Effect of a vitamin/mineral supplement on children and adults with autism

James B Adams, Tapan Audhy, Sharon McDonough-Means, Robert A Rubin, DavidQuig, Elizabeth Geis, Eva Gehn, Melissa Loresto, Jessica Mitchell, Sharon Atwood,Suzanne Barnhouse and Wondra Lee: From Arizona State University FROM ABSTRACT Background: Vitamin/mineral supplements are among the most commonly usedtreatments for autism, but the research on their use for treating autism has beenlimited. Method: This study is a randomized, double-blind, placebo-controlled three monthvitamin/mineral treatment study. The study involved 141 children and adults withautism, and pre and post symptoms of autism were assessed. Results: The vitamin/mineral supplement was generally well-tolerated. Levels ofmany vitamins, minerals, and biomarkers improved/increased showing goodcompliance and absorption. Statistically significant improvements in metabolic status were many including:Total sulfate +17%Sadenosylmethionine (SAM) +6% Reduced glutathione +17%Ratio of oxidized glutathione to reduced glutathione (GSSG:GSH) -27%ATP +25%NADH +28%NADPH +30% The supplement group had significantly greater improvements than the placebogroup on the Parental Global Impressions-Revised (PGI-R), and on the subscoresfor Hyperactivity, Tantrumming, Overall, and Receptive Language. The degree of improvement of the PGI-R was strongly associated with the initiallevels of biotin and vitamin K; both biotin and vitamin K are made by beneficialintestinal flora. [Important] Conclusions: Oral vitamin/mineral supplementation is beneficial in improving thenutritional and metabolic status of children with autism, including improvements inmethylation, glutathione, oxidative stress, sulfation, ATP, NADH, and NADPH. The supplement group had significantly greater improvements than did the placebogroup on the PGI-R. This suggests that a vitamin/mineral supplement is a reasonable adjunct therapyto consider for most children and adults with autism. [Important] KEY POINTS FROM THIS STUDY: 1) This study presents the effect of nutritional supplements on the nutritional/metabolic status and symptoms of autism in children and adults. It is arandomized, double-blind, placebo-controlled study lasting three months. 2) Inadequate intake of vitamins and minerals due to poor diet is a majorcontributing factor to many child health problems in the US and around the world. 3) Metabolic disturbances may be linked to neuro-developmental disordersincluding attention deficit disorder, learning disorders, and intellectual development. 4) Vitamin/ mineral supplements are among the most widely recommendedmedical interventions for autism, recommended by 49% of physicians. 5) Children with autism have: * Impaired methylation (decreased SAM, [decreased B vitamins]) * Decreased glutathione * Increased oxidative stress [free radical damage] 6) Supplementation with vitamin methyl-B12, folinic acid, and trimethylglycine inautistic children significantly improves methylation, glutathione, and reducesoxidative stress. [Key Point] 7) Supplementation with high-dose vitamin C reduces autism severity. Childrenwith autism have high oxidative stress, and supplementation with vitamin Csignificantly decreases the level of oxidative stress. 8) Supplementation with very high dose vitamin B6 with magnesium, almostalways shows positive behavioral improvements. 9) Subjects and controls were given a liquid supplement or placebo,administered in three equally divided doses with food at breakfast, lunch, anddinner. 10) Both the supplements and placebos formulations were sweetened withsucralose [a known organochloride toxin that also alters gut flora: Article44-09] and contained preservatives potassium sorbate and sodium benzoate[known to cause ADD/ADHD: Article 18-08], and also contained sucrose. 11) The minerals iron and copper were not included in the supplement. 12) The form of vitamin B6 used was pyridoxine, because that form can enter the cell and be converted into the active form, pyridoxal-5-phosphate (P5P); incontrast, P5P cannot enter cells. 13) The amount of vitamin B6 is moderately high because autistic children haveabnormally low B6-dependent biomarkers such as glutathione. 14) Methylsulfonylmethane (MSM) was used as a source of sulfate, becausechildren with autism have very low levels of plasma sulfate. 15) Lithium was included because children with autism and their mothers are lowin lithium, and low lithium is linked to a wide range of psychological disorders. 16) Coenzyme Q-10 was added to support mitochondrial function. 17) A low dose of N-acetylcysteine was included to enhance production ofglutathione. [Important] 18) This formulation contained a water soluble form of vitamin E (d-Alpha-TocopherylPolyethylene Glycol-1000 Succinate) that has shown to improve theabsorption of fat-soluble vitamins in patients with malabsorption. 19) Dosage levels of nutrients in the supplement were significantly higher thanRDA levels. 20) Autism assessment included the revised Parent Global Impressions (PGI-R),which includes:Expressive Language,Receptive Language,General Behavior (Hyperactivity, Tantrums, Cognition, and Play),Gastrointestinal Symptoms, Sleep, Sociability, and Eye Contact. 