Ординатура / Офтальмология / Английские материалы / Handbook of Nutrition and Ophthalmology_Semba_2007

90.Kirkham TH, Wrigley PFM, Holt JM. Central retinal vein occlusion complicating iron deficiency anemia. Br J Ophthalmol 1971;55:777–780.

91.Kurzel RB, Angerman NS. Venous stasis retinopathy after long-standing menorrhagia. J Reprod Med 1978;20:239–242.

92.Matsuoka Y, Hayasaka S, Yamada K. Incomplete occlusion of central retinal artery in a girl with iron deficiency anemia. Ophthalmologica 1996;210:358–360.

93.Kacer B, Hattenbach LO, Hörle S, Scharrer I, Kroll P, Koch F. Central retinal vein occlusion and nonarteritic ischemic optic neuropathy in 2 patients with mild iron deficiency anemia. Ophthalmologica 2001;215:128–131.

94.Shorb SR. Anemia and diabetic retinopathy. Am J Ophthalmol 1985;100:434–436.

95.Lubeck MJ. Papilledema caused by iron-deficiency anemia. Trans Am Acad Ophthal Oto-Lar 1959;63: 306–310.

96.Beutler E, Fairbanks VF, Fahey JL. Clinical Disorders of Iron Metabolism. New York, Grune and Stratton: 1963; pp. 131–132.

97.Capriles L. Intracranial hypertension and iron-deficiency anemia. Arch Neurol 1963;9:147–153.

98.Knizley H, Noyes WD. Iron deficiency anemia, papilledema, thrombocytosis, and transient hemiparesis. Arch Intern Med 1972;129:483–486.

99.Fleming DJ, Jacques PF, Tucker KL, et al. Iron status of the free-living, elderly Framingham Heart Study cohort: an iron-replete population with a high prevalence of elevated iron stores. Am J Clin Nutr 2001;73:638–646.

100.Beard J. Iron status of free-living elderly individuals. Am J Clin Nutr 2001;73:503–504.

101.Tuomainen T, Punnonen K, Nyyssonen K, Salonen JT. Association between total body iron stores and risk of acute myocardial infarction in men. Circulation 1998;97:1461–1466.

102.Stevens RG, Jones DY, Micoaazi MS, Taylor PR. Body iron stores and the risk of cancer. N Engl J Med 1988;319:1047–1052.

103.Salonen JT, Tuomainen TP, Nyyssonen K, Lakka HM, Punnonen K. Relation between iron stores and non-insulin dependent diabetes in men: case-control study. Br Med J 1998;317:727.

104.Sullivan JL. Retinopathy of prematurity and iron: a modification of the oxygen hypothesis. Pediatrics 1986;78:1171–1172.

105.Sullivan JL. Iron, plasma antioxidants, and the ‘oxygen radical disease of prematurity.’ Am J Dis Child 1988;142:1341–1344.

106.Sullivan JL. Retinopathy of prematurity. Low iron binding capacity may contribute. Br Med J 1993;307: 1353–1354.

107.Cooke RWI, Clark D, Hickey-Dwyer M, Weindling AM. The apparent role of blood transfusions in the development of retinopathy of prematurity. Eur J Pediatr 1993;152:833–836.

108.Sacks LM, Schaffer DB, Anday EK, Peckham GJ, Delivoria-Papadopoulos M. Retrolental fibroplasia and blood transfusion in very low-birth-weight infants. Pediatrics 1981;68:770–774.

109.Clark C, Gibbs JAH, Maniello R, Outerbridge EW, Aranda JV. Blood transfusion: a possible risk factor in retrolental fibroplasia. Acta Pediatr Scand 1981;70:535–539.

110.Inder TE, Clemett RS, Austin NC, Graham P, Darlow BA. High iron status in very low birth weight infants is associated with an increased risk of retinopathy of prematurity. J Pediatr 1997;131:541–544.

