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Benfotiamine is a form of Vitamin B-1 used in Germany for the treatment and prevention of diabetic health complications.
Advanced Glycation Endproducts, or "AGEs” as they're appropriately called, are the end result of the complex chemical process through which the structure of proteins is warped by exposure to sugars or by other, much more reactive molecules. AGE chemistry is the cause of the "browning” you see when you roast a chicken or make toast, but the same "browning” chemistry is at work in your body every day of your life. In your arteries. In your kidneys. In your heart, your eyes, your skin, your nerves. In every cell, the sugar that your body uses for fuel is busily at work at this very moment, caramelizing your body through exactly the same chemical processes that caramelize onions or peanut brittle.
Glycation math is simple: more sugar equals more AGEd proteins. As a result, people with diabetes begin to feel the effects of glycation at much younger ages than do people with more normal blood sugar levels. Watching people with diabetes age is like watching "normal” aging played on fast-forward. Slowly, imperceptibly, AGE reactions create chemical handcuffs, which gum up your proteins, deactivate your enzymes, trigger unhealthy biochemical signaling in your cells, and damage your DNA. Aging you.
Two Ways to AGE
There are two major ways that AGEs can form inside the body. One way is through a simple series of chemical reactions known as the "Maillard Pathway,” known from food chemistry for a century.
But more recently, scientists have come to understand another pathway of AGE formation – a distinctly biological pathway, which only occurs within your cells because of the body's metabolism of carbohydrates.
When blood sugar levels rise, some key kinds of cell – including- nerve cells (neurons) and the cells that make up the fine blood cells of the retina of the eye and the filtering units (glomeruli) of the kidney – are also flooded with glucose. The resulting high sugar levels within these cells cause a logjam in the normal cellular metabolism of glucose. This backlog results in a buildup within the cell of super-reactive glucose-metabolic intermediates known as triosephosphates. And once that happens, the excess triosephosphates attack the surrounding proteins, lipids, and DNA, causing AGE damage from within the heart of the cell. It's these cells are thus the most vulnerable to the complications of diabetes.
Drugs do exist which can inhibit the formation of AGE, but none are available on the market as yet, and one of the most promising candidate (aminoguanidine) has shown signs of toxicity in human trials and appears to have been abandoned by its developers. On the other hand, some companies are selling supplements are marketed as "AGE-inhibitors.” But while many of the herbs and other nutrients may be valuable, and many even inhibit AGEing in a test tube, there's no evidence that most of these "AGE-blocking” ingredients have any effect on AGEing in your body at the dosages used. Examples include thyme extract, inositol, acetyl-L-carnitine, taurine, and a whole host of antioxidants (including n-acetyl-cysteine (NAC) and flavonoids, such as quercetin and resveratrol).
TPP: Our Hero … in Chains!
There is a nutrient that could, in theory, pack a potent wallop against the AGE onslaught: Thiamin Pyrophosphate (TPP), the active coenzyme form of the B-complex vitamin thiamin. In 1996, researchers showed that TPP could step in to stop AGE formation at the most important point in the process: the late, irreversible conversion of Amadori products into full-blown AGEs. What's more, TPP can exert a two-pronged AGE-inhibiting effect in the body, because boosting TPP in cells stressed by high glucose concentrations opens up an important biochemical "safety valve” in the normal metabolism of blood sugar through an enzyme known as transketolase. Activating transketolase allows the body to shunt excess triosephosphates into a safe alternative metabolic pathway, preventing the logjam that leads to the buildup of triosephosphates and the formation of AGE.
Unfortunately, this does not mean that loading up on regular thiamin (vitamin B1) will free you from glycation's sticky shackles. The problem is that your body's ability to absorb and metabolize conventional thiamin supplements is very limited. In fact, no matter how much thiamin you take, you don't materially increase plasma levels beyond what you get from the first 12 milligrams of the dose. And then getting thiamin into the cells to do its job is just as tricky.
You might think that you can get around this problem by taking supplements containing TPP itself, instead of plain old thiamin. Unfortunately, as part of the normal cellular absorption process, specific enzymes actually strip TPP of its phosphate groups. As a result, you get no additional AGE-battling benefit from taking preformed thiamin pyrophosphate instead of standard thiamin. In fact, when you take supplements based on TPP itself, studies show that thiamin levels and biological activity are actually lower than if you take the same amount of regular thiamin!
Benfotiamine: the TPP Solution
Fortunately, an effective way to boost thiamin pyrophosphate in your cells does exist: Benfotiamine (S-benzoylthiamine-O-monophosphate). Benfotiamine is the most potent of the allithiamines, a unique class of thiamin-derived compounds present in trace quantities in roasted crushed garlic and other vegetables from the Allium genus (such as onions, shallots, and leeks). Benfotiamine's unique open-ringed structure makes it able to pass directly through cell membranes, readily crossing the intestinal wall and being taken straight into the cell.
