Thiamine deficiency is a medical condition of low levels of
thiamine
Thiamine, also known as thiamin and vitamin B1, is a vitamin, an essential micronutrient, that cannot be made in the body. It is found in food and commercially synthesized to be a dietary supplement or medication. Phosphorylated forms of thi ...
(Vitamin B
1).
[ A severe and chronic form is known as beriberi.] The two main types in adults are wet beriberi and dry beriberi.[ Wet beriberi affects the ]cardiovascular system
The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, tha ...
, resulting in a fast heart rate, shortness of breath
Shortness of breath (SOB), also medically known as dyspnea (in AmE) or dyspnoea (in BrE), is an uncomfortable feeling of not being able to breathe well enough. The American Thoracic Society defines it as "a subjective experience of breathing disc ...
, and leg swelling.[ Dry beriberi affects the ]nervous system
In biology, the nervous system is the highly complex part of an animal that coordinates its actions and sensory information by transmitting signals to and from different parts of its body. The nervous system detects environmental changes th ...
, resulting in numbness of the hands and feet, confusion, trouble moving the legs, and pain.[ A form with loss of appetite and ]constipation
Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the bowel movement ...
may also occur. Another type, acute beriberi, found mostly in babies, presents with loss of appetite, vomiting, lactic acidosis
Lactic acidosis is a medical condition characterized by a build-up of lactate (especially -lactate) in the body, with formation of an excessively low pH in the bloodstream. It is a form of metabolic acidosis, in which excessive acid accumulates ...
, changes in heart rate, and enlargement of the heart.
Risk factors include a diet of mostly white rice
White rice is milled rice that has had its husk, bran, and germ removed. This alters the flavor, texture and appearance of the rice and helps prevent spoilage, extend its storage life, and makes it easier to digest. After milling (hulling), the ...
, alcoholism
Alcoholism is, broadly, any drinking of alcohol (drug), alcohol that results in significant Mental health, mental or physical health problems. Because there is disagreement on the definition of the word ''alcoholism'', it is not a recognize ...
, dialysis Dialysis may refer to:
*Dialysis (chemistry), a process of separating molecules in solution
**Electrodialysis, used to transport salt ions from one solution to another through an ion-exchange membrane under the influence of an applied electric pote ...
, chronic diarrhea
Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin wi ...
, and taking high doses of diuretics
A diuretic () is any substance that promotes diuresis, the increased production of urine. This includes forced diuresis. A diuretic tablet is sometimes colloquially called a water tablet. There are several categories of diuretics. All diuretics in ...
.[ In rare cases, it may be due to a genetic condition that results in difficulties absorbing thiamine found in food.][ ]Wernicke encephalopathy
Wernicke encephalopathy (WE), also Wernicke's encephalopathy, or wet brain is the presence of neurological symptoms caused by biochemical lesions of the central nervous system after exhaustion of B-vitamin reserves, in particular thiamine (vita ...
and Korsakoff syndrome
Korsakoff syndrome (KS) is a disorder of the central nervous system characterized by amnesia, deficits in explicit memory, and confabulation. This neurological disorder is caused by a deficiency of thiamine (vitamin B1) in the brain, and it i ...
are forms of dry beriberi. Diagnosis is based on symptoms, low levels of thiamine in the urine, high blood lactate, and improvement with thiamine supplementation
Thiamine, also known as thiamin and vitamin B1, is a vitamin, an essential micronutrient, that cannot be made in the body. It is found in food and commercially synthesized to be a dietary supplement or medication. Phosphorylated forms of thia ...
.
Treatment is by thiamine supplementation, either by mouth or by injection.[ With treatment, symptoms generally resolve in a few weeks.][ The disease may be prevented at the population level through the ]fortification of food
Food fortification or enrichment is the process of adding micronutrients (essential trace elements and vitamins) to food. It can be carried out by food manufacturers, or by governments as a public health policy which aims to reduce the number of p ...
.[
Thiamine deficiency is rare in the United States. It remains relatively common in ]sub-Saharan Africa
Sub-Saharan Africa is, geographically, the area and regions of the continent of Africa that lies south of the Sahara. These include West Africa, East Africa, Central Africa, and Southern Africa. Geopolitically, in addition to the List of sov ...
. Outbreaks have been seen in refugee camps
A refugee camp is a temporary settlement built to receive refugees and people in refugee-like situations. Refugee camps usually accommodate displaced people who have fled their home country, but camps are also made for internally displaced peo ...
.[ Thiamine deficiency has been described for thousands of years in Asia, and became more common in the late 1800s with the increased processing of rice.]
Signs and symptoms
Symptoms of beriberi include weight loss, emotion
Emotions are mental states brought on by neurophysiological changes, variously associated with thoughts, feelings, behavioral responses, and a degree of pleasure or displeasure. There is currently no scientific consensus on a definition. ...
al disturbances, impaired sensory perception
Perception () is the organization, identification, and interpretation of sensory information in order to represent and understand the presented information or environment. All perception involves signals that go through the nervous system ...
