Dehydrogenase (DLD) Deficiency in an Iranian Patient with Recurrent Intractable Vomiting: Successful Treatment with Thiamine Supplementation.

Dihydrolipoamide dehydrogenase (DLD) deficiency is a rare disease of genetic origin due to the malfunctioning of a shared subunit of three mitochondrial multi-enzyme complexes. Phenotypes of this disease are a set of clinical manifestations ranging from neonatal disorders to myopathy or recurrent episodes of liver failures, and vomiting for which no adequate or definitive treatment is currently available. This study described a case involving a 16-year-old boy who had experienced recurrent vomiting of unknown cause from age two. Normal value ranges for the basic metabolic panel were reported in previous years. The patient was admitted with Wernicke's encephalopathy after the last vomiting attack, also indicating metabolites of organic acids compatible with DLD deficiency. Whole exome sequencing identified a known pathogenic mutation in the DLD gene, leading to a diagnosis of DLD deficiency. Our patient was treated with a high dose of thiamine supplementation and continued treatment, has not experienced any vomiting attacks or related problems in the last two years and has adequately responded to the treatment prescribed. Normal urine organic acid levels in patients with recurrent vomiting cannot roll out DLD deficiency. However, although thiamine deficiency typically induces Wernicke's encephalopathy, it can also be implicated in pyruvate dehydrogenase complex (PDHc) deficiency, and high-dose thiamine therapy (with doses up to 30 mg/kg) is recommended for deficient patients.

Effects of dietary thiamin (vitamin B1) on the growth performance, serum biochemical factors, immune response, and antioxidant activity of great sturgeon (Huso huso) juveniles.

The present research evaluated the positive effects of dietary thiamin (vitamin B1) levels on the growth performance, serum biochemistry factors, immune response, and antioxidant activity of great sturgeon (Huso huso) juveniles. Thiamin was included in diets with levels of 0 (control, T0), 7 (T7), 15 (T15), and 25 (T25) mg/kg diet. Measurements of thiamin levels in diets indicated that they contained 1.80 (T0), 8.02 (T7), 16.2 (T15), and 26.6 (T25) mg thiamin/kg feed. Sturgeon juveniles (240 individuals) with average weight of 44.8 ± 1.96 g were distributed into 12 tanks, and fed with the experimental diets for 8 weeks. Final weight, body weight gain (%), specific growth rate, and feed conversion ratio (FCR) of great sturgeon were significantly influenced by dietary thiamin levels, and the maximum fish performance (P < 0.05) was obtained at a level of 15 mg/kg diet. The trypsin, chymotrypsin, creatine kinase, lipase, α-amylase, and alkaline phosphatase activities were notably (P < 0.05) affected by the dietary thiamin levels. The glucose content was not significantly (P > 0.05) different among the experimental treatments. Diets supplemented with thiamine increased significantly (P < 0.05) triglyceride, cholesterol, and total protein levels accompanied with significant (P < 0.05) decreases in aminotransferase aspartate and alanine aminotransferase activities. Serum antioxidant enzymes were remarkably (P < 0.05) higher, while serum malondialdehyde was significantly (P < 0.05) lower in the thiamin-treated fish compared with the control group. Total immunoglobulin, lysozyme, and ACH50 values were significantly (P < 0.05) higher in fish fed with thiamin-supplemented diets than in the control group. The results of the present study demonstrated that dietary thiamin have an important role in enhancing the growth performance, immune response, and antioxidant activity of great sturgeon. Based on the regression fitting curve of final weight, weight gain, specific growth rate, and FCR values, the optimal level of thiamin is found to be 15.0-17.5 mg/kg diet.

Bacterial lipopolysaccharide inhibits colonic carrier-mediated uptake of thiamin pyrophosphate: roles for TLR4 receptor and NF-κB/P38/JNK signaling pathway.

