This page lists the key components in the fUS formula.  Below is a nutrient list that gives a description and medical references for the elements.

This page addresses the below nutrients:

  • NIACIN (B-3)
  • VITAMIN B-12
  • THIAMIN (B-1)
  • L-Methionine
  • DL-Phenylalanine
  • L-Valine
  • L-Leucine



L-ALANINE Main Functions: Alanine plays a major role in the transfer of nitrogen from peripheral tissue to the liver. It aids in the metabolism of glucose, a simple carbohydrate that the body uses for energy. It guards against the buildup of toxic substances that are released into muscle cells when muscle protein is broken down quickly to meet energy needs, such as what happens with aerobic exercise. Alanine strengthens the immune system by producing antibodies.


HISTIDINE HCL Main Functions: Histidine is found abundantly in hemoglobin. It has been used in the treatment of rheumatoid arthritis, allergies, ulcers and anemia. It is essential for the growth and repair of tissues; important for the maintenance of the myelin sheaths, which protect nerve cells. It is needed for the production of both red and white blood cells. Histidine protects the body from radiation damage; lowers blood pressure. It aids in the removal of heavy metals from the body; aids in sexual arousal.


L-ISOLEUCINE Main functions: Isoleucine is needed for hemoglobin formation; stabilizes and regulates blood sugar and energy levels. It is valuable to athletes because it aids in the healing and repair of muscle tissue, skin and bones. It has been found to be deficient in people suffering from certain mental and physical disorders.


L-Leucine Main Functions: Leucine works with Isoleucine and Valine to promote the healing of muscle tissue, skin, and bones. It is recommended for those recovering from surgery. It lowers blood sugar levels. It aids in increasing growth hormone production.


L-Valine Main Functions: Valine is needed for muscle metabolism and coordination, tissue repair, and for the maintenance of proper nitrogen balance in the body. It is used as an energy source by muscle tissue. It has been used to treat liver and gallbladder disease. It promotes mental vigor and can calm emotions.


DL-Phenylalanine Main Functions: Phenylalanine is used by the brain to produce norepinephrine, a chemical that transmits signals between nerve cells in the brain. It promotes alertness and vitality and elevates mood. It decreases pain; aids memory and learning. It has been used to treat arthritis, depression, menstrual cramps, migraines, obesity, Parkinson’s disease, and schizophrenia.


L-Methionine Main functions: Methionine is a powerful anti-oxidant and a good source of sulfur, which prevents disorders of the hair, skin, and nails. It assists the breakdown of fats, thus helping to prevent a buildup of fat in the liver and arteries, that might obstruct blood flow to the brain, heart, and kidneys. It helps to detoxify harmful agents such as lead and other heavy metals. It helps diminish muscle weakness; prevents brittle hair; protects against the affects of radiation. It is beneficial for women who take oral contraceptives because it promotes the excretion of estrogen. It reduces the level of histamine in the body which can cause the brain to relay wrong messages. Methionine can be helpful to individuals suffering from schizophrenia.


L-GLUTAMINE Main Functions: Precursor to the neurotransmitter GABA. This is a vital function, as GABA is an inhibitory neurotransmitter that produces serenity and relaxation. Important glycogenic amino acid, meaning that it is essential for helping to maintain normal and steady blood sugar levels. Involved with muscle strength and endurance. Essential to gastrointestinal function; provides energy to the small intestines. The intestines are the only organs in the body that uses Glutamine as its primary source of energy. Glutamine has the highest blood concentration of all the amino acids. Precursor to the neurotransmitter amino acid Glutamate (Glutamic Acid). Involved in DNA synthesis.

  • REFERENCES: 1.Cynober, Luc (edited by), Amino Acid Metabolism and Therapy in Health & Nutritional Disease, 1995. 2.IDi Pasquale, M, Amino Acids and Proteins for the Athlete, the Anabolic Edge, 1997. 3.ILatifi, Rifat, M.D., Ami no Acids in Critical Care and Cancer, 1994. 4.ISouba, W., Glutamine: Physiology, Biochemistry, and Nutrition in Clinical Illness, 1992. 5.IJungas R., Halperin, M., Brosnan, J, “Quant. Analy.of Amino Acid Oxidation and Rela. Gluconeogen. in Humans”, Physiol. Review, 1992. 7.IFarr M, Kornbluth, et al: Research Award.”Glutamine Enhances Immunoregulation of Tumor Growth”, J. Parent. Enteral. Nut., 1994. 8.IByrne T, Persinger R., Young L, Zigler T, Wilmore D: “A New Treatment for Patients with Short-Bowel Syndrome, Growth Hormone Treatment, Glutamine, and a Modified Diet.” Annals of Surgery, 1995.9.INewsholme E, Newsholme P et al: “A Role for Muscle in the Immune System and its Importance in Surgery, Trauma, Sepsis and Burns, Nutrition, 1988. 10.IVarnier M, Leese G, Thompson J, Rennie,M, :”Stim. Eff. of Glut. on Glycogen Accum. in Human Skeletal Muscle,” Am. J. Physiol, 1995.

Glutamine is a neutral amino acid and is the most abundant amino acid found in human muscle and plasma. In fact, 60% of the free-floating amino acid pool in your skeletal muscle cells is made up of glutamine. Glutamine has come to be known as a “conditionally essential” amino acid because in times of stress (exercise is stress), the body requires more of it to maintain both blood and muscle stores of glutamine. It is derived from wheat molasses for commercial production. Glutamine has a tremendous amount of benefits to exercising individuals and those looking to increase lean muscle mass and decrease body fat. Supplemental glutamine can help promote cell volumization. This phenomenon is the drawing of water INSIDE muscle cells which can help increase muscle “fullness”, increase protein synthesis (the making of proteins), and decrease proteolysis (the breakdown of protein). In fact, some of the “muscle building” benefits of taking creatine have to do with its ability to enhance cell volumization. Glutamine has also been shown to aid in recovery and recuperation, help boost immune function by being one of the building blocks for the body’s most powerful anti-oxidant, glutathione, possibly cause extra growth hormone release with just a 2 gram oral dosage (it is yet to be determined whether that leads to an ergogenic benefit but it couldn’t hurt), partially determine the rate of protein turnover in muscles, boost antiinflammatory cell function, and helps increase muscle glycogen deposition through an unknown mechanism. Many of these powerful effects can help increase lean body mass and prevent the breakdown of hard earned muscle. While glutamine has its great benefits, a large majority of ingested free form L-glutamine does not actually make it into the blood stream and get into muscle tissue. Anywhere from 50-85% of an oral glutamine load is used by the intestines, liver, and the immune system. This is what many scientists refer to as the “glutamine paradox”. Well, with the use of glutamine peptide, this problem may be solved. This form of glutamine is peptide bonded (a chain of amino acids) to allow for better transport into the blood stream and muscle tissue where it is needed. Glutamine peptide is also much more stable in solution, higher temperatures, and low PH than free form glutamine (free form L-glutamine tends to break down to ammonia and glutamic acid rather quickly in solution). The digestive tract has peptide transport systems that allow peptides to be better absorbed and utilized than free form amino acids. So basically, the peptide bonded glutamine enhances bioavailability of glutamine in the bloodstream which may allow more glutamine to be available to the muscle tissue. L-Serine Serine is needed for the proper metabolism of fats and fatty acids, the growth of muscle, and the maintenance of a healthy immune system. It is a component of the protective myelin sheaths that cover nerve fibers. It is important in RNA & DNA function and cell formation. Serine aids in the production of immunoglobulins and antibodies. L-Taurine Taurine strengthens the heart muscle, boosts vision, and helps prevent macular degeneration. It is the key component of bile, which is needed for the digestion of fats. It is useful for people with atherosclerosis, edema, heart disorders, hypertension, or hypoglycemia. It is vital for the proper utilization of sodium, potassium, calcium and magnesium. It helps prevent the development of potentially dangerous cardiac arrhythmias. Taurine has been used to treat anxiety, epilepsy, hyperactivity, poor brain function, and seizures. L-Threonine Threonine helps maintain proper protein balance in the body. It is important for the formation of collagen, elastin and tooth enamel. It aids liver and Lipotropic function when combined with Aspartic Acid and Methionine. It prevents the buildup of fat in the liver; assists metabolism and assimilation.