, weakness
Weakness is a symptom of a number of different conditions. The causes are many and can be divided into conditions that have true or perceived muscle weakness. True muscle weakness is a primary symptom of a variety of skeletal muscle diseases, i ...
and pain
Pain is a distressing feeling often caused by intense or damaging stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sensory and emotional experience associated with, or resembling that associated with, ...
in the limbs, and periods of irregular heart rate
Heart rate (or pulse rate) is the frequency of the heartbeat measured by the number of contractions (beats) of the heart per minute (bpm). The heart rate can vary according to the body's physical needs, including the need to absorb oxygen and excr ...
. Edema
Edema, also spelled oedema, and also known as fluid retention, dropsy, hydropsy and swelling, is the build-up of fluid in the body's Tissue (biology), tissue. Most commonly, the legs or arms are affected. Symptoms may include skin which feels t ...
(swelling of bodily tissues) is common. It may increase the amount of lactic acid
Lactic acid is an organic acid. It has a molecular formula . It is white in the solid state and it is miscible with water. When in the dissolved state, it forms a colorless solution. Production includes both artificial synthesis as well as natu ...
and pyruvic acid
Pyruvic acid (CH3COCOOH) is the simplest of the alpha-keto acids, with a carboxylic acid and a ketone functional group. Pyruvate, the conjugate base, CH3COCOO−, is an intermediate in several metabolic pathways throughout the cell.
Pyruvic aci ...
within the blood. In advanced cases, the disease may cause high-output cardiac failure
High-output heart failure is a heart condition that occurs when the cardiac output is higher than normal due to increased peripheral demand. There is a circulatory overload which may lead to pulmonary edema secondary to an elevated diastolic press ...
and death.
Symptoms may occur concurrently with those of Wernicke's encephalopathy, a primarily neurological thiamine deficiency-related condition.
Beriberi is divided into four categories. The first three are historical and the fourth, gastrointestinal beriberi, was recognized in 2004:
*Dry beriberi especially affects the peripheral nervous system.
*Wet beriberi especially affects the cardiovascular system and other bodily systems.
*Infantile beriberi affects the babies of malnourished mothers.
*Gastrointestinal beriberi affects the digestive system and other bodily systems.
Dry beriberi
Dry beriberi causes wasting and partial paralysis
Paralysis (also known as plegia) is a loss of motor function in one or more muscles. Paralysis can also be accompanied by a loss of feeling (sensory loss) in the affected area if there is sensory damage. In the United States, roughly 1 in 50 ...
resulting from damaged peripheral nerve
A nerve is an enclosed, cable-like bundle of nerve fibers (called axons) in the peripheral nervous system.
A nerve transmits electrical impulses. It is the basic unit of the peripheral nervous system. A nerve provides a common pathway for the e ...
s. It is also referred to as endemic neuritis. It is characterized by:
*Difficulty with walking
*Tingling or loss of sensation (numbness
Hypoesthesia or numbness is a common side effect of various medical conditions that manifests as a reduced sense of touch or sensation, or a partial loss of sensitivity to sensory stimuli. In everyday speech this is generally referred to as num ...
) in hands and feet
*Loss of tendon reflexes[
*Loss of muscle function or paralysis of the lower legs
*Mental confusion/speech difficulties
*Pain
*Involuntary eye movements (]nystagmus
Nystagmus is a condition of involuntary (or voluntary, in some cases) eye movement. Infants can be born with it but more commonly acquire it in infancy or later in life. In many cases it may result in reduced or limited vision. Due to the invol ...
)
*Vomiting
A selective impairment of the large proprioceptive sensory fibers without motor impairment can occur and present as a prominent sensory ataxia
Ataxia is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in eye movements. Ataxia is a clinical manifestation indicating dysfunction of ...
, which is a loss of balance and coordination due to loss of the proprioceptive inputs from the periphery and loss of position sense.
Brain disease
Wernicke's encephalopathy (WE), Korsakoff syndrome
Korsakoff syndrome (KS) is a disorder of the central nervous system characterized by amnesia, deficits in explicit memory, and confabulation. This neurological disorder is caused by a deficiency of thiamine (vitamin B1) in the brain, and it i ...
(also called alcohol amnestic disorder), and Wernicke–Korsakoff syndrome
Wernicke–Korsakoff syndrome (WKS) is the combined presence of Wernicke encephalopathy (WE) and Korsakoff syndrome. Due to the close relationship between these two disorders, people with either are usually diagnosed with WKS as a single syndrome ...
are forms of dry beriberi.[
Wernicke's encephalopathy is the most frequently encountered manifestation of thiamine deficiency in Western society,] though it may also occur in patients with impaired nutrition from other causes, such as gastrointestinal disease, those with HIV/AIDS
Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV), a retrovirus. Following initial infection an individual ...
, and with the injudicious administration of parenteral
A route of administration in pharmacology and toxicology is the way by which a drug, fluid, poison, or other substance is taken into the body.
Routes of administration are generally classified by the location at which the substance is applied. ...
glucose or hyperalimentation
Overnutrition (also known as hyperalimentation) is a form of malnutrition in which the intake of nutrients is oversupplied. The amount of nutrients exceeds the amount required for normal growth, development, and metabolism.
The term can also ref ...
without adequate B-vitamin supplementation. This is a striking neuro-psychiatric disorder characterized by paralysis of eye movements, abnormal stance and gait, and markedly deranged mental function.
