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Protect Your Brain from Sugar Damage

Benfotiamine offers neuroprotective qualities that help protect against sugar damage and cognitive decline.

Scientifically reviewed by: Gary Gonzalez, MD, in September 2026. Written by: Marsha McCulloch.

Most people know high blood sugar is bad for the body.

Few understand the damage it inflicts on the brain.

Insulin resistance and impaired glucose metabolism in the brain are so harmful that it is sometimes called "type 3 diabetes." This is linked to Alzheimer's and other dementias.1

Here's the good news: Benfotiamine is a more bioavailable form of vitamin B1 with greater tissue penetration. It has demonstrated neuroprotective properties.2

Benfotiamine also helps inhibit formation of harmful Advanced Glycation End Products (AGEs) in the brain and throughout the body.3,4

A study in individuals with type 2 diabetes showed that benfotiamine reduces AGEs levels and oxidative stress markers.4

In a year-long randomized, placebo-controlled clinical trial of people with mild cognitive impairment or early-stage Alzheimer's, benfotiamine reduced worsening on a clinical dementia rating scale by 77%.3

The Brain-Blood Sugar Link

The brain depends on glucose for energy, but when blood sugar is chronically elevated, the brain becomes less efficient at using that fuel.5

A systematic review of 213 studies found that insulin resistance plays a major role in the development and progression of dementia.6

Analyses of brain tissue from people with Alzheimer's consistently reveal reduced insulin signaling,7 and people with type 2 diabetes (a condition defined by insulin resistance) have a 60% higher risk of developing dementia than those without diabetes.8

When the brain is under heavy demand, insulin enhances glucose utilization during periods of high cognitive demand.9,10 In Alzheimer's, PET imaging has demonstrated regional declines in cerebral glucose utilization, with the hippocampus among the greatest reductions.11 Diminished cerebral glucose metabolism is region-specific and progressive. Longitudinal PET studies have shown cortical glucose metabolism declining by approximately 20% over two years in Alzheimer's patients.12

The hippocampus, the brain's memory center, is especially vulnerable to these energy shortages.1 Impaired insulin signaling also promotes the buildup of amyloid-beta and the formation of tau tangles, two hallmarks of Alzheimer's.6,13,14

High blood sugar adds another layer of stress by increasing the formation of Advanced Glycation End Products.15 These toxic compounds, formed when sugars bind to proteins or fats, are linked to cognitive decline.16

An Essential Brain Nutrient

Thiamine (vitamin B1) is vital for converting glucose into energy in the brain and supporting antioxidant defenses.2,17

In a retrospective study of 77 people with Alzheimer's seen at a memory clinic, subjects with the most severe thiamine deficiency consistently scored lower on the Mini-Mental State Examination, an assessment of cognitive status, than those with higher thiamine levels.18

Restoring thiamine in the brain is not as simple as increasing dietary intake.19

Thiamine is water-soluble and cleared quickly, limiting its beneficial bioavailability.2,20

High blood glucose can also impair the transporters that move thiamine into cells21-23 and blood-brain barrier24,25 making it harder for the body to maintain and replenish adequate thiamine levels.21-23

Benfotiamine, a fat-soluble form of thiamine, is more bioavailable than standard water-soluble thiamine. It can raise blood thiamine concentrations to levels at least five times higher than those achieved with standard thiamine.2

Animal studies have confirmed that oral benfotiamine increases active thiamine (thiamine diphosphate) in memory-critical brain regions, including the hippocampus.26

Encouraging Results in Animal Studies

Scientists first linked benfotiamine to brain benefits in 2010, when an eight-week study in an Alzheimer's mouse model showed that it improved memory and reduced amyloid plaques and abnormal tau.27

Since then, rodent models of Alzheimer's have produced similarly strong findings:

In a seven-day study, benfotiamine reduced neuro-inflammation in the hippocampus and protected against oxidative damage in the cortex.28

In a 15-day study, benfotiamine restored glutathione, a key antioxidant that helps protect the brain from oxidative stress, a major driver of Alzheimer's progression.29

