Nutritional Supplement Use for Autistic Spectrum Disorder by Jon B. Pangborn, Ph.D. A Summary Table of Contents Prerequisite Strategies ............................................................................................................................... 3 Strategies and Priorities for Use of Nutritional Supplements for ASD .............................................. 3 Six Rules for Trial/Use of Nutritional Supplements ............................................................... 3 A Dozen Don’t/Dos ..................................................................................................................... 3 Supplement Intervention Schedule ......................................................................................................... 4 Preliminaries and Prerequisites .................................................................................................. 4 Initial Tests ..................................................................................................................................... 4 Tier Explanations .......................................................................................................................... 5 Technical Information on Nutritional Supplements (omitted)............................................................ 6 Nutrient Descriptions and Use Information .......................................................................................... 6 Alpha-ketoglutaric acid................................................................................................................ 6 Amino acids (except taurine) ...................................................................................................... 7 L-Carnitine ..................................................................................................................................... 7 Carnosine ....................................................................................................................................... 7 Creatine .......................................................................................................................................... 7 Digestive Enzymes........................................................................................................................ 8 DMG, TMG .................................................................................................................................... 8 Fatty Acids ..................................................................................................................................... 9 Glutathione .................................................................................................................................... 9 Herbals.......................................................................................................................................... 10 Anti-yeast/fungal .......................................................................................................... 10 Olive leaf extract ............................................................................................... 10 Pau d’Arco ......................................................................................................... 10 Goldenseal.......................................................................................................... 10 Saccharomyces boulardii (probiotic) .............................................................. 10 caprylic acid ....................................................................................................... 10 calcium caprylic ................................................................................................ 10 Antibacterial Herbals..................................................................................................... 10 Oregano .............................................................................................................. 10 Thyme ................................................................................................................. 10 Goldenseal.......................................................................................................... 10 1 Antioxidant/Anti-inflammatory Herbals .................................................................. 10 Turmeric (curcumin) ........................................................................................ 10 Silymarin (from milk thistle) ........................................................................... 10 Cognitive Improvement Herb ...................................................................................... 10 Bacopa................................................................................................................. 10 Melatonin ..................................................................................................................................... 10 Minerals and Elements ............................................................................................................... 