Natural B Vitamins Are Better Than Synthetic Ones

Natural B Vitamins Are Better Than Synthetic Ones

By: Robert J Thiel, Ph.D., N.D.

Introduction

At our office, we sometimes recommend products which contain various B vitamins. Some of our clients have indicated that the synthetic B vitamins that they take are at least as good because they normally contain higher amounts of the individual vitamins than the food formulas we normally recommend. Is this true? Are humans better off eating higher amounts of un-natural synthetics or smaller amounts of food complex B vitamins?

United States Pharmacopoeia (USP) synthetic vitamin B isolates are not food, even though they are often called “natural” and are sometimes added to foods—they are synthesized, standardized chemical isolates [1]. In nature, vitamins are never isolated: they are always present in the form of food vitamin-complexes [2-4]. This paper will discuss some of the physiochemical differences between individual natural B vitamins and synthetic ones, as well as cite clinical research which suggest that vitamins in a food complex are superior to USP isolated ones.

Vitamin B1, Thiamin

The free vitamin B1 (called thiamin) is a base. When it is synthesized it becomes a solid salt such as thiamin hydrochloride or thiamin mononitrate [5]. Synthetically thiamin is usually marketed as thiamin hydrochloride or thiamin mononitrate [6] and is a made from Grewe diamine (a coal tar derivative [7]) processed with ammonia and other chemicals [8]. No thiamin hydrochloride (often listed as thiamin HCL) or thiamin mononitrate is naturally found in food or the body (thiamin pyrophosphate is the predominant form in the body [9]) [6]. Yeast and legumes are excellent food sources of natural thiamin [9]. “Thiamin is rapidly destroyed above pH 8…the addition of sodium bicarbonate to green beans and peas to retain their color or to dried beans to soften their skins inactivates thiamin” [9]. High heat, x-rays, and UV irradiation also destroy thiamin [9,10]. Thiamin mononitrate tends to be used for food fortification since it is more stable under storage and processing conditions [6]. An animal study found that a natural food complex vitamin B1 was absorbed 1.38 times more into the blood and was retained 1.27 times more in the liver than an isolated USP thiamin hydrochloride [11].

Vitamin B2, Riboflavin

The free vitamin B2 (called riboflavin) is a weak base. When synthesized it becomes an orange amorphous solid [12]. Some synthetic riboflavin analogues have very weak vitaminic activity [12]. Some natural variations, especially in coenzyme forms, occur in plant (including fungal) species [13]. One study found that the pasteurization of bovine milk seems to reduce the bound form of riboflavin from 13.6% to 2% [14]. An animal study found that a natural food complex vitamin B2 was absorbed into the blood and was retained 1.92 times more in the liver than an isolated USP riboflavin [11].

Vitamin ‘B3’, Niacinamide

“Niacin is a generic term…the two coenzymes that are the metabolically active forms of niacin (are)…nicotinamide adenine dinucleotide (NAD) and NAD phosphate (NADP)…Only small amounts of free forms of niacin occur in nature. Most of the niacin in food is present as a component of NAD and NADP…nicotinamide is more soluble in water, alcohol, and ether than nicotinic acid…many analogues of niacin have been synthesized, some of which have antivitamin activity ” [15]. Niacinamide (also called nicotinamide) is considered to have less potential side-effects than niacin [15]; it also does not seem to cause gastrointestinal upset or hepatotoxicity that the synthetic time-released niacin can cause [16]. Beef, legumes, cereal grains, yeast, and fish are significant natural food sources of vitamin B3 [16]. Processing losses for this vitamin are mainly due to water leaching [17]. Synthetic niacin is usually made in a process involving formaldehyde and ammonia [8]. An animal study found that natural food complex niacinamide is 3.94 times more absorbed in the blood than USP niacinamide and 1.7 times more retained in the liver than isolated USP niacinamide [11].

Vitamin ‘B5’, Pantothenate

Pantothenate was once known as vitamin B5 [18]. USP “Pantothenic acid consists of pantoic acid in amide linkage to beta-alanine”, but the vitamin sometimes referred to as B-5 is not found that way in nature [19]. In food it is found as pantothenate; foods do not naturally contain pantothenic acid [19]. “Synthetic D-pantothenate, the active enantiomer is available as a calcium or sodium salt. However, multivitamin preparations commonly contain its more stable alcohol derivative, panthenol” [20]. Producing synthetic pantothenic acid involves the use of formaldehyde [8]. Organ meats, yeast, egg yolks, and broccoli are rich dietary sources of natural pantothenate [20]. Cooking meat and the processing of vegetables lead to significant losses of pantothenate (15-50% and 37-78% respectively) [20].