This study investigated the effect of the bacterial endotoxin lipopolysaccharide (LPS) on colonic uptake of thiamin pyrophosphate (TPP), the biologically active form of vitamin B1 that is generated by gut microbiota. We used three complementary models in our study: in vitro (human-derived colonic epithelial NCM460), ex vivo (human differentiated colonoid monolayers), and in vivo (mouse colonic tissue). The results showed that exposure of NCM460 cells to LPS leads to a significant inhibition of carrier-mediated TPP uptake as well as in decreased expression of the colonic TPP transporter (cTPPT) protein, mRNA, and heterologous nuclear RNA (hnRNA) compared with untreated controls. Similarly, exposure of human differentiated colonoid monolayers and mice to LPS caused significant inhibition in colonic carrier-mediated TPP uptake and in cTPPT protein, mRNA, and hnRNA expression. The effect of LPS on colonic TPP uptake and cTTPT expression was also found to be associated with a significant reduction in activity of the SLC44A4 promoter as well as in decreased expression of the nuclear factor Elf-3 (E74-like ETS transcription factor 3), which is needed for promoter activity. Finally, we found that knocking down the Toll-like receptor 4 (TLR4) and blocking the nuclear factor kappa B (NF-κB), JNK, and p38 signaling pathways with the use of pharmacological inhibitors lead to significant abrogation in the degree of LPS-mediated inhibition in TPP uptake and cTPPT expression. These results demonstrated that exposure of colonic epithelia to LPS inhibits colonic TPP uptake via transcriptional mechanism(s) and that the effect is mediated via TLR4 receptor and NF-κB/p38/JNK signaling pathways.NEW & NOTEWORTHY This study examined the effect of the bacterial lipopolysaccharide (LPS) on the colonic uptake of thiamin pyrophosphate (TPP), the biologically active form of vitamin B1. Three complementary models were used: in vitro (human NCM460 cells), ex vivo (human colonoids), and in vivo (mice). The results showed LPS to significantly suppress TPP uptake and the expression of its transporter, and that these effects are mediated via the membrane TLR4 receptor, and involve the NF-κB/p38/JNK signaling pathways.

Impact of supplemental thiamin on lactate levels in adults with septic shock.

BACKGROUND: Elevated lactate levels at 24 h are highly predictive of in-hospital mortality in adults with septic shock. Thiamin is closely involved in carbohydrate metabolism, and in thiamin-deficient states, increased lactic acid levels can be found, exacerbated by critical illness. This integrative literature review focused on the relationship between supplemental thiamin, lactate clearance, and impact on mortality in sepsis. METHODS: A search in PubMed, Embase, and CINAHL was conducted for literature published between January 2016 and January 2021. We included observational studies and clinical trials with ≥10 participants. We excluded studies involving pediatric (<18 years old) populations, animal studies, case studies, dropout rate of >20%, nonhospitalized patients, or patients receiving comfort measures only. RESULTS: A total of 48 full-text articles were assessed for eligibility, with 15 evaluated for this integrative review. Included were five retrospective, two prospective observational, and eight randomized controlled trials. In almost all retrospective studies, thiamin administration was associated with decreased mortality, and in observational studies, with decreased lactate and improved clinical outcomes. In clinical trials, thiamin with or without vitamin C/hydrocortisone did not impact clinical outcomes or mortality. However, four trials testing intravenous thiamin 200-500 mg two to three times daily for up to 3 days reported improved lactate clearance. CONCLUSIONS: Thiamin supplementation may improve lactate clearance when administered in the first 24 h. Those deficient in thiamin may benefit more from supplementation. The combination of thiamin, vitamin C, and/or hydrocortisone may not be advantageous. Lactate reduction in response to thiamin needs further rigorous research.

Recognizing neonatal refeeding syndrome and thiamin supplementation: A case report.

Refeeding syndrome (RS) is a condition characterized by electrolyte derangements, thiamin deficiency, and organ dysfunction after the provision of nutrition to an individual who had been deprived of nutrients. Published guidelines outlining the recognition and definition of RS exist for adult and children, but there are limited newborn-specific guidelines because of a paucity of available literature and variation in reporting. We describe a small-for-gestational-age, full-term newborn with neonatal encephalopathy who underwent therapeutic hypothermia. Electrolyte derangements and lactic acidosis developed and persisted after the introduction of intravenous nutrition. After the exclusion of other etiologies, neonatal RS was suspected, and the newborn was treated with thiamin. We provide a brief review of the current literature on neonatal RS, present a case report consistent with neonatal RS, and provide suggestions for the utility of thiamin replacement in newborns with suspected neonatal RS.

Effects of Storage Time and Thawing Method on Selected Nutrients in Whole Fish for Zoo Animal Nutrition.