11 Calcium............................................................................................................................ 11 Iodine and thyroid support .......................................................................................... 11 Magnesium ..................................................................................................................... 12 Selenium .......................................................................................................................... 12 Zinc .................................................................................................................................. 12 Probiotics ...................................................................................................................................... 13 Taurine.......................................................................................................................................... 13 Vitamins ....................................................................................................................................... 14 B-vitamins and folate..................................................................................................... 14 B1 Thiamine ....................................................................................................... 14 B2 Riboflavin ..................................................................................................... 14 B3 Niacin ............................................................................................................ 14 B6 Pyridoxine .................................................................................................... 14 Pantothenic Acid ............................................................................................... 14 B12 Cobalamin................................................................................................... 14 Folic Acid, Folate............................................................................................... 14 Vitamin A ........................................................................................................................ 15 Vitamin C ........................................................................................................................ 15 Vitamin D ........................................................................................................................ 15 Vitamin E......................................................................................................................... 16 Supplements to be Wary of .................................................................................................................... 16 Also Consider (not from Pangborn’s book)......................................................................................... 16 Chromium .................................................................................................................................... 16 Alka Seltzer Gold ........................................................................................................................ 16 Biotin ............................................................................................................................................. 16 Choline, phosphatidylcholine, or GPC (Glycerophosphocholine) ...................................... 16 2 Nutritional Supplement Use for Autistic Spectrum Disorder by Jon B. Pangborn, Ph.D. A Summary Prerequisite Strategies Prerequisite Strategy 1: Remove/avoid potentially toxic chemical stressors Organochlorides - the beginning of acquired ASD Organophosphate toxicants Other toxicants of concern Purifying your living space, food, and drink Prerequisite Strategy 2: Remove/avoid infectious stressors Yeast overgrowth [anti-fungal medications, low sugar diet] Bacterial dysbiosis and excessive use of antibiotic medications Killing persistent pathogens naturally Prerequisite Strategy 3: Fix the diet Prerequisite or Concurrent Strategy 4: Relational Therapy and Special Education Strategies and Priorities for Use of Nutritional Supplements for ASD Six Rules for Trial/Use of Nutritional Supplements 1. Use the purest, highest-grade nutritional supplements available. 2. Coordinate supplement trials with the other interventions such as diet trials and medical procedures that your doctor may have underway. 3. Always start with a low amount. 4. Discontinue the supplement if there are adverse effects, except in a few cases, such as digestive enzymes or perhaps probiotics, where “worse” may precede “better.” 5. Introduce new supplements one at a time with few exceptions. B6 and magnesium together is such an exception. 6. Keep records religiously. A Dozen Don’t-Dos 1. Don’t start two or more different intervention trials at the same time. 2. Don’t begin with detoxification interventions. 3. Hold off on sophisticated metabolic manipulations until later. 4. Don’t use vitamin B12 in any form as a separate supplement until you already have L-carnitine in use (acetyl-L-carnitine). 