Korsakoff syndrome
Korsakoff syndrome (KS) is a disorder of the central nervous system characterized by amnesia, deficits in explicit memory, and confabulation. This neurological disorder is caused by a deficiency of thiamine (vitamin B1) in the brain, and it i ...
, in general, is considered to occur with deterioration of brain function in patients initially diagnosed with WE. This is an amnestic-confabulatory syndrome characterized by retrograde and anterograde amnesia
In neurology, anterograde amnesia is the inability to create new memories after the event that caused amnesia, leading to a partial or complete inability to recall the recent past, while long-term memories from before the event remain intact. T ...
, impairment of conceptual functions, and decreased spontaneity and initiative.[Butterworth RF. Thiamin. In: Shils ME, Shike M, Ross AC, Caballero B, Cousins RJ, editors. Modern Nutrition in Health and Disease, 10th ed. Baltimore: Lippincott Williams & Wilkins; 2006.]
Alcoholics may have thiamine deficiency because of:
* Inadequate nutritional intake: Alcoholics tend to intake less than the recommended amount of thiamine.
* Decreased uptake of thiamine from the GI tract: Active transport of thiamine into enterocytes is disturbed during acute alcohol exposure.
* Liver thiamine stores are reduced due to hepatic steatosis or fibrosis.
* Impaired thiamine utilization: Magnesium, which is required for the binding of thiamine to thiamine-using enzymes within the cell, is also deficient due to chronic alcohol consumption. The inefficient use of any thiamine that does reach the cells will further exacerbate the thiamine deficiency.
* Ethanol ''per se'' inhibits thiamine transport in the gastrointestinal system and blocks phosphorylation of thiamine to its cofactor form (ThDP).
Following improved nutrition and the removal of alcohol consumption, some impairments linked with thiamine deficiency are reversed, in particular poor brain functionality, although in more severe cases, Wernicke–Korsakoff syndrome leaves permanent damage. (See delirium tremens
Delirium tremens (DTs) is a rapid onset of confusion usually caused by withdrawal from alcohol. When it occurs, it is often three days into the withdrawal symptoms and lasts for two to three days. Physical effects may include shaking, shiver ...
.)
Wet beriberi
Wet beriberi affects the heart
The heart is a muscular organ in most animals. This organ pumps blood through the blood vessels of the circulatory system. The pumped blood carries oxygen and nutrients to the body, while carrying metabolic waste such as carbon dioxide t ...
and circulatory system. It is sometimes fatal, as it causes a combination of heart failure
Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...
and weakening of the capillary
A capillary is a small blood vessel from 5 to 10 micrometres (μm) in diameter. Capillaries are composed of only the tunica intima, consisting of a thin wall of simple squamous endothelial cells. They are the smallest blood vessels in the body: ...
walls, which causes the peripheral tissues to become edematous. Wet beriberi is characterized by:
*Increased heart rate
*Vasodilation
Vasodilation is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. The process is the opposite of vasoconstriction, ...
leading to decreased systemic vascular resistance, and high-output heart failure
*Elevated jugular venous pressure
The jugular venous pressure (JVP, sometimes referred to as ''jugular venous pulse'') is the indirectly observed pressure over the venous system via visualization of the internal jugular vein. It can be useful in the differentiation of different for ...
*Dyspnea (shortness of breath) on exertion
*Paroxysmal nocturnal dyspnea
Shortness of breath (SOB), also medically known as dyspnea (in AmE) or dyspnoea (in BrE), is an uncomfortable feeling of not being able to breathing, breathe well enough. The American Thoracic Society defines it as "a subjective experience of brea ...
*Peripheral edema
Edema, also spelled oedema, and also known as fluid retention, dropsy, hydropsy and swelling, is the build-up of fluid in the body's Tissue (biology), tissue. Most commonly, the legs or arms are affected. Symptoms may include skin which feels t ...
[ (swelling of lower legs) or generalized edema (swelling throughout the body)
*]Dilated cardiomyopathy
Dilated cardiomyopathy (DCM) is a condition in which the heart becomes enlarged and cannot pump blood effectively. Symptoms vary from none to feeling tired, leg swelling, and shortness of breath. It may also result in chest pain or fainting. Co ...
Gastrointestinal beriberi
Gastrointestinal beriberi causes abdominal pain. It is characterized by:
*Abdominal pain
*Nausea
*Vomiting
*Lactic acidosis
Infants
Infantile beriberi usually occurs between two and six months of age in children whose mothers have inadequate thiamine intake. It may present as either wet or dry beriberi.[
In the acute form, the baby develops ]dyspnea
Shortness of breath (SOB), also medically known as dyspnea (in AmE) or dyspnoea (in BrE), is an uncomfortable feeling of not being able to breathing, breathe well enough. The American Thoracic Society defines it as "a subjective experience of brea ...
and cyanosis
Cyanosis is the change of body tissue color to a bluish-purple hue as a result of having decreased amounts of oxygen bound to the hemoglobin in the red blood cells of the capillary bed. Body tissues that show cyanosis are usually in locations ...
and soon dies of heart failure. These symptoms may be described in infantile beriberi:
*Hoarseness, where the child makes moves to moan, but emits no sound or just faint moans caused by nerve paralysis[
*Weight loss, becoming thinner and then ]marasmic
Marasmus is a form of severe malnutrition characterized by energy deficiency. It can occur in anyone with severe malnutrition but usually occurs in children. Body weight is reduced to less than 62% of the normal (expected) body weight for the a ...
as the disease progresses[
*Vomiting][
*Diarrhea][
*Pale skin]
*Edema[
*Ill temper][
*Alterations of the cardiovascular system, especially ]tachycardia
Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal (su ...
