beriberi

What is beriberi

Beriberi is a condition that occurs in people who are deficient in thiamin (vitamin B1). There are two major types of beriberi: wet beriberi which affects the cardiovascular system and dry beriberi which affects the nervous system 1). People with wet beriberi may experience increased heart rate, shortness of breath, and swelling of the lower legs 2). Signs and symptoms of dry beriberi include difficulty walking; loss of feeling in the hands and/or feet; paralysis of the lower legs; mental confusion; speech difficulty; pain; and/or vomiting.

Beriberi is rare in the United States since many foods are now vitamin enriched; however, alcohol abuse, dialysis and taking high doses of diuretics increases the risk of developing the condition 3). In most cases, beriberi occurs sporadically in people with no family history of the condition. A rare condition known as genetic beriberi is inherited (passed down through families) and is associated with an inability to absorb thiamine from foods. Beriberi treatment generally includes thiamine supplementation, given by injection or taken by mouth. With treatment, symptoms usually improve quickly.

Untreated, beriberi can be fatal. Heart damage is usually reversible. A full recovery is expected in these cases. However, if acute heart failure has already occurred, the outlook is poor. Nervous system damage is also reversible, if caught early. If it is not caught early, some symptoms (such as memory loss) may remain even with treatment.

If a person with Wernicke encephalopathy receives thiamine replacement, language problems, unusual eye movements, and walking difficulties may go away. However, Korsakoff syndrome (or Korsakoff psychosis) tends to develop as Wernicke symptoms go away.

Wernicke-Korsakoff syndrome

Wernicke-Korsakoff syndrome is one of the most severe neuropsychiatric sequelae of alcohol abuse 4). 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 5). 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 6). 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 7). 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.

Beriberi complications

Beriberi complications may include:

  • Coma
  • Congestive heart failure
  • Death
  • Psychosis

Beriberi causes

Beriberi is caused by thiamine (vitamin B1) deficiency or the lack of thiamine pyrophosphate, the active form of thiamine (also spelled thiamin). Thiamine pyrophosphate, the biologically active form of thiamine, acts as a coenzyme in carbohydrate metabolism through the decarboxylation of alpha ketoacids. It also takes part in the formation of glucose by acting as a coenzyme for the transketolase in the pentose monophosphate pathway. 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 8). Thiamine diphosphate serves as an essential cofactor for five enzymes involved in glucose, amino acid, and lipid metabolism 9), 10).

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 11). 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 12). 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 13).

Beriberi is rare in the United States. This is because most foods are now vitamin enriched. If you eat a normal, healthy diet, you should get enough thiamine. Today, beriberi occurs mostly in people who abuse alcohol. Drinking heavily can lead to poor nutrition. Excess alcohol makes it harder for the body to absorb and store vitamin B1 (thiamine).

In rare cases, beriberi can be genetic. This condition is passed down through families. People with this condition lose the ability to absorb thiamine from foods. This can happen slowly over time. The symptoms occur when the person is an adult. However, this diagnosis is often missed. This is because health care providers may not consider beriberi in nonalcoholics.

There are two major types of beriberi:

  • Wet beriberi: Affects the cardiovascular system.
  • Dry beriberi and Wernicke-Korsakoff syndrome: Affects the nervous system.

Beriberi can occur in infants when they are:

  • Breastfed and the mother’s body is lacking in thiamine
  • Fed unusual formulas that don’t have enough thiamine

Some medical treatments that can raise your risk of beriberi are:

  • Getting dialysis
  • Taking high doses of diuretics (water pills)

Beriberi signs and symptoms

Symptoms of dry beriberi include:

  • Difficulty walking
  • Loss of feeling (sensation) in hands and feet
  • Loss of muscle function or paralysis of the lower legs
  • Mental confusion/speech difficulties
  • Pain
  • Strange eye movements (nystagmus)
  • Tingling
  • Vomiting

Symptoms of wet beriberi include:

  • Awakening at night short of breath
  • Increased heart rate
  • Shortness of breath with activity
  • Swelling of the lower legs

Beriberi diagnosis

A physical examination may show signs of congestive heart failure, including:

  • Difficulty breathing with neck veins that stick out
  • Enlarged heart
  • Fluid in the lungs
  • Rapid heartbeat
  • Swelling in both lower legs

A person with late-stage beriberi may be confused or have memory loss and delusions. The person may be less able to sense vibrations.

A neurological exam may show signs of:

  • Changes in the walk
  • Coordination problems
  • Decreased reflexes
  • Drooping of the eyelids

The following tests may be done:

  • Blood tests to measure the amount of thiamine in the blood
  • Urine tests to see if thiamine is passing through the urine

Beriberi treatment

The goal of treatment is to replace the thiamine your body is lacking. This is done with thiamine supplements. Thiamine supplements are given through a shot (injection) or taken by mouth.

Your provider may also suggest other types of vitamins.

Blood tests may be repeated after the treatment is started. These tests will show how well you are responding to the medicine.

Thiamine Deficiency

In addition to insufficient intakes of thiamine from the diet, the causes of thiamine 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 14).

  • 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, thiamine 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) 15).

The most common effect of thiamin deficiency is beriberi, which is characterized mainly by peripheral neuropathy and wasting 16), 17), 18). 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 19), 20). Although beriberi is rare in the United States and other developed countries, people in these countries do occasionally develop the condition 21), 22), 23), 24). Administration of supplemental thiamine, often parenterally, quickly cures beriberi 25), 26).