5. Don’t use amino acid supplements (except taurine) until intestinal health has been addressed and dysbiosis has been remedied. 6. Don’t supplement vitamin B6 without also supplementing magnesium. 3 7. Don’t use supplements that metabolize homocysteine to methionine (such as TMG or DMG) without having taurine in use. 8. Don’t rely on laboratory tests of urine analytes for guidance on supplementation when analytes are ratioed to creatinine and creatinine itself is subnormal. 9. If your ASD individual has excessive urine levels of oxalate, be sure that calcium and lipase (a digestive enzyme) are supplemented, as well as taurine, vitamin B6, and magnesium. 10. At supper or in the evening, don’t give supplements that contain phenylalanine, tyrosine, or histidine, and don’t feed high-protein meals late in the day. 11. Don’t use cysteine, cysteine, or alpha-lipoic acid as nutritional supplements except under medical supervision and with periodic checks of intestinal yeast content. 12. Don’t use N-acetylcysteine unless it is certified to be the reduced, active form, and then do periodic checks of intestinal yeast content. Supplement Intervention Schedule Preliminaries and Prerequisites Diagnosis of ASD Find a qualified doctor or physician assistant Find a qualified nutrition counselor Record patient and family histories Environmental cleanup Diet cleanup Arrange for relational therapy Initial tests Physical exam Blood chemistry, CBC Thyroid markers Urinalysis Stool analysis including digestive and inflammation markers, microbiology, mycology and parasitology Blood ammonia? Other doctor-ordered tests metric tests of autism severity 4 Tier Explanations TIER 1, Basic for ASD, CF (Casein-free) Trial 6 weeks Digestive aids (enzymes) Alpha-ketoglutarate if ammonia is elevated Activated charcoal (use as needed) Calcium, magnesium, multiminerals? Taurine L-carnitine Multivitamins: B complex, folate, A, C, D, E Melatonin Omega-3 Fatty acids TIER 2, Intestinal Cleanup, GF (Gluten-free) Trial 12-16 weeks Continue Tier 1 supplements, plus Herbal antibiotics: oregano, thyme Activated charcoal Probiotics & S. boulardii Turmeric, silymarin More antioxidant nutrients? Zinc Carnosine, esp. with seizure cases TIER 3, Healing Period, Carbohydrate check, Gut check Try or continue Low Oxalate Diet? More Omega-3 fatty acids Continue Tier 1 supplements; perhaps more L-carnitine Continue but reduce Tier 2 supplements to maintenance levels for intestinal health If oxalate was high initially, retest now. If still high, check fat content of stool with new stool analysis; Recheck intestinal flora and digestive markers 5 TIER 4, Detox and Antioxidant Brigade Choose and stay on most beneficial diet Detoxification therapies - chelation, saunas, sulfate baths Clean environment is essential Continue supplements as in Tier 3, plus Extra vitamin C Glutathione, NAC Extra taurine Magnesium malate CoQ10 Watch out for reoccurance of dysbiosis TIER 5, Special Metabolic Measures Continue diet Continue supplements as in Tier 3 Continue Tier 4 detox and antioxidant supplements at reduced or maintenance levels, plus: Creatine Amino Acids DMG or TMG, folinic acid Methylcobalamin (B12) Carnosine (may have been tried in Tier2) Bacopa Technical Information on Nutritional Supplements (omitted) Nutrient Descriptions and Use Information 1 pound = about .454 kilograms (multiply your child’s weight in pounds by .454 to find out how many kilograms they weigh) doses indicated are per day Alpha-ketoglutaric acid If ammonia excess is the problem, 50-200 mg per kg body weight - Tier 1 Other problems, 25-100 mg per kg body weight Divided doses with meals works best Do not use unbuffered alpha-ketoglutaric acid 6 Amino acids (except taurine) An amino acid supplement is a Tier 5 item Never begin nutritional intervention with amino acid supplements, except taurine Our bodies are supposed to break food down into amino acids Amino acid test will show deficiencies balanced blends are generally safe in amounts suggested by the manufacturer Pangborn formulated a blend specific to ASD (see page 53) Don’t use if there’s hyperammonemia (elevated ammonia in the blood) Adverse responses are possible, and some unusual metabolic conditions are contraindications for amino acids L-Carnitine Tier 1, perhaps more in Tier 3 Can be supplemented quite effectively Diagnosis of autism is sufficient to warrant trial use of L-carnitine Never use D,L-carnitine Acetyl-L-carnitine is an excellent form 50 mg per kg of body weight - more than 1140 mg/day at the discretion of a doctor Goes well with meals Can be sprinkled on prepared foods or dissolved in drinks - it is water soluble Carnosine Tier 2, may try again in Tier 5 Enhances muscle mass, alleviates autistic traits in some ASD children, especially those with seizure conditions Make sure carnosine is not excessive per plasma or urine amino acid analysis Histidine deficiency could indicate benefit from carnosine supplementation Children 3-5 years old - 400-600 mg Children 6-12 years old - 600-1200 mg Adverse effects