Cheat a Little with Benfotiamine

Benfotiamine Counteracts the
AGEs in Your Meals

This thiamine derivative may enable us to continue
enjoying the browned (unhealthy) foods we love
By Will Block

I cannot pretend to feel impartial about colors.
I rejoice with the brilliant ones and am
genuinely sorry for the poor browns.

— Winston Churchill

t’s about 800,000 years ago, and you’re sitting by a campfire (a recent invention), eating raw meat from a kill made earlier in the day. Unnoticed at first, a small chunk of flesh falls into the fire and is quickly seared. Intrigued by the tidbit’s brown color, you pick it up and sniff cautiously. You smile. Then you taste it, and the smile becomes a wide grin. A grunt of pleasure is heard as you swallow the treat.

A light bulb goes on over your head (don’t quibble, OK?), and you think, “Fire . . . meat . . . brown . . . good” (you’ve had a way with words ever since they were invented by your Uncle Grok). You’ve just discovered cooking!

That was the beginning of civilization, or at least the beginning of mankind’s enduring love affair with food that has been roasted, barbequed, baked, or fried—in other words, browned. It has brought us to an age when gazillions of burgers and fries are wolfed down daily by people whom Grok would recognize only by their little grunts of gustatory satisfaction—the same kind that made him think, “There’s got to be a better way than this to communicate our feelings . . .”

The Tragedy of the AGEs

In food, we celebrate the virtues of the brilliant colors red, orange, yellow, blue, and purple, because they signal the health-giving benefits of flavonoids in our fruits and veggies. But for lip-smacking, “gruntling” goodness, the F&V’s don’t hold a candle (for most people, anyway) to a brown, juicy, sizzling steak or burger. Ah, the aroma! Ah, the taste! Oh, the injustice!

Huh? What injustice? Alas, it’s one we’re all too familiar with: something that we really love turns out to be bad for us, so we should try to avoid it for our own good. In this case, the delicious culprit is the browning of meats and other foods cooked at temperatures well above that of boiling water. Even the appealing golden brown crust on baked goods, such as bread, bagels, and pretzels, can be harmful to our health.

It’s the tragedy of the AGEs; that’s an acronym for advanced glycation endproducts, about which you have heard before in the pages of this magazine.* The aptly named AGEs are implicated in many degenerative diseases, and they’re believed to be an important feature of the aging process itself, in part because of the oxidative stress they induce throughout our bodies. (Conversely, an oxidative environment is known to accelerate the formation of AGEs.) Naturally, we want to combat them in every way possible. One way is with benfotiamine (ben·fo·TIE·ah·meen), a fat-soluble form of an old nutritional friend, thiamine, aka vitamin B1. (For an overview of this important nutrient, see the sidebar.)

*See, e.g., the article on page 11 of this issue. For a recent overview of the subject, see “How and Why to Prevent AGE Damage” in the March 2008 issue.

Of Thiamine and Benfotiamine

Of the 13 known vitamins, nine (vitamin C and the eight B-vitamins) are water-soluble, and the other four (A, D, E, and K) are fat-soluble. That makes a difference in bioavailability, because the fat-soluble vitamins tend to be absorbed better and retained longer (in fatty tissues) than the water-soluble vitamins. Thiamine (vitamin B1), being water-soluble, has relatively poor bioavailability, but this problem can be circumvented by taking benfotiamine, which is fat-soluble and can be absorbed in much larger amounts.

Benfotiamine, a synthetic derivative of thiamine, was developed in Japan in the 1950s and patented in the USA in 1962, and it has been in widespread use in Japan and Europe for several decades.1 It’s related to a family of naturally occurring thiamine derivatives called allithiamines, which are found in trace amounts in plants of the genus Allium, such as garlic, onions, shallots, and leeks. There is no known toxicity associated with either thiamine or benfotiamine, even in very large amounts, nor are there any known adverse interactions between these compounds and any other nutrients or medications.

In the body, benfotiamine is quickly metabolized to thiamine and then to thiamine’s most active form, thiamine pyrophosphate (TPP). It is thus reasonable to conclude that any condition that can be treated with thiamine can also be treated with benfotiamine. TPP acts as a coenzyme for a small number of important enzymes involved in metabolic pathways that play critical roles in the production of energy from food.

Thiamine is found mainly in milk, meat, yeast, and the bran coat of grains. It’s essential for the normal growth and development of children, for various aspects of carbohydrate metabolism, and for normal neural activity. Thiamine deficiency is rare in the industrialized world except in alcoholics, in whom the condition can be due to low dietary intake, impaired absorption and utilization, or increased excretion of the vitamin. In eastern and southern Asia, thiamine deficiency is endemic; it causes the disease beriberi, which is characterized by neurological symptoms, cardiovascular abnormalities, and edema.


  1. Ito A, Hamanaka W, Takagi H, Wada T, Kawada K. S-Benzoylthiamine O-monophosphate and a process for preparing the same. United States Patent 3,064,000, Nov. 13, 1962.