21) It appears that much higher levels of vitamin D are needed to affect bloodlevels of vitamin D. [They only used 300 IUs; I suggest 2500 IUs] 22) Copper is not included in the supplement since children with autism seem togenerally have adequate or slightly high levels of it. [Important] 23) Supplementation with MSM substantially improved sulfate status, but sulfatelevels were still low, suggesting that higher levels of MSM or other sources ofsulfate such as Epsom salt (magnesium sulfate) baths are needed. 24) Sulfur is important for many reactions including detoxification, inactivation ofcatecholamines, and synthesis of brain tissue. 25) Autistic children have low sulfate levels. Low sulfate decreases the ability todetoxify acetaminophen [Tylenol], which is linked to increased autism.[Important, Article Review 10-12] 26) ATP is required for the kidneys, and low levels of ATP are a contributor todecreased sulfate in children with autism. [The May 2012 Pediatrics indicatesthat pregnant mothers with insulin resistance {reduced ability to makeATP from glucose} increase their babys risk of autism by 61%: ArticleReview 09-13] 27) Autistic children have a problem of converting sulfite to sulfate in themitochondria; the conversion enzyme (sulfite oxidase) contains molybdenum. Theconversion is improved by supplementing with molybdenum (about 150 mcg). 28) The supplement substantially improved glutathione (an important antioxidantand defense against toxic metals). 29) Oral folinic acid, trimethylglycine, and methyl Vitamin B12 greatly improvemethylation, glutathione, and oxidative stress. 30) ATP is the primary energy source for the body and the brain. Supplementingwith CoQ10 significantly increased the levels of ATP. 31) The supplement group had significantly greater improvement than theplacebo group on the Average Change of the PGI-R. 32) The supplement resulted in many significant improvements in nutritional andmetabolic status after three months. 33) Children with low levels of biotin are more likely to benefit fromsupplementation. Biotin is an important cofactor that regulates gluconeogenesis(generation of glucose from non-carbohydrate sources), fatty acid synthesis, andthe Krebs cycle. 34) Approximately half of the biotin and half of the vitamin K in humans comefrom their intestinal bacteria. One of the common causes of biotin or vitamin Kdeficiency is antibiotic usage. One major difference in the medical history ofchildren with autism compared to neurotypical children is a much higher usage oforal antibiotics. Antibiotics lower levels of biotin and vitamin K in children. 35) The correlation of improvement in autism symptoms with biotin and vitamin Kmay relate to a lack of beneficial bacteria which produce biotin and vitamin K. 36) Children with low biotin or low vitamin K were most likely to benefit from themulti-vitamin/mineral supplement. 37) Autistic children have low levels of biotin, glutathione, SAM, plasma ATP,NADH, NADPH, plasma sulfate (free and total), and plasma tryptophan; and highlevels of oxidative stress biomarkers and evidence of impaired methylation (highuridine). By the end of the treatment study, these biomarkers had all improved oreven normalized. 38) Vitamins and minerals are required co-factors for the production of manyneurotransmitters. 39) This study is consistent with several other studies that reported thatvitamin/mineral supplementation is beneficial in treating children with autism. 40) Some children and adults with autism require very high doses of vitamin B6,500-1000 mg/day. [This study used only 40 mg] 41) The length of the study (three months) may not have been long enough toobserve the full-effect of the supplement, and longer treatment may result in largereffect. 42) The supplement group improved significantly more than the placebo groupon the PGI-R Average Change and on several of the PGI-R subscales. 43) The data from this study strongly suggests that oral vitamin/mineralsupplementation is beneficial in improving the nutritional and metabolic status ofchildren with autism, and in reducing their symptoms. 44) Based on the present findings, vitamin/mineral supplementation should beconsidered as an adjunct therapy for most children and adults with autism.The autism pediatric (for 60 lb. child) formula used in this study: VITAMINS Vitamin A (palmitate) 1000 IU Vitamin C (calcium ascorbate) 600 mg Vitamin D3 (cholecalciferol) 300 IU Vitamin E 150 IU Mixed Tocopherols 70 mg Vitamin K2 55 mcg B1 (thiamin HCl) 20 mg B2 (riboflavin) 20 mg B3 (niacin/niacinamide) 15 mg niacin/10 mg niacinamide B5 (calcium d-pantothenate) 15 mg B6 (pyridoxine HCl) 40 mg B12 (cyanocobalamin) 500 mcg Folic Acid 100 mcg Folinic Acid 550 mcg Biotin 150 mcg Choline (choline chloride) 250 mg Inositol 100 mg Mixed Carotenoids 3.6 mg Coenzyme Q10 50 mg N-acetyl cysteine (NAC) 50 mg MINERALS Calcium (calcium ascorbate) 100 mg Chromium (chromium amino acid chelate) 70 mcg Copper NONE Iodine (potassium iodide) 100 mcg Iron NONE Lithium (lithium orotate) 500 mcg Magnesium (magnesium chloride hexahydrate) 100 mg Manganese (manganese amino acid chelate) 3 mg Molybdenum (sodium molybdate dihydrate) 150 mcg Phosphorus NONE Potassium (potassium chloride) 50 mg Selenium (selenomethionine and sodium selenite) 22 mcg Sulfur (MSM) 500 mg Zinc (zinc gluconate) 12 mg