy.
Date & Journal: PLoS One. 2019 Jan 18
• Advanced colorectal cancer (CRC) survival rates are still low despite advances in cytotoxic and targeted therapies. The development of new effective or alternative therapies is therefore urgently needed. Bromelain, an extract of pineapple, was shown to have anticancer effects, but its mechanisms in CRC have not been fully explored. Therefore, the roles of bromelain in CRC progression were investigated using different CRC cell lines, a zebrafish model, and a xenograft mouse model. The anticancer mechanisms were explored by assessing the role of bromelain in inducing reactive oxygen species (ROS), superoxide, autophagosomes, and lysosomes. The role of bromelain in the induction of apoptosis was also assessed. It was found that bromelain inhibited CRC cell growth in cell lines and tumor growth in the zebrafish and xenograft mouse models. It also induced high levels of ROS and superoxide, plus autophagosome and lysosome formation. High levels of apoptosis were also induced, which were associated with elevated amounts of apoptotic proteins like apoptotic induction factor, Endo G, and caspases-3, -8, and -9 according to a qPCR analysis. In a Western blot analysis, increases in levels of ATG5/12, beclin, p62, and LC3 conversion rates were found after bromelain treatment. Levels of cleaved caspase-3, caspase-8, caspase-9, and poly(ADP ribose) polymerase (PARP)-1 increased after bromelain exposure. This study explored the role of bromelain in CRC while giving insights into its mechanisms of action. This compound can offer a cheap alternative to current therapies. Bratisl Lek Listy. 2016;117(7):381-7. SAFFRON (ITS ACTIVE CONSTITUENT, CROCIN) SUPPLEMENTATION ATTENUATES LIPID PEROXIDATION AND PROTECTS AGAINST TISSUE INJURY.
■ The aim of the current study was to investigate the outcomes in a rat model of an acute swimming exercise induced oxidative stress in brain, kidney, liver, skeletal and cardiac muscles using supplementation with crocin. Rats were divided into the eight groups; Normal Control (NC: Untreated and did not swim), Crocin Control (CC: Received crocin and did not swim), Exercise-1 (E-1: Untreated and swam), Exercise-24 (E-24: Untreated and swam), Exercise-48 (E-48: Untreated and swam), Exercise+Crocin-1 (EC-1: Received crocin and swam), Exercise +Crocin-24 (EC-24: Received crocin and swam), Exercise+Crocin-48 (EC-48: Received crocin and swam). The malondialdehyde (MDA) and xanthine oxidase (XO) enzymes levels increased after swimming in untreated and crocin treated groups, but there was a lower increase in crocin treated groups. The highest MDA levels in all tissues were observed in E-1 compared to all other groups. There were significant differences between control and exercise groups in MDA levels of tissues (p < 0.001). In contrast, there were significant differences between control and exercise groups in glutathione (GSH) levels of tissues.In addition, the crocin supplementation significantly increased GSH levels and decreased MDA and XO enzyme levels when compared to untreated exercise groups. Crocin can protect the tissues against exercise induced oxidative stress by enhancing antioxidant activity (Tab. 3, Fig. 1, Ref. 37). J Physiol Biochem. 2016 Dec;72(4):711-719. Epub 2016 Aug 10. SAFFRON (CROCUS SATIVUS) PRETREATMENT CONFERS CARDIOPROTECTION AGAINST ISCHEMIA-REPERFUSION INJURIES IN ISOLATED RABBIT HEART.
■ Restoration of blood flow to the ischemic myocardium is imperative to avoid demise of cardiomyocytes, but is paradoxically associated with irreversible damage to cardiac tissues due to the excessive generation of reactive oxygen species (ROS). We have previously reported that saffron, a natural antioxidant, attenuated ischemia- reperfusion (IR) injuries in vitro; however, its role in a meaningful cardiac recovery remains unknown. Here, we show that saffron supplement (oral administration for 6 weeks) reduced myocardial damage and restored cardiac function in an IR model of rabbit hearts. This was evidenced by improved left ventricle pressure, heart rate and coronary flow, and left ventricle end diastolic pressure (LVEDP) in IR hearts (isolated from rabbits pre- exposed to saffron (S/IR)). Electrophysiological recordings revealed a significant decline in both premature ventricle contraction and ventricle tachycardia/fibrillation in S/IR compared to IR hearts. This was paralleled by increased expression of the contractile proteins α-actinin and Troponin C in the myocardium of S/IR hearts. Histological examination combined to biochemical analysis indicated that hearts pre-exposed to saffron exhibited reduced infarct size, lower lipid peroxidation, with increased glutathione peroxidase activity, and oxidation of nitro blue tetrazolium (by reactive oxygen species). Furthermore, in contrast with IR hearts, saffron pretreatment induced restoration of the phosphorylation level of the survival proteins Akt and 4EBP1 and reduced activity of p38. Collectively, our data demonstrate that the natural antioxidant saffron plays a pivotal role in halting IR-associated cardiac injuries and emerges as a novel preventive tool for ischemic heart disease. Biomed Rep. 2016 Sep;5(3):283-288. Epub 2016 Jul 18.
POTENTIAL ROLE OF BROMELAIN IN CLINICAL AND THERAPEUTIC APPLICATIONS.
■ Pineapple has been used as part of traditional folk medicine since ancient times and it continues to be present in various herbal preparations. Bromelain is a complex mixture of protease extracted from the fruit or stem of the pineapple plant. Although the complete molecular mechanism of action of bromelain has not been completely identified, bromelain gained universal acceptability as a phytotherapeutic agent due to its history of safe use and lack of side effects. Bromelain is widely administered for its well-recognized properties, such as its anti-inflammatory, antithrombotic and fibrinolytic affects, anticancer activity and immunomodulatory effects, in addition to being a wound healing and circulatory improvement agent. The current review describes the promising clinical applications and therapeutic properties of bromelain. Adv Colloid Interface Sci. 2018 Apr;254:48-55. doi: 10.1016/j.cis.2018.03.006. Epub 2018 Mar 27.
BROMELAIN-LOADED NANOPARTICLES: A COMPREHENSIVE REVIEW OF THE STATE OF THE ART ■ Stem bromelain is a common available cysteine protease derived from pineapple (Ananas comosus L.). Bromelain finds widespread applications in several areas, such as medicine, health, food, and cosmetics, and its strong proteolytic activity supports its future application in many additional fields. However, most proteins and/or enzymes are fragile, leading to important considerations about increase storage and operational stability to enable their practical application. In this scenario, the use of nanoparticles to deliver proteins is increasing exponentially, given that these systems are capable of enhance active's stability, solubility and permeability, and decrease toxicity. In the pharmaceutical nanotechnology field, bromelain has played different roles and thus this paper aims to review the available literature for the use of nanoparticles and bromelain. Biotechnol Prog. 2016 Jan-Feb;32(1):5-13. doi: 10.1002/btpr.2190. Epub 2015 Nov 17. ANTICANCER PROPERTY OF BROMELAIN WITH THERAPEUTIC POTENTIAL IN MALIGNANT PERITONEAL MESOTHELIOMA
■Bromelain is a mixture of proteolytic enzymes that is capable of hydrolyzing glycosidic linkages in glycoprotein. Glycoprotein's are ubiquitously distributed throughout the body and serve a variety of physiologic functions. Faulty glycosylation of proteins may lead to cancer. Antitumor properties of bromelain have been demonstrated in both, in vitro and in vivo studies, along with scanty anecdotal human studies. Various mechanistic pathways have been proposed to explain the anticancer properties of bromelain. However, proteolysis by bromelain has been suggested as a main pathway by some researchers. MUC1 is a glycoprotein that provides tumor cells with invasive, metastatic, and chemo-resistant properties. To date, there is no study that examines the effect of bromelain on MUC1. However, the viability of MUC1 expressing pancreatic and breast cancer cells are adversely affected by bromelain. Further, the efficacy of cisplatin and 5-FU are enhanced by adjuvant treatment with bromelain, indicating that the barrier function of MUC1 may be affected. Other studies have also indicated that there is a greater accumulation of 5-FU in the cell compartment on treatment with 5-FU and bromelain. Malignant peritoneal mesothelioma (MPM) expresses MUC1 and initial studies have shown that the viability of MPM cells is adversely affected by exposure to bromelain. Further, bromelain in combination with either 5-FU or cisplatin, the efficacy of the chemotherapeutic drug is enhanced. Hence, current evidence indicates that bromelain may have the potential of being developed into an effective anticancer agent for MPM. References
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Dietary Recommendations ■ Adhere to an anti-inflammatory diet – Eliminate triggers - Dairy, gluten, etc. – Avoid Nightshade vegetables- eggplant, peppers, tomatoes – Increase omega 3’s – Limit red meat intake, increase lean meat – Balanced Meals – Minimize Pro inflammatory oils- ex.) corn oil, safflower, sunflower, soybean oil, & cottonseed oil. – Eat smaller more frequent meals throughout the day Nutrition
A.Digestion a. Green Alkaline foods for fiber and digestion b.Minerals and Collagen Protein c.Colon Health Title: A Randomized Clinical Trial of the Effects of Leafy Green Vegetables and Inorganic Nitrate on Blood Pressure Background: A diet rich in fruits and vegetables is associated with lowering of blood pressure (BP), but the nutrient(s) responsible for these effects remain unclear. Research suggests that inorganic nitrate present in leafy green vegetables is converted into NO in vivo to improve cardiovascular function.
Results: A total of 231 subjects (95%) completed the study. The insignificant change in ambulatory SBP (mean ± standard deviation) was -0.6 ± 6.2 mm Hg in the placebo group, -1.2 ± 6.8 mm Hg in the potassium nitrate group, and -0.5 ± 6.6 mm Hg in the leafy green vegetable group. There was no significant difference in change between the 3 groups.
Conclusions: A 5-wk dietary supplementation with leafy green vegetables or pills containing the same amount of inorganic nitrate does not decrease ambulatory SBP in subjects with elevated BP. This trial was registered at clinicaltrials.gov as NCT02916615.
Sundqvist ML, Larsen FJ, Carlström M, et al. A randomized clinical trial of the effects of leafy green vegetables and inorganic nitrate on blood pressure. Am J Clin Nutr. 2020;111(4):749‐756. doi:10.1093/ajcn/nqaa024 Title: Application of HPLC and ESI-MS Techniques in the Analysis of Phenolic Acids and Flavonoids From Green Leafy Vegetables (GLVs)
Abstract
Diets containing high proportions of fruits and vegetables reduce the risk of onset of chronic diseases. The role of herbal medicines in improving human health is gaining popularity over the years, which also increases the need for safety and efficiency of these products. Green leafy vegetables (GLVs) are the richest source of phenolic compounds with excellent antioxidant properties. Increased consumption of diets containing phenolic compounds may give positive and better results to human health and significantly improves the immune system. Highly selective, susceptible and versatile analytical techniques are necessary for extraction, identification, and quantification of phenolic compounds from plant extracts, which helps to utilize their important biological properties. Recent advances in the pre-treatment procedures, separation techniques and spectrometry methods are used for qualitative and quantitative analysis of phenolic compounds. The online coupling of liquid chromatography with mass spectrometry (LC-MS) has become a useful tool in the metabolic profiling of plant samples. In this review, the separation and identification of phenolic acids and flavonoids from GLVs by LC-MS have been discussed along with the general extraction procedures and other sources of mass spectrometer used. The review is devoted to the understanding of the structural configuration, nature and accumulation pattern of phenolic acids and flavonoids in plants and to highlighting the recent developments in the chemical investigation of these compounds by chromatographic and spectroscopic techniques. It concludes with the advantages of the combination of these two methods and prospects.
Kumar BR. Application of HPLC and ESI-MS techniques in the analysis of phenolic acids and flavonoids from green leafy vegetables (GLVs). J Pharm Anal. 2017;7(6):349‐364. doi:10.1016/j.jpha.2017.06.005 Title: Effects of Dietary Nitrate on Inflammation and Immune Function, and Implications for Cardiovascular Health Abstract
Inorganic dietary nitrate, found abundantly in green leafy and some root vegetables, elicits several beneficial physiological effects, including a reduction in blood pressure and improvements in blood flow through nitrate-nitrite-nitric oxide signaling. Recent animal and human studies have shown that dietary nitrate and nitrite also modulate inflammatory processes and immune cell function and phenotypes. Chronic low-grade inflammation and immune dysfunction play a critical role in cardiovascular disease. This review outlines the current evidence on the efficacy of nitrate-rich plant foods and other sources of dietary nitrate and nitrite to counteract inflammation and promote homeostasis of the immune and vascular systems. The data from these studies suggest that immune cells and immune-vasculature interactions are important targets for dietary interventions aimed at improving, preserving, or restoring cardiovascular health. Raubenheimer K, Bondonno C, Blekkenhorst L, Wagner KH, Peake JM, Neubauer O. Effects of dietary nitrate on inflammation and immune function, and implications for cardiovascular health [published online ahead of print, 2019 May 30]. Nutr Rev. 2019;nuz025. doi:10.1093/nutrit/nuz025 Title: Bioactivity Evaluations of Leaf Extract Fractions From Young Barley Grass and Correlation With Their Phytochemical Profiles Abstract
Background: The pressed juice of Barley Grass (BG) has become very popular among people for various assumed benefits along with many testimonies of people who have been healed from various ailments such as anemia, cancer, GI problems by consuming BG. The aim of our research was to validate the claims of its medicinal values such as chemo-protective action, high anti-oxidants, RBC membrane stabilization activity, and toxicity level.
Conclusion: The study reveals the strong antioxidant and RBC membrane stabilization activity of BG. The Brine Shrimp Lethality Assay found extracts to be bioactive suggesting extracts as a promising candidate for plant-derived anti-tumor compounds. Further, studies are needed to validate the data on cancer cell lines. Panthi M, Subba RK, Raut B, Khanal DP, Koirala N. Bioactivity evaluations of leaf extract fractions from young barley grass and correlation with their phytochemical profiles. BMC Complement Med Ther. 2020;20(1):64. Published 2020 Feb 28. doi:10.1186/s12906-020-2862-4 Title: Extraction of Polysaccharides From Maca: Characterization and Immunoregulatory Effects on CD4 + T Cells
Abstract
The immunomodulatory effects of maca polysaccharides (MCPs) on macrophages have been demonstrated in many studies. However, the effects of MCPs on CD4+ T cells have not been studied. Four water-soluble MCPs, labeled MCP1 (weight-average molecular weights [Mws] of 896.1 and 276.6 kDa), MCP2 (Mws of 337.8 and 219.0 kDa), MCP3 (Mws of 110.6, 58.1, and 38.9 kDa), and MCP4 (Mws of 15.7, 12.6, and 12.1 kDa), were obtained from maca by graded ethanol precipitation. The immunoregulatory effects of MCPs on CD4+ T cells were evaluated for the first time. The experimental results indicated that all MCPs had immunoregulatory effects on CD4+ T cells. However, the effects of MCP2 were stronger compared to the other three components, not only in promoting the proliferation of CD4+ T cells but also in terms of secretion of interferon-γ (IFN- γ). The molecular weight and monosaccharide compositions of MCPs were analyzed to explore the structure-activity relationship. The results suggested that the molecular weight and the galactosamine (GalN) of MCPs might be determining factors for its bioactivity. These findings suggest that the MCP2 isolated in our study have immune potentiation effects on CD4+ T cells.
Chang Y, Lu W, Chu Y, et al. Extraction of polysaccharides from maca: Characterization and immunoregulatory effects on CD4+ T cells. Int J Biol Macromol. 2020;154:477‐485. doi:10.1016/j.ijbiomac.2020.03.098 Title: Nopal (Opuntia Spp.) and Its Effects on Metabolic Syndrome: New Insights for the Use of a Millenary Plant
Abstract
Background: Nopal (Opuntia spp.) is by excellence the most utilized cactus in human and animal nutrition. It is also a very noble plant; its main physicochemical, nutritional and nutraceutical characteristics allow the use of nopal in diverse food applications. Special focus has been given over the past decades in the use of Opuntia for the treatment of metabolic syndrome (MetS), which is predominantly related to Diabetes Mellitus. In this sense, the prevalence of MetS is increasing at a worldwide level. This in turn has led to a notorious demand for natural and nutraceutical food sources.
Conclusion: Nopal constitutes one of the most studied members of the Cactaceae family; its potential effects on human health have been described since ancient times, mostly through traditional medicine. The present work highlights the importance of this plant in the treatment of MetS related maladies and points out the importance of elucidating new compounds and their validation for the interactions of nutraceutical compounds which could be related to MetS. Angulo-Bejarano PI, Gómez-García MDR, Valverde ME, Paredes-López O. Nopal (Opuntia spp.) and its Effects on Metabolic Syndrome: New Insights for the Use of a Millenary Plant. Curr Pharm Des. 2019;25(32):3457‐3477. doi: 10.2174/1381612825666191010171819 Title: Antioxidant, Immunomodulating, and Microbial-Modulating Activities of the Sustainable and Ecofriendly Spirulina
Abstract
The highly nutritional and ecofriendly Spirulina (Arthrospira platensis) has hypolipidemic, hypoglycemic, and antihypertensive properties. Spirulina contains functional compounds, such as phenolics, phycocyanins, and polysaccharides, with antioxidant, anti-inflammatory, and immunostimulating effects. Studies conducted on Spirulina suggest that it is safe in healthy subjects, but attitude to eating probably affects the acceptability of Spirulina containing foods. Although the antioxidant effect of Spirulina is confirmed by the intervention studies, the concerted modulation of antioxidant and inflammatory responses, suggested by in vitro and animal studies, requires more confirmation in humans. Spirulina supplements seem to affect more effectively the innate immunity, promoting the activity of natural killer cells. The effects on cytokines and on lymphocytes' proliferation depend on age, gender, and body weight differences. In this context, ageing and obesity are both associated with chronic low grade inflammation, immune impairment, and intestinal dysbiosis. Microbial- modulating activities have been reported in vitro, suggesting that the association of Spirulina and probiotics could represent a new strategy to improve the growth of beneficial intestinal microbiota. Although Spirulina might represent a functional food with potential beneficial effects on human health, the human interventions used only supplements. Therefore, the effect of food containing Spirulina should be evaluated in the future. Finamore A, Palmery M, Bensehaila S, Peluso I. Antioxidant, Immunomodulating, and Microbial-Modulating Activities of the Sustainable and Ecofriendly Spirulina. Oxid Med Cell Longev. 2017;2017:3247528. doi:10.1155/2017/3247528 Title: Functional Properties of Spinach (Spinacia Oleracea L.) Phytochemicals and Bioactives
Abstract
Overwhelming evidence indicates that diets rich in fruits and vegetables are protective against common chronic diseases, such as cancer, obesity and cardiovascular disease. Leafy green vegetables, in particular, are recognized as having substantial health-promoting activities that are attributed to the functional properties of their nutrients and non-essential chemical compounds. Spinach (Spinacia oleracea L.) is widely regarded as a functional food due to its diverse nutritional composition, which includes vitamins and minerals, and to its phytochemicals and bioactives that promote health beyond basic nutrition. Spinach- derived phytochemicals and bioactives are able to (i) scavenge reactive oxygen species and prevent macromolecular oxidative damage, (ii) modulate expression and activity of genes involved in metabolism, proliferation, inflammation, and antioxidant defence, and (iii) curb food intake by inducing secretion of satiety hormones. These biological activities contribute to the anti-cancer, anti-obesity, hypoglycemic, and hypolipidemic properties of spinach. Despite these valuable attributes, spinach consumption remains low in comparison to other leafy green vegetables. This review examines the functional properties of spinach in cell culture, animals and humans with a focus on the molecular mechanisms by which spinach-derived non- essential phytochemicals and bioactives, such as glycolipids and thylakoids, impart their health benefits. Roberts JL, Moreau R. Functional properties of spinach (Spinacia oleracea L.) phytochemicals and bioactives. Food Funct. 2016;7(8):3337‐3353. doi:10.1039/c6fo00051g Title: The Gut Microbiota at the Intersection of Diet and Human Health Abstract
Diet affects multiple facets of human health and is inextricably linked to chronic metabolic conditions such as obesity, type 2 diabetes, and cardiovascular disease. Dietary nutrients are essential not only for human health but also for the health and survival of the trillions of microbes that reside within the human intestines. Diet is a key component of the relationship between humans and their microbial residents; gut microbes use ingested nutrients for fundamental biological processes, and the metabolic outputs of those processes may have important impacts on human physiology. Studies in humans and animal models are beginning to unravel the underpinnings of this relationship, and increasing evidence suggests that it may underlie some of the broader effects of diet on human health and disease. Gentile CL, Weir TL. The gut microbiota at the intersection of diet and human health. Science. 2018;362(6416):776‐780. doi:10.1126/science.aau5812 Title: Targeting the Gut Microbiota by Dietary Nutrients: A New Avenue for Human Health
Abstract
The gut microbiota is a complex ecosystem consisted of trillions of microbes that have co-evolved with their host for hundreds of millions of years. During the last decade, a growing body of knowledge has suggested that there is a compelling set of connections among diet, gut microbiota and human health. Various physiological functions of the host, ranging from metabolic and immune regulation to nerve and endocrine development, are possibly mediated by the structural components of microbial cell or the products of microbial metabolism, which are greatly influenced by dietary macronutrients and micronutrients. Thus, governing the production and activity of these microbial-associated small molecules and metabolites through dietary intervention may provide promising strategies for the improvement of human health and disease. In this review article, we first provide an overview of current findings about the intimate interrelationships between diet and gut microbiota. We also introduce the physiological effects of some microbial-associated small molecules and metabolites on the host as well as the detailed signaling mechanisms.