Piscivores in human care receive whole fish that were frozen, stored and thawed before feeding. Nutrient losses have been documented, but exact changes during storage and with different thawing methods are unknown. Primarily, it was hypothesized that frozen fish lose different vitamins and trace minerals during a storage period of six months. Secondly, that different thawing methods have a significant influence on the degree of vitamin loss. Three fish species, herring (Clupeus harengus), mackerel (Scomber scombrus) and capelin (Mallotus villosus) were analyzed at four time points within a storage period of 6 months at -20 °C. At each time point, three thawing methods were applied: thawing in a refrigerator (R), thawing at room temperature (RT), and thawing under running water (RW). The following nutrients were analyzed: vitamin A, B1, D3 and E, iron (Fe), copper (Cu), zinc (Zn) and selenium (Se). The statistical method used was a linear mixed effect model. Cu was below detection limits in all analyzed samples, vitamin B1 in most analyzed herring (44/48 samples) and capelin (in 25/36 samples), respectively. In addition, the vitamin D3 concentration was also below detection limits in half of the capelin samples (18/36). No concentration changes of Fe (p = 0.616), Zn (p = 0.686) or Se (p = 0.148) were observed during a storage period of six months, in contrast to a significant decrease in vitamin A (p = 0.019), D3 (p = 0.034) and E (p = 0.003) concentrations. Thawing fish with different thawing methods did not result in concentration changes of Fe (p = 0.821), Zn (p = 0.549) or Se (p = 0.633), but in a significant concentration change of vitamin A (p = 0.002). It is essential to supplement vitamins B1 and E in diets containing whole fish to avoid deficiencies in piscivorous species, and care should be taken not to store fish longer than six months, due to the depletion of vitamins A, D3 and E.

B1 Vitamin Deficiency After Bariatric Surgery, Prevalence, and Symptoms: a Systematic Review and Meta-analysis.

B1 deficiency is a very prevalent complication of bariatric surgery. This study reviews prevalence and symptoms of B1 vitamin deficiency after bariatric surgery. PubMed, Scopus, and Web of Science published were searched up to 10 Feb 2022, with the following keywords: Roux-en-Y gastric bypass, one anastomosis gastric bypass, Omega bypass, Mini bypass, Bariatric surgery OR Bariatric surgery, metabolic surgery, Weight loss surgery, Classic gastric bypass, Loop gastric bypass, Gastric Bypass, thiamine OR thiamin, beriberi, B1. A total of 11 studies examining 1494 patients were included in this meta-analysis. Twenty-seven percent of patients who underwent bariatric surgeries experience vitamin B1 deficiency. Thiamine supplements should be prescribed for the patients for the rest of their lives, and also standard post-surgery follow-ups are necessary in terms of monitoring dietary factors.

ESPEN micronutrient guideline.

BACKGROUND: Trace elements and vitamins, named together micronutrients (MNs), are essential for human metabolism. Recent research has shown the importance of MNs in common pathologies, with significant deficiencies impacting the outcome. OBJECTIVE: This guideline aims to provide information for daily clinical nutrition practice regarding assessment of MN status, monitoring, and prescription. It proposes a consensus terminology, since many words are used imprecisely, resulting in confusion. This is particularly true for the words "deficiency", "repletion", "complement", and "supplement". METHODS: The expert group attempted to apply the 2015 standard operating procedures (SOP) for ESPEN which focuses on disease. However, this approach could not be applied due to the multiple diseases requiring clinical nutrition resulting in one text for each MN, rather than for diseases. An extensive search of the literature was conducted in the databases Medline, PubMed, Cochrane, Google Scholar, and CINAHL. The search focused on physiological data, historical evidence (published before PubMed release in 1996), and observational and/or randomized trials. For each MN, the main functions, optimal analytical methods, impact of inflammation, potential toxicity, and provision during enteral or parenteral nutrition were addressed. The SOP wording was applied for strength of recommendations. RESULTS: There was a limited number of interventional trials, preventing meta-analysis and leading to a low level of evidence. The recommendations underwent a consensus process, which resulted in a percentage of agreement (%): strong consensus required of >90% of votes. Altogether the guideline proposes sets of recommendations for 26 MNs, resulting in 170 single recommendations. Critical MNs were identified with deficiencies being present in numerous acute and chronic diseases. Monitoring and management strategies are proposed. CONCLUSION: This guideline should enable addressing suboptimal and deficient status of a bundle of MNs in at-risk diseases. In particular, it offers practical advice on MN provision and monitoring during nutritional support.