111.Hesse L, Eberl W, Schlaud M, Poets CF. Blood transfusion: iron load and retinopathy of prematurity. Eur J Pediatr 1997;156:465–470.

112.Romagnoli C, Zecca E, Gallini F, Girlando P, Zuppa AA. Do recombinant human erythropoietin and iron supplementation increase the risk of retinopathy of prematurity? Eur J Pediatr 2000;159:627– 634.

113.Yamaguchi K, Takahashi S, Kawanami T, Kato T, Sasaki H. Retinal degeneration in hereditary ceruloplasmin deficiency. Ophthalmologica 1998;212:11–14.

114.Dunaief JL, Richa C, Franks EP, et al. Macular degeneration in a patient with aceruloplasminemia, a disease associated with retinal iron overload. Ophthalmology 2005;112:1062–1065.

115.Shibuya Y, Hayasaka S. Central retinal vein occlusion in a patient with anorexia nervosa. Am J Ophthalmol 1995;119:109–110.

116.Miller D. A case of anorexia nervosa in a young woman with development of subcapsular cataracts. Trans Ophthalmol Soc U K 1958;78:217–222.

117.Stigmar G. Anorexia nervosa associated with cataract (report of a case). Acta Ophthalmol 1965;43: 787–789.

118.Abraham SF, Banks CN, Beumont PJV. Eye signs in patients with anorexia nervosa. Aust J Ophthalmol 1980;8:55–57.

119.Havel RJ, Kane JP. Introduction: structure and metabolism of plasma lipoproteins. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds). The Metabolic & Molecular Bases of Inherited Disease. Eighth Edition. New York, McGraw-Hill: 2001; pp. 2705–2716.

120.Spaeth GL. Ocular manifestations of lipoprotein disease. J Cont Educ Ophthalmol 1979;41:11–24.

121.Heyl AG. Intra-ocular lipemia. Trans Am Ophthalmol Soc 1880;3:54–66.

122.Wagener HP. Lipemia retinalis: reports of three cases. Am J Ophthalmol 1922;5:521–525.

123.McCann WS. Lipemia retinalis. Bull Johns Hopkins Hosp 1923;34:302–304.

124.Chase LA. Diabetic lipaemia retinalis with report of a case. Canad Med Assoc J 1927;17:197–204.

125.Parker WR, Culler AC. Lipemia retinalis. Am J Ophthalmol 1930;13:573–584.

126.McKee SH, Rabinowitch IM. Lipaemia retinalis. Canad Med Assoc J 1931;25:530–534.

127.Marble A, Smith RM. Blood lipids in lipaemia retinalis. Arch Ophthalmol 1936;15:86–94.

128.Holt LE Jr, Aylward FX, Timbres HG. Idiopathic familial lipemia. Bull Johns Hopkins Hosp 1939;64: 279–314.

129.Goodman M, Shuman H, Goodman S. Idiopathic lipemia with secondary xanthomatosis, hepatosplenomegaly and lipemic retinalis. J Pediatr 1940;16:596–606.

130.Falls HF. Lipemia retinalis. Report of a case. Arch Ophthalmol 1943;30:358–361.

131.Kauffman ML. Lipaemia retinalis. Am J Ophthalmol 1943;26:1205–1208.

132.Lepard CW. Lipemia retinalis in the non-diabetic patient. Arch Ophthalmol 1944;32:37–38.

133.Grossmann EE, Hitz JB. Lipemia retinalis associated with essential hyperlipemia. Arch Ophthalmol 1948;40:570–573.

134.Lewis N. Intra-ocular involvement in a case of xanthomatous biliary cirrhosis. Br J Ophthalmol 1950; 34:506–508.

135.Frank L, Levitt LM. Idiopathic hyperlipemia with secondary xanthomatosis. Report of a case. Arch Derm Syph 1951;64:434–436.

136.Everett WG. Nondiabetic lipemia retinalis: report of a case. Arch Ophthalmol 1952;48:712–715.

