- What is Thiamin (Vitamin B1)
- What Does Vitamin B1 (Thiamine) Do
- What are some effects of thiamin on health ?
- How much thiamin do you need ?
- What foods provide thiamine ?
- Thiamine (Vitamin B1) Deficiency
What is Thiamin (Vitamin B1)
Thiamin (or thiamine) is one of the water-soluble B vitamins. It is also known as vitamin B1. Thiamin is naturally present in some foods, added to some food products, and available as a dietary supplement. This vitamin plays a critical role in energy metabolism and, therefore, in the growth, development, and function of cells 1).
Ingested thiamin (vitamin B1) from food and dietary supplements is absorbed by the small intestine through active transport at nutritional doses and by passive diffusion at pharmacologic doses 2). Most dietary thiamin (vitamin B1) is in phosphorylated forms, and intestinal phosphatases hydrolyze them to free thiamin before the vitamin is absorbed 3). The remaining dietary thiamin (vitamin B1) is in free (absorbable) form 4), 5). Humans store thiamin (vitamin B1) primarily in the liver, but in very small amounts 6). The vitamin B1 has a short half-life, so people require a continuous supply of it from the diet.
What Does Vitamin B1 (Thiamine) Do
Thiamine (also called vitamin B1) helps turn the food you eat into the energy you need. Thiamine is important for the growth, development, and function of the cells in your body.
About 80% of the approximately 25–30 mg of thiamine (vitamin B1) in the adult human body is in the form of thiamine diphosphate (TDP; also known as thiamin pyrophosphate), the main metabolically active form of thiamine (vitamin B1). Bacteria in the large intestine also synthesize free thiamine (vitamin B1) and thiamine diphosphate, but their contribution, if any, to thiamine nutrition is currently unknown 7). Thiamine diphosphate serves as an essential cofactor for five enzymes involved in glucose, amino acid, and lipid metabolism 8), 9).
Levels of thiamine in the blood are not reliable indicators of thiamin status. Thiamine status is often measured indirectly by assaying the activity of the transketolase enzyme, which depends on thiamine diphosphate, in erythrocyte hemolysates in the presence and absence of added thiamine diphosphate 10). The result, known as the “thiamine diphosphate effect,” reflects the extent of unsaturation of transketolase with thiamine diphosphate. The result is typically 0%–15% in healthy people, 15%–25% in those with marginal deficiency, and higher than 25% in people with deficiency. Another commonly used measure of thiamin status is urinary thiamin excretion, which provides data on dietary intakes but not tissue stores 11). For adults, excretion of less than 100 mcg/day thiamin in urine suggests insufficient thiamin intake, and less than 40 mcg/day indicates an extremely low intake 12).
What are some effects of thiamin on health ?
Scientists are studying thiamin to better understand how it affects health. Here are some examples of what this research has shown.
People with diabetes often have low levels of thiamine in their blood. Scientists are studying whether thiamin supplements can improve blood sugar levels and glucose tolerance in people with type 2 diabetes. They are also studying whether benfotiamine (a synthetic form of thiamin) supplements can help with nerve damage caused by diabetes.
The proportion of people with type 1 or type 2 diabetes who have poor thiamin status based on erythrocyte transketolase activity ranges from 17% to 79% in studies conducted to date 13). In a study of 76 consecutive patients with type 1 or type 2 diabetes, for example, 8% had mild thiamine deficiency and 32% had moderate deficiency based on assays of the transketolase enzyme 14).
Some small studies have shown that oral supplementation with 150–300 mg/day thiamin can decrease glucose levels in patients with type 2 diabetes or impaired glucose tolerance 15), 16). However, the authors of these studies did not assess the potential clinical significance of these findings.
A few small randomized studies have assessed the effects of benfotiamine supplements on diabetic neuropathy. Three studies found that, compared to placebo, 120–900 mg/day benfotiamine with or without other B-vitamins decreased the severity of neuropathy symptoms and lowered urinary albumin excretion (a marker of early-stage diabetic nephropathy) 17), 18), 19). However, another study found no effect of 900 mg/day benfotiamine on urinary excretion of albumin or kidney injury molecule-1, a marker of kidney injury 20).
Well-designed studies with larger sample sizes and longer durations are required to determine whether thiamin supplements can reduce glucose levels in patients with diabetes or decrease diabetic compications.
- Heart failure
Many people with heart failure have low levels of thiamin. Scientists are studying whether thiamin supplements might help people with heart failure.
The rates of poor thiamin status in patients with heart failure have ranged in studies from 21% to 98% 21). Explanations for this association include older age, comorbidities, insufficient dietary intake, treatment with diuretics, and frequent hospitalizations 22).
The authors of one study reported that 33% of 100 patients with chronic heart failure had thiamin deficiency compared to 12% of 50 healthy volunteers 23). Rates of deficiency were even higher when the investigators excluded those who used thiamin supplements. The different rates of thiamin deficiency in patients with heart failure in these and other studies are probably due to differences in nutrition status, comorbidities, medications and dietary supplements used, and techniques used to measure thiamin status 24).
The authors of a systematic literature review and meta-analysis found two randomized, double-blind, placebo-controlled trials of thiamin supplementation in people with heart failure that met their eligibility criteria 25). In these trials, thiamin supplements significantly improved net change in left ventricular ejection fraction. The authors did not assess the clinical significance of this finding, however.