(rapid heart rate)[
*]Convulsions
A convulsion is a medical condition where the body muscles contract and relax rapidly and repeatedly, resulting in uncontrolled shaking. Because epileptic seizures typically include convulsions, the term ''convulsion'' is sometimes used as a s ...
occasionally observed in the terminal stages[
]
Cause
Beriberi is often caused by eating a diet with a very high proportion of calorie rich polished rice
White rice is milled rice that has had its husk, bran, and germ removed. This alters the flavor, texture and appearance of the rice and helps prevent spoilage, extend its storage life, and makes it easier to digest. After milling (hulling), th ...
(common in Asia) or cassava root
''Manihot esculenta'', commonly called cassava (), manioc, or yuca (among numerous regional names), is a woody shrub of the spurge family, Euphorbiaceae, native to South America. Although a perennial plant, cassava is extensively cultivated a ...
(common in sub-Saharan Africa), without much if any thiamine containing animals or vegetables.
It may also be caused by shortcomings other than inadequate intake - diseases
A disease is a particular abnormal condition that negatively affects the structure or function of all or part of an organism, and that is not immediately due to any external injury. Diseases are often known to be medical conditions that ar ...
or operations on the digestive tract, alcoholism
Alcoholism is, broadly, any drinking of alcohol (drug), alcohol that results in significant Mental health, mental or physical health problems. Because there is disagreement on the definition of the word ''alcoholism'', it is not a recognize ...
, dialysis Dialysis may refer to:
*Dialysis (chemistry), a process of separating molecules in solution
**Electrodialysis, used to transport salt ions from one solution to another through an ion-exchange membrane under the influence of an applied electric pote ...
or genetic deficiencies
A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders ...
. All those causes mainly affect the central nervous system, and provoke the development of Wernicke's encephalopathy.
Wernicke's disease is one of the most prevalent neurological or neuropsychiatric diseases. In autopsy
An autopsy (post-mortem examination, obduction, necropsy, or autopsia cadaverum) is a surgical procedure that consists of a thorough examination of a corpse by dissection to determine the cause, mode, and manner of death or to evaluate any di ...
series, features of Wernicke lesions are observed in approximately 2% of general cases. Medical record research shows that about 85% had not been diagnosed, although only 19% would be asymptomatic. In children, only 58% were diagnosed. In alcohol abuse
Alcohol abuse encompasses a spectrum of unhealthy alcohol drinking behaviors, ranging from binge drinking to alcohol dependence, in extreme cases resulting in health problems for individuals and large scale social problems such as alcohol-relat ...
rs, autopsy series showed neurological damages at rates of 12.5% or more. Mortality caused by Wernicke's disease reaches 17% of diseases, which means 3.4/1000 or about 25 million contemporaries. The number of people with Wernicke's disease may be even higher, considering that early stages may have dysfunctions prior to the production of observable lesions at necropsy. In addition, uncounted numbers of people can experience fetal damage and subsequent diseases.
Genetics
Genetic diseases of thiamine transport are rare but serious. Thiamine responsive megaloblastic anemia syndrome
Thiamine responsive megaloblastic anemia syndrome (also known as Rogers Syndrome) is a very rare autosomal recessive genetic disorder affecting a thiamine transporter, which is characterized by megaloblastic anemia, diabetes mellitus, and hearing ...
(TRMA) with diabetes mellitus
Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...
and sensorineural deafness
Sensorineural hearing loss (SNHL) is a type of hearing loss in which the root cause lies in the inner ear or sensory organ (cochlea and associated structures) or the vestibulocochlear nerve (cranial nerve VIII). SNHL accounts for about 90% of rep ...
is an autosomal recessive disorder caused by mutations in the gene SLC19A2, a high affinity thiamine transporter. TRMA patients do not show signs of systemic thiamine deficiency, suggesting redundancy in the thiamine transport system. This has led to the discovery of a second high-affinity thiamine transporter, SLC19A3
Thiamine transporter 2 (ThTr-2), also known as solute carrier family 19 member 3, is a protein that in humans is encoded by the ''SLC19A3'' gene. SLC19A3 is a thiamine transporter.
Function
ThTr-2 is a ubiquitously expressed transmembrane thiam ...
. Leigh disease
Leigh syndrome (also called Leigh disease and subacute necrotizing encephalomyelopathy) is an inherited neurometabolic disorder that affects the central nervous system. It is named after Archibald Denis Leigh, a British neuropsychiatrist who fir ...
(subacute necrotising encephalomyelopathy) is an inherited disorder that affects mostly infants in the first years of life and is invariably fatal. Pathological similarities between Leigh disease and WE led to the hypothesis that the cause was a defect in thiamine metabolism. One of the most consistent findings has been an abnormality of the activation of the pyruvate dehydrogenase
Pyruvate dehydrogenase is an enzyme that catalyzes the reaction of pyruvate and a lipoamide to give the acetylated dihydrolipoamide and carbon dioxide. The conversion requires the coenzyme thiamine pyrophosphate.
