Life Extension Magazine®

Man having blood sugar being tested for excess blood sugar that leads to glycation

Protect Your Cells from Sugar Damage

Excess blood sugar can lead to glycation which accelerates body-wide aging. Benfotiamine helps protect against glycation.

Scientifically reviewed by: Amanda Martin, DC, in April 2023. Written by: Edward R. Rosick, DO, MPH, DABIHM.

When glucose binds to proteins, fats, or nucleic acids in our body, toxic compounds are formed.1

These cellular poisons are called advanced glycation end products or AGEs. 2,3

Diabetics suffer accelerated glycation, but destructive glycation processes happen in people with normal blood glucose levels as well.3

Glycation is linked to faster aging,1 cardiovascular disorders, 2,4-6 diabetic complications,3,6-8 and other chronic conditions.2,6,9-11

Fortunately, there are ways to reduce damage inflicted by advanced glycation end products (AGEs).

Hidden Side Effect of Glucose

Maintaining sufficient blood glucose is essential to life.

But glucose itself has a deadly side effect.

With age, even normal glucose levels bind to the body’ s proteins and fats to accumulate non-functional structures called advanced glycation end products.

Those with higher glycation levels suffer more damage to cells and blood vessels.5,8,14-16 This pertains to diabetic and non-diabetic individuals.

Glycation end products are partly responsible for many diabetic complications,16,17 including kidney6,16 and nerve damage,16,18 blindness, 16,19 and heart disease.16,20

Rates of diabetes have more than doubled in the last 20 years.21 Almost 100 million Americans have pre-diabetes, meaning blood sugar levels between 100 mg/ml and 125 mg/ml. 22,23

Controlling blood sugar is essential to reduce diabetic morbidities. Guarding against excess glycation is equally important.

Human studies have demonstrated a relationship between advanced glycation products contributing to muscle weakness in older healthy individuals. 24

A recent review of studies has shown that glycation products reduce skin elasticity, produce wrinkles, accumulate pigments, and destroy the skin barrier by stimulating inflammation.13

Cardiovascular Damage

Those with the highest glycation levels have been shown to be at greater risk of suffering nonfatal and fatal cardiovascular diseases.20,25,26

A report in the journal Molecular Basis of Disease27 detailed the ways in which glycation contributes to heart disease, including:

  • Decreased blood vessel flexibility,
  • Increased heart muscle stiffness,
  • Decreased production of nitric oxide, a vital biochemical needed for optimal blood vessel dilation, and
  • Increased oxidative stress and inflammation.

Research from Japan confirmed that high glycation levels are associated with the progression of dangerous cardiac plaque in patients with and without diabetes.28

Another study of patients with acute coronary syndrome (a range of conditions marked by reduced blood flow to the heart) showed high levels of advanced glycation end products as a predictor of death and further heart disease.29

How Benfotiamine Helps

Vitamin B1 (also known as thiamine) is essential for energy production and brain health. Deficiencies of thiamine can lead to serious problems, including cardiovascular, immune system, and visual impairments, neurological disorders, and neuropathy.30

Benfotiamine is a fat-soluble form of thiamine with increased absorbability and bioavailability. 31-34

It has been shown in studies to protect against diabetic complications and vascular damage by acting as an anti-inflammatory agent and by combating the damaging effects of advanced glycation end products (AGEs).17,35-44

In one study, diabetic patients with polyneuropathy (painful damage to nerves throughout the body) who took 400 mg daily of benfotiamine had significantly fewer complaints of pain.40 A study in rats showed that benfotiamine prevented diabetes-induced damage in the animals’ eyes, hearts, and kidneys.45

A randomized controlled trial published in 2020 examined the effects of benfotiamine in patients with diabetic sensorimotor polyneuropathy, nerve damage that causes difficulty moving and feeling sensation.41 In an earlier randomized controlled trial, patients taking 600 mg of benfotiamine a day for six weeks, had improved neuropathy symptoms as compared to patients receiving 300 mg or placebo.46

And, 300 mg of thiamine supplementation improved renal function in diabetic patients over a three-month period.47

Protecting the Heart and Blood Vessels

One of the hallmarks of both diabetes and heart disease is damage to blood vessels brought about by oxidative stress, inflammation, and glycation.

Benfotiamine can help prevent these types of damage.