More research is needed to determine whether thiamin supplements might benefit people with heart failure, even if they have normal thiamine status.
- Alzheimer’s disease
Scientists are studying the possibility that thiamin deficiency could affect the dementia of Alzheimer’s disease. Whether thiamine supplements may help mental function in people with Alzheimer’s disease needs further study.
According to animal model studies, thiamin deficiency might play a role in the development of Alzheimer’s disease 26). For example, thiamin deficiency produces oxidative stress in neurons, death of neurons, loss of memory, plaque formation, and changes in glucose metabolism—all markers of Alzheimer’s disease. Autopsy studies have shown that transketolase and other thiamin-dependent enzymes have decreased activity in the brains of people with Alzheimer’s disease 27), 28).
Few studies have assessed the prevalence of thiamine deficiency in people with Alzheimer’s disease. One of these studies found that 13% of 150 patients with cognitive impairment and acute-onset behavioral disturbances were considered thiamin deficient based on plasma levels 29).
The authors of a 2001 Cochrane review assessed three double-blind, randomized trials (including two crossover trials) that compared the effects of 3 g/day oral thiamin to placebo on cognitive function in patients with Alzheimer’s type dementia 30). The three studies randomly assigned fewer than 20 patients each, and the two crossover studies did not include a washout period 31), 32), 33). The review authors stated that it was not possible to draw any conclusions from these three studies because they were small and the publications describing them did not provide enough detail to combine these data in a meta-analysis.
Larger, well-designed studies are needed to determine whether thiamin supplements are beneficial for Alzheimer’s disease.
Thiamin has not been shown to cause any harm.
- Wernicke-Korsakoff syndrome
Wernicke-Korsakoff syndrome is one of the most severe neuropsychiatric sequelae of alcohol abuse 34). The authors of a 2013 Cochrane review of thiamine to treat or prevent Wernicke-Korsakoff syndrome found only two studies that met their inclusion criteria, and one of these studies has not been published 35). These randomized, double-blind, placebo-controlled trials compared 5 mg/day by mouth for 2 weeks or daily intramuscular doses of 5 to 200 mg/day thiamin over 2 consecutive days in a total of 177 people with a history of chronic alcohol use. The Cochrane review authors concluded that the evidence from randomized clinical trials is insufficient to guide health care providers in selecting the appropriate dose, frequency, duration, or route of thiamin supplementation to treat or prevent Wernicke-Korsakoff syndrome in patients with alcohol abuse.
The authors of the European Federation of Neurological Societies guidelines for diagnosing, preventing, and treating Wernicke’s encephalopathy note that even high doses of oral thiamin supplements might not be effective in raising blood thiamin levels or curing Wernicke’s encephalopathy 36). They recommend 200 mg thiamine, preferably intravenously, three times daily (total of 600 mg/day) until the signs and symptoms stop, along with a balanced diet. In its guidelines for managing Wernicke’s encephalopathy in emergency departments, the Royal College of Physicians in London supports the administration of oral thiamin hydrochloride (100 mg three times a day) in patients with adequate dietary intakes of thiamin and no signs or symptoms of Wernicke’s encephalopathy 37). However, the authors recommend parenteral thiamin supplementation for patients at high risk, such as those with ataxia, confusion, and a history of chronic alcohol misuse, because oral supplementation is unlikely to produce adequate blood levels.
Thiamine (Vitamin B1) Supplements
Thiamin is available in many dietary supplements. Multivitamin/multimineral supplements with thiamin typically provide about 1.5 mg thiamin (100% of the Dietary Value) and sometimes more 38). Supplements containing B-complex vitamins (including thiamin) or thiamine only are also available. The most commonly used forms of thiamin in supplements are thiamine mononitrate and thiamin hydrochloride, which are stable and water soluble 39), 40).
Benfotiamine is a synthetic thiamin derivative that is used in some dietary supplements. Benfotiamine is not water soluble and is converted to thiamin in the body 41).
How much thiamin do you need ?
The amount of thiamin you need depends on your age and sex. Average daily recommended amounts are listed below in milligrams (mg).
|Life Stage||Recommended Amount|
|Birth to 6 months||0.2 mg|
|Infants 7–12 months||0.3 mg|
|Children 1–3 years||0.5 mg|
|Children 4–8 years||0.6 mg|
|Children 9–13 years||0.9 mg|
|Teen boys 14–18 years||1.2 mg|
|Teen girls 14–18 years||1.0 mg|
|Pregnant teens and women||1.4 mg|
|Breastfeeding teens and women||1.4 mg|
What foods provide thiamine ?
Food sources of thiamin include whole grains, meat, and fish 42). Breads, cereals, and infant formulas in the United States and many other countries are fortified with thiamine 43).The most common sources of thiamin in the U.S. diet are cereals and bread 44). Pork is another major source of the vitamin. Dairy products and most fruits contain little thiamine 45). About half of the thiamine in the U.S. diet comes from foods that naturally contain thiamin; the remainder comes from foods to which thiamine has been added 46).
The U.S. Department of Agriculture’s (USDA’s) Nutrient Database website 47) lists the nutrient content of many foods and provides a comprehensive list of foods containing thiamin arranged by nutrient content 48) and by food name 49).
