Thiamine or benfotiamine use in people with diabetes

This is another draft document (see yesterday's on glucosamine and chondroitin) - written by me and no-one else - based on my reading of the literature. It might be wrong and I would strongly advise anyone reading to consider this 'preliminary' and to take any medical advice not from me (not medically trained) but from their own doctor / healthcare team.

Having said that, I'd be grateful if you told me if this did or didn't make sense - or if you think I've missed an important paper or given undue weight to a less important one.

A short URL for this page is http://is.gd/a3kR8

Thiamine or benfotiamine use in people with diabetes
The Vitamin B complex is a group of water-soluble vitamins including thiamine (vitamin B1), riboflavin (vitamin B2), nicotinic acid (vitamin B3), pantothenic acid (vitamin B5), pyridoxine (vitamin B6), biotin (vitamin B7), folic acid (vitamin B9) and cyanocobalamin (vitamin B12) with other compounds (Ang 2008). All of the B vitamins are required in the diet in very small amounts as these essential substances cannot be synthesised by the body.

Specific vitamin B deficiency diseases in humans include beriberi (thiamine, vitamin B1), megaloblastic anaemia (folic acid, vitamin B9), and pernicious anaemia (cobalamin, vitamin B12); these B vitamins may be of particular importance in people with diabetes.

I'm planning a follow up on folic acid and cobalamins - women with diabetes who are or wish to be pregnant are currently advised to take 5mg (available only on prescription) of folic acid to prevent neural tube defects, and in long-term use of metformin there can be a reduction in the absorption of cobalamin / B12.

Folic acid supplementation in pregnancy
http://www.diabetes.org.uk/about_us/our_views/care_recommendations/folic_acid_supplementation_in_pregnancy/

Metformin SPC (go to section 4.8 - undesirable effects)
http://emc.medicines.org.uk/medicine/1043/SPC/Glucophage+500+mg+and+850+mg+film+coated+tablets/

Thiamine (Vitamin B1)
Recommended levels of thiamine are 1mg a day for men and 0.8mg for women (Food Standards Agency) and up to 1.8mg/day in pregnant or breastfeeding women (Expert group on vitamins and minerals, 2003). Thiamine present in food is efficiently absorbed; however water-soluble supplements may be less well absorbed (Expert group on vitamins and minerals, 2003).

Good sources of Vitamin B1 include "unrefined grain products, meat products, vegetables, dairy products, legumes, fruits and eggs" (Expert group on vitamins and minerals, 2003). Fortification of white and brown flour with thiamine (not less than 0.24mg/100g flour) to replace that lost during processing means that cereal products are also a rich source of this vitamin (Expert group on vitamins and minerals, 2003).

Benfotiamine is a fat-soluble derivative of Vitamin B1 / thiamine and may have greater bioavailability (Stracke 1996).

Thiamine (Vitamin B1) deficiency in people with diabetes
In the general population a severe lack of thiamine, resulting from malnutrition, leads to the deficiency syndrome known as beriberi which is characterised by serious painful neurological and muscular problems, including cardiovascular problems. Heavy alcohol use can also impair the uptake and use of thiamine leading to its deficiency and can result in painful alcoholic neuropathy.

A small pilot study has indicated that people with Type 1 or Type 2 diabetes may be generally deficient in thiamine, perhaps as a consequence of increased renal clearance of the vitamin rather than a lack in the diet or problems with absorption. This may increase the risk of microvascular complications, in particular diabetic kidney disease (Thornalley 2007).

Thiamine or benfotiamine in the treatment of diabetic neuropathy (nerves)
Although thiamine supplementation has been used to treat generalised peripheral neuropathy its effectiveness in this, or in diabetic neuropathy is not clear. A Cochrane review concluded that “there are only limited data in randomised trials testing the efficacy of vitamin B for treating peripheral neuropathy and the evidence is insufficient to determine whether vitamin B is beneficial or harmful” (Ang 2008).

One trial suggested that short-term (eight weeks) use of benfotiamine could improve vibration-perception threshold in people with general peripheral neuropathy (Ang 2008).

The BENDIP (benfotiamine in diabetic polyneuropathy) study, a double-blinded, randomised, placebo-controlled trial funded by a company which produces benfotiamine, compared the effect of two doses (300 and 600mg daily) of benfotiamine on people with diabetic neuropathy (Stracke 2008). This study built on a previous pilot trial (41 patients in a trial of three weeks' duration) which suggested that benfotiamine produced improvements in the symptoms of neuropathic pain (Haupt 2005) without any change in blood glucose levels. The BENDIP trial indicated that the higher dose of benfotiamine was helpful in reducing pain symptoms, though other neuropathic symptoms (eg numbness, burning or the sensation of pins and needles) were not improved.

A Cochrane review of trials using Vitamin B1 or benfotiamine in the treatment of general peripheral neuropathy found that benfotiamine was effective in improving, in the short term, the ability to detect vibrations (Ang 2008).

