Functional Nutrition

Functional Nutrition:

“Seeing More” During the Functional Nutrition Physical Exam P. Michael Stone M.D., M.S P. Michael Stone M.D., M.S. Sydney Australia

©2014 The Institute for Functional Medicine Nutritional defects, “like deer in the forest” do not announce their presence but must be looked for” (Sanstead 1969) ©2014 The Institute for Functional Medicine Nutrition Evaluation

1) Vitals and Body Composition 2) Evaluate Smell and taste 3) Look in the Mouth 4) Look at and feel the Skin 5) Look at the Nails 6) Evaluate Peripheral Sensation

• Smell and Taste are Closely Linked • Evaluate the History: Trauma, Exposure, Allergy, Obstruction • Other physical exam findings- peripheral neuropathy • Evaluate Medications • Evaluate Nutritional Status: Mineral Status: Zinc, Copper, Iron, Iodine Vitamin Status: A, E: B complex-B2, B3, Pantothenic Acid, Biotin, Folate, B12

• Obstruction: Allergies, Nasal polyposis*, Deviated Septum*, Intranasal tumor • Sensory: Viral infection*, Chronic sinusitis*, Allergic Rhinitis*, Cigarette Smoke*, Toxic Chemical exposure, heavy metals (Al, Si, Pb, As, Cd) Drugs-calcium channel blockers • Neural: Head Injury*, Alzheimer's disease, Parkinson’s disease, Intracranial tumor, Schizophrenia • Endocrine: Hypothyroidism, DM • Nutritional: Iron, Zinc, Copper, Vitamin A, B1,12

Drug Group Examples z Calcium Channel Blocker Nifedipine, amlodipine, diltiazem Lipid Lowering Cholestyramine, clofibrate, pravastatin Antibiotic/Antifungal Streptomycin, doxycycline, terbinafine Antithyroid Carbimazole Opiate Codeine, morphine Antidepressant Amityptyline Sympathomimetic Dexamphetamine, phenmetrazine Antiepileptic Phenytoin Nasal Decongestant Phenylephrine, pseudoephedrine, oxymetazoline Miscellaneous Smoking, agyria (topical silver nitrate), cadmium fumes, phenothiazines, pesticides, Betnesol-N, Cocaine snorted

Pocket Smell Test 1) With the patient sitting, test nasal patency by having them cover one nostril and breath in. Listen for the sound of abnormal air flow. If present do not test, investigate cause of obstruction. 2) Open the card. Use the tongue depressor and scratch the scratch and sniff odorant. Have the client cover one nostril and sniff. Inquire as to the smell. If they are not sure, then offer choices. Repeat with the other nostril. 3) Repeat this with all three odors. The total score should be 6. If 2 or more are missed, then further work up of disordered smell and taste should begin.

• Smell (Quick Card), – Apple – Natural Gas – Rose OR – Lemon – Lilac – Smoke

How easily can you detect the tastes Easily Somewhat Not At All 1. Saltiness (chips, pretzels, salted nuts) 2. Sourness (vinegar, pickles, or lemons) 3. Sweetness (soda, cookies, ice cream) 4. Bitterness (coffee, beer, tonic water)

Negative Predictive value for easily: saltiness 95%, sourness 89%, Sweetness 98%, Bitterness 92%. Positive predictive values range from 5-26% (when a person can Easily taste each of the 4 senses then there is a high degree of confidence that they Can taste. Easily is negative for gustatory loss, and somewhat or not at all is positive For loss.

Malaty J, IAC Malaty: Smell and Taste Disorders in Primary Care Am Fam Physician 88;12; 852-859, 2013.

Genetics of Taste

m.stone md Supertasters vs non tasters: Vegetable avoidance, increased fat and sweet intake, disinhibited eating behavior among women, More Alcohol dependence.

1) Taste perception affects food selection 2) Supertasters have a tendency to eat less vegetables, eat vegetables more with sauces, dislike coffee, moderate to little like for sweets, pepper/chili and alcohol are more irritating, and perceive feel not tast of fat. 3) Non bitter tasters more susceptible to eating spoilage, and poisonous alkaloids. 4) Can change your therapeutic interventions.