L-TYROSINE Main Functions: Precursor to neurotransmitters dopamine, norepinephrine, epinephrine (adrenalin) and melanin. Effective anti-depressant for norepinephrinedeficient depressions Precursor to thyroxine and growth hormone Increases energy Improves mental clarity and concentration REFERENCES Endocrinology (USA), 1996, 137/4 (1313-1318) Journal of Biological Chemistry (USA), 1996, 271/8 (4002-4008) Neurochemistry International (United Kingdom), 1996, 28/3 (277-281) European Journal of Endocrinology (Norway), 1995, 132/5, (611-617) Eur J Pharmacol (Netherlands) Jun 13, 1994, 258 (3) 173-178 Annu Rev Med (USA) 19811, 32 (413-425) Med Hypotheses (England) Mar 1981, 7 (3) 271-28L-Pyroglutamic Acid L-Pyroglutamic Acid is believed to be associated with activity of the key neurotransmitter, acetylcholine, and with the production of natural GABA and glycine, two other important neurotransmitters. It is an amino acid found in fruits and vegetables. L-Pyrogutamic Acid naturally occurs in the body and is sometimes refproperties in that it is a key neurotransmitter, which may promote cognitive function in both men and women. L-Carnitine

  • REFERENCES: 1. Di Pasquale, M, Amino Acids and Proteins for the Athlete, the Anabolic Edge, 1997. 2. Cynober, Luc (edited by), Amino Acid Metabolism and Therapy in Health & Nutritional Healing, 1997. 3. Balch, J. M.D., Balch, P., C.N.C., Prescription for Disease, 1995 4. Gusev, Skvortsova et al., “Neuroprotective Effects of Glycine for Therapy of Acute Ischaemic Stroke”, Cerebrovasc Dis., Jan.-Feb.2000. 5. Rose, Cattley, Dunn, wong et al, Univ. of N. Carolina, “Dietary Glycine Prevent the Develop. Of Liver Tumors Caused by the Peroxisome Proliferator WY-14, 643″, Carcinogenesis, Nov. 1999. 6. Rose, Madren et al, U. of N. Carolina, ” Dietary Glycine Inhibits the Growth of B 16 Melanoma Tumors in Mice”, Carcinogenesis, May 1999. 7. Kasai, Kobayashi, Shimoda, “Stimulatory Effect of Glycine on Human Growth Hormone Secretion”, Metabolism, 1978. 8. Banay-Schwartz, Palkovitis, Lajtha, ” A Heterogeneous Distribution of Functionally Important Acids in Brain Areas of Adult and Aging Humans”. Neurochem. Res., 1993.9. Evins, Fitzgerald, Wine, Rosselli, Goff, Mass. Gen. Hospital, “PlaceboControlled Trial , Glycine to Clozapine in Schizophrenia”, Am. J. Psychiatry, May 2000.


CHOLINE Main functions: Choline and pantothenic acid are substances needed by the brain to produce acetylcholine, a major brain/motor neuron neurotransmitter that facilitates the transmission of impulses between neurons. Choline chloride and phosphatidylcholine are two forms of choline that have been the subject of most the research, some of which has shown that high doses of choline are an effective way of achieving optimal acetylcholine levels. Lower levels of acetylcholine are associated with memory loss and learning difficulties that occur in aging brains. In one experiment, university students improved test scores after taking supplemental choline.

  • RESEARCH 1. Blusztajn, J.K. Choline, a vital amine. Science. 1998; volume 281: pages 794- 795. (PubMed) 2. Zeisel, S.H. Choline and phosphatidylcholine. In Shils, M. et al. Eds. Nutrition in Health and Disease, 9th Edition. Baltimore: Williams & Wilkins, 1999: pages 513-523. 3. Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes: Thiamin, Riboflavin, Niacin, Vitamin B-6, Vitamin B-12, Pantothenic Acid, Biotin, and Choline. Washington, DC: National Academy Press, 1998: pages 390- 422. (National Academy Press) 4. Zeisel, S.H. Choline: an essential nutrient for humans. Nutrition. 2000; volume 16: pages 669-671. 5. Jacob, R.A. et al. Folate nutriture alters choline status of women and men fed low choline diets. Journal of Nutrition. 1999; volume 129: pages 712-717. (PubMed) 6. Zeisel, S.H. & Blusztajn, J.K. Choline and human nutrition. Annual Review of Nutrition. 1994; volume 14: pages 269-296. (PubMed) 7. Gerhard, G.T. & Duell, P.B. Homocysteine and atherosclerosis. Current Opinion in Lipidology. 1999; volume 10: pages 417-428. (PubMed) 8. Lundberg, P. et al. 1H NMR determination of urinary betaine in patients with premature vascular disease and mild hyperhomocysteinemia. Clinical Chemistry. 1995; volume 41: pages 275-283. (PubMed) 9. Blom, H. Determinants of plasma homocysteine. American Journal of Clinical Nutrition. 1998; volume 68: pages 919-921. (PubMed) 10. Whitehouse, P.J. The cholinergic deficit in Alzheimer’s disease. Journal of Clinical Psychiatry. 1998; volume 59 (supplement 13): pages 19-22. (PubMed) 11. Higgins, J.P. & Flicker, L. Lecithin for dementia and cognitive impairment. Cochrane Database of Systematic Reviews. 2000. 2:CD001015. (PubMed)
  • RESEARCH 1. Munro HN, Crim MC, In Shila Me, Young VR (eds) “Modern Nutrition in Health and Disease” (7th ed). Philadelphia. Lea and Febiger, 1986. pp 1-37. 2. “Concise Encyclopedia of Biochemistry” New York. Walter de Gruyter, 1983. p 180. 3. Rodwell VW. In Martin Jr, DW et at (eds). “Harper’s Review of Biochemistry” (20th ed) Los Altos, CA. Lange, 1985. pp 293-318. 4. Rodwell VW. Biosynthesis of Amino Acids. In Martin Jr. DW et al (eds) “Harper’s Review of Biochemistry” (20th ed). Los Altos, CA Lange, 1985. pp 275-282. 5. Plaitakis A, Berl S. “J Neural Transmission.” 1983; Suppl 19: 65-74. 6. Windmueller HG, Spaeth AE. “Arch Biochem Biophys.” 1975; 171: 662- 672. 7. Mindell, Earl. Vitamin Bible for the 21st Century, 2001. 8. Cooper, Dr. Kenneth H. Advanced Nutritional Therapies, 1996. 9. Kirschmann, John. Nutrition Almanac. New York: McGraw-Hill, 1984. 10. Borton, Benjamin. Human Nutrition. New York: McGraw-Hill, 1978. 11. Mindell, Earl. Vitamin Bible. New York: Rawson, Wade, 1980. 12. Benowieez, Robert. Vitamins & You. New York: Berklett books, 1981. 13. Gottlieb, William. The Complete Book of Vitamins. Emmaus, PA: Rodale Press, 1984. 14. Tierra, Michael. The Way of Herbs. New York: Washington Square Press, 1983. 15. McCarty, Mark. Health Benefits of Supplemental Nutrition. San Diego, CA Nutri Guard Research,1985.


POTASSIUM Main Functions: Potassium is an essential dietary mineral that is also known as an electrolyte. The term electrolyte refers to a substance that dissociates into ions (charged particles) in solution making it capable of conducting electricity. The normal functioning of our bodies depends on the tight regulation of potassium concentrations both inside and outside of cells (1). FUNCTION Maintenance of membrane potential: Potassium is the principal positively charged ion (cation) in the fluid inside of cells, while sodium is the principal cation in the fluid outside of cells. Potassium concentrations are about 30 times higher inside than outside cells, while sodium concentrations are more than 10 times lower inside than outside cells. The concentration differences between potassium and sodium across cell membranes create an electrochemical gradient knownas the membrane potential. A cell’s membrane potential is maintained by ion pumps in the cell membrane, especially the sodium, potassium-ATPase pumps. These pumps use ATP (energy) to pump sodium out of the cell in exchange for potassium. Their activity has been estimated to account for 20%-40% of the resting energy expenditure in a typical adult. The large proportion of energy dedicated to maintaining sodium/potassium concentration gradients emphasizes the importance of this function in sustaining life. Tight control of cell membrane potential is critical for nerve impulse transmission, muscle contraction, and heart function (2,3). Cofactor for enzymes: A limited number of enzymes require the presence of potassium for their activity. The activation of sodium, potassium-ATPase requires the presence of sodium and potassium. The presence of potassium is also required for the activity of pyruvate kinase, an important enzyme in carbohydrate metabolism (3).