Heating foods containing thiamin can reduce their thiamin content. For example, bread has 20%–30% less thiamin than its raw ingredients, and pasteurization reduces thiamin content (which is very small to begin with) in milk by up to 20% 50). Because thiamin dissolves in water, a significant amount of the vitamin is lost when cooking water is thrown out 51). Processing also alters thiamine levels in foods; for example, unless white rice is enriched with thiamin, it has one tenth the amount of thiamin in unenriched brown rice 52).
Data on the bioavailability of thiamine from food are very limited 53). Some studies do show, however, that thiamin absorption increases when intakes are low 54).
Thiamin is found naturally in many foods and is added to some fortified foods. You can get recommended amounts of thiamine by eating a variety of foods, including the following:
- Whole grains and fortified bread, cereal, pasta, and rice
- Meat (especially pork) and fish
- Legumes (such as black beans and soybeans), seeds, and nuts
Several food sources of thiamine are listed in Table 2.
- Recommended Dietary Allowance (RDA): average daily level of intake sufficient to meet the nutrient requirements of nearly all (97%–98%) healthy individuals.
- Adequate Intake (AI): established when evidence is insufficient to develop an RDA; intake at this level is assumed to ensure nutritional adequacy.
- Estimated Average Requirement (EAR): average daily level of intake estimated to meet the requirements of 50% of healthy individuals. It is usually used to assess the adequacy of nutrient intakes in populations but not individuals.
- Tolerable Upper Intake Level (UL): maximum daily intake unlikely to cause adverse health effects.
Table 2: Selected Food Sources of Thiamine
|Breakfast cereals, fortified with 100% of the DV for thiamin, 1 serving||1.5||100|
|Rice, white, long grain, enriched, parboiled, ½ cup||1.4||73|
|Egg noodles, enriched, cooked, 1 cup||0.5||33|
|Pork chop, bone-in, broiled, 3 ounces||0.4||27|
|Trout, cooked, dry heat, 3 ounces||0.4||27|
|Black beans, boiled, ½ cup||0.4||27|
|English muffin, plain, enriched, 1 muffin||0.3||20|
|Mussels, blue, cooked, moist heat, 3 ounces||0.3||20|
|Tuna, Bluefin, cooked, dry heat, 3 ounces||0.2||13|
|Macaroni, whole wheat, cooked, 1 cup||0.2||13|
|Acorn squash, cubed, baked, ½ cup||0.2||13|
|Rice, brown, long grain, not enriched, cooked, ½ cup||0.1||7|
|Bread, whole wheat, 1 slice||0.1||7|
|Orange juice, prepared from concentrate, 1 cup||0.1||7|
|Sunflower seeds, toasted, 1 ounce||0.1||7|
|Beef steak, bottom round, trimmed of fat, braised, 3 ounces||0.1||7|
|Yogurt, plain, low fat, 1 cup||0.1||7|
|Oatmeal, regular and quick, unenriched, cooked with water, ½ cup||0.1||7|
|Corn, yellow, boiled, 1 medium ear||0.1||7|
|Milk, 2%, 1 cup||0.1||7|
|Barley, pearled, cooked, 1 cup||0.1||7|
|Cheddar cheese, 1½ ounces||0||0|
|Chicken, meat and skin, roasted, 3 ounces||0||0|
|Apple, sliced, 1 cup||0||0|
*DV = Daily Value. DVs were developed by the U.S. Food and Drug Administration (FDA) to help consumers compare the nutrient contents of products within the context of a total diet. The DV for thiamine is 1.5 mg for adults and children age 4 and older. Foods providing 20% or more of the DV are considered to be high sources of a nutrient.[Source 55)]
Are you getting enough thiamin ?
Most people in the United States consume the recommended amounts of thiamine. An analysis of data from the 2003-2006 National Health and Nutrition Examination Survey showed that only 6% of the U.S. population has a usual intake below the estimated average requirement (average daily level of intake estimated to meet the requirements of 50% of healthy individuals. It is usually used to assess the adequacy of nutrient intakes in populations but not individuals) 56).
Among children and teens, the average daily thiamin intake from foods is 1.27 mg for ages 2–5 years, 1.54 mg for ages 6–11 years, and 1.68 mg for ages 12–19 years 57). In adults aged 20 and older, the average daily thiamin intake from foods is 1.95 mg in men and 1.39 mg in women. The average daily thiamin intake from foods and supplements in children and teens is 1.51 mg for ages 2–5 years, 1.76 mg for ages 6–11 years, and 1.95 mg for ages 12–19 years. In adults aged 20 and older, the average daily thiamin intake from foods and supplements is 4.89 mg in men and 4.90 mg in women.
No current data on rates of thiamine deficiency in the U.S. population are available.
Most people in the United States get enough thiamin from the foods they eat. Thiamin deficiency is rare in this country. However, certain groups of people are more likely than others to have trouble getting enough thiamin:
- People with alcohol dependence
- Older individuals
- People with HIV/AIDS
- People with diabetes
- People who have had bariatric surgery
What happens if you don’t get enough thiamin ?
You can develop thiamin deficiency if you don’t get enough thiamin in the foods you eat or if your body eliminates too much or absorbs too little thiamin.
