Grape Seeds—As Good as Wine?

Grape Seed Extract May
Inhibit Fat Absorption

Beyond its many other health benefits, it may act
as a safe, effective, natural weight-loss agent
By Richard P. Huemer, M.D.

Better be merry with the fruitful Grape
Than sadden after none, or bitter, Fruit.

— Omar Khayyám

n medieval Persia, the great mathematician and astronomer Omar Khayyám, best known to most of us as a poet, ruminated over the mysteries of existence. It was all too depressing, he concluded, so the answer lay in liberally imbibing wine, presumably the red kind. There are those who have taken his advice to heart—perhaps too much so, with dire consequences for their livers, and even their lives. Those, however, who drink sensibly can reap benefits in health—and even, perhaps, longevity—that people throughout the ages have suspected (and written about).

Modern science has taught us much about the wonders of wine and the grapes from which it comes, including the fact that most of the beneficial chemical compounds are found in the seeds and skins of the grapes. Thus, to enjoy many of the health benefits of Vitis vinifera, we need not necessarily partake of the fermented juice of the grape—the seeds will do nicely, as we will see shortly.

Resist Insulin Resistance!

One of the challenges of modern life is how to stay slim and trim in an era of supersized portions, high-glycemic-index foods, and empty-calorie snacks. Over 60 million adult Americans are now obese, and that condition is the primary risk factor for type 2 diabetes, the incidence of which is skyrocketing. (About 90% of all diabetes is type 2.) The precursor condition to diabetes is insulin resistance, in which the body becomes resistant to its own insulin as the latter tries to reduce blood sugar levels by facilitating the transport of glucose molecules into the cells. This condition is linked with the release into our blood of free fatty acids from fat cells.

A comparison between daily caloric intake in 1985 and in 2000 shows that Americans are consuming, on average, 300 more calories than before—that’s 110,000 calories per year! If all those calories were converted to stored fat, they would add 30 pounds of body weight annually, and in 10 years we would gain 300 pounds. (Some of the excess calories are converted to fat, as we know all too well, but the rest are burned up, because the heavier we get, the more calories must be expended just to maintain our basal metabolism and to move our bodies around—basic physics.) If only it were possible to block the absorption of some of those extra calories!

Inhibiting Fat-Digesting Lipases Is One Way

Actually, it is possible. Since 1999, a prescription drug called orlistat (Xenical®), has been available to block fat absorption, and in February 2007, the FDA approved the over-the-counter sale of orlistat (at half the strength) as a drug called alli™. Orlistat works by inhibiting (by about 30%) the action of lipases made in the stomach and pancreas. The function of these digestive enzymes is to catalyze the breakdown of dietary triglycerides (fats) to free fatty acids in the small intestine, thus permitting their absorption by the body, where they can be used for various purposes—including reconstitution as fat molecules for storage, as such, in fat cells.

When the digestion of fats is thwarted, the undigested molecules continue on down the line—and that’s where the trouble starts. Orlistat is notorious for its unpleasant consequences, notably increased flatulence and frequent or urgent bowel movements that produce loose, oily stools.* Not exactly a recipe for social success! To minimize these problems, the manufacturer recommends avoiding fatty foods in favor of a low-fat, low-calorie diet—good advice, which, if followed, would pretty much obviate the need for orlistat in the first place.

*A more serious problem is impaired absorption of the fat-soluble vitamins (A, D, E, and K) and other fat-soluble nutrients.

Grape Seed Extract Inhibits Lipases without the, uh, Bottom Effects

For those whose dietary and exercise habits are less than perfect and who would like to battle the bulge without setting up shop in the bathroom, there is a promising alternative: grape seed extract. Its abundance of polyphenolic compounds is believed to be largely responsible for its health benefits, which include an antiobesity effect and an enhancement of insulin sensitivity (which is the opposite of insulin resistance). Most notable among these compounds are anthocyanins and proanthocyanidins, which are two types of flavonoids. Also present are nonflavonoid polyphenols, such as the longevity-inducing compound resveratrol (see “Revolutionary Antiaging Discovery with Resveratrol” in the January 2007 issue).

