MAGNESIUM MALATE

dimagnesium malate significantly more bioavailable than either APPLICATIONS oxide or .*11 Magnesium malate may help to support muscle health and energy production more than either one alone, due to different • Muscle Support mechanisms of support.* • Energy Production Our magnesium malate is free of dairy, soy, gluten, sugar, yeast, and mold. It is cGMP NSF Certified (ANSI Standards 173 Section 8), as well as FDA (Food and • Support Drug Administration) and FSMA (Food Safety Modernization Act) Compliant. It • Bone Health is also kosher certified, halal certified, and suitable for vegetarians and vegans. • Sleep Support MUSCLE SUPPORT • Antioxidant support • Magnesium participates in energy metabolism, and may help to support Stress Management and maintain skeletal muscle health.*12 It may also support skeletal muscle relaxation.*13 may assist with skeletal muscle support by helping to maintain lactic acid levels already within the normal range.*14 Magnesium and malic acid work synergistically to support skeletal muscle health.* Additionally, magnesium may also help to support both cardiac and smooth muscle, helping to maintain both cardiac and vascular health.*15 Because of this, magnesium may help to maintain cardiac output and peripheral vascular resistance already within the normal range.*15 ENERGY PRODUCTION Magnesium helps to create energy in the form of ATP from dietary sources, and may support the utilization of other essential nutrients.* Magnesium may also help to support healthy daytime energy levels.*16 In a study with healthy male volleyball players, compared to control, the magnesium group had lactic acid levels significantly closer to normal, post exercise, suggesting thatmagnesium supplementation can support metabolism in anaerobic conditions.*17 Malic acid may help to maintain serum lactate levels within the normal range during and after exertion.*14 Together, magnesium and malic acid play important roles in energy production via ATP, under both aerobic and anerobic conditions.*14,17 INTRODUCTION OTHER USES Magnesium is an essential mineral in the human diet. It is the second most Mineral Support Given that as many as 70% of Americans may be magnesium deficient, abundant intracellular cation (Mg+2) and is involved in more than 350 enzymatic *7 1,2,3 magnesium intake may benefit from support. For prevention of deficiency, the reactions and over 80% of metabolic functions. Magnesium is needed for cellular RDA for elemental magnesium in ages 19-30 is 310 mg/day for women and 400 energy metabolism, DNA transcription, RNA synthesis, membrane stabilization, mg/day for men.5 In ages 31 and older, the RDA is 320 mg/day for women and and metabolism, among many other functions.1,2 Magnesium may help 420 mg/day for men.5 to support muscular, skeletal, and neural health.*1,2,4 Dietary magnesium may be found in seeds such as pumpkin and chia; nuts and their butters such as Bone Health almonds, cashews and peanuts; legumes such as black beans, kidney beans, and Approximately 50% of the body’s magnesium is located within bone, where it edamame; and spinach, among others.5 It can also be found in hard water, due contributes to structural integrity.2 Magnesium is a cofactor for the synthesis, 6 transport, and activation of vitamin D,18,19 and may also help to regulate calcium to the high mineral content. As many as 70% of Americans may be magnesium 2 7 8 absorption. Magnesium’s role in both of these processes helps to support and deficient, and subclinical deficiency occurs before serum magnesium adjusts. *2,18 Because of this, serum magnesium levels do not reliably correlate with either maintain healthy bones. total body magnesium or amounts in specific tissues.9 Sleep Support Malic acid is commonly found in apples and other fruits. Malic acid is often added Magnesium may help to support healthy sleep by supporting healthy NMDA and GABA levels already within the normal range.