Benfotiamine supplement health benefit and side effects, use in diabetes, neuropathy treatment, research studies, 120 capsules
April 22 2018 by
Ray Sahelian, M.D. 

Benfotiamine, or benphothiamine, is marketed as a lipid soluble form of the B vitamin thiamine. Preliminary human studies indicate that it may be helpful in diabetic neuropathy and to reduce microvascular damage from high blood sugar. Much more research is needed before we determine the appropriate dosage and whether long term use has side effects that are of concern. There are some scientists who are skeptical of the benefits of this nutrient. More research is needed.
   Advanced glycation and lipoxidation end products (AGEs / ALEs) have been implicated in the causation of some of the major microvascular complications of diabetes mellitus: diabetic neuropathy, nephropathy, and retinopathy. Benfotiamine is a transketolase activator that directs these substrates to the pentose phosphate pathway, thus perhaps reducing tissue AGEs.



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Alcohol rehab
Drug Alcohol Depend. 2015. Change in psychiatric symptomatology after benfotiamine treatment in males is related to lifetime alcoholism severity. Severe alcoholism can be associated with significant nutritional and vitamin deficiency, especially vitamin B1 (thiamine) which is associated with neurological deficits impacting mood and cognition. Alcohol consumption was reduced among female but not male alcoholics after supplementation with the high potency thiamine analog benfotiamine (BF). We examined the relationship between lifetime alcoholism severity, psychiatric symptoms and response to BF among the alcohol dependent men from this cohort. Eighty-five adult men  meeting criteria for a current alcohol use disorder who were abstinent < 30days participated in a randomized, double-blind, placebo-controlled trial of 600mg BF vs placebo (PL) for 6 months.  BF appears to reduce psychiatric distress and may facilitate recovery in severely affected males with a lifetime alcohol use disorder and should be considered for adjuvant therapy in alcohol rehabilitation.

Alzheimer's disease
Neurosci Bull. 2016. Long-Term Cognitive Improvement After Benfotiamine Administration in Patients with Alzheimer's Disease. Five patients with mild to moderate AD received oral benfotiamine (300 mg daily) over 18 months. Benfotiamine significantly improved the cognitive abilities of mild to moderate AD patients independently of brain amyloid accumulation.

Benfotiamine exhibits direct antioxidative capacity and prevents induction of DNA damage in vitro.
Diabetes Metab Res Rev. 2008.
This lipophilic thiamine diphosphate medicine prevented early renal and retinal changes in animal studies, and reduced neuropathic pain in clinical studies. A potential DNA protective effect was found.

Benfotiamine alleviates diabetes-induced cerebral oxidative damage independent of advanced glycation end-product, tissue factor and TNF-alpha.
Neurosci Lett. 2005.
Diabetes mellitus leads to thiamine deficiency and multiple organ damage including diabetic neuropathy. This study was designed to examine the effect of benfotiamine on streptozotocin-induced cerebral oxidative stress. Benfotiamine alleviated diabetes-induced cerebral oxidative stress without affecting levels of AGE, protein carbonyl, tissue factor and TNF-alpha. Collectively, our results indicated it may antagonize diabetes-induced cerebral oxidative stress through a mechanism unrelated to AGE, tissue factor and TNF-alpha.

Cancer and tumors
PLoS One. 2015. Paraptosis cell death induction by the thiamine analog benfotiamine in leukemia cells. We recently reported that oral benfotiamine induced a temporary but remarkable recovery from acute myeloid leukemia in an elderly patient who was ineligible for standard chemotherapy due to dementia and renal failure. In the present study we present evidences that benfotiamine possess antitumor activity against leukemia cells. In a panel of nine myeloid leukemia cell lines benfotiamine impaired the viability of HL-60, NB4, K562 and KG1 cells and also inhibited the growing of primary leukemic blasts. Our findings suggest that benfotiamine has antitumor therapeutic potential.

Q. I've read that it can possibly cause tumors - not sure how large a dose is needed for this to happen - is there any truth to this claim? I have peripheral neuropathy due to chemo therapy and was looking for ways to treat it - but found it a bit troubling that Benfotiamine might actually be a cause of tumors?
   A. I am not aware of any human studies that indicated this supplement as a causation for tumor or cancer formation. In fact, early studies indicate quite the opposite.

Diabetes patients benefit
There is a possibility that benfotiamine pills may be helpful in diabetic neuropathy and other conditions due to high blood sugar levels in those who have diabetes but more research is needed.