Cardiac Dysfunction Due to Thiamine Deficiency after Hemodialysis for Biguanide-related Lactic Acidosis.

Biguanide is an ideal drug for the treatment of type 2 diabetes mellitus. When used appropriately, the incidence of lactic acidosis is reported to be very low. Risk factors associated with biguanide-related lactic acidosis include chronic kidney disease, congestive heart failure, alcohol use, severe dehydration, shock, hypoxic states, sepsis, and advanced age. We herein report a case of cardiac dysfunction due to thiamine deficiency after hemodialysis in a patient with suspected biguanide-related lactic acidosis. Patients who develop severe lactic acidosis while taking biguanides should be given a large dose of thiamine without delay, given the possibility of thiamine deficiency as a complication.

Dietary thiamin requirement of fingerling major carp Catla catla (Hamilton).

Dietary thiamin requirement of fingerling Catla catla (3.5 ± 0.15 g) was evaluated by feeding casein-gelatin-based iso-nitrogenous (350 g/kg crude protein) and iso-caloric (16.72 kJ/g GE) diets containing six graded levels of thiamin (0, 0.2, 0.4, 0.8, 1.6 and 3.2 mg/kg dry diet) for 12 weeks. Significantly (p < 0.05) higher weight gain (AWG), best feed conversion ratio (FCR), protein retention efficiency (PRE), RNA/DNA ratio and haematological indices were recorded in fish fed diet containing 0.8 mg/kg thiamin. Dietary thiamin supplementation improved transketolase activity (TKA) and maximum value was recorded in fish fed 0.8 mg/kg thiamin beyond which stagnation in TKA activity was evident. Liver thiamin concentration was found to be maximum in fish fed diet containing 1.6 mg/kg thiamin. A significant (p < 0.05) consistent reduction in the hepatic thiobarbituric acid reactive substances (TBARS) activity was displayed with incremental concentration of thiamin up to 0.8 mg/kg, beyond which a reverse trend was evident. However, a significant (p < 0.05) improvement was noted in superoxide dismutase (SOD) and catalase (CAT) activity with the increasing level of dietary thiamin from 0 to 0.8 mg/kg. Broken-line regression analysis of AWG, FCR, PRE and TKA estimated the requirement in the range of 0.74-0.79 mg/kg dry diet.

Anti-inflammatory and antioxidative effects of thiamin supplements in patients with gestational diabetes mellitus.

OBJECTIVE: The aim of this study was to evaluate the effects of thiamin supplementation on biomarkers of inflammation and oxidative stress in patients with gestational diabetes mellitus (GDM). METHODS: This randomized, double-blind, placebo-controlled trial was conducted among 60 patients with GDM. Patients were randomly allocated into two groups to receive either 100 mg/day thiamin supplements (n = 30) or placebo (n = 30) for 6 weeks. RESULTS: Thiamin supplementation significantly decreased serum high-sensitivity C-reactive protein (hs-CRP) (ß - 0.98 mg/L; 95% CI, -1.54, -0.42; p = .001) and plasma malondialdehyde (MDA) levels (ß - 0.86 µmol/L; 95% CI, -1.15, -0.57; p < .001) when compared with the placebo. In addition, thiamin supplementation downregulated gene expression of tumor necrosis factor-alpha (TNF-α) (p = .002) in peripheral blood mononuclear cells of patients with GDM. Thiamin supplementation did not affect other biomarkers of inflammation and oxidative stress. CONCLUSION: Overall, thiamin supplementation for 6 weeks to patients with GDM significantly reduced hs-CRP and MDA levels, and gene expression of TNF-α, but did not affect other biomarkers of inflammation and oxidative stress. CLINICAL TRIAL REGISTRATION NUMBER: Clinical Trials.govIdentifier no. http://www.irct.ir: IRCT20170513033941N58.

The Thiamin-Requiring 3 Mutation of Arabidopsis 5-Deoxyxylulose-Phosphate Synthase 1 Highlights How the Thiamin Economy Impacts the Methylerythritol 4-Phosphate Pathway.