137.Martinez KR, Cibis GW, Tauber JT. Lipemia retinalis. Arch Ophthalmol 1992;110:1171.

138.Rayner S, Lee N, Leslie D, Thompson G. Lipaemia retinalis: a question of chylomicrons? Eye 1996;10: 603–608.

139.El-Harazi SM, Kellaway J, Arora A. Lipaemia retinalis. Austr N Z J Ophthalmol 1998;26:255–257.

140.Dunphy EB. Ocular conditions associated with idiopathic hyperlipemia. Am J Ophthalmol 1950;33: 1579–1586.

141.Thomas PK, Smith EB. Ocular manifestations in idiopathic hyperlipaemia and xanthomatosis. Br J Ophthalmol 1958;42:501–506.

142.Bron AJ, Williams HP. Lipaemia of the limbal vessels. Br J Ophthalmol 1972;56:343–346.

143.Slatter DH, Nelson AW, Stringer JM. Effects of experimental hyperlipoproteinemia on the canine eye. Exp Eye Res 1979;29:437–447.

144.Yanko L, Michaelson IC, Rosenmann E, Ivri M, Lutsky I. Effects of experimental hyperlipoproteinaemia on the retina and optic nerve in rhesus monkeys. Br J Ophthalmol 1983;67:32–36.

145.Vinger PF, Sachs BA. The ocular manifestations of hyperlipoproteinemia. Am J Ophthalmol 1970;70: 563–573.

146.Hayasaka S, Fukuyo T, Kitaoka M, et al. Lipaemia retinalis in a 29-day-old infant with type 1 hyperlipoproteinaemia. Br J Ophthalmol 1985;69:280–282.

147.Dodson PM, Galton DJ, Winder AF. Retinal vascular abnormalities in the hyperlipidaemias. Trans Ophthalmol Soc UK 1981;101:17–21.

148.Dodson PM, Galton DJ, Hamilton AM, Blach RK. Retinal vein occlusion and the prevalence of lipoprotein abnormalities. Br J Ophthalmol 1982;66:161–164.

149.Orlin C, Lee K, Jampol LM, Farber M. Retinal arteriolar changes in patients with hyperlipidemias. Retina 1988;8:6–9.

150.Kurz GH, Shakib M, Sohmer KK, Friedman AH. The retina in type V hyperlipoproteinaemia. Am J Ophthalmol 1976;82:32–43.

wasting, difficulty walking, and “claw” hand and foot (1,2), findings that were consistent with advanced beriberi (3). Patients developed retrobulbar involvement of the optic nerve, with occasional hyperemia of the optic disc and a well marked scotoma, but optic atrophy was not observed. Dermatological findings included irritation and ezcema at the margin of the nostrils and mouth, with redness of the lips and inside of the mouth, and with loss of surface epithelium of the tongue. The disease seemed to occur nearly always among black Jamaicans, and Strachan had the opportunity to observe and treat 510 patients and to make more detailed observations on 121 of these patients.

The treatment adopted by the Public Hospital of Kingston consisted of bed rest, nourishing food, and quinine and strychnine in modest doses combined with iodide of potassium. No patients died. Strachan raised the question whether the condition was caused by “the poison of beri-beri” as beriberi was widely attributed to some type of toxin at the time. Strachan also speculated that a toxin produced by malaria parasites was possibly the cause, however, he concluded that “good food was important” in treatment of the disease (1). At the same time as Strachan’s work in Jamaica, several Japanese physicians began to describe large case series of adults with beriberi who had reduced vision, central or centrocecal scotomas, and temporal optic disc atrophy (4–6). Visual recovery was noted when the patients were put on a diet protective against beriberi (3).