Zh Nevrol Psikhiatr Im S S Korsakova. 2013. The effect of long-chain polyunsaturated higher ω-3 fatty acids, benfotiamine and α-lipoic acid on the lipid metabolism in patients with diabetes mellitus type 2 and cardiovascular autonomic neuropathy. Eighty-one patients with diabetes mellitus type 2 (DM) and cardiovascular autonomic neuropathy were studied. The combined treatment with ω-3 PUFA, benfotiamine, and α-lipoic acid resulted in significant positive changes in total cholesterol, triacylglycerol, LDL and HDL cholesterol levels. The efficacy of this treatment was not associated with the improved compensation of DM but was a result of the direct influence of pharmacological agents on the metabolic rate studied.

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. Heart and Diabetes Center NRW, Georgstrassen, Germany.
Thirteen people with type 2 diabetes were given a heat-processed test meal with a high advanced glycation end products content before and after a 3-day therapy with benfotiamine (1,050 mg/day). Macrovascular flow-mediated dilatation (FMD) and microvascular reactive hyperemia, along with serum markers of endothelial disfunction (E-selectin, vascular cell adhesion molecule-1, and intracellular adhesion molecule-1), oxidative stress, AGE, and MG were measured during both test meal days after an overnight fast and then at 2, 4, and 6 h postprandially. Our study confirms micro- and macrovascular endothelial dysfunction accompanied by increased oxidative stress following a real-life, heat-processed, AGE-rich meal in individuals with type 2 diabetes and suggests benfotiamine as a potential treatment.
   Comments: For long term use, the dosage may be much less than what the researchers used in this short term study.

Diabetic nephropathy, not of benefit
A Double-Blind, Randomized, Placebo-Controlled Clinical Trial on Benfotiamine Treatment in Patients with Diabetic Nephropathy.
Diabetes Care. 2010. Alkhalaf A, Klooster A, Achenbach U, Kleefstra N. Department of Internal Medicine, University Medical Center Groningen, Groningen, the Netherlands.
To investigate the effect of benfotiamine on urinary excretion of albumin and the tubular damage marker kidney injury molecule-1 (KIM-1) in patients with type 2 diabetes and nephropathy. Patients with type 2 diabetes and UAE equivalent to 15-300 mg/24h despite angiotensin-converting enzyme inhibitors (ACE-Is) or angiotensin-receptor blockers (ARBs), were randomly assigned to 12-week benfotiamine (900mg/day) or placebo. Results - In 39 patients on benfotiamine versus 43 patients on placebo, benfotiamine treatment resulted in significant improvement of thiamine status. In patients with type 2 diabetes and nephropathy, high-dose benfotiamine treatment for 12 weeks as add-on to ACE-Is or ARBs did not reduce UAE or KIM-1 excretion despite improvement of thiamine status.

Diabetic neuropathy
Benfotiamine in the treatment of diabetic polyneuropathy -- a three-week randomized, controlled pilot study (BEDIP study).
Int J Clin Pharmacol Ther. 2005.
The aim of the study was to evaluate the efficacy of benfotiamine administered over three weeks (allithiamine; a lipid-soluble vitamin B1 prodrug with high bioavailability) to patients with diabetic polyneuropathy in a randomized, placebo-controlled, double-blind, two-center pilot study. Forty inpatients with a history of type 1 or 2 diabetes and polyneuropathy of not longer than two years, were included in the study. Twenty Patients received two 50 mg benfotiamine tablets four times daily and 20 patients received placebo over the three-week study period. A statistically significant improvement in the neuropathy score was observed in the group given active drug when compared to the placebo-treated controls. There was no statistically significant change observed in the tuning fork test. The most pronounced effect on complaints was a decrease in pain. More patients in the benfotiamine-treated group than in the placebo group considered their clinical condition to have improved. No side effects were observed.

Effectiveness of different benfotiamine dosage regimens in the treatment of painful diabetic neuropathy.
Arzneimittelforschung 1999.
The therapeutic effectiveness of a benfotiamine-vitamin B combination (Milgamma-N), administered in high (4 x 2 capsules / day, = 320 mg / day) and medium doses (3 x 1 capsules / day), was compared to a monotherapy with benfotiamine (Benfogamma) (3 x 1 tablets / day, = 150 mg / day) in diabetic patients suffering from painful peripheral diabetic neuropathy. In a 6-week open clinical trial, 36 patients (aged 40 to 70 yrs) having acceptable metabolic control (HbA1c < 8%) were randomly assigned to three groups, each of them comprising 12 participants. It is concluded that benfotiamine is most effective in large doses, although even in smaller daily dosages, either in combination or in monotherapy, it is effective.

