A fresh look at thiamine deficiency-new analyses by the global thiamine alliance.

Severe thiamine (vitamin B1 ) deficiency is generally regarded as a problem affecting mostly infants in low-income communities of Southeast Asia and adult alcoholics regardless of their location. However, recent scholarship shows that the disorders associated with thiamine deficiency may also affect heretofore unsuspected populations, and that the scope of disorders, including some long-lasting neurocognitive consequences, is broader than previously thought.

Perinatal Consumption of Thiamine-Fortified Fish Sauce in Rural Cambodia: A Randomized Clinical Trial.

IMPORTANCE: Infantile beriberi, a potentially fatal disease caused by thiamine deficiency, remains a public health concern in Cambodia and regions where thiamine-poor white rice is a staple food. Low maternal thiamine intake reduces breast milk thiamine concentrations, placing breastfed infants at risk of beriberi. OBJECTIVE: To determine if consumption of thiamine-fortified fish sauce yields higher erythrocyte thiamine diphosphate concentrations (eTDP) among lactating women and newborn infants and higher breast milk thiamine concentrations compared with a control sauce. DESIGN, SETTING, AND PARTICIPANTS: In this double-blind randomized clinical trial, 90 pregnant women were recruited in the Prey Veng province, Cambodia. The study took place between October 2014 and April 2015. INTERVENTIONS: Women were randomized to 1 of 3 groups (n = 30) for ad libitum fish sauce consumption for 6 months: control (no thiamine), low-concentration (2 g/L), or high-concentration (8 g/L) fish sauce. MAIN OUTCOMES AND MEASURES: Maternal eTDP was assessed at baseline (October 2014) and endline (April 2015). Secondary outcomes, breast milk thiamine concentration and infant eTDP, were measured at endline. RESULTS: Women's mean (SD) age and gestational stage were 26 (5) years and 23 (7) weeks, respectively. April 2015 eTDP was measured among 28 women (93%), 29 women (97%), and 23 women (77%) in the control, low-concentration, and high-concentration groups, respectively. In modified intent-to-treat analysis, mean baseline-adjusted endline eTDP was higher among women in the low-concentration (282nM; 95% CI, 235nM to 310nM) and high-concentration (254nM; 95% CI, 225nM to 284nM) groups compared with the control group (193nM; 95% CI, 164nM to 222M; P < .05); low-concentration and high-concentration groups did not differ (P = .19). Breast milk total thiamine concentrations were 14.4 µg/dL for the control group (95% CI, 12.3 µg/dL to 16.5 µg/dL) (to convert to nanomoles per liter, multiply by 29.6); 20.7 µg/dL for the low-concentration group (95% CI, 18.6 µg/dL to 22.7 µg/dL ); and 17.7 µg/dL for the high-concentration group (95% CI, 15.6 µg/dL to 19.9 µg/dL). Mean (SD) infant age at endline was 16 (8) weeks for the control group, 17 (7) weeks for the low-concentration group, and 14 (8) for the high-concentration group. Infant eTDP was higher among those in the high-concentration group (257nM; 95% CI, 222nM to 291nM; P < .05) compared with the low-concentration (212nM; 95% CI, 181nM to 244nM) and control (187nM; 95% CI, 155nM to 218nM) groups. CONCLUSIONS AND RELEVANCE: Compared with women in the control group, women who consumed thiamine-fortified fish sauce through pregnancy and early lactation had higher eTDP and breast milk thiamine concentrations and their infants had higher eTDP, which was more pronounced in the high group. Thiamine-fortified fish sauce has the potential to prevent infantile beriberi in this population. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT02221063.

[Experimental Approach to Analysis of the Relationship between Food Environments and Lifestyle-Related Diseases, Including Cardiac Hypertrophy, Fatty Liver, and Fatigue Symptoms].