Chemical Gene Allele Sucrose TAS1R3 -1572 C/T Glutamate TAS1R3 R757C Isothiocyanate TAS2R38 A49P, V262A, 1296V Isovaleric acid OR11H7P C/T at nt 679 Androstenone OR7D4 R88W

Gene Quality Genotype Rating of Good Child 1 Child 2 Taste TAS1R3 Sweet in Onion +/+ -/- YUM! TAS1R3 Umami in Tomato +/+ -/- TAS2R38 Bitter in Watercress -/- +/+ OR11H7P Sweat odor in Cheese -/- +/+ OR7D4 Boar Taint in Ham -/- +/+ YUCK!

Reed DR, Knaapila A: Genetics of Taste and Smell: Poisons and Pleasures. Prog Mol Biol Trans Sci: 2010:94:213-40 ©2014 The Institute for Functional Medicine Taste Loss Infection: Oral Candida, Periodontal disease, gingivitis oral abscess, viral URI, HIV Oral Appliances: Dentures, prosthetics Postsurgical: Middle ear surgery affecting corda tympany, oral or dental surgery especially 3rd molar extraction Radiation: HEENT irradiation with oral mucositis, xerostomia Nutrition insufficiency: Protein malnutrition, zinc, copper deficiency, B12, niacin deficiency Medications: Intranasal zinc, chlorhexidine, chemotherapy, ACE Inhibitors, ARBs, calcium channel blockers, diuretics, macrolides, terbinafine, fluoroquinolones, protease inhibitors, griseofulvin, PCN, tetracyclines, metronidazole, antiarrhythmics, antidepressants, anti convulsants, lipid lowering agents. Head Trauma: Toxins: pepper gas, weed killer, ammonia, benzene, cadmium, iron, lead Medical Conditions: Cancers, Type 2 DM, Hypothyroidism, Renal Failure

1) Jaw Movement 2) Lips 3) Soft and Hard Palate 4) Tongue 5) Gums 6) Buccal Mucosa 7) Teeth 8) Chew/swallow

Oral mucosal condition Associated micronutrient deficiency Angular Cheilitis Riboflavin, Nicotinic acid, Folic Acid, Biotin Cobalamin, Vit C, Cheilosis (dry cracking) Fe, Zn. /Riboflavin, Niacin, Pyridoxine Burning Mouth Syndrome Pyridoxine Candidiasis Folic acid , cobalamin, Iron Glossitis Riboflavin, nicotinic acid, pyridoxine, folic acid, cobalamin, iron, protein energy malnutrition Lip fissures Pyridoxine Oral Sensitivity Thiamine, pyridoxine Recurrent apthae Riboflavin, Folic acid, Cobalamin, Ascorbic Acid Stomatitis Nicotinic acid, Folic acid, Cobalamin. Periodontal disease Vitamin A, D, E, B-Carotene, Thiamin, Folate B12, E, C, Ca, Se Poor mucocutaneous Riboflavin, Niacin, pyridoxine, Zinc border Moynihan P. : Nutrition and its effect on oral health and disease. Ch 5, pp 83-99. In M. Wilson: Food constituents and oral health. Current status and future prospects. CRC Press Boca Raton Fl 2009. ©2014 The Institute for Functional Medicine ©2014 The Institute for Functional Medicine 2-Lips Cracks, Lesions, Sores

Which Nutrients are Associated With Each Condition? Zinc, Vitamin A, C

Riboflavin, B-6, B-12 Folate, Minerals: Zinc, Fe

Perlèche-angular cheilitis

Herpes Labialis Lysine/Arginine Balance Lower levels of A,E,C

Recurrent Aphthous Stomatitis

• Movement • Color • Coating • Fissuring • Scalloping • Piercing • Taste Bud Distribution • Lesions

Tongue Coating Score

0= No tongue coating 1= Thin tongue coating 2= Thick tongue coating difficult to see papillae Significantly more anaerobic bacteria the thicker the coat, No significant difference in candida

4-Tongue Glossitis with Taste Bud Atrophy

B12, Thiamin, Riboflavin Niacin, Pellagra

mstone

Median Rhomboid Glossitis

Erythema Migrans Oral Hygeine, Candidiasis Candida, Abx Leukoplakia Dysbiosis-oral Iron and Selenium Hairy tongue