Li D, Wang P, Wang P, Hu X, Chen F. Targeting the gut microbiota by dietary nutrients: A new avenue for human health. Crit Rev Food Sci Nutr. 2019;59(2):181‐195. doi:10.1080/10408398.2017.1363708 Title: The Food-gut Human Axis: The Effects of Diet on Gut Microbiota and Metabolome
Abstract
Gut microbiota, the largest symbiont community hosted in human organism, is emerging as a pivotal player in the relationship between dietary habits and health. Oral and, especially, intestinal microbes metabolize dietary components, affecting human health by producing harmful or beneficial metabolites, which are involved in the incidence and progression of several intestinal related and non-related diseases. Habitual diet (Western, Agrarian and Mediterranean omnivore diets, vegetarian, vegan and gluten-free diets) drives the composition of the gut microbiota and metabolome. Within the dietary components, polymers (mainly fibers, proteins, fat and polyphenols) that are not hydrolyzed by human enzymes seem to be the main leads of the metabolic pathways of gut microbiota, which in turn directly influence the human metabolome. Specific relationships between diet and microbes, microbes and metabolites, microbes and immune functions and microbes and/or their metabolites and some human diseases are being established. Dietary treatments with fibers are the most effective to benefit the metabolome profile, by improving the synthesis of short chain fatty acids and decreasing the level of molecules, such as p-cresyl sulfate, indoxyl sulfate and trimethylamine N-oxide, involved in disease state. Based on the axis diet-microbiota-health, this review aims at describing the most recent knowledge oriented towards a profitable use of diet to provide benefits to human health, both directly and indirectly, through the activity of gut microbiota. De Angelis M, Garruti G, Minervini F, Bonfrate L, Portincasa P, Gobbetti M. The Food-gut Human Axis: The Effects of Diet on Gut Microbiota and Metabolome. Curr Med Chem. 2019;26(19):3567‐3583. doi: 10.2174/0929867324666170428103848 Title: Impact of a Probiotic Product on Bowel Habits and Microbial Profile in Participants With Functional Constipation: A Randomized Controlled Trial
Abstract
Objective: To investigate the clinical efficacy of a multi-strain probiotic product on bowel habits and microbial profile in participants with functional constipation.
Results: There were no significant between-group differences in the PAC-SYM score, despite significant within-group differences (P < 0.001) over the study period. The probiotic group showed a faster normalization of stool frequency and consistency, with most participants achieving a normalized profile after 1 week. Fecal samples of the probiotic group exhibited higher relative abundance of Ruminococcaceae (P = 0.0047), including the Ruminococcus genus, and lower relative abundance of Erysipelotrichaceae (P = 0.0172) at end-point compared with baseline. Placebo group samples showed similar abundance profiles over the study, with the exception of Clostridiaceae, which was lower at the study end-point (P = 0.0033). Among treated participants, all four probiotic strains were significantly more abundant after the intervention.
Conclusions: No significant differences were observed in symptomology, with both groups showing a more than 20% improvement. However, the probiotic helped modulate bowel function earlier than the placebo, with a corresponding shift to a more fibrolytic microbiota.
Martoni CJ, Evans M, Chow CT, Chan LS, Leyer G. Impact of a probiotic product on bowel habits and microbial profile in participants with functional constipation: A randomized controlled trial. J Dig Dis. 2019;20(9):435‐446. doi: 10.1111/1751-2980.12797 Title: The Chemical Composition and Nutritional Value of Chia Seeds-Current State of Knowledge Abstract
Chia (Salvia hispanica) is an annual herbaceous plant, the seeds of which were consumed already thousands of years ago. Current research results indicate a high nutritive value for chia seeds and confirm their extensive health-promoting properties. Research indicates that components of chia seeds are ascribed a beneficial effect on the improvement of the blood lipid profile, through their hypotensive, hypoglycaemic, antimicrobial and immunostimulatory effects. This article provides a review of the most important information concerning the potential application of chia seeds in food production. The chemical composition of chia seeds is presented and the effect of their consumption on human health is discussed. Technological properties of chia seeds are shown and current legal regulations concerning their potential use in the food industry are presented. Kulczyński B, Kobus-Cisowska J, Taczanowski M, Kmiecik D, Gramza-Michałowska A. The Chemical Composition and Nutritional Value of Chia Seeds-Current State of Knowledge. Nutrients. 2019;11(6):1242. Published 2019 May 31. doi: 10.3390/nu11061242 Title: Chia Seeds (Salvia Hispanica): Health Promoting Properties and Therapeutic Applications – A Review Abstract
Chia has been known for over 5,500 years. Chia seeds were one of the most important components of the diet of Mayas and Aztecs. The chemical composition and technological properties of chia give the plant a high nutritional potential. Chia is a good source of polyunsaturated fatty acids: omega-3 and omega-6, soluble dietary fiber. It also contains appreciable amount of proteins and phytochemicals. Nutritional value of chia is the reason why it is used in prophylaxis of several non-infectious diseases such as obesity, hypertension, cardiovascular diseases (CVDs), cancer and diabetes. Nutritional and therapeutic aspects of chia are currently being researched by many scientific centres. The aim of this article is to present the nutritional and therapeutic values of chia. Marcinek K, Krejpcio Z. Chia seeds (Salvia hispanica): health promoting properties and therapeutic applications – a review. Rocz Panstw Zakl Hig. 2017;68(2):123‐129. Title: Flaxseed Bioactive Compounds and Colorectal Cancer Prevention
Abstract
Purpose of review: Flaxseed and its bioactive components have been associated with a decreased risk of colorectal cancer incidence and progression. This review aims to summarize recent research regarding the role of flaxseed and each of its major dietary bioactive components in reducing colorectal cancer.
Recent findings: In both human and animal model experiments, flaxseed consumption had beneficial effects on colon physiology associated with reduction in colorectal cancer risk or occurrence. Considered separately, each of flaxseed's major bioactive components, including fiber, alpha-linolenic acid, lignans, and other phytochemicals, is also associated with decreased risk of colonic neoplasms and regulation of cell growth through several potential mechanisms. Collectively, experimental data suggests that consumption of flaxseed and/or its bioactive components may reduce colorectal cancer risk by a variety of mechanisms. Future studies should focus on the mechanisms by which whole flaxseed can prevent colorectal cancer.. DeLuca JAA, Garcia-Villatoro EL, Allred CD. Flaxseed Bioactive Compounds and Colorectal Cancer Prevention. Curr Oncol Rep. 2018;20(8):59. Published 2018 Jun 5. doi:10.1007/s11912-018-0704-z Title: Chia Seeds: An Ancient Grain Trending in Modern Human Diets
Abstract
Currently, in order to ensure adequate intake of nutrients to complement the normal diet, the consumption of seeds such as Salvia hispanica L. (commonly known as chia seeds) is increasing. For this reason, investigations concerning the composition and potential health effects of chia seeds are being carried out. Moreover, the recent approval of chia seeds as a Novel Food by the European Parliament allows its consumption and incorporation in a wide range of foods; thus, they have become widely available. Concerning their nutritional aspects, chia seeds are an excellent source of fat (20% to 34%), particularly polyunsaturated fatty acids such as α-linolenic (60%) and linoleic (20%) acids. Moreover, high levels of protein (16% to 26%), mainly prolamins, and dietary fibre contents (23% to 41%) have been reported. Vitamins (mostly B complex) and minerals (calcium, phosphorus, and potassium, among others) have also been described in appreciable amounts. Additionally, due to the absence of gluten, these seeds are appropriate for coeliac patients. Regarding other bioactive compounds, chia seeds are also a source of antioxidants, such as chlorogenic and caffeic acids, quercetin and kaempferol. Due to their described composition, chia seeds have been related to different medicinal effects, particularly anti-inflammatory and antidiabetic activities and positive effects on cardiovascular disease and hypertension. The aim of this paper is to perform a systematic review of chia seeds to provide an update of the knowledge about their morphology, nutritional and chemical composition, possible human health benefits and role as a functional food.
Melo D , Machado TB , Oliveira MBPP . Chia seeds: an ancient grain trending in modern human diets. Food Funct. 2019;10(6):3068‐3089. doi:10.1039/c9fo00239a Title: Effects of Oat Bran on Nutrient Digestibility, Intestinal Microbiota, and Inflammatory Responses in the Hindgut of Growing Pigs Abstract
Oat bran has drawn great attention within human research for its potential role in improving gut health. However, research regarding the impact of oat bran on nutrient utilization and intestinal functions in pigs is limited. The purpose of this study was to investigate the effects of oat bran on nutrient digestibility, intestinal microbiota, and inflammatory responses in the hindgut of growing pigs. Twenty-six growing pigs were fed either a basal diet (CON) or a basal diet supplemented with 10% oat bran (OB) within a 28 day feeding trial. Results showed that digestibility of dietary gross energy, dry matter, organic matter, and crude protein were lower in the OB group compared to the CON group on day 14, but no differences were observed between the two groups on day 28. In the colon, the relative abundance of operational taxonomic units (OTUs) associated with Prevotella, Butyricicoccus, and Catenibacterium were higher, while those associated with Coprococcus and Desulfovibrio were lower in the OB group compared to the CON group. Oat bran decreased mRNA expression of caecal interleukin-8 (IL-8), as well as colonic IL-8, nuclear factor-κB (NF-κB), and tumor necrosis factor-α (TNF-α) of the pigs. In summary, oat bran treatment for 28 day did not affect dietary nutrient digestibility, but promoted the growth of cellulolytic bacteria and ameliorated inflammatory reactions in the hindgut of growing pigs. He B, Bai Y, Jiang L, et al. Effects of Oat Bran on Nutrient Digestibility, Intestinal Microbiota, and Inflammatory Responses in the Hindgut of Growing Pigs. Int J Mol Sci. 2018;19(8):2407. Published 2018 Aug 15. doi:10.3390/ijms19082407 Title: Oat Bran, but Not Its Isolated Bioactive β-Glucans or Polyphenols, Have a Bifidogenic Effect in an in Vitro Fermentation Model of the Gut Microbiota
Abstract
Wholegrain oats are known to modulate the human gut microbiota and have prebiotic properties (increase the growth of some health-promoting bacterial genera within the colon). Research to date mainly attributes these effects to the fibre content; however, oat is also a rich dietary source of polyphenols, which may contribute to the positive modulation of gut microbiota. In vitro anaerobic batch-culture experiments were performed over 24 h to evaluate the impact of two different doses (1 and 3 % (w/v)) of oat bran, matched concentrations of β-glucan extract or polyphenol mix, on the human faecal microbiota composition using 16S RNA gene sequencing and SCFA analysis. Supplementation with oats increased the abundance of Proteobacteria (P <0·01) at 10 h, Bacteroidetes (P <0·05) at 24 h and concentrations of acetic and propionic acid increased at 10 and 24 h compared with the NC. Fermentation of the 1 % (w/v) oat bran resulted in significant increase in SCFA production at 24 h (86 (sd 27) v. 28 (sd 5) mm; P <0·05) and a bifidogenic effect, increasing the relative abundance of Bifidobacterium unassigned at 10 h and Bifidobacterium adolescentis (P <0·05) at 10 and 24 h compared with NC. Considering the β-glucan treatment induced an increase in the phylum Bacteroidetes at 24 h, it explains the Bacteriodetes effects of oats as a food matrix. The polyphenol mix induced an increase in Enterobacteriaceae family at 24 h. In conclusion, in this study, we found that oats increased bifidobacteria, acetic acid and propionic acid, and this is mediated by the synergy of all oat compounds within the complex food matrix, rather than its main bioactive β-glucan or polyphenols. Thus, oats as a whole food led to the greatest impact on the microbiota.
Kristek A, Wiese M, Heuer P, et al. Oat bran, but not its isolated bioactive β-glucans or polyphenols, have a bifidogenic effect in an in vitro fermentation model of the gut microbiota. Br J Nutr. 2019;121(5):549‐559. doi:10.1017/ S0007114518003501 Title: Pumpkin Seed Extract: Cell Growth Inhibition of Hyperplastic and Cancer Cells, Independent of Steroid Hormone Receptors
Abstract
Pumpkin seeds have been known in folk medicine as remedy for kidney, bladder and prostate disorders since centuries. Nevertheless, pumpkin research provides insufficient data to back up traditional beliefs of ethnomedical practice. The bioactivity of a hydro-ethanolic extract of pumpkin seeds from the Styrian pumpkin, Cucurbita pepo L. subsp. pepo var. styriaca, was investigated. As pumpkin seed extracts are standardized to cucurbitin, this compound was also tested. Transactivational activity was evaluated for human androgen receptor, estrogen receptor and progesterone receptor with in vitro yeast assays. Cell viability tests with prostate cancer cells, breast cancer cells, colorectal adenocarcinoma cells and a hyperplastic cell line from benign prostate hyperplasia tissue were performed. As model for non-hyperplastic cells, effects on cell viability were tested with a human dermal fibroblast cell line (HDF-5). No transactivational activity was found for human androgen receptor, estrogen receptor and progesterone receptor, for both, extract and cucurbitin. A cell growth inhibition of ~40-50% was observed for all cell lines, with the exception of HDF-5, which showed with ~20% much lower cell growth inhibition. Given the receptor status of some cell lines, a steroid-hormone receptor independent growth inhibiting effect can be assumed. The cell growth inhibition for fast growing cells together with the cell growth inhibition of prostate-, breast- and colon cancer cells corroborates the ethnomedical use of pumpkin seeds for a treatment of benign prostate hyperplasia. Moreover, due to the lack of androgenic activity, pumpkin seed applications can be regarded as safe for the prostate.
Medjakovic S, Hobiger S, Ardjomand-Woelkart K, Bucar F, Jungbauer A. Pumpkin seed extract: Cell growth inhibition of hyperplastic and cancer cells, independent of steroid hormone receptors. Fitoterapia. 2016;110:150‐156. doi:10.1016/ j.fitote.2016.03.010 Title: An Appraisal of Pumpkin Seed Extract in 1, 2- Dimethylhydrazine Induced Colon Cancer in Wistar Rats
Abstract
Background: Cancer is one of the most important public health burdens in developed and developing countries. Colon cancer (CC) is the sixth most common cause of death in India and third most important cause in developed countries. For treating cancer, several synthetic agents are available but they cause side effects. Therefore, there is a need to investigate plant derived anticancer agents with lesser side effects. In this direction, we have made an attempt to unravel the potential of pumpkin seed extract for treating colon cancer.
Results: A significant difference in the aberrant crypt foci (ACF) number in all treatment groups compared to control and DMH groups were noted. Pretreatment group at a dose of 200 mg/kg showed a significant decrease in the colon length/weight ratio. Pretreatment groups showed a significant change in the colonic glutathione (GSH) and superoxide dismutase (SOD) levels when compared to control and DMH control. The nitrite content was decreased in treatment group 200 mg/kg at 5.203±0.852 when compared to DMH control at 8.506±3.866. All treatment groups demonstrated decreased hyperplasia and ACF in histology. Chari KY, Polu PR, Shenoy RR. An Appraisal of Pumpkin Seed Extract in 1, 2-Dimethylhydrazine Induced Colon Cancer in Wistar Rats. J Toxicol. 2018;2018:6086490. Published 2018 Sep 2. doi:10.1155/2018/6086490 Title: Does Larch Arabinogalactan Enhance Immune Function? A Review of Mechanistic and Clinical Trials
Abstract
The common cold is a viral infection with important economic burdens in Western countries. The research and development of nutritional solutions to reduce the incidence and severity of colds today is a major focus of interest, and larch arabinogalactan seems to be a promising supportive agent. Arabinogalactan has been consumed by humans for thousands of years and is found in a variety of common vegetables as well as in medicinal herbs. The major commercial sources of this long, densely branched, high-molecular-weight polysaccharide are North American larch trees. The aim of this article is to review the immunomodulatory effects of larch arabinogalactan derived from Larix laricina and Larix occidentalis (North American Larix species) and more specifically its role in the resistance to common cold infections. In cell and animal models, larch arabinogalactan is capable of enhancing natural killer cells and macrophages as well as the secretion of pro-inflammatory cytokines. In humans a clinical study demonstrated that larch arabinogalactan increased the body's potential to defend against common cold infection. Larch arabinogalactan decreased the incidence of cold episodes by 23 %. Improvements of serum antigen-specific IgG and IgE response to Streptococcus pneumoniae and tetanus vaccination suggesting a B cell dependent mechanism have been reported in vaccination studies with larch arabinogalactan, while the absence of response following influenza vaccination suggests the involvement of a T cell dependent mechanism. These observations suggest a role for larch arabinogalactan in the improvement of cold infections, although the mode of action remains to be further explored. Different hypotheses can be envisaged as larch arabinogalactan can possibly act indirectly through microbiota- dependent mechanisms and/or have a direct effect on the immune system via the gut-associated lymphoid tissue (GALT).
Dion C, Chappuis E, Ripoll C. Does larch arabinogalactan enhance immune function? A review of mechanistic and clinical trials. Nutr Metab (Lond). 2016;13:28. Published 2016 Apr 12. doi:10.1186/s12986-016-0086-x Title: Dietary Inulin and Trichuris suis Infection Promote Beneficial Bacteria Throughout the Porcine Gut
Abstract
The gut microbiota (GM) displays a profound ability to adapt to extrinsic factors, such as gastrointestinal pathogens and/ or dietary alterations. Parasitic worms (helminths) and host-associated GM share a long co-evolutionary relationship, exerting mutually modulatory effects which may impact the health of the host. Moreover, dietary components such as prebiotic fibers (e.g. inulin) are capable of modulating microbiota toward a composition often associated with a healthier gut function. The effect of helminth infection on the host microbiota is still equivocal, and it is also unclear how parasites and prebiotic dietary components interact to influence the microbiota and host health status. Some helminths, such as Trichuris suis (porcine whipworm), also exhibit strong immunomodulatory and anti-inflammatory effects. We therefore explored the effects of T. suis, alone and in interaction with inulin, both in fecal microbiota during the infection period and luminal microbiota across four intestinal segments at the end of a 4-week infection period. We observed that T. suis generally had minimal, but mainly positive, effects on the microbiota. T. suis increased the relative abundance of bacterial genera putatively associated with gut health such as Prevotella, and decreased bacteria such as Proteobacteria that have been associated with dysbiosis. Interestingly, dietary inulin interacted with T. suis to enhance these effects, thereby modulating the microbiota toward a composition associated with reduced inflammation. Our results show that administration of T. suis together with the consumption of prebiotic inulin may have the potential to positively affect gut health.
Stolzenbach S, Myhill LJ, Andersen LO, et al. Dietary Inulin and Trichuris suis Infection Promote Beneficial Bacteria Throughout the Porcine Gut. Front Microbiol. 2020;11:312. Published 2020 Mar 4. doi:10.3389/fmicb.2020.00312 Title: Dietary Supplementation With Inulin-Propionate Ester or Inulin Improves Insulin Sensitivity in Adults With Overweight and Obesity With Distinct Effects on the Gut Microbiota, Plasma Metabolome and Systemic Inflammatory Responses: A Randomised Abstract Cross-Over Trial
Objective: To investigate the underlying mechanisms behind changes in glucose homeostasis with delivery of propionate to the human colon by comprehensive and coordinated analysis of gut bacterial composition, plasma metabolome and immune responses.
Results: Both IPE and inulin supplementation improved insulin resistance compared with cellulose supplementation, measured by homeostatic model assessment 2 (mean±SEM 1.23±0.17 IPE vs 1.59±0.17 cellulose, p=0.001; 1.17±0.15 inulin vs 1.59±0.17 cellulose, p=0.009), with no differences between IPE and inulin (p=0.272). Fasting insulin was only associated positively with plasma tyrosine and negatively with plasma glycine following inulin supplementation. IPE supplementation decreased proinflammatory interleukin-8 levels compared with cellulose, while inulin had no impact on the systemic inflammatory markers studied. Inulin promoted changes in gut bacterial populations at the class level (increased Actinobacteria and decreased Clostridia) and order level (decreased Clostridiales) compared with cellulose, with small differences at the species level observed between IPE and cellulose.
Conclusion: These data demonstrate a distinctive physiological impact of raising colonic propionate delivery in humans, as improvements in insulin sensitivity promoted by IPE and inulin were accompanied with different effects on the plasma metabolome, gut bacterial populations and markers of systemic inflammation. Chambers ES, Byrne CS, Morrison DJ, et al. Dietary supplementation with inulin-propionate ester or inulin improves insulin sensitivity in adults with overweight and obesity with distinct effects on the gut microbiota, plasma metabolome and systemic inflammatory responses: a randomised cross-over trial. Gut. 2019;68(8):1430‐1438. doi:10.1136/ gutjnl-2019-318424 Title: Dried Fruit Intake and Cancer: A Systematic Review of Observational Studies Abstract
Insufficient intake of total fruits and vegetables is linked to an increased cancer risk, but the relation is not understood for dried fruits. Dried fruits are generally perceived, by both consumers and researchers, as a less attractive but shelf-stable equivalent to fresh fruits and constitute a small but significant proportion of modern diets. Chemical compositions of raw and dried fruits, however, may differ substantially. Several clinical and laboratory intervention studies have reported the protective effects of dehydrated fruits against the progression of some cancers and the modulating effects of dried fruits on common cancer risk factors. In this systematic review, we identified, summarized, and critically evaluated 9 prospective cohort and 7 case-control studies that examined the relations between traditional dried fruit (raisins, prunes, dates) consumption and cancer risk in humans. Prospective cohort studies determined that significant reductions in relative risk of precancerous colorectal polyps, incidence of prostate cancer, or mortality from pancreatic cancer, by, respectively, 24%, 49%, and 65%, were associated with 3-5 or more servings of dried fruits per week. Selected case-control studies revealed inverse associations between dried fruit intake and risk of cancer as well. The reported associations were comparable to or stronger than those observed for total or raw fruits. Although the small number and high heterogeneity impede meta-analysis of these studies, we conclude that currently available data provide some initial evidence that consumption of dried fruits may be associated with a lower cancer incidence or mortality in populations. The data suggest that higher intake of raisins and other dried fruits may be important in the prevention of cancers of the digestive system. Because only a limited number of health outcome and dried fruit intake relations have been evaluated in prospective studies to date, reanalyzing existing high-quality epidemiological data may expand the knowledge base.
Mossine VV, Mawhinney TP, Giovannucci EL. Dried Fruit Intake and Cancer: A Systematic Review of Observational Studies. Adv Nutr. 2020;11(2):237‐250. doi:10.1093/advances/nmz085 Title: Intake of Dietary Fiber, Fruits, and Vegetables and Risk of Diverticulitis Abstract
Objectives: Although low fiber intake has been considered a risk factor for diverticulitis, prospective evidence is limited in women despite having a disproportionate burden of disease, with little known about variation in the protective effects according to food sources. We assessed the associations of intakes of fiber and major food sources of fiber including fruits and vegetables with risk of diverticulitis in a large cohort of women.
