SUPPLEMENT MONOGRAPHS THIAMIN (VITAMIN B I ) /609

CONTRAINDICATIONS, PRECAUTIONS, ADVERSE REACTIONS

CONTRAINDICA nONS

Taurine is contraindicated in those hypersensitive to anycomponent of a taurine-containing nutritional supplement.

PRECAUTIONS

Pregnant women and nursing mothers should avoid taurinesupplements unless recommended by their physicians. Thosewith congestive heart failure should only use taurine undermedical supervision.

ADVERSE REACTIONS

No reports of adverse reactions.

INTERACTIONS

DRUGS

In animal studies, taurine was found to ameliorate thepulmonary side effects (pulmonary fibrosis) of bleomycin.

DOSAGE AND ADMINISTRATION

Doses are variable and range from 500 mg to 3 grams daily.

LITERATURE

Azuma 1, Sawamura A, Awata N, et al. Therapeutic effect oftaurine in congestive heart failure: a double-blind, crossovertrial. Clin Cardiol. 1985; 8:267-282.

Azuma 1, Sawamura Z, Awata N. Usefulness of taurine in .congestive heart failure and its prospective application. Jpn CircJ. 1992; 56:95-99.

Barbeau A, Donaldson 1. Taurine in epilepsy. Lancet. 1973;2(7825):387.

Chesney RW. Taurine: its biological role and clinicalimplications. Advances in' Pediatrics. 1985:22: 1-42.

Chesney RW. Taurine: is it required for infant nutrition? JNutr. 1988; I 18:6-10.

Darling PB, Lepage G, Leroy C, et al. Effect of taurinesupplements on fat absorption in cystic fibrosis. Pediatr Res.1985; 19:578-582.

Geggel HS, Ament ME, Heckenlively lR, et al. Nutritionalrequirement for taurine in patients receiving long-termparenteral supplementation.N Engl J Med. ]985; 3I2:142-146.

Gurujeyalakshmi G, Wang Y, Giri SN. Taurine and niacinblock lung injury and fibrosis by down-regulating bleomycin-induced activation of transcription nuclear factor-kappa B inmice. J Pharmacal Exp Ther. 2000; 293:82-90.

Hayes KC, Carey RE. Retinal degeneration associated withtaurine deficiency in the cat. Science. 1975; ] 88:949-951.

Hayes KC, Sturman lA. Taurine in metabolism. Ann Rev Nutr.1981; 1:40]-425.

McCarty MF. The reported clinical utility of taurine in ischemicdisorders may reflect a down-regulation of neutrophil activationand adhesion. Med Hypothesis. 1999; 53:290-299.

Murakami S, Kondo Y, Tomisawa K, Nagate T. Prevention ofatherosclerotic lesion development in mice by taurine. DrugsExp Clin Res. ]999; 25:227-234.

Nakamura T, Ogasawara M, Koyama I, et al. The protectiveeffect of taurine on the biomembrane against damage producedby oxygen radicals. Bioi Pharm Bull. 1993; ]6:970-972.

Niitynen L, Nurminen M-L, Korpe]a R, et al. Role of arginine,taurine and homocysteine in cardiovascular diseases. Ann Med.]999; 31:318-326.

Pierson HF, Fisher 1M, Rabinovitz M. Modu]ation by taurine ofthe toxicity of taumustine, a compound with antitumor activity.J Natl Canc Inst. 1985; 75:905-909.

Pion PO, Kitt]eson MD, Rogers QR, Morris 10. Myocardia]failure in cats associated with low plasma taurine: a reversiblecardiomyopathy. Science. ]987; 237: 764-767.

Rivas-Arancibia S, Dorado-MartInez C, Borgonio-Perez G, et al.Effects of taurine on ozone-induced memory deficits and lipidperoxidation in brains of young, mature, and old rats. EnvironRes. 2000; 82:7-]7.

Stipanuk MH. Homocysteine, Cysteine, and Taurine. In: ShilsME, Olson lA, Shike M, Ross AC, eds. Modern Nutrition inHealth and Disease, 9th ed. Baltimore, MD: Williams andWilkins; 1999:543-558.

Wang Q, Giri SN, Hyde OM, Nakashima 1M. Effects of taurineon bleomycin-inducedlung fibrosis in hamsters. Proc Sac ExpBioi Med. 1989; 190:330-338.