Thiamin deficiency can cause loss of weight and appetite, confusion, memory loss, muscle weakness, and heart problems. Severe thiamin deficiency leads to a disease called beriberi with the added symptoms of tingling and numbness in the feet and hands, loss of muscle, and poor reflexes. Beriberi is not common in the United States and other developed countries.
A more common example of thiamin deficiency in the United States is Wernicke-Korsakoff syndrome, which mostly affects people with alcoholism. It causes tingling and numbness in the hands and feet, severe memory loss, disorientation, and confusion.
Thiamine (Vitamin B1) Deficiency
In addition to insufficient intakes of thiamin from the diet, the causes of thiamin deficiency include lower absorption or higher excretion rates than normal due, for example, to certain conditions (such as alcohol dependence or HIV/AIDS) or use of some medications 58).
- Thiamin deficiency causes degeneration of peripheral nerves, thalamus, mammillary bodies, and cerebellum. Cerebral blood flow is markedly reduced, and vascular resistance is increased.
- The heart may become dilated; muscle fibers become swollen, fragmented, and vacuolized, with interstitial spaces dilated by fluid. Vasodilation occurs and can result in edema in the feet and legs. Arteriovenous shunting of blood increases. Eventually, high-output heart failure may occur.
In its early stage, thiamin deficiency can cause weight loss and anorexia, confusion, short-term memory loss, and other mental signs and symptoms; muscle weakness; and cardiovascular symptoms (such as an enlarged heart) 59).
The most common effect of thiamin deficiency is beriberi, which is characterized mainly by peripheral neuropathy and wasting 60), 61), 62). It’s most common among people subsisting on white rice or highly refined carbohydrates in developing countries and among alcoholics.
People with this condition have impaired sensory, motor, and reflex functions. In rare cases, beriberi causes congestive heart failure that leads to edema in the lower limbs and, occasionally, death 63), 64). Although beriberi is rare in the United States and other developed countries, people in these countries do occasionally develop the condition 65), 66), 67), 68). Administration of supplemental thiamine, often parenterally, quickly cures beriberi 69), 70).
A more common manifestation of thiamin deficiency in the United States is Wernicke-Korsakoff syndrome 71). This disorder is about 8–10 times more common in people with chronic alcoholism than in the general population, but it can also develop in patients who have severe gastrointestinal disorders, rapidly progressing hematologic malignancies, drug use disorders, or AIDS 72). In many patients, Wernicke-Korsakoff syndrome has two phases. The first, acute, and life-threatening stage, Wernicke’s encephalopathy, is usually characterized by peripheral neuropathy 73), 74). Without treatment, up to 20% of people with Wernicke’s encephalopathy die; those who survive develop Korsakoff’s psychosis, although some people with Korsakoff’s psychosis have not previously had Wernicke’s encephalopathy 75), 76). Korsakoff’s psychosis, an effect of chronic thiamine deficiency, is associated with severe short-term memory loss, disorientation, and confabulation (confusion between real and imagined memories) 77), 78), 79). At this chronic state of the disorder, parenteral thiamin treatment does not lead to recovery in about one-quarter of patients 80).
The World Health Organization recommends daily oral doses of 10 mg thiamin for a week, followed by 3–5 mg/daily for at least 6 weeks, to treat mild thiamin deficiency 81). The recommended treatment for severe deficiency consists of 25–30 mg intravenously in infants and 50–100 mg in adults, then 10 mg daily administered intramuscularly for approximately one week, followed by 3–5 mg/day oral thiamin for at least 6 weeks.
Causes of Thiamin (Vitamin B1) Deficiency
Primary thiamin deficiency is caused by
- Inadequate intake of thiamin
It is commonly due to a diet of highly refined carbohydrates (eg, polished rice, white flour, white sugar) in developing countries. It also develops when intake of other nutrients is inadequate, as may occur in young adults with severe anorexia; it often occurs with other B vitamin deficiencies.
Infantile beriberi occurs in infants (usually by age 3 to 4 wk) who are breastfed by thiamin-deficient mothers. Heart failure (which may occur suddenly), aphonia, and absent deep tendon reflexes are characteristic.
Secondary thiamin deficiency is caused by
- Increased demand (eg, due to hyperthyroidism, pregnancy, lactation, strenuous exercise, or fever)
- Impaired absorption (eg, due to prolonged diarrhea)
- Impaired metabolism (eg, due to hepatic insufficiency)
In alcoholics, many mechanisms contribute to thiamin deficiency; they include decreased intake, impaired absorption and use, increased demand, and possibly an apoenzyme defect.
Because thiamin is necessary for glucose metabolism, glucose infusions may precipitate or worsen symptoms of deficiency in thiamin-deficient people.
Groups at Risk of Thiamin Deficiency
The following groups are among those most likely to have inadequate thiamin status.
- People with alcohol dependence
In highly industrialized countries, chronic alcohol use disorders appear to be the most common cause of thiamin deficiency 82). Up to 80% of people with chronic alcoholism develop thiamine deficiency because ethanol reduces gastrointestinal absorption of thiamin, thiamin stores in the liver, and thiamin phosphorylation 83), 84). Also, people with alcoholism tend to have inadequate intakes of essential nutrients, including thiamine.