Like orlistat, grape seed extract (GSE) inhibits lipases—but not as strongly, so social faux pas are not as likely to occur. Furthermore, and unlike orlistat, GSE is absorbed by the gut and enters the circulation, where it can also exert its effects on lipases found there. In a paper published in 2003, a group of American researchers who were interested in this effect wrote,1

Ingestion of natural antioxidants, such as grape seed extract (GSE) rich in proanthocyanidins, has been demonstrated to improve insulin sensitivity and/or ameliorate free radical formation and reduce the signs and symptoms of chronic age-related disorders, including syndrome X.

(Syndrome X is the metabolic syndrome; see the sidebar.) To gain insight on how GSE accomplishes this, the researchers studied its inhibitory effects on three lipases: pancreatic lipase, which is found in the intestine and is the most important enzyme for digesting dietary fats; lipoprotein lipase, which is found in the blood; and hormone-sensitive lipase, which is found in adipose tissue (fat). All three tend to promote the storage of body fat, but by somewhat different mechanisms.

Chrome-Plated Grape Seeds, Anyone?

A medical condition that presages nothing but bad news on many fronts afflicts over 75 million Americans, yet most people have never even heard of it. It’s the metabolic syndrome—a vague-sounding name, which may be one reason for its obscurity. It used to be called (and some still do call it) syndrome X, which sounds mysterious and is even less descriptive than metabolic syndrome. The original name fit when the syndrome was poorly understood, but that is no longer true.

There are many kinds of syndromes arising from or affecting our metabolism in some way, but this one is the big kahuna. It’s defined mainly by insulin resistance and excessive insulin in the blood, but other characteristic features are central (abdominal) obesity, high blood pressure, high triglycerides, low HDL-cholesterol, and high blood sugar (the natural consequence of insulin resistance)—a disastrous recipe for health!

In a paper published in 2002, a group of American researchers summarized prior work suggesting that a combination of grape seed proanthocyanidin extract and chromium polynicotinate (also known as niacin-bound chromium) can be more effective than either one alone in helping to protect rats and humans against the metabolic syndrome.1 The extract acts as an antioxidant and, not coincidentally, as an insulin-sensitivity enhancer—the two phenomena are closely related. Chromium, an essential trace mineral, is known to enhance insulin sensitivity; it also has antioxidant properties when it occurs in the form of chromium polynicotinate, which is highly absorbable. Some scientists believe it to be superior to the widely used chromium picolinate, which has been suspected of mutagenic propensities.*

*For those who remember the movie Erin Brockovich, we hasten to add that the nutritional kind of chromium is trivalent chromium, Cr(III), and not hexavalent chromium, Cr(VI); the latter is the kind that contributed to the poisoning of Ms. Brockovich’s clients.

Together, the grape seed extract and chromium polynicotinate lowered blood pressure (a marker for insulin sensitivity) in rats. And in a randomized, double-blind, placebo-controlled study of 40 people with high cholesterol, this combination lowered total cholesterol by 16.5% and LDL-cholesterol (“bad cholesterol”) by 20%.2 There were no changes in HDL-cholesterol (“good cholesterol”) or triglycerides.

From this and other evidence reported elsewhere, the authors concluded that ingesting a combination of grape seed proanthocyanidin extract and chromium polynicotinate can significantly lower cholesterol levels, improve insulin sensitivity, reduce oxidative stress, and reduce the manifestations of chronic age-related disorders, including the metabolic syndrome.


  1. Preuss HG, Bagchi D, Bagchi M. Protective effects of a novel niacin-bound chromium complex and a grape seed proanthocyanidin extract on advancing age and various aspects of syndrome X. Ann NY Acad Sci 2002;957:250-9.
  2. Preuss HG, Wallerstedt D, Talpur N, Tutuncuoglu SO, Echard B, Myers A, Bui M, Bagchi D. Effects of niacin-bound chromium and grape seed proanthocyanidin extract on the lipid profile of hypercholesterolemic subjects: a pilot study. J Med 2000;31:227-46.