Allergy-Intolerance

Scalloping

• Macroglossia- any cause • Hypothyroid, acromegaly, amyloidosis, down syndrome • Sleep apnea • Increased in autoimmune conditions* • Increased in food allergy and hypersensitivity*

m.stone md

Filiform (coating)

• Tendency toward Allergy • If painful and geographic: -Iron, folic acid, B2, B12, Niacin • Associated with systemic inflammation

Evid Based Complement Alternat Med. 2013; 2013: 204908 BMC Complement Altern Med. 2013; 13: 227 Sci Rep. 2012; 2: 936

•

• Glossitis (Red Tongue) Protein Undernutrition, Iron, Riboflavin, niacin, B6, folate, B12 • Decreased taste/smell Burning tongue: Zinc, Vitamin C

• Tongue fissuring Niacin, gut triggered immune issues • Tongue –taste bud atrophy Iron, Riboflavin, niacin, B12

• Leukoplakia Vitamin A, B2, niacin, B6, Folate, B12

• Hairy black tongue Not Specific; associated with smoking, sulfur granule positive bacteria, antibiotics PFC-MVP

Gingivitis Periodontitis

IL1, IL6, IL10, VDR, genes may be associated with Chronic Peritonitis

Treating Periodontal disease aggressively and early in pregnancy increases the chance of a full term vs preterm delivery by 6 fold.

M. Jeffcoat, S. Parry, M. Sammel, B. Clothier, A. Catlin, and G. MacOnes, “Periodontal infection and preterm birth: successful periodontal therapy reduces the risk of preterm birth,” British Journal of Obstetrics and Gynaecology, vol. 118, no. 2, pp. 250–256, 2011

1) Cigarette smoking 2) Systemic diseases autoimmune, diabetes, CVD... 3) Medications such as steroids, anti-epilepsy drugs cancer therapy drugs 4) Ill-fitting bridges 5) Crooked teeth and loose fillings 6) Pregnancy 7) Oral contraceptive use 8) Low Vitamin D, Vitamin A, Low Vit C, Low Fe, Zn

Jemin Kim-Periodontal disease and systemic conditions: a bidirectional relationship.

5-Gums, Gingival findings can cause you to look elsewhere...

Hemorrhages: Vitamin C Bleeding gums and...

m.stone md

Pretreatment Post-treatment

Dark Lines: Lead (Burton’s Line)

Some discolorations from other heavy metals toxicity and therapeutics have been documented- cadmium, bismuth, mercury, cis-platinum

. J A Regezi, J L Sciubba and RCK Jordan: Oral Pathology Clinical Pathologic Correlations. 2008. 5th Edition©2014 The Institute for Functional Medicine 60 y.o. male T2DM, Arrhythmia, Htn, worsening evening vision with mouth findings... What do you see and think?

• Low Vitamin D • Low ionized calcium • Low Vitamin A • Low Vitamin C • Low pH

m.stone md • Low salivary output secondary to beta blocker for arrhythmia • Occult infection

Missing Teeth/Repairs Amalgam and Alloy Load

MStone MStone

• 1 in 5 Celiacs have Enamel Dystophic Changes. Those without celiac 1/100

El-Hodhod, MA et al: Screening for celiac disease in children with

• Erosions of Recurrent Vomiting- Bulemia

EX EX A A GC/RC A A A A = Amalgam EX EX EX EX GC = Gold Crown A A A A PC = Porcelain Crown A A EX EX PD = Periodontal Dz RC = Root Canal EX = Extraction

Possible Antecedents and Triggers

Missing Teeth/Repairs Amalgam and Alloy Load

2-28 mcg/facet/day 80 % absorbed

MStone MStone

RA Bernhoft: Mercury Toxicity and Treatment. J Env Public Health 2012

Marek, M. "Interactions Between Dental Amalgams and the Oral Environment." Advances in Dental Research Sept. 1992: 100-09. A.sagepup.com. Web. 19 Nov. 2011.

