Protecting Against Glycation and High Blood Sugar with Benfotiamine part 1

For decades, European doctors have prescribed diabetic patients a fat-soluble form of vitamin B1 called benfotiamine to treat neuropathies and help prevent complications such as blindness, kidney failure, heart attack, and limb amputation.

Benfotiamine blocks destructive biochemical pathways that enable high blood sugar levels to damage nerves and small blood vessels.

Benfotiamine also inhibits the formation of advanced glycation end products in both diabetic and normal aging organisms. Glycation not only causes kidney, nerve, and retinal damage in diabetics, but is also a significant contributory factor in cardiovascular disease and other aging disorders in adults without diabetes.1-6

Here, we’ll explore how to use benfotiamine to help protect against the dangers of elevated blood sugar and toxic glycation reactions.

AGE, RAGE, and Tissue Damage

Sugar molecules, in excess quantity or over long periods of time, wreak havoc on human tissues. As the number of people with type 2 diabetes has skyrocketed over the past 20 years, we’ve learned to recognize strong relationships between blood sugar levels and many chronic conditions previously thought to be purely age-related. The link seems to be the total lifetime exposure to blood sugar that’s the culprit. In other words, diabetics develop problems sooner because of their chronic higher sugar levels, but even non-diabetic people eventually suffer tissue injury related to the interaction between blood sugar and tissue proteins.

Studies of diabetic patients have shown that prolonged tissue exposure to elevated glucose levels results in the production of a class of molecules called “advanced glycation end products” (AGEs).1-4 These molecules are proteins and lipids that have become bonded to some of the sugar molecules found in high concentrations in diabetics’ blood.5 Advanced glycation end products are well known for their destructive activities in diabetes, where they contribute to vascular disease, kidney failure, eye damage, and other kinds of dysfunction,5,6 including the nerve damage known as diabetic peripheral neuropathy.3,4,7 In patients with this kind of neuropathy, AGEs directly damage vital components of nerve cells,8 insidiously reducing their ability to conduct warning sensations such as pain and pressure.

People with peripheral neuropathies may not perceive the need to shift their weight, for example, to allow an even distribution of blood flow to a pressure point such as the buttock or foot.9 Inadequate blood flow to such areas in turn can result in tissue death (necrosis), producing pressure sores that invite infection.10 And because AGEs also impair immune function, those infections in vulnerable diabetic patients can rapidly become life- and limb-threatening; in fact, amputation of an entire extremity can often be the only treatment if the condition cannot be prevented (foot infections are the single most common cause of hospitalization and amputations in persons with diabetes).11

Our rapidly expanding experience with the diabetic population has taught us that the AGE-related damage to tissues involves a specific chemical receptor that responds to the presence of AGE molecules by inducing inflammation. That receptor molecule is appropriately termed RAGE (for “receptor for AGE”).8

And we’re learning that it’s not just diabetics who are affected—with enough time and exposure, we all develop “AGE-related” problems.6 Ominously, AGE/RAGE reactions occur even in people without known diabetes or insulin resistance, although those conditions hasten the process.12 With advancing age, even normal blood sugar levels, given sufficient time, produce AGEs that act on RAGEs to induce deadly inflammation in blood vessels, nerves, liver, and other vital tissues.6,13,14 A growing number of studies are now demonstrating links between levels of AGEs in the blood of non-diabetics and major risk factors for atherosclerosis and heart disease.15,16

Credible scientists have even speculated that these AGE-related changes could ultimately contribute to an “upper limit” of the human life span17—with the implication that if we could prevent them from happening, we could conceivably extend human life expectancy dramatically!

Thiamine—The Natural Anti-AGE/RAGE Vitamin

One of the most important natural anti-AGE compounds is vitamin B1, or thiamine, and its natural derivative, benfotiamine. Thiamine is a well-known nutrient that has myriad roles throughout the body, particularly in maintaining the healthy, normal functioning of nerve cells.18 Thiamine has been shown to interfere with the AGE/RAGE process in meaningful ways.19,20

A vivid demonstration of thiamine’s ability to block AGE production and its effects in the laboratory was provided in 1996 by researchers in Italy, who subjected cells in culture to high glucose levels both with and without thiamine supplementation.21 The researchers measured the cells’ ability to function normally and also their production of AGE molecules. High glucose inhibited normal cell reproduction and metabolic activity—but the addition of thiamine significantly reduced total AGE formation, increased cell survival, and restored reproductive activity to normal levels.21 These findings and those of other laboratory investigators have led to calls for trials of high-dose thiamine to prevent glycation-induced damage to nerve cells8 and other tissues such as the liver, where AGE-induced damage plays a key role in the development of cirrhosis.5,22

Scientists in Toronto were able to prevent glycation damage to liver cells in culture by supplementing them with thiamine.23 They also showed that when liver cells were made thiamine-deficient, they were susceptible to damage at much lower levels of glycation products than were normal cells, which suggests that avoiding thiamine deficiency might be an important cirrhosis-prevention strategy.

