Thiamine supplementation holds neurocognitive benefits for breastfed infants during the first year of life.

Women reliant on mostly rice-based diets can have inadequate thiamine intake, placing breastfed infants at risk of thiamine deficiency and, in turn, physical and cognitive impairments. We investigated the impact of maternal thiamine supplementation doses on infants' cognitive, motor, and language development across the first year. In this double-blind, four-parallel-arm, randomized controlled trial, healthy mothers of exclusively breastfed newborn infants were recruited in Kampong Thom, Cambodia. At 2 weeks postnatal, women (n = 335) were randomized to one of four treatment groups to consume one capsule/day with varying amounts of thiamine for 22 weeks: 0, 1.2, 2.4, and 10 mg. At 2, 12, 24, and 52 weeks of age, infants were assessed with the Mullen Scales of Early Learning (MSEL) and the Caregiver Reported Early Development Instrument (CREDI). Multiple regression and mixed effects modeling suggest that by 6 months of age, the highest maternal thiamine dose (10 mg/day) held significant benefits for infants' language development, but generally not for motor or visual reception development. Despite having achieved standardized scores on the MSEL that approximated U.S. norms by 6 months, infants showed a significant drop relative to these norms in both language domains following trial completion, indicating that nutritional interventions beyond 6 months may be necessary.

Thiamine fortification strategies in low- and middle-income settings: a review.

Thiamine (vitamin B1 ) is an essential micronutrient in energy metabolism and cognitive and neurological health. Thiamine deficiency disorders (TDDs) have a range of clinical presentations that result in various morbidities and can be fatal if not promptly recognized and treated, especially in infants. To intervene, thiamine intakes by breastfeeding mothers and others at risk of thiamine deficiency should be increased to ensure adequate thiamine intake. Although thiamine fortification programs have a long history in high-income countries, there are few mandatory fortification programs to address TDDs in low- and middle-income countries (LMICs), particularly in the regions of greatest concern, South and Southeast Asia. This review highlights essential aspects for consideration in the development of a mandatory fortification program in LMICs, including an overview of the data required to model fortification dosing schemes, available thiamine fortificants, and potential fortification vehicles, as well as identifies current knowledge gaps.

Assessment of salt intake to consider salt as a fortification vehicle for thiamine in Cambodia.

Thiamine deficiency is a public health issue in Cambodia. Thiamine fortification of salt has been proposed; however, the salt intake of lactating women, the target population, is currently unknown. We estimated salt intakes among lactating women (<6 months postpartum) using three methods: repeat observed-weighed intake records and 24-h urinary sodium excretions (n = 104), and household salt disappearance (n = 331). Usual salt intake was estimated by adjusting for intraindividual intakes using the National Cancer Institute method, and a thiamine salt fortification scenario was modeled using a modified estimated average requirement (EAR) cut-point method. Unadjusted salt intake from observed intakes was 9.3 (8.3-10.3) g/day, which was not different from estimated salt intake from urinary sodium excretions, 9.0 (8.4-9.7) g/day (P = 0.3). Estimated salt use from household salt disappearance was 11.3 (10.7-11.9) g/person/day. Usual (adjusted) salt intake from all sources was 7.7 (7.4-8.0) g/day. Assuming no stability losses, a modeled fortification dose of 275 mg thiamine/kg salt could increase thiamine intakes from fortified salt to 2.1 (2.0-2.2) mg/day, with even low salt consumers reaching the EAR of 1.2 mg/day from fortified salt alone. These findings, in conjunction with future sensory and stability research, can inform a potential salt fortification program in Cambodia.

Modeling thiamine fortification: a case study from Kuria atoll, Republic of Kiribati.

In 2014, there was an outbreak of beriberi on Kuria, a remote atoll in Kiribati, a small Pacific Island nation. A thiamine-poor diet consisting mainly of rice, sugar, and small amounts of fortified flour was likely to blame. We aimed to design a food fortification strategy to improve thiamine intakes in Kuria. We surveyed all 104 households on Kuria with a pregnant woman or a child 0-59 months. Repeat 24-h dietary recalls were collected from 90 men, 17 pregnant, 44 lactating, and 41 other women of reproductive age. The prevalence of inadequate thiamine intakes was >30% in all groups. Dietary modeling predicted that rice or sugar fortified at a rate of 0.3 and 1.4 mg per 100 g, respectively, would reduce the prevalence of inadequate thiamine intakes to <2.5% in all groups. Fortification is challenging because Kiribati imports food from several countries, depending on price and availability. One exception is flour, which is imported from Fiji. Although resulting in less coverage than rice or sugar, fortifying wheat flour with an additional 3.7 mg per 100 g would reduce the prevalence of inadequacy to under 10%. Kiribati is small and has limited resources; thus, a regional approach to thiamine fortification is needed.

