Vitamin B1 (thiamine)BackgroundThiamine is a water-soluble vitamin of the B complex. It is a coenzyme in the metabolism of carbohydrates and branched chain amino acids. In this capacity, it acts as an enzymatic cofactor in oxidative decarboxylation reactions mediated by pyruvate dehydrogenase. It is also involved in the transketolation of the pentose phosphate pathway. Thiamine has functions independent of its coenzyme function in the initiation of nerve impulse propagation.Thiamine is absorbed in the upper small intestine. Most thiamine in the circulation is within red blood cells and the remaining amount is albumin-bound. Thiamine and its metabolites are excreted principally in urine [3].Thiamine is found in enriched, fortified, or whole grain products. The RDA for thiamine is 1.2 mg/day in males and 1.1 mg/day in females [4]. The tolerable upper intake level (UL) for toxicity is not determined [4].General PopulationThiamine deficiency manifests clinically as anaerobic metabolism (leading to lactic acidosis), neurologic impairment (peripheral neuropathy), and cardiovascular disease (congestive heart failure). Wernicke's encephalopathy is the most frequently encountered clinical manifestation of thiamine deficiency and occurs in individuals with impaired nutrition from any cause. No adverse effects associated with excess thiamine from food or supplements have been reported.Thiamine deficiency can be ascertained by its direct measurement in whole blood or serum (normal range: 60–112 nmol/l) or by measuring the activity of the enzyme transketolase in erythrocytes (ETK) before (ETKo) and after an in vitro vitamin supplement is added. This is then expressed as the ratio of enzyme activity after/before vitamin addition (α-ETK). A value of greater than one reflects a large increase in enzyme activity after exogenous addition of the vitamin and reflects intra-cellular deficiency [5].People with Low Glomerular Filtration Rate & End-Stage Renal DiseaseThe median thiamine intake in patients with ESRD is insufficient compared with the RDA for the healthy population [6]. Studies evaluating circulating plasma concentrations of thiamine report normal levels in dialysis patients [7], whereas those reporting ETKo activity either report normal or low thiamine status [5, 8]. Two studies have evaluated both simultaneously and demonstrated that most of these patients had normal concentrations of circulating thiamine, but close to 50% of dialysis patients had low or marginal ETKo levels highlighting the controversy in interpreting thiamine status [5, 9]. The single longitudinal study of thiamine status in a nonsupplemented group of 15 dialysis patients demonstrated that nearly all patients maintained normal plasma and erythrocyte thiamine levels over 12 months of observation [7]. Cross-sectional studies of dialysis patients identify a very low proportion of patients with thiamine deficiency in patients who receive a postdialysis oral multivitamin containing 100 mg thiamine two or three times per week [5, 10].Thiamine Status and the Dialysis ProcedureThree studies have reported the change in plasma thiamine concentrations before and after a single dialysis treatment. One study demonstrated that hemodialysis resulted in a small, but potentially clinically significant, lowering of thiamine levels. Although there was a difference between dialyzer types (4% and 9% reduction in thiamine with a low-flux and high-flux dialyzer, respectively), this difference was not statistically significant [11]. However, two other studies demonstrated slightly higher concentrations of thiamine after treatment [9, 12]. Taken together, a consistent effect of dialysis has not been demonstrated.Thiamine SupplementationCurrent recommendations suggest a daily supplement of 1.1–1.2 mg thiamine. We did not identify any comprehensive studies. One study, and a number of case reports, suggests that supplementary thiamine should be particularly considered in dialysis patients with mental status changes [13-16]. Baseline thiamine levels pre- and postintravenous thiamine supplementation was assessed in 10 dialysis patients with unexplained encephalopathy and values were compared with those of healthy patients on hemodialysis and healthy controls [16]. Dialysis patients with encephalopathy had lower thiamine concentrations (35.3 ± 6.0 nmol/l) than dialysis patients without encephalopathy (85.6 ± 12.2 nmol/l). Healthy control subjects had even higher (96.8 ± 18.6 nmol/l) levels.Extended-hours DialysisThiamine levels were lower in patients on extended hours dialysis than in patients on conventional hours (median 211 vs. 439 nmol/l, p = 0.0005), but the clinical significance of this is doubtful as no patient was deficient in the extended-hours group and one patient (3.8%) was deficient in the conventional group (Table 3) [17]. Patients in this study received a multi-vitamin containing 7.27 mg thiamine daily, six fold more than the RDA.SummaryThe available evidence indicates that there are exceedingly few cases of thiamine deficiency identified in dialysis patients who are routinely exposed to a postdialysis multivitamin supplement containing thiamine. A daily supplement of thiamine hydrochloride (1.1–1.2 mg/day) is recommended by the European Best Practice Guidelines on Nutrition [18]. The 2005 recommendations from the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (K/DOQI) for cardiovascular disease do not provide specific recommendation for thiamine supplementation [19]. To the best of our knowledge, there is no trial with a clinical endpoint that has evaluated thiamine supplementation in any CKD population. The association between poor thiamine status and unexplained encephalopathy and its improvement with intravenous thiamine support future studies evaluating thiamine status in a people with low GFR and on dialysis.
Water soluble vitamins (summary)
Vitamin B1 (thiamine)
Vitamin B2 (Riboflavin), Vitamin B3 (Niacin = nicotinic acid; niacinamide = nicotinamide)
Vitamin B7 (biotin), Vitamin B9 (folic acid, folate)
Clase, C. M., Ki, V. and Holden, R. M. (2013), Water-Soluble Vitamins in People with Low Glomerular Filtration Rate or On Dialysis: A Review. Seminars in Dialysis, 26: 546–567. doi: 10.1111/sdi.12099
Comments