In a pilot study, 13 adults with type II diabetes were given a meal that had high amounts of advanced glycation end products in it. Taking 1,050 mg of benfotiamine daily for three days before the meal decreased markers of oxidative stress and damaging changes to large and small blood vessels.35

In another human study, taking 1,050 mg of benfotiamine daily improved blood flow in volunteer smokers. Short-term treatment with benfotiamine was shown to reduce effects of smoking as a result of its protective vascular qualities.44 Benfotiamine does not make smoking safer, but this study indicates protective effects for anyone exposed to inhaled environmental toxins.

Studies also show that benfotiamine can effectively combat oxidative stress and vascular dysfunction, drivers of heart disease. In an animal study, benfotiamine use acted as an effective antioxidant for the heart.42

A significant body of evidence demonstrates that benfotiamine interferes with glycation pathways.48 It was used in Europe as a neuropathy medication long before Americans gained access to it as a low-cost supplement.

What you need to know

Stop Damage Done by Glycation

  • When sugar binds to proteins and other compounds in the body in a process called glycation, toxic compounds are formed called advanced glycation end products (AGEs).
  • AGEs are linked to diabetic complications, accelerated aging, heart disease, and other chronic illnesses.
  • AGEs are also detrimental to nondiabetics causing skin aging, loss of muscle strength and chronic inflammation.
  • Benfotiamine is a bioavailable form of vitamin B1. It has been shown to prevent the damaging effects of AGEs. Benfotiamine also reduces inflammation and oxidative stress associated with diabetes and heart disease.
  • Human studies show that benfotiamine is effective in decreasing debilitating symptoms of type II diabetes including nerve damage and can help protect the heart and blood vessels against damage from AGEs.

Life Extension suggests supplementing with benfotiamine in daily doses of 250-1,000 mg to help reduce glycation damage. Those with higher blood sugar levels or unhealthy dietary practices should consider the higher benfotiamine dose range.

Meals that contain damaging glycation products include foods cooked at high temperature such as frying, grilling, broiling, and roasting. Safer ways of food preparation to reduce ingestion of advanced glycation end products include boiling, stewing, steaming, and poaching.

Summary

Advanced glycation end products or AGEs are harmful compounds formed when blood sugar interacts with proteins and other compounds in the body. They contribute to diabetic complications, heart disease, and accelerated aging.

Benfotiamine is a safe, fat-soluble form of vitamin B1 that can help reduce the production of AGEs.

Multiple studies have shown that benfotiamine can help protect against oxidative stress, vascular dysfunction, and other hallmarks of conditions like diabetes and heart disease.

Optimal Blood Sugar Levels

Life Extension considers these to be the ideal glycemic marker blood levels:

  • Fasting Glucose: 80-86 mg/dL
  • HbA1c (Hemoglobin A1C): 5.0%-5.4%
  • Fasting insulin <5.0 uIU/mL

 

Thiamine Deficiency 30

  • Thiamine, vitamin B1 is essential for metabolism, energy production, and for normal nervous and cardiovascular function.
  • Deficiency can cause fatigue, poor memory, loss of appetite, sleep disturbances, abdominal discomfort, and weight loss.
  • A diet high in processed carbohydrates and sugars can cause its deficiency. Consumption of excess alcohol is also associated with thiamine deficiency.
  • Severe thiamine deficiency may cause nerve, heart, and brain abnormalities.
  • Health disorders that warrant an increase in thiamine intake include overactive thyroid and liver disorders.
  • Benfotiamine is a fat-soluble form of thiamine with increased absorbability and bioavailability.31-34