Thiamine dose response in human milk with supplementation among lactating women in Cambodia: study protocol for a double-blind, four-parallel arm randomised controlled trial.

INTRODUCTION: Thiamine (vitamin B1) deficiency remains a concern in Cambodia where women with low thiamine intake produce thiamine-poor milk, putting their breastfed infants at risk of impaired cognitive development and potentially fatal infantile beriberi. Thiamine fortification of salt is a potentially low-cost, passive means of combating thiamine deficiency; however, both the dose of thiamine required to optimise milk thiamine concentrations as well as usual salt intake of lactating women are unknown. METHODS AND ANALYSIS: In this community-based randomised controlled trial, 320 lactating women from Kampong Thom, Cambodia will be randomised to one of four groups to consume one capsule daily containing 0, 1.2, 2.4 or 10 mg thiamine as thiamine hydrochloride, between 2 and 24 weeks postnatal. The primary objective is to estimate the dose where additional maternal intake of thiamine no longer meaningfully increases infant thiamine diphosphate concentrations 24 weeks postnatally. At 2, 12 and 24 weeks, we will collect sociodemographic, nutrition and health information, a battery of cognitive assessments, maternal (2 and 24 weeks) and infant (24 weeks only) venous blood samples (biomarkers: ThDP and transketolase activity) and human milk samples (also at 4 weeks; biomarker: milk thiamine concentrations). All participants and their families will consume study-provided salt ad libitum throughout the trial, and we will measure salt disappearance each fortnight. Repeat weighed salt intakes and urinary sodium concentrations will be measured among a subset of 100 participants. Parameters of Emax dose-response curves will be estimated using non-linear least squares models with both 'intention to treat' and a secondary 'per-protocol' (capsule compliance ≥80%) analyses. ETHICS AND DISSEMINATION: Ethical approval was obtained in Cambodia (National Ethics Committee for Health Research 112/250NECHR), Canada (Mount Saint Vincent University Research Ethics Board 2017-141) and the USA (University of Oregon Institutional Review Board 07052018.008). Results will be shared with participants' communities, as well as relevant government and scientific stakeholders via presentations, academic manuscripts and consultations. TRIAL REGISTRATION NUMBER: NCT03616288.

Thiamine Use in Sepsis: B1 for Everyone?

Every year, sepsis affects nearly 30 million people worldwide, with current annual estimates reporting as many as 6 million deaths. To combat the staggering number of patients who are affected by sepsis, clinicians continue to investigate novel treatment approaches. One treatment approach that has gained interest is the role that vitamins and nutrients play in the body's response to sepsis. Thiamine, in particular, has been studied because of its role in glucose metabolism and lactate production. This review provides a summary of the current literature surrounding the use of thiamine in the treatment of sepsis and describes the function of this essential nutrient in sepsis pathology. We also aim to provide clinicians with the necessary understanding to recognize the potential for thiamine deficiency, as well as detail the role of thiamine supplementation in the treatment of sepsis.

A review of micronutrients in sepsis: the role of thiamine, l-carnitine, vitamin C, selenium and vitamin D.

Sepsis is defined as the dysregulated host response to an infection resulting in life-threatening organ dysfunction. The metabolic demand from inefficiencies in anaerobic metabolism, mitochondrial and cellular dysfunction, increased cellular turnover, and free-radical damage result in the increased focus of micronutrients in sepsis as they play a pivotal role in these processes. In the present review, we will evaluate the potential role of micronutrients in sepsis, specifically, thiamine, l-carnitine, vitamin C, Se and vitamin D. Each micronutrient will be reviewed in a similar fashion, discussing its major role in normal physiology, suspected role in sepsis, use as a biomarker, discussion of the major basic science and human studies, and conclusion statement. Based on the current available data, we conclude that thiamine may be considered in all septic patients at risk for thiamine deficiency and l-carnitine and vitamin C to those in septic shock. Clinical trials are currently underway which may provide greater insight into the role of micronutrients in sepsis and validate standard utilisation.

Thiamin.

Starting with a brief history of beriberi and the discovery that thiamin deficiency is its cause, the symptoms and signs are reviewed. None are pathognomonic. The disease has a low mortality and a long morbidity. The appearance of the patient can be deceptive, often being mistaken for psychosomatic disease in the early stages. The chemistry of thiamin and the laboratory methodology for depicting its deficiency are outlined. The diseases associated with thiamin deficiency, apart from malnutrition, include a number of genetically determined conditions where mutations, either in the cofactor relationship or a transporter, provide the etiology. It is emphasized that such mutations are often epigenetically responsive to megadoses of thiamin or one of its derivatives. The use of thiamin in clinical practice requires a high index of suspicion on the part of the clinician since it has a part to play in eating disorders, diabetes, neurodegenerative disease, and cancer. A high rate of critical illness and postsurgery thiamin deficiency have been reported, particularly those associated with gastrointestinal bypass. Emphasis is placed on thiamin deficiency as a major cause of asymmetric dysautonomia, because of the high degree of sensitivity to thiamin deficiency in the brainstem, cerebellum, and hypothalamus. The relationship of thiamin with regional pain syndrome, eosinophilic esophagitis, its analgesic capacity, and its preventive use in obstetrics is raised as a potential issue. The role of thiamin in SIDS and autism is outlined. It is emphasized that megadose thiamin is being used as a drug, either in stimulating the damaged cofactor/enzyme combination, or mitochondria.