Thiamin (Vitamin Bl)DESCRIPTION

In 1911, the chemist Casimir Funk isolated a substance fromrice bran extracts which he thought was the anti-beriberifactor. Because the substance was an amine and because hethought the substance had a vital dietary function, he namedit vitamine. As it turned out, Funk's vitamine was not theanti-beriberi factor which was subsequently isolated andcalled thiamin or vitamin B ,.Nevertheless, Funk did coin theterm vitamin and the concept that vitamins are essentialdietary factors.

Thiamin is a water-soluble vitamin. Structurally it consists ofa substituted pyrimidine ring joined by a methylene bridge toa substituted thiazole ring. The free vitamin is a base. Thethiazolium salts of thiamin, thiamin hydrochloride andthiamin mononitrate, are the forms of thiamin which aretypically used in nutritional supplements and for foodfortification. In addition to being known as vitamin BI,thiamin is known as thiamine, aneurin and 3-[(4-amino-2-methy1-5-pyrimidin y I) methyl] -5-(2-hydroxyethy I)-4-methyl-thiazonium. The structural formula of thiaminfollows:

610 ITHIAMIN (VITAMIN B1 )PDR FOR NUTRITIONAL SUPPLEMENTS

Thiamin

The classic deficiency state of thiamin is beriberi. Ananalogous disorder in fowl is called polyneuritis. The termberiberi is derived from the Sinhalese word meaning extremeweakness. Beriberi was very common during the early partof the last century in those whose diets consisted principallyof highly polished rice. Interestingly, those who ate par-boiled rice-partially boiled rice-did not develop beriberi.Milling removes the husk, which contains most of thethiamin, while parboiling the rice before husking dispersesthiamin throughout the grain. Beriberi still occurs in thosewhose diet mainly consists of polished rice. Thiamindeficiency is also associated with alcoholism and occurs insome cases of malnutrition, those receiving total parenteralnutrition without thiamin, malabsorption syndromes, in-creased carbohydrate intake, major catabolic and physiologicstress states, acute infection, folate deficiency, thyrotoxicosisand those on long-term loop diuretics (furosemide, ethacryn-ic acid, bumetanide). Subclinical thiamin deficiency may notbe uncommon.

There are three types of beriberi: dry beriberi, wet beriberiand cerebral beriberi or Wernicke-Korsakoff syndrome. Dryor neurologic beriberi occurs when thiamin deficiencyaffects the peripheral nervous system resulting in peripheralneuropathy. The peripheral neuropathy is characterized by abilateral, symmetric impairment of sensory, motor and reflexfunctions involving predominantly the lower extremities.Symptoms and signs of dry beriberi, include paresthesias ofthe toes, burning of the feet, calf muscle tenderness andcramps, difficulty in rising from a squatting position, adecrease in the vibratory sensation in the toes, loss of ankleand knee jerks and footdrop and toedrop. Wet or cardiovas-cular beriberi involves the heart and circulatory system.Cardiovascular manifestations of thiamin deficiency arecharacterized by peripheral vasodilatation with increasedcardiac output, sodium and water retention and myocardialfailure. The most extreme form of wet beriberi is shoshinberiberi. Shoshin is Japanese for damage to the heart and ischaracterized by global heart failure with lactic acidosis inthe context of blood tests showing thiamin deficiency.Shoshin beriberi, if not promptly treated, is rapidly fatal.Alcoholics who present with unexplained lactic acidosis, ahyperdynamic state and high output failure, or cardiogenicshock without evidence of a myocardial infarction, areunlikely to have anything but Shoshin beriberi.

Alcoholism is the major cause of thiamin deficiency inWernicke-Korsakoff syndrome or cerebral beriberi. Wer-nicke-Korsakoff syndrome is characterized by abnormalocular motor signs, ataxia and derangement of mentalfunctions. The ocular motor signs include paresis of abduc-tion which is accompanied by horizontal diplopia, strabismusand nystagmus. Derangement of mental functions include aglobal-confusional apathetic state and amnesia. Wernicke-Korsakoff syndrome represents the full-blown clinical stateof cerebral beriberi. Wernicke's disease itself is character-ized by abnormal ocular motor signs and ataxia without anevident amnesic state. Korsakoff s psychosis itself is charac-terized by the mental derangements mentioned above.