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

References

  1. Fournet M, Bonté F, Desmoulière A. Glycation Damage: A Possible Hub for Major Pathophysiological Disorders and Aging. Aging Dis. 2018 Oct;9(5):880-900.
  2. Yamagishi SI. Role of Advanced Glycation Endproduct (AGE)-Receptor for Advanced Glycation Endproduct (RAGE) Axis in Cardiovascular Disease and Its Therapeutic Intervention. Circ J. 2019 Aug 23;83(9):1822-8.
  3. Baye E, Kiriakova V, Uribarri J, et al. Consumption of diets with low advanced glycation end products improves cardiometabolic parameters: meta-analysis of randomised controlled trials. Sci Rep. 2017 May 23;7(1):2266.
  4. Yubero-Serrano EM, Perez-Martinez P. Advanced Glycation End Products and Their Involvement in Cardiovascular Disease. Angiology. 2020 Sep;71(8):698-700.
  5. Pinto RS, Machado UF, Passarelli M. Advanced glycation end products as biomarkers for cardiovascular disease: browning clarifying atherogenesis. Biomark Med. 2020 Jun;14(8):611-4.
  6. Moldogazieva NT, Mokhosoev IM, Mel’nikova TI, et al. Oxidative Stress and Advanced Lipoxidation and Glycation End Products (ALEs and AGEs) in Aging and Age-Related Diseases. Oxid Med Cell Longev. 2019;2019:3085756.
  7. Yamagishi SI, Nakamura N, Matsui T. Glycation and cardiovascular disease in diabetes: A perspective on the concept of metabolic memory. J Diabetes. 2017 Feb;9(2):141-8.
  8. Vlassara H, Striker GE. Advanced glycation endproducts in diabetes and diabetic complications. Endocrinol Metab Clin North Am. 2013 Dec;42(4):697-719.
  9. Li J, Liu D, Sun L, et al. Advanced glycation end products and neurodegenerative diseases: mechanisms and perspective. J Neurol Sci. 2012 Jun 15;317(1-2):1-5.
  10. Simm A. Protein glycation during aging and in cardiovascular disease. J Proteomics. 2013 Oct 30;92:248-59.
  11. Ward MS, Fortheringham AK, Cooper ME, et al. Targeting advanced glycation endproducts and mitochondrial dysfunction in cardiovascular disease. Curr Opin Pharmacol. 2013 Aug;13(4):654-61.
  12. Kim CS, Park S, Kim J. The role of glycation in the pathogenesis of aging and its prevention through herbal products and physical exercise. J Exerc Nutrition Biochem. 2017 Sep 30;21(3):55-61.
  13. Chen CY, Zhang JQ, Li L, et al. Advanced Glycation End Products in the Skin: Molecular Mechanisms, Methods of Measurement, and Inhibitory Pathways. Front Med (Lausanne). 2022;9:837222.
  14. Janda K, Krzanowski M, Gajda M, et al. Vascular effects of advanced glycation end-products: content of immunohistochemically detected AGEs in radial artery samples as a predictor for arterial calcification and cardiovascular risk in asymptomatic patients with chronic kidney disease. Dis Markers. 2015;2015:153978.
  15. Stirban A, Gawlowski T, Roden M. Vascular effects of advanced glycation endproducts: Clinical effects and molecular mechanisms. Mol Metab. 2014 Apr;3(2):94-108.
  16. Singh VP, Bali A, Singh N, et al. Advanced glycation end products and diabetic complications. Korean J Physiol Pharmacol. 2014 Feb;18(1):1-14.
  17. Coughlan MT, Cooper ME, Thomas MC. Can you reduce your AGE?: Strategies to prevent AGE accumulation in diabetes. Drug Discovery Today: Therapeutic Strategies. 2007 2007/03/01/;4(1):85-92.
  18. Wada R, Yagihashi S. Role of advanced glycation end products and their receptors in development of diabetic neuropathy. Ann N Y Acad Sci. 2005 Jun;1043:598-604.
  19. Milne R, Brownstein S. Advanced glycation end products and diabetic retinopathy. Amino Acids. 2013 Jun;44(6):1397-407.
  20. Hegab Z, Gibbons S, Neyses L, et al. Role of advanced glycation end products in cardiovascular disease. World J Cardiol. 2012 Apr 26;4(4):90-102.
  21. Available at: https://www.cdc.gov/diabetes/basics/quick-facts.html#:~:text=Type%202%20diabetes%20accounts%20for,become%20more%20overweight%20or%20obese. Accessed January, 5, 2023.
  22. Available at: https://www.cdc.gov/diabetes/data/statistics-report/. Accessed January, 4, 2023.
  23. Available at: https://www.cdc.gov/diabetes/basics/getting-tested.html. Accessed January, 5, 2023.
  24. Arnold P, Njemini R, Vantieghem S, et al. Reaction time in healthy elderly is associated with chronic low-grade inflammation and advanced glycation end product. Exp Gerontol. 2018 Jul 15;108:118-24.