A more common manifestation of thiamin deficiency in the United States is Wernicke-Korsakoff syndrome 27). 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 28). 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 29), 30). 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 31), 32). 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) 33), 34), 35). At this chronic state of the disorder, parenteral thiamin treatment does not lead to recovery in about one-quarter of patients 36).

The World Health Organization recommends daily oral doses of 10 mg thiamine for a week, followed by 3–5 mg/daily for at least 6 weeks, to treat mild thiamin deficiency 37). 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 thiamine for at least 6 weeks.

What foods provide thiamine ?

Food sources of thiamin include whole grains, meat, and fish 38). Breads, cereals, and infant formulas in the United States and many other countries are fortified with thiamine 39).The most common sources of thiamin in the U.S. diet are cereals and bread 40). Pork is another major source of the vitamin. Dairy products and most fruits contain little thiamine 41). 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 42).

The U.S. Department of Agriculture’s (USDA’s) Nutrient Database website 43) lists the nutrient content of many foods and provides a comprehensive list of foods containing thiamin arranged by nutrient content 44) and by food name 45).

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% 46). Because thiamin dissolves in water, a significant amount of the vitamin is lost when cooking water is thrown out 47). 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 48).

Data on the bioavailability of thiamine from food are very limited 49). Some studies do show, however, that thiamin absorption increases when intakes are low 50).

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 1: Selected Food Sources of Thiamine

FoodMilligrams
(mg) per
serving
Percent
DV*
Breakfast cereals, fortified with 100% of the DV for thiamin, 1 serving1.5100
Rice, white, long grain, enriched, parboiled, ½ cup1.473
Egg noodles, enriched, cooked, 1 cup0.533
Pork chop, bone-in, broiled, 3 ounces0.427
Trout, cooked, dry heat, 3 ounces0.427
Black beans, boiled, ½ cup0.427
English muffin, plain, enriched, 1 muffin0.320
Mussels, blue, cooked, moist heat, 3 ounces0.320
Tuna, Bluefin, cooked, dry heat, 3 ounces0.213
Macaroni, whole wheat, cooked, 1 cup0.213
Acorn squash, cubed, baked, ½ cup0.213
Rice, brown, long grain, not enriched, cooked, ½ cup0.17
Bread, whole wheat, 1 slice0.17
Orange juice, prepared from concentrate, 1 cup0.17
Sunflower seeds, toasted, 1 ounce0.17
Beef steak, bottom round, trimmed of fat, braised, 3 ounces0.17
Yogurt, plain, low fat, 1 cup0.17
Oatmeal, regular and quick, unenriched, cooked with water, ½ cup0.17
Corn, yellow, boiled, 1 medium ear0.17
Milk, 2%, 1 cup0.17
Barley, pearled, cooked, 1 cup0.17
Cheddar cheese, 1½ ounces00
Chicken, meat and skin, roasted, 3 ounces00
Apple, sliced, 1 cup00

*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 51)]

The amount of thiamin you need depends on your age and sex. Average daily recommended amounts are listed below in milligrams (mg).

Life StageRecommended Amount
Birth to 6 months0.2 mg
Infants 7–12 months0.3 mg
Children 1–3 years0.5 mg
Children 4–8 years0.6 mg
Children 9–13 years0.9 mg
Teen boys 14–18 years1.2 mg
Teen girls 14–18 years1.0 mg
Men1.2 mg
Women1.1 mg
Pregnant teens and women1.4 mg
Breastfeeding teens and women1.4 mg

Causes of Thiamin (Vitamin B1) Deficiency

Primary thiamine deficiency is caused by

  • Inadequate intake of thiamine

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 thiamine-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 thiamine deficiency; they include decreased intake, impaired absorption and use, increased demand, and possibly an apoenzyme defect.

Because thiamine is necessary for glucose metabolism, glucose infusions may precipitate or worsen symptoms of deficiency in thiamine-deficient people.

Groups at Risk of Thiamine Deficiency

The following groups are among those most likely to have inadequate thiamine status.

  • People with alcohol dependence

In highly industrialized countries, chronic alcohol use disorders appear to be the most common cause of thiamine deficiency 52). 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 53), 54). 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 thiamine deficiency 55), 56). 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 57), 58). Some small studies have found that the risk of deficiency is particularly high in elderly people who reside in an institution 59), 60).

  • People with HIV/AIDS

People with HIV infection have an increased risk of thiamine deficiency and its sequelae, including beriberi and Wernicke-Korsakoff syndrome 61), 62). Autopsies of 380 people with AIDS found that almost 10% had Wernicke’s encephalopathy 63), and some experts believe that thiamin deficiency is underdiagnosed in this population 64). The association between thiamine 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 thiamine 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 65), 66). 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 67), 68). 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 69). 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 70).

Diagnosis of Thiamine Deficiency

  • Favorable response to thiamine

Diagnosis of thiamine deficiency is usually based on a favorable response to treatment with thiamine 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 thiamine, with dose based on clinical manifestations

Ensuring that dietary supplies of thiamine are adequate is important regardless of symptoms.

Because IV glucose can worsen thiamine deficiency, alcoholics and others at risk of thiamine deficiency should receive IV thiamine 100 mg before receiving IV glucose solutions.

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