The thiamin-requiring mutants of Arabidopsis have a storied history as a foundational model for biochemical genetics in plants and have illuminated the central role of thiamin in metabolism. Recent integrative genetic and biochemical analyses of thiamin biosynthesis and utilization imply that leaf metabolism normally operates close to thiamin-limiting conditions. Thus, the mechanisms that allocate thiamin-diphosphate (ThDP) cofactor among the diverse thiamin-dependent enzymes localized in plastids, mitochondria, peroxisomes, and the cytosol comprise an intricate thiamin economy. Here, we show that the classical thiamin-requiring 3 (th3) mutant is a point mutation in plastid localized 5-deoxyxylulose synthase 1 (DXS1), a key regulated enzyme in the methylerythritol 4-phosphate (MEP) isoprene biosynthesis pathway. Substitution of a lysine for a highly conserved glutamate residue (E323) located at the subunit interface of the homodimeric enzyme conditions a hypomorphic phenotype that can be rescued by supplying low concentrations of thiamin in the medium. Analysis of leaf thiamin vitamers showed that supplementing the medium with thiamin increased total ThDP content in both wild type and th3 mutant plants, supporting a hypothesis that the mutant DXS1 enzyme has a reduced affinity for the ThDP cofactor. An unexpected upregulation of a suite of biotic-stress-response genes associated with accumulation of downstream MEP intermediate MEcPP suggests that th3 causes mis-regulation of DXS1 activity in thiamin-supplemented plants. Overall, these results highlight that the central role of ThDP availability in regulation of DXS1 activity and flux through the MEP pathway.

Metabolic Therapy of Heart Failure: Is There a Future for B Vitamins?

Heart failure (HF) is a plague of the aging population in industrialized countries that continues to cause many deaths despite intensive research into more effective treatments. Although the therapeutic arsenal to face heart failure has been expanding, the relatively short life expectancy of HF patients is pushing towards novel therapeutic strategies. Heart failure is associated with drastic metabolic disorders, including severe myocardial mitochondrial dysfunction and systemic nutrient deprivation secondary to severe cardiac dysfunction. To date, no effective therapy has been developed to restore the cardiac energy metabolism of the failing myocardium, mainly due to the metabolic complexity and intertwining of the involved processes. Recent years have witnessed a growing scientific interest in natural molecules that play a pivotal role in energy metabolism with promising therapeutic effects against heart failure. Among these molecules, B vitamins are a class of water soluble vitamins that are directly involved in energy metabolism and are of particular interest since they are intimately linked to energy metabolism and HF patients are often B vitamin deficient. This review aims at assessing the value of B vitamin supplementation in the treatment of heart failure.

Vitamin B1 Intake and the Risk of Colorectal Cancer: a Systematic Review of Observational Studies.

Colorectal cancer is the main leading cause of death from cancer worldwide. Protective effects of vitamin B1 on colorectal cancer have been observed in some epidemiological studies. A systematic review and meta-analysis of observational studies evaluated the association of intake of vitamin B1 with the incidence of colorectal cancer. Relevant studies were identified in MEDLINE via PubMed (published up to September 2020). We extracted data from articles on vitamin B1 and used a multivariable-adjusted odds ratio (OR) and a random-effects model for analysis. We found seven articles meeting the inclusion criteria (1 of cohort studies and 6 case-control studies) and a total of 6,184 colorectal cancer cases were included in this meta-analysis. The multivariable-adjusted OR for pooled studies for the association of roughly the same high dose level versus the lowest vitamin B1 intake and the risk of colorectal cancer was 0.76 (95% confidence interval ([95%CI]: 0.65, 0.89). This meta-analysis studied the relationship between vitamin B1 and colorectal cancer. We found vitamin B1 intake was inversely associated with the risk of colorectal cancer. However, further research and large sample studies need to be conducted to better validate the result.

B-Vitamins and Choline in Human Milk Are Not Impacted by a Preconception Lipid-Based Nutrient Supplement, but Differ Among Three Low-to-Middle Income Settings-Findings From the Women First Trial.