4. EPIDEMIOLOGY

Nutritional amblyopia has usually been described in epidemic or sporadic form, primarily among impoverished individuals, prisoners of war, inmates in jails, poorly fed soldiers, alcoholics, refugees, students in boarding schools where the diet is poor, among people subject to economic or trade embargo, and in populations following natural disasters such as hurricanes, droughts, or crop failures. Nutritional amblyopia has been described nearly worldwide. An estimated 1–7% of British prisoners-of-war who survived captivity in southeast Asia in Japanese prison camps during World War II were affected by nutritional amblyopia (7,8). In the recent epidemic in Cuba, the attack rate of neuropathy was 461.4 per 100,000 (9). The incidence of nutritional amblyopia in many industrialized countries has dropped since the beginning of the 20th century.

5. CLINICAL FEATURES

Nutritional amblyopia typically presents as a gradual decrease in vision, with difficulty reading and recognizing faces. Most patients complain that the decrease in vision has taken place over several days or weeks. A central or cecocentral scotoma is usually present, either as a scotoma to red or green or as an absolute scotoma. The absolute scotoma rarely exceeds five degrees in diameter. At first, there may be no associated ophthalmological findings. Slight hyperemia of the optic disc and occasional retinal hemorrhages may occur in the early stage of the disease, and later, temporal disc pallor and loss of the papillomacular bundle are usually seen. The condition may fluctuate with temporary changes in diet. The condition is generally reversible if treated with proper diet and vitamins within 2 or 3 mo of onset of visual loss, but the chance of visual recovery is decreased with longstanding disease and atrophy of the papillomacular bundle. Associated findings may include skin, mucosal, neurological, gastrointestinal, and hematological signs and symptoms characteristic of specific or mixed B vitamin deficiencies.

6. PATHOGENESIS

Nutritional amblyopia is caused by deficiencies of one or more B complex vitamins, and clinical and experimental evidence suggests that thiamin deficiency, niacin deficiency, vitamin B12 deficiency, and folate deficiency alone or in combination may cause nutritional amblyopia. The clinical presentation of many patients with nutritional amblyopia shows that multiple B vitamin deficiencies may occur simultaneously, and the metabolism of many B vitamins is closely interrelated, with a deficiency in one vitamin affecting the metabolism of another. So-called “tobacco-alcohol amblyopia” and “tobacco amblyopia” should be considered nutritional amblyopia, as these apparent disorders have not stood rigorous scrutiny over the last few decades. The epidemiological and experimental evidence implicating tobacco as the primary etiology in so-called “tobacco amblyopia” is weak. Many of the so-called “tropical amblyopias”occurring in epidemic form are likely due to dietary deficiency. The role of specific micronutrients in the pathogenesis of nutritional amblyopia is presented below.

6.1. Thiamin Deficiency

Thiamin is a water-soluble vitamin that plays a role in the metabolism of carbohydrates and branched-chain amino acids. Thiamin deficiency is the cause of several disorders, most notably beriberi, a syndrome that involves the cardiovascular and nervous systems, Wernicke encephalopathy and Korsakoff psychosis, usually found among chronic alcoholics, and more rare conditions such as congenital lactic acidosis, intermittent ataxia of childhood, and subacute necrotizing encephalomyelopathy (Leigh disease). Thiamin deficiency has been implicated as a cause of nutritional amblyopia, and there are three lines of evidence that support this idea: (1) the association of disorders of thiamin deficiency with nutritional amblyopia, (2) experimental animal models of thiamin deficiency, and (3) reversal of nutritional amblyopia with thiamin treatment in humans.