Thiamin occurs in cells principally in its active coenzymeform called thiamin pyrophosphate (TPP, cocarboxylase).Thiamin, in the form of thiamin pyrophosphate, plays anessential role as a cofactor in key reactions in carbohydratemetabolism. It is also involved in the metabolism ofbranched-chain amino acids and may have non-coenzyme(non-cofactor) roles in excitable cells. TPP is a coenzyme inthe oxidative decarboxylation of pyruvate to acetyl-coen-zyme A (acetyl-CoA), of alpha-ketoglutarate to succinyl-CoA, and of the oxidative decarboxylation of the branched-chain alpha-keto acids, which are metabolites of thebranched-chain amino acids L-leucine, L-isoleucine and L-valine. TPP is also a cofactor in the reversible transketolasereactions in the phosphogluconate pathway, also know as thepentose phosphate pathway and the hexose monophosphateshunt. The two transketolase reactions are the reversibleconversions of D-xylulose 5-phosphate and D-ribose 5-phosphate to D-sedoheptulose 7-phosphate and D-glyceral-dehyde 3-phosphate, and D-xylulose-5-phosphate and D-erythrose-4-phosphate to D-fructose 6-phosphate and D-glyceraldehyde 3-phosphate. The first of these two reactionsrepresents the pathway for the non-oxidative production ofribose.

The total metabolic pool of thiamin in the body isapproximately 30 milligrams. The predominant form ofthiamin in the body is thiamin pyrophosphate (TPP, alsoknown as thiamin diphosphate or TDP and cocarboxylase).Approximately 80% of thiamin in blood is present inerythrocytes as TPP. About 50% of total body thiamin ispresent in skeletal muscles. Thiamin is also found in heart,liver kidneys and brain. Other forms of thiamin present in thebody include, thiamin triphosphate (TIP, about 10%),thiamin monophosphate (TMP) and free thiamin. TMP andfree thiamin comprise about 10% of total body thiamin. Themost reliable method of evaluating thiamin status is themeasurement of erythrocyte transketolase activity and thepercentage enhancement of the transketolase activity result-ing from added thiamin pyrophosphate.

SUPPLEMENT MONOGRAPHS THIAMIN (VITAMIN HI) /611

All plant and animal foods contain thiamin. Good dietarysources of the vitamin, include whole-grain products, brownrice, meat products, vegetables, fruits, legumes and seafood.

ACTIONS AND PHARMACOLOGY

ACTIONS

Thiamin may have antioxidant, erythropoietic, cognition-andmood-modulatory, antiatherosclerotic and detoxification ac-tivities. It has putative ergogenic activity.

MECHANISM OF ACTION

Thiamin has been found to protect against lead-induced lipidperoxidation in rat liver and kidney. Thiamin deficiencyresults in selective neuronal death in animal models. Theneuronal death is associated with increased free radicalproduction, suggesting that oxidative stress may play animportant early role in brain damage associated with thiamindeficiency. The mechanism of the possible antioxidantactivity of thiamin is unknown.

Even though anemia is not one of the consequences ofthiamin deficiency, there is a type of anemia, called thiamin-responsive megaloblastic anemia, that responds well to largedoses of thiamin. It is thought that those with thiamin-responsive megaloblastic anemia may actually be thiamin-deficient secondary to reduced thiamin transport andabsorption, and to impaired intracellular thiaminpyrophosphorylation.

Thiamin deficiency is associated with cogmtIve and emo-tional changes. For example, Korsakoff's psychosis ischaracterized by the inability to form new memories, thepoorly organized retrieval of remote memories, apathy andemotional blandness. The treatment of Korsakoff's patientswith thiamin often results in significant improvement inthese symptoms. Marginal thiamin deficiency may alsoresult in cognitive and emotional changes. There are a fewstudies suggesting that high-dose thiamin supplementationmay have a positive effect on mood and cognition in thosewith marginal deficiency, and even adequate status, of thevitamin. In one study with female subjects, improvedthiamin status was associated with improved mood, and adecline in thiamin status was associated with poorer mood.In another study, again with female subjects, those taking 50

-milligrams of thiamin daily for 20 months were found tohave improvement in thiamin status associated with reportsof being more clearheaded, composed and energetic. Reac-tion times were also faster. The study was placebo-controlledand performed in subjects whose thiamin status was ade-quate. The mechanism of the neurophysiological actions ofthiamin are not well understood. Thiamin may playa role inneurophysiology independent of its coenzyme function.Thiamin is located in nerve cell membranes and phosphoryl-ated forms of thiamin are associated with sodium channel

proteins. It is thought that phosphorylated forms of thiaminmay play roles in the control of sodium conductance ataxonal membranes and in other neurological processes.