Vitamin B6

“An understanding of the various forms and quantities of these forms in foods is important in the evaluation of the bioavailability and metabolism of vitamin B-6”… one of the forms that vitamin B-6 exists is in the form of “5’0-(beta-D-glycopyransosyl) pyridoxine. To date only plant foods have been found to contain this interesting form of vitamin B-6” [21]. Yeast and rice bran contain more natural vitamin B6 than other foods [22]. The most common form in vitamin pills is USP pyridoxine hydrochloride which is not naturally found in food [23]. At least one synthetic vitamin B-6 analogue has been found to inhibit natural vitamin B6 action [24]. Vitamin B6 supports the nervous, skin, and tongue; severe shortages result in abnormal brain patterns and convulsions [25]. Synthetic B6 usually requires formaldehyde in its production [49] and the extremely high amounts used in some synthetic supplements poses more risk than the lower amounts generally found in food vitamins [23]. An animal study found that natural food complex vitamin B6 was absorbed 2.54 times more into the blood and was retained 1.56 times more in the liver than an isolated USP form [11].

Vitamin ‘B9’, Folate

The vitamin once known as vitamin M (and also vitamin B9 [18]) exists in foods as folate (also known as pteroylglutamate) [26]. Initially, natural food complex folate was given for people with a pregnancy-related anemia in the form of autolyzed yeast; later a synthetic USP isolate was developed [26]. Pteroylglutamic acid, the common pharmacological (USP) form known as folic acid, is not found significantly as such in the body and appears to be absorbed differently than folate [26]. Folic acid is not found in foods, but folate is [26]. Herbert reports a study found “that consumption of more than 266mcg of synthetic folic acid (PGA) results in absorption of unreduced PGA , which may interfere with folate metabolism for a period of years” [26].

Fortification with synthetic folic acid has been found to increase consumption for those who already have higher dietary intakes of folate more than those with lower intakes [27]. It is believed that fortification with synthetic folic acid may put a portion of the population at risk for vitamin B12 deficiency [28], yet all grain products advertised as enriched must (according to the US FDA) be fortified with folic acid [29]. “Foods with the highest folate content per dry weight include yeast, liver and organ meats, fresh green vegetables and some fruits” [26]. Food processing is a concern since “50-95% of folate in food may be destroyed by protracted cooking or other processing such as canning, and all folate is lost from refined foods such as sugars, hard liquor, and hard candies” [26]. An animal study found that a natural food complex folate was absorbed only 1.07 times more into the blood, yet was retained 2.13 times more in the liver than isolated USP folic acid [11].

Vitamin B12

Initially natural food complex vitamin B12 was given for people with pernicious anemia in the form of raw liver, but due to cost considerations a synthetic USP isolate was developed [30]. Cyanocobalamin (the common pharmacological/USP form of vitamin B12) is not found significantly as such in the body; it is usually present in reduced metabolically active coenzyme forms (without the cyanide) often conjugated in peptide linkage [31, 32]. According to Herbert (and others) vitamin B-12 when ingested in its human-active form is non-toxic, yet Herbert and Das have warned that “the efficacy and safety of the vitamin B12 analogues created by nutrient-nutrient interaction in vitamin-mineral supplements is unknown” [31]. Some synthetic vitamin B12 analogues seem to be antagonistic to vitamin B12 activity in the body [33, 34]. Synthetic B-12 is made through a fermentation process with the addition of cyanide [8]. An animal study found that a natural food complex vitamin B12 was absorbed 2.56 times more into the blood and was retained 1.59 times more in the liver than isolated USP cyanocobalamin [11].