If Amalgam Fillings might be a root cause of health problems…

For a Biologic Dentist near you! International Academy of Oral Medicine & Toxicology www.iaomt.org

1) The pH of the mouth helps determine and is determined in part by the microflora- oral dysbiosis, infection, salivary flow, and buffering capacity of the saliva. 2) pH<6.8-7.4 is associated in increased endothelial dysfunction, inflammation, and oxidative stress. 3) pH<5.8 associated with enamel disruption and cariogenesis 4) Intervention with increased vegetable intake, alkalization of the diet, and treating causes of low salivary flow or poor buffering improves pH and oral dysbiosis

• pH paper or sticks • Different Techniques- Touch, Spit, Collect • Compare to the pH guide • pH>6.8-7.4 “ideal” • pH <6.8 is acidic • pH<5.8 enamel erosion “Alters environment”

Oscillating. pH Conditions in the Mouth

1) Vitals and Body Composition 2) Evaluate Smell and taste 3) Look in the Mouth 4) Look at and feel the Skin 5) Look at the Nails 6) Evaluate Peripheral Sensation

Character: • Temperature • Texture • Color • Hydration • Lesions • Hair Distribution

• Barrier Health • Membrane Health • Cellular Health • Requires Cofactors Atopic Dermatitis – Elongases – Desaturases

Psoriasis

Hyperkeratosis pilari

Seborrhea, dry scaly skin Dry eczematous rash

+Deficiency in EFAs, Vit A, zinc, biotin +Dysbiosis +Food allergy / sensitivity

• Highly variable • BCMO1 – encodes enzyme converts beta carotene to retinol • In summary, a range of SNPs can influence the effectiveness of using plant-based carotenoids to increase vitamin A status in at-risk population groups and this effect may vary depending on ethnic origin. • Other influences – food source, BMI (increased BMI = decreased conversion), hypothyroidism, zinc, copper and selenium • Zinc deficiency limits bio availability of vitamin A • Often give vitamin A and zinc together

Lietz, G. J Nutr. 2012;142:161S-165C

Gluten Sensitivity vs. Celiac; Innate vs. Adaptive Immune Balance

Celiac Dermatitis Herpetiformis

• Smooth, velvet-like, hyperkeratotic plaques in intertriginous areas (e.g., groin, axillae, neck). • Will resolve when insulin resistance resolves.

• Type I is associated with malignancy. Sudden onset. Extensive truncal distribution, including the face, palms, and trunk. • Type II is the familial type, with autosomal dominant transmission. Rare and appears at birth or soon after. • Type III: obesity and insulin resistance. Most Common • Drugs: systemic corticosteroids, nicotinic acid, diethylstilbestrol, and isoniazid (INH).

Type 2 DM, PCOS

Glucocorticoids, niacin insulin, oral contraceptives protease inhibitors

Skin Tags

Vitamin A, B complex, EFA, Vitamin C undernutrition

Follicular Purpura

Swan neck hairs

Bruising

Actas Dermosifiliogr. 2005 Jul-Aug;96(6):400-2. Léger D. Can Fam Physician 2008;54:1403-6

Deficiency in Zinc, Dietary Allergens, Vit A, EFAs. High GL diet, Dairy.

• Hypochlorhydria results in increase risk of SIBO / gut infections • SIBO leads to decreased absorption of protein, fats, carbs and vitamins secondary to inflammation • Injury to enterocytes in small intestine = increased intestinal permeability • SIBO associated with depression and anxiety and eradication improves emotional symptoms • SIBO is associated with a 10X increase in acne rosacea • LPS endotoxins are more common in people with acne Bowe + Logan. Gut Pathogens. 2011;3:1.

March 28, 2002 Dec 6 2004

Dioxin Poisoning Typical blood dioxin level: 15-45 units / gram of blood fat Yushchenko: 100,000 units / gram

• Chlorinated phenols • Chloronaphthalenes • Polychlorinated biphenols • Other polychlorinated compounds: polyhalogenated dibenzofuranes, polychlorinated dibenzo-p-dioxins, chlorinated azo and azoxybenzenes. • Location of the halogen on the benzene rings determines the acnegenicity.