Pyruvate dehydrogenase is us ...
complex.
Mutations in the ''SLC19A3
Thiamine transporter 2 (ThTr-2), also known as solute carrier family 19 member 3, is a protein that in humans is encoded by the ''SLC19A3'' gene. SLC19A3 is a thiamine transporter.
Function
ThTr-2 is a ubiquitously expressed transmembrane thiam ...
''gene have been linked to biotin-thiamine responsive basal ganglia disease, which is treated with pharmacological doses of thiamine and biotin
Biotin (or vitamin B7) is one of the B vitamins. It is involved in a wide range of metabolic processes, both in humans and in other organisms, primarily related to the utilization of fats, carbohydrates, and amino acids. The name ''biotin'', bor ...
, another B vitamin
B vitamins are a class of water-soluble vitamins that play important roles in Cell (biology), cell metabolism and synthesis of red blood cells. Though these vitamins share similar names (B1, B2, B3, etc.), they are chemically distinct compounds th ...
.
Other disorders in which a putative role for thiamine has been implicated include subacute necrotising encephalomyelopathy
Leigh syndrome (also called Leigh disease and subacute necrotizing encephalomyelopathy) is an inherited neurometabolic disorder that affects the central nervous system. It is named after Archibald Denis Leigh, a British neuropsychiatry, neuropsy ...
, opsoclonus myoclonus syndrome
Opsoclonus myoclonus syndrome (OMS), also known as opsoclonus-myoclonus-ataxia (OMA), is a rare neurological disorder of unknown cause which appears to be the result of an autoimmune process involving the nervous system. It is an extremely rare co ...
(a paraneoplastic syndrome), and Nigerian seasonal ataxia
''Anaphe venata'' is a moth of the family Notodontidae. It was described by Arthur Gardiner Butler in 1878. It lives in Angola, Cameroon, the Central African Republic, the Republic of the Congo, the Democratic Republic of the Congo, Equatorial G ...
(or African seasonal ataxia). In addition, several inherited disorders of ThDP-dependent enzymes have been reported, which may respond to thiamine treatment.
Pathophysiology
Thiamine in the human body has a half-life of 18 days and is quickly exhausted, particularly when metabolic demands exceed intake. A derivative of thiamine, thiamine pyrophosphate
Thiamine pyrophosphate (TPP or ThPP), or thiamine diphosphate (ThDP), or cocarboxylase is a thiamine (vitamin B1) derivative which is produced by the enzyme thiamine diphosphokinase. Thiamine pyrophosphate is a cofactor that is present in all liv ...
(TPP), is a cofactor involved in the citric acid cycle
The citric acid cycle (CAC)—also known as the Krebs cycle or the TCA cycle (tricarboxylic acid cycle)—is a series of chemical reactions to release stored energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and proteins ...
, as well as connecting the breakdown of sugars with the citric acid cycle. The citric acid cycle is a central metabolic pathway involved in the regulation of carbohydrate, lipid, and amino acid metabolism, and its disruption due to thiamine deficiency inhibits the production of many molecules including the neurotransmitters glutamic acid
Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can synt ...
and GABA. Additionally, thiamine may also be directly involved in neuromodulation
Neuromodulation is the physiological process by which a given neuron uses one or more chemicals to regulate diverse populations of neurons. Neuromodulators typically bind to metabotropic, G-protein coupled receptors (GPCRs) to initiate a second m ...
.
Diagnosis
A positive diagnosis test for thiamine deficiency involves measuring the activity of the enzyme transketolase
Transketolase (abbreviated as TK) is an enzyme that is encoded by the TKT gene. It participates in both the pentose phosphate pathway in all organisms and the Calvin cycle of photosynthesis. Transketolase catalyzes two important reactions, which ...
in erythrocyte
Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "holl ...
s (Erythrocyte transketolase activation assay). Alternatively, thiamine and its phosphorylated derivatives can directly be detected in whole blood, tissues, foods, animal feed, and pharmaceutical preparations following the conversion of thiamine to fluorescent
Fluorescence is the emission of light by a substance that has absorbed light or other electromagnetic radiation. It is a form of luminescence. In most cases, the emitted light has a longer wavelength, and therefore a lower photon energy, tha ...
thiochrome derivatives (thiochrome assay) and separation by high-performance liquid chromatography
High-performance liquid chromatography (HPLC), formerly referred to as high-pressure liquid chromatography, is a technique in analytical chemistry used to separate, identify, and quantify each component in a mixture. It relies on pumps to pa ...
(HPLC). Capillary electrophoresis (CE) techniques and in-capillary enzyme reaction methods have emerged as alternative techniques in quantifying and monitoring thiamine levels in samples.
The normal thiamine concentration in EDTA-blood is about 20-100 µg/L.
Treatment
Many people with beriberi can be treated with thiamine alone. Given thiamine intravenously (and later orally), rapid and dramatic[ recovery occurs, generally within 24 hours.][Tanphaichitr V. Thiamin. In: Shils ME, Olsen JA, Shike M et al., editors. ''Modern Nutrition in Health and Disease''. 9th ed. Baltimore: Lippincott Williams & Wilkins; 1999]
Improvements of peripheral neuropathy may require several months of thiamine treatment.