  • REFERENCES: 1. Peterson, L.N. Potassium in nutrition. In O’Dell, B.L. & Sunde, R.A. Eds. Handbook of nutritionally essential minerals. New York: Marcel Dekker, Inc.1997: pages 153-183. 2. Brody, T. Nutritional Biochemistry, 2nd Edition. San Diego, CA: Academic Press, 1999: pages 697-730. 3. Sheng, H.-W. Sodium, chloride and potassium. In Stipanuk, M. Ed. Biochemical and Physiological Aspects of Human Nutrition. Philadelphia, PA: W.B. Saunders Co., 2000: pages 686-710. 4. National Research Council. Recommended Dietary Allowances. 10th Ed. Washington, D.C.: National Academy Press, 1989: pages 247-261. 5. F.J. Genarri. Hypokalemia. The New England Journal of Medicine. 1998; volume 339: pages 451-458.6. Young, D.B. et al. Potassium’s cardiovascular protective mechanisms. American Journal of Physiology. 1995; volume 268: pages R825-R837. (PubMed) 7. Barri, Y.M. & Wingo, C.S. The effects of potassium depletion and supplementation on blood pressure: a clinical review. American Journal of the Medical Sciences. 1997; volume 314: pages 37-40. (PubMed) 8. Hajjar, I.M. et al. Impact of diet on blood pressure and age-related change in blood pressure n the U.S. population: analysis of NHANES III. Archives of Internal Medicine. 2001; volume 161: pages 589- 593. (PubMed) 9. Appel, L.J. et al. A clinical trial of the effects of dietary patterns on blood pressure. The New England Journal of Medicine. 1997; volume 336: pages 1117-1124. (PubMed) 10. Whelton, P.K. et al. Effects of oral potassium on blood pressure. Meta-analysis of randomized controlled clinical triglyceride trials. Journal of the American Medical Association (JAMA). 1997; volume 277: pages 1624-1632. (PubMed) 11. Gu, D. et al. Effect of potassium supplementation on blood pressure in Chinese: a randomized placebo-controlled trial. Journal of Hypertension. 2001; volume 19: pages 1325-1331.(PubMed) 12. Ascherio, A. et al. Intake of potassium, magnesium, calcium, and fiber and risk of stroke among US men. Circulation. 1998; volume 98: pages 1198-1204. (PubMed) 13. Iso, H. et al. Prospective study of calcium, potassium, and magnesium intake and risk of stroke in women. Stroke. 1999; volume 30: pages 1772-1779.(PubMed) 14. Fang, J. et al. Dietary potassium intake and stroke mortality. Stroke. 2000; volume 31: pages 1532-1537. (PubMed) 15. Bazzano, L.A. et al. Dietary potassium intake and risk of stroke in US men and women: National Health and Nutrition Examination Survey I epidemiologic follow-up study. Stroke. 2001; volume 32: pages 1473-1480. (PubMed) 16. New, S.A. et al. Dietary influences on bone mass and bone metabolism: further evidence of a positive link between fruit and vegetable consumption and bone health? American Journal of Clinical Nutrition. 2000; volume 71: pages 142-151. (PubMed) 17. New, S.A. et al. Nutritional influences on bone mineral density: a cross-sectional study in premenopausal women. American Journal of Clinical Nutrition. 1997; volume 65: pages 1831-9. (PubMed) 18. Tucker, K. L. et al. Potassium, magnesium, and fruit and vegetable intakes are associated with greater bone mineral density in elderly men and women. 1999; volume 69: pages 727-736. (PubMed) 19. Morris, R.C. et al. Expression of osteoporosis as determined by diet-disordered electrolyte and acid-base metabolism. In Eds. Burkhardt P., Dawson-Hughes, B. & Heaney, R. Nutritional Aspects of Osteoporosis. San Diego, CA: Academic Press. 2001: pages 357-378. 20. Sebastian, A. et al. Improved mineral balance and skeletal metabolism in postmenopausal women treated with potassium bicarbonate. The New England Journal of Medicine. 1994; volume 330: pages 1776-1781. (PubMed) 21. Trinchieri, A. et al. Effect of potential renal acid load of foods on calcium metabolism of renal calcium stone formers. European Urology. 2001; volume 39 (supplement 2): pages 33-37. (PubMed) 22. Morris, R.C. et al. Differing effects of supplemental KCl and KHCO3: pathophysiological and clinical implications. Seminars in Nephrology. 1999; volume 19: pages 487-493. (PubMed) 23. Lemann J. et al. Potassium causes calcium retention in healthy adults. Journal of Nutrition. 1993: 123(9):1623-6. (PubMed) 24. Curhan, G.C. et al. A prospective study of dietary calcium and other nutrients and the risk of symptomatic kidney stones. New England Journal of Medicine. 1993; volume 328 (12): pages 833- 838.(PubMed) 25. Curhan, G.C. et al. Comparison of dietary calcium with supplemental calcium and other nutrients as factors affecting the risk for kidney stones in women. Annals of Internal Medicine. 1997; volume 126: pages 497-504. (PubMed)26. PDR® for Nutritional Supplements. Hendler, S.S. & Rorvik, D.R. Eds. 1st Edition. Montvale: Medical Economics Company, Inc., 2001: pages 368-372. 27. Mandal, A.K. Hypokalemia and Hyperkalemia. Medical Clinics of North America. 1997; volume 81: pages 611-639. (PubMed) 28. Liu, S. et al. Fruit and vegetable intake and risk of cardiovascular disease: the Women’s Health Study. American Journal of Clinical Nutrition. 2000; volume 72: pages 922-928. (PubMed) 29. Joshipura, K.J. Fruit and vegetable intake in relation to ischemic stroke. Journal of the American Medical Association (JAMA). 1999; volume 282: pages 1233-1239. (PubMed)


MAGNESIUM Main Functions: Magnesium plays important roles in the structure and the function of the human body. The adult human body contains about 25 grams of magnesium. Over 60% of all the magnesium in the body is found in the skeleton, about 27% is found in muscle, while 6 to 7% is found in other cells, and less than 1% is found outside of cells (1). FUNCTION Magnesium is involved in more than 300 essential metabolic reactions, some of which are discussed below (2,3). Energy production: The metabolism of carbohydrates and fats to produce energy requires numerousmagnesium-dependent chemical reactions. Magnesium is required by the adenosine triphosphate (ATP) synthesizing protein in mitochondria. ATP, the molecule that provides energy for almost all metabolic processes, exists primarily as a complex with magnesium (MgATP). Synthesis of essential molecules: Magnesium is required at a number of steps during the synthesis of nucleic acids (DNA and RNA) and proteins. A number of enzymes participating in the synthesis of carbohydrates and lipids require magnesium for their activity. Glutathione, an important antioxidant, requires magnesium for its synthesis. Structural roles: Magnesium plays a structural role in bone, cell membranes, and chromosomes. Ion transport across cell membranes: Magnesium is required for the active transport of ions like potassium and calcium across cell membranes. Through its role in ion transport systems, magnesium affects the conduction of nerve impulses, muscle contraction, and the normal rhythm of the heart. Cell signaling: Cell signaling requires MgATP for the phosphorylation of proteins and the formation of the cell signaling molecule, cyclic adenosine monophosphate (cAMP). cAMP is involved in many processes, including the secretion of parathyroid hormone (PTH) from the parathyroid glands (see Vitamin D and Calcium for additional discussions of the role of PTH). Cell migration: Calcium and magnesium levels in the fluid surrounding cells affect the migration of a number of different cell types. Such affects on cell migration may be important in wound healing.

