Protecting Against Glycation and High Blood Sugar with Benfotiamine part 2

Preventing Diabetic Complications in Animals

Studies in animals powerfully support these encouraging findings with research from a number of quarters revealing the benefits of benfotiamine in preventing diabetic complications. German researchers working with diabetic rats studied the effects of benfotiamine and thiamine on nerve function and on the formation of AGEs in nerve tissue.28 In one group of animals, they studied the preventive effects of the supplements, administering them immediately after diabetes was chemically induced. A second group of animals received supplements only two months later, to study the supplements’ treatment effects. As expected, nerve conduction speeds dropped off in diabetic animals, while AGE levels increased by up to five-fold. In the prevention group, nerve conduction increased substantially compared with control animals, and was nearly normal by six months in the benfotiamine-supplemented group (no further improvement was seen after three months in the thiamine-supplemented animals). Remarkably, similar results were also found in the benfotiamine treatment group—but not in the thiamine-treated animals. Benfotiamine also dramatically reduced AGE formation in nerve cells, which probably explains its dramatic effects. These researchers concluded that “timely administration of benfotiamine was effective in prevention of functional damage and of AGE formation in nerves of diabetic rats”—a radically promising finding!

In 2003, British researchers treated rats with benfotiamine and thiamine aimed at preventing diabetic nephropathy (kidney disease), a condition that is associated with a very high risk of cardiovascular disease and death.34 They found that high-dose therapy with benfotiamine and thiamine prevented the accumulation of molecules that trigger the formation of AGEs, oxidative stress, and inflammation—the major factors that ultimately produce kidney damage. They also found that kidney function actually improved in the animals treated with benfotiamine and thiamine, demonstrating not only biochemical but actual whole-organism benefits.

In related studies, German and American physicians showed that treating diabetic rats with high doses of benfotiamine prevented retinopathy, another complication of diabetes.35 The researchers pointed out that benfotiamine works by simultaneously inhibiting three major pathways by which high sugar levels cause tissue damage, such as retinopathy.36 Benfotiamine was also shown to stimulate a key enzyme called transkelotase, which converts potentially damaging glucose breakdown products into harmless compounds that are safely eliminated. Together, these actions make benfotiamine a front-runner in preventing the development of diabetic complications.35,36

Another important and life-threatening complication of diabetes is the heart condition known as diabetic cardiomyopathy, in which individual heart muscle cells cannot contract as strongly as they normally would. The reasons for these changes are only partially understood, but appear to be related both to oxidative stress and inflammation at least in part caused by AGEs affecting the contractile proteins that cause heart muscle cells to beat.37-40

Cardiovascular and alternative medicine researchers at the University of Wyoming put these ideas to the test, treating mice with benfotiamine therapy 14 days after inducing diabetes in the animals. They then studied characteristic features of heart muscle performance that indicated how strongly the hearts were beating and how well the heart tissue responded to chemical signals. Astonishingly, benfotiamine treatment abolished the muscle cell abnormalities induced by diabetes in these animals! Oxidative stress was also measurably reduced though in this short-term study, the researchers did not find effects on AGEs.41

Further research has also shown that benfotiamine is effective at preventing slow-to-heal pressure sores, which are a major cause of suffering and even death in diabetic patients. A group of researchers in Italy used benfotiamine to speed the healing of such wounds.42 Diabetic mice were given oral benfotiamine or a control liquid, and then underwent ischemia (restricted blood flow) of one limb. The scientists then measured tissue indicators of cell death and destruction. Remarkably, benfotiamine completely prevented ischemia-induced necrosis (tissue death) in animals’ toes, improved blood flow and oxygenation, and restored normal blood vessel relaxation (an important control mechanism that is lost in AGE-induced endothelial injury). But that’s not all—closer microscopic examination of the tissue showed substantially improved new blood vessel formation and inhibition of cell death in the affected limbs. Supplementation also prevented accumulation of AGEs in the blood vessels, which probably accounts for the remarkable benefits. The authors were understandably exuberant in their concluding statement, “We have demonstrated, for the first time, that benfotiamine aids the post-ischemic healing of diabetic animals…”

An explosion of convincing animal studies further supports benfotiamine’s remarkable benefits. Benfotiamine has now been shown to counteract AGE-related toxicity on endothelial cells,43 to relieve inflammatory and neuropathic (nerve-induced) pain in both diabetic and non-diabetic rats,44 and to alleviate diabetes-induced oxidative damage to brain tissue.45 Interestingly, benfotiamine’s protective effect on brain tissue is produced by mechanisms that seem to be unrelated to AGE formation, opening the door to even greater benefits in this area!

There is clearly no doubt that benfotiamine has proven itself in laboratory studies, and research is now yielding convincing evidence from human trials as well. Dramatic results are flowing in from top-level researchers around the world, demonstrating that benfotiamine’s potent AGE/RAGE inhibition translates directly into measurable benefits for humans.

Aging and AGEs

Bizarrely, AGEs are formed by the interaction of glucose and proteins through a specific kind of chemical reaction, called the “Maillard” reaction, that is identical to the so-called “browning reactions” found in ripening fruits and foods cooked at high temperatures.58,59 Maillard reactions are distinctly unwelcome in human tissues, where their AGE-related products produce powerfully destructive oxidative stress and inflammatory reactions,6,15,19 which ultimately lead to atherosclerosis and its deadly consequences.6,15 By “cross-linking” with collagen and other long-lived proteins, AGEs have far-reaching deleterious effects by reducing the elasticity of tissues such as blood vessels where these proteins reside.60 Furthermore, the biochemical changes induced by AGEs may also damage DNA,24 which, together with inflammation, can promote the development of cancer.57

Clearly, the Maillard “browning” reactions occur all the time in our bodies, gradually adding to our burden of oxidative stress, inflammation, and tissue dysfunction—and ultimately to our cumulative risk of serious chronic age-related diseases.