Grape Seed Extract May Help Prevent Insulin Resistance

The researchers tested GSE’s effects on the first two of these enzymes (from human sources) in test-tube experiments and on the third enzyme in cultured mouse adipocytes (fat cells). Test tubes and mouse fat are far cries from actual human beings, but it’s a start. The results showed that, in a dose-dependent manner, GSE strongly inhibited pancreatic lipase; it also inhibited lipoprotein lipase, less strongly but still significantly.

In the third experiment, the researchers incubated the cultured mouse adipocytes with GSE for 18 hours and then used a chemical agent to stimulate the breakdown of triglycerides to produce fatty acids and glycerol. They observed that GSE inhibited the breakdown (again in a dose-dependent manner), presumably by inhibiting hormone-sensitive lipase. This finding implies that human adipocytes might take up GSE from the circulation (in contrast to orlistat, which, as noted above, works only in the intestine and never reaches the circulation in the first place). If this were true, it could potentially reduce the levels of circulating free fatty acids and thus help prevent the development of insulin resistance in obese people.

A Single High Dose Improves Lipid Profile

In related research, Spanish investigators analyzed the acute effects of grape seed proanthocyanidins, the most abundant polyphenols in red wine, on healthy male rats with normal blood lipid levels.2 Each rat received a very high but nontoxic oral dose of an extract consisting almost exclusively of proanthocyanidins. Five hours later, the animals were killed for analysis of their blood lipids and their liver, muscle, and fat tissues. The purpose was to evaluate the rats’ “atherosclerotic risk index” by examining the effects of red wine polyphenols that reportedly protect and enhance the function of both heart and blood vessels.

In the authors’ words, the extract “drastically improved plasma lipidic profile.” Specifically, it lowered triglycerides by 50% and apolipoprotein B (a potentially harmful lipoprotein) by 40%. It also significantly lowered free fatty acids and LDL-cholesterol (“bad cholesterol”) while slightly increasing HDL-cholesterol (“good cholesterol”); oddly, though, total cholesterol levels were unchanged.

The rats’ livers showed suppression of some enzymes and enhancement of others, including one whose overexpression implies an increased elimination of cholesterol via the bile. Muscles had more lipoprotein lipase (useful for extracting energy from fats), and fat tissue had less. A key signaling protein was also increased. (The level of each enzyme or protein was inferred from the measured amount of the mRNA molecule that codes for it.)

Paradox? What Paradox?

This short-term experiment showed that a single large dose of the grape seed proanthocyanidin extract can improve the atherosclerotic risk index in rats. We don’t know whether or not the same effect would result from long-term ingestion of lower doses by humans, in whom fat-laden blood after meals increases the risk of atherosclerosis and coronary heart disease. If it did, then the consumption of red wine with meals might explain the vexing “French paradox,” a relatively low incidence of cardiovascular mortality in people whose diet is high in cholesterol and saturated fats. The French love their fats, but they also love their wine.

Probably the best thing for us is to consume both grape seed extract and red wine, for different but related reasons. With regard to wine, the key, of course, is moderate consumption—we’re OK with that. But we’ve found no scientific support for Omar Khayyám’s immoderate exhortation, “Drink! for you know not whence you came, nor why: Drink! for you know not why you go, nor where.” Oh, that Omar! Always looking for an excuse to party.


  1. Moreno DA, Ilic N, Poulev A, Brasaemle DL, Fried SK, Raskin I. Inhibitory effects of grape seed extract on lipases. Nutrition 2003;19:876-9.
  2. Del Bas JM, Fernández-Larrea J, Blay M, Ardèvol A, Salvadó MJ, Arola L, Bladé C. Grape seed procyanidins improve atherosclerotic risk index and induce liver CYP7A1 and SHP expression in healthy rats. FASEB J 2005; 19(3):479-81.

Dr. Richard P. Huemer received his M.D. from UCLA and did postdoctoral research in cancer immunology at CalTech. He has specialized in orthomolecular medicine for most of his career, has written and lectured extensively on alternative medicine, and has served on the editorial boards of professional journals. His published books include The Roots of Molecular Medicine: A Tribute to Linus Pauling and, with coauthor Jack Challem, The Natural Health Guide to Beating the Supergerms.

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