Comparable Performance Characteristics of Plasma Thiamine and Erythrocyte Thiamine Diphosphate in Response to Thiamine Fortification in Rural Cambodian Women.

Background: Traditionally, vitamin B1 status is assessed by a functional test measuring erythrocyte transketolase (ETK) activity or direct measurement of erythrocyte thiamine diphosphate (eThDP) concentration. However, such analyses are logistically challenging, and do not allow assessment of vitamin B1 status in plasma/serum samples stored in biobanks. Using a multiplex assay, we evaluated plasma concentrations of thiamine and thiamine monophosphate (TMP), as alternative, convenient measures of vitamin B1 status. Methods: We investigated the relationships between the established biomarker eThDP and plasma concentrations of thiamine and TMP, and compared the response of these thiamine forms to thiamine fortification using samples from 196 healthy Cambodian women (aged 18-45 years.). eThDP was measured by high performance liquid chromatography with fluorescence detection (HPLC-FLD) and plasma thiamine and TMP by high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results: Plasma thiamine and TMP correlated significantly with eThDP at baseline and study-end (p < 0.05). Among the fortification groups, the strongest response was observed for plasma thiamine (increased by 266%), while increases in plasma TMP (60%) and eThDP (53%) were comparable. Conclusions: Plasma thiamine and TMP correlated positively with eThDP, and all thiamine forms responded significantly to thiamine intervention. Measuring plasma concentrations of thiamine forms is advantageous due to convenient sample handling and capacity to develop low volume, high-throughput, multiplex assays.

Adaptation of New Colombian Food-based Complementary Feeding Recommendations Using Linear Programming.

OBJECTIVE: The aim of the study was to use linear programming (LP) analyses to adapt New Complementary Feeding Guidelines (NCFg) designed for infants aged 6 to 12 months living in poor socioeconomic circumstances in Bogota to ensure dietary adequacy for young children aged 12 to 23 months. DESIGN: A secondary data analysis was performed using dietary and anthropometric data collected from 12-month-old infants (n = 72) participating in a randomized controlled trial. LP analyses were performed to identify nutrients whose requirements were difficult to achieve using local foods as consumed; and to test and compare the NCFg and alternative food-based recommendations (FBRs) on the basis of dietary adequacy, for 11 micronutrients, at the population level. RESULTS: Thiamine recommended nutrient intakes for these young children could not be achieved given local foods as consumed. NCFg focusing only on meat, fruits, vegetables, and breast milk ensured dietary adequacy at the population level for only 4 micronutrients, increasing to 8 of 11 modelled micronutrients when the FBRs promoted legumes, dairy, vitamin A-rich vegetables, and chicken giblets. None of the FBRs tested ensured population-level dietary adequacy for thiamine, niacin, and iron unless a fortified infant food was recommended. CONCLUSIONS: The present study demonstrated the value of using LP to adapt NCFg for a different age group than the one for which they were designed. Our analyses suggest that to ensure dietary adequacy for 12- to 23-month olds these adaptations should include legumes, dairy products, vitamin A-rich vegetables, organ meat, and a fortified food.

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.

Pharmacotherapy prevention and management of nutritional deficiencies post Roux-en-Y gastric bypass.

Roux-en-Y gastric bypass is the most commonly performed bariatric procedure. It is associated with nutritional deficiencies due to gastric reduction, intestinal bypass, reduced caloric intake, avoidance of nutrient-rich foods, noncompliance with supplementation and poor food tolerability. Although there are multiple publications on this topic, there is a lack of consistent guidance for the healthcare practitioner caring for the bariatric patient. This article will encompass literature reviewing the pharmacotherapy approach to prevention and management of nutritional deficiencies since the American Society of Metabolic and Bariatric Surgery guidelines were published in 2008.

A novel scoring system to guide risk assessment of Wernicke's encephalopathy.