Migration and proliferation of arterial smooth muscle cellsare thought to play an important role in the development ofatherosclerosis. Glucose and insulin have been found to havean additive effect on the proliferation of infrageniculararterial smooth muscle cells in vitro. Thiamin has been foundto inhibit human infragenicular arterial muscle cell prolifera-tion induced by high glucose and insulin, in cell culture.Thiamin plays a key role in intracellular glucose metabolismand it is thought that thiamin inhibits the effect of glucoseand insulin on arterial smooth muscle cell proliferation.However, the mechanism of this in vitro effect is not wellunderstood. Inhibition of endothelial cell proliferation mayalso promote atherosclerosis. Endothelial cells in culturehave been found to have a decreased proliferative rate anddelayed migration in response to hyperglycemic conditions.Thiamin has been shown to inhibit this effect of glucose onendothelial cells. It is thought that the mechanism of actionof thiamin on endothelial cells is related to a reduction inintracellular protein glycation by redirecting the glycolyticflux. Atherosclerosis and peripheral artery disease aresignificant problems in those with type 2 diabetes mellitus.Further study of the possible anti-atherosclerotic activity ofthiamin, particularly in those with type 2 diabetes, iswarranted.

Some animal studies have found that high doses of thiaminblock some of the toxic symptoms from orally administeredlead. Thiamin may protect against lead toxicity by inhibitinglead-induced lipid peroxidation.

There are few studies investigating the effect of large dosesof thiamin as an aid to exercise performance. In one suchstudy, carbohydrate-loaded mice administered very highdoses of thiamin demonstrated an improvement in swim timeto exhaustion. In another study, experienced cyclists admin-istered 900 milligram daily of thiamin for three days werefound to have lower exercise heart rates, blood glucose andblood lactate concentrations. In still another study, thiaminsupplementation at 100 milligram/day was found to decreaseexercise-induced fatigue in male athletes. A recent study,however, using a thiamin derivative, thiamin tetrahydrofur-furyI disulfide, which is better absorbed than thiamin,showed no effect on high-intensity exercise performance.There is insufficient evidence to suggest that thiamin mayhave exercise performance-enhancing activity. The possiblemechanism of this putative effect is unknown.

PHARMACOKINETICS

Thiamin is absorbed from the lumen of the small intestine-mainly the jejunum-by active transport and passive diffu-

612/THIAMIN (VITAMIN BI) PDR FOR NUTRITIONAL SUPPLEMENTS

sion mechanisms. At lower amounts, absorption from thesmall intestine is by an active, carrier-mediated process thatis energy-dependent as well as sodium-dependent. Passivediffusion occurs with higher amounts of thiamin. Absorptionof thiamin appears to be limited by a saturable rate-limitingtransport mechanism~ Only a small percentage of a high doseof thiamin is absorbed. Certain lipid-soluble thiamin deriva-tives known as allithiamins, do not appear to be subject tothe rate-limiting transport mechanism. Thiamin is transport-ed by the portal circulation to the liver and by the systemiccirculation to various tissues in the body. Thiamin ismetabolized to thiamin monophosphate (TP, TMP), thiaminpyrophosphate (TPP, cocarboxylase, thiamin diphosphate,TDP) and thiamin triphosphate (TIP). Thiamin is phospho-rylated directly to thiamin pyrophosphate by thiamin diphos-phokinase and thiamin pyrophosphate is dephosphorylated tothiamin monophosphate via thiamin diphosphatase. Approxi-mately 80% of thiamin in blood is present in erythrocytes asTPP. The transport of thiamin into erythrocytes appears tooccur by facilitated diffusion; it enters other cells by anactive process. Total thiamin content in the adult body isabout 30 milligrams. Thiamin and its metabolites are mainlyexcreted by the kidneys.

INDICATIONS AND USAGE

Frank and marginal thiamin deficiency may not be uncom-mon and may be a particular problem among alcoholics, theelderly and the chronically ill. Thiamin supplementation maybe useful in these subgroups, among others. There isevidence that supplemental thiamin can help protect againstsome of the -metabolic imbalances caused by heavy alcoholconsumption. It may help protect against Wernicke's en-cephalopathy and some other forms of brain damage seen insome alcoholics, some with HIV-disease, some with anorex-ia nervosa and others. It may be helpful in alcoholwithdrawal. It is needed in those who receive total parenteralnutrition, particularly to prevent lactic acidosis due tothiamin deficiency. It may increase glucose tolerance andmay help prevent atherosclerosis, particularly in diabetics. Ithas been used in congestive heart failure with benefit undercertain circumstances and may be helpful in some otherforms of heart disease. There is preliminary evidence that itcan improve mood and cognition in some. Data are in shortsupply and results mixed with respect to claims that thiamincan enhance exercise performance and increase energy.Thiamin's use in cancer might be ill-advised, as there isevidence that it may promote tumor-cell proliferation.