- Older adults
Up to 20%–30% of older adults have laboratory indicators that suggest some degree of thiamin deficiency 85), 86). Possible reasons include low dietary intakes, a combination of chronic diseases, concomitant use of multiple medications, and low absorption of thiamin as a natural result of aging 87), 88). Some small studies have found that the risk of deficiency is particularly high in elderly people who reside in an institution 89), 90).
- People with HIV/AIDS
People with HIV infection have an increased risk of thiamin deficiency and its sequelae, including beriberi and Wernicke-Korsakoff syndrome 91), 92). Autopsies of 380 people with AIDS found that almost 10% had Wernicke’s encephalopathy 93), and some experts believe that thiamin deficiency is underdiagnosed in this population 94). The association between thiamin deficiency and HIV/AIDS is probably due to malnutrition as a result of the catabolic state associated with AIDS.
- People with diabetes
Some small studies have found that thiamin levels in plasma are up to 76% lower in people with type 1 diabetes than in healthy volunteers and 50%–75% lower in people with type 2 diabetes 95), 96). Other studies have shown a higher risk of thiamin deficiency in people with type 1 and/or type 2 diabetes based on tests of erythrocyte transketolase activity 97), 98). These lower thiamine levels might be due to increases in clearance of thiamine by the kidneys. The relevance of these effects to clinical prognosis or outcomes is not known.
- People who have undergone bariatric surgery
Bariatric surgery for weight loss is associated with some risks, including severe thiamin deficiency due to malabsorption that can lead to beriberi or Wernicke’s encephalopathy. A 2008 literature review identified 84 cases of Wernicke’s encephalopathy after bariatric surgery (primarily gastric bypass surgery) between 1991 and 2008 99). About half of these patients experienced long-lasting neurologic impairments. Micronutrient supplements that include thiamin are almost always recommended for patients following bariatric surgery to avoid deficiencies 100).
Diagnosis of Thiamine Deficiency
- Favorable response to thiamin
Diagnosis of thiamin deficiency is usually based on a favorable response to treatment with thiamin in a patient with symptoms or signs of deficiency. Similar bilateral lower extremity polyneuropathies due to other disorders (eg, diabetes, alcoholism, vitamin B12deficiency, heavy metal poisoning) do not respond to thiamin. Single-nerve neuritides (mononeuropathies—eg, sciatica) and multiple mononeuropathies (mononeuritis multiplex) are unlikely to result from thiamin deficiency.
Electrolytes, including magnesium, should be measured to exclude other causes. For confirmation in equivocal cases, erythrocyte transketolase activity and 24-h urinary thiamin excretion may be measured.
Diagnosis of cardiovascular beriberi can be difficult if other disorders that cause heart failure are present. A therapeutic trial of thiamin can help.
Treatment of Thiamine Deficiency
- Supplemental thiamin, with dose based on clinical manifestations
Ensuring that dietary supplies of thiamin are adequate is important regardless of symptoms.
Because IV glucose can worsen thiamin deficiency, alcoholics and others at risk of thiamin deficiency should receive IV thiamin 100 mg before receiving IV glucose solutions.
References [ + ]
|1, 2, 3, 4, 8, 39, 54, 60, 63, 77, 82, 91.||↵||Said HM. Thiamin. In: Coates PM, Betz JM, Blackman MR, et al., eds. Encyclopedia of Dietary Supplements. 2nd ed. London and New York: Informa Healthcare; 2010:748-53.|
|5, 42, 43, 61, 69, 71, 72, 78, 85.||↵||Bettendorff L. Thiamin. In: Erdman JW, Macdonald IA, Zeisel SH, eds. Present Knowledge in Nutrition. 10th ed. Washington, DC: Wiley-Blackwell; 2012:261-79.|
|6, 9, 10, 45, 50, 51, 58, 62, 64, 70, 73, 79, 83.||↵||Bemeur C, Butterworth RF. Thiamin. In: Ross AC, Caballero B, Cousins RJ, Tucker KL, Ziegler TR, eds. Modern Nutrition in Health and Disease. 11th ed. Baltimore, MD: Lippincott Williams & Wilkins; 2014:317-24.|
|7.||↵||Nabokina SM, Said HM. A high-affinity and specific carrier-mediated mechanism for uptake of thiamine pyrophosphate by human colonic epithelial cells. Am J Physiol Gastrointest Liver Physiol 2012;303:G389-95. https://www.ncbi.nlm.nih.gov/pubmed/22628036?dopt=Abstract|