6.1.1. HISTORICAL BACKGROUND

Beriberi has been known since antiquity in Asia, where it was described in ancient Chinese and Japanese medical texts (10). In the East Indies, Jacob de Bondt (1592–1631) noted that the word “beriberi” was derived from a local word for sheep because of the tottering walk of those affected by the disease (11). Polished rice began to be consumed more widely in Japan during the Tokugawa era (1603–1867), and a large epidemic of kakké, or beriberi, occurred in Edo, now present day Tokyo, in 1691. Beriberi became highly prevalent in the Japanese navy, and a physician, Kanehiro Takaki (1849–1920), found that provision of more meat, beans, and milk in the standard diet would virtually eliminate beriberi from the navy (12). In the East Indies, the Dutch physician Christaan Eijkman (1858– 1930) produced a disease resembling human beriberi in chickens that were fed polished rice, and rice polishings were found to protect against this type of polyneuritis in chickens (13–15). Human investigations conducted in mental institutions (16,17), in prisons (18,19), and in labor camps (20) showed that those who ate unpolished rice, which still contained the germ of the rice, had a lower risk of developing beriberi compared to those who ate polished rice. In spite of the large reduction of beriberi in the Japanese military with early dietary reforms, the incidence of beriberi reached a peak in the Japanese civilian population in the 1920s. Worldwide, the highest incidence of beriberi has occurred

Fig. 1. Structural formulas of thiamin and thiamin pyrophosphate.

in east and southeast Asia, and most reports of nutritional amblyopia associated with beriberi have come from this region and are summarized later in the section.

In 1911, Casimir Funk (1884–1967), working at the Lister Institute in London, claimed to have isolated a substance, “vitamine,” that prevented beriberi (21). Although further work did not verify Funk’s claim, his term “vitamine” endured and was later shortened to “vitamin.” Umetaro Suzuki (1874–1943) and colleagues prepared a crystalline substance from rice bran, named “oryzanin” which protected chickens from polyneuritis (22). In the East Indies, two Dutch chemists, Barend Jansen (1884–1962) and Willem Donath (1889–1957), succeeded in isolating thiamin in 1926 (23). Thiamin was synthesized by Robert Williams (1886–1965) and Joseph Cline (b. 1908) in 1936 (24). Fortification of family flour and baker’s white bread with thiamin, riboflavin, niacin, and iron began in the United States in the early 1940s, with a subsequent marked reduction in cases of beriberi and pellagra seen in urban hospitals serving the poor, such as Bellevue Hospital in New York City (25). Similar action was taken in Great Britain and Canada at this time, but other countries followed much later. The mandatory thiamin enrichment of bread flour in the 1990s was associated with a subsequent reduction in the prevalence of Wernicke-Korsakoff syndrome in Australia (26,27). In the nomenclature of thiamin, obsolete terms for this vitamin include vitamin B1, oryzamin, torulin, polyneuramin, vitamin F, antineuritic vitamin, and antiberiberi vitamin. General historical accounts of beriberi and thiamin can be found elsewhere (10,28–30).

6.1.2. BIOCHEMISTRY OF THIAMIN

Thiamin has the formula 3-(4-amino-2-methylpyrimidin-5-ylmethyl)-5-(2-hydroxy- ethyl)-4-methylthiazolium and consists of one pyrimidine ring and one thiazole ring that are linked by a methylene group (Fig. 1). In a normal adult, about 80% of total thiamin is found in the form of thiamin pyrophosphate (TPP), with about 10% as thiamin triphosphate (TTP), and the remainder as thiamin monophosphate (TMP) and thiamin (30a). The four forms of thiamin can be introconverted by tissue enzymes: (1) thiamin pyrophosphokinase (TPK) catalyzes the formation of TPP from thiamin and adenosine triphosphate (ATP), (2) TPP-ATP phosphoryl transferase (P-transferase) catalyzes the formation of TTP from TPP and ATP, (3) thiamin monophosphatase that hydrolyzes TMP to form thiamin, (4) thiamin pyrophosphatase that hydrolyzes TPP to form TMP, and (5) thiamin triphosphatase that hydrolyzes TTP to form TPP. Thiamin hydrochloride, a commercial form of thiamin, is a white crystalline substance that is water-soluble and relatively stable in dry form, but it can be destroyed in soluble form by heat at pH >5.0 and can be cleaved by sulfites that are used in the processing of some foods.