  25. Joseph JJ, Deedwania P, Acharya T, et al. Comprehensive Management of Cardiovascular Risk Factors for Adults With Type 2 Diabetes: A Scientific Statement From the American Heart Association. Circulation. 2022 Mar;145(9):e722-e59.
  26. Collaboration TERF. Glycated Hemoglobin Measurement and Prediction of Cardiovascular Disease. JAMA. 2014;311(12):1225-33.
  27. Kosmopoulos M, Drekolias D, Zavras PD, et al. Impact of advanced glycation end products (AGEs) signaling in coronary artery disease. Biochim Biophys Acta Mol Basis Dis. 2019 Mar 1;1865(3):611-9.
  28. Fukushima Y, Daida H, Morimoto T, et al. Relationship between advanced glycation end products and plaque progression in patients with acute coronary syndrome: the JAPAN-ACS sub-study. Cardiovasc Diabetol. 2013 Jan 7;12:5.
  29. Raposeiras-Roubin S, Rodino-Janeiro BK, Paradela-Dobarro B, et al. Advanced glycation end-products as long-term predictors of death and reinfarction after an acute coronary syndrome. Biomark Med. 2015;9(3):209-16.
  30. Wiley KD, Gupta M. Vitamin B1 Thiamine Deficiency. StatPearls. Treasure Island (FL): StatPearls Publishing Copyright © 2022, StatPearls Publishing LLC.; 2022.
  31. Sheng L, Cao W, Lin P, et al. Safety, Tolerability and Pharmacokinetics of Single and Multiple Ascending Doses of Benfotiamine in Healthy Subjects. Drug Des Devel Ther. 2021;15:1101-10.
  32. Pai ST. Peripheral Neuropathy. In: Rakel D, ed. Integrative Medicine: Elsevier; 2018:120-32.e8.
  33. Raj V, Ojha S, Howarth FC, et al. Therapeutic potential of benfotiamine and its molecular targets. Eur Rev Med Pharmacol Sci. 2018 May;22(10):3261-73.
  34. Bhawal R, Fu Q, Anderson ET, et al. Serum Metabolomic and Lipidomic Profiling Reveals Novel Biomarkers of Efficacy for Benfotiamine in Alzheimer’s Disease. Int J Mol Sci. 2021 Dec 7;22(24).
  35. 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.
  36. Balakumar P, Rohilla A, Krishan P, et al. The multifaceted therapeutic potential of benfotiamine. Pharmacol Res. 2010 Jun;61(6):482-8.
  37. Ziegler D, Papanas N, Schnell O, et al. Current concepts in the management of diabetic polyneuropathy. J Diabetes Investig. 2021 Apr;12(4):464-75.
  38. Djedovic N, Bozic I, Miljkovic D, et al. Benfotiamine Reduces Dendritic Cell Inflammatory Potency. Endocr Metab Immune Disord Drug Targets. 2021;21(7):1344-51.
  39. Shoeb M, Ramana KV. Anti-inflammatory effects of benfotiamine are mediated through the regulation of the arachidonic acid pathway in macrophages. Free Radic Biol Med. 2012 Jan 1;52(1):182-90.
  40. Haupt E, Ledermann H, Kopcke W. Benfotiamine in the treatment of diabetic polyneuropathy--a three-week randomized, controlled pilot study (BEDIP study). Int J Clin Pharmacol Ther. 2005 Feb;43(2):71-7.
  41. Stirban OA, Zeller-Stefan H, Schumacher J, et al. Treatment with benfotiamine in patients with diabetic sensorimotor polyneuropathy: A double-blind, randomized, placebo-controlled, parallel group pilot study over 12 months. J Diabetes Complications. 2020 Dec;34(12):107757.
  42. Goncalves AC, Moreira EJS, Portari GV. Benfotiamine supplementation prevents oxidative stress in anterior tibialis muscle and heart. J Integr Med. 2019 Nov;17(6):423-9.
  43. 43. Ahmed LA, Hassan OF, Galal O, et al. Beneficial effects of benfotiamine, a NADPH oxidase inhibitor, in isoproterenol-induced myocardial infarction in rats. PLoS One. 2020;15(5):e0232413.
  44. Stirban A, Nandrean S, Kirana S, et al. Benfotiamine counteracts smoking-induced vascular dysfunction in healthy smokers. Int J Vasc Med. 2012;2012:968761.
  45. Chakrabarti R, Chen M, Liu W, et al. Preventive effects of benfotiamine in chronic diabetic complications. J Diabetes Investig. 2011 Apr 7;2(2):123-31.
  46. Stracke H, Gaus W, Achenbach U, et al. Benfotiamine in diabetic polyneuropathy (BENDIP): results of a randomised, double blind, placebo-controlled clinical study. Exp Clin Endocrinol Diabetes. 2008 Nov;116(10):600-5.
  47. Rabbani N, Thornalley PJ. Emerging role of thiamine therapy for prevention and treatment of early-stage diabetic nephropathy. Diabetes Obes Metab. 2011 Jul;13(7):577-83.
  48. Schalkwijk CG, Miyata T. Early- and advanced non-enzymatic glycation in diabetic vascular complications: the search for therapeutics. Amino Acids. 2012 Apr;42(4):1193-204.