  • REFERENCES: 1. Shils, M.E. Magnesium. In O’Dell, B.L. & Sunde, R.A. Eds. Handbook of nutritionally essential minerals. New York: Marcel Dekker, Inc.1997: pages 117-152.2. Shils, M.E. Magnesium. In Shils, M. et al. Eds. Nutrition in Health and Disease, 9th Edition. Baltimore: Williams & Wilkins, 1999: pages 169-192. 3. Brody, T. Nutritional Biochemistry, 2nd Edition. San Diego, CA: Academic Press, 1999: pages 794-802. 4. Spencer, H. et al. Inhibitory effects of zinc on magnesium balance and magnesium absorption in man. Journal of the American College of Nutrition. 1994; volume 13: pages 479-484. (PubMed) 5. Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes: Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. Washington, DC: National Academy Press, 1997: pages 190-249. (National Academy Press) 6. Ascherio, A. et al. A prospective study of nutritional factors and hypertension among U.S. men. Circulation. 1992; volume 86: pages 1475-1484. (PubMed) 7. Ascherio A. et al. Prospective study of nutritional factors, blood pressure and hypertension among U.S. women. Hypertension. 1996; volume 27: pages 1065-1072. (PubMed) 8. Peacock, J.M. et al. Relationship of serum and dietary magnesium to incident hypertension: the Atherosclerosis Risk in Communities (ARIC) Study. Annals of Epidemiology. 1999; volume 9: pages 159-165. (PubMed) 9. Marx, A. & Neutra, R.R. Magnesium in drinking water and ischemic heart disease. Epidemiologic Reviews. 1997; volume 19: pages 258-272. (PubMed) 10. Liao, F. et al. Is low magnesium concentration a risk factor for coronary heart disease? The Atherosclerosis Risk in Communities (ARIC) Study. American Heart Journal. 1998; volume 136: pages 480-490. (PubMed) 11. Witteman, J.C. et al. Reduction of blood pressure with oral magnesium supplementation in women with mild to moderate hypertension. American Journal of Clinical Nutrition. 1994; volume 60: pages 129-135. (PubMed) 12. Kawano, Y. et al. Effects of magnesium supplementation in hypertensive patients: assessment by office, home, andambulatory blood pressures. Hypertension. 1998; volume 32: pages 260-265. (PubMed) 13. Shils, M.E. Magnesium. In Ziegler, E.E. & Filer, L.J. Eds. Present Knowledge in Nutrition. Washington D.C.: ILSI Press, 1996: pages 256-264. 14. Cromblehome, W.R. Obstetrics. In Current Medical Diagnosis and Treatment. Tierney, al. Eds. 1998; Appleton & Lange, Stamford, CT; pages 724-747. 15. Woods, K.L. et al. Intravenous magnesium sulfate in suspected acute myocardial infarction: results of the second Leicester Intravenous Magnesium Intervention Trial (LIMIT-2). The Lancet. 1992; volume 339: pages 1553-1558. (PubMed) 16. Woods, K.L. & Fletcher, S. Long-term outcome after intravenous magnesium sulfate in suspected acute myocardial infarction: the second Leicester Intravenous Magnesium Intervention Trial (LIMIT-2). The Lancet. 1994; volume 343: pages 816-819. (PubMed) 17. ISIS-4 Collaborative Group. ISIS-4: A randomized factorial trial assessing early oral captopril, oral mononitrate, and intravenous magnesium sulphate in 58,050 patients with suspected acute myocardial infarction. The Lancet. 1995; volume 345: pages 669-685. (PubMed) 18. Shecter, M. et al. Oral magnesium therapy improves endothelial function in patients with coronary artery disease. Circulation. 2000; volume 102: pages 2353-2358. (PubMed) 19. Shecter, M. et al. Oral magnesium supplementation inhibits platelet dependent thrombosis in patients with coronary artery disease. American Journal of Cardiology. 1999; volume 84: pages 152-156. (PubMed) 20. Tosiello, L. Hypomagnesemia and diabetes mellitus: A review of clinical implications. Archives of Internal Medicine. 1996; volume 156: pages 1143-1148. (PubMed) 21. Paolisso, G. et al. Daily magnesium supplements improve glucose handling in elderly subjects. American Journal of Clinical Nutrition. 1992; volume 55: pages 1161-1167. (PubMed)22. Sojka, J.E. & Weaver, C.M. Magnesium supplementation and osteoporosis. Nutrition Reviews. 1995; volume 53: pages 71-74. (PubMed) 23. Tucker, K.L. et al. Potassium, magnesium, and fruit and vegetable intakes are associated with greater bone mineral density in elderly men and women. American Journal of Clinical Nutrition. 1999; volume 69: pages 727-736. (PubMed) 24. Stendig-Lindberg, G. et al. Trabecular bone density in a two-year controlled trial of peroral magnesium in osteoporosis. Magnesium Research. 1993; volume 6: pages 155-163. (PubMed) 25. Abraham, G.E. & Grewal, H. A total dietary program emphasizing magnesium instead of calcium: effect on the mineral density of calcaneous bone in postmenopausal women on hormonal therapy. Journal of Reproductive Medicine. 1990; volume 35: pages 503-507. (PubMed) 26. Peikert, A. et al. Prophylaxis of migraine with oral magnesium; results from a prospective multi-center, placebo-controlled and double-blind randomized study. Cephalgia. 1996; volume 16: pages 257-263. (PubMed) 27. Mauskop A. & Altura, B.M. Role of magnesium in the pathogenesis and treatment of migraines. Clinical Neuroscience. 1998; volume 5: pages 766-767. (PubMed) 28. Pfaffenrath, V. et al. Magnesium in the prophylaxis of migraine: a double-blind placebo-controlled study. Cephalgia. 1996; volume 16: pages 436-440. (PubMed) 29. Skobeloff, E.M. et al. Intravenous magnesium sulfate in acute severe bronchial asthma. Journal of the American Medical Society (JAMA). 1989; volume 262: pages 1210-1213. (PubMed) 30. Tiffany, B.R. et al. Magnesium bolus fails or infusion fails to improve expiratory flow in acute asthma exacerbations. Chest. 1993; volume 104: pages 831-834. (PubMed) 31. Montelone, C.A. & Sherman, A.R. Nutrition and asthma. Archives of Internal Medicine. 1997; volume 157: pages 23-34. (PubMed) 32. Silverman, H. et al. The Vitamin Book, 2nd edition. New York: Bantam Books, 1999: pages 270-276.33. Minerals. In Drug Facts and Comparisons. 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THIAMIN (B-1) Main Functions: Thiamin (also spelled thiamine) is a water-soluble B-complex vitamin, previously known as vitamin B1 or aneurine (1). Isolated and characterized in the 1930’s, thiamin was one of the first organic compounds to be recognized as a vitamin (2). Thiamin occurs in the human body as free thiamin and its phosphorylated forms: thiamin monophosphate (TMP), thiamin triphosphate (TTP), and thiamin pyrophosphate (TPP), which is also known as thiamin diphosphate. FUNCTION Coenzyme function Thiamin pyrophosphate (TPP) is a required coenzyme for a small number of very important enzymes. The synthesis of TPP from free thiamin requires magnesium, adenosine triphosphate (ATP), and the enzyme, thiamin pyrophosphokinase. Pyruvate dehydrogenase, a-ketoglutarate dehydrogenase, and branched chain ketoacid (BCKA) dehydrogenase each comprise a different enzyme complex found within cellular organelles called mitochondria. They catalyze the decarboxylation of pyruvate, a-ketoglutarate, and branched-chain amino acids to form acetyl-coenzyme A, succinyl-coenzyme A, and derivatives of branched chain amino acids, respectively, all of which play critical roles in the production of energy from food (2). In addition to the thiamin coenzyme (TPP), each dehydrogenase complex requires a niacin-containing coenzyme (NAD), a riboflavin-containing coenzyme (FAD), and lipoic acid. Transketolase catalyzes critical reactions in another metabolic pathway known as the pentose phosphate pathway. One of the most important intermediates of this pathway is ribose-5-phosphate, a phosphorylated 5-carbon sugar, required forthe synthesis of the high-energy ribonucleotides, ATP and guanosine triphosphate (GTP), the nucleic acids, DNA and RNA, and the niacin-containing coenzyme NADPH, which is essential for a number of biosynthetic reactions (1, 3). Because transketolase decreases early in thiamin deficiency, measurement of its activity in red blood cells has been used to assess thiamin nutritional status (2). Non-coenzyme function Thiamin triphosphate (TTP) is concentrated in nerve and muscle cells. Research in animals indicates that TTP activates membrane ion channels, possibly by phosphorylating them (4). The flow of electrolytes like sodium or potassium in or out of nerve and muscle cells through membrane ion channels plays a role in nerve impulse conduction and voluntary muscle action. Impaired formation of TTP may play a role in the neurologic symptoms of severe thiamin deficiency.