Epidemiology
Beriberi is a recurrent nutritional disease in detention houses, even in this century. In 1999, an outbreak of beriberi occurred in a detention center in Taiwan. High rates of illness and death in overcrowded Haitian jails in 2007 were traced to the traditional practice of washing rice before cooking. In the Ivory Coast
Ivory Coast, also known as Côte d'Ivoire, officially the Republic of Côte d'Ivoire, is a country on the southern coast of West Africa. Its capital is Yamoussoukro, in the centre of the country, while its largest city and economic centre is ...
, among a group of prisoners with heavy punishment, 64% were affected by beriberi. Before beginning treatment, prisoners exhibited symptoms of dry or wet beriberi with neurological signs (tingling: 41%), cardiovascular signs (dyspnoea: 42%, thoracic pain: 35%), and edemas of the lower limbs (51%). With treatment, the rate of healing was about 97%.
Populations under extreme stress may be at higher risk for beriberi. Displaced populations, such as refugee
A refugee, conventionally speaking, is a displaced person who has crossed national borders and who cannot or is unwilling to return home due to well-founded fear of persecution. s from war, are susceptible to micronutritional deficiency, including beriberi. The severe nutritional deprivation caused by famine
A famine is a widespread scarcity of food, caused by several factors including war, natural disasters, crop failure, Demographic trap, population imbalance, widespread poverty, an Financial crisis, economic catastrophe or government policies. Th ...
also can cause beriberis, although symptoms may be overlooked in clinical assessment or masked by other famine-related problems. An extreme weight-loss diet
Diet may refer to:
Food
* Diet (nutrition), the sum of the food consumed by an organism or group
* Dieting, the deliberate selection of food to control body weight or nutrient intake
** Diet food, foods that aid in creating a diet for weight loss ...
can, rarely, induce a famine-like state and the accompanying beriberi.[
]
History
Earliest written descriptions of thiamine deficiency are from ancient China in the context of Chinese medicine
Traditional Chinese medicine (TCM) is an alternative medical practice drawn from traditional medicine in China. It has been described as "fraught with pseudoscience", with the majority of its treatments having no logical mechanism of action ...
. One of the earliest is by Ge Hong
Ge Hong (; b. 283 – d. 343 or 364), courtesy name Zhichuan (稚川), was a Chinese linguist, Taoist practitioner, philosopher, physician, politician, and writer during the Eastern Jin dynasty. He was the author of '' Essays on Chinese Characte ...
in his book ''Zhou hou bei ji fang'' (''Emergency Formulas to Keep up Your Sleeve'') written sometime during the third century. Hong called the illness by the name ''jiao qi'', which can be interpreted as "foot qi". He described the symptoms to include swelling, weakness, and numbness of the feet. He also acknowledged that the illness could be deadly, and claimed that it could be cured by eating certain foods, such as fermented soybeans in wine. Better known examples of early descriptions of "foot qi" are by Chao Yuanfang
Chao Yuanfang () was a Chinese physician and medical author who was court physician at the Sui Dynasty (581–618 CE) between the years 605 and 616. Traditionally, he had been attributed the co-authorship or authorship of the Chinese medical clas ...
(who lived during 550–630) in his book ''Zhu bing yuan hou lun'' (''Sources and Symptoms of All Diseases'')[HA Smith, p. 26-28] and by Sun Simiao
Sun Simiao (; died 682) was a Chinese physician and writer of the Sui and Tang dynasty. He was titled as China's King of Medicine (, Yaowang) for his significant contributions to Chinese medicine and tremendous care to his patients.
Books
Sun ...
(581–682) in his book ''Bei ji qian jin yao fang'' (''Essential Emergency Formulas Worth a Thousand in Gold'').
In the late 19th century, beriberi was studied by Takaki Kanehiro
Baron was a Japanese naval physician.
Early life
Born in Hyūga Province (present-day Miyazaki Prefecture) as the son of a ''samurai'' retainer to the Satsuma domain, Takaki studied Chinese medicine as a youth and served as a medic in the Bos ...
, a British-trained Japanese medical doctor of the Imperial Japanese Navy
The Imperial Japanese Navy (IJN; Kyūjitai: Shinjitai: ' 'Navy of the Greater Japanese Empire', or ''Nippon Kaigun'', 'Japanese Navy') was the navy of the Empire of Japan from 1868 to 1945, when it was dissolved following Japan's surrender ...
. Beriberi was a serious problem in the Japanese navy; sailors fell ill an average of four times a year in the period 1878 to 1881, and 35% were cases of beriberi.[ In 1883, Takaki learned of a very high incidence of beriberi among cadets on a training mission from Japan to Hawaii, via New Zealand and South America. The voyage lasted more than nine months and resulted in 169 cases of sickness and 25 deaths on a ship of 376 men. With the support of the Japanese Navy, he conducted an experiment in which another ship was deployed on the same route, except that its crew was fed a diet of meat, fish, barley, rice, and beans. At the end of the voyage, this crew had only 14 cases of beriberi and no deaths. This convinced Takaki and the Japanese Navy that diet was the cause.][ In 1884, Takaki observed that beriberi was common among low-ranking crew who were often provided free rice, thus ate little else, but not among crews of Western navies, nor among Japanese officers who consumed a more varied diet.