Thiamine or benfotiamine in the treatment of diabetic nephropathy (kidneys)
A pilot study of 40 subjects with Type 2 diabetes compared the effect on urinary albumin excretion of a high dose of thiamine (3 x 100mg capsules per day) with a placebo pill (Rabbani 2009). Over a period of three months the 20 patients taking thiamine had a decrease in their urinary albumin excretion compared to those taking the placebo and it was reported that the effect of thiamine might persist beyond treatment (the urinary albumin excretion continued to decrease after the treatment had finished) however factors other than thiamine may have contributed to this (Alkhalaf 2009).

This suggests that thiamine supplementation in people with Type 2 diabetes may result in regression of albuminuria (urinary albumin excretion). However the issue of baseline differences between the treatment and placebo groups may mean that the subsequent differences were less significant, particularly given the small size of the two groups (Alkhalaf 2009).

Current or future clinical trials
At the time of writing (May 2010) there are a number of registered trials which are or will examine the effects of thiamine or benfotiamine supplementation in people with diabetes, in particular any effects on the prevention or improvement of microvascular complications including diabetic nephropathy and neuropathy (ClinicalTrials.gov).

References
Alkhalaf A. (2009) Thiamine in diabetic nephropathy: a novel treatment modality? Diabetologia 52(6): 1212-1213.
Available from http://pubget.com/paper/19296076?title=Thiamine+in+diabetic+nephropathy%3A+a+novel+treatment+modality%3F

Ang, CD, Alvia, MJM, Dans AL et al (2008) Vitamin B for treating peripheral neuropathy (review). Cochrane Collaboration, 4.
Available from http://mrw.interscience.wiley.com/cochrane/clsysrev/articles/CD004573/pdf_fs.html

ClinicalTrials.gov – search resultshttp://www.clinicaltrials.gov/ct2/results?term=benfotiamine
http://www.clinicaltrials.gov/ct2/results?term=thiamine+and+diabetes
http://www.clinicaltrials.gov/ct2/results?term=vitamin+b1+and+diabetes

Expert Group on Vitamins and Minerals (2003) Risk assessment: Thiamin (Vitamin B1) Food Standards Agency
Available from http://www.food.gov.uk/multimedia/pdfs/evm_thiamin.pdf

Food Standards Agency: Thiamin Food Standards Agency website
Available from http://www.eatwell.gov.uk/healthydiet/nutritionessentials/vitaminsandminerals/thiamin/?lang=en

Haupt E et al (2005) Benfotiamine in the treatment of diabetic polyneuropathy - a three week randomized, controlled pilot study (BEDIP study). International Journal of Clinical Pharmacological Therapeutics, 43 (2): 71-77.
Abstract available from http://www.ncbi.nlm.nih.gov/pubmed/15726875

Rabbani, N, Alam, SS, Riaz, S et al ((2009) High-dose thiamine therapy for patients with Type 2 diabetes and microalbuminuria: a randomised, double-blind placebo-controlled pilot study. Diabetologia, 52: 208–212.
Abstract available from http://www.ncbi.nlm.nih.gov/pubmed/19057893

Stracke H, Lindemann A, Federlin K (1996) A benfotiamine-vitamin B combination in treatment of diabetic polyneuropathy Exp Clin Endocrinol Diabetes 104 (4): 311-316.
Abstract available from http://www.ncbi.nlm.nih.gov/pubmed/8886748

Stracke H, Gaus W, Achenbach U et al (2008) Benfotiamine in diabetic polyneuropathy (BENDIP): results of a randomised, double blind, placebo-controlled clinical study. Experimental and Clinical Endocrinology and Diabetes, 116 (10): 600-605.
Available from http://www.biovita.fi/uusi/pdf/Stracke_2008.pdf

Thornalley PJ, Babaei-Jadidi R, Al Ali H et al. (2007) High prevalence of low plasma thiamine concentration in diabetes linked to a marker of vascular disease. Diabetologia, 50 (10): 2164-2170.
Available from http://ukpmc.ac.uk/articlerender.cgi?artid=1091977

Further reading
Brownlee, M (2004) The pathobiology of diabetic complications: a unifying mechanism. Diabetes, 54 (6): 1616-1625.
Available from http://diabetes.diabetesjournals.org/content/54/6/1615.full.pdf

Manzella D (2007) Is benfotiamine effective for treating diabetic complications? About.com: Type 2 diabetes website.
Available from http://diabetes.about.com/od/whatsonthehorizon/p/benfotiamine.htm

Medline Plus
Thiamin (thiamine), vitamin B1
http://www.nlm.nih.gov/medlineplus/druginfo/natural/patient-thiamin.html

TRIP (2007) Is there evidence supporting the use of thiamine or benfotiamine to reduce complications in diabetics? If there is what dose would be recommended? tripanswers website
http://www.tripanswers.org/answer.aspx?criteria=&tagtrail=%2fdiabetes%2fbenfotiamine%2f&qid=4059&src=0