Introduction: Optimal human milk (HM) B-vitamin concentrations remain undefined, especially in areas where undernutrition is prevalent. The impact of supplementation pre-conception through pregnancy on HM B-vitamin composition remains unknown. Methods: Human milk (HM) was collected at 2-weeks postpartum from 200 women in Guatemala, India, and Pakistan (the Women First Trial). The women were randomized to start a lipid-based nutrient supplement before conception, at end of the first trimester, or not at all; intervention continued until delivery. HM concentrations of eight B-vitamins and choline were assessed via ultra-performance liquid chromatography-tandem mass spectrometry. Maternal diet was assessed in early pregnancy, and infant growth followed through 6 months post-delivery. Results: Despite supplement exposure averaging 15.7 (pre-conception arm) and 6.0 months (prenatal arm), HM B-vitamins did not differ between arms, but site differences were evident. Guatemala had higher HM concentrations of vitamin B3 than Pakistan and India. Pakistan had higher HM concentrations of thiamin and vitamin B6 than India and Guatemala. Cohort average HM vitamin B2 (162 ± 79 µg/L) and B6 (31.8 ± 24.6 µg/L) fell below values defined as deficient in 81.5 and 85.5% of samples, potentially reflecting sampling procedures and timing. Maternal dietary intakes of only vitamin B6 and choline were associated with the corresponding concentrations in HM (p < 0.005). No HM B-vitamin concentrations were associated with infant growth. Conclusion: Prenatal supplementation for at least 6 months had no impact on HM B-vitamin concentrations at 2-weeks postpartum. Results suggest that the adequacy of HM composition was generally maintained, with potential exceptions of vitamin B2 and B6.

Lactic Acidosis Secondary to Thiamin Deficiency Following Autologous Stem Cell Transplantation.

A 22-month-old female with high-risk neuroblastoma completed 5 cycles of chemotherapy then underwent high-dose chemotherapy with autologous stem cell rescue (ASCR). Parenteral nutrition was administered from day +2 following ASCR, as she was unable to tolerate nasogastric feeds because of grade IV mucositis and vomiting. On day +12, she developed worsening metabolic acidosis with above reportable levels of lactic acid. Given the patient's well clinical appearance and paucity of evidence of end-organ dysfunction on physical examination and on laboratory studies, there was high suspicion that the patient's lactic acidosis did not result from tissue hypoxia and was, in fact, a type B lactic acidosis. Thiamin was empirically administered, with rapid improvement in lactic acidosis. Thiamin deficiency was later confirmed by laboratory studies drawn prior to thiamin administration.

Thiamin supplementation does not improve left ventricular ejection fraction in ambulatory heart failure patients: a randomized controlled trial.

BACKGROUND: Thiamin, a water-soluble B-complex vitamin, functions as a coenzyme in macronutrient oxidation and in the production of cellular ATP. Data suggest that thiamin depletion occurs in heart failure (HF). Therefore, thiamin supplementation in HF patients may improve cardiac function. OBJECTIVE: We sought to determine whether oral thiamin supplementation improves left ventricular ejection fraction (LVEF), exercise tolerance, and quality of life among patients with HF and reduced LVEF. METHODS: In this prospective, multicenter, double-blind, placebo-controlled randomized trial, eligible ambulatory patients with HF and reduced LVEF were recruited from 4 academic and community hospitals between 2010 and 2015. Participants were randomly assigned to receive either 200 mg oral thiamin mononitrate per day or placebo for 6 mo. RESULTS: Sixty-nine patients (mean ± SD age: 64 ± 12 y; 83% men; LVEF: 37% ± 11%) were randomly assigned: 34 received placebo and 35 received thiamin supplementation. Erythrocyte thiamin pyrophosphate and urine thiamin concentrations were significantly higher in the supplemented group than in the placebo group at 6 mo (P = 0.02 and <0.001, respectively). At 6 mo, LVEF was significantly higher in the placebo group than in the thiamin group (38%; 95% CI: 36%, 39% compared with 35%; 95% CI: 33%, 37%, P = 0.047) after adjusting for baseline measurements. There were no significant differences in Minnesota Living with Heart Failure score, distance walked in 6 min, and N-terminal prohormone of brain natriuretic peptide concentrations between the 2 groups. One patient (2.9%) in the thiamin-supplemented group and none in the control group died at 6 mo. CONCLUSIONS: In ambulatory patients with HF and reduced LVEF, thiamin supplementation for 6 mo did not improve LVEF, quality of life, or exercise capacity, despite increases in thiamin concentrations. These findings do not support routine thiamin supplementation in the treatment of HF and reduced LVEF.This trial was registered at clinicaltrials.gov as NCT00959075.