  • REFERENCES: 1. Tanphaichitr V. Thiamin. In: Shils M, ed. Nutrition in Health and Disease. 9th ed. Baltimore: Williams & Wilkins; 1999:381-389. 2. Rindi G. Thiamin. In: Ziegler EE, Filer LJ, eds. Present Knowledge in Nutrition. 7th ed. Washington D.C.: ILSI Press; 1996:160-166. 3. Brody T. Nutritional Biochemistry. 2nd ed. San Diego: Academic Press; 1999. 4. Bender DA. Optimum nutrition: thiamin, biotin and pantothenate. Proc Nutr Soc. 1999;58(2):427-433. (PubMed) 5. Todd K, Butterworth RF. Mechanisms of selective neuronal cell death due to thiamine deficiency. Ann N Y Acad Sci. 1999;893:404-411. (PubMed) 6. Krishna S, Taylor AM, Supanaranond W, et al. Thiamine deficiency and malaria in adults from southeast Asia. Lancet. 1999;353(9152):546-549. (PubMed)7. Muri RM, Von Overbeck J, Furrer J, Ballmer PE. Thiamin deficiency in HIVpositive patients: evaluation by erythrocyte transketolase activity and thiamin pyrophosphate effect. Clin Nutr. 1999;18(6):375-378. (PubMed) 8. Hung SC, Hung SH, Tarng DC, Yang WC, Chen TW, Huang TP. Thiamine deficiency and unexplained encephalopathy in hemodialysis and peritoneal dialysis patients. Am J Kidney Dis. 2001;38(5):941-947. (PubMed) 9. Rieck J, Halkin H, Almog S, et al. Urinary loss of thiamine is increased by low doses of furosemide in healthy volunteers. J Lab Clin Med. 1999;134(3):238-243. (PubMed) 10. Suter PM, Haller J, Hany A, Vetter W. Diuretic use: a risk for subclinical thiamine deficiency in elderly patients. J Nutr Health Aging. 2000;4(2):69-71. (PubMed) 11. Wilcox CS. Do diuretics cause thiamine deficiency? J Lab Clin Med. 1999;134(3):192-193. 12. Nishimune T, Watanabe Y, Okazaki H, Akai H. Thiamin is decomposed due to Anaphe spp. entomophagy in seasonal ataxia patients in Nigeria. J Nutr. 2000;130(6):1625-1628. (PubMed) 13. IFood and Nutrition Board, Institute of Medicine. Thiamin. Dietary Reference Intakes: Thiamin, Riboflavin, Niacin, Vitamin B-6, Vitamin B-12, Pantothenic Acid, Biotin, and Choline. Washington D.C.: National Academy Press; 1998:58-86. (National Academy Press) 14. Kish SJ. Brain energy metabolizing enzymes in Alzheimer’s disease: alphaketoglutarate dehydrogenase complex and cytochrome oxidase. Ann N Y Acad Sci. 1997;826:218-228. (PubMed) 15. Heroux M, Raghavendra Rao VL, Lavoie J, Richardson JS, Butterworth RF. Alterations of thiamine phosphorylation and of thiamine-dependent enzymes in Alzheimer’s disease. Metab Brain Dis. 1996;11(1):81-88. (PubMed) 16. Mastrogiacoma F, Bettendorff L, Grisar T, Kish SJ. Brain thiamine, its phosphate esters, and its metabolizing enzymes in Alzheimer’s disease. Ann Neurol. 1996;39(5):585-591. (PubMed)17. Meador K, Loring D, Nichols M, et al. Preliminary findings of high-dose thiamine in dementia of Alzheimer’s type. J Geriatr Psychiatry Neurol. 1993;6(4):222-229. (PubMed) 18. Mimori Y, Katsuoka H, Nakamura S. Thiamine therapy in Alzheimer’s disease. Metab Brain Dis. 1996;11(1):89-94. (PubMed) 19. Rodriguez-Martin JL, Qizilbash N, Lopez-Arrieta JM. Thiamine for Alzheimer’s disease (Cochrane Review). Cochrane Database Syst Rev. 2001;2:CD001498. (PubMed) 20. Wilkinson TJ, Hanger HC, George PM, Sainsbury R. Is thiamine deficiency in elderly people related to age or co-morbidity? Age Ageing. 2000;29(2):111-116. (PubMed) 21. Shimon I, Almog S, Vered Z, et al. Improved left ventricular function after thiamine supplementation in patients with congestive heart failure receiving long-term furosemide therapy. Am J Med. 1995;98(5):485-490. (PubMed) 22. Leslie D, Gheorghiade M. Is there a role for thiamine supplementation in the management of heart failure? Am Heart J. 1996;131(6):1248-1250. 23. Comin-Anduix B, Boren J, Martinez S, et al. The effect of thiamine supplementation on tumour proliferation. A metabolic control analysis study. Eur J Biochem. 2001;268(15):4177-4182. (PubMed) 24. Boros LG, Brandes JL, Lee WN, et al. Thiamine supplementation to cancer patients: a double edged sword. Anticancer Res. 1998;18(1B):595-602. (PubMed) 25. Russell RM, Suter PM. Vitamin requirements of elderly people: an update. Am J Clin Nutr. 1993;58(1):4-14. (PubMed) 26. Hendler SS, Rorvik DR, eds. PDR for Nutritional Supplements. Montvale: Medical Economics Company, Inc; 2001. 27. Flodin N. Pharmacology of micronutrients. New York: Alan R. Liss, Inc.; 1988. 28. Schumann K. Interactions between drugs and vitamins at advanced age. Int J Vitam Nutr Res. 1999;69(3):173-178. (PubMed)


RIBOFLAVIN (B-2) Main Functions: Riboflavin is a water-soluble B-complex vitamin, also known as vitamin B2. In the body, riboflavin is primarily found as an integral component of the coenzymes, flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) (1). Coenzymes derived from riboflavin are also called flavins. Enzymes that use a flavin coenzyme are called flavoproteins (2). FUNCTION Oxidation-reduction (redox) reactions Living organisms derive most of their energy from oxidation-reduction (redox) reactions, which are processes involving the transfer of electrons. Flavin coenzymes participate in redox reactions in numerous metabolic pathways (3). Flavins are critical for the metabolism of carbohydrates, fats, and proteins. FAD is part of the electron transport (respiratory) chain, which is central to energy production. In conjunction with cytochrome P-450, flavins also participate in the metabolism of drugs and toxins (4). Antioxidant functions Glutathione reductase is an FAD-dependent enzyme that participates in the redox cycle of glutathione. The glutathione redox cycle plays a major role in protecting organisms from reactive oxygen species, such as hydroperoxides. Glutathione peroxidase, a selenium-containing enzyme, requires two molecules of reduced glutathione to break down hydroperoxides (see diagram). Glutathione reductase requires FAD to regenerate two molecules of reduced glutathione from oxidized glutathione. Riboflavin deficiency has been associated with increased oxidative stress (4). Measurement of glutathione reductase activity in red blood cells is commonly used to assess riboflavin nutritional status (5). Xanthine oxidase, another FAD-dependent enzyme, catalyzes the oxidation of hypoxanthine and xanthine to uric acid. Uric acid is one of the most effective water-soluble antioxidants in the blood. Riboflavin deficiency can result in decreased xanthine oxidase activity, reducing blood uric acid levels (6). Nutrient Interactions B-complex vitamins: Because flavoproteins are involved in the metabolism of several other vitamins (vitamin B6, niacin, and folic acid), severe riboflavin deficiency may impact many enzyme systems. Conversion of most naturally available vitamin B6 to its coenzyme form, pyridoxal 5′-phosphate (PLP), requires the FMN-dependent enzyme, pyridoxine 5′-phosphate oxidase (PPO) (7). At least two studies in the elderly have documented significant interactions between indicators of vitamin B6 and riboflavin nutritional status (8, 9). The synthesis of the niacin-containing coenzymes, NAD and NADP, from the amino acid, tryptophan, requires the FAD-dependent enzyme, kynurenine mono-oxygenase. Severe riboflavin deficiency can decrease the conversion of tryptophan to NAD and NADP, increasing the risk of niacin deficiency (3). Methylene tetrahydrofolate reductase (MTHFR) is an FADdependent enzyme, which plays an important role in maintaining the specific folate coenzyme required to form methionine from homocysteine (see diagram). Along with other B-vitamins, increased riboflavin intake has been associated with decreased plasma homocysteine levels (10). Recently, increased plasma riboflavin levels were associated with decreased plasma homocysteine levels mainly in those individuals who were homozygous for the C677T polymorphism of the MTHFR gene and whose folate intake was low (11). Such results illustrate the potential for complex interactions between genetic and dietary factors on chronic disease risk. Iron: Riboflavin deficiency alters iron metabolism. Although the mechanism is not clear, research in animals suggests that riboflavin deficiency may impair iron absorption, increase intestinal loss of iron, and/or impair iron utilization for thesynthesis of hemoglobin. In humans, improving riboflavin nutritional status has been found to increase circulating hemoglobin levels. Correction of riboflavin deficiency in individuals who are both riboflavin deficient and iron deficient improves the response of iron-deficiency anemia to iron therapy (12).