The food habit is involved in the onset and development of lifestyle-related diseases. In this review I would like to describe a historical case of vitamin B1 deficiency, as well as our case study of fatty acid metabolism abnormality due to carnitine deficiency. In history, the army and navy personnel in Japan at the end of the 19th century received food rations based on a high-carbohydrate diet including white rice, resulting in the onset of beriberi. An epidemiological study by Kenkan Takaki revealed the relationship between the onset of beriberi and rice intake. Then, Takaki was successful in preventing the onset of beriberi by changing the diet. However, the primary cause had yet to be elucidated. Finally, Christian Eijkman established an animal model of beriberi (chickens) showing peripheral neuropathy, and he identified the existence of an anti-beriberi substance, vitamin B1. This is an example of the successful control of a disease by integrating the results of epidemiological and experimental studies. In our study using a murine model of fatty acid metabolism abnormality caused by carnitine deficiency, cardiac abnormality and fatty liver developed depending on the amount of dietary fat. In addition, the mice showed disturbance of orexin neuron activity related to the sleep-arousal system, which is involved in fatigue symptoms under fasting condition, one of the states showing enhanced fatty acid metabolism. These findings suggest that fatty acid toxicity is enhanced when the mice are more dependent on fatty acid metabolism. Almost simultaneously, a human epidemiological study showed that narcolepsy, which is caused by orexin system abnormality, is associated with the polymorphism of the gene coding for carnitine palmitoyltransferase 1B, which is involved in carnitine metabolism. To understand the pathological mechanism of fatty acid toxicity, not only an experimental approach using animal models, but also an epidemiological approach is necessary. The results will be applied to preventing and treating lifestyle-related diseases associated with fatty acid metabolism abnormality.

Thiamine pharmacokinetics in Cambodian mothers and their breastfed infants.

BACKGROUND: Thiamine deficiency is common in parts of Asia and causes beriberi. Pharmacokinetics of thiamine in deficient populations are unknown. OBJECTIVE: We characterized thiamine pharmacokinetics in Cambodian mothers and their breastfed infants. DESIGN: Total plasma thiamine, whole-blood thiamine diphosphate (TDP), and breast milk total thiamine were measured in 16 healthy Cambodian mothers and their infants before and after mothers received oral thiamine hydrochloride (100 mg for 5 d). Assays were also performed in 16 healthy American mothers. RESULTS: On day 1, Cambodian mothers were thiamine deficient, with median (range) total plasma thiamine and TDP concentrations of 2.4 nmol/L (0-4.4 nmol/L) and 58.0 nmol/L (27-98 nmol/L), respectively. After a single oral dose, the mean ± SD maximal concentration of thiamine and net area under the thiamine concentration-time curve were 73.4 ± 45.6 nmol/L and 465 ± 241 h · nmol ∙ L⁻¹. Day 6 median maternal total plasma thiamine and TDP concentrations were normal [18.6 nmol/L (13.4-25.3 nmol/L) and 76.5 nmol/L (48-107 nmol/L), respectively; P ≤ 0.001 compared with day 1]. Median Cambodian total breast milk thiamine concentration increased from 180 nmol/L (85-359 nmol/L) on day 1 to 403 nmol/L (314-415 nmol/L) on day 2 and 503 nmol/L (360-808 nmol/L) on day 6; the corresponding American breast milk value was 500 nmol/L (114-622 nmol/L). Median Cambodian infant total plasma thiamine and TDP concentrations increased from 3.0 nmol/L (0-7.3 nmol/L) and 38.5 nmol/L (23-57 nmol/L), respectively, on day 1 to 5.6 nmol/L (0-9.7 nmol/L) and 45.5 nmol/L (32-70 nmol/L), respectively, on day 6. CONCLUSIONS: Thiamine-deficient Cambodian mothers effectively absorb oral thiamine, with sharp increases in breast milk thiamine concentrations, but their breastfed infants remain thiamine deficient after 5 d of maternal supplementation. Longer-term maternal supplementation may be necessary to correct thiamine deficiency in breastfed infants. This trial was registered at clinicaltrials.gov as NCT01864057.