are possible, sometimes help then relapse Creatine It’s a Tier 5 supplement because toxicants can interfere with it Indications of need include low muscle mass/strength, hypotonia, “floppy baby syndrome” in infancy, dystonic-hyperkinetic movement disorder (sometimes), seizures (sometimes), language delay, deficient expressive speech, x-linked mental retardation (sometimes), autism (sometimes) Relatively large, therapeutic amounts of oral creatine are needed to be effective 7 300-1000 mg per kg body weight, in divided servings One study used 350-2000 mg per kg in adults with no serious side effects Be sure to get this supplement from a reputable supplier - at high doses impurities can add up Notable improvement in 5-10% of children with ASD following creatine supplementation Digestive Enzymes Tier 1 supplement Diet adjustment and digestive enzymes are the best ways to start nutritional intervention for at least 60% of those with ASD No good lab tests to tell which enzymes are needed Best bet is comprehensive enzyme supplement that includes proteases, peptidases, amylases, disaccharidases, and lipase Best taken at the beginning of each meal How much depends on how much food is eaten, not how big the person is - follow instructions on the label or from your health care professional Expect to have a period of “worse before better” - adverse symptoms usually appear after a day or two of use, and may continue for 1-2 weeks A capsule of activated charcoal, 3 times a day (away from meds and supplements) may help with adverse symptoms from “die-off” Dimethylglycine (DMG), Trimethylglycine (TMG or betaine) Tier 4 or preferably Tier 5 DMG and TMG are of value to those with ASD who can derive benefit from increased methylation of homocysteine to form more methionine. When one or the other works, parents report improved verbal communication Start with DMG, then try TMG Some DMG and TMG supplements contain added folate (or folinic acid) and vitamin B12 - some individuals may need those Dosage tables on page 74 DMG: 125-1300 mg or higher, depending on body weight TMG: 150-2000 mg or higher, depending on body weight Do not use betaine hydrochloride, betaine HCl, pluchine, or trimethylglycine hydrochloride If you have an adverse reaction to TMG, try it again after adding taurine for a week or so 8 Fatty Acids End of Tier 1, add more in Tier 3 Cell walls and membranes around cell parts are composed of fatty acids A common abnormality in autism is a depressed level of omega-3 fatty acids, especially DHA Most infants and children with ASD benefit from Omega-3 fatty acid supplements Lab tests of red blood cell fatty acids are indicative of need, but not conclusive Before using fatty acid supplements, add taurine and maybe glycine Dosage: 20-40 mg per Kg of body weight Beware, often the omega-3 portion of a capsule is only 25-30% of entire capsule Refrigerate supplements, and make sure they are fresh by breaking capsule and smelling; respect expiration dates Make sure supplements are mercury-free Start with one capsule/day and work up to desired amount Too much can cause intestinal or bowel symptoms in some people, such as gas Glutathione Tier 4, after the intestinal tract is cleaned up and contains a populace of normal and friendly flora, and when it’s time to do detox (or use IV glutathione) Frequently people with autism don’t have enough glutathione, and too much of it is in the inactive, oxidized form Can be measured by lab tests In Pangborn’s opinion, ASD alone warrants trial use of glutathione Ages 2-4, 50-150 mg oral glutathione Ages 5-10, 100-250 mg oral glutathione Age 11+, 100-300 mg oral glutathione Also, TMG and folinic acid supplements raise glutathione levels Use reduced L-glutathione, GSH, with no significant amount of oxidized glutathione, GSSG (5% is too much) Over time, some GSH users develop yeast, and regular use of anti-yeast supplements is recommended If insulin-dependent condition, consult doctor If cystinuria (renal wasting of cystine), risk of renal cystine stones 9 Herbals Be sure to get herbals from reputable sources, as purity is an issue Get them in capsule form to avoid powerful flavors and aromas Anti-yeast/fungal (Tier 2 and beyond) Olive leaf extract - 200-400 mg in divided doses ages 5-12, less for younger Pau d’Arco - 200-400 mg for ages 5-12, less for younger Oregano Goldenseal Saccharomyces boulardii (probiotic) caprylic acid - 25-100 mg orally calcium caprylic Antibacterial Herbals (Tier 2 and beyond) Oregano - 250-500 mg for ages 5-12, less for younger, 500-1000 mg for teens and adults Thyme - Same doses as Oregano Goldenseal - 100-200 mg for ages 5-12, less for younger, 200-400 mg for teens and adults Antioxidant/Anti-inflammatory Herbals (Tier 1 and beyond) (Tier 2?) Turmeric (curcumin) - 200 mg 3xday for ages 5-12, less for younger, 200-400 mg 3xday for teens and adults Silymarin (from milk thistle) - extracts should be 60-80% silymarin - 50-100 mg 2xday for ages 5-12 years, less for younger, 100-200 mg 3xday for teens and adults Cognitive Improvement Herb - Bacopa Tier 5 