In 1897, ]Christiaan Eijkman
Christiaan Eijkman ( , , ; 11 August 1858 – 5 November 1930) was a Dutch physician and professor of physiology whose demonstration that beriberi is caused by poor diet led to the discovery of antineuritic vitamins (thiamine). Together with S ...
, a Dutch
Dutch commonly refers to:
* Something of, from, or related to the Netherlands
* Dutch people ()
* Dutch language ()
Dutch may also refer to:
Places
* Dutch, West Virginia, a community in the United States
* Pennsylvania Dutch Country
People E ...
physician
A physician (American English), medical practitioner (Commonwealth English), medical doctor, or simply doctor, is a health professional who practices medicine, which is concerned with promoting, maintaining or restoring health through th ...
and pathologist
Pathology is the study of the causal, causes and effects of disease or injury. The word ''pathology'' also refers to the study of disease in general, incorporating a wide range of biology research fields and medical practices. However, when us ...
, demonstrated that beriberi is caused by poor diet, and discovered that feeding unpolished rice (instead of the polished variety) to chickens helped to prevent beriberi. The following year, Sir Frederick Hopkins
Sir Frederick Gowland Hopkins (20 June 1861 – 16 May 1947) was an English biochemist who was awarded the Nobel Prize in Physiology or Medicine in 1929, with Christiaan Eijkman, for the discovery of vitamins, even though Casimir Funk, a Po ...
postulated that some foods contained "accessory factors"—in addition to proteins, carbohydrates, fats, and salt—that were necessary for the functions of the human body. In 1901, Gerrit Grijns, a Dutch physician and assistant to Christiaan Eijkman
Christiaan Eijkman ( , , ; 11 August 1858 – 5 November 1930) was a Dutch physician and professor of physiology whose demonstration that beriberi is caused by poor diet led to the discovery of antineuritic vitamins (thiamine). Together with S ...
in the Netherlands, correctly interpreted beriberi as a deficiency syndrome, and between 1910 and 1913, Edward Bright Vedder established that an extract of rice bran
Bran, also known as miller's bran, is the hard outer layers of cereal grain. It consists of the combined aleurone and pericarp. Corn (maize) bran also includes the pedicel (tip cap). Along with germ, it is an integral part of whole grains, a ...
is a treatment for beriberi. In 1929, Eijkman and Hopkins were awarded the Nobel Prize for Physiology or Medicine
The Nobel Prize in Physiology or Medicine is awarded yearly by the Nobel Assembly at the Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Prize is not a single prize, but five separate prizes that, according ...
for their discoveries.
Etymology
Although according to the ''Oxford English Dictionary
The ''Oxford English Dictionary'' (''OED'') is the first and foundational historical dictionary of the English language, published by Oxford University Press (OUP). It traces the historical development of the English language, providing a com ...
'', the term "beriberi" comes from a Sinhalese
Sinhala may refer to:
* Something of or related to the Sinhalese people of Sri Lanka
* Sinhalese people
* Sinhala language, one of the three official languages used in Sri Lanka
* Sinhala script, a writing system for the Sinhala language
** Sinha ...
phrase meaning "weak, weak" or "I cannot, I cannot", the word being duplicated for emphasis, the origin of the phrase is questionable. It has also been suggested to come from Hindi, Arabic, and a few other languages, with many meanings like "weakness", "sailor", and even "sheep". Such suggested origins were listed by Heinrich Botho Scheube
Heinrich Botho Scheube (August 18, 1853 – 4 March 1923) was a German physician born in Zeitz.
In 1876 he earned his doctorate from the University of Leipzig, and following graduation remained in Leipzig as an assistant in Carl Reinhold Augu ...
, among others. Edward Vedder wrote in his book ''Beriberi'' (1913) that "it is impossible to definitely trace the origin of the word beriberi". Word ''berbere'' was used in writing at least as early as 1568 by Diogo do Couto
Diogo do Couto (Lisbon, c. 1542 – Goa, 10 December 1616) was a Portuguese historian.
Biography
He was born in Lisbon in 1542 to Gaspar do Couto and Isabel Serrão Calvos. He studied Latin and Rhetoric at the College of Saint Anthony the Great ...
, when he described the deficiency in India.
''Kakke'', which is a Japanese synonym for thiamine deficiency, comes from the way "jiao qi" is pronounced in Japanese.[HA Smith, p. 149] "''Jiao qi'' is an old word used in Chinese medicine to describe beriberi. "''Kakke'' is supposed to have entered into the Japanese language sometime between the sixth and eighth centuries.
Other animals
Poultry
As most feedstuffs used in poultry diets contain enough quantities of vitamins to meet the requirements in this species, deficiencies in this vitamin do not occur with commercial diets. This was, at least, the opinion in the 1960s.
Mature chickens show signs three weeks after being fed a deficient diet. In young chicks, it can appear before two weeks of age. Onset is sudden in young chicks, with anorexia and an unsteady gait. Later on, locomotor signs begin, with an apparent paralysis of the flexor of the toes. The characteristic position is called "stargazing", with the affected animal sitting on its hocks with its head thrown back in a posture called opisthotonos
Opisthotonus or opisthotonos (from grc, ὄπισθεν, translit=opisthen, lit=behind and grc, τόνος, translit=tonos, lit=tension, label=none) is a state of severe hyperextension and spasticity in which an individual's head, neck and spinal ...