RESEARCH SUMMARY

Alcoholics are at particularly high risk of thiamin deficiency.Alcohol interferes with the absorption of thiamin and itsstorage in tissue. It also inhibits conversion of thiamin to itsactive form. In addition, alcoholics generally have unbal-anced diets low in thiamin. Some alcoholics suffer from

frank beriberi, which, among other things, can lead tocongestive heart failure. More frequently, alcoholics sufferfrom such beriberi symptoms as mental confusion, visualdisturbances and staggering gait. Beriberi can be preventedand, in some cases, successfully treated with high doses ofthiamin (up to 100 milligrams daily).

Thiamin can also help prevent some cases of Wernicke'sencephalopathy, a potentially fatal disorder that occurs insome who consume very large amounts of alcohol. Symp-toms include double vision, mental confusion, muscleweakness and disturbed gait. Untreated, this disorder canresult in permanent brain damage and memory impairment.In extreme cases it leads to coma and death. It is oftenreversible with prompt thiamin treatment. Some use thiaminas part of alcohol-withdrawal therapy.

Others at higher than average risk of Wernicke's encepha-lopathy include those suffering from anorexia nervosa,typically young women. Older people are also at higher risk.So are people with HIV disease. Thiamin deficiency wasfound in 23% of HIV patients in one study, and brain lesionscharacteristic of those found in sufferers of Wernicke'sencephalopathy have been seen in some with HIV-disease.Some researchers have recommended dietary thiamin sup-plementation in all newly diagnosed cases of HIV-disease.

It is now recognized that thiamin deficiency may occur withtotal parenteral nutrition (TPN). Several cases of lacticacidosis have been reported in TPN patients not receivingthiamin. Administration of thiamin has resolved the acidosiswith attendant clinical improvement. Researchers stress thatthiamin deficiency should always be included in the differen-tial diagnosis of lactic acidosis. A recent shortage ofmultivitamin preparations for TPN is said to have resulted ina number of cases of lactic acidosis due to thiamindeficiency. A previous shortage led to several TPN-relateddeaths.

Thiamin deficiency is associated with abnormal glucosetolerance, and there is some evidence that supplementalthiamin may, in some cases, help correct the abnormality. Ina recent in vitro study, thiamin inhibited accelerated prolifer-ation of arterial smooth muscle cells. This proliferationcontributes to atherosclerosis and preferentially affects theinfragenicular vasculature in patients with diabetes mellitus.High insulin and glucose levels demonstrate additive effectsin this process in vitro. This research gives some preliminaryindication that thiamin may help prevent or delay athero-sclerotic complications in some diabetics.

.

Thiamin supplementation has improved left ventricularfunction in patients with congestive heart failure beingadministered long-term furosemide therapy and, as notedabove, supplemental thiamin can help prevent and treat heart

SUPPLEMENT MONOGRAPHS THIAMIN (VITAMIN 81 )/613

disease related to beriberi. In addition, intravenous injectionof thiamin proved helpful in an animal model of myocardialinfarction, increasing strength of contractions and decreasingoxygen demand. Russian researchers have reported similarresults in humans. Thiamin pyrophosphate (cocarboxylase)was used in these heart attack experiments. Research isneeded to see whether thiamin itself might be beneficial.

Thiamin was found to have positive effects on mood andcognitive functioning in a recent study of 120 youngfemales. In a previous study, females receiving a multi-vitamin supplement for three months were said to haveimproved mood compared with controls who receivedplacebo. Using biochemical indices, an association was madebetween thiamin status and improved mood. These samemeasures did not support an association between any of eightother vitamins and elevated mood.

In this recent study, focus was on thiamin alone among thevitamins. All but one of the 120 women had normal thiaminlevels at baseline. They were randomized to receive 50milligrams of thiamin daily or placebo. After two months,the thiamin group significantly improved (more than dou-bled) their scores on the c1ear-headedness and mood subset~of the bipolar profile of mood states psychological test:There was no change in these measures in the placebo group.The thiamin group also showed nonsignificant improvementin feelings of confidence, composure and elation. Theresearchers considered their findings remarkable" given thatthey were obtained in a group which, as measured bytransketolase activation, had normal thiamin nutrition. Moreresearch is warranted.