|11.||↵||Allen L, de Benoist B, Dary O, Hurrell R, eds. Guidelines on Food Fortiﬁcation with Micronutrientsexternal link disclaimer. Geneva: World Health Organization and Food and Agricultural Organization of the United Nations; 2006.|
|12.||↵||Gibson GE, Blass JP. Thiamine-dependent processes and treatment strategies in neurodegeneration. Antioxid Redox Signal 2007;9:1605-19. https://www.ncbi.nlm.nih.gov/pubmed/17685850?dopt=Abstract|
|13.||↵||Page GL, Laight D, Cummings MH. Thiamine deficiency in diabetes mellitus and the impact of thiamine replacement on glucose metabolism and vascular disease. Int J Clin Pract 2011;65:684-90. https://www.ncbi.nlm.nih.gov/pubmed/21564442?dopt=Abstract|
|14, 97.||↵||Jermendy G. Evaluating thiamine deficiency in patients with diabetes. Diab Vasc Dis Res 2006;3:120-1. https://www.ncbi.nlm.nih.gov/pubmed/17058632?dopt=Abstract|
|15.||↵||Gonzalez-Ortiz M, Martinez-Abundis E, Robles-Cervantes JA, Ramirez-Ramirez V, Ramos-Zavala MG. Effect of thiamine administration on metabolic profile, cytokines and inflammatory markers in drug-naive patients with type 2 diabetes. Eur J Nutr 2011;50:145-9. https://www.ncbi.nlm.nih.gov/pubmed/20652275?dopt=Abstract|
|16.||↵||Alaei Shahmiri F, Soares MJ, Zhao Y, Sherriff J. High-dose thiamine supplementation improves glucose tolerance in hyperglycemic individuals: a randomized, double-blind cross-over trial. Eur J Nutr 2013;52:1821-4. https://www.ncbi.nlm.nih.gov/pubmed/23715873?dopt=Abstract|
|17.||↵||Stracke H, Gaus W, Achenbach U, Federlin K, Bretzel RG. Benfotiamine in diabetic polyneuropathy (BENDIP): results of a randomised, double blind, placebo-controlled clinical study. Exp Clin Endocrinol Diabetes 2008;116:600-5. https://www.ncbi.nlm.nih.gov/pubmed/18473286?dopt=Abstract|
|18.||↵||Carpenter KJ. The discovery of thiamin. Ann Nutr Metab 2012;61:219-23. https://www.ncbi.nlm.nih.gov/pubmed/23183292?dopt=Abstract|
|19.||↵||Rabbani N, Alam SS, Riaz S, Larkin JR, Akhtar MW, Shafi T, et al. High-dose thiamine therapy for patients with type 2 diabetes and microalbuminuria: a randomised, double-blind placebo-controlled pilot study. Diabetologia 2009;52:208-12. https://www.ncbi.nlm.nih.gov/pubmed/19057893?dopt=Abstract|
|20.||↵||Alkhalaf A, Klooster A, van Oeveren W, Achenbach U, Kleefstra N, Slingerland RJ, et al. A double-blind, randomized, placebo-controlled clinical trial on benfotiamine treatment in patients with diabetic nephropathy. Diabetes Care 2010;33:1598-601. https://www.ncbi.nlm.nih.gov/pubmed/20413516?dopt=Abstract|
|21.||↵||Wooley JA. Characteristics of thiamin and its relevance to the management of heart failure. Nutr Clin Pract 2008;23:487-93. https://www.ncbi.nlm.nih.gov/pubmed/18849553?dopt=Abstract|
|22, 24.||↵||DiNicolantonio JJ, Niazi AK, Lavie CJ, O’Keefe JH, Ventura HO. Thiamine supplementation for the treatment of heart failure: a review of the literature. Congest Heart Fail 2013;19:214-22. https://www.ncbi.nlm.nih.gov/pubmed/23910704?dopt=Abstract|
|23.||↵||Hanninen SA, Darling PB, Sole MJ, Barr A, Keith ME. The prevalence of thiamin deficiency in hospitalized patients with congestive heart failure. J Am Coll Cardiol 2006;47:354-61. https://www.ncbi.nlm.nih.gov/pubmed/16412860?dopt=Abstract|
|25.||↵||DiNicolantonio JJ, Lavie CJ, Niazi AK, O’Keefe JH, Hu T. Effects of thiamine on cardiac function in patients with systolic heart failure: systematic review and metaanalysis of randomized, double-blind, placebo-controlled trials. Ochsner J 2013;13:495-9. https://www.ncbi.nlm.nih.gov/pubmed/24357996?dopt=Abstract|
|26.||↵||Gibson GE, Hirsch JA, Cirio RT, Jordan BD, Fonzetti P, Elder J. Abnormal thiamine-dependent processes in Alzheimer’s Disease. Lessons from diabetes. Mol Cell Neurosci 2013;55:17-25. https://www.ncbi.nlm.nih.gov/pubmed/22982063?dopt=Abstract|
|27.||↵||Gibson GE, Sheu KF, Blass JP, Baker A, Carlson KC, Harding B, et al. Reduced activities of thiamine-dependent enzymes in the brains and peripheral tissues of patients with Alzheimer’s disease. Arch Neurol 1988;45:836-40. https://www.ncbi.nlm.nih.gov/pubmed/3395256?dopt=Abstract|