Testimonial received by email
I was taking the benfotiamone for around eight months for diabetic neuropathy - tingling, burning and numbness in my legs and feet. Three weeks after commencing the dosage of 600 mg, I noticed improvement. I felt a slight reversal when I ran out recently.

Diabetic retinopathy studies
Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy.
Natural Medicine. 2003.
Three of the major biochemical pathways implicated in the pathogenesis of hyperglycemia induced vascular damage (the hexosamine pathway, the advanced glycation end product (AGE) formation pathway and the diacylglycerol (DAG)-protein kinase C (PKC) pathway) are activated by increased availability of the glycolytic metabolites glyceraldehyde-3-phosphate and fructose-6-phosphate. In retinas of diabetic animals, benfotiamine treatment inhibited these three pathways and NF-kappaB activation by activating transketolase, and also prevented experimental diabetic retinopathy.

Insect bites
Q. I believe in taking extra vitamin B-1 because it reputedly helps to discourage biting insects, specifically mosquitoes and black-flies. I wonder if it would follow that it could also produce that effect?
    A. We have not seen any research regarding the role of benfotiamine supplements in discouraging insect bites.

Neuropathy pain research
Benfotiamine relieves inflammatory and neuropathic pain in rats.
Eur J Pharmacol. 2006.
Benfotiamine has shown therapeutic efficacy in the treatment of painful diabetic neuropathy in human beings. However, so far there is no evidence about the efficacy of this drug in preclinical models of pain. The purpose of this study was to assess the possible antinociceptive and antiallodynic effect of benfotiamine in inflammatory and neuropathic pain models in the rat. Inflammatory pain was induced by injection of formalin in non-diabetic and diabetic (2 weeks) rats. Reduction of flinching behavior was considered as antinociception. Neuropathic pain was induced by either ligation of left L5/L6 spinal nerves or administration of streptozotocin in Wistar rats. Benfotiamine significantly reduced inflammatory (10-300 mg/kg) and neuropathic (75-300 mg/kg) nociception in non-diabetic and diabetic rats. Results indicate that oral administration of benfotiamine is able to reduce tactile allodynia from different origin in the rat and they suggest the use of this drug to reduce inflammatory and neuropathic pain in humans.

Bendotiamine efficacy in alcoholic polyneuropathy therapy
Zh Nevrol Psikhiatr Im S S Korsakova. 2001.
Benfogamma efficacy in alcoholic polyneuropathy therapy with pain syndrome and other sensor disorders has been studied. Fourteen males with stage II-III chronic alcoholism have been examined. Clinical neurophysiological examination was conducted at the beginning and at the end of 6-week therapy, 300 mg/day (4 weeks). During the treatment the regress of algic, other sensor and movement disorders, as well as some neuropathy symptoms has been observed.

Prostate cancer
Please advise if it is safe to take benfotiamine and alpha lipoic acid for diabetes if one already has prostate cancer.
   A doctor has to know the full history, do a medical exam, and review lab studies before making any recommendations regarding combinations and interactions. The dosage makes a huge effect on tolerance and interactions.

Uveitis study in rodents
Uveitis -- an inflammation just below the outer surface of the eyeball which causes 10 percent to 15 percent of U.S. blindness and even higher rates of blindness globally -- is usually treated with antibiotics or steroid eye drops. Researchers at the University of Texas Medical Branch at Galveston found benfotiamene fed to laboratory rats with bacterial toxins that ordinarily produce a reaction mimicking uveitis, failed to develop any signs of the inflammatory disorder. The study, published in the January 2009 issue of Investigative Ophthalmology and Visual Science, found benfotiamene works by suppressing the activation of a crucial signaling molecule called NF-kappa B, which is normally triggered by the stress caused by infection. Shutting down NF-kappa B prevents the runaway production of inflammatory proteins that generates uveitis.

Safety, side effects, risk
Q. Is it possible that a daily dose of 600 mg benfotiamine could have a negative effect on red and white blood cells? Just wondered because a perfect blood test three months ago turned into a bad one and the only thing I took since the previous test was the mentioned doseage of this vitamin.
   A. I am not aware of human studies that have evaluated the influence of this supplement in high dosages on red or white blood cells. Unexpected side effects could occur with certain supplements.