Thiamin and a thiamin derivative have not shown any effecton exercise performance in two studies. High-dose thiamin(l00 milligrams daily) was found to be helpful in preventingor accelerating recovery from exercise-induced fatigue in athird study. This trial tested thiamin in 16 male volunteerathletes using bicycle ergometer exercises. Followup isneeded.

Finally, a group of researchers have recently calle~ thiaminsupplementation "a double-edged sword" in cancer patients.Like other seriously ill patients, cancer sufferers may benefitfrom improved thiamin status in terms of general nutrition,but, as these researchers observed, there is. some evidencethat thiamin may also, in effect, nourish some cancers. Thereis some indication that high-dose thiamin supplementationmay promote tumor cell proliferation. More research isneeded to help clarify this issue.

CONTRAINDICATIONS, PRECAUTIONS, ADVERSE REACTIONS

CONTRAINDICA T10NS

Thiamine is contraindicated in those hypersensitive to anycomponent of a thiamin-containing product.

PRECAUTIONS

The use of thiamin for the treatment of a thiamin-deficiencystate, lactic acidosis secondary to thiamin-deficiency, Wer-nicke- Korsakoff syndrome, Wemicke' s encephalopathy,Korsakoffs psychosis or any medical condition must only beundertaken under medical supervision.

A typical dose of thiamin used in pre- and postnatalmultivitaminlmultimineral supplements is three milligramsdaily. Pregnant women and nursing mothers should avoidintakes of thiamin greater than this amount unless higherdoses are prescribed by their physicians.

Those who are treated with parenteral thiamin for thiamindeficiency, should be given the thiamin prior to receivingparenteral glucose. Administration of intravenous glucoseprior to receiving thiamin could result in severe lacticacidosis.

ADVERSE REACTIONS

Oral thiamin is well tolerated even at doses up to 200milligrams daily or higher. There have been occasionalreports of serious and even fatal responses to parenteralthiamin. These have' probably been anaphylactic reactions.There are also reports of less serious allergic reactions toparenteral thia~in.

There is some animal evidence that high doses of parenteralthiamin may promote tumor growth.

INTERACTIONS

DRUGSLoop diuretics (furosemide, ethacrynic acid, bumetanide):Chronic use of loop diuretics may result in thiamindeficiency. Chronic use of furosemide for the treatment ofcongestive heart failure has been reported to result in thiamindeficiency. Thiamin repletion in such patients can improveleft ventricular function.

FOODSSubstances in food that inactivate thiamin are called anti-thiamin factors.

Sulfites: Concomitant intake of thiamin and foods andbeverages containing sulfites may inactivate thiamin.

Tea, coffee and decaffeinated coffee: Concomitant intake ofthese beverages and thiamin may inactivate thiamin. Tannicacid is most likely the substance in tea that inactivatesthiamin by forming a tannin-thiamin adduct.

OVERDOSAGE

Overdosage of thiamin has not been reported In the

literature.

614/THIAMIN (VITAMIN HI) PDR FOR NUTRITIONAL SUPPLEMENTS

DOSAGE AND ADMINISTRATION

Thiamin is available in nutritional supplements in the formof thiamin hydrochloride and thiamin nitrate. These are alsothe forms used for food fortification. Thiamin pyrophosphateor cocarboxylase may also be available in some products.Supplemental doses of thiamin are variable and range fromthe U.S. RDA amount of 1.5 milligrams/day to 10 milli-grams/day or higher. There is a rapid decline in absorptionthat occurs at oral doses above five milligrams. Thiamin istypically found in the form of multivitamin, multivitamin!multimineral or B-complex preparations. Single ingredientthiamin supplements are also available. Pre- and postnatalsupplements typically deliver a thiamin dose of 3 milligramsdaily.

Lipid-soluble thiamin derivatives called allithiamins are alsoavailable. These forms are better absorbed at higher intakesthan is thiamin.

