Benfotiamine

What it is

Benfotiamine belongs to the allithiamines, a group of fat-soluble thiamine derivatives. Unlike the water-soluble vitamin B1 from capsules or food, it is only converted into thiamine in the body after absorption. In a pharmacokinetic study in healthy people, the bioavailability of thiamine in plasma after benfotiamine was 1,147.3 percent compared with thiamine hydrochloride, and for the active thiamine diphosphate in red blood cells 195.8 percent. The figures show that the effect in blood plasma is much larger than in the cells.

In Germany, benfotiamine has been known as a medicine for decades; early studies with products such as Milgamma-N and Benfogamma date from 1996 and 1999. Today it is available from pharmacies, for example as milgamma protekt with 300 mg, approved for the treatment and prevention of vitamin B1 deficiency that cannot be corrected through diet, as well as of neuropathies and cardiovascular disorders caused by such a deficiency.

How it is supposed to work

The enthusiasm in biohacking goes back to a 2003 paper in Nature Medicine. High blood sugar levels cause intermediates of glycolysis to build up, which drive three known damage pathways: the hexosamine pathway, the formation of advanced glycation end products, known as AGEs, and the DAG–protein kinase C pathway. In diabetic animals, benfotiamine activated transketolase, a thiamine-dependent enzyme of the pentose phosphate pathway, blocked all three pathways at once and prevented experimental diabetic retinopathy.

From this arose the idea of benfotiamine as a shield against glycation that could also benefit people without diabetes. In humans, the first part of the chain is well measured: thiamine and its phosphate forms rise reliably in the blood. Whether fewer AGEs are actually formed as a result, however, is an open question. In a study with 13 people with type 2 diabetes, benfotiamine after three days prevented the vascular deterioration following an AGE-rich meal, without a placebo group. A placebo-controlled study over 12 weeks, by contrast, found no reduction of AGEs in blood or urine.

Why nerve damage is the focus

Thiamine deficiency damages nerves; that has long been known. Benfotiamine was therefore studied mainly in diabetic and alcohol-related polyneuropathy, that is, nerve damage in the feet and legs with tingling, burning and numbness. Heavy alcohol consumption often goes along with vitamin B1 deficiency; in diabetes, the disturbed sugar metabolism adds a possible point of attack. Newer research is also testing whether the mechanism can protect the brain in early Alzheimer’s disease.

What the studies show

BOND: one year against diabetic neuropathy

57 people with type 2 diabetes and mild to moderate symptomatic polyneuropathy took 300 mg benfotiamine twice daily or placebo for 12 months. The primary endpoint was corneal nerve fiber length, an early marker of nerve damage. It did not change, nor did skin biopsy, nerve conduction, 15 clinical scores and quality of life. Only the symptom score showed a trend in favor of benfotiamine. Thiamine levels rose markedly, and tolerability was equal to placebo.

Two years in type 1 diabetes

67 people with type 1 diabetes received 300 mg benfotiamine per day or placebo for 24 months; 59 completed the study. Thiamine and thiamine diphosphate in the blood rose sharply, but peripheral nerve function and inflammatory markers remained the same.

Alzheimer’s: phase IIa over one year

70 people with mild cognitive impairment or mild Alzheimer’s dementia took benfotiamine or placebo for 12 months. The increase in the ADAS-Cog memory test was 43 percent smaller on benfotiamine, but not significantly so; the primary endpoint was thus missed. On the CDR there was a significant advantage, and the rise of AGEs in the blood was slowed. The follow-up study BenfoTeam with 406 participants over 72 weeks is ongoing; results are expected for the end of 2027.

Where the data stop

The pattern is clear: the positive neuropathy studies lasted 3 to 8 weeks and measured symptoms; the long studies with objective measurements of nerve structure and function found no effect. A 2026 meta-analysis of 13 studies with 834 participants found better neuropathy scores for B vitamins overall, but no reliable pain relief, and combinations of several B vitamins tended to perform better than single substances. A current review does not recommend benfotiamine routinely outside of a proven thiamine deficiency.

Protection against glycation has not been confirmed in humans. In 82 patients with diabetic kidney damage, benfotiamine over 12 weeks lowered neither protein excretion nor AGEs or inflammatory markers, and in 31 people with type 2 diabetes vascular function remained unchanged after 6 weeks. For healthy people without diabetes or deficiency, there are no studies on aging, performance or AGEs. A small finding on alcohol dependence, lower drinking amounts in women, is based on 21 women and has not been confirmed.

Status, approval and legal

In the EU, benfotiamine is not a permitted form of vitamin B1 for food supplements; only thiamine hydrochloride and thiamine mononitrate are permitted there. In 2008, EFSA was unable to confirm the safety of benfotiamine as a nutrient source for lack of toxicological data, and in 2020 the Higher Administrative Court of Lower Saxony upheld the sales ban on a benfotiamine food supplement. In Germany, benfotiamine is approved as a medicine, pharmacy-only but not prescription-only. It is not on the WADA Prohibited List for 2026.

Safety

Benfotiamine is considered well tolerated in the studies. The prescribing information of a German product mentions, in isolated cases, hypersensitivity reactions such as hives or skin rash as well as gastrointestinal complaints. In phase I studies, the most common findings were slightly elevated liver values and white blood cells in the urine, with no difference from placebo in frequency. There are no dedicated studies for pregnancy and breastfeeding, and EFSA noted the absence of studies on reproduction, genotoxicity and long-term effects. Anyone with nerve symptoms should have the cause clarified by a doctor, because benfotiamine replaces neither good blood sugar control nor the treatment of other causes.

Sources

• Ziegler et al., BMJ Open Diabetes Res Care 2026 (BOND)
• Stracke et al., Exp Clin Endocrinol Diabetes 2008 (BENDIP)
• Fraser et al., Diabetes Care 2012
• Gibson et al., J Alzheimers Dis 2020
• Hammes et al., Nat Med 2003
• Alkhalaf et al., PLoS One 2012
• Xie et al., J Clin Pharmacol 2014
• Mandra et al., J Clin Med 2026
• EFSA ANS Panel, EFSA Journal 2008
• Higher Administrative Court of Lower Saxony (OVG Niedersachsen), 13 ME 400/20, 2020