AGEing from Within

AGEs can be confusing, because there are so many of them, and they come in different forms and from different sources. One of the two major kinds is endogenous, i.e., the AGEs come from within ourselves, via slow chemical reactions that occur naturally throughout our bodies, throughout our lives. Some of these AGEs accumulate indefinitely, slowly impairing the functions of many organs and tissues. Among the most damaging are chemically cross-linked proteins, which form a kind of cellular gunk that fouls the machinery of life.

The process begins with glycation, a chemical reaction between sugars (such as glucose and fructose) and proteins (such as collagen and hemoglobin). This initiates chains of further reactions involving many small molecular intermediates, of which hundreds are known. Some of these contain a group of atoms called the carbonyl group and are called reactive carbonyl species (RCS).

Cumulatively, these beasties cause carbonyl stress, a spectrum of chemical effects that are harmful to our cells and, therefore, to our health and longevity. The most notorious RCS is methylglyoxal, a highly cytotoxic (toxic to cells) compound produced naturally in the body as a byproduct of several metabolic pathways. It’s actually a dicarbonyl (a compound containing two carbonyl groups), and, like sugars, it can initiate AGE formation.

Dicarbonyls can also induce oxidative stress and promote inflammation. In diabetics, the condition of hyperglycemia (excessive blood sugar levels) is known to promote the rapid synthesis of dicarbonyls—one of the many reasons why hyperglycemia is so damaging to our system.

AGEing from Without

The other major kind of AGEs is exogenous, i.e., these ones come from outside our bodies, mainly in the form of browned food. The high heat of roasting, barbequing, baking, frying, etc., initiates complex cascades of chemical reactions that lead to over a thousand kinds of potentially harmful—but really delicious—small-molecule AGEs, which we consume with gusto, and often with ketchup. They’re so tasty, in fact, that they form the basis of the food-flavoring industry.

The browning reactions are similar to (but millions of times faster than) those that occur in our cells. Collectively, they’re called Maillard reactions, after the French chemist Louis-Camille Maillard (Mah·YAHR), who pioneered their study a century ago. The overall process of AGE formation, whether endogenous or exogenous, is called the Maillard process.

Accelerated AGEing in Diabetes

In our bodies, there is no way to prevent glycation, the first step in the Maillard process. As long as sugars and proteins come into contact with each other—and it’s impossible to prevent that—the laws of chemistry dictate that they will react with each other. These laws also dictate that the amount of AGEs produced will be in proportion to the concentrations of the reacting substances at every step of the way, starting with glycation.

And who has chronically high blood glucose levels? Diabetics, of course. As a result, their rate of AGE production—and therefore, in a sense, their rate of aging—is accelerated. The AGEs induce oxidative stress and carbonyl stress, opening a Pandora’s box of degenerative changes that damage organs and tissues throughout the body.

Much of the damage can be attributed to dysfunction of the vascular endothelium, the layer of smooth, flat, tightly packed cells that line the insides of our blood vessels and that play a critical role in regulating blood pressure and other aspects of our circulatory health. Since every cell in the body depends on the integrity of the circulatory system for proper nourishment and waste disposal, it’s easy to see how endothelial dysfunction could have negative repercussions almost everywhere—which is why diabetes leads to so many dreadful complications.

Care for a Little Postprandial Sabotage?

The scenario described above sounds grim—and it is. The good news, however, is that with certain chemical compounds, such as benfotiamine, it’s possible to sabotage the chain of events that glycation unleashes, thereby inhibiting the endogenous production of AGEs, and to suppress the damage done by ingesting exogenous AGEs from browned foods.

A German and American research team recently published a study on the effects of benfotiamine on endothelial dysfunction in diabetic patients who had eaten a meal with a high AGE content.1 Key to an understanding of this study is the fact that even a single unhealthy meal (high AGE content or high glycemic index) can induce postprandial (after-meal) endothelial dysfunction, especially in diabetics and other people with strong risk factors for cardiovascular disease. This dysfunction can also, however, occur in healthy people. And because most of our day is spent in the postprandial state, there is potential for chronic damage to our blood vessels and the tissues they serve.

The researchers used 13 diabetic patients, average age 57. Not surprisingly, the subjects were obese, with an average body mass index (BMI) of 30.3 (the threshold value for obesity is 30). During the 9-day period of the study, they were kept on a standard diabetes diet, except for two test meals (chicken breast, potatoes, carrots, tomatoes, and vegetable oil; 580 calories) that had a high AGE content (HAGE) due to frying or broiling. Of these two meals, one was eaten without benfotiamine, and one was preceded by benfotiamine supplementation (1050 mg/day) three times: on the 2 days prior and on the day of the test, 1 hour before the meal.

Benfotiamine Reverses AGE-Induced Endothelial Dysfunction

The results showed that the HAGE meal produced substantial endothelial dysfunction lasting for as much as 6 hours. The researchers suggested that this was due to a combination of two mechanisms: (1) a decrease in the rate of synthesis of nitric oxide (NO), a free radical that serves as the principal mediator of blood-pressure regulation; and (2) an increase in the scavenging of NO by entities such as AGEs, dicarbonyls, and reactive oxygen species.