  • REFERENCES: 1. Food and Nutrition Board, Institute of Medicine. Riboflavin. Dietary Reference Intakes: Thiamin, Riboflavin, Niacin, Vitamin B-6, Vitamin B-12, Pantothenic Acid, Biotin, and Choline. Washington D.C.: National Academy Press; 1998:87-122. (National Academy Press) 2. Brody T. Nutritional Biochemistry. 2nd ed. San Diego: Academic Press; 1999. 3. McCormick DB. Riboflavin. In: Shils M, Olson JA, Shike M, Ross AC, eds. Nutrition in Health and Disease. 9th ed. Baltimore: Williams & Wilkins; 1999:391-399. 4. Rivlin RS. Riboflavin. In: Ziegler EE, Filer LJ, eds. Present Knowledge in Nutrition. 7th ed. Washington D.C.: ILSI Press; 1996:167-173. 5. Powers HJ. Current knowledge concerning optimum nutritional status of riboflavin, niacin and pyridoxine. Proc Nutr Soc. 1999;58(2):435-440. (PubMed) 6. Bohles H. Antioxidative vitamins in prematurely and maturely born infants. Int J Vitam Nutr Res. 1997;67(5):321-328. (PubMed) 7. McCormick DB. Two interconnected B vitamins: riboflavin and pyridoxine. Physiol Rev. 1989;69(4):1170-1198. 8. Lowik MR, van den Berg H, Kistemaker C, Brants HA, Brussaard JH. Interrelationships between riboflavin and vitamin B6 among elderly people (Dutch Nutrition Surveillance System). Int J Vitam Nutr Res. 1994;64(3):198-203. (PubMed) 9. Madigan SM, Tracey F, McNulty H, et al. Riboflavin and vitamin B-6 intakes and status and biochemical response toriboflavin supplementation in free-living elderly people. Am J Clin Nutr. 1998;68(2):389-395. (PubMed) 10. Jacques PF, Bostom AG, Wilson PW, Rich S, Rosenberg IH, Selhub J. Determinants of plasma total homocysteine concentration in the Framingham Offspring cohort. Am J Clin Nutr. 2001;73(3):613-621. (PubMed) 11. Jacques PF, Kalmbach R, Bagley PJ, et al. The relationship between riboflavin and plasma total homocysteine in the Framingham Offspring cohort is influenced by folate status and the C677T transition in the methylenetetrahydrofolate reductase gene. J Nutr. 2002;132(2):283-288. (PubMed) 12. Powers HJ. Riboflavin-iron interactions with particular emphasis on the gastrointestinal tract. Proc Nutr Soc. 1995;54(2):509-517. (PubMed) 13. Crombleholme WR. Obstetrics. In: Tierney LM, McPhee SJ, Papadakis MA, eds. Current Medical Treatment and Diagnosis. 37th ed. Stamford: Appleton and Lange; 1998:731-734. 14. Wacker J, Fruhauf J, Schulz M, Chiwora FM, Volz J, Becker K. Riboflavin deficiency and preeclampsia. Obstet Gynecol. 2000;96(1):38-44. (PubMed) 15. Soares MJ, Satyanarayana K, Bamji MS, Jacob CM, Ramana YV, Rao SS. The effect of exercise on the riboflavin status of adult men. (PubMed) 16. Jacques PF. The potential preventive effects of vitamins for cataract and age-related macular degeneration. Int J Vitam Nutr Res. 1999;69(3):198-205. (PubMed) 17. Leske MC, Wu SY, Hyman L, et al. Biochemical factors in the lens opacities. Case-control study. The Lens Opacities Case-Control Study Group. Arch Ophthalmol. 1995;113(9):1113-1119. (PubMed) 18. Cumming RG, Mitchell P, Smith W. Diet and cataract: the Blue Mountains Eye Study. Ophthalmology. 2000;107(3):450-456. (PubMed) 19. Hankinson SE, Stampfer MJ, Seddon JM, et al. Nutrient intake and cataract extraction in women: a prospective study. BMJ. 1992;305(6849):335-339. (PubMed)20. Schoenen J, Jacquy J, Lenaerts M. Effectiveness of high-dose riboflavin in migraine prophylaxis. A randomized controlled trial. Neurology. 1998;50(2):466-470. (PubMed) 21. Zempleni J, Galloway JR, McCormick DB. Pharmacokinetics of orally and intravenously administered riboflavin in healthy humans. Am J Clin Nutr. 1996;63(1):54-66. (PubMed) 22. Sandor PS, Afra J, Ambrosini A, Schoenen J. Prophylactic treatment of migraine with beta-blockers and riboflavin: differential effects on the intensity dependence of auditory evoked cortical potentials. Headache. 2000;40(1):30-35. (PubMed) 23. Hendler SS, Rorvik DR, eds. PDR for Nutritional Supplements. Montvale: Medical Economics Company, Inc; 2001. 24. Sugiyama M. Role of physiological antioxidants in chromium(VI)-induced cellular injury. Free Radic Biol Med. 1992;12(5):397-407. (PubMed) 25. Blumberg J. Nutritional needs of seniors. J Am Coll Nutr. 1997;16(6):517- 523. (PubMed) 26. Russell RM, Suter PM. Vitamin requirements of elderly people: an update. Am J Clin Nutr. 1993;58(1):4-14. (PubMed) 27. Lopez-Sobaler AM, Ortega RM, Quintas ME, et al. The influence of vitamin B2 intake on the activation coefficient of erythrocyte glutation reductase in the elderly. J Nutr Health Aging. 2002;6(1):60-62. (PubMed)

NIACIN (B-3) Main Functions: Niacin is a water-soluble vitamin, also known as vitamin B3. The term niacin refers to nicotinic acid and nicotinamide, which are both used by the body to form the coenzymes, nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phospate (NADP). Neither form is related to the nicotine found in tobacco, although their names aresimilar (1). FUNCTION Oxidation-reduction (redox) reactions: Living organisms derive most of their energy from oxidation-reduction (redox) reactions, which are processes involving the transfer of electrons. As many as 200 enzymes require the niacin coenzymes, NAD and NADP, mainly to accept or donate electrons for redox reactions. NAD functions most often in reactions involving the degradation (catabolism) of carbohydrates, fats, proteins, and alcohol to produce energy. NADP functions more often in biosynthetic (anabolic) reactions, such as in the synthesis of fatty acids and cholesterol (1, 2). Non-redox reactions: The niacin coenzyme, NAD, is the substrate (reactant) for two classes of enzymes (mono-ADP-ribosyltransferases and poly-ADP-ribose polymerase) that separate the niacin moiety from NAD and transfer ADP-ribose to proteins (diagram). Mono-ADP-ribosyltransferase enzymes were first discovered in certain bacteria where they were found to produce toxins such as those of cholera and diptheria. These enzymes and their products, ADP-ribosylated proteins, have also been found in the cells of mammals and are thought to play a role in cell signaling by affecting G-protein activity.(3) G-proteins are proteins that bind guanosine-5′-triphosphate (GTP) and act as intermediaries in a number of cell-signaling pathways. Poly-ADP-ribose polymerases (PARPs) are enzymes that catalyze the transfer of many ADP-ribose units from NAD to acceptor proteins. PARPs appear to function in DNA replication and repair, as well as cell differentiation, suggesting a possible role for NAD in cancer prevention (2). At least 5 different PARPs have been identified, and although their functions are not yet well understood, their existence indicates a potential for considerable consumption of NAD (4). A third class of enzyme (ADP-ribosyl cyclase) catalyzes the formation of cyclic ADP-ribose, a molecule that works within cells to provoke the release of calcium ions from internal storage sites, and probably also plays a role in cell signaling (1).