extract should include bacosides A and B 20-40 mg of bacosides A and B for ages 5-12 20 mg for younger 40-80 mg for teens and adults Melatonin Tier 1 Many parents report it helps sleep and behavior Effective daily amount is quite variable from one individual to another, from ½ mg to 5 mg, but usually 1 to 2 mg sufficient - use trial and error If you use the time-release type, don’t break, crush, or dissolve the tablet You must keep the child’s bedroom dark and quiet - light causes the body to begin destroying the melatonin 10 too much can produce an opposite effect may need to add taurine before adding melatonin, or may need to wait until Tier 4 or 5 avoid high-protein meals before bedtime, get diet and digestion in shape Elements and minerals Calcium Tier 1 600-900 mg supplemental calcium is needed when a casein-free diet is used, some can be from food Digestive enzymes that include lipase may increase uptake of dietary fats and calcium Best time to give is supper, lunch, breakfast, in that order, in divided doses, such as supper 300 mg, lunch 200 mg, breakfast 100 mg Often has a calming effect Don’t give a lot of calcium at the same time as zinc (Pangborn discusses different forms of calcium) Iodine and thyroid support Iodine is used exclusively for formation of thyroid hormones If ASD individual needs iodine or thyroid hormone supplementation, has to be done before healthy intestinal flora can thrive Indications of need include abnormal thyroid tests, subnormal basal body temperature, periodic regrowth of intestinal yeast despite various antiyeast measures, low iodine according to hair element analysis, living in an area known to be contaminated with perchlorate, or living near a military base where solid-fuel rockets have been fired If hypothyroid condition, then dr will probably prescribe hormone supplementation If using lithium at pharmacologic doses, consult dr before using iodine Use potassium iodide Too much is just as bad as not enough, so seek nutritional advice Recommended amounts of dietary iodine are 50-150 mcg (NOT mg), depending on age Don’t give iodine if there’s autoimmune thyroiditis or cystic fibrosis Pangborn very strongly favors use of a multi-vitamin/multimineral containing iodine, over a stand-alone iodine supplement Symptoms of iodine overdose include acne flare-ups, skin rash, numbness and tingling in hands and feet, and headache 11 Magnesium Tier 1, magnesium malate in Tier 4 Deficiency occurs when taurine is deficient or after toxicant exposures Need is determined by lab tests, especially element levels in blood cells Symptoms consistent with magnesium insufficiency include Muscle twitches (not tics of Tourette’s Syndrome) Constipation Muscle cramps, “tight” muscles Anxiety, panic attacks Insomnia Limited physical endurance Numbness or tingling in fingers, hands, toes, feet Multiple chemical sensitivities, inflammation If lithium is given by prescription, consult dr before giving magnesium Give magnesium when vitamin B6 is used Magnesium malate can be especially beneficial for ASD, but other good forms too Best time to give is with calcium at supper Has a calming effect 3-8 mg per kg of body weight If causes loose stools, reduce the amount Selenium Selenium deficiency is uncommon in the ASD population lab tests can show deficiencies Pangborn prefers seleno-L-methionine Dosage is 20-50 mcg/day (NOT mg/day), depending on age Pangborn favors multivitamin/multimineral supplements with selenium included Zinc Tier 2 Dozens of metabolic processes depend on zinc blood cell or plasma analysis (against a correct reference range) will indicate whether zinc levels are subnormal symptoms of zinc deficiency include: diminished acuity of taste and smell, poor appetite, pica, slow visual adaptation to darkness, growth retardation, skin rash, suppressed immune response, slow wound healing, and ataxia 12 zinc citrate is a good form, but there are other good forms avoid zinc picolinate, zinc aspartate, and zinc sulfate Best given away from meals, but with 15-30 mg, not a problem Evening is a good time, but not when relatively large amounts of calcium are also given Dosages are 5-45 mg/day, depending on body weight Sometimes it’s very difficult to correct a zinc deficiency with supplements Pangborn gives ideas on things that might help If adverse reaction, try a different form of zinc Probiotics Tier 2 These are friendly bacteria Indications of need: when you change the diet when you start to use digestive enzymes when a stool analysis shows imbalanced or pathogenic flora, or maldigestion when a lab report on intestinal permeability shows excessive transfer of test substances into the blood (“leaky gut”) when chemical markers consistent with intestinal dysbiosis are high in urine per a lab report chronic or frequent diarrhea or constipation during any detox treatment while using antibacterial herbal supplements such as thyme or oregano during and after use of antibiotic medications sprinkling on food to be eaten right away works okay, but giving it between meals washed down with lots