In a 30-day study, benfotiamine increased active thiamine in memory-critical brain regions including the hippocampus, improved cellular energy production, reduced inflammation, supported healthier insulin signaling, and improved cognitive performance.26

Benfotiamine Supports Human Brain Function

Early human evidence came from an 18-month study in five adults with mild to moderate Alzheimer's who took 300 mg of benfotiamine daily.30

Instead of the usual, expected 1- to 3-point decline on the Mini-Mental State Examination over this period,31 participants improved by an average of 3.2 points.30

Stronger support for benfotiamine comes from a clinical trial of 70 people with mild cognitive impairment or early-stage Alzheimer's. Participants took either 300 mg of benfotiamine or a placebo twice daily for 12 months.3 Those receiving benfotiamine showed:

  • \A 161-fold increase in blood thiamine levels from baseline.
  • 77% less decline than the placebo group on the Clinical Dementia Rating, which evaluates memory, problem solving, and daily functioning.
  • A significant reduction in advanced glycation end products, compared to an increase in the placebo group.

Together, findings from human and animal studies suggest that oral benfotiamine shows promise in supporting cognitive function.

Summary

High blood sugar and insulin resistance interfere with the brain's ability to use glucose, contributing to cognitive decline.

Thiamine is essential for healthy brain glucose metabolism, yet people with high blood sugar often have low thiamine levels. Benfotiamine, a fat-soluble form of thiamine, offers much better bioavailability.

Findings from animal and human studies suggest that benfotiamine may support cognitive function and slow early cognitive decline in people with mild cognitive impairment or early-stage Alzheimer's disease.

If you have any questions on the scientific content of this article, please call a Life Extension Wellness Specialist at 1-866-864-3027.

What You Need To Know

Benfotiamine Bolsters Brain Function

  • High blood sugar and insulin resistance reduce the brain's ability to use glucose, a condition strongly linked to cognitive decline and dementia.
  • Thiamine (vitamin B1) is required for healthy brain glucose metabolism, yet people with elevated blood sugar are frequently low in this vitamin.
  • Benfotiamine is a fat-soluble, highly bioavailable form of thiamine that achieves substantially higher thiamine levels than standard thiamine.
  • In a year-long trial of people with mild cognitive impairment or early-stage Alzheimer's, benfotiamine resulted in 77% less decline on a clinical dementia rating scale compared with placebo.