BACKGROUND: Thiamine deficiency in patients who abuse alcohol can cause Wernicke's encephalopathy (WE). Thiamine supplements are given to prevent this complication. Guidelines exist for giving thiamine supplementation in the inpatient population. However, similar guidelines are not available for clinicians detoxifying patients in the community, and consequently, assessment of risk of WE and prophylaxis can be inconsistent. METHODS: A scoring system to assess risk of WE was developed and evaluated by comparing practice before and after introduction of the system. One hundred and twenty-six cases requiring alcohol detoxification were examined: 94 before introduction of the scoring system and 32 afterward. RESULTS: Before introduction of the scoring system, a risk assessment for developing WE was performed in 30% of patients and parenteral thiamine prescribed in 32%. After introduction of the scoring system, risk assessment and administration of parenteral thiamine increased to 100 and 75%, respectively. There was 1 probable case of WE before introduction of the scoring system and none afterward. CONCLUSIONS: We conclude that assessment of WE is often inadequate, leading to inadequate thiamine administration. The new scoring system allows simple, structured risk assessment for WE and thus guides appropriate thiamine administration. This is of most value to clinicians treating the consequences of alcohol dependence in the community.

Increased thiamine intake may be required to maintain thiamine status during weight loss in patients with type 2 diabetes.

During weight loss, erythrocyte thiamine pyrophosphate (TPP) decreased (221±52 to 195±39 nmol/L, P<0.05) on a diet with adequate thiamine (1.1 mg/day) but was unchanged (217±55 vs 218±52 nmol/L, NS) on a high thiamine diet (2.8 mg/day). Attention to thiamine status may be required in patients with diabetes after weight loss.

Thiamine in nutrition therapy.

Clinicians involved with nutrition therapy traditionally concentrated on macronutrients and have generally neglected the importance of micronutrients, both vitamins and trace elements. Micronutrients, which work in unison, are important for fundamental biological processes and enzymatic reactions, and deficiencies may lead to disastrous consequences. This review concentrates on vitamin B(1), or thiamine. Alcoholism is not the only risk factor for thiamine deficiency, and thiamine deficiency is often not suspected in seemingly well-nourished or even overnourished patients. Deficiency of thiamine has historically been described as beriberi but may often be seen in current-day practice, manifesting as neurologic abnormalities, mental changes, congestive heart failure, unexplained metabolic acidosis, and so on. This review explains the importance of thiamine in nutrition therapy and offers practical tips on prevention and management of deficiency states.

Thiamine (vitamin B1) deficiency and associated brain damage is still common throughout the world and prevention is simple and safe!

Many different population groups throughout the world have thiamine deficiency and are at risk of developing severe neurological and cardiac disorders. Alcoholics are most at risk but other important clinical groups should be monitored carefully. The most severe, potentially fatal disease caused by thiamine deficiency is the neurological disorder Wernicke-Korsakoff syndrome. This can be difficult to diagnose and many cases remain undiagnosed. Treatment with thiamine generally results in a dramatic clinical improvement. Thiamine supplementation of stable food products like flour is an effective, simple and safe public health measure that can improve the thiamine status of all population groups.

The repeating history of objections to the fortification of bread and alcohol: from iron filings to folic acid.

The fortification of staple foods has eliminated many deficiency diseases. Despite this, "tampering" with people's food always provokes opposition, much of it from health professionals. Opposition is often based on self-interest, tunnel vision and theory rather than research. A historical perspective of the patterns of objections to fortification and its outcomes may help resolve the anxieties and opposing ethical positions of advocates and opponents of fortification.

Water-soluble vitamins: research update.

For more than 50 years, the Food and Nutrition Board of the National Academy of Sciences has been reviewing nutrition research and defining nutrient requirements for healthy people, referred to as the recommended dietary allowances (RDA). As new nutrition research is published, the importance of vitamins as vital nutrients is underscored, and new physiologic roles and applications to human health are examined and considered with regard to updating the RDA. Each year a substantial amount of research is published on vitamins. This article examines and summarizes noteworthy research published on individual water-soluble vitamins (excluding vitamin C) in the past 12 months, provides relevant background information on these vitamins, and offers critical reviews as appropriate.

[Is thiamine supplementation necessary in patient with cardiac insufficiency?]. / Une supplémentation en thiamine est-elle nécessaire chez les insuffisants cardiaques?

Interest has recently risen regarding thiamine deficiency in patients with cardiac deficiency who are receiving long-term diuretic therapy. Thiamine deficiency can lead biventricular myocardial failure (cardiac beriberi), and treatment consists of thiamine administration. Studies have shown that long-term furosemide use may be associated with thiamine deficiency through urinary loss, contributing to cardiac insufficiency in patients with congestive heart failure. Thiamine supplementation could improved left ventricular function. However, the results of those studies are controversial, and none study have till proved the clinical impact of a systematic administration of thiamine in a cohort of patients with cardiac insufficiency. To date, and waiting for available literature, thiamine administration should be consider in patients at risk for thiamine deficiency (elderly, malnourished, alcoholic), and in patients receiving very large doses of diuretics.