• Chloracne is most consistent manifestation of dioxin intoxication • Absorbed by direct contact, inhalation, ingestion • Normally TCDD <10 ppt (parts per trillion) in patients with chloracne levels in the several hundreds. • Dioxin: highly lipophilic • Half life 7-11 years

• Early: face and neck • Later: trunk, extremities, genitalia • Comedone appearance more often on the face and neck, below and to the outer side of the eye (malar crescent), Posterior auricular triangles. • Ear lobes, suboccipital hairline and groin involved. • Nose, perioral skin and supraorbital regions usually spaired. • Other skin lesions: xerosis from decreased sebum secretion, pigmentation, porphyrinopathy, hirsutism, skin thickening , palmoplantar hydrosis, palmoplantar hyperkeratosis.

Predilection site Localized, face, chest, back Generalized: retroauricular, malar, axillae, groin, extremities Major Lesions Limited comedones, papules, pustules, Myriad comedones cysts Pathogenic factors

Inflammatory lesions common Very rare

Sebum production Increased Decrease

Microflora Propionibacterium acnes No bacteria Propionibacterium granulosum Androgen sensitivity Dependent Unknown

Therapy Effective under treatment of Calorie Restriction and Dietary fat antibiotics, substitute (Olestra) up to a 30 Resistant to therapy retinoids and fold increase in excretion other treatment

Ju Q, CC Zouboulis, L Xia: Environmental pollution and acne: Chloracne Dermato-Endocrinology 1:3,125-128, 2009 ©2014 The Institute for Functional Medicine Drug Induced Acneiform Eruptions Du-Thouh A, N Kluger, H Bensalleh, B GuillitAm J Clin Derm 2011; 12(4)233-245

Categories Causitive Agents Hormones Corticosteroids, Corticotropin(ACTH), Androgens/Anabolic steroids, Hormone contraceptives, TSH

Neuropsychotherapeutics Tricyclic antidepresents, Lithium, Antiepileptics, SSRI... Vitamins Excess Vitamin A, Thiamine, Pyridoxine, B12 Cytostatic Drugs Azathioprine, thiourea, thiouracil, Dactinomycin (actinomycin D)

Immune Modulators Cyclosporin Antituberculin Isoniazide, Rifampin, Ethionamide Halogens Iodine, Bromine, Chlorine, Halothane, Lithium

©2014 The Institute for Functional Medicine Iodine Low Iodine High Iodine • Cold dry skin • Iododerma (multiple • Sparse hair nodular, ulcerating, • Decreased pustular, fungating perspiration lesions • Frank Myxedema • Kelp Acne

• Increased dermatographia • Acrodynia of the hands and feet • Xerosis and peeling palms and soles of feet • Autonomic dysfunction with increased flushing/sweating/hypersalivation (acute) • Methyl mercury, ethyl mercury, elemental mercury with different findings dependent on exposure.

Weinstein M, S Bernstein CMAJ • JAN. 21, 2003; 168 (2) 201. ©2014 The Institute for Functional Medicine Weinstein M, S Bernstein CMAJ • JAN. 21, 2003; 168 (2) 201. ©2014 The Institute for Functional Medicine Weinstein M, S Bernstein CMAJ • JAN. 21, 2003; 168 (2) 201. ©2014 The Institute for Functional Medicine Hg+ Dose Burden

©2014 The Institute for Functional Medicine 91 pmstone©2014 The Institute, md,ms for Functional 2013Medicine Seborrheic keratosis: common benign epithelial tumors. Do not appear until age 30 and over the lifetime. Small to large barely elevated papules to “stuck on” Plaques Lesions do not require treatment except for cosmetic reasons. They can become irritated or traumatized with pain and bleeding, squamous cell cancer should be ruled out.

Wolff, K, RA Johnson: Benign Tumors pp 215-218. Fitzpatrick’s Color Atlas and Synopsis of Clinical Dermatology. 6th ed 2009

92 pmstone©2014 The Institute, md,ms for Functional 2013Medicine Seborrheic Keratosis Key Question….. When Did They Appear? All at once, over a short period of time…? Patient…Why do you ask? Provider…I am wondering, what was the trigger?

Significant associations between low intakes of various nutrients (retinol, calcium, fiber, folate, iron, riboflavin, thiamin, vitamins A, C, and E) and Keratotic skin lesion incidence in people exposed to environmental arsenic.