Q. Could benfotiamine cause nausea after extended use like 2 months use of 3 per day 150 mg?
   A. Yes, it is possible.

I am a type 2 Diabetic and have had problems with numbness and no feeling in part of both feet. I have been taking Benfotiamine 150 mg 3 time a day for about 2 months. I can tell a difference now. I use to not be able to walk barefoot in the house due to pain. All that is gone and walking on floor bare foot now doesn't bother me.

Your site is beyond fantastic, your decrying of megadoses admirable! The below link is to this June '08 article downplaying benefits of Benfotiamine. Comments?
Vitamin Supplement Little More Than 'Snake Oil,' Researcher Claims. Science Daily (2008) — A popular vitamin supplement is being advertised with claims that are demonstrably untrue, as revealed by research published in the open access journal BMC Pharmacology. Benfotiamine is a synthetic derivative of thiamine (vitamin B1). It is marketed heavily as a dietary supplement using a selection of unsubstantiated, 'not-quite-medical' claims that tend to characterize this field. A large part of this campaign has been built around the belief that benfotiamine is lipid-soluble and, therefore, more physiologically active. Scientific research led by Dr Lucien Bettendorff of the Center for Cellular and Molecular Neurobiology at the University of Liège, Belgium, has entirely disproved these claims. According to Lucien Bettendorff, "We suspect that those companies selling benfotiamine have poisoned much of the recent literature in an attempt to bestow it with properties that it does not have". Benfotiamine has been previously shown to prevent several diabetic complications in experimental animal models. The researchers carried out experiments in mice in which it was administered using several different techniques and the resulting levels of thiamine were measured in various parts of the body. Contrary to other claims about its solubility, the results show that it is only sparingly soluble in water under physiological conditions and cannot be dissolved in octanol or oils. As Lucien Bettendorff explains, "Benfotiamine is very often considered a 'lipid-soluble' thiamine precursor from the disulfide derivative family though it is neither lipid-soluble, nor a disulfide. Sometimes, it is considered to have more biological activity than thiamine disulfides, but our study shows that it does not even penetrate cell membranes, except in those cells containing an ecto-alkaline phosphatase. There is no evidence that benfotiamine would be more effective than other precursors as a therapeutic agent for complications of diabetes." Journal reference: Marie-Laure Volvert, Sandrine Seyen, Marie Piette, Brigitte Evrard, Marjorie Gangolf, Jean-Christophe Plumier and Lucien Bettendorff. Benfotiamine, a synthetic S-acyl thiamine derivative, has different mechanisms of action and a different pharmacological profile than lipid-soluble thiamine disulfide derivatives. BMC Pharmacology, 2008.
    A. As with many supplements or medications, it often takes many years of research from various centers to finally have a good understanding of whether the supplement or medication works or whether is is ineffective. We happen to be in the early stages in terms of benfotiamine research and it is not easy for me to predict the outcome.

Q. I am a doctor of podiatric medicine and have dispensed benfotiamine before with mixed results, and and stopped it for a while. After a couple of patient's queries, I've decided to try it again, but wanted some advice on dosage. I had gotten my supplement from One Source. Each capsule is 150mg. Their advice was to start with two caps BID for the first month, then one cap BID. However, in doing a little research, I see there are different strengths of benfotiamine, from 80mg to 300mg per cap.
   A. I have not used this supplement enough in my practice to have a good sense of how effective it is and what dosage works best. I am not ready yet to rely on it as a single treatment for any medical condition.

Additional products on sale
Buy Benfotiamine supplement ( S-benzyolthiamine-O-monophosphate )
80 mg pill - 120 Veggie Capsules, Doctor's Best

Early research indicates benofotiamine is fat-soluble and more bioavailable and physiologically active than thiamin. This nutrient raises the blood level of thiamin pyrophosphate (TPP, the biologically active co-enzyme of thiamin, and stimulates transkotelase, a cellular enzyme essential for maintenance of normal glucose metabolic pathways. It helps maintain healthy cells in the presence of blood glucose and controls formation of advanced glycation end products (AGEs).

Buy benfotiamine supplement, alpha lipoic acid
Amount Per capsule: Benfotiamine 80 mg each pill
Suggested Use: One capsule a few times a week or as recommended by your health care provider.

Benfotiamine Inc., Benfotiamine, 150 mg, 120 Capsules

Supplement Facts
Serving Size: 1 capsule
Servings Per Container: 120
  Amount Per Serving % Daily Value
Providing Thiamine
(as benfotiamine, 150 mg) S-benzoylthiamine-O-monophosphate (C 19H23N4O6PS)
103 mg 6,867%