Thiamine deficiency

Thiamine deficiency is a medical condition of low levels of

Dry beriberi causes wasting and partial paralysis resulting from damaged peripheral nerves. It is also referred to as endemic neuritis. It is characterized by:

• Difficulty with walking
• Tingling or loss of sensation (numbness) in hands and feet
• Loss of tendon reflexes^[12]
• Loss of muscle function or paralysis of the lower legs
• Mental confusion/speech difficulties
• Pain
• Involuntary eye movements (
  nystagmus
  )
• Vomiting

A selective impairment of the large proprioceptive sensory fibers without motor impairment can occur and present as a prominent sensory ataxia, which is a loss of balance and coordination due to loss of the proprioceptive inputs from the periphery and loss of position sense.^[13]

Brain disease

Korsakoff syndrome, in general, is considered to occur with deterioration of brain function in patients initially diagnosed with WE.^[18] This is an amnestic-confabulatory syndrome characterized by retrograde and anterograde amnesia, impairment of conceptual functions, and decreased spontaneity and initiative.^[19]

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.^[20]
• 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).^[21]

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.)

Wet beriberi

Wet beriberi affects the

• Increased heart rate
• Vasodilation leading to decreased systemic vascular resistance, and high-output heart failure^[22]
• Elevated jugular venous pressure^[23]
• Dyspnea (shortness of breath) on exertion
• Paroxysmal nocturnal
  dyspnea
• Peripheral
  edema^[23] (swelling of lower legs) or generalized edema^{[24][25][26][27]}
  (swelling throughout the body)
• Dilated cardiomyopathy

Gastrointestinal beriberi

Gastrointestinal beriberi causes abdominal pain. It is characterized by:

• Abdominal pain
• Nausea
• Vomiting
• Lactic acidosis^[28][29]

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.^[2]

In the acute form, the baby develops

• Hoarseness, where the child makes moves to moan, but emits no sound or just faint moans[30] caused by nerve paralysis^[12]
• Weight loss, becoming thinner and then
  marasmic as the disease progresses^[30]
• Vomiting[30]
• Diarrhea^[30]
• Pale skin^[12]
• Edema^[12][30]
• Ill temper^[12]
• Alterations of the cardiovascular system, especially tachycardia (rapid heart rate)^[12]
• Convulsions occasionally observed in the terminal stages^[30]

Beriberi is often caused by eating a diet with a very high proportion of calorie rich polished rice (common in Asia) or cassava root (common in sub-Saharan Africa), without much if any thiamine-containing animal products or vegetables.^[2]

It may also be caused by shortcomings other than inadequate intake –

Wernicke's disease is one of the most prevalent neurological or neuropsychiatric diseases.^[31] In autopsy series, features of Wernicke lesions are observed in approximately 2% of general cases.^[32] 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 abusers, 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.^[33][34] 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.

Nigerian seasonal ataxia (or African seasonal ataxia). In addition, several inherited disorders of ThDP-dependent enzymes have been reported,^[41] which may respond to thiamine treatment.^[19]

Pathophysiology

Thiamine in the human body has a half-life of 17 days and is quickly exhausted, particularly when metabolic demands exceed intake. A derivative of thiamine,

neuromodulation.^[43]

Diagnosis

A positive diagnosis test for thiamine deficiency involves measuring the activity of the enzyme

fluorescent thiochrome derivatives (thiochrome assay) and separation by high-performance liquid chromatography (HPLC).^[44][45][46] Capillary electrophoresis (CE) techniques and in-capillary enzyme reaction methods have emerged as alternative techniques in quantifying and monitoring thiamine levels in samples.^[47]

The normal thiamine concentration in EDTA-blood is about 20–100 µg/L.

Treatment

Many people with beriberi can be treated with thiamine alone.[48] Given thiamine intravenously (and later orally), rapid and dramatic^[23] recovery occurs, generally within 24 hours.^[49]

Improvements of peripheral neuropathy may require several months of thiamine treatment.^[50]

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.^[51] High rates of illness and death from beriberi in overcrowded Haitian jails in 2007 were traced to the traditional practice of washing rice before cooking; this removed a nutritious coating which had been applied to the rice after processing (enriched white rice).^[52] In the Ivory Coast, 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%.^[53]

Populations under extreme stress may be at higher risk for beriberi. Displaced populations, such as refugees from war, are susceptible to micronutritional deficiency, including beriberi.^[54] The severe nutritional deprivation caused by famine also can cause beriberis, although symptoms may be overlooked in clinical assessment or masked by other famine-related problems.^[55] An extreme weight-loss diet can, rarely, induce a famine-like state and the accompanying beriberi.^[23]

Workers on Chinese squid ships are at elevated risk of beriberi due to the simple carbohydrate-rich diet they are fed and the long period of time between shoring. Between 2013 and 2021, 15 workers on 14 ships have died with symptoms of beriberi.^[56]

History

Earliest written descriptions of thiamine deficiency are from ancient China in the context of

Chinese medicine. One of the earliest is by Ge Hong 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 (who lived during 550–630) in his book Zhu bing yuan hou lun (Sources and Symptoms of All Diseases)^[57][58] and by Sun Simiao (581–682) in his book Bei ji qian jin yao fang (Essential Emergency Formulas Worth a Thousand in Gold).^{[59][58][60][61]}