|28.||↵||Butterworth RF, Besnard AM. Thiamine-dependent enzyme changes in temporal cortex of patients with Alzheimer’s disease. Metab Brain Dis 1990;5:179-84. https://www.ncbi.nlm.nih.gov/pubmed/2087217?dopt=Abstract|
|29, 87.||↵||Vognar L, Stoukides J. The role of low plasma thiamin levels in cognitively impaired elderly patients presenting with acute behavioral disturbances. J Am Geriatr Soc 2009;57:2166-8. https://www.ncbi.nlm.nih.gov/pubmed/20121971?dopt=Abstract|
|30.||↵||Rodriguez-Martin JL, Qizilbash N, Lopez-Arrieta JM. Thiamine for Alzheimer’s disease. Cochrane Database Syst Rev 2001:CD001498. https://www.ncbi.nlm.nih.gov/pubmed/10796655?dopt=Abstract|
|31.||↵||Blass JP, Gleason P, Brush D, DiPonte P, Thaler H. Thiamine and Alzheimer’s disease. A pilot study. Arch Neurol 1988;45:833-5. https://www.ncbi.nlm.nih.gov/pubmed/2969232?dopt=Abstract|
|32.||↵||Nolan KA, Black RS, Sheu KF, Langberg J, Blass JP. A trial of thiamine in Alzheimer’s disease. Arch Neurol 1991;48:81-3. https://www.ncbi.nlm.nih.gov/pubmed/1986730?dopt=Abstract|
|33.||↵||Meador K, Loring D, Nichols M, Zamrini E, Rivner M, Posas H, et al. Preliminary findings of high-dose thiamine in dementia of Alzheimer’s type. J Geriatr Psychiatry Neurol 1993;6:222-9. https://www.ncbi.nlm.nih.gov/pubmed/8251051?dopt=Abstract|
|34, 35.||↵||Day E, Bentham PW, Callaghan R, Kuruvilla T, George S. Thiamine for prevention and treatment of Wernicke-Korsakoff Syndrome in people who abuse alcohol. Cochrane Database Syst Rev 2013;7:CD004033. https://www.ncbi.nlm.nih.gov/pubmed/23818100?dopt=Abstract|
|36.||↵||Galvin R, Brathen G, Ivashynka A, Hillbom M, Tanasescu R, Leone MA. EFNS guidelines for diagnosis, therapy and prevention of Wernicke encephalopathy. Eur J Neurol 2010;17:1408-18. https://www.ncbi.nlm.nih.gov/pubmed/20642790?dopt=Abstract|
|37.||↵||Thomson AD, Cook CC, Touquet R, Henry JA. The Royal College of Physicians report on alcohol: guidelines for managing Wernicke’s encephalopathy in the accident and Emergency Department. Alcohol Alcohol 2002;37:513-21. https://www.ncbi.nlm.nih.gov/pubmed/12414541?dopt=Abstract|
|38, 40.||↵||National Institutes of Health. Dietary Supplement Label Database. 2014.|
|41.||↵||Aguilar F, Charrondiere UR, Dusemund B, Galtier P, Gilbert J, Gott DM, et al. Benfotiamine, thiamine monophosphate chloride and thiamine pyrophosphate chloride, as sources of vitamin B1 added for nutritional purposes to food supplements: Scientific Opinion of the Panel on Food Additives and Nutrient Sources added to Food (ANS). EFSA J 2008;864:1-31.|
|44.||↵||Sharma S, Sheehy T, Kolonel LN. Ethnic differences in grains consumption and their contribution to intake of B-vitamins: results of the Multiethnic Cohort Study. Nutr J 2013;12:65. https://www.ncbi.nlm.nih.gov/pubmed/23688109?dopt=Abstract|
|46, 56.||↵||Fulgoni VL, 3rd, Keast DR, Bailey RL, Dwyer J. Foods, fortificants, and supplements: Where do Americans get their nutrients? J Nutr 2011;141:1847-54. https://www.ncbi.nlm.nih.gov/pubmed/21865568?dopt=Abstract|
|47, 52.||↵||The USDA Food Composition Databases. https://ndb.nal.usda.gov/ndb/|
|48.||↵||The USDA Food Composition Databases. Thiamine Content. https://ods.od.nih.gov/pubs/usdandb/Thiamin-Content.pdf|
|49.||↵||The USDA Food Composition Databases. Foods Thiamine Content. https://ods.od.nih.gov/pubs/usdandb/Thiamin-Food.pdf|
|53, 59, 86.||↵||Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes: Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington, DC: National Academy Press; 1998.|
|55.||↵||U.S. Department of Agriculture, Agricultural Research Service. USDA National Nutrient Database for Standard Reference, Release 27. Nutrient Data Laboratory home page, 2014. https://ndb.nal.usda.gov/ndb/|
|57.||↵||U.S. Department of Agriculture, Agricultural Research Service. What We Eat in America, 2013-2014. 2012. https://www.ars.usda.gov/northeast-area/beltsville-md/beltsville-human-nutrition-research-center/food-surveys-research-group/docs/wweia-data-tables/|
|65.||↵||Yang JD, Acharya K, Evans M, Marsh JD, Beland S. Beriberi disease: is it still present in the United States? Am J Med 2012;125:e5. https://www.ncbi.nlm.nih.gov/pubmed/22800868?dopt=Abstract|
|66.||↵||Howard AJ, Kulkarni O, Lekwuwa G, Emsley HC. Rapidly progressive polyneuropathy due to dry beriberi in a man: a case report. J Med Case Rep 2010;4:409. https://www.ncbi.nlm.nih.gov/pubmed/21176139?dopt=Abstract|