Methods: We followed 50,019 women in the Nurses' Health Study (1990-2014) who were aged 43-70 years and free of diverticulitis, cancer, and inflammatory bowel disease at baseline. Incident diverticulitis was identified through self-report with validity confirmed by review of medical records.
Results: We documented 4,343 incident cases of diverticulitis, encompassing 1,106,402 person-years of follow-up. Compared with participants in the lowest quintile, the multivariable hazard ratio of diverticulitis in the highest quintile of total fiber intake was 0.86 (95% confidence interval: 0.78-0.95; P-trend = 0.002). Fiber from fruits and cereals, but not vegetables, was associated with a decreased risk of diverticulitis. Furthermore, intake of total whole fruit intake and specific fruits such as apples/pears and prunes were associated with reduced risk of diverticulitis with a multivariable hazard ratio for diverticulitis of 0.95 (0.92-0.98; P-trend < 0.001) for every serving increase of total whole fruit intake per day.
Discussion: Higher intake of dietary fiber and fiber from different food sources, except for vegetable fiber, are associated with a lower risk of diverticulitis in women. A greater intake of whole fruit is also associated with reduced risk. Ma W, Nguyen LH, Song M, et al. Intake of Dietary Fiber, Fruits, and Vegetables and Risk of Diverticulitis. Am J Gastroenterol. 2019;114(9):1531‐1538. doi:10.14309/ajg.0000000000000363 Title: Bioactivity and Potential Health Benefits of Licorice
Abstract
Licorice is an herbal plant named for its unique sweet flavor. It is widely used in the food and tobacco industries as a sweetener. Licorice is also used in traditional Chinese medicine (TCM) and complementary medicine. Because the use of licorice has long been a part of TCM, the details of its therapeutic applications have been thoroughly established. In modern science, licorice is of interest because of its broad range of applications. Extracts of and compounds isolated from licorice have been well studied and biologically characterized. In this review, we discuss the nutraceutical and functional activities of licorice as well as those of the extracts of and the isolated compounds from licorice, including agents with anti-inflammatory activity, cell-protective abilities, and chemopreventive effects. The side effects of licorice are also enumerated. A comparison of the activities of licorice described by modern science and TCM is also presented, revealing the correspondence of certain characteristics.
Kao TC, Wu CH, Yen GC. Bioactivity and potential health benefits of licorice. J Agric Food Chem. 2014;62(3):542‐553. doi: 10.1021/jf404939f Title: Prevention and Treatment of Influenza, Influenza-Like Illness, and Common Cold by Herbal, Complementary, and Natural
Abstract Therapies
In recent years viral respiratory tract infections, especially influenza viruses, have had a major impact on communities worldwide as a result of unavailability of effective treatment or vaccine. The frequent alterations in the antigenic structures of respiratory viruses, particularly for RNA viruses, pose difficulties in production of effective vaccines. The unavailability of optimal medication and shortage of effective vaccines suggests the requirement for alternative natural therapies. Several herbal remedies were used for prevention and treatment viral respiratory illnesses. Among those that were found effective included maoto, licorice roots, antiwei, North American ginseng, berries, Echinacea, plants extracted carnosic acid, pomegranate, guava tea, and Bai Shao. There is scientific evidence regarding the effectiveness of several complementary therapies for colds. Oral zinc may reduce the length and severity of a cold. Taking vitamin C supplements on a regular basis only slightly reduces the length and severity of colds. Probiotics were found better than placebo in reducing the number episodes of acute upper respiratory tract infections, the rate of episodes of acute upper respiratory tract infection and reducing antibiotic use. Alkaline diets or drinks might have antiviral properties as in vitro studies demonstrated inactivation effect of alkaline medium on respiratory virus. Earthing might have a natural anti-inflammatory effect for human body. It is now accepted that an overwhelming inflammatory response is the cause of human deaths from avian H5N1 influenza infection. Earthing accelerates immune response following vaccination, as demonstrated by increases of gamma globulin concentration. No in vivo or clinical studies were found that investigate the role of alkalization or earthing on respiratory viral infections. Thus, future studies are recommended to reveal any potential curative effects.
Mousa HA. Prevention and Treatment of Influenza, Influenza-Like Illness, and Common Cold by Herbal, Complementary, and Natural Therapies. J Evid Based Complementary Altern Med. 2017;22(1):166‐174. doi:10.1177/2156587216641831 Title: Astragalus Membranaceus Nanoparticles Markedly Improve Immune and Anti-Oxidative Responses; And Protection Against Aeromonas Veronii in Nile Tilapia Oreochromis Niloticus Abstract
The effects of dietary administration of Astragalus membranaceus nanoparticles (ANP) on immune and anti-oxidative responses, growth performance and disease resistance of Oreochromis niloticus were evaluated in the present study. Fish were divided into three groups and received the ANP at rates of 0 (control), 1, and 2%/kg diet for four weeks. After the four-week feeding trial, three fish from each replicate were sampled for immune and anti-oxidative responses evaluation, ten fish from each group were challenged with A. veronii, and nine fish from each group were subjected to cold and hypoxia challenges. It was obvious from the results that ANP significantly enhanced lysozyme activity and nitrous oxide (NO) activities, as well as improved superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities. Also, aspartate aminotransferase, alanine transaminase, glucose, and cortisol measurements showed significantly lower levels in incorporated groups compared to the control. Growth performance; and amylase and lipase digestive enzymes activities also showed markedly improved results. Expression of heat shock protein 70 (HSP70) and interleukin 1, beta (IL-1β) genes were significantly upregulated throughout the entire experimental period. When challenged with A. veronii, the mortality of treated groups was significantly (P < 0.05) lower than the control. Current results proofs that dietary ANP had a synergistic effect on immune and anti-oxidative responses, growth performance and disease resistance of Oreochromis niloticus.
Elabd H, Wang HP, Shaheen A, Matter A. Astragalus membranaceus nanoparticles markedly improve immune and anti- oxidative responses; and protection against Aeromonas veronii in Nile tilapia Oreochromis niloticus. Fish Shellfish Immunol. 2020;97:248‐256. doi:10.1016/j.fsi.2019.12.025 Title: Astragalus Polysaccharides Enhance the Immune Response to Avian Infectious Bronchitis Virus Vaccination in Chickens Abstract
Astragalus polysaccharides (APS) are biological macromolecules extracted from Astragalus species that have strong immunoregulatory properties. In this study, APS were employed as an adjuvant for an avian infectious bronchitis virus (IBV) vaccine, and its effects on the cellular immune and humoral immune responses to vaccination in chicken were investigated. One hundred and fifty chicken were randomly divided into five groups (n = 30, each group). The chickens in all groups, except for the unvaccinated control group, were vaccinated with an IBV DNA vaccine. Three of the four vaccinated groups were administered different doses of APS (APSL, 10 mg/kg; APSM, 50 mg/kg; and APSH, 100 mg/kg) after the first vaccination, and the remaining vaccinated group served as a control, without any additional treatment. At 14, 28, and 42 days after the first vaccination, serum anti- IBV antibody titers; peripheral lymphocyte proliferation; and the mRNA expression of IL-1β, IL-2, IL-8, and TNF-α in the spleen were assessed by enzyme-linked immunosorbent assay (ELISA), the cell counting kit-8 (CCK-8), and real time quantitative RT-PCR (qRT-PCR), respectively. At most time points, the titer of IBV-specific antibodies, lymphocyte proliferation, and IL-1β, IL-2, IL-8, and TNF-α mRNA expression levels were higher in three APS groups than in the vaccine control group, and these increases were dose-dependent. These data suggest that APS could be used as an adjuvant for IBV vaccination to provide better protection against IBV infection.
Zhang P, Wang J, Wang W, et al. Astragalus polysaccharides enhance the immune response to avian infectious bronchitis virus vaccination in chickens. Microb Pathog. 2017;111:81‐85. doi:10.1016/j.micpath.2017.08.023
ALKALINE GREENS TO DEAL WITH ACIDIFICATION
■ Most foods in the Standard American Diet create an acidic environment. Acid interferes with digestion food stagnates and rots lowering the pH of the body. ■ A 16oz bottle of soda has a pH= 2. Very acidic. To bring the pH back up to our normal 7.3, we would have to dilute the soda with about 10 gallons of water. ■ The blood must maintain a pH = 7.3-7.45. (Guyton) The body begins to sweep the extra acids into the tissues (muscles & joints). (lactic acid) ■ As a final effort to keep from acidifying, the body will actually precipitate acids out of solution, in the form of crystals, salts, and stones (Kidney & Gall). This is a sign that the body’s systems are functioning as they should. Otherwise we’d be dead of acidosis. Sources
1. http://greenopedia.com/alkaline-acid-food-chart/ J Nutr. 2017 May;147(5):841-849. doi: 10.3945/jn.117.247494. Epub 2017 Apr 5.
CRUCIFEROUS VEGETABLE INTAKE IS INVERSELY ASSOCIATED WITH LUNG CANCER RISK AMONG CURRENT NONSMOKING MEN IN THE JAPAN PUBLIC HEALTH (JPHC) STUDY
■Background: Cruciferous vegetables, a rich source of isothiocyanates, have been reported to lower the risk of several types of cancer, including lung cancer. However, evidence from prospective observations of populations with a relatively high intake of cruciferous vegetables is sparse.Objective: We investigated the association between cruciferous vegetable intake and lung cancer risk in a large-scale population-based prospective study in Japan.Methods: We studied 82,330 participants (38,663 men; 43,667 women) aged 45-74 y without a past history of cancer. Participants were asked to respond to a validated questionnaire that included 138 food items. The association between cruciferous vegetable intake and lung cancer incidence was assessed with the use of Cox proportional hazard regression analysis to estimate HRs and 95% CIs (with adjustments for potential confounding factors).Results: After 14.9 y of follow-up, a total of 1499 participants (1087 men; 412 women) were diagnosed with lung cancer. After deleting early-diagnosed cancer and adjusting for confounding factors, we observed a nonsignificant inverse trend between cruciferous vegetable intake and lung cancer risk in men in the highest compared with the lowest quartiles (multivariate HR: 0.85; 95% CI: 0.69, 1.06; P-trend = 0.13). Stratified analysis by smoking status revealed a significant inverse association between cruciferous vegetable intake and lung cancer risk among those who were never smokers and those who were past smokers after deleting lung cancer cases in the first 3 y of follow-up [multivariate HR for never smokers: 0.49 (95% CI: 0.27, 0.87; P-trend = 0.04); multivariate HR for past smokers: 0.59 (95% CI: 0.35, 0.99; P-trend = 0.10)]. No association was noted in men who were current smokers and women who were never smokers.Conclusion: This study suggests that cruciferous vegetable intake may be associated with a reduction in lung cancer risk among men who are currently nonsmokers. Lipids Health Dis. 2018 Jun 15;17(1):140. doi: 10.1186/s12944-018-0723-7.
GREEN LEAFY VEGETABLES IN DIETS WITH A 25:1 OMEGA-6/ OMEGA-3 FATTY ACID RATIO MODIFY THE ERYTHROCYTE FATTY ACID PROFILE OF SPONTANEOUSLY HYPERTENSIVE RATS
■BACKGROUND: In addition to the actual composition of the diet (i.e. nutrient composition, food groups), the omega-6/omega-3 fatty acid ratio has been demonstrated to influence the tissue fatty acid profile and subsequently the risk for cardiovascular and other diseases. Likewise, the consumption of green leafy vegetables (GLVs) may favorably reduce the risks associated with disease. Although an ~ 3:1 omega-6/omega-3 fatty acid ratio (ω-6/ω-3 FAR) is recommended, the typical American diet has an ~ 25:1 ω-6/ω-3 FAR. Previous research affirms the ability of collard greens (CG), purslane (PL), and sweet potato greens (SPG) to improve the hepatic profile of spontaneously hypertensive rats (SHRs). The aim of the present study was to determine the influence of GLVs, incorporated (4%) into diets with a 25:1 ω-6/ω-3 FAR, on the erythrocyte fatty acid profile of male SHRs. ■RESULTS: Significantly lower percentages of total saturated fatty acids (p < 0.05) and greater percentages of polyunsaturated fatty acids were present among SHR erythrocytes following the consumption of diets containing CG, PL and SPG. Total polyunsaturated fatty acids were greatest among SHRs consuming diets containing purslane. ■CONCLUSIONS: The present study demonstrates the ability of GLVs to mitigate the potential effects of an elevated ω-6/ω-3 FAR, which may contribute to an atherogenic fatty acid profile, inflammation and disease pathogenesis. Dietary recommendations for disease prevention should consider the inclusion of these GLVs, particularly among those consuming diets with an ω-6/ω-3 FAR that may promote disease. Food Sci Nutr. 2018 Mar 15;6(4):860-870. doi: 10.1002/fsn3.628. eCollection 2018 Jun.
GREEN LEAFY VEGETABLES FROM TWO SOLANUM SPP. (SOLANUM NIGRUM L. AND SOLANUM MACROCARPON L) AMELIORATE SCOPOLAMINE-INDUCED COGNITIVE AND NEUROCHEMICAL IMPAIRMENTS IN RATS.
■This study examined the modulatory effect of Black nightshade (Solanum nigrum L) and African eggplant (Solanum macrocarpon L) leaves on cognitive function, antioxidant status, and activities of critical enzymes of monoaminergic and cholinergic systems of neurotransmission in scopolamine-administered rats. Cognitive impairment was induced in albino rats pretreated with dietary inclusions of Black nightshade (BN) and African eggplant (AE) leaves by single administration (i.p.) of scopolamine (2 mg/kg body weight). Prior to termination of the experiment, the rats were subjected to spontaneous alternation (Y-maze) test to assess their spatial working memory. Thereafter, activities of acetylcholinesterase (AChE), butyrylcholinesterase (BChE), monoamine oxidase (MAO), arginase, and antioxidant enzymes (catalase, SOD, and GST) of rat brain homogenate were determined. Also, the malondialdehyde (MDA), nitrite, and GSH contents of the homogenate were determined. The results showed that pretreatment with dietary inclusions of AE and BN significantly reversed the impairment in the rats' spatial working memory induced by scopolamine. Similarly, elevations in activities of AChE, BChE, and MAO induced by scopolamine were significantly reversed in rats pretreated with dietary inclusions of AE and BN. In addition, impaired antioxidant status induced by scopolamine was reversed by pretreatment with dietary inclusions of AE and BN. This study has shown that dietary inclusions of AE and BN could protect against cognitive and neurochemical impairments induced by scopolamine, and hence, these vegetables could be used as a source of functional foods and nutraceuticals for the prevention and management of cognitive impairments associated diseases such as Alzheimer's disease In Vitro Cell Dev Biol Anim. 2017 Mar;53(3):217224. doi: 10.1007/s1162601601007. Epub 2016 Oct 3.
INTEGRATED IN VITRO APPROACHES TO ASSESS THE BIOACCESSIBILITY AND BIOAVAILABILITY OF SILICON BIOFORTIFIED LEAFY VEGETABLES AND PRELIMINARY Food industries are increasingly orientedEFFECTS toward new ON foods BONE. to improve nutritional status and/or to combat nutritional deficiency diseases. In this context, silicon biofortification could be an innovative tool for obtaining new foods with possible positive effects on bone mineralization. In this paper, an alternative and quick in vitro approach was applied in order to evaluate the potential healthpromoting effects of five siliconbiofortified leafy vegetables (tatsoi, mizuna, purslane, Swiss chard and chicory) on bone mineralization compared with a commercial silicon supplement. The silicon bioaccessibility and bioavailability of the five leafy vegetables (biofortified or not) and of the supplement were assessed by applying a protocol consisting of in vitro gastrointestinal digestion coupled with a Caco2 cell model. Silicon bioaccessibility ranged from 0.89 to 8.18 mg/L and bioavailability ranged from 111 to 206 µg/L of Si for both vegetables and supplement. Furthermore, the bioavailable fractions were tested on a human osteoblast cell model following the expression of type 1 collagen and alkaline phosphatase. The results obtained highlighted that the bioavailable fraction of biofortified purslane and Swiss chard improved the expression of both osteoblast markers compared with the supplement and other vegetables. These results underline the potentially beneficial effect of biofortified leafy vegetables and also indicate the usefulness of in vitro approaches for selecting the best vegetable with positive bone effects for further in vivo research. Minerals & Collagen Minerals
■Functions of minerals: Structural: bones, teeth, ligaments Solutes and electrolytes in the blood Enzyme actions Nerve transmission Muscle action Best Type of Mineral Supplements
■ CHELATED = a mineral is bound or stuck to certain carrier molecules Chelation can include minerals, vitamins, or enzymes. Minerals in food may be bound with organic molecules already in a chelated state. Many molecules in the body are chelated in normal metabolic processes. Chelation Therapy = treatment for removing heavy metals from the blood. The toxic metals are bound to a therapeutic amino acid ligand called EDTA. Article Title: Invited review: Mineral absorption mechanisms, mineral interactions that affect acid- base and antioxidant status, and diet considerations to improve mineral status.
Date & Journal: J Dairy Sci. 2018 Apr
• Several minerals are required for life to exist. In animals, 7 elements (Ca, P, Mg, Na, K, Cl, and S) are required to be present in the diet in fairly large amounts (grams to tens of grams each day for the dairy cow) and are termed macrominerals. Several other elements are termed microminerals or trace minerals because they are required in much smaller amounts (milligrams to micrograms each day). In most cases the mineral in the diet must be absorbed across the gastrointestinal mucosa and enter the blood if it is to be of value to the animal. The bulk of this review discusses the paracellular and transcellular mechanisms used by the gastrointestinal tract to absorb each of the various minerals needed. Unfortunately, particularly in ruminants, interactions between minerals and other substances within the diet can occur within the digestive tract that impair mineral absorption. The attributes of organic or chelated minerals that might permit diet minerals to circumvent factors that inhibit absorption of more traditional inorganic forms of these minerals are discussed. Once absorbed, minerals are used in many ways. One focus of this review is the effect macrominerals have on the acid-base status of the animal. Manipulation of dietary cation and anion content is commonly used as a tool in the dry period and during lactation to improve performance. A section on how the strong ion theory can be used to understand these effects is included. Many microminerals play a role in the body as cofactors of enzymes involved in controlling free radicals within the body and are vital to antioxidant capabilities. Those same minerals, when consumed in excess, can become pro-oxidants in the body, generating destructive free radicals. Complex interactions between minerals can compromise the effectiveness of a diet in promoting health and productivity of the cow. The objective of this review is to provide insight into some of these mechanisms. Article Title: Magnesium and malic acid supplement for fibromyalgia.
Date & Journal: Medwave. 2019 May 28
• INTRODUCTION:Fibromyalgia is characterized by myalgia and a combination of different symptoms including pain, fatigue, insomnia, morning rigidity, depression and a reduction in every-day functioning. Its aetiology is not clear, but it has been suggested that deficiency in certain minerals such as magnesium may play a role both in the physiopathology and in contributing to the symptoms.
• METHODS:We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach.
• RESULTS AND CONCLUSIONS:We identified seven systematic reviews which included 11 primary studies of which one was a randomized trial. Our conclusion is that the use of magnesium and malic acid in patients with fibromyalgia makes little or no difference on pain and on depressive symptoms.
Title: Effects of Magnesium Citrate, Magnesium Oxide and Magnesium Sulfate Supplementation on Arterial Stiffness in Healthy Overweight Individuals: A Study Protocol for a Randomized Controlled Trial Abstract
Background: Arterial stiffness is closely related to the process of atherosclerosis, an independent cardiovascular risk factor, and predictive of future cardiovascular events and mortality. Recently, we showed that magnesium citrate supplementation results in a clinically relevant improvement of arterial stiffness. It remained unclear whether the observed effect was due to magnesium or citrate, and whether other magnesium compounds may have similar effects. Therefore, we aim to study the long-term effects of magnesium citrate, magnesium oxide and magnesium sulfate on arterial stiffness. In addition, we aim to investigate possible underlying mechanisms, including changes in blood pressure and changes in gut microbiota diversity.
Discussion: The present study is expected to provide evidence for the effects of different available magnesium formulations (organic and inorganic) on well-established cardiovascular risk markers, including arterial stiffness and blood pressure, as well as on the human gut microbiota. As such, the study may contribute to the primary prevention of cardiovascular disease in slightly obese, but otherwise healthy, individuals.
Schutten JC, Joris PJ, Mensink RP, et al. Effects of magnesium citrate, magnesium oxide and magnesium sulfate supplementation on arterial stiffness in healthy overweight individuals: a study protocol for a randomized controlled trial. Trials. 2019;20(1):295. Published 2019 May 28. doi:10.1186/s13063-019-3414-4 Title: Selenium and Autoimmune Diseases: A Review Article
Abstract
Background: Selenium is an essential trace element with fundamental effects on human biology. Trace elements deficiency is not an uncommon finding in autoimmune diseases. This deficiency may be a consequence of autoimmune diseases or may contribute to their etiology. With regard to evidence showing the association between selenium deficiency and generation of reactive oxygen species and subsequent inflammation, reviewing the role of selenium in collagen vascular diseases could help researchers to devise strategies for managing these diseases.
Objective: The present study aimed to evaluate the role of selenium and autoimmune rheumatic diseases.