Preventing Diabetic Complications in Humans

Since benfotiamine has such potent anti-AGE and oxidative stress-reducing effects, scientists wondered if it would be helpful in treatment of diabetic neuropathies in humans. To investigate, German researchers conducted a randomized, double-blind, controlled study of benfotiamine plus vitamins B6 and B12 in patients with diabetic polyneuropathy.46 This study of 24 patients lasted 12 weeks, and demonstrated dramatic improvement in nerve conduction velocity (the speed with which electrical signals move along nerves) in benfotiamine recipients versus controls. There was also an improvement of patients’ ability to sense vibration (again, an important measure of the ability to perceive pressure and motion). None of the patients experienced side effects related to treatment. These researchers concluded that benfotiamine (in combination with the B vitamins) “represents a starting point in treatment of diabetic polyneuropathy.”

Three years later, Hungarian researchers conducted dose-finding studies of benfotiamine. These scientists treated patients who had painful diabetic neuropathy with a higher-dose benfotiamine treatment of 320 mg/day or with medium-dose treatment of 150 mg/day. This was a six-week-long, open trial among 36 subjects ranging from 40 to 70 years old whose diabetes was under reasonably good control. All patients experienced significant improvements in pain and vibration sensation, as well as in objective measurements of nerve function, with most improvements being evident by the third week of the study. The greatest changes were seen in the high-dose recipients. The researchers concluded that benfotiamine is effective even in the medium-dose range, but that maximum benefits would be found with higher doses. These findings represent a major breakthrough in the management of this heartbreaking and deadly complication of diabetes.47

Results such as these have now been confirmed by independent research groups, one of whom studied 40 inpatients with diabetic polyneuropathy of not more than two years’ duration.48 Twenty of their subjects received benfotiamine 100 mg four times daily, while the others got only placebo tablets. The researchers used a standardized neuropathy score that included measurements of vibration perception as well as patients’ and their physicians’ subjective assessments (it’s just as important to know that the patient feels better as it is to know that their “numbers” are improving). Dramatic improvements were seen in benfotiamine patients’ scores compared with controls, with the most pronounced effect being a reduction in pain. More benfotiamine patients than placebo patients also felt that their overall condition improved, and no patients in either group experienced side effects. The authors pointed out that their findings confirmed the results of earlier trials, and provided “further evidence for the beneficial effects of benfotiamine in patients with diabetic neuropathy.”

Nutritional research on benfotiamine has now expanded, with a growing number of studies evaluating its benefits in areas other than diabetic neuropathy. One important area is the prevention of endothelial dysfunction in both large and microscopic blood vessels, a major contributor to atherosclerosis in diabetic as well as non-diabetic patients.

In the first study of its kind, investigators looked at the effects of benfotiamine in blocking endothelial dysfunction and oxidative stress after consuming a meal rich in dietary AGEs.49 They provided type 2 diabetic subjects with a heat-processed test meal that had a high AGE content, both before and after a three-day period of supplementation with 1,050 mg/day of benfotiamine. The scientists measured standard indicators of large- and small-vessel function, as well as blood levels of AGEs, oxidants, and markers of endothelial dysfunction throughout the study. The high-AGE meals before the supplement period had a profound effect on capillary blood flow in reaction to a stimulus, reducing it by 60%, while the ability of larger vessels to dilate (relax) in response to increased blood flow was diminished by 35%.50 These changes are typical of findings in people with early atherosclerosis, which can lead to heart attack or stroke.51-53

Remarkably, these detrimental effects on blood vessels were completely prevented by the three-day period of benfotiamine supplementation! Similarly, the AGE-induced post-meal increases in serum markers of endothelial dysfunction and oxidative stress were also significantly reduced after the supplement period. This landmark study, in the authors’ own words, “confirms micro- and macrovascular endothelial dysfunction accompanied by increased oxidative stress following a real-life, AGE-rich meal in individuals with type 2 diabetes and suggests benfotiamine as a potential treatment.”50 A follow-up study by the same research team late last year further showed that the vital molecule adiponectin—which promotes glucose uptake into skeletal muscle and increases fat burning54— decreases after a similar high-AGE meal. Again, benfotiamine prevented this detrimental effect of a meal rich in AGEs.55

Summary

We have come a long way in a few short years of nutritional research. Just over a decade ago, the devastating effects of AGE/RAGE reaction products on tissues were believed to be inevitable in people with diabetes, presenting the grim prospects of progressive loss of nerve, blood vessel, and kidney function, and their consequences on quality and quantity of life.3 Thanks to the discovery of the fat-soluble form of thiamine, benfotiamine, the past decade has witnessed an abundance of promising research to help dispel those ominous predictions and offers new hope for people with diabetes.7,14 Equally exciting work is now beginning to emerge, suggesting that this is only the beginning. Benfotiamine is currently being studied for its benefits in non-diabetic people as well, where it may help reduce DNA damage in people with end-stage renal disease,57 ensure protection from the endothelial dysfunction that leads to atherosclerosis and congestive heart failure, and provide relief in a host of additional painful nerve conditions.18 Benfotiamine’s impressive safety record supports its use in both diabetic and non-diabetic people interested in reducing the impact of AGE/RAGE on their longevity and quality of life.
Material used with permission of Life Extension. All rights reserved.