In the mid-19th century, interest in beriberi steadily rose as the disease became more noticeable with changes in diet in East and Southeast Asia. There was a steady uptick in medical publications, reaching one hundred and eighty-one publications from 1880 and 1889, and hundreds more in the following decades. The link to white rice was clear to Western doctors, but a confounding factor was that some other foods like meat failed to prevent beriberi, so it could not be easily explained as a lack of known chemicals like carbon or nitrogen. With no knowledge of vitamins, the etiology of beriberi was among the most hotly debated subjects in Victorian medicine.^[62]

The first successful preventative measure against beriberi was discovered by Takaki Kanehiro, a British-trained Japanese medical doctor of the Imperial Japanese Navy, in the mid-1880s.^[63] 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.^[63] In 1882, 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. 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. 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.^[63] This emphasis on varied diet contradicted observations by other doctors, and Takaki's carbon-based etiology was just as incorrect as similar theories before him, but the results of his experiment impressed the Japanese Navy, which adopted his proposed solution. By 1887 beriberi had been completely eliminated on Navy ships.^[62]

Takaki's experiment was described favorably in

Nobel Prize for Physiology or Medicine

for their discoveries.

Japanese Army denialism

Although the identification of beriberi as a deficiency syndrome was proven beyond a doubt by 1913, a Japanese group headed by

Tokyo Imperial University continued to deny this conclusion until 1926. In 1886, Mori, then working in the Japanese Army Medical Bureau, asserted that white rice was sufficient as a diet for soldiers. Simultaneously, Navy surgeon general Takaki Kanehiro published the groundbreaking results described above. Mori, who had been educated under German doctors, responded that Takaki was a "fake doctor" due to his lack of prestigious medical background, while Mori himself and his fellow graduates of Tokyo Imperial University constituted the only "real doctors" in Japan and that they alone were capable of "experimental induction", although Mori himself had not conducted any beriberi experiments.^[68]

The Japanese Navy sided with Takaki and adopted his suggestions. In order to prevent himself and the Army from losing face, Mori assembled a team of doctors and professors from Tokyo Imperial University and the Japanese Army who proposed that beriberi was caused by an unknown pathogen, which they described as etowasu (from the German Etwas, meaning "something"). They employed various social tactics to denounce vitamin deficiency experiments and prevent them from being published, while beriberi ravaged the Japanese Army. During the First Sino-Japanese War and Russo-Japanese War, Army soldiers continued to die in mass numbers from beriberi, while Navy sailors survived. In response to this severe loss of life, in 1907, the Army ordered the formation of a Beriberi Emergency Research Council, headed by Mori. Its members pledged to find the cause of beriberi.^[69] By 1919, with most Western doctors acknowledging that beriberi was a deficiency syndrome, the Emergency Research Council began conducting experiments using various vitamins, but stressed that "more research was necessary". During this period, more than 300,000 Japanese soldiers contracted beriberi and over 27,000 died.^[70]

Mori died in 1922. The Beriberi Research Council disbanded in 1925, and by the time Eijkman and Hopkins were awarded the Nobel Prize, all of its members had acknowledged that beriberi was a deficiency syndrome.

Etymology

Although according to the

Edward Vedder wrote in his book Beriberi (1913) that "it is impossible to definitely trace the origin of the word beriberi". The word berbere was used in writing at least as early as 1568 by Diogo do Couto, when he described the deficiency in India.^[72]

Kakke (脚気), which is a Japanese synonym for thiamine deficiency, comes from the way "jiao qi" is pronounced in Japanese.[73] "Jiao qi" is an old word used in Chinese medicine to describe beriberi.^[57] "Kakke" is supposed to have entered into the Japanese language sometime between the sixth and eighth centuries.^[73]

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.^[74]

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. Response to administration of the vitamin is rather quick, occurring a few hours later.^[75][76]

Ruminants

Polioencephalomalacia (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.^[77] 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 fern), or inhibition of thiamine absorption by high sulfur intake are also possible.^[78] Another cause of PEM is Clostridium sporogenes or Bacillus aneurinolyticus infection. These bacteria produce thiaminases that can cause an acute thiamine deficiency in the affected animal.^[79]

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.^[80]

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.^[81] 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 (Larus argentatus), common starling (Sturnus vulgaris), and common eider (Somateria mollissima). Researchers 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."^{[81]p. 12006}

In the counties of

salmon (Salmo salar) in the river Mörrumsån is reported, and mammals such as the Eurasian elk (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.^[82]

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Further reading

• Arnold D (2010). "British India and the beri-beri problem". Medical History. 54 (3): 295–314.
  PMID 20592882
  .
• Chisholm H, ed. (1911). "Beri-Beri" . Encyclopædia Britannica. Vol. 03 (11th ed.). Cambridge University Press. pp. 774–775.
• Smith HA (2017). Forgotten Disease: Illnesses Transformed in Chinese Medicine.
  OCLC 993877848
  .

External links

• Media related to Beriberi at Wikimedia Commons