Study eligibility criteria: All the studies on the use of selenium without any limitations in terms of the preparation method, administration route, or formulation process were included in the study. The exclusion criteria were: 1) Articles published in languages other than English, 2) Administration of chemical and hormonal drugs rather than selenium, 3) Investigation of the effects of selenium on the autoimmune problems in animal models, and 4) Insufficiency of the presented data or poor description of the applied methods. Furthermore, review articles, meta-analyses, expert opinions, editorial letters, case reports, consensus statements, and qualitative studies were excluded from the study. Sahebari M, Rezaieyazdi Z, Khodashahi M. Selenium and Autoimmune Diseases: A Review Article. Curr Rheumatol Rev. 2019;15(2):123‐134. doi:10.2174/1573397114666181016112342 Title: Selenomethionine Relieves Inflammation in the Chicken Trachea Caused by LPS Though Inhibiting the NF-κB Pathway
Abstract
Selenomethionine is able to relieve the effect of inflammation in various tissues and organs. However, there are few studies about the influences of organic selenium resisting inflammation induced by LPS in chicken trachea. Therefore, the purpose of this experiment is to explore the organic selenium (selenomethionine) can raise immune function and relieve the LPS-induced inflammation of chicken trachea via inhibiting the NF-κB pathway. To investigate the mechanism of organic selenium on chicken trachea, the supplement of selenomethionine and/or LPS-induced chicken models were established. One hundred 46-week-old isa chickens were randomly divided into four groups (n = 25). The four groups were the control group, the selenomethionine group (Se group), the LPS-induced group (LPS group), and the Se and LPS interaction group (Se + LPS group). Then, the expressions of inflammatory factors (including induced nitric oxide synthase (iNOS), nuclear factor-kappa B(NF-κB), tumor necrosis factor (TNF-α), cyclooxygenase-2 (COX-2), and prostaglandin E (PTGEs) synthase), inflammation-related cytokines (including interleukin (IL-2, IL-6, IL-8, IL-17) and immunoglobulin (IgA, IgM, IgY)), the marker of immune function (avian β-defensins (AvBD6, AvBD7)), heat shock proteins (including HSP60, HSP90), and selenoproteins (including Selo, Sels, Selm, Selh, Selu, Seli, SPS2, GPx1, GPx2, Dio1, Sepx1, Sep15, Sepp1, Txnrd1) were detected in our experiment. The above genes were significantly changed in different groups (p < 0.05). We can conclude that organic selenium can increase the function of immunity and the expression of selenoproteins, and mitigate the inflammation induced by LPS via suppression of the NF-κB pathway.
Shi X, Wang W, Zheng S, Zhang Q, Xu S. Selenomethionine relieves inflammation in the chicken trachea caused by LPS though inhibiting the NF-κB pathway. Biol Trace Elem Res. 2020;194(2):525‐535. doi:10.1007/s12011-019-01789-1 Title: Selenomethionine Supplementation Reduces Lesion Burden, Improves Vessel Function and Modulates the Inflammatory Response Within the Setting of Atherosclerosis Abstract
Atherosclerosis is a chronic inflammatory disease of the vasculature characterised by the infiltration of activated neutrophils and macrophages at sites of damage within the vessel wall, which contributes to lesion formation and plaque progression. Selenomethionine (SeMet) is an organic form of selenium (Se), an essential trace element that functions in the regulation of the immune response by both bolstering the endogenous thioredoxin and glutathione antioxidant defence systems and by directly scavenging damaging oxidant species. This study evaluated the effect of dietary SeMet supplementation within a high fat diet fed apolipoprotein E deficient (ApoE-/-) mouse model of atherosclerosis. Dietary supplementation with SeMet (2 mg/kg) increased the tissue concentration of Se, and the expression and activity of glutathione peroxidase, compared to non-supplemented controls. Supplementation with SeMet significantly reduced atherosclerotic plaque formation in mouse aortae, resulted in a more stable lesion phenotype and improved vessel function. Concurrent with these results, SeMet supplementation decreased lesion accumulation of M1 inflammatory type macrophages, and decreased the extent of extracellular trap release from phorbol myristate acetate (PMA)-stimulated mouse bone marrow-derived cells. Importantly, these latter results were replicated within ex-vivo experiments on cultured neutrophils isolated from acute coronary syndrome patients, indicating the ability of SeMet to alter the acute inflammatory response within a clinically-relevant setting. Together, these data highlight the potential beneficial effect of SeMet supplementation as a therapeutic strategy for atherosclerosis.
Zhang Y, Cartland SP, Henriquez R, et al. Selenomethionine supplementation reduces lesion burden, improves vessel function and modulates the inflammatory response within the setting of atherosclerosis. Redox Biol. 2020;29:101409. doi: 10.1016/j.redox.2019.101409 Cochrane Database Syst Rev. 2017 Jul 31;7:CD000254. doi: 10.1002/14651858.CD000254.pub4. ANTIOXIDANT VITAMIN AND MINERAL SUPPLEMENTS FOR SLOWING THE PROGRESSION OF AGE-RELATED MACULAR DEGENERATION.
MAIN RESULTS: We included 19 studies conducted in USA, Europe, China, and Australia. We judged the trials that contributed data to the review to be at low or unclear risk of bias. Nine studies compared multivitamins with placebo (7 studies) or no treatment (2 studies) in people with early and moderate AMD. The duration of supplementation and follow-up ranged from nine months to six years; one trial followed up beyond two years. Most evidence came from the Age-Related Eye Disease Study (AREDS) in the USA. People taking antioxidant vitamins were less likely to progress to late AMD (odds ratio (OR) 0.72, 95% confidence interval (CI) 0.58 to 0.90; 2445 participants; 3 RCTs; moderate-certainty evidence). In people with very early signs of AMD, who are at low risk of progression, this would mean that there would be approximately 4 fewer cases of progression to late AMD for every 1000 people taking vitamins (1 fewer to 6 fewer cases). In people at high risk of progression (i.e. people with moderate AMD) this would correspond to approximately 8 fewer cases of progression for every 100 people taking vitamins (3 fewer to 13 fewer). In one study of 1206 people, there was a lower risk of progression for both neovascular AMD (OR 0.62, 95% CI 0.47 to 0.82; moderate-certainty evidence) and geographic atrophy (OR 0.75, 95% CI 0.51 to 1.10; moderate-certainty evidence) and a lower risk of losing 3 or more lines of visual acuity (OR 0.77, 95% CI 0.62 to 0.96; 1791 participants; moderate-certainty evidence). Low-certainty evidence from one study of 110 people suggested higher quality of life scores (National Eye Institute Visual Function Questionnaire) in treated compared with the non-treated people after 24 months (mean difference (MD) 12.30, 95% CI 4.24 to 20.36). Six studies compared lutein (with or without zeaxanthin) with placebo. The duration of supplementation and follow-up ranged from six months to five years. Most evidence came from the AREDS2 study in the USA. People taking lutein or zeaxanthin may have similar or slightly reduced risk of progression to late AMD (RR 0.94, 95% CI 0.87 to 1.01; 6891 eyes; low-certainty evidence), neovascular AMD (RR 0.92, 95% CI 0.84 to 1.02; 6891 eyes; low-certainty evidence), and geographic atrophy (RR 0.92, 95% CI 0.80 to 1.05; 6891 eyes; low- certainty evidence). A similar risk of progression to visual loss of 15 or more letters was seen in the lutein and control groups (RR 0.98, 95% CI 0.91 to 1.05; 6656 eyes; low-certainty evidence). Quality of life (measured with Visual Function Questionnaire) was similar between groups in one study of 108 participants (MD 1.48, 95% -5.53 to 8.49, moderate-certainty evidence). One study, conducted in Australia, compared vitamin E with placebo. This study randomised 1204 people to vitamin E or placebo, and followed up for four years. Participants were enrolled from the general population; 19% had AMD. The number of late AMD events was low (N = 7) and the estimate of effect was uncertain (RR 1.36, 95% CI 0.31 to 6.05, very low-certainty evidence). There were no data on neovascular AMD or geographic atrophy.There was no evidence of any effect of treatment on visual loss (RR 1.04, 95% CI 0.74 to 1.47, low-certainty evidence). There were no data on quality of life. Five studies compared zinc with placebo. The duration of supplementation and follow-up ranged from six months to seven years. People taking zinc supplements may be less likely to progress to late AMD (OR 0.83, 95% CI 0.70 to 0.98; 3790 participants; 3 RCTs; low-certainty evidence), neovascular AMD (OR 0.76, 95% CI 0.62 to 0.93; 2442 participants; 1 RCT; moderate-certainty evidence), geographic atrophy (OR 0.84, 95% CI 0.64 to 1.10; 2442 participants; 1 RCT; moderate-certainty evidence), or visual loss (OR 0.87, 95% CI 0.75 to 1.00; 3791 participants; 2 RCTs; moderate-certainty evidence). There were no data reported on quality of life. Very low-certainty evidence was available on adverse effects because the included studies were underpowered and adverse effects inconsistently reported. Nutrients. 2017 Aug 9;9(8). pii: E849. doi: 10.3390/nu9080849.
IMPACT OF FREQUENCY OF MULTI-VITAMIN/MULTI-MINERAL SUPPLEMENT INTAKE ON NUTRITIONAL ADEQUACY AND NUTRIENT DEFICIENCIES IN U.S. ADULTS. Although >50% of U.S. adults use dietary supplements, little information is available on the impact of supplement use frequency on nutrient intakes and deficiencies. Based on nationally representative data in 10,698 adults from the National Health and Nutrition Examination Surveys (NHANES) 2009 to 2012, assessments were made of intakes from food alone versus food plus multi-vitamin/multi-mineral supplements (MVMS) of 17 nutrients with an Estimated Average Requirement (EAR) and a Tolerable Upper Intake Level (UL), and of the status of five nutrients with recognized biomarkers of deficiency. Compared to food alone, MVMS use at any frequency was associated with a lower prevalence of inadequacy (p < 0.01) for 15/17 nutrients examined and an increased prevalence of intakes >UL for 7 nutrients, but the latter was ≤4% for any nutrient. Except for calcium, magnesium, and vitamin D, most frequent MVMS use (≥21 days/30 days) virtually eliminated inadequacies of the nutrients examined, and was associated with significantly lower odds ratios of deficiency for the examined nutrient biomarkers except for iron. In conclusion, among U.S. adults, MVMS use is associated with decreased micronutrient inadequacies, intakes slightly exceeding the UL for a few nutrients, and a lower risk of nutrient deficiencies. Rom J Intern Med. 2017 Aug 28. pii: /j/rjim.ahead-of-print/rjim-2017-0032/rjim-2017-0032.xml. doi: 10.1515/ rjim-2017-0032. HYPONATREMIA, BONE MINERAL DENSITY AND FALLS IN THE ELDERLY; RESULTS FROM AHAP STUDY.
BACKGROUND:Hyponatremia (HN) can be associated with osteoporosis, falls and bone fractures in the elderly. Recent researches demonstrated different results about the correlation of HN with bone mineral density and bone fractures. METHODS:This analytic research came from the AHAP project in northern IRAN. All people aged 60 years and over were included in the study. Individuals with severe comorbidities and them who had concurrent conditions which could have impact on bone mineral densities (BMD) such as long-term use of steroids, calcium and/or vitamin D supplements, bisphosphonates, calcitonin, thiazides and hormonal medications were excluded. RESULTS:One thousand and one hundred and thirteen older persons were entered in the study. More than 10 percent of the participants had HN (serum Na+ level ≤ 137mEq/L). No significant difference has been observed between hyponatremic and nonhyponatremic individuals about their balance abilities; bone mineral density; incidence of falls and/or bone fracture during the previous 6 month; dependency in activities of daily living; and osteoporosis. CONCLUSION:HN was not a prevalent problem in older adults who met the inclusion criteria of this research. No significant difference has been observed between HN and bone mineral density and falls in the elderly. Collagen Protein ■Largest Protein in our body. 65% of our total protein. ■Collagen Protein make up heart, lungs, blood vessels, discs, muscle, bone, internal organs. ■Ptosis = loss of collagen, droopy organs and skin. Caused by hormonal changes, drugs alcohol ,processed foods, white sugar, hydrogenated oils, fluoridated water, dehydration, stress, and trauma. Hydrolyzed Collagen ■Results Lean Muscle, muscle tone, skin tone, joint rebuilding, stronger arteries, increased energy, and organ rebuilding.
Long Term Improvements in: Osteoporosis, high blood pressure, arthritis, weak bladder, obesity, chronic fatigue, and autoimmune diseases. Process of Enzymatic Hydrolysis
Definition: Catalytic decomposition of a chemical compound by reaction with water.
In supplements it is used for the breakdown of proteins into amino acids by the addition of the enzyme protease.
J Biol Chem. 2018 Jul 10. pii: jbc.RA118.001801. doi: 10.1074/jbc.RA118.001801. A COLLAGEN DOMAIN-DERIVED SHORT ADIPONECTIN PEPTIDE ACTIVATES APPL1 AND AMPK SIGNALING PATHWAYS AND IMPROVES GLUCOSE AND FATTY ACID METABOLISMS
■Adiponectin is a fat tissue-derived adipokine with beneficial effects against diabetes, cardiovascular diseases, and cancer. Accordingly, adiponectin-mimetic molecules possess significant pharmacological potential. Oligomeric states of adiponectin appear to determine its biological activity. We identified a highly conserved, 13-residue segment (ADP-1) from adiponectin's collagen domain which comprises GXXG motifs and has one asparagine and two histidine residues that assist in oligomeric protein assembly. We therefore hypothesized that ADP-1 promotes oligomeric assembly and thereby mediates potential metabolic effects. We observed here that ADP-1 is stable in human serum and oligomerizes in aqueous environments. We also found that ADP-1 activates AMP-activated protein kinase (AMPK) in an adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1 (APPL1)-dependent pathway and stimulates glucose uptake in rat skeletal muscle cells (L-6 myotubes). ADP-1-induced glucose transport coincided with ADP-1-induced biosynthesis of glucose transporter 4 and its translocation to the plasma membrane. ADP-1 induced an interaction between APPL1 and the small GTPase Rab5 resulting in AMPK phosphorylation, in turn leading to phosphorylation of p38MAP kinase, acetyl coenzyme-A carboxylase, and peroxisome proliferator- activated receptor alpha. Similar to adiponectin, ADP-1 increased the expression of the adiponectin receptor 1 gene. Of note, ADP-1 decreased blood glucose levels and enhanced insulin production in pancreatic β cells in db/db mice. Further, ADP-1 beneficially affected lipid metabolism by enhancing lipid globule formation in mouse 3T3-L1 adipocytes. To our knowledge this is the first repo Food Chem. 2018 Mar 1;242:568-578. doi: 10.1016/j.foodchem.2017.09.045. Epub 2017 Sep 11.
SEQUENTIAL EXTRACTION OF GEL FORMING PROTEINS, COLLAGEN AND COLLAGEN HYDROLYSATE FROM GUTTED SILVER CARP (HYPOPHTHALMICHTHYS MOLTRIX) A BIOREFINERY APPROACH
■ Collagen and collagen hydrolysate (CH) was recovered from the bone and skin containing sediment residue emerging during pH-shift-based protein isolation from silver carp. Hydrolysis resulted in higher yield (15.1-15.4%) compared to collagen isolation by acid or pepsin (3.1-5.9%) (p<0.05). Isolated collagens were characterized as type I and maintained their triple-helical structure, confirmed by SDS-PAGE and FTIR. Pepsin- hydrolysis and sequential hydrolysis by pepsin and trypsin hydrolyzed all heavy molecular weight chains of collagen but sequential hydrolysis yielded higher degree of hydrolysis. When CH was added to a silver carp protein isolate prior to gelation, the gel behavior was dependent on molecular weight of the added CH. More hydrolyzed collagen emerging from sequential hydrolysis improved water holding capacity of the gel while reducing its breaking force. Thus, residue from pH-shift processing of fish can be used for isolation of high quality collagen/CH and provides a promising basis for a multiple-product fish biorefinery. PLoS One. 2017 Apr 6;12(4):e0174705. doi: 10.1371/journal.pone.0174705. eCollection 2017.
DAILY ORAL CONSUMPTION OF HYDROLYZED TYPE 1 COLLAGEN IS CHONDROPROTECTIVE AND ANTI-INFLAMMATORY IN MURINE POST TRAUMATIC OSTEOARTHRITIS. Osteoarthritis (OA) is a degenerative joint disease for which there are no disease modifying therapies. Thus, strategies that offer chondroprotective or regenerative capability represent a critical unmet need. Recently, oral consumption of a hydrolyzed type 1 collagen(hCol1) preparation has been reported to reduce pain in human OA and support a positive influence on chondrocyte function. To evaluate the tissue and cellular basis for these effects, we examined the impact of orally administered hCol1 in a model of posttraumatic OA (PTOA). In addition to standard chow, male C57BL/6J mice were provided a daily oral dietary supplement of hCol1 and a meniscal-ligamentous injury was induced on the right knee. At various time points post-injury, hydroxyproline (hProline) assays were performed on blood samples to confirm hCol1 delivery, and joints were harvested for tissue and molecular analyses were performed, including histomorphometry, OARSI and synovial scoring, immunohistochemistry and mRNA expression studies. Confirming ingestion of the supplements, serum hProline levels were elevated in experimental mice administered hCol1. In the hCol1 supplemented mice, chondroprotective effects were observed in injured knee joints, with dose-dependent increases in cartilage area, chondrocyte number and proteoglycan matrix at 3 and 12 weeks post-injury. Preservation of cartilage and increased chondrocyte numbers correlated with reductions in MMP13 protein levels and apoptosis, respectively. Supplemented mice also displayed reduced synovial hyperplasia that paralleled a reduction in Tnf mRNA, suggesting an anti-inflammatoryeffect. These findings establish that in the context of murine knee PTOA, daily oral consumption of hCol1 is chondroprotective, anti-apoptotic in articular chondrocytes, and anti-inflammatory. While the underlying mechanism driving these effects is yet to be determined, these findings provide the first tissue and cellular level information explaining the already published evidence of symptom relief supported by hCol1 in human knee OA. These results suggest that oral consumption of hCol1 is disease modifying in the context of PTOA. COMING SOON!
Colon Cleanser Type One Collagen Face Cream Article Title: Topical skin therapies in subjects undergoing full facial rejuvenation.
Date & Journal: J Cosmet Dermatol. 2019 Apr 29. ■ BACKGROUND: Cosmeceutical therapies including face washes, moisturizers, chemical peels and antioxidant formulations are intended to improve the esthetic appearance of skin. The use of these products as adjuncts to full facial rejuvenation with hyaluronic acid filler and abobotulinumtoxinA may improve cosmetic and socio-esthetic outcomes. ■ OBJECTIVE: To characterize the effect of skin care products in subjects undergoing full facial rejuvenation with abobotulinumtoxinA and hyaluronic acid in improving facial skin appearance, patient satisfaction, and projected first impressions. ■ METHODS: Twenty subjects were recruited and divided into two treatment groups. Subjects in Group A followed a standard skin care regimen, whereas subjects in Group B received a more robust skin care regimen including chemical peels and antioxidant formulations. All subjects underwent facial rejuvenation treatments with hyaluronic acid at Visit 2 and with abobotulinumtoxinA at Visit 7. Patient esthetic improvement, satisfaction, self-esteem, and first impression were evaluated via the Fitzpatrick Wrinkle Assessment Scale, Global Aesthetic Improvement Scale, Skin Quality Assessment, Heatherton & Polivy State Self-Esteem Scale, Subject Satisfaction Scale, and the First Impressions Questionnaire. ■ RESULTS: Both treatment groups experienced significant improvements in the Skin Quality Assessment, Fitzpatrick Wrinkle Assessment Scale, Heatherton and Polivy State Self-Esteem Scale, and First Impressions Questionnaire. ■ CONCLUSION: The cosmeceutical therapies used in this study in combination with abobotulinumtoxinA and hyaluronic acid filler improved subjects' skin quality, self-esteem, and projected first impressions. Larger studies are needed to determine the most efficacious combination of topical skin therapies with facial rejuvenation therapy. Article Title: Hyaluronic acid-cross-linked filler stimulates collagen type 1 and elastic fiber synthesis in skin through the TGF-β/Smad signaling pathway in a nude mouse model.
Date & Journal: J Plast Reconstr Aesthet Surg. 2019 Apr 11
■ Compared to pure hyaluronic acid filler, cross-linked hyaluronic acid (HAc) exhibits superior biocompatibility and longevity as a dermal filler. We previously developed composite HAc- hydroxyapatite (HAp) fillers. Herein, we systematically compared the protein-level increase and gene expression between HAc-micro-HAp and HAc-nano-HAp in mice and determined the mechanisms underlying the biological responses to HAc and HAp. Five-week-old female BALB/ c-nude mice were classified into five groups: normal skin, Radiesse, Restylane, HAc-nano-HAp, and HAc-micro-HAp. Fillers (200 μl) were injected to evenly fill the back of mice. Skin biopsies were performed to investigate collagen and elastic fiber synthesis after filler injections. Western blot analysis, real-time polymerase chain reaction analysis, and immunohistochemistry were performed to investigate protein and gene expression changes. Organ (liver, lung, spleen, and kidney) toxicity of HAc-nano-HAp was determined by hematoxylin and eosin staining after 12 weeks. Protein and gene expression analyses indicated that, compared with pure fillers, HAc- nano-HAp and HAc-micro-HAp hydrogels preferentially promoted collagen and elastic fiber formation through the TGF-β pathway. The composite fillers also exhibited no evidence of organ toxicity. HAc-HAp filler might play an important role in collagen and elastic fiber regeneration. HAc filler stimulates collagen type 1 and elastic fiber synthesis through the TGF-β/Smad pathway. The role of HAc-HAp composite fillers in photoaging in animal models and their effects on skin, including elasticity and tensile strength, should be investigated. Article Title: A comparative study of the epiligament of the medial collateral and the anterior cruciate ligament in the human knee. Immunohistochemical analysis of collagen type I and V and procollagen type III.