Food Processing and Fortification

The primary reason that nutrition became recognized as a separate science was the result of food processing. The refining of brown rice into white rice reduced B-complex vitamins and initially led to deaths in Asia due to beriberi [5, 35]. At first beri-beri was thought to be due to an infection, until it was learned that it was due to a lack of B vitamins. Actually, the reason they are called ‘B’ vitamins, is that the B initially stood for ‘beri-beri’. The ‘solution’ to beri-beri was to add synthetic USP vitamins. Even though synthetic USP vitamins are added to white rice and does help prevent beri-beri, this ‘fortified’ white rice does not contain the same nutrients as unpolished brown rice (nor does white flour contain the same nutrients as whole flour) [35, 36] and can contribute to other health problems (such as constipation due to lack of fiber). Adding synthetics, most of which are not in the same chemical form as found in food vitamins, forces the body to digest them in ways it never should have to—why add this unnatural digestive stress?

The earlier refining of corn meal which reduced natural vitamin B-3 and amino acid levels was so devastating it produced around U.S. 7,000 deaths per year for several decades [37]. The refining of whole grains (including wheat, rice, and corn) has resulted in a dramatic reduction of their natural food complex nutrients [25, 35]. The milling of wheat to white flour reduces the natural food complex vitamin and mineral content by 40-60% [35]. Various food processing techniques (including pasteurization of milk) reduce the available vitamin B6 in foods by 10-50% [35, 36]. Irradiation of meat and other foods “changes the characteristics of food” [6] and has been found to reduce levels of vitamins B1, B6, and other nutrient levels [6, 22, 37].

Unknown nutrients may also be affected from food processing. No one yet knows how the combinations of these more recent food processing techniques will effect human health [38], but it is not likely that they will promote optimal nutrition. In nature, vitamins are never isolated. The primary reason that isolated USP vitamins were developed was cost [30]. A secondary reason probably was standardization (it is harder to standardize food), including stability [1, 6, 26]. Neither reason justifies placing USP isolates on the same health level as natural vitamins as found in foods.

Conclusion

Studies suggest that the bioavailability of natural food complex B vitamins is better than that of isolated USP vitamins [e.g. 5,12], that they may have better effects on maintaining aspects of human health beyond traditional vitamin deficiency syndromes, and at least some seem to be preferentially retained by the human body [11]. It is not always clear if these advantages are due to the physiochemical form of the vitamin, with the other food constituents that are naturally found with them, or some combination.

Regardless, it seems logical to conclude that for purposes of maintaining normal health, natural vitamins are superior to synthetic ones. Eating high dose synthetic B vitamins is like trying to make a computer when you only have 90% of the pieces with many of those pieces being larger than normal size; eating natural B vitamins is like trying to make a computer with 100% of the parts with all the parts the correct size. Which of the ‘computers’ would work better? Obviously the one with 100% of the right parts!

Most people can improve their health by eating health-building whole foods such as fruits and vegetables and whole grains (and consuming less refined carbohydrates) [25]. This alone can help increase the consumption of natural B vitamins. Vitamin B nutrition should come from food or from supplements which are as close to food as possible. Since no one knows everything there is to know about nutrition, it seems logical from both a historical and modern perspective to consume vitamins in the forms found in natural food complexes and not to try to build health based on chemical isolates.