Beribéri: revisão histórica e documental na Marinha do Brasil / Beriberi: historical and documental review in the Navy of Brasil

O autor apresenta os resultados de pesquisa documental, realizada com a finalidade de conhecer os procedimentos médico-periciais utilizados nas avaliações das guarnições da Marinha do Brasil, no período 1900-1901, realizadas no Hospital Central da Marinha, na Ilha das Cobras. observa a alta frequência de beribéri como causa de incapcidade para o Serviço Ativo da Marinha. Desenvolve ainda um breve relato da epidemia de beribéri que assolava as tripulações dos navios das Marinhas em todo o mundo no início do século XX, relembrando as condutas tomadas diante da doença em nosso país. Finalmente, apresenta documentação e fatos pouco conhecidos, testemunhando o significativo valor histórico do material coletado nos arquivos do Centro de Perícias Médicas da Marinha. (AU)

The great disease enemy, Kak'ke (beriberi) and the Imperial Japanese Army.

Although Japanese military officials had discovered that an improved diet could prevent beriberi by the late 19th century, their soldiers in the army suffered from beriberi during the Russo-Japanese War and World War II. A change in diet at the end of the Russo-Japanese War solved the problem and the army applied the lesson learned, along with postwar scientific discoveries about nutrition, toward the diet used during World War II. However, beriberi again plagued Japanese soldiers, this time due to poor logistics and unpalatable dietary supplements.

Outbreak of beri-beri in a prison in West Africa.

The International Committee of the Red Cross investigated an outbreak of beri-beri in a prison in West Africa. Twenty-five prisoners out of a total of 1020 died over a period of 11 weeks--exceeding the crude mortality rate of 1/10,000/day, a threshold for serious concern. Two hundred and eleven prisoners had clinical signs of beri-beri. An immediate response to treatment with thiamine was seen and no further deaths occurred. The triad of a positive squatting test, oedema and a diet consisting exclusively of white rice should lead to the diagnosis of beri-beri. The disease is more common than generally assumed, also in Africa and especially in prisons.

Beri-beri: age-gender bias in The Gambia.

This paper investigates a suspected outbreak of beri-beri which occurred in The Gambia in 1988. The outbreak was spatially specific and had a distinct age and gender bias, with young men aged 15-49 being the group mainly affected. The age and gender bias of the outbreak is particularly interesting as women and children in the developing world are usually more susceptable to conditions associated with malnourishment, than men. The authors investigate the peculiar nature of the outbreak and find that they cannot easily explain the apparent age and gender bias. The authors note that at the time of the outbreak medical treatment took precedence over socio-economic investigations. This makes it difficult to ascertain why certain age and gender groups were affected and thus to target them for future preventative health education programmes. This case study therefore concludes, that where possible, medical investigations must be combined with socio-economic studies if future outbreaks of this kind are to be avoided.

The prevention and conquest of scurvy, beri-beri, and pellagra.

I have described how many years of research were needed to overcome three nutritional diseases that occurred throughout the world. When human beings migrated from tropical and subtropical regions to the temperate zone, they lost their year-round supplies of vitamin C, and scurvy began to occur. The emergence of beri-beri had a mechanical basis; the introduction of milling, which prevented the rancidity of rice and wheat, also removed the essential vitamin B1. The circumstance leading to the third deficiency disease was reliance on maize, without supplementing it with "protective" foods, such as meat, milk, and vegetables. Under conditions of poverty, the protective foods became expensive, and pellagra appeared. Synthetic chemistry, together with improvements in the diet and in education, largely overcame scurvy, beri-beri, and pellagra, but deficiencies of vitamins A, C, and folic acid still occur widely in economically disadvantaged populations, and this is a challenge to those who wish to improve public health. The brilliant prophesies of Casimir Funk, made in 1912, were fulfilled within 25 years. Today, his word "vitamin" is universally familiar. The account of the discovery, identification and synthesis of the vitamins is the story of how human beings have overcome nutritional deficiencies that were imposed by cultural and economic disadvantages or just plain ignorance. These discoveries were a triumph of science and technology. Much of the research depended on the use of experimental animals: guinea-pigs, rats, dogs, monkeys, and chickens. Vitamins are now added to the diets of both animals and human beings.