Date & Journal: Ann Anat. 2019 Apr 22
■ BACKGROUND:Recent reports in rat models have shown that fibroblasts in the epiligament, an enveloping tissue of the ligament, are not static cells and play an important role during the early ligament healing of isolated grade III injury of the collateral ligaments of the knee. Fibroblasts produce collagen types I, III and V and infiltrate within the ligament body via the endoligament. In addition, similarities have been reported between the structure of the epiligament of the medial collateral ligament and anterior cruciate ligament of the knee in rat and in human. In line with the ascribed role of the epiligament tissue and the synthesis of these collagens and their role in ligament healing, the aim of this study was to determine their presence in the normal epiligament of the aforementioned ligaments in humans, to compare their differential expression and to present a novel hypothesis about the failure of healing of the anterior cruciate ligament in contrast to the medial collateral ligament. ■ MATERIALS AND METHODS:We used samples from the mid-substance of the medial collateral and the anterior cruciate ligament of the knee joint, acquired from 12 fresh knee joints. Routine histological analysis was performed through hematoxylin and eosin stain, Mallory's trichrome stain and Van Gieson's stain. The immunohistochemical analysis was conducted using monoclonal antibodies against collagen type I and V and procollagen type III. The number of cells in the epiligament, endoligament and the ligament tissue was assessed quantitatively through a computerized system for image analysis NIS-Elements Advanced Research and Statistica software. ■ RESULTS:Our observations revealed certain differences in the morphology of the epiligament, as well as variations in the expression of the investigated molecules. Expression of collagen type I was mostly low-positive (1+) in the epiligament and positive (2+) in the ligament tissue of both ligaments. Expression of procollagen type III was mostly positive (2+) in the epiligament and ligament tissue of the medial collateral ligament, low-positive (1+) in the epiligament and negative (0) in ligament tissue of the anterior cruciate ligament. Expression of collagen type V was predominantly low-positive (1+) in the epiligament and negative (0) in the ligament tissue of both ligaments. The immunoreactivity for all three molecules was always higher in the epiligament of the medial collateral ligament than that of the anterior cruciate ligament. ■ CONCLUSIONS:The results of our study illustrate for the first time that fibroblasts in the human epiligament are indeed responsible for the synthesis of the main types of collagen participating in the early ligament healing, thus corresponding to previous data of the medial collateral ligament healing in animal models. The differences between the epiligament of the investigated ligaments could add a novel explanation for the failed anterior cruciate ligament healing. Article Title: Hyaluronic acid, a promising skin rejuvenating biomedicine: A review of recent updates and pre-clinical and clinical investigations on cosmetic and nutricosmetic effects.
Date & Journal: Int J Biol Macromol. 2018 Dec ■ Hyaluronic acid (HA) plays multifaceted role in regulating the various biological processes such as skin repairmen, diagnosis of cancer, wound healing, tissue regeneration, anti-inflammatory, and immunomodulation. Owing to its remarkable biomedical and tissue regeneration potential, HA has been numerously employed as one of the imperative components of the cosmetic and nutricosmetic products. The present review aims to summarize and critically appraise recent developments and clinical investigations on cosmetic and nutricosmetic efficacy of HA for skin rejuvenation. A thorough analysis of the literature revealed that HA based formulations (i.e., gels, creams, intra-dermal filler injections, dermal fillers, facial fillers, autologous fat gels, lotion, serum, and implants, etc.) exhibit remarkable anti-wrinkle, anti-nasolabial fold, anti-aging, space-filling, and face rejuvenating properties. This has been achieved via soft tissue augmentation, improved skin hydration, collagen and elastin stimulation, and face volume restoration. HA, alone or in combination with lidocaine and other co-agents, showed promising efficacy in skin tightness and elasticity, face rejuvenation, improving aesthetic scores, reducing the wrinkle scars, longevity, and tear trough rejuvenation. Our critical analysis evidenced that application/administration of HA exhibits outstanding nutricosmetic efficacy and thus is warranted to be used as a prime component of cosmetic products. COLON HEALTH.
This Photo by Unknown Author is licensed under CC BY-SA ■There are three primary Colon reasons for rotting food persisting in the digestive tract: Cleansin We kill our friendly bacteria from an acidic diet. g- Why Acidification of the body decreases enzyme the production. Mucoid plaque from rotting need? food in the intestinal lining halts peristalsis. Transit Time= 3 Meals Only
■Transit time: We’re only supposed to store three meals before a meal comes out(Jensen), but most Americans store nine, twelve, or even more. ■ This increased transit time is irritating to the intestinal lining. We absorb less and less nutrients and we lose more and more water and minerals. Endosc Int Open. 2018 Apr;6(4):E410-E413. doi: 10.1055/s-0043-121985. Epub 2018 Mar 29. COLON CLEANSING PROTOCOL IN CHILDREN: RESEARCH CONDITIONS VS. CLINICAL PRACTICE
■BACKGROUND AND STUDY AIMS: Colon preparation rates are the limiting factor for a successful diagnostic colonoscopy in children. Different colon cleansing protocols have been published for use in children. Unfortunately, the applicability of those published research protocols has not been formally evaluated in routine clinical practice. We investigated the success rate of our previously published colon cleansing protocol as utilized in our clinical practice. ■RESULTS:The success rate of the colon preparation in our clinical practice was similar to the results observed under our research protocol (75 % vs. 73.6 %). Moreover, the total number of stools, stool consistency, and the intubation rate of the terminal ileum were also similar. We concluded, that in our experience, the colon cleansing protocol used under research conditions was effective and appropriate for use in routine clinical practice. ■CONCLUSION:We recommend testing each new protocol under the routine conditions of clinical practice to confirm its applicability for general practitioners. Med Hypotheses. 2017 Oct;108:133143. doi: 10.1016/j.mehy.2017.07.032. Epub 2017 Jul 29.
THE COLON REVISITED OR THE KEY TO WELLNESS, HEALTH AND DISEASE.
The hypothesis being advanced in this paper is that there is a new medical paradigm emerging from the biomedical research carried out in this century, mainly due to the explosion of the so called "omics" and associated techniques. The main idea is that there is a common pathway from wellbeing and health to chronic disease ("chronopathy") and even to death, which comprises following steps: 1) unhealthy diet, sedentary life style and permanent exposition to xenobiotics and all kinds of noxious stimuli;→2) intestinal dysbiosis;→3) alteration of the intestinal mucus layer (especially that of the colon);→4) disruption of the endothelial tight junctions;→5) metabolic endotoxemia+bacterial translocation;→6) inflammation;→7) exacerbation of the enteric nervous system (ENS) and consequent maladaptation and malfunctioning of the colon;→8) epigenetic manifestations;→9) "chronopathy" and premature death. Therefore, in order to maintain a good health or to improve or even reverse chronic diseases in a person, the main outcome to look for is a homeostatic balance of the intestinal microbiota (eubiosis), most of which is located in the colon. Lynn Margulis was one of the main scientists to highlight the importance of the role played by bacteria not only in the origin of all biological species now present on earth, but also on their role in global homeostasis. Bacteria do not rely on other living beings for their existence, while the latter depend completely on the former. Humans are no exemption, and new evidence emerges each day about the pivotal role of intestinal microbiota in human health, disease and, in general, in its wellbeing. The following facts about intestinal microbiota are nowadays generally accepted: there are about 10 times more bacteria in the gut than human cells in every human being; the microbioma is about 100150 times bigger that the human genome, and there is a clear link between intestinal microbiota and many of the most common chronic diseases, from obesity and diabetes to depression and Parkinson disease and different kinds of cancer. The main implication of this theory is that we should become a sort of microbiota farmers, that is, we ought to be more conscious of our intestinal microbiota, take care of it and monitor it permanently. Thus, as part of our good life habits (healthy eating, physical exercise), we should probably undergo periodic seasons of fasting and colon cleansing, as it was common in older times. PLoS One. 2017 Oct 19;12(10):e0186178. doi: 10.1371/journal.pone.0186178. eCollection 2017.
LOW COMPLEXITY MICROBIOTA IN THE DUODENUM OF CHILDREN WITH NEWLY DIAGNOSED ULCERATIVE COLITIS.
BACKGROUND: Inflammatory bowel disease (IBD) is characterized by gut dysbiosis. To date, the large bowel microbiota has been in focus. However, the microbiota of the small intestine may also be of importance, as the small bowel is a site for the induction and control of mucosal immune responses, which can be modulated by constituents of the local microbiota. METHODS: Duodenal fluids were collected during diagnostic workup of treatment naïve children who were suspected of having IBD. The duodenal fluids were analyzed by pyrosequencing (average of 32,000 reads/sample, read length of 500 nucleotides). After diagnosis, the duodenal microbiota of subjects with ulcerative colitis (N = 8) or Crohn's disease (N = 5), and nonIBD controls (N = 8) were compared. RESULTS: Pyrosequencing revealed that the duodenal microbiota of children with ulcerative colitis contained fewer Operational Taxonomic Units (OTUs) per individual than the duodenal microbiota of the controls (P = 0.005). This reduction in richness of the duodenal microbiota was seen for three major phyla: Firmicutes, Actinobacteria, and Bacteroidetes. Several bacterial genera were detected less frequently in the children with ulcerative colitis than in the nonIBD controls, including Collinsella (P = 0.001), Lactobacillus (P = 0.007), and Bacillus (P = 0.007), as well as a nonidentified member of the order Sphingobacteriales (P = 0.007). CONCLUSIONS: In this pilot study, we show that the duodenal microbiota of children with ulcerative colitis exhibits reduced overall richness, despite the fact that the inflammation is primarily localized to the colon. These results should be corroborated in a larger study.
Pain Pract. 2017 Sep 25. doi: 10.1111/papr.12646. ORAL PROLONGED RELEASE OXYCODONE/NALOXONE FOR MANAGING PAIN AND OPIOID INDUCED CONSTIPATION: A REVIEW OF THE EVIDENCE. BACKGROUND: Opioids provide effective relief from moderate to severe pain and should be prescribed as part of a multifaceted approach to pain management when other treatments have failed. Fixed dose oxycodone/naloxone prolonged release tablets (OXN PR) were designed to address the opioid class effect of opioid induced constipation (OIC) by combining the analgesic efficacy of oxycodone with the opioid receptor antagonist, naloxone, which has negligible systemic availability when administered orally. This formulation has abuse deterrent properties, since systemic exposure to naloxone by parenteral administration would antagonise the euphoric effects of oxycodone. METHODS: A literature search was conducted to assess the evidence base for OXN PR to treat moderate to severe pain and its impact on bowel function, based on published clinical trials and observational studies. RESULTS: Extensive data demonstrate that OXN PR provides effective analgesia and clinically relevant improvements in bowel function in patients with OIC and moderate to severe cancer related pain and noncancer pain types such as low back pain, neuropathic pain and musculoskeletal pain. OXN PR has also been found to improve bowel function in patients with OIC refractory to multiple types of laxatives, and improve Parkinson's disease related pain. No unanticipated safety concerns have been reported in elderly patients. CONCLUSIONS: Evidence from clinical trials and observational studies confirms that for selected patients OXN PR significantly improves moderate to severe chronic pain and provides relief from OIC. Treatment should be tailored to individual patients to establish the lowest effective dose. An absence of analgesic ceiling effect was seen across the clinically relevant dose range investigated (≤160/80 mg/day). This article is protected by copyright. All rights reserved. Nutrition
A.Water a.pH, Ionization, Molecular size b.Filtration and nutritional benefits c.Lab Testing of bottled waters for pH & safety Water- A major factor in Cancer
• Fresh water, ice caps, & icebergs contain measurable amounts of toxic chemicals, heavy metals, and other contaminants. • Your cancer risks are directly related to the degree to which your drinking water is polluted. • Recent research indicates that cancer risks from drinking chlorinated/polluted water may be as high as 300%. [1] • Solution: Upgrade your water machines & whole house units.
1. Igram C, Igram C, Igram C. How To Eat Right And Live Longer. Buffalo Grove, IL: Knowledge House Publishers; 2005. Water & Constipation
✓ Up to one half of all Americans have it. ✓ Drinking Chlorinated water = Constipation ✓ Chlorine compounds in tap water kill the helpful good gut bacteria, leading to overgrowth of harmful bacteria, yeasts, or even parasites. ✓ The solution is NOT to drink distilled drinking water, as that increases the excretion of valuable minerals: calcium, silicon, zinc, & selenium. ✓ Solution: Upgrade your water machines & whole house units.
1. Igram C, Igram C, Igram C. How To Eat Right And Live Longer. Buffalo Grove, IL: Knowledge House Publishers; 2005. Water & Bathing
• Water is absorbed and evaporated while taking a shower or bath, but toxic chemicals like chlorine remain. • Another danger: pharmaceutical drugs. Residues of drugs are found in virtually all public water supplies. • Researchers are finding high levels of potent drugs, including estrogenic and psychotropic, genetically engineered drugs found in public water. • For example children are prematurely developing breasts, pubic hair, and men are developing breasts.
1. Igram C, Igram C, Igram C. How To Eat Right And Live Longer. Buffalo Grove, IL: Knowledge House Publishers; 2005. Purifying Your Water- What are your options? ■ Distillation - Water is heated to the points where it becomes steam. The steam along with the other vapors (potentially toxic ones), goes through tubes where it condenses back into water. ■ Reverse Osmosis- takes 3-6 gallons to make 1 gallon of purified water. Only about 10%-25% of the water is actually forced through the membrane producing demineralized water. Models that constantly run waste about 40 gallons a day. ■ Bottled Water- In 2001, the NRDC commissioned an independent lab to test over 1000 bottles of water over a 4 year period. They found that 23% of the bottled water tested WORSE for chemicals and bacteria than did water from the tap. There are NO regulatory agencies for the bottled water industry.
1. Igram C, Igram C, Igram C. How To Eat Right And Live Longer. Buffalo Grove, IL: Knowledge House Publishers; 2005. Solution- Tap Water Purifiers
• Tap water is far from perfect. It contains both useful and harmful elements. However, the harmful elements CAN be removed through an in-house water filtration and purification units. • The best filters: remove toxic substances, including chlorine & toxic hydrocarbons, BUT keep healthy minerals (Ca, Mg, Se)
1. Igram C, Igram C, Igram C. How To Eat Right And Live Longer. Buffalo Grove, IL Knowledge House Publishers; 2005. References
: 1. Salinity Fact Sheet. Southern California salinity Coalition. 2016. Available at: http:// www.socalsalinity.org/pdfs/ SCSCFactSheetonSalinityandWaterS oftenersAugust2009.pdf. Accessed October 17, 2016 What to look for in a whole house water filtration system
• Find a system that uses a pharmaceutical grade of granular-activated carbon filtration - most effective in removing chlorine, & bad odors • A system that is certified in the Quality Water standards • Life Source Whole House System- Pasadena, CA Drinking Water Ionizers http:// www.molecularhydrogenfoundation.org/ studies/ Alkaline - Alkalized/ Ionized water has a negative hydrogen Water charge, oxidation reduction potential (ORP) -Our normal body functions cause a rising oxidation in the body -Alkaline water’s negative ORP counteracts oxidation Benefits of Molecular Hydrogen
■WaterWhat is it? I has the chemical formula H2 — and is composed of two bonded hydrogen atoms and is the smallest molecule in existence. ■ The molecules size enables molecular hydrogen to be dispersed readily in the body and across the blood/ brain barrier. ■ Benefits – More than 1,000 clinical studies done on the benefits of consuming molecular hydrogen – Reducing inflammation – Helping with pain relief – Reducing pain in joints – Decelerating natural aging process – Decreasing muscle fatigue Is Ionized Water the Same as Molecular Hydrogen Water?
Yes! - The ionizer machine uses your water from the tap to be hydrogen- rich alkaline water using a system of filtration and ionization. Example- ACE-13 & UCE-11 have a revolutionary Extreme Molecular hydrogen boost technology that maximizes the hydrogen and antioxidant output. Hydrogen water is an excellent antioxidant because the microscopic size of H2 enables the water to enter the mitochondria of each cell to neutralize free radicals, which are volatile molecules that corrupt other healthy molecules in an attempt to stabilize themselves.
How much Water should we drink?-Half your body weight in oz. per day (minimum!)
■ Half your body weight in oz. of ionized/alkalized water per day can have a curative effect on almost any degenerative process, especially aging! Water = Hydration
•Hydration usually takes 4-8 weeks. If drinking half body weight in oz per day. • Some physicians believe that it is not good to “stress” the kidneys and bladder in this way, making so many trips to the bathroom, etc. Cardiologists correlating high blood pressure with “too much water in the blood” is a huge myth. What to look for in Water Systems
■ Filtration (Carbon Ceramic Fiber Filter) ■ Being able to control the pH/acid/alkalinity ■ Number of plates in the machine (9-11 preferred) ■ Less molecules per cluster ■ Self Cleaning ■ No adding of minerals ■ Lifetime Warranty Solid Mesh Hybrid Plate • Solid plates offer strength, but lack premium electrical distribution. • Since electricity is drawn to edges a solid plate’s electrical current will only be transmitted around the outer edge of the plate. • Edges are key, which is why mesh plates seem ideal; but since they lack durability. • TA Solid/Mesh Hybrid plate was engineered according to Faraday’s electrolysis distribution methods. Alkaline Water Machine New Model as of 8/12/19 ACE-13 Above Counter Extreme Water Ionizer
•13 Platinum- Coated Titanium Plates
•Largest plates and patented solid/ mesh hybrid design •Powerful Dual Filtration System- with TM Ceramic and Carbon Block Filtration
•Customizable LCD Design Display
•First Motion Proximity Sensor Function for Automatic Water Outflow Acidic • Benefits of Acidic Water: • Natural astringent & skin Water cleanser Skin & Hair • Helps clear up bacteria that causes acne are • Soothes the itch & sting of Between insect bites, eczema & psoriasis 4.5 to 5.5 • Removes tooth plaque PH • Improves plant growth Water Studies Water Studies Water Studies Water- References Nutrition
A.Amino Acids a.Definitions b.Amino acids for cardiovascular health c.Nitric oxide production What is an amino acid?
➢Organic compounds that contain an amine and carboxyl which are functional group, along with a side chain (R-group) which make each amino acid different. ➢Building blocks of protein ➢Basis of all life, essential to all metabolic processes Article Title: Glutamine Supplementation Ameliorates Chronic Stress-induced Reductions in Glutamate and Glutamine Transporters in the Mouse Prefrontal Cortex. Date & Journal: Exp Neurobiol. 2019 Apr;28
• Chronic immobilization stress (CIS) induces low levels of glutamate (Glu) and glutamine (Gln) and hypoactive glutamatergic signaling in the mouse prefrontal cortex (PFC), which is closely related to the Glu-Gln cycle. A Gln-supplemented diet ameliorates CIS-induced deleterious changes. Here, we investigated the effects of CIS and Gln supplementation on Glu-Gln cycle-related proteins to characterize the underlying mechanisms. Using the CIS-induced depression mouse model, we examined the expression of 11 proteins involved in the Glu-Gln cycle in the PFC. CIS decreased levels of glutamate transporter 1 (GLT1) and sodium-coupled neutral amino acid transporter (SNAT) 1, SANT2, SNAT3, and SNAT5. Gln supplementation did not affect the non-stressed group but significantly increased GLT1 and SNATs of the stressed group. By immunohistochemical analysis, we confirmed that SNAT1 and SNAT2 were decreased in neurons and GLT1, SNAT3, and SNAT5 were decreased in astrocytes in the medial PFC of the stressed group, but Gln- supplemented diet ameliorated these decrements. Collectively, these results suggest that CIS may cause depressive-like behaviors by decreasing Glu and Gln transportation in the PFC and that a Gln-supplemented diet could prevent the deleterious effects of CIS. Article Title: Dietary Branched-chain Amino Acids Regulate Food Intake Partly through Intestinal and Hypothalamic Amino Acid Receptors in Piglets. Date & Journal: J Agric Food Chem. 2019 May 28
• Strategies to increase feed intake is of great importance for producing more meat in swine production. Intestinal and hypothalamic amino acid receptors are found largely participated in feed intake regulation. The purpose of the current research was to study the function of branched-chain amino acids (BCAAs) supplementation in the regulation of feed intake through sensors which can detect amino acids in piglets. Twenty-four piglets were assigned to four treatments and fed to one of the experimental diets for either short period (Expt. 1) or long period (Expt. 2): normal protein diet (NP, 20.04% CP), reduced-protein diet (RP, 17.05% CP), reduced-protein test diets supplemented with two doses of BCAAs (BCAA1, supplemented with 0.13% L-isoleucine, 0.09% L-leucine and 0.23% L-valine; BCAA2, supplemented with the 150% standardized ileal digestibility BCAAs requirement as recommended by the National Research Council (2012)). In Expt. 1, no differences were observed in feed intake among piglets fed with different diets (P > 0.05). In Expt. 2, when compared with the RP group, feed intake of piglets was significantly increased after sufficient BCAAs was supplemented in the BCAA1 group, which was associated with decreased cholecystokinin (CCK) secretion (P < 0.05), down-regulated expression of type 1 taste receptor 1/3 (T1R1/T1R3) in intestine, as well as increased expression of pro-opiomelanocortin (POMC) and activated general control nonderepressible 2 (GCN2) and eukaryotic initiation factor 2α (eIF2α) in the hypothalamus (P < 0.05). However, feed intake was decreased when the piglets were fed with BCAAs over supplemented diet for unknown reasons. In conclusion, our study confirmed that BCAAs deficit diet inhibited feed intake through two potential ways: regulating amino acid T1R1/T1R3 receptor in the intestine and/or activating GCN2/eIF2α pathways in the hypothalamus. Curr Atheroscler Rep. 2018 Mar 17;20(5):21. doi: 10.1007/s11883-018-0723-0. FUNCTIONAL NITRIC OXIDE NUTRITION TO COMBAT CARDIOVASCULAR DISEASE
■Research over the past decade has revealed that inorganic nitrate and nitrite found naturally in green leafy vegetables and other vegetables such as beets can provide the human body with a source of bioactive nitric oxide. NO is one of the most important molecules produced within the cardiovascular system that maintains normal blood pressure and prevents inflammation, immune dysfunction, and oxidative stress, hallmarks of cardiovascular disease. This pathway is dependent upon the amount of inorganic nitrate and nitrite in the foods we eat, the presence of oral nitrate-reducing bacteria, and sufficient stomach acid production. The concept of food being medicine and medicine being food has lost its place in the practice and implementation of modern medicine over the past century. Certain dietary patterns and specific foods are known to confer very significant protective effects for many human diseases, including cardiovascular disease, the number one killer of men and women in the developed world. However, identification of single or multiple bioactive molecules that are responsible for these effects has escaped scientists and nutritionists for many years. This review will highlight the biochemical, physiological, and epidemiological basis for functional nitric oxide nutrition that can be safely and effectively utilized in patients. Nutrients. 2018 Jul 19;10(7). pii: E925. doi: 10.3390/nu10070925.