References

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  2. Bozic I, Lavrnja I. Thiamine and benfotiamine: Focus on their therapeutic potential. Heliyon. 2023 Nov;9(11):e21839.
  3. Gibson GE, Luchsinger JA, Cirio R, et al. Benfotiamine and Cognitive Decline in Alzheimer's Disease: Results of a Randomized Placebo-Controlled Phase IIa Clinical Trial. J Alzheimers Dis. 2020 Oct 16;78(3):989-1010.
  4. 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 Sep;29(9):2064-71.
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  8. Chatterjee S, Peters SA, Woodward M, et al. Type 2 Diabetes as a Risk Factor for Dementia in Women Compared With Men: A Pooled Analysis of 2.3 Million People Comprising More Than 100,000 Cases of Dementia. Diabetes Care. 2016 Feb;39(2):300-7.
  9. Kciuk M, Kruczkowska W, Galeziewska J, et al. Alzheimer's Disease as Type 3 Diabetes: Understanding the Link and Implications. Int J Mol Sci. 2024 Nov 7;25(22).
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  11. Mosconi L, Tsui WH, Rusinek H, et al. Quantitation, regional vulnerability, and kinetic modeling of brain glucose metabolism in mild Alzheimer's disease. Eur J Nucl Med Mol Imaging. 2007 Sep;34(9):1467-79.
  12. Daulatzai MA. Cerebral hypoperfusion and glucose hypometabolism: Key pathophysiological modulators promote neurodegeneration, cognitive impairment, and Alzheimer's disease. Journal of Neuroscience Research. 2017 2017/04/01;95(4):943-72.
  13. Wei Z, Koya J, Reznik SE. Insulin Resistance Exacerbates Alzheimer Disease via Multiple Mechanisms. Front Neurosci. 2021;15:687157.
  14. Kellar D, Craft S. Brain insulin resistance in Alzheimer's disease and related disorders: mechanisms and therapeutic approaches. Lancet Neurol. 2020 Sep;19(9):758-66.
  15. Raza A, Saleem S, Imran S, et al. From metabolic dysregulation to neurodegenerative pathology: the role of hyperglycemia, oxidative stress, and blood-brain barrier breakdown in T2D-driven Alzheimer's disease. Metab Brain Dis. 2025 Sep 26;40(7):276.
  16. Chou PS, Wu MN, Yang CC, et al. Effect of Advanced Glycation End Products on the Progression of Alzheimer's Disease. J Alzheimers Dis. 2019;72(1):191-7.
  17. Dhir S, Tarasenko M, Napoli E, et al. Neurological, Psychiatric, and Biochemical Aspects of Thiamine Deficiency in Children and Adults. Front Psychiatry. 2019;10:207.
  18. Higaki Y, Kobayashi Y. A Retrospective Study of the Association between Low Vitamin B1 in the Blood and Cognitive Impairment in Patients with Alzheimer's Disease. J Nutr Sci Vitaminol (Tokyo). 2025;71(5):421-6.
  19. Nolan KA, Black RS, Sheu KF, et al. A trial of thiamine in Alzheimer's disease. Arch Neurol. 1991 Jan;48(1):81-3.
  20. Bitsch R, Wolf M, Moller J, et al. Bioavailability assessment of the lipophilic benfotiamine as compared to a water-soluble thiamin derivative. Ann Nutr Metab. 1991;35(5):292-6.
  21. Chalasova K, Pacal L, Pleskacova A, et al. Transketolase Activity but not Thiamine Membrane Transport Change in Response to Hyperglycaemia and Kidney Dysfunction. Exp Clin Endocrinol Diabetes. 2018 Apr;126(4):255-62.
  22. Ziegler D, Reiners K, Strom A, et al. Association between diabetes and thiamine status - A systematic review and meta-analysis. Metabolism. 2023 Jul;144:155565.
  23. Larkin JR, Zhang F, Godfrey L, et al. Glucose-induced down regulation of thiamine transporters in the kidney proximal tubular epithelium produces thiamine insufficiency in diabetes. PLoS One. 2012;7(12):e53175.
  24. Ramamoorthy K, Yoshimura R, Al-Juburi S, et al. Alzheimer's disease is associated with disruption in thiamin transport physiology: A potential role for neuroinflammation. Neurobiol Dis. 2022 Sep;171:105799.
  25. Beltramo E, Mazzeo A, Porta M. Thiamine and diabetes: back to the future? Acta Diabetol. 2021 Nov;58(11):1433-9.
  26. Moraes RCM, Singulani MP, Goncalves AC, et al. Oral benfotiamine reverts cognitive deficit and increase thiamine diphosphate levels in the brain of a rat model of neurodegeneration. Exp Gerontol. 2020 Nov;141:111097.
  27. Pan X, Gong N, Zhao J, et al. Powerful beneficial effects of benfotiamine on cognitive impairment and beta-amyloid deposition in amyloid precursor protein/presenilin-1 transgenic mice. Brain. 2010 May;133(Pt 5):1342-51.
  28. C AEFC, Martins YA, R CMM, et al. Benfotiamine Ameliorates Streptozotocin-Induced Alzheimer's Disease in Rats by Modulating Neuroinflammation, Oxidative Stress, and Microglia. Mol Neurobiol. 2025 Jul;62(7):8695-717.
  29. Mallika B, Sudha K, Massand A, et al. Evaluation of neuroprotective role of benfotiamine in Alzheimer's disease model: A randomized control study. Clin Ter. 2025 Mar-Apr;176(2):127-35.
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