References

  1. Cotran RS, Kumar V, Collins T. Pathologic Basis of Disease, 6th ed. WB Saunders, Phil., 1999.
  2.  Van Dyke DC, Lang DJ, Heide F, van Duyne S, Soucek MJ, editors. Standardized anthropometric techniques. In Clinical Perspectives in the Management of Down Syndrome. Springer-Verlag, NY, 1990:230-237
  3. Kissane JM. Anderson’s Pathology, 9th ed. CV Mosby Co., St. Louis, 1990
  4. Turkel H, Nusbaum I. Medical Treatment of Down Syndrome and Genetic Diseases, 4th ed. Ubiotica, Southfield (MI), 1985
  5. Sacks BI, Buckley RF. Multi-nutrient formulas and other substances as therapies for Down syndrome: an overview. Down Syndrome News and Update 1(2):70-83, 1998
  6. Cohen B, Thiel RJ. What to do about borderline elevated TSH levels? Presentation at the Down Syndrome Medical Interest Group, San Diego, July 8, 2001
  7. Thiel RJ, Fowkes SW. Down syndrome and epilepsy: A nutritional connection? Accepted for review, Medical Hypotheses, December 2002
  8. Baer MT, Waldron J, Gumm H, Van Dyke DC, Chang H. Nutrition assessment of the child with Down syndrome. In Clinical Perspectives in the Management of Down Syndrome. Springer-Verlag, NY, 1990:107-125
  9. Filippello M, Cascone G, Zagami A, Scimone G. Impression cytology in Down’s syndrome. Br J Opthalmol,1997;81(8):683-685
  10. Palmer S. Influence of vitamin A nutriture on the immune response: findings in children with Down’s syndrome. Int J Vitam Nutr Res 1978;48(2):188-216
  11. Schmid F, Christeller S, Rehm W. Studies on the state of vitamins B1, B2 and B6 in Down’s syndrome. Fortschr Med 1975;93(25):1170-1172
  12. Chad K, Jobling A, Frail H. Metabolic rate: a factor of developing obesity in children with Down syndrome? Am J Ment Retard 1990;95(2):228-235
  13. McCoy EE, Columbini C, Ebadi M. The metabolism in vitamin B6 in Down’s syndrome. Ann NY Scie 1969;166(1):116-125
  14. Tu JB, Zellweger H. Blood serotinin deficiency in Down’s syndrome. Lancet 1965;2(415):715-716
  15. Frager J, Barnet A, Weiss I, Coleman M. A double blind study of vitamin B6 in Down’s syndrome infants. J Ment Def Res 1985;29(Pt3):241-246
  16. David O, Fiorucci GC, Tosi MT, Altare F, Valori A, Saracco P, Asinardi P, Ramenghi U, Gabutti V. Hematological studies in children with Down syndrome. Pediatr Hematol Oncol 1996;13(3):271-275
  17. Ibarra B, Rivas F, Medina C, Franco ME, Romero-Garcia F, Enrique C, Galarza M, Hernandez-Cordova A, Hernandez T. Hematological and biochemical studies in children with Down syndrome. Ann Genet 1990;33(2):84-87
  18. Wachtel TJ, Pueschel SM. Macrocytosis in Down syndrome. Am J Ment Retard 1991;95(4):417-420
  19. Gericke GS, Hesseling PB, Birnk S, Tiedt FC. Leukocyte ultrastructure and folate metabolism in Down’s syndrome. S Afr Med J 1977;51(12):369-374
  20. Hestnes A, Stovner LJ, Husoy O, Folling I, Fougner KJ, Sjaastad O. Hormonal and biochemical studies in children with Down’s syndrome. J Ment Defic Res 1991;35 (Pt 3):179-193
  21. Colombo MI, Girdardo E, Incarbone E, Conti R, Ricci BM, Maina D. Vitamin C in children with trisomy 21. Minerva Pediatr,1989;41(4):189-192
  22. Hilty N, Sepp N, Rammal E, Pechlaner C, Hintner H, Fritsch P. Scurvy in trisomy 21. Hautarzt 1991;42(7):464-466
  23. Center J, Beange H, McElduff A. People with mental retardation have an increased prevalence of osteoporosis. Am J Ment Retard,1998;103(1):19-28
  24. Molteno C, Smit I, Mills J, Huskisson J. Nutritional status of patients in a long-stay hospital for people with mental handicap. S Afr Med J 2000;90(11):11351140
  25. Cengiz M, Seven M. Vitamin and mineral status in Down syndrome. Trace Elem Elec 2000;17(3):156-160
  26. Werbach M. Down syndrome. In Textbook of Nutritional Medicine. Third Line Press, Tarzana (CA), 1999:340-348
  27. McCoy EE, Sneddon JM. Decreased calcium content and 45Ca2+ uptake in Down’s syndrome blood platelets. Pediatr Res 1984;18(9):914-916