COMBINED SUPPLEMENTATION OF PRE-EXERCISE CARBOHYDRATE, ALANINE, AND PROLINE AND CONTINUOUS INTAKE OF GREEN TEA CATECHINS EFFECTIVELY BOOST ENDURANCE PREFORMANCE IN MICE
■Continuous intake of green tea catechins (GTC) increases fatty acid utilization as an energy source and improves endurance capacity. Conversely, the single pre-exercise intake of maltodextrin (MD) as a carbohydrate source and the gluconeogenic amino acids alanine (Ala) and proline (Pro) effectively maintain blood glucose levels and increase endurance performance. In this study, we investigated the synergistic combinational effect of these interventions on endurance performance in mice. Male BALB/c mice were fed a 0.5% GTC diet or Control diet for 8 weeks. Maximum running time was measured every 2 weeks. MD (2 g/kg body weight (B.W.)), MD (1 g/kg B.W.) + AlaPro (9:1, 1 g/kg B.W.), and vehicle were orally administrated 60 mins before measurements in each diet group. The GTC + MD + AlaPro group showed significantly higher endurance performance than the Control-Vehicle group at all measurements. Indirect calorimetry analysis during running exercise at 4 weeks in the Control and GTC groups supplemented with pre-exercise MD + AlaPro administration revealed significantly higher fat oxidation in the GTC groups compared to the Control group. The combined increase in fatty acid utilization through continuous GTC intake and pre-exercise MD + AlaPro carbohydrate energy supplementation synergistically improves endurance capacity. Nutrients. 2018 Jun 25;10(7). pii: E820. doi: 10.3390/nu10070820. WHAT IS THE ROLE OF NUTRITIONAL SUPPLEMENTS IN SUPPORT OF TOATL HIP REPLACEMENT AND TOTAL KNEE REPLACEMENT SURGERIS? A SYSTEMATIC REVIEW
■Nutritional supplements can influence outcomes for individuals undergoing major surgery, particularly in older persons whose functional reserve is limited. Accelerating recovery from total hip replacement (THR) and total knee replacement (TKR) may offer significant benefits. Therefore, we explored the role of nutritional supplements in improving recovery following THR and TKR. A systematic review was conducted to source randomized clinical trials that tested nutritional supplements in cohorts of THR or TKR patients. Our search yielded nine relevant trials. Intake of a carbohydrate-containing fluid is reported to improve insulin-like growth factor levels, reduce hunger, nausea, and length of stay, and attenuate the decrease in whole-body insulin sensitivity and endogenous glucose release. Amino acid supplementation is reported to reduce muscle atrophy and accelerate return of functional mobility. One paper reported a suppressive effect of beta-hydroxy beta-methylbutyrate, L-arginine, and L-glutamine supplementation on muscle strength loss following TKR. There is limited evidence for nutritional supplementation in THR and TKR pathways; however, the low risk profile and potential benefits to adjunctive treatment methods, such as exercise programs, suggest nutritional supplements may have a role. Optimizing nutritional status pre-operatively may help manage the surgical stress response, with a particular benefit for undernourished, frail, or elderly individuals. Pharmacol Ther. 2013 Dec;140(3):239-57. doi: 10.1016/j.pharmthera.2013.07.004. Epub 2013 Jul 13.
NITRIC OXIDE SYNTHASE INHIBITION AND OXIDATIVE STRESS IN CARDIOVASCULAR DISEASES: POSSIBLE THERAPEUTIC TARGETS?
Nitric oxide (NO) is synthetized enzymatically from l-arginine (l-Arg) by three NO synthase isoforms, iNOS, eNOS and nNOS. The synthesis of NO is selectively inhibited by guanidino-substituted analogs of l-Arg or methylarginines such as asymmetric dimethylarginine (ADMA), which results from protein degradation in cells. Many disease states, including cardiovascular diseases and diabetes, are associated with increased plasma levels of ADMA. The N-terminal catalytic domain of these NOS isoforms binds the heme prosthetic group as well as the redox cofactor, tetrahydrobiopterin (BH(4)) associated with a regulatory protein, calmodulin (CaM). The enzymatic activity of NOS depends on substrate and cofactor availability. The importance of BH(4) as a critical regulator of eNOS function suggests that BH(4) may be a rational therapeutic target in vascular disease states. BH(4) oxidation appears to be a major contributor to vascular dysfunction associated with hypertension, ischemia/reperfusion injury, diabetes and other cardiovascular diseases as it leads to the increased formation of oxygen-derived radicals due to NOS uncoupling rather than NO. Accordingly, abnormalities in vascular NO production and transport result in endothelial dysfunction leading to various cardiovascular disorders. However, some disorders including a wide range of functions in the neuronal, immune and cardiovascular system were associated with the over-production of NO. Inhibition of the enzyme should be a useful approach to treat these pathologies. Therefore, it appears that both a lack and excess of NO production in diseases can have various important pathological implications. In this context, NOS modulators (exogenous and endogenous) and their therapeutic effects are discussed. Neurol Sci. 2017 Jul;38(7):1287-1291. doi: 10.1007/s10072-017-2970-1. Epub 2017 Apr 28. HIGH ASYMMETRIC DIMETHYLARGININE, SYMMETRIC DIMETHYLARGININE AND L-ARGININE LEVELS IN MIGRAINE PATIENTS.
Experimental and clinical data strongly suggests that nitric oxide (NO) plays a pivotal role in migraine. This is also supported by studies of migraine induced by substances that release NO. NO is synthesized from L-arginine by endothelial NO synthase (NOS). Asymmetric dimethylarginine (ADMA) is the major endogenous competitive inhibitor of NOS. Symmetric dimethylarginine (SDMA) is an inactive stereoisomer of ADMA. It may reduce NO production by competing with arginine for cellular uptake. The aim of this study was to measure the levels of ADMA, SDMA and L-arginine in migraine patients during the interictal period. One hundred migraine patients and 100 healthy volunteers were recruited. The patients were in the interictal period and classified into two groups as having migraine with aura and migraine without aura. Their serum ADMA, SDMA and L-arginine levels were measured by high-performance liquid chromatography (HPLC) method. ADMA, SDMA and L-arginine levels were significantly higher in migraine patients compared to the control group. But there was no difference between the patients with and without aura. These results suggest that NOS inhibitors and L-arginine/NO pathway plays an important role in migraine pathophysiology. Title: Functional Nitric Oxide Nutrition to Combat Cardiovascular Disease
Purpose of review: To reveal the mechanisms of nitric oxide (NO) production in humans and how lifestyle, drug therapy, and hygienic practices can decrease NO production. Furthermore, to show how functional nitric oxide nutrition can overcome these limitations to restore endogenous NO production and combat cardiovascular disease.
Recent findings: Research over the past decade has revealed that inorganic nitrate and nitrite found naturally in green leafy vegetables and other vegetables such as beets can provide the human body with a source of bioactive nitric oxide. NO is one of the most important molecules produced within the cardiovascular system that maintains normal blood pressure and prevents inflammation, immune dysfunction, and oxidative stress, hallmarks of cardiovascular disease. This pathway is dependent upon the amount of inorganic nitrate and nitrite in the foods we eat, the presence of oral nitrate-reducing bacteria, and sufficient stomach acid production. The concept of food being medicine and medicine being food has lost its place in the practice and implementation of modern medicine over the past century. Certain dietary patterns and specific foods are known to confer very significant protective effects for many human diseases, including cardiovascular disease, the number one killer of men and women in the developed world. However, identification of single or multiple bioactive molecules that are responsible for these effects has escaped scientists and nutritionists for many years. This review will highlight the biochemical, physiological, and epidemiological basis for functional nitric oxide nutrition that can be safely and effectively utilized in patients.
Bryan NS. Functional Nitric Oxide Nutrition to Combat Cardiovascular Disease. Curr Atheroscler Rep. 2018;20(5):21. Published 2018 Mar 17. doi:10.1007/s11883-018-0723-0
Nutrition
A.Immune System Research a.Resent studies from the NIH/PubMed Title : [Anti-virus Research of Triterpenoids in Licorice]
Abstract
Licorice is a leguminous plant of glycyrrhiza. It is a traditional Chinese herbal medicine. Triterpenoid is one of the mainly active components of licorice. In recent years, the broad-spectrum antiviral activity of many triterpenoids in licorice was confirmed, and these findings have become a hot spot of antiviral immunity. The triterpenoids of licorice has the potential to become a novel broad-spectrum antiviral medicine and will be widely used in the clinical treatment. This review provided a summary of the recent anti-virus research progress on several triterpenoids in licorice, such as glycyrrhizic acid, glycyrrhizin, glycyrrhetinic acid and its derivatives. The antiviral roles of triterpenoids in licorice against herpes virus, HIV, hepatitis virus, SARS coronavirus and influenza virus were briefly summarized.
Source: Bing Du Xue Bao. 2013 Nov;29(6):673-9. Title :Effect of mushroom Agaricus blazei on immune response and development of experimental cerebral malaria
Background: Cerebral malaria (CM) is debilitating and sometimes fatal. Disease severity has been associated with poor treatment access, therapeutic complexity and drug resistance and, thus, alternative therapies are increasingly necessary. In this study, the effect of the administration of Agaricus blazei, a mushroom of Brazilian origin in a model of CM caused by Plasmodium berghei, strain ANKA, was investigated in mice.
Results: Mice treated with A. blazei aqueous extract or fraction C, that shows antioxidant activity, displayed lower parasitaemia, increased survival, reduced weight loss and protection against the development of CM. The administration of A. blazei resulted in reduced levels of TNF, IL-1β and IL-6 production when compared to untreated P. berghei-infected mice. Agaricus blazei (aqueous extract or fraction C) treated infected mice displayed reduction of brain lesions. Although chloroquine treatment reduced parasitaemia, there was increased production of proinflammatory cytokines and damage in the CNS not observed with A. blazei treatment. Moreover, the in vitro pretreatment of infected erythrocytes followed by in vivo infection resulted in lower parasitaemia, increased survival, and little evidence of clinical signs of disease.
Conclusions: This study strongly suggests that the administration of A. blazei (aqueous extract or fraction C) was effective in improving the consequences of CM in mice and may provide novel therapeutic strategies.
Val, C.H., Brant, F., Miranda, A.S. et al. Effect of mushroom Agaricus blazei on immune response and development of experimental cerebral malaria. Malar J 14, 311 (2015). https://doi.org/10.1186/s12936-015-0832-y Title :Low-molecular-weight Polysaccharides From Agaricus blazei Murrill Modulate the Th1 Response in Cancer Immunity Abstract
To assess the effect of low-molecular-weight polysaccharides from Agaricus blazei Murrill (ABP-AW1) as an immunoadjuvant therapy for type 1 T-helper (Th1) responses in tumorigenesis, C57BL/6 mice were inoculated subcutaneously with ovalbumin (E.G7-OVA). After 3, 10 and 17 days, the mice were immunized with PBS, OVA alone, or OVA and ABP-AW1, at low (50 µg), intermediate (100 µg) or high (200 µg) doses. Tumor growth was examined and compared among the groups, as were the following parameters: Splenocyte viability/proliferation, peripheral blood CD4+/CD8+ T cell ratio, serum OVA-specific IgG1 and IgG2b, secretion of interleukin (IL)-2 and interferon (IFN)-γ, and IFN-γ production on a single cell level from cultured splenocytes. Tumor growth in mice treated with OVA and ABP-AW1 (100 or 200 µg) was significantly slower, compared with in the other groups at the same time-points. OVA with 100 or 200 µg ABP-AW1 was associated with a higher number of total splenocytes, a higher ratio of peripheral blood CD4+/CD8+ T- lymphocytes, higher serum levels of OVA-specific Th1-type antibody IgG2b and greater secretion of the Th1 cytokines IL-1 and IFN-γ from splenocytes. ABP-AW1 is a promising immunoadjuvant therapy candidate, due to its ability to boost the Th1 immune response when co-administered with a cancer vaccine intended to inhibit cancer progression.
Jiang L, Yu Z, Lin Y, et al. Low-molecular-weight polysaccharides from Agaricus blazei Murrill modulate the Th1 response in cancer immunity. Oncol Lett. 2018;15(3):3429‐3436. doi:10.3892/ol.2018.7794 Title :Antitumor Activity of Orally Administered Maitake α-Glucan by Stimulating Antitumor Immune Response in Murine Tumor Abstract
Maitake α-glucan, YM-2A, isolated from Grifola frondosa, has been characterized as a highly α-1,6-branched α-1,4 glucan. YM-2A has been shown to possess an anti-virus effect in mice; however, it does not directly inhibit growth of the virus in vitro, indicating that the anti-virus effect of YM-2A might be associated with modulation of the host immune system. In this study, we found that oral administration of YM-2A could inhibit tumor growth and improve survival rate in two distinct mouse models of colon-26 carcinoma and B16 melanoma. Orally administered YM-2A enhanced antitumor immune response by increasing INF-γ-expressing CD4+ and CD8+ cells in the spleen and INF-γ-expressing CD8+ cells in tumor-draining lymph nodes. In vitro study showed that YM-2A directly activated splenic CD11b+ myeloid cells, peritoneal macrophages and bone marrow-derived dendritic cells, but did not affect splenic CD11b- lymphocytes or colon-26 tumor cells. YM-2A is more slowly digested by pancreatic α-amylase than are amylopectin and rabbit liver glycogen, and orally administered YM-2A enhanced the expression of MHC class II and CD86 on dendritic cells and the expression of MHC class II on macrophages in Peyer's patches. Furthermore, in vitro stimulation of YM-2A increased the expression of pro-inflammatory cytokines in Peyer's patch CD11c+ cells. These results suggest that orally administered YM-2A can activate dendritic cells and macrophages in Peyer's patches, inducing systemic antitumor T-cell response. Thus, YM-2A might be a candidate for an oral therapeutic agent in cancer immunotherapy.
Masuda Y, Nakayama Y, Tanaka A, Naito K, Konishi M. Antitumor activity of orally administered maitake α-glucan by stimulating antitumor immune response in murine tumor. PLoS One. 2017;12(3):e0173621. Published 2017 Mar 9. doi: 10.1371/journal.pone.0173621 Title :Antigenotoxic and Antioxidant Potential of Medicinal Mushrooms (Immune Assist) Against DNA Damage Induced by Free Radicals-An in Vitro Study Abstract
Immune Assist (IA) is produced from extract of six species of medical mushrooms: Agaricus blazei - Cordyceps sinensis - Grifola frondosa - Ganoderma lucidum - Coriolus versicolor - Lentinula edodes. The genoprotective potential of IA was evaluated for the first time. Significant antigenotoxic effects were detected in human peripheral blood cells against H2O2 induced DNA damage, in the pretreatment and in the posttreatment. The most efficient concentration of IA in pretreatment was 500 μg/mL, while in posttreatment it was the concentration of 250 μg/mL. Kinetics of attenuation of H2O2 induced DNA damage in posttreatment with the optimal concentration of IA showed significant decrease in the number of damaged cells at all time periods (15-60 min), reaching the greatest reduction after 15 and 45 min. Remarkable ·OH scavenging properties and moderate reducing power, together with the modest DPPH scavenging activity, could be responsible for the great attenuation of DNA damage after 15 min of exposure to IA, while reduction of DNA damage after 45 min could be the result in additional stimulation of the cell's repair machinery. Our results suggest that IA displayed antigenotoxic and antioxidant properties. A broader investigation of its profile in biological systems is needed.
Živković L, Bajić V, Bruić M, et al. Antigenotoxic and antioxidant potential of medicinal mushrooms (Immune Assist) against DNA damage induced by free radicals-an in vitro study. Mutat Res. 2019;845:403078. doi:10.1016/ j.mrgentox.2019.06.008 Title :Impact of Ingestion of Rice Bran and Shitake Mushroom Extract on Lymphocyte Function and Cytokine Production in Healthy Rats
Abstract
This article provides a controlled evaluation of the ability of dietary supplementation with a commercially available rice bran extract modified with shitake mushroom extract (MGN-3) to support the immune function by assessing the ability of immunocytes to proliferate and produce cytokines in response to a mitogenic challenge. Twenty-four male Lewis rats were fed a control diet (Maypo sweetened oatmeal) or Maypo containing the recommended daily dose of MGN-3 for 2 weeks. This treatment modestly enhanced mitogen enhanced proliferation of splenocytes and interferon-gamma (IFN-g) production, and significantly increased proliferation of splenocytes to the superantigen toxic shock syndrome toxin-1 (TSST-1) as well as natural killer (NK) cell activity and production of interleukin-2 (IL-2) by stimulated lymphocytes. These data support the contention that ingestion of MGN-3 can support immune cell function. These data add to a growing body of data showing that ingestion of MGN-3 improves the ability of immune cells to proliferate the lyse tumor cells, suggesting that it may have utility as a dietary aid to support the immune system.
Giese S, Sabell GR, Coussons-Read M. Impact of ingestion of rice bran and shitake mushroom extract on lymphocyte function and cytokine production in healthy rats. J Diet Suppl. 2008;5(1):47‐61. doi: 10.1080/19390210802329196 Title :A Multiherbal Formulation Influencing Immune Response in Vitro Abstract
Aim: Aim of this study was to evaluate the effects of phytocomplexes of Uncaria, Shiitake and Ribes in terms of viability and inflammatory response on immune cell-derived cultures.
Results: Cell viability was not affected by extracts, except subtle variations observed only at higher doses (>250 µg/mL). The extract mixture was well tolerated, with no effects on cell viability up to doses of 500 µg/mL. Pre-treatment of macrophages with subtoxic doses of the extracts reduced the basal release of oxidative markers and enhanced the cell response to exogenous oxidant stimulation, as revealed by ROS and PGE2 release reduction. The same treatment on macrophage resulted in a selective modulation of the immune response, as shown by an increase of IL-6 mRNA and, partially, IL-8 mRNA, while a reduction was observed for TNFα mRNA.
Conclusion: Data confirm that extracts and their formulations can act as regulator of the immune system with mechanisms involving the oxidative stress and the release of selected proinflammatory cytokines.
Menghini L, Leporini L, Scanu N, et al. A multiherbal formulation influencing immune response in vitro. Minerva Med. 2012;103(1):13‐21. Title :The Effect of Olive Leaf Extract on Upper Respiratory Illness in High School Athletes: A Randomised Control Trial Abstract
Upper respiratory illness (URI) has a major impact on both training and competition in an athletic setting. High school athletes are a sub-category who have reported higher illness rates than professional and sub- elite high school athletes of the same sport. Olive leaf extract (OLE) is an over-the-counter supplement that contains polyphenols, notably oleuropein and hydroxytyrosol, that have antiviral, antibacterial, anti- inflammatory and antioxidant properties that may reduce URI rates. Thirty-two high school students who play sport for the elite team at their school were recruited to a randomised controlled trial and allocated to a daily placebo or OLE (extent equivalent to 20 g of olive leaf, containing 100 mg oleuropein) supplementation for nine weeks during their competitive season. Twice weekly measures of wellbeing, training load and respiratory illness (sporting upper respiratory illness (SUPPRESS) questionnaire) were recorded at trainings, meetings or games. There was no significant difference in illness incidence (odds ratio (OR): 1.02 (95% confidence interval (CI) 0.21⁻4.44)), but there was a significant 28% reduction in sick days (OR: 0.72 (95% CI 0.56⁻0.93) p-value = 0.02) when supplemented with OLE. The dietary intakes of the athletes were sub- optimal with regard to immune support. OLE supplementation over a season did not significantly reduce URI incidence, but did decrease duration in high school athletes, potentially aiding return to play.
Somerville V, Moore R, Braakhuis A. The Effect of Olive Leaf Extract on Upper Respiratory Illness in High School Athletes: A Randomised Control Trial. Nutrients. 2019;11(2):358. Published 2019 Feb 9. doi:10.3390/nu11020358 Title :New Semi-Synthetic Analogs of Oleuropein Show Improved Anticancer Activity in Vitro and in Vivo Abstract
Oleuropein is a glucosylated seco-iridoid present in olive fruits and leaves. Due to its broad spectrum of biological activities, including anticancer properties, oleuropein has attracted scientific attention for the past 20 years. The promising antiproliferative activity of an olive leaf extract enriched in oleuropein against a series of human cancer cell lines, prompted us to proceed with the semi-synthesis of 51 analogs of oleuropein. Following their initial screening against the estrogen receptor negative breast cancer cell line SKBR3, 7 analogs were shown to display significant cytotoxicity and were further tested against 6 additional solid tumor-derived and leukemic cell lines. The analog with the most promising antitumor activity (24) was selected for more detailed studies. 24 was non-toxic to peripheral blood mononuclear cells derived from healthy blood donors when tested at concentrations close to its half maximal inhibitory concentration. In vivo administration of 24 in melanoma-bearing mice resulted in reducing tumor size in a dose-dependent manner and in inducing anti-melanoma-reactive immune responses. Our results suggest that analog 24, emerging from the initial structure of oleuropein, represents a promising lead structure for further optimization.
Samara P, Christoforidou N, Lemus C, et al. New semi-synthetic analogs of oleuropein show improved anticancer activity in vitro and in vivo. Eur J Med Chem. 2017;137:11‐29. doi:10.1016/j.ejmech.2017.05.029 Title :Olive Leaf Extracts Act as Modulators of the Human Immune Response
Abstract
Background: Olive tree leaves have been used in the Mediterranean area as traditional medicine in virtue of their healthy effects. Olive leaf extracts (OLEs) contain higher amounts of polyphenols than those detected in the extra virgin olive oil and fruit. Several lines of evidence support the cardioprotective, anti-oxidant and anti-inflammatory activities exerted by OLEs.
Results: Both extracts, but especially extract A, increased absolute numbers of CD8+ and natural killer (NK) cells. In addition, an increased production of interferon (IFN)-γ by both extracts as an expression of T helper (h)1 activation was observed. Finally, both extracts enhanced NO release.
Conclusion: OLEs, and mostly extract A, are able to in vitro modify healthy human immune response by increasing IFN-γ production which seems to be associated to the higher absolute numbers of CD8+ and NK cells and this may suggest a reinforcement of the anti-tumor activity. Furthermore, increased levels of NO may indicate the potential cardioprotective effects exerted by OLEs in virtue of their vasodilation dependent activity. Finally, OLEs are able to maintain the equilibrium between T regulatory cells and Th17 cells as evidenced by unmodified levels of interleukin (IL)-IL-10 and IL-17, respectively. In the light of these results, OLEs are potential therapeutic compounds for the treatment of chronic inflammatory disease, also preventing cardiovascular event outcome.