6.1.3. DIETARY SOURCES OF THIAMIN

The richest dietary sources of thiamin are yeast, pork, and legumes. The thiamin content of cereal grains is high in the germ portion but low in the endosperm, thus, removal of the

Based on US Department of Agriculture National Nutrient Database for

Standard Reference (http://www.nal.usda.gov/fnic/foodcomp/search) (31).

germ through food processing, as in highly milled polished rice and white flour, will substantially reduce the thiamin content of cereals. Fruits and vegetables, dairy products, and seafood are not good dietary sources of thiamin. The thiamin content of some selected foods is shown in Table 1 (31). Some types of food processing can destroy thiamin, such as high temperatures during cooking, and the addition of sodium bicarbonate to preserve the green color of vegetables and legumes. After losses following some types of food processing, there is relatively little quantitative data regarding the bioavailability of thiamin, and most evidence suggests that the thiamin in most foods tested is highly available for absorption and utilization by humans (32).

6.1.4. ABSORPTION, STORAGE, AND METABOLISM OF THIAMIN

During digestion, thiamin phosphoesters in food are broken down by phosphatases to yield free thiamin in the intestinal lumen. The jejunum and ileum in the small intestine are the main sites for thiamin absorption, and thiamin is absorbed by both active transport and passive diffusion. At low concentrations in the intestinal lumen, thiamin is mainly absorbed through active transport. At higher concentrations, active transport follows saturation kinetics and some passive diffusion occurs (33). The entry of thiamin into the

enterocyte is reduced by ethanol administration and aging (34). Single large doses of oral thiamin greater than 5 mg are mostly unabsorbed (35–37). In the blood, thiamin is transported mostly within erythrocytes as TPP, and about 20% is bound to proteins in the plasma as free thiamin and TPP. The total thiamin content of the normal adult human body is about 30 mg (0.11 mmol), and the biological half-life of thiamin is about 9-18 d. The highest concentrations of thiamin are found in the liver, heart, kidney, and brain. Skeletal muscle, because of its overall mass, contains about 40–50% of the total thiamin in the human body. Thiamin metabolites are mostly excreted in the urine, and pyrimidine carboxylic acid, thiazole acetic acid, and thiamin acetic acid are the main urinary metabolites of thiamin. In healthy lactating women, human milk thiamin content increases with the progression of lactation, and mature milk contains about 200 μg/L of thiamin (38). The absorption of thiamin may be impaired during folate or protein deficiency (39,40).

6.1.5. FUNCTIONS

Thiamin, in the form of TPP, acts as a coenzyme in the oxidative phosphorylation of α-ketoacids and in transketolase reactions, two processes that are important in carbohydrate and lipid metabolism (Fig. 2). Pyruvate, α-ketoglutarate, and α-ketoacids derived from leucine, isoleucine, and valine (all branched chain amino acids) undergo oxidative decarboxylation through multienzyme complexes that include TPP and are located within the mitochondria. Pyruvate undergoes oxidative decarboxylation by pyruvate dehydrogenase to form acetyl-coenzyme A (CoA), and CoA subsequently enters the tricarboxylic acid (Krebs) cycle. α-ketoglutarate undergoes oxidative decarboxylation by α-ketoglut- arate dehydrogenase to succinyl-CoA in the tricarboxylic acid cycle. α-ketoacids derived from branched-chain amino acids undergo decarboxylation by branched-chain dehydrogenase. In the cytoplasm, a TPP-dependent transketolase is involved in the transketolation of ketosugars that contain three to seven carbons. This pathway is important for the production of nicotinamide adenine dinucleotide phosphate (NADPH) for many biosynthetic reactions including fatty acid synthesis, for conversion to pentoses, especially ribose- 5-phosphate, a component of many important molecules such as RNA, DNA, ATP, CoA, NAD, and FAD, and for interconversion of ketosugars, some of which can enter the glycolysis pathway (41). Thiamin has been postulated to play a role in nerve conduction. TTP may influence the gating mechanism for Na+ and K+ transport via (Na+-K+)-ATPase. Thiamin deficiency may potentially affect metabolism of some neurotransmitters, as acetylcholine, γ-aminobutyric acid, glutamate, and aspartate are produced primarily through the metabolism of glucose (41).