Thiamin deficiency in low- and middle-income countries: Disorders, prevalences, previous interventions and current recommendations.

BACKGROUND: Thiamin deficiency is a major public health concern in several low- and middle-income countries (LMICs)-current attention to the problem is lacking. AIM: This review discusses prevalence of thiamin insufficiency and thiamin-deficiency disorders (TDDs) in LMICs, outlines programmatic experience with thiamin interventions, and offers recommendations to improve public-health and research attention to thiamin in LMICs. DISCUSSION: Thiamin insufficiency, i.e. low-blood-thiamin status, is endemic among several Southeast Asian countries: Cambodia (70-100% of infants and 27-100% of reproductive-age women); Laos (13% of hospitalized infants); Thailand (16-25% of children and 30% of elderly adults). Thiamin deficiency accounts for up to 45% of under-5 deaths in Cambodia, 34% of infant deaths in Laos, and 17% of infant deaths in Myanmar. Deficiency also exists in Africa, Asia, and the Americas, but these instances have typically been isolated. Exclusively breastfed infants of thiamin-deficient mothers are at highest risk for TDD and related death. Intervention strategies that have been employed to combat thiamin deficiency include food processing, fortification, supplementation, dietary diversification, and dietary behaviors, all of which have shown varying levels of effectiveness. CONCLUSIONS: We recommend universal thiamin-fortification of context-specific staple-foods in LMICs as a promising solution, as well as thiamin supplementation, particularly for pregnant and lactating women. Food processing regulations, dietary diversification, and modification of dietary behaviors to increase consumption of thiamin-rich foods may provide benefits in some circumstances, especially in countries without universal fortification programs or in populations dependent on food aid.

Role of Thiamin in Health and Disease.

Thiamin is a hydrosoluble vitamin that plays a role in several biological processes, mainly in glucose metabolism. There are several risk factors for developing thiamin deficiency, such as malnutrition, refeeding syndrome, gastrointestinal surgery, and alcoholism. Recently, the role of thiamin in critically ill patients has gained prominence, and the prevalence of thiamin deficiency was found to be increased in patients with severe burns, major surgery, septic shock, end-stage renal disease, and heart failure. In adults, thiamin deficiency presents as encephalopathy, dry beriberi (with neurological signs and symptoms), or wet beriberi (with cardiovascular signs and symptoms). Thiamin deficiency can be diagnosed clinically, and all clinicians should be aware of this disease, especially in patients with risk factors for thiamin deficiency. Thiamin supplementation should be started as early as possible in patients suspected to have thiamin deficiency. Treatment is safe, inexpensive, simple, and life-saving. Diagnosis is confirmed on a positive response to treatment.

Global Concerns with B Vitamin Statuses: Biofortification, Fortification, Hidden Hunger, Interactions, and Toxicity.

The prevalence of undernutrition due to insufficient energy intake has been reduced by nearly 50% since 1990. This reduction is largely attributed to improved yields of staple crops, such as wheat, rice, and maize; however, these improvements did little for micronutrient deficiencies that affect an estimated two billion people worldwide. Starchy staple crops are energy dense but are often lacking in one or more B vitamins, making resource-constrained people who consume monotonous diets comprised predominantly of these staples at risk for developing deficiency. B vitamin deficiencies occur due to a poor overall nondiversified diet and rarely occur alone. Many B vitamins are essential cofactors involved in the metabolism of other nutrients, including other B vitamins, whereby the deficiency of one B vitamin affects the metabolism and status measurements of another. Food fortification efforts have nearly eradicated diseases of extreme B vitamin deficiency, such as beriberi from thiamin deficiency and pellagra from niacin deficiency. However, subclinical deficiency, sometimes referred to as hidden hunger, is still common especially in low-income countries. Most dietary B vitamins, due to their water-soluble nature, are not a concern for excessive intakes, but synthetic forms used for fortification and supplements sometimes can have adverse effects when consumed in high amounts. Biofortified crops offer a long-term sustainable method to increase the amount of dietary B vitamins for people who rely on staple crops for most of their caloric intake. Efforts have been made to improve B vitamin content of crops, especially for thiamin, vitamin B6 , and folate, but none have undergone human feeding trials; therefore, more research is needed to provide sustainable and scalable solutions in many parts of the world.