|67.||↵||Essa E, Velez MR, Smith S, Giri S, Raman SV, Gumina RJ. Cardiovascular magnetic resonance in wet beriberi. J Cardiovasc Magn Reson 2011;13:41. https://www.ncbi.nlm.nih.gov/pubmed/21838901?dopt=Abstract|
|68.||↵||Imai N, Kubota M, Saitou M, Yagi N, Serizawa M, Kobari M. Increase of serum vascular endothelial growth factors in wet beriberi: two case reports. Intern Med 2012;51:929-32. https://www.ncbi.nlm.nih.gov/pubmed/22504253?dopt=Abstract|
|74, 84.||↵||Agabio R. Thiamine administration in alcohol-dependent patients. Alcohol Alcohol 2005;40:155-6. https://www.ncbi.nlm.nih.gov/pubmed/15550446?dopt=Abstract|
|75.||↵||Thomson AD, Marshall EJ. The natural history and pathophysiology of Wernicke’s Encephalopathy and Korsakoff’s Psychosis. Alcohol Alcohol 2006;41:151-8. https://www.ncbi.nlm.nih.gov/pubmed/16384871?dopt=Abstract|
|76.||↵||Thomson AD, Guerrini I, Marshall EJ. The evolution and treatment of Korsakoff’s syndrome: out of sight, out of mind? Neuropsychol Rev 2012;22:81-92. https://www.ncbi.nlm.nih.gov/pubmed/22569770?dopt=Abstract|
|80.||↵||Kopelman MD, Thomson AD, Guerrini I, Marshall EJ. The Korsakoff syndrome: clinical aspects, psychology and treatment. Alcohol Alcohol 2009;44:148-54. https://www.ncbi.nlm.nih.gov/pubmed/19151162?dopt=Abstract|
|81.||↵||World Health Organization. Thiamine Deficiency and Its Prevention and Control in Major Emergencies. Geneva; 1999. http://www.who.int/nutrition/publications/en/thiamine_in_emergencies_eng.pdf|
|88.||↵||Wilkinson TJ, Hanger HC, George PM, Sainsbury R. Is thiamine deficiency in elderly people related to age or co-morbidity? Age and Ageing 2000;29:111-6. https://www.ncbi.nlm.nih.gov/pubmed/10791444?dopt=Abstract|
|89.||↵||O’Rourke NP, Bunker VW, Thomas AJ, Finglas PM, Bailey AL, Clayton BE. Thiamine Status of Healthy and Institutionalized Elderly Subjects: Analysis of Dietary Intake and Biochemical Indices. Age Ageing 1990;19:325-9. https://www.ncbi.nlm.nih.gov/pubmed/2251966?dopt=Abstract|
|90.||↵||Ito Y, Yamanaka K, Susaki H, Igata A. A cross-investigation between thiamin deficiency and the physical condition of elderly people who require nursing care. J Nutr Sci Vitaminol (Tokyo) 2012;58:210-6. https://www.ncbi.nlm.nih.gov/pubmed/22878392?dopt=Abstract|
|92.||↵||Lu’o’ng KV, Nguyen LT. The role of thiamine in cancer: possible genetic and cellular signaling mechanisms. Cancer Genomics Proteomics 2013;10:169-85. https://www.ncbi.nlm.nih.gov/pubmed/23893925?dopt=Abstract|
|93.||↵||Boldorini R, Vago L, Lechi A, Tedeschi F, Trabattoni GR. Wernicke’s encephalopathy: occurrence and pathological aspects in a series of 400 AIDS patients. Acta Biomed Ateneo Parmense 1992;63:43-9. https://www.ncbi.nlm.nih.gov/pubmed/1340667?dopt=Abstract|
|94.||↵||Larsen TR, Dragu D, Williams M. Wernicke’s Encephalopathy: An Unusual Consequence of the Acquired Immune Deficiency Syndrome-Case Report and Literature Review. Case Rep Med 2013;2013:709474. https://www.ncbi.nlm.nih.gov/pubmed/23935638?dopt=Abstract|
|95.||↵||Thornalley PJ, Babaei-Jadidi R, Al Ali H, Rabbani N, Antonysunil A, Larkin J, et al. High prevalence of low plasma thiamine concentration in diabetes linked to a marker of vascular disease. Diabetologia 2007;50:2164-70. https://www.ncbi.nlm.nih.gov/pubmed/17676306?dopt=Abstract|
|96.||↵||Al-Attas OS, Al-Daghri NM, Alfadda AA, Abd-Alrahman SH, Sabico S. Blood thiamine and its phosphate esters as measured by high-performance liquid chromatography: levels and associations in diabetes mellitus patients with varying degrees of microalbuminuria. J Endocrinol Invest 2012;35:951-6. https://www.ncbi.nlm.nih.gov/pubmed/22107884?dopt=Abstract|
|98.||↵||Saito N, Kimura M, Kuchiba A, Itokawa Y. Blood thiamine levels in outpatients with diabetes mellitus. J Nutr Sci Vitaminol (Tokyo) 1987;33:421-30. https://www.ncbi.nlm.nih.gov/pubmed/3451944?dopt=Abstract|
|99.||↵||Aasheim ET. Wernicke encephalopathy after bariatric surgery: a systematic review. Ann Surg 2008;248:714-20. https://www.ncbi.nlm.nih.gov/pubmed/18948797?dopt=Abstract|
|100.||↵||Xanthakos SA. Nutritional deficiencies in obesity and after bariatric surgery. Pediatr Clin North Am 2009;56:1105-21. https://www.ncbi.nlm.nih.gov/pubmed/19931066?dopt=Abstract|