The Food and Nutrition Board of the Institute of Medicine ofthe National Academy of Sciences recommends the follow-ing dietary reference intakes (DRIs) for thiamin:

Infants0-6 months7-12 months

Adequate Intakes (AI)0.2 mg/day 0.03 mglkg0.3 mg/day 0.03 mglkg

Recommended DietaryAllowances (RDA)

Children1-3 years4-8 years

Boys9-13 years14-18 years

Girls9-13 years14-18 years

Men19 years and older

0.5 mg/day0.6 mg/day

0.9 mg/day1.2 mg/day

0.9 mg/day1.0 mg/day

1.2 mg/day

Women19 years and older

Pregnancy14-50 years

1.1 mglday

1.4 mg/day

Lactation14-50 years 1.4 mg/day

The DV (Daily Value) for thiamin (vitamin BI), which isused for determining percentage of nutrient daily values onnutritional supplement and food labels, is 1.5 mg. This isbased on the U.S. RDA for thiamin.

LITERATURE

Avena R, Arora S, Cannody BJ, el al. Thiamin (vitamin BI)protects against glucose- and insulin-mediated proliferation ofhuman infragenicular arterial smooth muscle cells. Ann VascSurg. 2000; 14:37-43.

Bakker SJL, Hoogeveen EK, Nijpels G, et al. The associationof dietary fibres with glucose tolerance is partly explained byconcomitant intake of thiamin: The Hoorn Study. Diabetologia.1998; 41: 1168-1175.

Benton D, Griffiths R, Haller 1. Thiamin supplementationmoodand cognitive functioning. Psychopharmacol. 1997; 129:66-71.

Bettendorff L. A non-cofactor role of thiamin derivatives inexcitable cells? Arch Physiol Biochem. 1996; 104:745-751.

Blanc P, Boussuges A. [Cardiac beriberi]. [Article in French].Arch Mal Coeur Vaiss. 2000; 93:371-379.

Boros LG. Population thiamine status and varying cancer ratesbetween western, Asian and African countries. Anticancer Res.2000; 20(3B):2245-2248.

Boros LG, Brandes JL, Lee WN, et al. Thiaminesupplementation to cancer patients: a double edge sword.Anticancer Res. 1998; 18(1B):595-602.,

Boros LG, Comin B, Boren J, et al. Over-expression oftransketolase: a mechanism by which thiamine supplementationpromotes cancer growth. Am Assoc Cancer Res. 2000; 41 :66(Ab#4234).

Butterworth RF, Gaudreau C, Vincelette J, et al. Thiamindeficiency and Wernicke's encephalopathy in AIDS. MetabBrain Dis. 1991; 6:207-212.

Dietary Reference intakes for Thiamin, Riboflavin, Niacin,Vitamin B6' Folate, Vitamin B12, Pantothenic Acid, Biotin,and Choline. Washington, DC: National Academy Press;1998.

Frank T, Bitsch R, Maiwald J, Stein G. High thiaminediphosphate concentrations in erythrocytes can be achieved indialysis patients by oral administrationof benfotiamine.Eur JClin Pharmacol. 2000; 56:251-257.

Hiirdig L, Daae C, Dellborg M, et al. Reduced thiaminephosphate, but not thiamine diphosphate, in erythrocytes inelderly patients with congestive heart failure treated withfurosemide. J lnt Med. 2000; 247:597-600.

La Selva M, Beltramo E, Pagnozzi F, et al. Thiamine correctsdelayed replication and decreases production of lactate andadvanced glycation end-products in bovine retinal and humanumbilical vein endothelial cells cultured under high glucoseconditions. Diabetologia. 1996; 39: 1263-1268.

Muri RM, Von Overbeck J, Furrer J, Ballmer PE. Thiamindeficiency in HIV-positive patients: evaluations by erythrocytetransketolase activity and thiamin pyrophosphate effect. ClinNutr. 1999; 18:375-378.

Pekovich SR, Martin PR, Singleton CK. Thiamine deficiencydecreases steady-state transketolase and pyruvate dehydrogenase

SUPPLEMENT MONOGRAPHS TIN /615

but not alpha-ketoglutarate dehydrogenase mRNA levels in threehuman cell types. J Nutr. 1998; 128:683-687.

Romanski SA, McMahon MM. Metabolic acidosis and thiaminedeficiency. Mayo Clin Proc. 1999; 74:259-263.

Sato Y, Nakagawa M, Higuchi I, et al. Mitochondrial myopathyand familial thiamine deficiency. Muscle Nerve. 2000; 23: 1069-1075.

Senapati SK, Dey S, Dwivedi SK, et al. Effect of thiaminehydrochloride on lead induced lipid peroxidation in rat liver andkidney. Vet Hum Toxicol. 2000; 42:236-237.