Magrone T, Spagnoletta A, Salvatore R, et al. Olive Leaf Extracts Act as Modulators of the Human Immune Response. Endocr Metab Immune Disord Drug Targets. 2018;18(1):85‐93. doi:10.2174/1871530317666171116110537 Title :Efficacy of Andrographis Paniculata Supplements Induce a Non-Specific Immune System Against the Pathogenicity of Aeromonas Hydrophila Infection in Indian Major Carp (Labeo Rohita) Abstract
Aeromonas hydrophila, an opportunistic fish pathogen, which causes several major diseases including skin ulcer and haemorrhagic septicemia, contributes considerably to the lethality in aquaculture. Chemical and antibiotic treatment employed against A. hydrophila for disease management are expensive and consequently prompted the advent of drug resistance among the pathogens. To overcome these draw backs, alternative aquatic disease control methods using conventional plant-based medicines are focussed. Our present study aimed to augment the fish non-specific immune system with the implementation of methanolic crude extracts of Andrographis paniculata to Labeo rohita, for evaluating their efficacy against A. hydrophila. Histology of major organs of A. hydrophila-infected fish such as the gills and liver displayed severe tissue damage. A. paniculata extracts exhibited the strong antibacterial activity against A. hydrophila even at lower concentrations (50 μl). The extracts also altered the haematological profile of treated infected fishes by increasing the levels of haemoglobin and total erythrocyte-leucocyte counts, along with the phagocytic index. The extracts also had a significant impact on modifying the anatomy and swimming pattern of infected fish, post treatment with the extracts. Also, A. paniculata treated infected fishes in all the plant extract administration methods, viz. injection, oral feeding and diffusion, and reduced the cumulative mortality rate to less than 30%. Even lower concentrations of A. paniculata extracts (50 μl) resulted in maximum relative percentage survival of treated fishes. Therefore, our findings suggest that A. paniculata was effective against A. hydrophila infection in aquaculture, thereby maintaining a healthy status of these fishes in aquaculture.
Palanikani R, Chanthini KM, Soranam R, et al. Efficacy of Andrographis paniculata supplements induce a non-specific immune system against the pathogenicity of Aeromonas hydrophila infection in Indian major carp (Labeo rohita) [published online ahead of print, 2019 Jul 30]. Environ Sci Pollut Res Int. 2019;10.1007/s11356-019-05957-7. doi: 10.1007/s11356-019-05957-7 Title :Multiple Modulatory Activities of Andrographis Paniculata on Immune Responses and Xenograft Growth in Esophageal Cancer Preclinical Models Abstract
Background: Esophageal cancer (EC) is a malignant gastrointestinal cancer with high morbidity worldwide and is the fourth leading cause of cancer-related deaths in China. Even though surgery and/or chemotherapy/chemoradiation might achieve good therapeutic response, recurrence rate is high due to cancer metastasis. Hence, the use of alternative adjuvant treatments, such as herbal medicines, for metastatic EC remains a great desire of the patients. Our previous studies have demonstrated the anti-metastatic efficacy of hot water extract of Andrographis paniculata (APW) in human esophageal cancer cells and tumor-bearing nude mice.
Conclusion: APW was shown to possess anti-tumor, anti-metastatic and immunomodulatory activities in esophageal cancer cell-based and animal models, including immunocompromised mice model and clinically relevant PDX model. Our findings illustrated the potential multi-targeted efficacies of APW in esophageal cancer management.
Yue GG, Li L, Lee JK, et al. Multiple modulatory activities of Andrographis paniculata on immune responses and xenograft growth in esophageal cancer preclinical models. Phytomedicine. 2019;60:152886. doi:10.1016/j.phymed. 2019.152886 Title: Critical Care Management of Adults With Community-Acquired Severe Respiratory Viral Infection
Abstract
With the expanding use of molecular assays, viral pathogens are increasingly recognized among critically ill adult patients with community-acquired severe respiratory illness; studies have detected respiratory viral infections (RVIs) in 17-53% of such patients. In addition, novel pathogens including zoonotic coronaviruses like the agents causing Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS) and the 2019 novel coronavirus (2019 nCoV) are still being identified. Patients with severe RVIs requiring ICU care present typically with hypoxemic respiratory failure. Oseltamivir is the most widely used neuraminidase inhibitor for treatment of influenza; data suggest that early use is associated with reduced mortality in critically ill patients with influenza. At present, there are no antiviral therapies of proven efficacy for other severe RVIs. Several adjunctive pharmacologic interventions have been studied for their immunomodulatory effects, including macrolides, corticosteroids, cyclooxygenase-2 inhibitors, sirolimus, statins, anti- influenza immune plasma, and vitamin C, but none is recommended at present in severe RVIs. Evidence-based supportive care is the mainstay for management of severe respiratory viral infection. Non-invasive ventilation in patients with severe RVI causing acute hypoxemic respiratory failure and pneumonia is associated with a high likelihood of transition to invasive ventilation. Limited existing knowledge highlights the need for data regarding supportive care and adjunctive pharmacologic therapy that is specific for critically ill patients with severe RVI. There is a need for more pragmatic and efficient designs to test different therapeutics both individually and in combination.
Arabi YM, Fowler R, Hayden FG. Critical care management of adults with community-acquired severe respiratory viral infection. Intensive Care Med. 2020;46(2):315‐328. doi:10.1007/s00134-020-05943-5 Title: Platelet-to-lymphocyte Ratio Is Associated With Prognosis in Patients With Coronavirus disease-19
Abstract
Since December 2019, novel coronavirus infected pneumonia emerged in Wuhan city and rapidly spread throughout China. In severe novel coronavirus pneumonia cases, the number of platelets, their dynamic changes during the treatment, platelet-to- lymphocyte ratio (PLR) were a concern. We sought to describe the platelet feature of these cases. Single-center case series of the 30 hospitalized patients with confirmed coronavirus disease (COVID)-19 in Huizhou municipal central hospital from January 2020 to February 2020 were retrospectively analyzed. Demographic, clinical, blood routine results, other laboratory results, and treatment data were collected and analyzed. Outcomes of severe patients and nonsevere patients were compared. Univariate analysis showed that: age, platelet peaks, and PLR at peak platelet were the influencing factors in severe patients, multivariate analysis showed that the PLR value at peak platelet during treatment was an independent influencing factor in severe patients. The average hospitalization day of patients with platelet peaks during treatment was longer than those without platelet peaks (P < .05). The average age of patients with platelet peaks during treatment was older than those without platelet peaks (P < .05). The patients with significantly elevated platelets during treatment had longer average hospitalization days. And the higher PLR of patients during treatment had longer average hospitalization days. Single-center case series of the 30 hospitalized patients with confirmed COVID-19 in Huizhou Municipal Central Hospital, presumed that the number of platelets and their dynamic changes during the treatment may have a suggestion on the severity and prognosis of the disease. The patient with markedly elevated platelets and longer average hospitalization days may be related to the cytokine storm. The PLR of patients means the degree of cytokine storm, which might provide a new indicator in the monitoring in patients with COVID-19.
Qu R, Ling Y, Zhang YH, et al. Platelet-to-lymphocyte ratio is associated with prognosis in patients with coronavirus disease-19 [published online ahead of print, 2020 Mar 17]. J Med Virol. 2020;10.1002/jmv.25767. doi:10.1002/jmv. 25767 Title: Estimating the Asymptomatic Proportion of Coronavirus Disease 2019 (COVID-19) Cases on Board the Diamond Princess Cruise Ship, Yokohama, Japan, 2020
Abstract
On 5 February 2020, in Yokohama, Japan, a cruise ship hosting 3,711 people underwent a 2-week quarantine after a former passenger was found with COVID-19 post-disembarking. As at 20 February, 634 persons on board tested positive for the causative virus. We conducted statistical modelling to derive the delay-adjusted asymptomatic proportion of infections, along with the infections' timeline. The estimated asymptomatic proportion was 17.9% (95% credible interval (CrI): 15.5-20.2%). Most infections occurred before the quarantine start.
Mizumoto K, Kagaya K, Zarebski A, Chowell G. Estimating the asymptomatic proportion of coronavirus disease 2019 (COVID-19) cases on board the Diamond Princess cruise ship, Yokohama, Japan, 2020. Euro Surveill. 2020;25(10): 2000180. doi:10.2807/1560-7917.ES.2020.25.10.2000180 Title: Guide to the Forensic Pathology Practice on Death Cases Related to Corona Virus Disease 2019 COVID-19
Abstract
Autopsy is of great significance to the elucidation of the pathological changes, pathogeneses and causes of death of corona virus disease 2019 COVID-19 and can provide theoretical basis for more scientific and accurate prevention and control of the outbreak. Based on related laws and regulations, such as the Law of the People's Republic of China on Prevention and Control of Infectious Diseases, the clinical manifestations and epidemiological characteristics of COVID-19, and the related guidelines on the prevention and control of the outbreak, combined with the practical work of forensic pathology examination, the Guide to the Forensic Pathology Practice on Death Cases Related to Corona Virus Disease 2019 COVID-19 Trial Draft has been developed. This guide includes information on the background investigation of the cases, autopsy room requirements, personal prevention and protections, external examinations, autopsy, auxiliary examinations, and so on. This guide can be used as a reference by forensic and pathological examination institutions, as well as examination staff.
Mao DM, Zhou N, Zheng D, et al. Guide to the Forensic Pathology Practice on Death Cases Related to Corona Virus Disease 2019 COVID-19 Trial Draft. Fa Yi Xue Za Zhi. 2020;36(1):6‐5. doi:10.12116/j.issn. 1004-5619.2020.01.003 Title: Review and Prospect of Pathological Features of Corona Virus Disease
Abstract
Since 2003, coronavirus has caused multiple major public health events that resulted in global epidemics, such as severe acute respiratory syndrome SARS , Middle East respiratory syndrome MERS and corona virus disease 2019 COVID-19 . Especially since COVID-19 outbroke in Wuhan, Hubei, in December 2019, coronavirus has had a significant impact on people's health and lives. But so far, the pathological diagnosis of COVID-19 has been relatively deficient it is still confined to the pathological findings of punctured organs, and the majority of medical workers have poor awareness of its pathological characteristics. The COVID-19, as same as SARS and MERS, is caused by coronaviruses and can cause viral pneumonia. They have certain similarities. This article comprehensively reviews the pathological features observed in the autopsies of the aforementioned three diseases, in order to provide reference to the analysis of pathological changes of COVID-19.
Wang HJ, Du SH, Yue X, Chen CX. Review and Prospect of Pathological Features of Corona Virus Disease. Fa Yi Xue Za Zhi. 2020;36(1):16‐20. doi:10.12116/j.issn.1004-5619.2020.01.004 Title: The Effect of Ascorbic Acid on Infection Chick-Embryo Ciliated Tracheal Organ Cultures by Coronavirus
Abstract
Chick embryo tracheal organ cultures showed increased resistance to infection by a coronavirus after exposure to ascorbate, while chick respiratory epithelium and allantois-on-shell preparations showed no increase in resistance to infection by an influenza virus or a paramyxovirus.
Atherton JG, Kratzing CC, Fisher A. The effect of ascorbic acid on infection chick-embryo ciliated tracheal organ cultures by coronavirus. Arch Virol. 1978;56(3):195‐199. doi:10.1007/BF01317848 Title: Vitamin C and SARS Coronavirus
Sir,
Recently, a new coronavirus was identified as the cause of the severe acute respiratory syndrome (SARS).1 In the absence of a specific treatment for SARS, the possibility that vitamin C may show non-specific effects on severe viral respiratory tract infections should be considered. There are numerous reports indicating that vitamin C may affect the immune system,2,3 for example the function of phagocytes, transformation of T lymphocytes and production of interferon. In particular, vitamin C increased the resistance of chick embryo tracheal organ cultures to infection caused by an avian coronavirus.4 Studies in animals found that vitamin C modifies susceptibility to various bacterial and viral infections,3 for example protecting broiler chicks against an avian coronavirus.5 Placebo-controlled trials have shown quite consistently that the duration and severity of common cold episodes are reduced in the vitamin C groups,3 indicating that viral respiratory infections in humans are affected by vitamin C levels. There is also evidence indicating that vitamin C may affect pneumonia.3 In particular, three controlled trials with human subjects reported a significantly lower incidence of pneumonia in vitamin C-supplemented groups,6 suggesting that vitamin C may affect susceptibility to lower respiratory tract infections under certain conditions. The possibility that vitamin C affects severe viral respiratory tract infections would seem to warrant further study, especially in light of the recent SARS epidemic.
Hemilä H. Vitamin C and SARS coronavirus. J Antimicrob Chemother. 2003;52(6):1049‐1050. doi:10.1093/jac/dkh002 Title: Immune-enhancing Role of Vitamin C and Zinc and Effect on Clinical Conditions
Abstract
Vitamin C concentrations in the plasma and leukocytes rapidly decline during infections and stress. Supplementation of vitamin C was found to improve components of the human immune system such as antimicrobial and natural killer cell activities, lymphocyte proliferation, chemotaxis, and delayed-type hypersensitivity. Vitamin C contributes to maintaining the redox integrity of cells and thereby protects them against reactive oxygen species generated during the respiratory burst and in the inflammatory response. Likewise, zinc undernutrition or deficiency was shown to impair cellular mediators of innate immunity such as phagocytosis, natural killer cell activity, and the generation of oxidative burst. Therefore, both nutrients play important roles in immune function and the modulation of host resistance to infectious agents, reducing the risk, severity, and duration of infectious diseases. This is of special importance in populations in which insufficient intake of these nutrients is prevalent. In the developing world, this is the case in low- and middle-income countries, but also in subpopulations in industrialized countries, e.g. in the elderly. A large number of randomized controlled intervention trials with intakes of up to 1 g of vitamin C and up to 30 mg of zinc are available. These trials document that adequate intakes of vitamin C and zinc ameliorate symptoms and shorten the duration of respiratory tract infections including the common cold. Furthermore, vitamin C and zinc reduce the incidence and improve the outcome of pneumonia, malaria, and diarrhea infections, especially in children in developing countries.
Wintergerst ES, Maggini S, Hornig DH. Immune-enhancing role of vitamin C and zinc and effect on clinical conditions. Ann Nutr Metab. 2006;50(2):85‐94. doi:10.1159/000090495 Title: Vitamin C and Immune Function
Abstract
Vitamin C is an essential micronutrient for humans, with pleiotropic functions related to its ability to donate electrons. It is a potent antioxidant and a cofactor for a family of biosynthetic and gene regulatory enzymes. Vitamin C contributes to immune defense by supporting various cellular functions of both the innate and adaptive immune system. Vitamin C supports epithelial barrier function against pathogens and promotes the oxidant scavenging activity of the skin, thereby potentially protecting against environmental oxidative stress. Vitamin C accumulates in phagocytic cells, such as neutrophils, and can enhance chemotaxis, phagocytosis, generation of reactive oxygen species, and ultimately microbial killing. It is also needed for apoptosis and clearance of the spent neutrophils from sites of infection by macrophages, thereby decreasing necrosis/NETosis and potential tissue damage. The role of vitamin C in lymphocytes is less clear, but it has been shown to enhance differentiation and proliferation of B- and T-cells, likely due to its gene regulating effects. Vitamin C deficiency results in impaired immunity and higher susceptibility to infections. In turn, infections significantly impact on vitamin C levels due to enhanced inflammation and metabolic requirements. Furthermore, supplementation with vitamin C appears to be able to both prevent and treat respiratory and systemic infections. Prophylactic prevention of infection requires dietary vitamin C intakes that provide at least adequate, if not saturating plasma levels (i.e., 100-200 mg/day), which optimize cell and tissue levels. In contrast, treatment of established infections requires significantly higher (gram) doses of the vitamin to compensate for the increased inflammatory response and metabolic demand.
Carr AC, Maggini S. Vitamin C and Immune Function. Nutrients. 2017;9(11):1211. Published 2017 Nov 3. doi:10.3390/ nu9111211 Title: Zinc and Immunity: An Essential Interrelation
Abstract
The significance of the essential trace element zinc for immune function has been known for several decades. Zinc deficiency affects immune cells, resulting in altered host defense, increased risk of inflammation, and even death. The micronutrient zinc is important for maintenance and development of immune cells of both the innate and adaptive immune system. A disrupted zinc homeostasis affects these cells, leading to impaired formation, activation, and maturation of lymphocytes, disturbed intercellular communication via cytokines, and weakened innate host defense via phagocytosis and oxidative burst. This review outlines the connection between zinc and immunity by giving a survey on the major roles of zinc in immune cell function, and their potential consequences in vivo. Maares M, Haase H. Zinc and immunity: An essential interrelation. Arch Biochem Biophys. 2016;611:58‐65. doi: 10.1016/j.abb.2016.03.022 Title: Zinc as a Gatekeeper of Immune Function
Abstract
After the discovery of zinc deficiency in the 1960s, it soon became clear that zinc is essential for the function of the immune system. Zinc ions are involved in regulating intracellular signaling pathways in innate and adaptive immune cells. Zinc homeostasis is largely controlled via the expression and action of zinc "importers" (ZIP 1-14), zinc "exporters" (ZnT 1-10), and zinc-binding proteins. Anti-inflammatory and anti-oxidant properties of zinc have long been documented, however, underlying mechanisms are still not entirely clear. Here, we report molecular mechanisms underlying the development of a pro- inflammatory phenotype during zinc deficiency. Furthermore, we describe links between altered zinc homeostasis and disease development. Consequently, the benefits of zinc supplementation for a malfunctioning immune system become clear. This article will focus on underlying mechanisms responsible for the regulation of cellular signaling by alterations in zinc homeostasis. Effects of fast zinc flux, intermediate "zinc waves", and late homeostatic zinc signals will be discriminated. Description of zinc homeostasis-related effects on the activation of key signaling molecules, as well as on epigenetic modifications, are included to emphasize the role of zinc as a gatekeeper of immune function.
Wessels I, Maywald M, Rink L. Zinc as a Gatekeeper of Immune Function. Nutrients. 2017;9(12):1286. Published 2017 Nov 25. doi:10.3390/nu9121286 Title: Future Perspectives in Addressing the Global Issue of Vitamin D Deficiency
Abstract
Vitamin D is a fundamentally critical nutrient that the human body requires to function properly. It plays an important role in musculoskeletal health due to its involvement in the regulation of calcium and phosphorus. Having a low level of vitamin D in the body may be detrimental for a wide range of health outcomes, including risk of osteoporotic and stress fractures, risk of CVD and some cancers, and lowering of the capability of the immune system. Vitamin D is an unusual nutrient; it is not a vitamin, in the true sense of the word but a pro-hormone. The main source of vitamin D is UV exposure, not dietary intake. Interestingly, there are two forms of vitamin D, vitamin D2 and vitamin D3, both of which are metabolised into 25-hydroxyvitamin D (25(OH)D) in the liver, the biomarker of vitamin D status. Vitamin D deficiency is a global public health problem, especially amongst older people and ethnic minority groups. The newest publication from the UK Government's Public Health England Department recommends that vitamin D intake should be 10 μg daily and this recommendation compares well (albeit lower) with other guidelines such as the Institute of Medicine recommendation of 15 μg for those aged 1-70 years and 20 μg for those 70 years or over. Few countries, however, have a specific vitamin D policy to prevent deficiency in populations. Finland leads the way, demonstrating impressive results in reducing population-level vitamin D deficiency through mandatory food fortification programmes. Collaboration between academia, government and industry, including countries from varying latitudes, is essential to identify long-term solutions to the global issue of vitamin D deficiency. This paper provides a narrative review of the evidence related to the role of vitamin D deficiency in health outcomes, outlines controversies regarding setting levels of adequacy, identifies the prevalence of vitamin D deficiency across the globe, and identifies population-level strategies adopted by countries to prevent vitamin D deficiency.
Mendes MM, Charlton K, Thakur S, Ribeiro H, Lanham-New SA. Future perspectives in addressing the global issue of vitamin D deficiency. Proc Nutr Soc. 2020;79(2):246‐251. doi:10.1017/S0029665119001538 Nutrition
A.Evidence Based Diet Related Research a.Intermittent Fasting b.Ketogenic Diet c.Plant Based Nutrition Intermittent Fasting
Complete Alternate-day Involves alternating fasting days (no energy-containing foods or beverages fasting consumed) with eating days (food and beverages consumed ad libitum) Allows consumption of 20-25% of energy needs on scheduled fasting days; the Modified fasting regimens basis for the popular 5:2 diet, with involves severe energy restriction for 2 nonconsecutive days per week and ad libitum eating for the other 5 days Allows ad libitum energy intake within specific time frames, including regular Time restricted Feeding extended fasting intervals; studies of <3 meals per day are indirect examinations of a prolonged daily or nightly fasting period
Religious Fasting variety of fasting regimens undertaken for religious or spiritual purposes
A fast from sunrise to sunset during the holy month of Ramada; the most common dietary practice is to consume one large meal after sunset and one lighter meal Ramadan Fasting before dawn. Thus, the feast and fast periods of Ramadan are approximately 12 hours in length Members of the Church of Jesus Christ of Latter-Day Saints routinely abstain from food and drink for extended periods of time. Some Seventh-day Adventists Other Religious fasts consume their last of two daily meals in the afternoon, resulting in an extended nighttime fasting interval that may be biologically important
Tinsley GM, La Bounty PM. Effects of intermittent fasting on body composition and clinical health markers in humans. Nutr Rev. 2015;73(10):661‐674. doi:10.1093/nutrit/nuv041 Title: Effects of Intermittent Fasting on Body Composition and Clinical Health Markers in Humans
Intermittent fasting is a broad term that encompasses a variety of programs that manipulate the timing of eating occasions by utilizing short-term fasts in order to improve body composition and overall health. This review examines studies conducted on intermittent fasting programs to determine if they are effective at improving body composition and clinical health markers associated with disease. Intermittent fasting protocols can be grouped into alternate-day fasting, whole-day fasting, and time-restricted feeding. Alternate-day fasting trials of 3 to 12 weeks in duration appear to be effective at reducing body weight (≈3%-7%), body fat (≈3-5.5 kg), total cholesterol (≈10%-21%), and triglycerides (≈14%-42%) in normal-weight, overweight, and obese humans. Whole-day fasting trials lasting 12 to 24 weeks also reduce body weight (≈3%-9%) and body fat, and favorably improve blood lipids (≈5%-20% reduction in total cholesterol and ≈17%-50% reduction in triglycerides). Research on time-restricted feeding is limited, and clear conclusions cannot be made at present. Future studies should examine long-term effects of intermittent fasting and the potential synergistic effects of combining intermittent fasting with exercise.