*20 It may also help to maintain to food products to contribute a sour taste. Malic acid in the form of malate is an *21 important part of the Krebs’ cycle, which helps to metabolize food into energy in healthy sleep quality. the form of ATP. Malic acid may help to support overall muscle health.* Antioxidant support Magnesium may help to contribute antioxidant activity, as it is a cofactor of In magnesium malate, magnesium is bound to malic acid. Magnesium levels *22,23,24 depend on intestinal absorption and renal excretion.2 Magnesium malate has superoxide dismutase and other antioxidant enzymes. * been found to be more bioavailable than many of its magnesium counterparts. In Stress Management a single dose rat study, magnesium malate had the highest area under the curve Magnesium may help to support relaxation and stress management in everyday followed by magnesium acetyl taurate, while magnesium citrate and magnesium stress.*25,26 oxide had the lowest bioavailability.*10 A small single-center, randomized, double- blind, four-arm crossover trial with 14 healthy adults found similar results, with

PROFESSIONAL USE ONLY SAFETY & CAUTIONS Magnesium is generally well-tolerated. At higher doses, loose stools and/or gastrointestinal irritation can occur. This is less likely to occur in doses under the tolerable upper intake level (UL) of 350 mg per day.5 Do not take magnesium with levodopa/carbidopa, as it may reduce the bioavailability of levodopa/carbidopa.27 When taken with aminoglycoside antibiotics, magnesium can increase the risk of neuromuscular weakness.28 Magnesium can decrease absorption with bisphosphonates when taken together, and doses should be separated by at least two hours.29 Magnesium may decrease the absorption of quinolone antibiotics, which should be taken at least 2 hours before, or 4-6 hours after magnesium.30 It may also decrease the absorption of tetracyclines,31 as well as the absorption of digoxin.32 Magnesium may have additive effects with calcium channel blockers,33 and may increase the risk for ketamine toxicity.34 It may also increase the absorption of sulfonylureas.35 Use caution when taking magnesium with sparing diuretics, as these can decrease magnesium excretion and increase magnesium levels.36 Malic acid is generally recognized as safe (GRAS) in food and food products. As a supplement, it is generally well-tolerated. While one study has shown that malic acid may cause loose stools, it may have been due, instead, to the magnesium that was taken concurrently. In one animal study, malic acid derived from tagetes root was shown to decrease blood pressure.37 As with magnesium, malic acid may have additive effects with antihypertensives. * This statement has not been evaluated by the Food and Drug Administration. This product is not intended to treat, cure, or prevent any diseases.

SUGGESTED USE: Take two capsules twice daily before meals or as directed by your physician. Do not use if Supplement Facts pregnant or nursing. Stop use if adverse reactions Serving Size 2 Capsules V000000 develop. Keep out of reach of children. Servings Per Container 60 †These statements have not been evaluated by the Food and Drug Administration. This product is not intended to MAGNESIUM Amount Per Serving % Daily Value diagnose, treat, cure or prevent any disease. Magnesium 200 mg 50% (from dimagnesium TM Albion TM and the Albion Gold Medallion design malate), (Albion ) are trademarks of Albion Laboratories, Inc. U.S. Patent 6,706,904. MALATE Other ingredients: Vegetable Capsule, Vegetable Magnesium Stearate SUPPORTS MUSCLES AND ENERGY GLUTEN, SUGAR & DAIRY FREE PRODUCTION † Jupiter, Florida 33458 USA Dietary Supplement www.nutramedix.com