Shimon I, Almog S, Vered Z, et al. Improved left ventricularfunction after thiamine supplementation in patients withcongestive heart failure receiving long-term furosemide therapy.Am J Med. 1995; 98:485-490.

Suter PM, Haller 1, Hany A. Diuretic use: a risk for subclinicalthiamine deficiency in elderly patients. J Nutr Health Aging.2000; 4:69-7 I.

Suzuki M, Itokawa Y. Effects of thiamine supplementation onexercise-induced fatigue. Metab Brain Dis. 1996; 11:95-106.

Tanphaichitr V. Thiamin. In: Shils ME, Olson lA, Shike M,Ross AC, eds. Modern Nutrition in Health and Disease. 9th ed.Baltimore, MD: Williams and Wilkins; 1999:381-389.

Todd K, Butterworth RF. Mechanisms of selective neuronal celldeath due to thiamine deficiency. Ann NY Acad Sci. 1999;893:404-41 I.

Webster Ml. Physiological and performance responses tosupplementation with thiamin and pantothenic acid derivatives.Eur J Appl Physiol Occup Physiol. 1998; 77:486-491.

Webster Ml, Scheett TP, Doyle MR, Branz M. The effect of athiamin derivative on exercise performance.Eur J Appl Physiol.1997; 75:520-524.

TinDESCRIPTION

Tin is a metallic element with atomic number 50 and symbolSn. It is a heavy metal. Tin is not considered an essentialnutrient for humans. A tin-deficiency state has been reportedin rats.

Rats fed a diet low in tin showed poor growth, alopecia andlowered response to sound compared with rats fed a tin-richdiet. Abnormalities in mineral status were also noted in thetin-deficient rat group. At least for rats tin, may serve as anessential nutrient.

.

The typical daily dietary intake of tin ranges from about 1 to40 milligrams. Tin intake is essentially dependent on foodstored in tin cans. Higher intakes of tin are obtained fromfoods preserved in unlacquered tin cans than from foodspreserved in lacquered tin cans.

Regarding potential drug applications of tin, an organotincompound, tin protoporphyrin or Sn-P, a potent inhibitor ofheme oxygenase and bilirubin formation, is being studied asa treatment for controlling severe hyperbilirubinemia in full-term breast-fed newborns with high bilirubin levels afterbirth. It is also being studied as a treatment for neuropathicand incisional pain.

ACTIONS AND PHARMACOLOGY

ACTIONS

The actions and pharmacology of dietary tin are not known.

INDICATIONS AND USAGE

There is no evidence that supplemental tin has immune-enhancing activity in humans; nor is there any evidence thatit has anticarcinogenic activity in humans.

RESEARCH SUMMARY

It has been hypothesized that the thymus gland secretes tin-containing substances that possess immune-enhancing prop-erties. There are some animal studies suggesting that tin mayhave immune-modulating activity and may also have anti-proliferative activity. There is no evidence that tin has theseactivities in humans. Such studies are needed, especially ifthe animal studies have any validity.

CONTRAINDICATIONS, PRECAUTIONS, ADVERSE REACTIONS

CONTRAINDICA TIONS

Tin supplementation is not recommended for anyone.

PRECAUTIONS

Given our present state of knowledge regarding tin, supple-mental tin is not recommended for anyone.

DOSAGE AND ADMINISTRATION

No recommended dosage. Tin may be found in colloidal orliquid mineral preparations. It is also found in somemultivitamin preparations, typically at a dose of about 10micrograms.

LITERATURE

Arakawa Y. [Biological activity of tin and immunity.] [Articlein lapanese.] Sangyo Eiseigaku Zasshi. 1997; 39:1-20

Biego GH, 10yeux M, Hartemann P, Debry G. Determination oftin intake in an adult French citizen. Arch Environ ContamToxicol. 1999; 36:227-232.

Cardarelli N. Tin and the thymus gland: a review. Thymus.1990; 15:223-23 I.

Martinez lC, Garcia HO, Otheguy LE, et al. Control of severehyperbilirubinemia in full-term newborns with the inhibitor ofbilirubin production Sn-mesoporphyrin. Pediatrics. 1999; 103:1-5.

Nielsen FH. Ultratrace minerals. In: Shils ME, Olson lA, ShikeM, Ross AC, eds. Modern Nutrition in Health and Disease. 9thed. Baltimore, MD: Williams and Wilkins; 1999; 283-303.