  28. Barlow PJ, Sylvestrer PE, Dickerson JW. Hair trace metal levels in Down syndrome patients. J Ment Def Res 1981;25(Pt 3):161-168
  29. Purice M, Maximillan C, Dumitru I, Ioan D. Zinc and copper in plasma and erythrocytes of Down’s syndrome children. Endocrinologie 1988;26(2):113-117
  30. Kadrobova J, Madaric A, Sustrova M, Ginter E. Changed serum element profile in Down’s syndrome. Biol Trace Elem Res 1996;54(3):201-206
  31. Anneren G, Johansson E, Lindu U. Trace element profiles in individual blood cells from patients with Down’s syndrome. Acta Paediatr Scand 1985;74(2):259-263
  32. Monteiro CP, Varela A, Pinto M, Neves J, Felisberto GM, Vaz C, Bicho MP, Laires MJ. Effects of an aerobic training program on magnesium, trace elements and antioxidant systems in Down syndrome population. Magnes Res 1997;10(1):65-71
  33. Barlow PJ, Sylvestrer PE, Dickerson JW. Hair trace metal levels in Down syndrome patients. J Ment Def Res 1981;25(Pt 3):161-168
  34. Anneren G, Magnusson CG, Nordvall SL. Increase in serum concentrations of IgG2 and IgG4 by selenium supplementation in children with Down’s syndrome. Arch Dis Child 1990;65(12):1353-1355
  35. Hamilton K. Down’s syndrome: selenium supplementation and trace elements. CP Currents 1994;4(3):46
  36. Kralik A, et al. Influence of zinc and selenium deficiency on parameters related to thyroid metabolism. Hormone Metabol Res 1996;28:223-226
  37. Sherman AR. Zinc, copper and iron nutriture and immunity. J Nutr,1992;122:604-609
  38. Stabile A, et al. Immunodeficiency and plasma zinc levels in children with Down’s syndrome: a long-term follow-up of oral zinc supplementation. Clin Immunolog Immunopath, 1991;58:207:216
  39. Bucci I, Napolitano G, Giuliani C, Lio S, Minnucci A, Di Giacomo F, Calabrese G, Sabatino G, Palka G, Monocao F. Zinc sulphate supplementation improves thyroid hypofunction in hypozincemic Down children. Biol Trace Elem Res 1999;67:257-268
  40. Napolitano G, Plaka G, Grimaldi S, Guilani C, Laglia G, Calabreese G, Satta MA, Neri G, Monaco F. Growth delay in Down syndrome and zinc sulphate supplementation. Amer J Med Genetics 1990;S7:63
  41. Abdallah SM, Samman S. The effect of increasing dietary zinc on the activity of superoxide and dismutase and zinc concentrations in healthy female subjects. Eur J Clin Nutr 1993;47:327-332
  42. Perry EK, Perry RH, Smith CJ, Purohit D, Bonham J, Dick DJ, Candy JM, Edwardson JA, Fairbairn A. Cholinergic receptors in cognitive disorders. Can J Neurol Sci 1986;13(S4):521-527 [43] Cantor DS, et al. A report on phosphatidylcholine therapy in a Down’s syndrome child. Psychol Rep 1986;58:207-217
  43. Lejeune J, Rethore MO, de Blois MC, Peeters M, Naffah J, Megarbane A, Cattaneo F, Mircher O, Rabier D, Parvey P, et al. Amino acids and trisomy 21. Ann Genet 1992;35(1):8-13
  44. Lemere CA, et al. The lysomal cysteine protease, cathepsin S, is increased in Alzheimer’s disease and Down syndrome brain. An imunocytochemical study. Am J Pathol 1995,146(4):848-860
  45. Werbach M. Epilepsy. In Textbook of Nutritional Medicine. Third Line Press, Tarzana (CA), 1999:363-375
  46. Meyers LF. Language development and intervention. In Clinical Perspectives in the Management of Down Syndrome. Springer-Verlag, NY, 1990:153-164
  47. Warner FJ. Nutrition and Down syndrome. Presentation at the Third Annual Convention of the California State Naturopathic Medical Association, Buena Park, February 11, 2001
  48. Shetty HU, Siarey RJ, Galdzicki Z, Stoll J, Rapoport SI. Ts65Dn mouse, a Down syndrome model, exhibits elevated myo-inositol in selected brain regions and regional and peripheral tissues. Neuochem Res 2000;25(4):431-435