120 Vegetable Capsules 561-745-2917 Lot # Exp. REFERENCES 1 Ross, A.C., Caballero, B., Cousins, R.J., Tucker, K.L., & Ziegler, T.R. (2014). Modern Nutrition in Health and Disease (11th ed., pp. 159-175). Wolters Kluwer/Lippincott Williams & Wilkins. 2 Stargrove, M., Treasure, J., & McKee, D. (2007). Herb, nutrient, and drug interactions (pp. 556-582). Mosby/Elsevier. 3 Case, D. R., Zubieta, J., & P Doyle, R. (2020). The Coordination Chemistry of Bio-Relevant Ligands and Their Magnesium Complexes. Molecules (Basel, Switzerland), 25(14), 3172. 4 Gröber, U., Schmidt, J., & Kisters, K. (2015). Magnesium in Prevention and Therapy. Nutrients, 7(9), 8199–8226. 5 Office of Dietary Supplements - Magnesium. Ods.od.nih.gov. (2021). Retrieved 20 June 2021, fromhttps://ods.od.nih.gov/factsheets/Magnesium-HealthProfessional/ . 6 Hardness of Water. Usgs.gov. (2021). Retrieved 20 June 2021, from https://www.usgs.gov/special-topic/water-science-school/science/hardness-water?qt-science_center_objects=0#qt-science_center_objects. 7 Ford, E. S. & Mokdad, A. H. (2003). Dietary magnesium intake in a national sample of US adults. Journal of Nutrition, 133, 2879-2882. 8 Volpe S. L. (2015). Magnesium and the Athlete. Current sports medicine reports, 14(4), 279–283. 9 Fiorentini, D., Cappadone, C., Farruggia, G., & Prata, C. (2021). Magnesium: Biochemistry, Nutrition, Detection, and Social Impact of Diseases Linked to Its Deficiency. Nutrients, 13(4), 1136. 10 Uysal, N., Kizildag, S., Yuce, Z., Guvendi, G., Kandis, S., Koc, B., Karakilic, A., Camsari, U. M., & Ates, M. (2019). Timeline (Bioavailability) of Magnesium Compounds in Hours: Which Magnesium Compound Works Best?. Biological trace element research, 187(1), 128–136. 11 Albion Human Nutrition. (2003). Malic acid can be the right ligand for certain applications. Research Notes, 12(2). 12 Bagis, S., Karabiber, M., As, I., Tamer, L., Erdogan, C., & Atalay, A. (2013). Is magnesium citrate treatment effective on pain, clinical parameters and functional status in patients with fibromyalgia?. Rheumatology international, 33(1), 167–172. 13 Russell, I. J., Michalek, J. E., Flechas, J. D., & Abraham, G. E. (1995). Treatment of fibromyalgia syndrome with Super Malic: a randomized, double blind, placebo controlled, crossover pilot study. The Journal of rheumatology, 22(5), 953–958. 14 Kiyici, F., Eroğlu, H., Kishali, N. F., & Burmaoglu, G. (2017). The Effect of Citrulline/Malate on Blood Lactate Levels in Intensive Exercise. Biochemical genetics, 55(5-6), 387–394. 15 de Baaij, J. H., Hoenderop, J. G., & Bindels, R. J. (2015). Magnesium in man: implications for health and disease. Physiological reviews, 95(1), 1–46. 16 Cao, Y., Zhen, S., Taylor, A. W., Appleton, S., Atlantis, E., & Shi, Z. (2018). Magnesium Intake and Sleep Disorder Symptoms: Findings from the Jiangsu Nutrition Study of Chinese Adults at Five-Year Follow-Up. Nutrients, 10(10), 1354. 17 Setaro, L., Santos-Silva, P. R., Nakano, E. Y., Sales, C. H., Nunes, N., Greve, J. M., & Colli, C. (2014). Magnesium status and the physical performance of volleyball players: effects of magnesium supplementation. Journal of sports sciences, 32(5), 438–445. 18 Rosanoff, A., Dai, Q., & Shapses, S. A. (2016). Essential Nutrient Interactions: Does Low or Suboptimal Magnesium Status Interact with Vitamin D and/or Calcium Status?. Advances in nutrition (Bethesda, Md.), 7(1), 25–43. 19 Dai, Q., Zhu, X., Manson, J. E., Song, Y., Li, X., Franke, A. A., Costello, R. B., Rosanoff, A., Nian, H., Fan, L., Murff, H., Ness, R. M., Seidner, D. L., Yu, C., & Shrubsole, M. J. (2018). Magnesium status and supplementation influence vitamin D status and metabolism: results from a randomized trial. The American journal of clinical nutrition, 108(6), 1249–1258. 