  • REFERENCES: 1. Brody T. Nutritional Biochemistry. 2nd ed. San Diego: Academic Press; 1999.2. Cervantes-Laurean D, McElvaney NG, Moss J. Niacin. In: Shils M, Olson JA, Shike M, Ross AC, eds. Nutrition in Health and Disease. 9th ed. Baltimore: Williams & Wilkins; 1999:401-411. 3. Jacob R, Swenseid M. Niacin. In: Ziegler EE, Filer LJ, eds. Present Knowledge in Nutrition. 7th ed. Washington D.C: ILSI Press; 1996:185-190. 4. Jacobson MK, Jacobson EL. Discovering new ADP-ribose polymer cycles: protecting the genome and more. Trends Biochem Sci. 1999;24(11):415-417. 5. Park YK, Sempos CT, Barton CN, Vanderveen JE, Yetley EA. Effectiveness of food fortification in the United States: the case of pellagra. Am J Public Health. 2000;90(5):727-738. (PubMed) 6. Gregory JF, 3rd. Nutritional Properties and significance of vitamin glycosides. Annu Rev Nutr. 1998;18:277-296. (PubMed) 7. Jacobson EL, Jacobson MK. Tissue NAD as a biochemical measure of niacin status in humans. Methods Enzymol. 1997;280:221-230. 8. Food and Nutrition Board, Institute of Medicine. Niacin. Dietary Reference Intakes: Thiamin, Riboflavin, Niacin, Vitamin B-6, Vitamin B-12, Pantothenic Acid, Biotin, and Choline. Washington, D.C.: National Academy Press; 1998:123-149. (National Academy Press) 9. Fu CS, Swendseid ME, Jacob RA, McKee RW. Biochemical markers for assessment of niacin status in young men: levels of erythrocyte niacin coenzymes and plasma tryptophan. J Nutr. 1989;119(12):1949-1955. (PubMed) 10. Hageman GJ, Stierum RH. Niacin, poly(ADP-ribose) polymerase-1 and genomic stability. Mutat Res. 2001;475(1-2):45-56. (PubMed) 11. Jacobson EL, Shieh WM, Huang AC. Mapping the role of NAD metabolism in prevention and treatment of carcinogenesis. Mol Cell Biochem. 1999;193(1-2):69-74. (PubMed) 12. Boyonoski AC, Spronck JC, Gallacher LM, et al. Niacin deficiency decreases bone marrow poly(ADP-ribose) and thelatency of ethylnitrosourea-induced carcinogenesis in rats. J Nutr. 2002;132(1):108-114. (PubMed) 13. Gensler HL, Williams T, Huang AC, Jacobson EL. Oral niacin prevents photocarcinogenesis and photoimmunosuppression in mice. Nutr Cancer. 1999;34(1):36-41. (PubMed) 14. Weitberg AB. Effect of nicotinic acid supplementation in vivo on oxygen radical-induced genetic damage in human lymphocytes. Mutat Res. 1989;216(4):197-201 (PubMed) 15. Hageman GJ, Stierum RH, van Herwijnen MH, van der Veer MS, Kleinjans JC. Nicotinic acid supplementation: effects on niacin status, cytogenetic damage, and poly(ADP-ribosylation) in lymphocytes of smokers. Nutr Cancer. 1998;32(2):113-120. (PubMed) 16. Jacobson EL. Niacin deficiency and cancer in women. J Am Coll Nutr. 1993;12(4):412-416. (PubMed) 17. Negri E, Franceschi S, Bosetti C, et al. Selected micronutrients and oral and pharyngeal cancer. Int J Cancer. 2000;86(1):122-127. (PubMed) 18. Franceschi S, Bidoli E, Negri E, et al. Role of macronutrients, vitamins and minerals in the aetiology of squamous-cell carcinoma of the oesophagus. Int J Cancer. 2000;86(5):626-631. (PubMed) 19. Lampeter EF, Klinghammer A, Scherbaum WA, et al. The Deutsche Nicotinamide Intervention Study: an attempt to prevent type 1 diabetes. DENIS Group. Diabetes. 1998;47(6):980-984. (PubMed) 20. Greenbaum CJ, Kahn SE, Palmer JP. Nicotinamide’s effects on glucose metabolism in subjects at risk for IDDM. Diabetes. 1996;45(11):1631-1634. (PubMed) 21. Schatz DA, Bingley PJ. Update on major trials for the prevention of type 1 diabetes mellitus: the American Diabetes Prevention Trial (DPT-1) and the European Nicotinamide Diabetes Intervention Trial (ENDIT). J Pediatr Endocrinol Metab. 2001;14 Suppl 1:619-622. (PubMed) 22. Knopp RH. Drug treatment of lipid disorders. N Engl J Med. 1999;341(7):498-511.23. Canner PL, Berge KG, Wenger NK, et al. Fifteen year mortality in Coronary Drug Project patients: long-term benefit with niacin. J Am Coll Cardiol. 1986;8(6):1245-1255. (PubMed) 24. Guyton JR, Capuzzi DM. Treatment of hyperlipidemia with combined niacinstatin regimens. Am J Cardiol. 1998;82(12A):82U-84U; discussion 85-86U. (PubMed) 25. Cheung MC, Zhao XQ, Chait A, Albers JJ, Brown BG. Antioxidant supplements block the response of HDL to simvastatin-niacin therapy in patients with coronary artery disease and low HDL. Arterioscler Thromb Vasc Biol. 2001;21(8):1320-1326. (PubMed) 26. Brown BG, Zhao XQ, Chait A, et al. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med. 2001;345(22):1583-1592. (PubMed) 27. Brown RR, Ozaki Y, Datta SP, Borden EC, Sondel PM, Malone DG. Implications of interferon-induced tryptophan catabolism in cancer, auto-immune diseases and AIDS. Adv Exp Med Biol. 1991;294:425-435. (PubMed) 28. Murray MF, Langan M, MacGregor RR. Increased plasma tryptophan in HIV-infected patients treated with pharmacologic doses of nicotinamide. Nutrition. 2001;17(7-8):654-656. (PubMed) 29. Tang AM, Graham NM, Saah AJ. Effects of micronutrient intake on survival in human immunodeficiency virus type 1 infection. Am J Epidemiol. 1996;143(12):1244-1256. (PubMed) 30. Hendler SS, Rorvik DR, eds. PDR for Nutritional Supplements. Montvale: Medical Economics Company, Inc; 2001 31. Knopp RH. Evaluating niacin in its various forms. Am J Cardiol. 2000;86(12A):51L-56L. (PubMed) 32. Vitamins. Drug Facts and Comparisons. St. Louis: Facts and Comparisons; 2000:6-33. 33. Flodin N. Pharmacology of micronutrients. New York: Alan R. Liss, Inc.; 1988.34. Brown BG, Cheung MC, Lee AC, Zhao XQ, Chait A. Antioxidant vitamins and lipid therapy: end of a long romance? Arterioscler Thromb Vasc Biol. 2002;22(10):1535-1546. (PubMed)


PANTOTHENIC ACID (B-5) Main Functions: Pantothenic acid, also known as vitamin B5, is essential to all forms of life (1). Pantothenic acid is found throughout living cells in the form of coenzyme A (CoA), a vital coenzyme in numerous chemical reactions (2). Coenzyme A: Pantothenic acid is a component of coenzyme A (CoA), an essential coenzyme in a variety of reactions that sustain life. CoA is required for chemical reactions that generate energy from food (fat, carbohydrates, and proteins). The synthesis of essential fats, cholesterol, and steroid hormones requires CoA, as does the synthesis of the neurotransmitter, acetylcholine, and the hormone, melatonin. Heme, a component of hemoglobin, requires a CoA-containing compound for its synthesis. Metabolism of a number of drugs and toxins by the liver requires CoA (3). Coenzyme A was named for its role in acetylation reactions. Most acetylated proteins in the body have been modified by the addition of an acetate group that was donated by CoA. Protein acetylation affects the 3-dimensional structure of proteins, potentially altering their function, the activity of peptide hormones, and appears to play a role in cell division and DNA replication. Protein acetylation also affects gene expression by facilitating the transcription of mRNA. A number of proteins are also modified by the attachment of long-chain fatty acids donated by CoA. These modifications are known as protein acylation, and appear to play a central role in cell signaling (1). Acyl-carrier protein: The acyl-carrier protein requires pantothenic acid in the form of 4′- phosphopantetheine for its activity as an enzyme (1, 4). Both CoA and the acyl-carrier protein are required for the synthesis of fatty acids. Fatty acids are a component of some lipids, which are fat molecules essential for normal physiological function. Among theseessential fats are sphingolipids, which are a component of the myelin sheath that enhances nerve transmission, and phospholipids in cell membranes.

  • REFERENCES 1. Plesofsky-Vig N. Pantothenic acid. In: Shils M, ed. Nutrition in Health and Disease,. 9th ed. Baltimore: Williams & Wilkins; 1999:423-432. 2. Tahiliani AG, Beinlich CJ. Pantothenic acid in health and disease. Vitam Horm. 1991;46:165-228. (PubMed) 3. Brody T. Nutritional Biochemistry. 2nd ed. San Diego: Academic Press; 1999. 4. Bender DA. Optimum nutrition: thiamin, biotin and pantothenate. Proc Nutr Soc. 1999;58(2):427-433. (PubMed) 5. Hodges RE, Ohlson MA, Bean WB. Pantothenic acid deficiency in man. J Clin Invest. 1958;37:1642-1657. 6. Fry PC, Fox HM, Tao HG. Metabolic response to a pantothenic acid deficient diet in humans. J Nutr Sci Vitaminol (Tokyo). 1976;22(4):339-346. (PubMed) 7. Plesofsky-Vig N. Pantothenic acid. In: Filer LJ, ed. Present Knowledge in Nutrition. 7th ed. Washington D.C.: ILSI Press; 1996. 8. Food and Nutrition Board, Institute of Medicine. Pantothenic acid. Dietary Reference Intakes: Thiamin, Riboflavin, Niacin, Vitamin B-6, Vitamin B-12, Pantothenic Acid, Biotin, and Choline. Washington, D.C.: National Academy Press; 1998:357-373. 9. Weimann BI, Hermann D. Studies on wound healing: effects of calcium Dpantothenate on the migration, proliferation and protein synthesis of human dermal fibroblasts in culture. Int J Vitam Nutr Res. 1999;69(2):113-119. (PubMed) 10. Vaxman F, Olender S, Lambert A, et al. Effect of pantothenic acid and ascorbic acid supplementation on human skinwound healing process. A double-blind, prospective and randomized trial. Eur Surg Res. 1995;27(3):158-166. (PubMed) 11. Gaddi A, Descovich GC, Noseda G, et al. Controlled evaluation of pantethine, a natural hypolipidemic compound, in patients with different forms of hyperlipoproteinemia. Atherosclerosis. 1984;50(1):73-83. (PubMed) 12. Coronel F, Tornero F, Torrente J, et al. Treatment of hyperlipemia in diabetic patients on dialysis with a physiological substance. Am J Nephrol. 1991;11(1):32-36. (PubMed) 13. Said HM, Ortiz A, McCloud E, Dyer D, Moyer MP, Rubin S. Biotin uptake by human colonic epithelial NCM460 cells: a carrier-mediated process shared with pantothenic acid. Am J Physiol. 1998;275(5 Pt 1):C1365-1371. (PubMed) 14. Hendler SS, Rorvik DR, eds. PDR for Nutritional Supplements. Montvale: Medical Economics Company, Inc; 2001 15. Flodin N. Pharmacology of micronutrients. New York: Alan R. Liss, Inc.; 1988.