  49. Huang W, Alexander GE, Daly EM, Shetty HU, Krasuski JS, Rapoport SI, Schapiro MB. High brain myo-inositol levels in the predementia phase of Alzheimer’s disease in adult’s with Down’s syndrome. Am J Psychiatry 1999;156(12):1879-1886
  50. Shonk T, Ross BD. Role of increased cerebral myo-inositol I the dementia of Down syndrome. Magn Reson Med 1995;33(6):858-861
  51. Shetty HU, Schapiro MB, Holloway HW, Rapaport SI. Polyol profiles in Down syndrome: myo-inositol, specifically is elevated in the cerebrospinal fluid. J Clin Invest 1995;95(2):542-546
  52. Hamilton K. Down’s syndrome. In Clinical Pearls in Nutrition and Preventative Medicine. ITServices, Sacramento, 1998:204
  53. Watkins SE, Thomas DE, Clifford M, Tidmarsh SF, Sweeney AE. Ah-Sing E, Dickerson JW, Cowie VA, Shaw DM. Plasma amino acids in patients with senile dementia and in subjects with Down’s syndrome at an age vulnerable to Alzheimer’s changes. J Ment Defic Res 1989;33(Pt 2):159-166
  54. Shaposhnikov AM, Khal’chitskii SE, Shvarts EI. Disorders of phenylalanine and tyrosine metabolism in Down’s syndrome. Vopr Med Khim 1979;25(1):1519
  55. Airaksinen EM. Tryptophan treatment of infants with Down’s syndrome. Ann Clin Res 1974;6(1):33-39
  56. Thiel RJ. Growth effects of Warner protocol for children with Down syndrome. J Orthomol Med, 2002, 17(1):42-48
  57. Thiel RJ. Facial effects of Warner protocol for children with Down syndrome. J Orthomol Med, 2002, 17(2):111-116
  58. Dwyer J. Fertile fields for fads and frauds: questionable nutritional therapies. NY State J Med, 1993:105-108
  59. Barness LA, Dallman PR, Anderson H, Collipp PJ, Nichols BL, Walker WA, Woodruff CW. Megavitamins and mental retardation. American Academy of Pediatrics Policy Statement, August 1981
  60. Luke A, Sutton M, Schoeller DA, Roizen NJ. Nutrient intake and obesity in prepubescent children with Down syndrome. J Am Diet Assoc,1996;96(12):1262-1267
  61. Reading CM. Down’s syndrome: nutritional interventions. Nutr Health,1984;3(1-2):91-111
  62. Harrell RF, Capp RH, Davis DR, Peerless J, Ravitz LR. Can nutritional supplementation help mentally retarded children? an exploratory study. Proc Natl Acad Sci U S A,1981;78(1):574-578
  63. Weathers C. Effects of nutritional supplementation on IQ and certain other variables associated with Down syndrome. Am J Ment Defic,1983;88(2):214-217
  64. Rimland B. Vitamin and mineral supplementation as a treatment for autistic and mentally retarded persons. Presentation to the President’s Committee on Mental Retardation, Washington (D.C.), September 20, 1984
  65. Prasher VP. Down syndrome and thyroid disorders: a review. Downs Syndr Res Pract,1999;6(1):25-42
  66. Karlsson B, et al. Thyroid dysfunction in Down’s syndrome: relation to age and thyroid antibody. Arch Dis Childhood 1998;79:242-245
  67. Hetzel BS, Clugston GA. Iodine. In Modern Nutrition in Health and Disease, 9th ed. Williams & Wilkins, Balt.,1999:253-264
  68. Guyton AC, Hall JE. Textbook of Medical Physiology, 9th ed. WB Saunders, Phil.,1996
  69. Kanavin OJ, Aaseth J, Birketvedt GS. Thyroid hypofunction in Down’s syndrome: is it related to oxidative stress? Biol Trace Elem Res 2000;78(1-3):35-42
  70. Pietz J. Neurological aspects of adult phenylketonuria. Curr Opin Neurol 1998;11(6):679-688
  71. Marsh RW, Cabaret JJ. Down’s syndrome treated with a low phenylalanine diet: case report. N Z Med J 1972;75(481):364-365
  72. Becker W, Joost HG. Structural and functional characteristics of Dyrk, a novel subfamily of protein kinases with dual specificity. Prog Nucleic Acid Mol Biol 1999;62:1-17
  73. Kentrup H, Joost HG, Heimann G, Becker W. Midbrain/DYRK1A gene: a candidate for mental retardation in Down syndrome? Klin Padiatr 2000;212(2):6063
  74. Himpel S, Panxer P, Eirmbter K, Czajkowska H, Sayed M, Packman L, Blundell T, Kentrup H, Grotzinger J, Joost HG, Becker W. Identification of the autophosphorylation sites and characterization of their effects in the protein kinase DYRK1A. Biochem J 2001;359(Pt3):497-505