Greater intakes of methionine, Cysteine, protein and vitamins such as thiamin and niacin increased arsenic secretion

Mekonian S et al: J Nutr 142:2126-2134,2012

Timing of Appearance Defense and Repair Exposures-toxins Structural Integrity -Repair-methylation status Nutrition Adequacy- Protein Fat Minerals Vitamins Phytonutrients 95 pmstone©2014 The, Institute md,ms for Functional 2013 Medicine Seborrheic Keratosis: When Did They Appear?

Physical Exam Finding of Seborrheic Keratosis Ask when they appeared- all at once or gradual Ask about water- well or city Ask about diet- adequate protein, essential fats Carbohydrates, Minerals, Vitamins, Phytonutrients Ask about cancer in family, consider MTHFR Status Ask about toxins (environmental, water, air, occupation) particularly heavy metals including arsenic Clinical Findings that may be associated: fatigue, peripheral neuropathy, digestive symptoms-nausea, vague tenderness Consider heavy metal testing (random serum), provoked urine collection of urine following oral chelator dose like DMSA at 20-30 mg/kg if creatinine is normal to harvest high levels of arsenic, lead, or mercury, cadmium, or tin Discuss Dietary and Lifestyle Changes which will aid in the repair of DNA, the excretion of arsenic and heavy metals and the adequacy of micronutrients in the setting of unique SNP patterns in the patient. Consider Evaluating other Abdominal Pathology. pmstone, md,ms 2013 96 ©2014 The Institute for Functional Medicine Seborrheic Keratosis

Nutrition Deficiency or Toxicity Sign?

©2014 The Institute for Functional Medicine SK, SSC, Melanoma Skin Cancer MTHFR and VDR polymorphisms • UVA breaks down plasma folate – Folate is involved in DNA synthesis and repair • UVB can synthesize vitamin D in the skin – Vit D has anti-proliferative effects • Highest risk for SCC (squamous cell carcinoma) VDR Receptor SNP’s with MTHFR 677TT Fokl T Increased risk of MM polymorphism and low Bsml Decreased risk of MM, folate intake Increased Sq Cell CA

Taq1 Increased risk of S.K. mstone Han J. Carcinogenesis. 2007;28:390-7 Dermato-Endocrinology 3:1, 11-17, 2011

• Shape Distal Edge Lateral recess • Color Lunula • Pattern of Color Cuticle Eponychium • Texture and Strength • Growth Pattern • Surrounding Tissue

• Koilonychia Fe, Cu, Zn, Protein • Transverse pigmentation Protein • White spots leukonychia Zinc, selenium, protein, niacin (pellagra) • Psoriatic nails Vitamin D • Beau’s lines Zinc • Pale nail beds Iron • Muehrcke's lines (bands) Protein, stationary and paired • Mees’ lines Transverse white lines: arsenic • Splinter hemorrhages Vitamin C • Onycholysis Iron, niacin • Chronic paronychia Zinc • Red lunula (CHF) CoQ10, Ribose, Mg, Carnitine (if DD) • Terry nails (white) Liver Failure, Hep B, DM, CHF • Brittle nails (onychorrhexis) Malnutrition, protein, calcium, low HCl • Diffuse milky white nails Niacin (pellagra), zinc, malnutrition • Variable white Hypocalcemia • Diffuse brown/black bands Malnutrition • Blue nails Wilson’s disease

Zinc Deficiency Selenium Deficiency

Shape, Color and Pattern of Color, Texture and Strength, Growth Pattern, Surrounding Tissue

Clubbing: Inflammatory Bowel, Sprue

Koilonychia: Iron, Protein, Median Zinc, Cu nail dystrophy: Malnutrition

Onychorrhexis: Iron, Folic Acid, Protein

• Deficiency: Zinc, Selenium • Toxicity: Arsenic, Selenium • Systemic disease: Renal (hemodialysis), Liver Disease • Medications: Chemotherapy • Trauma, manicure, biting tapping.

Shape, Growth Pattern: Beau’s Lines

• Zinc deficits • Other causes- • Severe illness • Measles/mumps • Syphilis • Poorly controlled DM • Myocarditis

Shape, Color and Pattern of Color, Texture and Strength, Growth Pattern, Surrounding Tissue

Core Aspects of the Nutrition Physical Exam

1) Vitals and Body Composition 2) Evaluate Smell and taste 3) Look in the Mouth 4) Look at and feel the Skin 5) Look at the Nails 6) Evaluate Peripheral Sensation

Light touch Hot/Cold Position Sense Vibratory Sense Reflexes Muscle Strength Balance Walking

• 128 Hz tuning • Normal Peripheral fork vibratory sense of the thumb and 5th distal finger, and the great toe and the 5th toe.