VITAMIN B-12 Main Functions: Vitamin B12 is the largest and most complex of all the vitamins. It is unique among vitamins in that it contains a metal ion, cobalt. For this reason cobalamin is the term used to refer to compounds having B12 activity. Methylcobalamin and 5-deoxyadenosyl cobalamin are the forms of vitamin B12 used in the human body (1). The form of cobalamin used in most supplements, cyanocobalamin, is readily converted to 5-deoxyadenosyl and methylcobalamin. Cofactor for methionine synthase Methylcobalamin is required for the function of the folate-dependent enzyme, methionine synthase. This enzyme is required for the synthesis of the amino acid, methionine, from homocysteine. Methionine is required for the synthesis of S-adenosylmethionine, a methyl group donor used in many biological methylation reactions, including the methylation of a number of sites within DNA and RNA (2). Methylation of DNA may be important in cancer prevention. Inadequate function of methionine synthase can lead to an accumulation of homocysteine, which has been associated with increasedrisk of cardiovascular diseases (diagram). Cofactor for L-methylmalonyl-CoA mutase 5-Deoxyadenosylcobalamin is required by the enzyme that catalyzes the conversion of L-methylmalonyl-CoA to succinyl-CoA. This biochemical reaction plays an important role in the production of energy from fats and proteins. Succinyl CoA is also required for the synthesis of hemoglobin, the oxygen carrying pigment in red blood cells (2).

  • REFERENCES 1. Brody T. Nutritional Biochemistry. 2nd ed. San Diego: Academic Press; 1999. 2. Shane B. Folic acid, vitamin B-12, and vitamin B-6. In: Stipanuk M, ed. Biochemical and Physiological Aspects of Human Nutrition. Philadelphia: W.B. Saunders Co.; 2000:483-518. 3. Baik HW, Russell RM. Vitamin B12 deficiency in the elderly. Annu Rev Nutr. 1999;19:357-377. (PubMed) 4. Herbert V. Vitamin B-12. In: Ziegler EE, Filer LJ, eds. Present Knowledge in Nutrition. 7th ed. Washington D.C.: ILSI Press; 1996:191-205. 5. Food and Nutrition Board, Institute of Medicine. Vitamin B12. Dietary Reference Intakes: Thiamin, Riboflavin, Niacin, Vitamin B-6, Vitamin B-12, Pantothenic Acid, Biotin, and Choline. Washington D.C.: National Academy Press; 1998:306-356. (National Academy Press) 6. Ho C, Kauwell GP, Bailey LB. Practitioners’ guide to meeting the vitamin B- 12 recommended dietary allowance for people aged 51 years and older. J Am Diet Assoc. 1999;99(6):725-727. (PubMed) 7. Weir DG, Scott JM. Vitamin B-12 “Cobalamin”. In: Shils M, ed. Nutrition in Health and Disease. 9th ed. Baltimore: Williams & Wilkins; 1999:447-458. 8. Homocysteine Lowering Trialists’ Collaboration. Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomised trials. Homocysteine Lowering Trialists’ Collaboration. BMJ. 1998;316(7135):894-898.(PubMed) 9. Quinlivan EP, McPartlin J, McNulty H, et al. Importance of both folic acid and vitamin B12 in reduction of risk of vascular disease. Lancet. 2002;359(9302):227-228. (PubMed) 10. Stabler SP, Lindenbaum J, Allen RH. Vitamin B-12 deficiency in the elderly: current dilemmas. Am J Clin Nutr. 1997;66(4):741-749. (PubMed) 11. Fenech M. Micronucleus frequency in human lymphocytes is related to plasma vitamin B12 and homocysteine. Mutat Res. 1999;428(1-2):299-304. (PubMed) 12. Wu K, Helzlsouer KJ, Comstock GW, Hoffman SC, Nadeau MR, Selhub J. A prospective study on folate, B12, and pyridoxal 5′-phosphate (B6) and breast cancer. Cancer Epidemiol Biomarkers Prev. 1999;8(3):209-217. (PubMed) 13. Eskes TK. Open or closed? A world of difference: a history of homocysteine research. Nutr Rev. 1998;56(8):236-244. (PubMed) 14. Mills JL, Scott JM, Kirke PN, et al. Homocysteine and neural tube defects. J Nutr. 1996;126(3):756S-760S. (PubMed) 15. Nourhashemi F, Gillette-Guyonnet S, Andrieu S, et al. Alzheimer disease: protective factors. Am J Clin Nutr. 2000;71(2):643S-649S. (PubMed) 16. Clarke R, Smith AD, Jobst KA, Refsum H, Sutton L, Ueland PM. Folate, vitamin B12, and serum total homocysteine levels in confirmed Alzheimer disease. Arch Neurol. 1998;55(11):1449-1455. (PubMed) 17. Wang HX, Wahlin A, Basun H, Fastbom J, Winblad B, Fratiglioni L. Vitamin B(12) and folate in relation to the development of Alzheimer’s disease. Neurology. 2001;56(9):1188-1194. (PubMed) 18. Seshadri S, Beiser A, Selhub J, et al. Plasma homocysteine as a risk factor for dementia and Alzheimer’s disease. N Engl J Med. 2002;346(7):476-483. (PubMed)19. Hutto BR. Folate and cobalamin in psychiatric illness. Compr Psychiatry. 1997;38(6):305-314. (PubMed) 20. Penninx BW, Guralnik JM, Ferrucci L, Fried LP, Allen RH, Stabler SP. Vitamin B(12) deficiency and depression in physically disabled older women: epidemiologic evidence from the Women’s Health and Aging Study. Am J Psychiatry. 2000;157(5):715-721. (PubMed) 21. Hendler SS, Rorvik DR, eds. PDR for Nutritional Supplements. Montvale: Medical Economics Company, Inc; 2001 22. Kasper H. Vitamin absorption in the elderly. Int J Vitam Nutr Res. 1999;69(3):169-172. 23. Termanini B, Gibril F, Sutliff VE, Yu F, Venzon DJ, Jensen RT. Effect of long-term gastric acid suppressive therapy on serum vitamin B12 levels in patients with Zollinger-Ellison syndrome. Am J Med. 1998;104(5):422-430. (PubMed) 24. Simon JA, Hudes ES. Relation of serum ascorbic acid to serum vitamin B12, serum ferritin, and kidney stones in US adults. Arch Intern Med. 1999;159(6):619-624. (PubMed) Alpha Lipoic Acid Enzyme cofactor R-Alpha-lipoic acid is normally bound to proteins by linkage of its carboxyl (COOH) group to a lysine residue in the protein. In its protein bound form, lipoamide, R-alphalipoic acid is a required cofactor for several multi-enzyme complexes that catalyze critical energy metabolism reactions inside the mitochondria. The pyruvate dehydrogenase complex catalyzes the conversion of pyruvate to acetyl-CoA, an important substrate for energy production, via the citric acid cycle. The alphaketoglutarate dehydrogenase complex catalyzes another important citric acid cycle reaction. The branched-chain alpha-keto acid dehyrogenase complex catalyzes the metabolism of three amino acids, leucine, isoleucine, and valine, also known as branched-chain amino acids. The glycine cleavage system is a multi-enzyme complex that catalyzes the formation of 5,10 methylene tetrahydrofolate, an important cofactor in nucleic acid synthesis (2).

FOLATE: Function:One-carbon metabolism The only function of folate coenzymes in the body appears to be mediating the transfer of one-carbon units (2). Folate coenzymes act as acceptors and donors of one-carbon units in a variety of reactions critical to the metabolism of nucleic acids and amino acids (3).