  75. Lohr JB. Oxygen radicals and neuropsychiatric illness: some speculations. Arch Gen Psychiat,1991;48:1097-1106
  76. Jovanoic SV, Clements D, MacLeod K. Biomarkers of oxidative stress are significantly elevated in Down syndrome. Free Radic Biol Med,1998;25(9):10441048
  77. Warner FJ, Stephens C. Metabolic supplementation for correction of raging free radicals in trisomy 21. Presentation at the International Down’s Conference. Madrid, Spain, 1997
  78. Murray M, Pizzorno J. Alzheimer’s disease. In Encyclopedia of Natural Medicine. Prima Publishing, Rocklin (CA), 1991:128-135
  79. Vinson JA, Jang J. In Vitro and In Vivo antioxidant effect of a citrus extract and ascorbic acid on normal and hypercholesterolemic human subjects. J Med Food, 2001:4(4):187-192
  80. Vinson J, Stella J, Flanagan T. Selenium yeast is an effective in vitro and in vivo antioxidant and hypolipemic agent in hamsters. Nutr Res,1998;18:735-742
  81. Traber MG. Vitamin E. In Modern Nutrition in Health and Disease, 9th ed. Williams & Wilkins, 1999:347-362
  82. Thiel RJ. Natural vitamins may be superior to synthetic ones. Med Hypo 2000, 55(6):461-469
  83. Thiel RJ. Mineral salts are for plants, food complexed minerals are for humans. ANMA Monitor, 1999;3(2):5-10
  84. DeCava JA. The Lee Philosophy–Part II. Nutrition News and Views, 2003;7(1):1-6
  85. Thiel RJ. The Truth About Vitamins in Supplements. ANMA Monitor, in press 2003
  86. Vinson J, Howard TB. Inhibition of protein glycation and advanced glycation end products by ascorbic acid and other nutrients. Nutr Biochem 1996;7:659663
  87. Odetti P, Angelini G, Dapino D, Zaccheo D, Garibaldi S, Dagna-Brica F, Piomba G, Perry G, Smith M, Traverso N, Tabaton M. Early glycation damage in the brains from Down’s syndrome. Biochem Biophys Res Commun 1998;243(3):849-851
  88. Brownson C, Hipkiss AR. Carnosine reacts with a glycated protein. Free Radic Biol Med 2000;28(10):1564-1570
  89. Seidler NW. Carnosine prevents glycation-induced changes in electrophoretic of aspartate aminotransferase. J Biochem Mol Toxicol 2000;14(4):215-220
  90. Kohen R, Misgav R, Ginsburg I. The SOD like activity of copper: carnosine, copper: anserine copper: homocarnosine complexes. Free Radic Res Commun 1991;12-13, pt1:179-185
  91. Choi SY, Kwon HY, Kwon OB, Kang JH. Hydrogen peroxide-mediated Cu,ZN-superoxide dismutase fragmentation: protection by carnosine, homocarnosine and anserine. Biochim Biophys Acta 1999;1472(3):651-657
  92. Kang JH, Eum WS. Enhanced oxidative damage by the familial amyotrophic lateral sclerosis-associated Cu,Zn-superoxide dismutase mutants. Biochim Biophys Acta 2000;1524(2-3):162-170
  93. De Falco FA D’Angelo E, Grimaldi G, Scafuro F, Sachez F, Caruso G. Effect of the chronic treatment with L-acetylcarnitine in Down’s syndrome. Clin Ter 1994;144(2):123-127
  94. Laryea MD, Steinhagen F, Pawliczek S, Wendel U. Simple method for the routine determination of betaine and N,N-dimethylglycine in blood and urine. Clin Chem,1998;44(9):1937-1941
  95. Kendall RV, Lawson JW. Recent findings on N,N-dimethylglycine (DMG): a nutrient for the new millenium. Townsend Letter,2000;202:75-85
  96. Hamilton K. Nutritional aspects of children with Down syndrome. In Clinical Pearls 1999. ITServices, Sacramento, 1999:256
  97. Storm W. Prevalence and diagnostic significance of gliaden antibodies in children with Down’s syndrome. Eur J Ped, 1990;149:833-834
  98. Dorfman K. Exploring the casein-free, gluten-free diet. New Developments;1(2):4
  99. Fuchtenbusch M, Karges W, Standl E, Dosch HM, Ziegler AG. Antibodies to bovine serum albumin in type 1 diabetes and other autoimmune disorders. Exp Clin Endocrinol Diabetes,1997;105(2):86-91