As a result, your body absorbs Benfotiamine better than thiamin itself, and levels of thiamin and TPP remain higher for longer. Thiamin absorption from Benfotiamine is about five times as great as from conventional thiamin supplements. And the effect is even more impressive at the tissue level: brain and muscle, for instance, take in five- to twentyfive-fold as much thiamin in the form of allithiamines as they do of an equal amount of regular thiamin. And Benfotiamine is even more bioavailable than the other allithiamines, including thiamin tetrahydrofurfuryl disulfide/TTFD. Yet Benfotiamine is actually less toxic than conventional thiamin supplements!
By effectively increasing levels of thiamin itself, Benfotiamine dramatically boosts AGE-fighting thiamin pyrophosphate and cell-shielding transketolase activity in your body.
Shielding Nerve Structure
While most "anti-AGE” supplements rely on test-tube "browning” experiments as the "evidence” of efficacy, Benfotiamine has been proven in multiple real-world human and animal studies to reduce AGE formation and support tissue structure and function in diabetics.
Most impressively, many randomized, double-blind, placebo-controlled human trials have proven that Benfotiamine powerfully supports nerve function in diabetic neuropathy. In one trial, 24 people suffering with diabetic neuropathy took either Benfotiamine (plus doses of common B6 and B12 similar to those used in mutivitamins) or a look-alike dummy pill, spread out into three pills over the course of the day, for twelve weeks. The participants started with 320 milligrams of Benfotiamine per day for the first two weeks, followed by 120 milligrams for the rest of the trial. Before and after the trial, the function of patients's nerve cells were tested using nerve conduction velocity (NCV) and vibratory perception threshold (which tests the nerves's sensitivity by determining the lowest level at which vibrations applied at key nerve sites are first felt).
At the end of the trial, the vibration perception threshold had "clearly” improved by 30% in those who had taken the Benfotiamine supplements, while it had worsened in the placebo group by 5% at one site and by 32% at another. At the same time, people taking Benfotiamine experienced statistically significant improvements in nerve conduction velocity from the feet, even as this aspect of nerve function deteriorated in those taking the look-alike pills!
The power of Benfotiamine to improve vibratory perception threshold and nerve conduction velocity have been confirmed in other trials. Clinical trials have also shown that Benfotiamine supports nerve function in diabetics as measured by many other methods. For instance, Benfotiamine users experience a 50% reduction in diabetic nerve pain, along with an increased ability of the nerves to detect an electrical current, respond to electrical stimulation, and regulate the heartbeat Similarly, Benfotiamine prevents this loss of control from happening in the first place in diabetic dogs. In another human clinical trial, a B-vitamin combination using Benfotiamine as its thiamin source was put head-to-head with a B-complex supplement that included a megadose of conventional thiamin. Benfotiamine proved its effectiveness on several of these key parameters, while the standard thiamin pill failed.
These benefits are not due to changes in blood sugar levels (either fasting, or after a meal, or averaged over several months (as measured by HbA1c), or improvements in metabolic benchmarks. They are the direct results of Benfotiamine's AGE-fighting, metabolic-balancing powers.
Benfotiamine in Other Vulnerable Tissues
More recently, new studies have begun to document Benfotiamine's ability to shield other tissues from AGE damage. One just-published study tested the ability of thiamin and Benfotiamine to protect diabetic rodents' retinas from the ravages of AGE.
The researchers then gave one group of diabetic rodents Benfotiamine supplements, and left another group unsupplemented, keeping a third group of nondiabetic animals as a control group. Nine months later, they examined the animals' eyes, testing the level of AGE in their retinas, examining metabolic abnormalities of the cells, and looking for acellular capillaries (the dead husks left behind when the cells of the tiny blood vessels of the eye die).
Benfotiamine supplements normalized AGE levels in the diabetics' retina, as well as several key metabolic parameters within the diabetic animals' cells – without influencing body weight or blood sugar (as measured by HbA1c). More importantly, Benfotiamine prevented the AGE-associated retinal damage. After nine months of diabetes, diabetic animals had suffered three times as many acellular capillaries as were found in healthy animals. But with the protection afforded by Benfotiamine, the number of acellular capillaries in the supplemented diabetics was indistinguishable from that of their normal, healthy cousins!
And there's another AGE-related disease that researchers believe Benfotiamine may fight: the loss of kidney function which accompanies "normal” aging, and which is accelerated by diabetes. Dr. Paul Thornalley of the University of Essex has just completed a study designed to see if Benfotiamine will protect diabetic rodents against kidney damage. While the results have not yet been published, Dr. Thornalley has indicated that both megadose thiamin and Benfotiamine caused clear-cut reductions in the leakage of protein – with Benfotiamine showing itself to be the superior intervention. A second study is now underway to see if Benfotiamine will actually improve kidney function in diabetic animals with pre-existing kidney damage, as it has already been shown to do in the nerves of diabetic animals and humans.
The End of an AGE
These are not test-tube studies. The results experienced when taking Benfotiamine occur not merely in labs, but in lives: in the bodies – and in the health – of living things, from experimental animals to human beings. In Benfotiamine, we finally have a proven way to protect tissues from the AGE assault.
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