Thiamine

Thiamine (vitamin B1) is a water-soluble sulphur-containing vitamin of the B-complex, also named as the ‘thio-vitamin’ and was isolated in 1926 by a Dutchman named Jansen. It is an essential cofactor in humans that must be obtained from diet, because humans cannot synthesise thiamine. Recommended daily intake of thiamine from exogenous sources e.g. yeasts and plants is between 1 and 1.4 mg/day. After absorption from the gastrointestinal tract, thiamine is taken up into tissues by transport proteins and converted to the active phosphorylated thiamine derivatives. This section will discuss thiamine supplementation as a treatment option in diabetes mellitus.

Diabetes mellitus and thiamine deficiency

Thiamine deficiencies have been found in patients with type 1 and type 2 diabetes mellitus, but the exact prevalence is not known and varies from 17% to 79%. Nowadays, it is still not completely understood which mechanism is responsible for thiamine deficiency in diabetes mellitus. Insulin deficiency has been found to be associated with a reduction in the rate of thiamine transport across the intestine[1]. Thiamine deficiency leads to an impairment in insulin synthesis and secretion in the pancreas and thereby insulin deficiency, which could potentially lead to a vicious circle[2]. Furthermore, the effects of renal dysfunction in diabetes on thiamine excretion remain unclear[3][4]. Finally, in theory, reduction in active thiamine absorption and reduced pancreatic function could also be due to altered functioning of thiamine transporter proteins[5].

Thiamine assessment and supplementation

Thiamine status can be assessed by measuring serum thiamine levels or red cell thiamine concentration as a well-known representative of thiamine body stores. Erythrocyte transketolase activity can also be measured as a functional assessment of thiamine status. Oral thiamine replacement is available as thiamine hydrochloride, a water-soluble compound. Benfotiamine is a lipid-soluble allithiamine derivative with a better intestinal absorption and improved bio-availability. After thiamine supplementation, normalized red cell thiamine levels have been found in patients with diabetes mellitus whereas an increased dietary intake above the daily recommended intake did not show higher levels [6].

Rationale for thiamine’s effectiveness in the treatment of diabetes

Thiamine acts as a coenzyme for transketolase, pyruvate dehydrogenase and α-ketoglutarate dehydrogenase complex, all playing a pivotal role in intracellular glucose metabolism. Thiamine and derivatives act as antioxidants and play a role in the defence mechanisms against adverse effects of hyperglycemia. Thiamine has shown a reduction of activity through the hexosamine and polyol pathway; it prevents hyperglycemia induced formation of advanced glycation endproducts and it plays a role in the reduction of protein kinase C activity. All these pathways of the glucose metabolism will finally have a beneficial effect on the endothelium [7].

Clinical evidence

There is less-convincing evidence that thiamine reduces fasting glucose and HbA1c levels. However, several in vitro and in vivo studies have shown a positive effect of thiamine and benfotiamine on endothelial function and oxidative stress parameters. Human studies have shown that thiamine improved endothelium-dependent vasodilatation in the presence of hyperglycemia and thiamine was also associated with different markers of the endothelium representing an improved vascular endothelial function[3][8]. In type 2 diabetes patients, benfotiamine prevented macro- and microvascular endothelial dysfunction reflected by improvement of flow mediated vasodilatation as well as reduced serum markers of endothelial dysfunction[9]. Thiamine supplementation also showed decreased urinary albumin excretion, whereas benfotiamine did not had that same effect in type 2 diabetes mellitus [10][11][12]. However, beneficial effects of benfotiamine have been seen in patients with diabetic neuropathy [13][14]. All these studies had small sample sizes and had limited follow up duration of maximum 5 months. One also could not rule out selection bias in some of the studies. Furthermore, there is no evidence about thiamine or benfotiamine as a treatment option in diabetes mellitus in reducing cardiovascular and mortality risk.

Conclusion

There is no convincing evidence that taking supplements of thiamine or benfotiamine has any beneficial effects in patients with diabetes mellitus.

References

  1. ^ Patrini CL, Gastaldi G, Verri A, Ferrari G, Rindi G. Effect of insulin on thiamine intestinal transport in rat everted jejunal sacs. J Physiol. 1996;493:100S-101S.

  2. ^ Mee LNS, Sekar VT, Subramanian VS, Maedler K, Said HM. Pancreatic beta cells and islets take up thiamin by a regulated carrier-mediated process: studies using mice and human pancreatic preparations. Am J Physiol Gastrointest Liver Physiol. 2009;297:G197-G206.

  3. ^ Thornalley PJ, Babaei-Jadidi R, Al Ali H et al. High prevalence of low plasma thiamine concentration in diabetes linked to a marker of vascular disease. Diabetologia. 2007;50:2164-2170.

  4. ^ Pascal L, Tomandl J, Svojanovsky J et al. Role of thiamine status and genetic variability in transketolase and other pentose phosphate cycle enzymes in the progression of diabetic nephropathy. Nephrol Dial Transplant. 2010; DOI:10.1093/ndt/gfq550.

  5. ^ Page GL, Laight D, Cummings MH. Thiamine deficiency in diabetes mellitus and the impact of thiamine replacement on glucose metabolism and vascular disease. Int J Clin Pract. 2011;65:684-90.

  6. ^ Vindedzis SA, Stanton KG, Sherriff JL, Dhaliwal SS. Thiamine deficieny in diabetes – is diet relevant? Diab Vasc Dis Res. 2008;5:215.

  7. ^ Hammes HP, Du X, Edelstein D et al. Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy. Nat Med. 2003;294-299.

  8. ^ Arora S, Lidor A, Abularrage CJ et al. Thiamin (vitamin B1) improves endothelium-dependent vasodilatation in the presence of hyperglycemia. Ann Vasc Surg. 20006;20:653-658.

  9. ^ Stirban A, Negrean M, Stratmann B et al. Benfotiamine prevents macro- and microvascular endothelial dysfunction and oxidative stress following a meal rich in advanced glycation end products in individuals with type 2 diabetes. Diabetes Care. 2006;29:2064-2071.

  10. ^ Rabbani N, Alam SS, Riaz S et al. High-dose thiamine therapy for patients with type 2 diabetes and microalbuminuria: a randomized, double-blind placebo-controlled pilot study. Diabetologia. 2009;52:208-212.

  11. ^ Riaz S, Skinner V, Srai SK. Effect of high dose thiamine on the levels of urinary protein biomarkers in diabetes mellitus type 2. J Pharm Biomed Anal. 2011;54;817-825.

  12. ^ Alkhalaf A, Klooster A, van Oeveren W et al. A double-blind, randomized, placebo-controlled clinical trial on benfotiamine treatment in patients with diabetic nephropathy. Diabetes Care. 2010;33(7):1598-1601.

  13. ^ Haupt E, Ledermann H, Köpcke W. Benfotiamine in the treatment of diabetic polyneuropathy-a three-week randomized, controlled pilot study (BEDIP study). Int J Clin Pharmacol Ther. 2005; 43:71-77.

  14. ^ Stracke H, Gaus W, Achenbach U, Federlin K, Bretzel RG. Benfotiamine in diabetic polyneuropathy (BENDIP): results of a randomized, double blind, placebo-controlled clinical study. Exp Clin Endocrinol Diabetes. 2008;116:600-605.

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