Tinsley GM, La Bounty PM. Effects of intermittent fasting on body composition and clinical health markers in humans. Nutr Rev. 2015;73(10):661‐674. doi:10.1093/nutrit/nuv041 Title: Metabolic Effects of Intermittent Fasting
The objective of this review is to provide an overview of intermittent fasting regimens, summarize the evidence on the health benefits of intermittent fasting, and discuss physiological mechanisms by which intermittent fasting might lead to improved health outcomes. A MEDLINE search was performed using PubMed and the terms "intermittent fasting," "fasting," "time-restricted feeding," and "food timing." Modified fasting regimens appear to promote weight loss and may improve metabolic health. Several lines of evidence also support the hypothesis that eating patterns that reduce or eliminate nighttime eating and prolong nightly fasting intervals may result in sustained improvements in human health. Intermittent fasting regimens are hypothesized to influence metabolic regulation via effects on (a) circadian biology, (b) the gut microbiome, and (c) modifiable lifestyle behaviors, such as sleep. If proven to be efficacious, these eating regimens offer promising nonpharmacological approaches to improving health at the population level, with multiple public health benefits.
Patterson RE, Sears DD. Metabolic Effects of Intermittent Fasting. Annu Rev Nutr. 2017;37:371‐393. doi:10.1146/annurev- nutr-071816-064634 Title: Impact of Intermittent Fasting on the Lipid Profile: Assessment Associated With Diet and Weight Loss Intermittent fasting, whose proposed benefits include the improvement of lipid profile and the body weight loss, has gained considerable scientific and popular repercussion. This review aimed to consolidate studies that analyzed the lipid profile in humans before and after intermittent fasting period through a detailed review; and to propose the physiological mechanism, considering the diet and the body weight loss. Normocaloric and hypocaloric intermittent fasting may be a dietary method to aid in the improvement of the lipid profile in healthy, obese and dyslipidemic men and women by reducing total cholesterol, LDL, triglycerides and increasing HDL levels. However, the majority of studies that analyze the intermittent fasting impacts on the lipid profile and body weight loss are observational based on Ramadan fasting, which lacks large sample and detailed information about diet. Randomized clinical trials with a larger sample size are needed to evaluate the IF effects mainly in patients with dyslipidemia.
Santos HO, Macedo RCO. Impact of intermittent fasting on the lipid profile: Assessment associated with diet and weight loss. Clin Nutr ESPEN. 2018;24:14‐21. doi:10.1016/j.clnesp.2018.01.002 Title: Fasting for Weight Loss: An Effective Strategy or Latest Dieting Trend?
With the increasing obesity epidemic comes the search for effective dietary approaches for calorie restriction and weight loss. Here I examine whether fasting is the latest 'fad diet' as portrayed in popular media and discuss whether it is a safe and effective approach or whether it is an idiosyncratic diet trend that promotes short-term weight loss, with no concern for long-term weight maintenance. Fasting has long been used under historical and experimental conditions and has recently been popularised by 'intermittent fasting' or 'modified fasting' regimes, in which a very low-calorie allowance is allowed, on alternate days (ADF) or 2 days a week (5:2 diet), where 'normal' eating is resumed on non-diet days. It is a simple concept, which makes it easy to follow with no difficult calorie counting every other day. This approach does seem to promote weight loss, but is linked to hunger, which can be a limiting factor for maintaining food restriction. The potential health benefits of fasting can be related to both the acute food restriction and chronic influence of weight loss; the long-term effect of chronic food restriction in humans is not yet clear, but may be a potentially interesting future dietary strategy for longevity, particularly given the overweight epidemic. One approach does not fit all in the quest to achieve body weight control, but this could be a dietary strategy for consideration. With the obesity epidemic comes the search for dietary strategies to (i) prevent weight gain, (ii) promote weight loss and (iii) prevent weight regain. With over half of the population of the United Kingdom and other developed countries being collectively overweight or obese, there is considerable pressure to achieve these goals, from both a public health and a clinical perspective. Certainly not one dietary approach will solve these complex problems. Although there is some long-term success with gastric surgical options for morbid obesity, there is still a requirement for dietary approaches for weight management for the overweight and obese population, particularly as invasive interventions carry post-operative risk of death due to complications. Effective dietary interventions are required that promote long-term adherence and sustained beneficial effects on metabolic and disease markers. In general, such interventions need to be palatable and satiating, meet minimal nutritional requirements, promote loss of fat and preserve lean body mass, ensure long-term safety, be simple to administer and monitor and have widespread public health utility. Intermittent fasting or alternate day fasting may be an option for achieving weight loss and maintenance.
Johnstone A. Fasting for weight loss: an effective strategy or latest dieting trend?. Int J Obes (Lond). 2015;39(5):727‐733. doi:10.1038/ijo.2014.214 Ketogenic Diet
• A diet high rich in proteins and fats, low in carbohydrates
• Causes the body to release ketones into the bloodstream.
• Most cells prefer to use blood sugar, which comes from carbohydrates, as the bodies main source of energy.
• In absence of circulating blood sugar from food, we start breaking down stored fat into ketone bodies to generate energy.
• Difficult to sustain over a long period of time. Title: History of the Ketogenic Diet
Abstract
Fasting and other dietary regimens have been used to treat epilepsy since at least 500 BC. To mimic the metabolism of fasting, the ketogenic diet (KD) was introduced by modern physicians as a treatment for epilepsy in the 1920s. For two decades this therapy was widely used, but with the modern era of antiepileptic drug treatment its use declined dramatically. By the end of the twentieth century this therapy was available in only a small number of children's hospitals. Over the past 15 years, there has been an explosion in the use, and scientific interest in the KD. This review traces the history of one of the most effective treatments for childhood epilepsy.
Wheless JW. History of the ketogenic diet. Epilepsia. 2008;49 Suppl 8:3‐5. doi:10.1111/j.1528-1167.2008.01821.x Title: Influence of the Mediterranean and Ketogenic Diets on Cognitive Status and Decline: A Narrative Review Abstract
Alzheimer's disease (AD) is the most common form of senile dementia, accounting for up to 70% of dementia cases. AD is a slowly progressive disease, which causes global mental deterioration by affecting various cognitive areas. A growing body of evidence has demonstrated that lifestyle habits and nutritional patterns could delay the natural course of the neurodegeneration process. There is no single dietary pattern unequivocally proven to prevent AD. Nevertheless, epidemiological data suggest that by adopting several dietary habits, especially if accompanied with a healthy lifestyle, the negative consequences of AD could potentially be delayed. Alongside with others, two specific eating patterns have been well investigated concerning their potential beneficial effect on cognitive status: the Mediterranean diet (MedDi) and the Ketogenic Diet (KD). Despite the different underlying mechanisms, both of them have demonstrated a fairly profitable role in reducing or delaying cognitive impairment. The aim of the present narrative review is to overview the existing research on the efficacy of MedDi and KD against AD-related cognitive decline, focusing on the proposed protective mechanisms of action. Although the current knowledge on this complex topic does not allow us, at this point, to make exhaustive conclusions, this information could be of help in order to better characterize the possible role of MedDi and KD as nonpharmacological therapies in the treatment of AD and, more generically, of neurodegenerative disorders.
Vinciguerra F, Graziano M, Hagnäs M, Frittitta L, Tumminia A. Influence of the Mediterranean and Ketogenic Diets on Cognitive Status and Decline: A Narrative Review. Nutrients. 2020;12(4):1019. Published 2020 Apr 8. doi:10.3390/ nu12041019 Title: New Insights Into the Mechanisms of the Ketogenic Diet
Abstract
Purpose of review: High-fat, low-carbohydrate ketogenic diets have been used for almost a century for the treatment of epilepsy. Used traditionally for the treatment of refractory pediatric epilepsies, in recent years the use of ketogenic diets has experienced a revival to include the treatment of adulthood epilepsies as well as conditions ranging from autism to chronic pain and cancer. Despite the ability of ketogenic diet therapy to suppress seizures refractory to antiepileptic drugs and reports of lasting seizure freedom, the underlying mechanisms are poorly understood. This review explores new insights into mechanisms mobilized by ketogenic diet therapies.
Recent findings: Ketogenic diets act through a combination of mechanisms, which are linked to the effects of ketones and glucose restriction, and to interactions with receptors, channels, and metabolic enzymes. Decanoic acid, a component of medium-chain triclycerides, contributes to seizure control through direct α-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid (AMPA) receptor inhibition, whereas drugs targeting lactate dehydrogenase reduce seizures through inhibition of a metabolic pathway. Ketogenic diet therapy also affects DNA methylation, a novel epigenetic mechanism of the diet.
Summary: Ketogenic diet therapy combines several beneficial mechanisms that provide broad benefits for the treatment of epilepsy with the potential to not only suppress seizures but also to modify the course of the epilepsy.
Boison D. New insights into the mechanisms of the ketogenic diet. Curr Opin Neurol. 2017;30(2):187‐192. doi:10.1097/ WCO.0000000000000432 Title: The Ketogenic Diet and Sport: A Possible Marriage?
Abstract
The ketogenic diet (KD) is used widely as a weight loss strategy and, more rarely, as therapy for some diseases. In many sports, weight control is often necessary (boxing, weightlifting, wrestling, etc.), but the KD usually is not considered. Our hypothesis is that KD might be used to achieve fat loss without affecting strength/ power performance negatively.
Paoli A, Bianco A, Grimaldi KA. The Ketogenic Diet and Sport: A Possible Marriage?. Exerc Sport Sci Rev. 2015;43(3):153‐ 162. doi:10.1249/JES.0000000000000050 Title: Ketogenic Diet in Alzheimer's Disease
Abstract
At present, the prevalence of Alzheimer's disease, a devastating neurodegenerative disorder, is increasing. Although the mechanism of the underlying pathology is not fully uncovered, in the last years, there has been significant progress in its understanding. This includes: Progressive deposition of amyloid β-peptides in amyloid plaques and hyperphosphorylated tau protein in intracellular as neurofibrillary tangles; neuronal loss; and impaired glucose metabolism. Due to a lack of effective prevention and treatment strategy, emerging evidence suggests that dietary and metabolic interventions could potentially target these issues. The ketogenic diet is a very high-fat, low-carbohydrate diet, which has a fasting-like effect bringing the body into a state of ketosis. The presence of ketone bodies has a neuroprotective impact on aging brain cells. Moreover, their production may enhance mitochondrial function, reduce the expression of inflammatory and apoptotic mediators. Thus, it has gained interest as a potential therapy for neurodegenerative disorders like Alzheimer's disease. This review aims to examine the role of the ketogenic diet in Alzheimer's disease progression and to outline specific aspects of the nutritional profile providing a rationale for the implementation of dietary interventions as a therapeutic strategy for Alzheimer's disease.
Rusek M, Pluta R, Ułamek-Kozioł M, Czuczwar SJ. Ketogenic Diet in Alzheimer's Disease. Int J Mol Sci. 2019;20(16):3892. Published 2019 Aug 9. doi:10.3390/ijms20163892 Title: Ketogenic Diet and Microbiota: Friends or Enemies? Abstract
Over the last years, a growing body of evidence suggests that gut microbial communities play a fundamental role in many aspects of human health and diseases. The gut microbiota is a very dynamic entity influenced by environment and nutritional behaviors. Considering the influence of such a microbial community on human health and its multiple mechanisms of action as the production of bioactive compounds, pathogens protection, energy homeostasis, nutrients metabolism and regulation of immunity, establishing the influences of different nutritional approach is of pivotal importance. The very low carbohydrate ketogenic diet is a very popular dietary approach used for different aims: from weight loss to neurological diseases. The aim of this review is to dissect the complex interactions between ketogenic diet and gut microbiota and how this large network may influence human health.
Paoli A, Mancin L, Bianco A, Thomas E, Mota JF, Piccini F. Ketogenic Diet and Microbiota: Friends or Enemies?. Genes (Basel). 2019;10(7):534. Published 2019 Jul 15. doi:10.3390/genes10070534 Title: Ketogenic Diet as a Metabolic Therapy for Mood Disorders: Evidence and Developments Abstract
Despite significant advances in pharmacological and non-pharmacological treatments, mood disorders remain a significant source of mental capital loss, with high rates of treatment resistance, requiring a coordinated effort in investigation and development of efficient, tolerable and accessible novel interventions. Ketogenic diet (KD) is a low-carb diet that substantially changes the energetic matrix of the body including the brain. It has been established as an effective anticonvulsant treatment, and more recently, the role of KD for mental disorders has been explored. Ketogenic diet has profound effects in multiple targets implicated in the pathophysiology of mood disorders, including but not limited to, glutamate/GABA transmission, monoamine levels, mitochondrial function and biogenesis, neurotrophism, oxidative stress, insulin dysfunction and inflammation. Preclinical studies, case reports and case series have demonstrated antidepressant and mood stabilizing effects of KD, however, to date, no clinical trials for depression or bipolar disorder have been conducted. Because of its potential pleiotropic benefits, KD should be considered as a promising intervention in research in mood disorder therapeutics, especially in treatment resistant presentations.
Brietzke E, Mansur RB, Subramaniapillai M, et al. Ketogenic diet as a metabolic therapy for mood disorders: Evidence and developments. Neurosci Biobehav Rev. 2018;94:11‐16. doi:10.1016/j.neubiorev.2018.07.020 Plant Based Diet
• Focuses on vegetables, fruits, grains (especially whole grains), beans and peas, lentils, nuts, and seeds (rather than on meat, poultry, fish, eggs, and dairy foods). It is not necessarily meatless or vegan. Title: A Plant-Based Diet, Atherogenesis, and Coronary Artery Disease Prevention
Abstract
A plant-based diet is increasingly becoming recognized as a healthier alternative to a diet laden with meat. Atherosclerosis associated with high dietary intake of meat, fat, and carbohydrates remains the leading cause of mortality in the US. This condition results from progressive damage to the endothelial cells lining the vascular system, including the heart, leading to endothelial dysfunction. In addition to genetic factors associated with endothelial dysfunction, many dietary and other lifestyle factors, such as tobacco use, high meat and fat intake, and oxidative stress, are implicated in atherogenesis. Polyphenols derived from dietary plant intake have protective effects on vascular endothelial cells, possibly as antioxidants that prevent the oxidation of low-density lipoprotein. Recently, metabolites of L- carnitine, such as trimethylamine-N-oxide, that result from ingestion of red meat have been identified as a potential predictive marker of coronary artery disease (CAD). Metabolism of L-carnitine by the intestinal microbiome is associated with atherosclerosis in omnivores but not in vegetarians, supporting CAD benefits of a plant-based diet. Trimethylamine- N-oxide may cause atherosclerosis via macrophage activation. We suggest that a shift toward a plant-based diet may confer protective effects against atherosclerotic CAD by increasing endothelial protective factors in the circulation while reducing factors that are injurious to endothelial cells. The relative ratio of protective factors to injurious endothelial exposure may be a novel approach to assessing an objective dietary benefit from a plant-based diet. This review provides a mechanistic perspective of the evidence for protection by a plant-based diet against atherosclerotic CAD.
Tuso P, Stoll SR, Li WW. A plant-based diet, atherogenesis, and coronary artery disease prevention. Perm J. 2015;19(1): 62‐67. doi:10.7812/TPP/14-036 Title: Plant-Based Diets: Considerations for Environmental Impact, Protein Quality, and Exercise Performance
Abstract
Plant-based diets provide well-established physical and environmental health benefits. These benefits stem in part from the degree of restriction of animal-derived foods. Historically, meat and other animal-derived proteins have been viewed as an integral component of athletes' diets, leading some to question the adequacy of vegetarian or vegan diets for supporting athletic performance. The purpose of this review is to examine the impact of plant-based diets on human physical health, environmental sustainability, and exercise performance capacity. Based on currently available literature, it is unlikely that plant-based diets provide advantages, but do not suffer from disadvantages, compared to omnivorous diets for strength, anaerobic, or aerobic exercise performance. However, plant-based diets typically reduce the risk of developing numerous chronic diseases over the lifespan and require fewer natural resources for production compared to meat- containing diets. As such, plant-based diets appear to be viable options for adequately supporting athletic performance while concurrently contributing to overall physical and environmental health. Given the sparse literature comparing omnivore, vegetarian, and vegan athletes, particularly at the elite level, further research is warranted to ascertain differences that might appear at the highest levels of training and athletic performance.
Lynch H, Johnston C, Wharton C. Plant-Based Diets: Considerations for Environmental Impact, Protein Quality, and Exercise Performance. Nutrients. 2018;10(12):1841. Published 2018 Dec 1. doi:10.3390/nu10121841 Title: Cardio-Metabolic Benefits of Plant-Based Diets
Abstract
Cardio-metabolic disease, namely ischemic heart disease, stroke, obesity, and type 2 diabetes, represent substantial health and economic burdens. Almost one half of cardio-metabolic deaths in the U.S. might be prevented through proper nutrition. Plant-based (vegetarian and vegan) diets are an effective strategy for improving nutrient intake. At the same time, they are associated with decreased all-cause mortality and decreased risk of obesity, type 2 diabetes, and coronary heart disease. Evidence suggests that plant-based diets may reduce the risk of coronary heart disease events by an estimated 40% and the risk of cerebral vascular disease events by 29%. These diets also reduce the risk of developing metabolic syndrome and type 2 diabetes by about one half. Properly planned vegetarian diets are healthful, effective for weight and glycemic control, and provide metabolic and cardiovascular benefits, including reversing atherosclerosis and decreasing blood lipids and blood pressure. The use of plant-based diets as a means of prevention and treatment of cardio-metabolic disease should be promoted through dietary guidelines and recommendations.
Kahleova H, Levin S, Barnard N. Cardio-Metabolic Benefits of Plant-Based Diets. Nutrients. 2017;9(8):848. Published 2017 Aug 9. doi:10.3390/nu9080848 Title: Association Between Red Meat Consumption and Colon Cancer: A Systematic Review of Experimental Results
Abstract
A role for red and processed meat in the development of colorectal cancer has been proposed based largely on evidence from observational studies in humans, especially in those populations consuming a westernized diet. Determination of causation specifically by red or processed meat is contingent upon identification of plausible mechanisms that lead to colorectal cancer. We conducted a systematic review of the available evidence to determine the availability of plausible mechanistic data linking red and processed meat consumption to colorectal cancer risk. Forty studies using animal models or cell cultures met specified inclusion criteria, most of which were designed to examine the role of heme iron or heterocyclic amines in relation to colon carcinogenesis. Most studies used levels of meat or meat components well in excess of those found in human diets. Although many of the experiments used semi-purified diets designed to mimic the nutrient loads in current westernized diets, most did not include potential biologically active protective compounds present in whole foods. Because of these limitations in the existing literature, there is currently insufficient evidence to confirm a mechanistic link between the intake of red meat as part of a healthy dietary pattern and colorectal cancer risk. Impact statement Current recommendations to reduce colon cancer include the reduction or elimination of red or processed meats. These recommendations are based on data from epidemiological studies conducted among cultures where meat consumption is elevated and consumption of fruits, vegetables, and whole grains are reduced. This review evaluated experimental data exploring the putative mechanisms whereby red or processed meats may contribute to colon cancer. Most studies used levels of meat or meat-derived compounds that were in excess of those in human diets, even in cultures where meat intake is elevated. Experiments where protective dietary compounds were used to mitigate the extreme levels of meat and meat-derived compounds showed protection against colon cancer, with some essentially negating the impact of meat in the diet. It is essential that better-designed studies be conducted that use relevant concentrations of meat or meat-derived compounds in complex diets representative of the foods consumed by humans.
Turner ND, Lloyd SK. Association between red meat consumption and colon cancer: A systematic review of experimental results. Exp Biol Med (Maywood). 2017;242(8):813‐839. doi:10.1177/1535370217693117 Title: Red and Processed Meats and Health Risks: How Strong Is the Evidence?
Abstract
Prevailing dietary guidelines have widely recommended diets relatively low in red and processed meats and high in minimally processed plant foods for the prevention of chronic diseases. However, an ad hoc research group called the Nutritional Recommendations (NutriRECS) consortium recently issued "new dietary guidelines" encouraging individuals to continue their current meat consumption habits due to "low certainty" of the evidence, difficulty of altering meat eaters' habits and preferences, and the lack of need to consider environmental impacts of red meat consumption. These recommendations are not justified, in large part because of the flawed methodologies used to review and grade nutritional evidence. The evidence evaluation was largely based on the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria, which are primarily designed to grade the strength of evidence for clinical interventions especially pharmacotherapy. However, the infeasibility for conducting large, long-term randomized clinical trials on most dietary, lifestyle, and environmental exposures makes the criteria inappropriate in these areas. A separate research group proposed a modified and validated system for rating the meta-evidence on nutritional studies (NutriGRADE) to address several limitations of the GRADE criteria. Applying NutriGRADE, the evidence on the positive association between red and processed meats and type 2 diabetes was rated to be of "high quality," while the evidence on the association between red and processed meats and mortality was rated to be of "moderate quality." Another important limitation is that inadequate attention was paid to what might be replacing red meat, be it plant-based proteins, refined carbohydrates, or other foods. In summary, the red/processed meat recommendations by NutriRECS suffer from important methodological limitations and involve misinterpretations of nutritional evidence. To improve human and planetary health, dietary guidelines should continue to emphasize dietary patterns low in red and processed meats and high in minimally processed plant foods such as fruits and vegetables, whole grains, nuts, and legumes.
Qian F, Riddle MC, Wylie-Rosett J, Hu FB. Red and Processed Meats and Health Risks: How Strong Is the Evidence?. Diabetes Care. 2020;43(2):265‐271. doi:10.2337/dci19-0063