. Response to administration of the vitamin is rather quick, occurring a few hours later.
Ruminants
Polioencephalomalacia
Polioencephalomalacia (PEM), also referred to as cerebrocortical necrosis (CCN), is a neurological disease seen in ruminants that is caused by multiple factors, one of which is thiamine depletion in the body. Thiamine (vitamin B1) is a key chemic ...
(PEM) is the most common thiamine deficiency disorder in young ruminant and nonruminant animals. Symptoms of PEM include a profuse, but transient, diarrhea, listlessness, circling movements, stargazing or opisthotonus (head drawn back over neck), and muscle tremors. The most common cause is high-carbohydrate feeds, leading to the overgrowth of thiaminase-producing bacteria, but dietary ingestion of thiaminase (e.g., in bracken
Bracken (''Pteridium'') is a genus of large, coarse ferns in the family Dennstaedtiaceae. Ferns (Pteridophyta) are vascular plants that have alternating generations, large plants that produce spores and small plants that produce sex cells (eggs ...
fern), or inhibition of thiamine absorption by high sulfur intake are also possible. Another cause of PEM is ''Clostridium sporogenes'' or ''Bacillus aneurinolyticus'' infection. These bacteria produce thiaminase
Thiaminase is an enzyme that metabolizes or breaks down thiamine into two molecular parts. It is an antinutrient when consumed.
The old name was "aneurinase".
There are two types:
* Thiamine pyridinylase, Thiaminase I (, )
* Aminopyrimidine ami ...
s that can cause an acute thiamine deficiency in the affected animal.
Snakes
Snakes that consume a diet largely composed of goldfish and feeder minnows are susceptible to developing thiamine deficiency. This is often a problem observed in captivity when keeping garter and ribbon snakes that are fed a goldfish-exclusive diet, as these fish contain thiaminase, an enzyme that breaks down thiamine.
Wild birds and fish
Thiamine deficiency has been identified as the cause of a paralytic disease affecting wild birds in the Baltic Sea area dating back to 1982. In this condition, there is difficulty in keeping the wings folded along the side of the body when resting, loss of the ability to fly and voice, with eventual paralysis of the wings and legs and death. It affects primarily 0.5–1 kg-sized birds such as the European herring gull
The European herring gull (''Larus argentatus'') is a large gull, up to long. One of the best-known of all gulls along the shores of Western Europe, it was once abundant. It breeds across Northern Europe, Western Europe, Central Europe, Eastern ...
(''Larus argentatus''), common starling
The common starling or European starling (''Sturnus vulgaris''), also known simply as the starling in Great Britain and Ireland, is a medium-sized passerine bird in the starling family, Sturnidae. It is about long and has glossy black plumage ...
(''Sturnus vulgaris''), and common eider
The common eider (pronounced ) (''Somateria mollissima''), also called St. Cuthbert's duck or Cuddy's duck, is a large ( in body length) sea-duck that is distributed over the northern coasts of Europe, North America and eastern Siberia. It bree ...
(''Somateria mollissima''). Researches noted, "Because the investigated species occupy a wide range of ecological niches and positions in the food web, we are open to the possibility that other animal classes may develop thiamine deficiency, as well."p. 12006
In the counties of Blekinge
Blekinge (, old da, Bleking) is one of the traditional Swedish provinces (), situated in the southern coast of the geographic region of Götaland, in southern Sweden. It borders Småland, Scania and the Baltic Sea. It is the country's second ...
and Skåne
Scania, also known by its native name of Skåne (, ), is the southernmost of the historical provinces (''landskap'') of Sweden. Located in the south tip of the geographical region of Götaland, the province is roughly conterminous with Skåne C ...
(southernmost Sweden
Sweden, formally the Kingdom of Sweden,The United Nations Group of Experts on Geographical Names states that the country's formal name is the Kingdom of SwedenUNGEGN World Geographical Names, Sweden./ref> is a Nordic country located on ...
), mass deaths of several bird species, especially the European herring gull, have been observed since the early 2000s. More recently, species of other classes seems to be affected. High mortality of salmon
Salmon () is the common name for several list of commercially important fish species, commercially important species of euryhaline ray-finned fish from the family (biology), family Salmonidae, which are native to tributary, tributaries of the ...
(''Salmo salar'') in the river Mörrumsån
Mörrumsån is a river in Blekinge County and Kronoberg County, Sweden. It is roughly long, with its tributary in the lake Asnen, from which it flows south, into the Baltic Sea. The river is known among fishing enthusiasts around the world, becau ...
is reported, and mammals such as the Eurasian elk
The moose (in North America) or elk (in Eurasia) (''Alces alces'') is a member of the New World deer subfamily and is the only species in the genus ''Alces''. It is the largest and heaviest extant species in the deer family. Most adult ma ...
(''Alces alces'') have died in unusually high numbers. Lack of thiamine is the common denominator where analysis is done. In April 2012, the County Administrative Board of Blekinge found the situation so alarming that they asked the Swedish government to set up a closer investigation.
References
Further reading
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External links
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Reduplicants
Vitamin deficiencies
Thiamine
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