of water works better Pangborn does not recommend enteric coated supplements for ASD Often symptoms will get worse before better due to die-off of bad flora - if so, give activated charcoal between meals Start gradually and work up to full dose (per doctor or label) over 2 weeks Taurine Tier 1, extra taurine in Tier 4 Taurine is really important and likely to be helpful Works especially well with breakfast 100-250 mg for ages 2-5 250-500 mg for ages 6-12 13 500-1000 mg for teens and adults Don’t go above 2000 mg adverse responses are very uncommon (rare) at these doses Intolerance can occur in hyperkalemia (excessive blood potassium), Addison’s disease, and insulin deficiency if gram quantities are used continuously start at a low level and work up Vitamins General rule, do not exceed daily serving amount (not RDI) on label without conferring with your doctor or nutritional counselor B-vitamins and folate Tier 1 B1 Thiamine, B2 Riboflavin, B3 Niacin, B6 Pyridoxine, B12 Cobalamin, Pantothenic acid, Folic acid Pangborn likes B-complex supplements, because the B vitamins work best taken together Thiamine - 10-25 mg is plenty when the rest of the vitamin team is present Riboflavin - 5-50 mg is appropriate - toxic levels are unknown if kidney function is normal Niacin - 20-100 mg of total nicotinamide and/or inositol nicotinate, but not more B6 is the grandfather of nutritional supplements reported by parents and many clinicians to improve autistic traits and behaviors - 21 out of 22 studies show beneficial outcomes, must give magnesium with B6 10 kg body weight, 25 mg B6+P5P, 15 mg additional magnesium 20-30 kg body weight, 50 mg B6+P5P, 30 mg additional magnesium 40+ kg body weight, 100 mg B6+P5P, 60 mg additional magnesium Pantothenic Acid - toxicity or overdose not an issue Cobalamin Tier 5 methylcobalamin or cyanocobalamin virtually no toxicity with regular supplements, even at high levels 50-1,000 mcg/day with oral supplements Folic Acid, Folate Tier 5 Folinic acid usually more helpful than folic acid or methylTHF but if genetic test shows MTHFR weakness, then methylTHF might be helpful 400 mcg of folinic acid or folinic+folic acids for ages 5+ is enough 14 half that for 2 year olds Should use vitamin B12 at the same time Vitamin A Tier 1 Two forms - retinal and beta-carotene - the body turns beta-carotene into retinal necessary for good vision [eye contact] helps decrease infection and inflammation Give as cod liver oil or in multivitamin products Give any time of day Don’t forget to supplement taurine Use a multivitamin that provides 3000-5000 IU via a mixture of retinal (30-60%) and beta-carotene (60-30%) for ages 5+. Half that for ages 3-5. If need more, use cod liver oil certified mercury-free. Adverse responses are unlikely, but start with low amount and work up long half-life of 3-6 weeks, so adverse reactions take long time to show up and disappear Vitamin C Tier 1, more in Tier 4 Less than 50 lbs body weight, 250 mg 50-100 lbs body weight, 500 mg or more 100 lbs+ body weight, at least 500-1000 mg Usually not more than 2000 mg except for short periods of time, as for constipation breakfast and/or lunch are best times, to avoid potty trips at bedtime Give at different times/meals from vitamin B12 loose stools are often due to too much of the laxative-acting supplements: magnesium, citrates, phosphatidylcholine, herbals, vitamin C most vitamin C is corn-based; those allergic to corn should use one that is not use multi-element buffered vitamin C when amounts over 500 mg are used Vitamin D Tier 1 Every person with autism/ASD should get a supplemental vitamin D in an amount at least equal to the recommended servings for their age ages 1-2, 50-100 IU ages 3-10, 100-200 IU ages 11+, 200-400 IU 15 A vitamin D analysis (blood) is advisable, except that a “normal” blood level may not actually be adequate when oxidant stress with inflammation is a persistent condition Hypervitaminosis D (too much D) is rare Don’t exceed 400 IU for ages 3-10 years, or 1200 IU for adults Use the D3 cholecalciferol form If using a stand alone supplement, then give with calcium at supper Problems with D for people with poor kidney function, or who have elevated blood calcium levels Vitamin E Tier 1 Has antioxidant and tissue-protective properties may be included in multivitamin, but additional E is often beneficial give stand alone E at supper 15-100 IU/day, depending on age If tolerated, you may try a “natural” product that includes additional tocopherols Most natural E is from corn, those allergic to corn may have adverse reaction, but quite uncommon Too much E can cause slowed blood clotting (nosebleeds), and other problems Supplement Products to Be Wary of N-acetylcysteine (NAC) S-adenosylmethionine Alpha-lipoic acid Cycloserine Cysteine Cystine 5-hydroxytryptophan Methylsulfonylmethane (MSM) Also consider (not from Pangborn’s book) Chromium - for sugar craving Alka Seltzer Gold - for acidity/to prevent fungal infections Biotin - prevents yeast Choline, phosphatidylcholine, or GPC (Glycerophosphocholine) 16