• 5.07 • Normal Monofilament Semmes- sensation Feet and Weinstein Hands Monofilament

Routine-Tier One • Hbg A1C, hsCRP, CBC dif • Serum B12, Methylmalonic acid, Homocysteine • Serum Heavy metals: Arsenic, Lead, Mercury, • Celiac Panel-gluten induced autoantibodies.

Tier Two or Three • RBC Lipids, • RBC Minerals • Organic Acid Testing – (metabolism of valine, leucine, and isolucine blocked by insufficiency of B1,B2,B3, Pantothenate, and Lipoate), – Isoleucine catabolism (blocked by deficiency of Biotin)

• Serum Amino acids

Further w/u with Nerve Conduction Studies may be warranted.

©2014 The Institute for Functional Medicine Vinik AL: Diabetic Neuropathy in Older Adults. Clin Geriatr Med 24(3)407-v, doi:10.1016/j.cger.2008.03.011, 2008. ©2014 The Institute for Functional Medicine Vinik AL: Diabetic Neuropathy in Older Adults. Clin Geriatr Med 24(3)407-v, doi:10.1016/j.cger.2008.03.011, 2008. ©2014 The Institute for Functional Medicine Peripheral Neuropathy: Presentation

1) Symmetry, sensory level dependent peripheral neuropathy 2) Proximal Weakness vs. Distal Weakness 3) Muscle loss 4) Periosteal Tenderness 5) Multilevel neurologic change vs isolated

1) Prominent pain: burning, superficial and associated allodynia (painful touch) 2) Hypoalgesia late in the condition 3) Defective autonomic function with decreased sweating, dry skin, impaired vasomotion and blood flow and cold feet. 4) Intact reflexes, motor strength 5) Silent electrophysiology 6) Reduced sensitivity to monofilament and pricking sensation using the Waardenberg (Wartenburg) wheel or similar instrument 7) Abnormal warm thermal perception, neurovascular function, pain, quantitative autonomic function tests.

1) Impaired vibration perception and position sense 2) Depressed tendon reflexes 3) Dull (like a toothache), crushing or cramp like pain in the bones of the feet 4) Sensory ataxia (waddling like a duck) 5) Wasting of small muscles of the feet with hammertoes and weakness of hands and feet 6) Shortening of the Achilles tendon with equines 7) Increased blood flow to the foot (hot foot) increased risk of charcot neuroarthropathy)

Vinik AL: Diabetic Neuropathy in Older Adults. Clin Geriatr Med 24(3)407-v, doi:10.1016/j.cger.2008.03.011, 2008

1) reduced vibration sense 2) reduced position sense 3) reduced light touch 4) weakness 5) muscle wasting 6) depressed tendon reflexes

At the end of their treatment, 73% of patients showed an increase in calf Endothelial Nerve Fiber Density, 82% of patients experienced both reduced frequency and intensity of paresthesias and/or dysesthesias. Greater improvement after 1 year

Methyl Folate: 3 mg, Methyl Cobalamin 2mg, Pyridoxine 5 Phosphate 35 mg twice a day

Jacobs AM, Cheng D Rev Neurol Dis. 2011;8(1-2):39-47. Walker MJ, Morris LM, Cheng D Rev Neurol Dis. 2010;7(4):132-9 Metanx® is an orally administered medical food for use only under medical supervision for the Abstracts of the Diabetic Foot Global Conference. Oral Presentations dietary management of endothelial dysfunction in patients with diabetic peripheral 2009. neuropathy. ©2014 The Institute for Functional Medicine Growing New Nerves in Diabetics with DPN

Nutrient Mechanism Methyl Folate Enhances production of tetrahydrobiopterin, enhances endothelial nitric oxide synthase. Counteracting oxidative- nitrosamine stress through restoration of endothelial nitric oxide synthase coupling vasonervorum. Methyl Cobalamin Neutralization of superoxide and peroxynitrite, promotes myelination and transport within the cytoskeleton of the peripheral nerves Pyridoxine 5 Chelation of transition metals and traps 3 deoxygluosone to Phosphate inhibit the formation of Advanced Glycosylation End products.