20 Abbasi, B., Kimiagar, M., Sadeghniiat, K., Shirazi, M. M., Hedayati, M., & Rashidkhani, B. (2012). The effect of magnesium supplementation on primary insomnia in elderly: A double-blind placebo-controlled clinical trial. Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences, 17(12), 1161–1169. 21 Nielsen, F. H., Johnson, L. K., & Zeng, H. (2010). Magnesium supplementation improves indicators of low magnesium status and inflammatory stress in adults older than 51 years with poor quality sleep. Magnesium research, 23(4), 158–168. 22 Szentmihályi, K., Szilágyi, M., Balla, J., Ujhelyi, L., & Blázovics, A. (2013). In vitro antioxidant activities of magnesium compounds used in food industry. Acta Alimentaria, 43(3), 419-425. 23 Morais, J. B., Severo, J. S., Santos, L. R., de Sousa Melo, S. R., de Oliveira Santos, R., de Oliveira, A. R., Cruz, K. J., & do Nascimento Marreiro, D. (2017). Role of Magnesium in Oxidative Stress in Individuals with Obesity. Biological trace element research, 176(1), 20–26. 24 Castellanos-Gutiérrez, A., Sánchez-Pimienta, T. G., Carriquiry, A., da Costa, T., & Ariza, A. C. (2018). Higher dietary magnesium intake is associated with lower body mass index, waist circumference and serum glucose in Mexican adults. Nutrition journal, 17(1), 114. 25 Boyle, N. B., Lawton, C., & Dye, L. (2017). The Effects of Magnesium Supplementation on Subjective Anxiety and Stress-A Systematic Review. Nutrients, 9(5), 429. 26 Pickering, G., Mazur, A., Trousselard, M., Bienkowski, P., Yaltsewa, N., Amessou, M., Noah, L., & Pouteau, E. (2020). Magnesium Status and Stress: The Vicious Circle Concept Revisited. Nutrients, 12(12), 3672. 27 Kashihara, Y., Terao, Y., Yoda, K., Hirota, T., Kubota, T., Kimura, M., Matsuki, S., Hirakawa, M., Irie, S., & Ieiri, I. (2019). Effects of on pharmacokinetics of L-dopa/carbidopa and assessment of pharmacodynamic changes by a model-based simulation. European journal of clinical pharmacology, 75(3), 351–361. 28 L'Hommedieu, C. S., Nicholas, D., Armes, D. A., Jones, P., Nelson, T., & Pickering, L. K. (1983). Potentiation of --induced neuromuscular weakness by gentamicin, tobramycin, and amikacin. The Journal of pediatrics, 102(4), 629–631. 29 Dunn, C. J., & Goa, K. L. (2001). Risedronate: a review of its pharmacological properties and clinical use in resorptive bone disease. Drugs, 61(5), 685–712. 30 Hansten, P.D., & Horn, (1997). J.R. Drug Interactions Analysis and Management. Vancouver, WA: Applied Therapeutics Inc. 31 Sompolinsky, D., & Samra, Z. (1972). Influence of magnesium and manganese on some biological and physical properties of tetracycline. Journal of bacteriology, 110(2), 468–476. 32 Allen, M. D., Greenblatt, D. J., Harmatz, J. S., & Smith, T. W. (1981). Effect of magnesium--aluminum hydroxide and kaolin--pectin on absorption of digoxin from tablets and capsules. Journal of clinical pharmacology, 21(1), 26–30. 33 Snyder, S. W., & Cardwell, M. S. (1989). Neuromuscular blockade with magnesium sulfate and nifedipine. American journal of obstetrics and gynecology, 161(1), 35–36. 34 McConnell, R., Pelham, A., Dewhurst, F., & Quibell, R. (2021). Magnesium-induced ketamine toxicity. BMJ supportive & palliative care, bmjspcare-2021-002886. Advance online publication. 35 Neuvonen, P. J., & Kivistö, K. T. (1994). Enhancement of drug absorption by antacids. An unrecognised drug interaction. Clinical pharmacokinetics, 27(2), 120–128. 36 Ryan M. P. (1987). Diuretics and potassium/magnesium depletion. Directions for treatment. The American journal of medicine, 82(3A), 38–47. 37 Saleem, R., Ahmad, M., Naz, A., Siddiqui, H., Ahmad, S. I., & Faizi, S. (2004). Hypotensive and toxicological study of citric acid and other constituents from Tagetes patula roots. Archives of pharmacal research, 27(10), 1037–1042.

PROFESSIONAL USE ONLY