At both the macrovascular (large-vessel) and microvascular (small-vessel) levels, benfotiamine reversed the observed endothelial dysfunction completely. The researchers attributed this to a reduction in the endogenous production of AGEs and dicarbonyls as well as to a reduction in oxidative stress. They based their conclusion in part on measurements of the levels of various compounds in the blood that serve as indicators of endothelial dysfunction and oxidative stress.

Benfotiamine Shows Anti-Inflammatory Effects

The researchers also observed that benfotiamine prevented a postprandial increase in circulating levels of methylglyoxal (MG) and carboxymethyllysine (CML), a commonly seen AGE. Finally, they observed that the HAGE meal induced a small rise in the subjects’ blood levels of CRP (C-reactive protein), a marker of systemic inflammation, and that benfotiamine prevented this effect. This finding jibes with previous reports suggesting that benfotiamine has both direct and indirect anti-inflammatory effects.

The authors stated,1

In conclusion, our study demonstrated that a heat-processed test meal, with a HAGE, induces endothelial dysfunction and oxidative stress and increases serum AGE and MG concentration, effects that are prevented by benfotiamine. We suggest that benfotiamine might play an important role in atherosclerosis preventive therapy in patients with diabetes.

The encouraging results of this small study must be tempered by the realization that certain potentially confounding factors cannot be ruled out. As the authors explained, high-temperature cooking of foods can induce various chemical modifications other than those associated with AGEs, such as the inactivation of vitamins and antioxidants and the generation of other toxic compounds. How such effects might have influenced the results of this study is unknown, but the authors reiterated their belief that the counteracting effects of benfotiamine on AGE-induced endothelial dysfunction are real.

How Does High Heat Affect Adiponectin?

A subsequent benfotiamine study by the same German research team (minus the American members) was designed similarly, but here the goal was to determine the effects of a high-heat-processed meal with high AGE content (HAGE) vs. a low-heat-processed meal with low AGE content (LAGE) on the subjects’ postprandial levels of adiponectin, a hormonelike protein produced in adipocytes (fat cells).2 Adiponectin enhances insulin sensitivity in peripheral tissues, which reduces the risk for type 2 diabetes and, therefore, for atherosclerosis, which is a common complication of diabetes. Low levels of adiponectin are characteristic of these diseases and of obesity, which is the number one risk factor for diabetes.

In the new study, the researchers used 19 patients with poorly controlled diabetes; their average age was 55, and they were just shy of being obese, with an average BMI of 29.2. The two types of test meals were identical in content but were prepared differently. The researchers calculated that the HAGE meal (frying/broiling at 450ºF for 20 minutes) had 5.5 times the AGE content of the LAGE meal (steaming/boiling at 212ºF for 10 minutes).

Cooking Methods Matter, Darn It

As expected, the HAGE meal caused a reduction in postprandial adiponectin levels, but the LAGE meal did not, indicating that adiponectin is affected not only by food composition (as was known from previous studies) but also by cooking method. The message here—and we’ve heard it before, but we still don’t want to hear it—is that it’s better to cook our food by steaming, boiling, stewing, etc., than by the browning methods so dear to our hearts and stomachs.

Just as benfotiamine reversed the AGE-related endothelial dysfunction in the first study, it reversed the reduction in adiponectin levels in the new study (in which the same dosing regimen was used). It also reduced the HAGE-induced increase in methylglyoxal levels, and it prevented the HAGE-induced oxidative stress.

Was Woody Wrong?

It is said that American Indians believe that the color brown represents the power of self-discipline. If that’s true, there’s probably an interesting story behind it. It’s likely, in any case, that Indians have always loved the tantalizing aromas and flavors of browned foods as much as anyone else on earth. And it was fortunate for them, in olden times, that they were not put to the stern test of self-discipline required of those who would forego browned foods in favor of better health and longer life.

That is the test that now confronts us all, Indians included. But must we forego such deliciously savory mainstays of our diet for the sake of longevity? Perhaps Woody Allen was off the mark when he said, “You can live to be a hundred if you give up all the things that make you want to live to be a hundred.” It seems that benfotiamine may allow us to “cheat” a little by inhibiting the damaging effects of browned-food AGEs. Hooray for that! Let’s eat!


  1. Stirban A, Negrean M, Stratmann B, Gawlowski T, Horstmann T, Götting C, Kleesiek K, Mueller-Roesel M, Koschinsky T, Uribarri J, Vlassara H, Tschoepe D. 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; 29:2064-71.
  2. Stirban A, Negrean M, Stratmann B, Götting C, Salomon J, Kleesiek K, Tschoepe D. Adiponectin decreases postprandially following a heat-processed meal in individuals with type 2 diabetes: an effect prevented by benfotiamine and cooking method. Diabetes Care 2007;30:2514-6.

Will Block is the publisher and editorial director of Life Enhancement magazine.

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