6.1.6. REQUIREMENT FOR THIAMIN

The Food and Nutrition Board of the Institute of Medicine has made new recommendations of thiamin intake by life stage and gender group (42) (Table 2). The Adequate Intake (AI) is the recommended level of intake for infants. The Estimated Average Requirement (EAR) is the daily intake value that is estimated to meet the requirement of half the healthy individuals in a group. The Recommended Dietary Allowance (RDA) is defined as the EAR plus twice the coefficient of variation (CV) to cover 97–98% of individuals in any particular group. The requirements for thiamin increased with pregnancy and lactation. Increased catabolism during infection, inflammatory, trauma, or surgery can increase the demand for thiamin. Studies in healthy human volunteers suggest that

Fig. 2. Thiamin-dependent metabolic pathways.

a higher carbohydrate intake will increase the requirement for thiamin (43). It has been thought that the requirement of thiamin is increased by physical exercise, since thiamin, as thiamin pyrophosphate, plays an important role in energy-producing metabolic pathways, but there is not much data to support this idea (44).

6.1.7. EPIDEMIOLOGY OF THIAMIN DEFICIENCY

Beriberi has been described nearly worldwide, and over the last 200 yr, the highest prevalence of beriberi has been found in Japan, China, southeast Asia, the Malay archipelago, New Guinea, Melanesia, south Asia, parts of Africa, northeast Brazil, the Caribbean region, and Newfoundland. Nutritional amblyopia associated with beriberi has also been

AI, Adequate Intake; EAR, Estimated Average Requirement;

RDA, Recommended Dietary Allowance. Based on ref. 42.

generally described within this geographical distribution. Heinrich Botho Scheube depicted the known areas for beriberi in Die Beriberi–Krankheit in 1894 (45) (Fig. 3), and the map demonstrates how widespread beriberi was at the turn of the century. The main risk factors for beriberi include an inadequate dietary intake of thiamin-containing foods, low socioeconomic class, low educational level, chronic alcoholism, and inadequate parenteral nutrition. Prolonged high consumption of tea or coffee and folate deficiency also increases the risk of thiamin deficiency. Increased excretion of thiamin can occur with diuretics, suggesting that diuretics may be a risk factor for thiamin deficiency (46). Impaired thiamin status occurs among an estimated 5% of the population over 60 yr of age in North America (47) and laboratory evidence of inadequate thiamin status has been found 12–23% of institutionalized and noninstitutionalized older adults (48–50). Adults with human immunodeficiency virus infection may be at higher risk of Wernicke encephalopathy (51).

6.1.8. ASSESSMENT OF THIAMIN STATUS

The three most widely used procedures for the assessment of thiamin status are measurement of erythrocyte transketolase activity, thiamin concentrations in the blood, and urinary excretion of thiamin (52). Transketolase is an enzyme that requires thiamin pyrophosphate, thus, erythrocyte transketolase assay is a functional test of thiamin status. Erythrocyte transketolase activity is measured with and without the addition of thiamin pyrophosphate. In the erythrocyte transketolase thiamin pyrophosphate stimulation assay, the thiamin pyrophosphate effect, or “TPP effect” is interpreted as normal, low, and deficient when values are 0–15%, 16–24%, and >25%, respectively (52). Serum and whole blood thiamin concentrations can be measured using high-performance liquid chromatography. Whole blood thiamin concentrations of 6.96 ± 1.26 μg/dL have been described in normal patients compared with 2.29 ± 1.06 μg/dL in patients with beriberi (53). Urinary excretion of thiamin is commonly used to assess thiamin status and is considered to correspond well with the development of thiamin deficiency. Urinary thiamin reflects more recent dietary intake of thiamin. Random urine samples are usually collected and the thia-