And Indian researchers recently demonstrated the potential anticancer activity of thiamine.24 They discovered thiamine to be one of the B vitamins that blocks the production of free radicals by AGE molecules, which in turn prevents dangerous DNA injury that can lead to cancer initiation.

These promising results with thiamine supplementation led to the natural question: why not simply use high-dose thiamine to prevent AGE formation in diabetics, and perhaps even in non-diabetic people as well? The answer is based on the concept of bioavailability—not all beneficial molecules are equally well absorbed from the digestive tract, and once absorbed, they may be extensively metabolized and/or poorly penetrate target tissues. Water-soluble nutrients like thiamine are well absorbed, but tend not to penetrate lipids to any great degree (oil and water don’t mix well)—so they aren’t as bioavailable to target tissues that are composed of lipids (fats). This is in part because cell membranes themselves are primarily made up of lipid molecules.

Thus, as a water-soluble vitamin, thiamine has an upper dose limit beyond which additional quantities are simply excreted in urine.25,26 Clearly, for the beneficial anti-AGE effects and related reduction in inflammatory markers to be realized, a better means of delivering thiamine to tissues is needed. Fortunately, thiamine’s fat-soluble cousin benfotiamine is a highly bioavailable nutrient that achieves better distribution throughout the body.27,28

Benfotiamine: A Supercharged Thiamine Derivative

Benfotiamine is better than thiamine at penetrating cell membranes and protecting AGE-vulnerable tissues from harmful glucose-protein and glucose-lipid reactions, helping to protect nerve, retinal, kidney, and other cells. Studies suggest that the benefits of benfotiamine may greatly outpace those of thiamine. Biochemical nutritionists at the Friedrich Schiller University in Germany studied three thiamine preparations in seven healthy volunteers and evaluated the bioavailability of each compound.29 Subjects took 100 mg of either benfotiamine, thiamine disulfide, or fursultiamin (another thiamine derivative), and their blood levels of thiamine were measured repeatedly over a 10-hour period, along with biochemical markers of whether cells were actually “seeing” the effects of thiamine. Benfotiamine produced a more rapid and earlier increase in blood and displayed significantly increased bioavailability, compared with either of the other two formulations. These researchers concluded that benfotiamine is the best form of thiamine for therapeutic use.

The same researchers found similar results in a more detailed study of benfotiamine versus thiamine mononitrate in patients with end-stage renal disease (who are frequently thiamine-deficient).30 Subjects who received 100 mg/day of benfotiamine had faster and higher peak levels than those receiving standard thiamine supplements, achieving nearly double the levels and allowing an amazing 420% increase in total 24-hour tissue exposure after a single dose. These results were interpreted as further justification for the use of benfotiamine in patients who require high intracellular concentrations of thiamine. Later studies from the same group demonstrated that the elevated tissue levels produced by benfotiamine markedly increased the all-important cellular content,31 providing conclusive evidence of benfotiamine’s overall superiority to thiamine in blocking formation of AGEs and the RAGE reactions that follow. Benfotiamine’s anti-AGE activity has now been shown to be superior to that of thiamine alone in the treatment of neurodegenerative diseases and cancer,32 as well as on the kidney, eye, and nerve damage seen in diabetic patients.4

Benfotiamine—Combating AGE and RAGE

It is clear that benfotiamine can reach AGE-vulnerable tissues and cells at high levels. In looking at how benfotiamine performs at actually preventing the AGE/RAGE reactions from taking place, Italian scientists collaborating with the World Health Organization studied its effects in correcting endothelial cell damage caused by elevated glucose levels33—just the kind of damage we know is caused by AGEs in both diabetic and non-diabetic people. The researchers cultured human endothelial cells in normal and very high glucose concentrations, treating them with benfotiamine or thiamine, and measuring the cells’ survival and rates of healthy reproduction. The high glucose levels predictably impaired cell replication by nearly 30%—and addition of thiamine raised survival to 80% of normal, while benfotiamine raised it to nearly 90%! Benfotiamine also cut AGE production in the high-glucose environment from 160% of normal to similar levels found in healthy glucose-exposed cells. The scientists speculated that these dramatic effects resulted from benfotiamine’s ability to help cells use glucose more efficiently, reducing the level of waste products that are most active in producing AGEs.
Material used with permission of Life Extension. All rights reserved.