Jacobs AM, Cheng D Rev Neurol Dis. 2011 8(1-2):39-47 .Miranda-MassariMetanx JR:® Curris an orallyClin Pharmacol administered6 (4):260medical- 273,food for2011 use only under medical supervision for the AbstractsShevalye of the, Diabetic H, et al:. Foot Diabetes Global 61:2126 Conference.-2133, Oral2013 Presentations Walker MJ, Morris LM,dietary Cheng management D Rev Neurol of endothelialDis. 2010;7(4):132 dysfunction-9 in patients with diabetic peripheral 2009. neuropathy. ©2014 The Institute for Functional Medicine • Highly Prevalent amongst patents with DM type 1,2,3 • Impaired Memory • Dementia • Delirium • Peripheral Neuropathy • Sub acute combined degeneration of the spinal cord • Megaloblastic anemia • Pancytopenia

Kibirige, D, R Mwebaze: Vitamin B12 deficiency among patients with diabetes mellitus: is routine screening and supplementation justified. J

Diabetes & Metabolic Disorders 12:17, 2013 ©2014 The Institute for Functional Medicine Retelling the Patient’s Story Physiology and Function: Organizing the Patient’s Clinical Imbalances Antecedents Assimilation Defense & Repair

MTHFR, • Inflammatory bowel • Food Allergy Methylation SNPs diseases leading to poor • Celiac, IBD/Crohn's with FHx DM absorption of nutrients. malabsorption. Postherpetic neuralgia • RA, SLE, Intrinsic Factor Triggering Events Autoantibodies, low ADE Structural Integrity Energy • Renal Failure, many • CoQ10 /statin causes, VAT, • B12 • Obesity, 3 Most common causes of Neuropathy in Adults transcobalamin • Endothelial 1) Insulin Resistance, DM deficiency, dysfunction 2) Alcohol • Methylation 3) OccupationalM or Therapeutic Exposures factors Mediators/Perpetuators Communication Spiritual Biotransformation & Elimination • IR and DM • Heavy metals, • Low testosterone MSG, Gentamicin, Cisplatinum, Alcohol • Salicylates, arsenic, gout,occupational DecreasedPersonalized LifestyleVibratory Factors Sense Sleep & Relaxation Exercise & Movement Nutrition & Hydration Stress & Resilience Relationships & Networks

Light touch- Monofilament Testing

©2014 The Institute for Functional Medicine Why Check Light Touch with a Monofilament? 1) Helps determine adequacy of one of the protective senses. 2) Helps determine whether there is large or small fiber involvement. 3) If abnormal points to heavy metal burden, dysglycemia, drug associated causes for neuropathy, mitochondrial dysfunction, or nutritional underlying cause of system dysfunction.

©2014 The Institute for Functional Medicine Asparagine Curcumin Choline Glutathione Green Tea Selenium Protein Copper Resveratrol Omega 3 Fatty Acids Inositol Magnesium Spices Microbiome Balance Vitamin E Alpha Lipoic Acid Propolis Reducing Oxidative Stress Niacin Acetyl L Carnitine Reducing the Biologic Dysfunction Nicotinamide Promoting Growth and Repair… Riboflavin Taurine

Thiamin Low Glycemic Diet

Manganese Vitamin C Pyridoxine 5 phosphate Methycobalamin Vitamin K Pantothenic Acid Zinc L methyl folate Rosemary Grape seed extract Hyperbaric Oxygen Biotin Vitamin A Sodium CoQ10 Gamma Linoleic Acid Glutamine ©2014 The Institute for Functional Medicine Core Aspects of the Nutrition Physical Exam

1) Vitals and Body Composition 2) Evaluate Smell and taste 3) Look in the Mouth 4) Look at and feel the Skin 5) Look at the Nails 6) Evaluate Peripheral Sensation

Context Company History-Timeline Symptoms, Other Signs Network Influences Current Biochemical Markers

Quantity Diet, Food, Nutrient

“Seeing More” During the Functional Nutrition Physical Exam P. Michael Stone M.D., M.S.