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Supplements for preventing atherosclerosis
Rosmarinic acid, lycopene, grape seed extract, and chromium
by Russell Mills

I’d like to acquaint readers with the possibility of preventing atherosclerosis (plaque formation in the large arteries — a major cause of heart ailments) through the use of rosmarinic acid and lycopene. I will also mention another pair of nutritional supplements: chromium and grape seed extract. Before discussing the use of combinations, I’ll review some facts about each these supplements.

Rosmarinic acid: its nature and sources

Rosemary, oregano, marjoram, thyme, peppermint, comfrey, parsley, balm, sage, hyssop, basil, lavender — these, and other plants closely related to them, have medicinal properties known since ancient times, but not understood until recently. These plants all produce significant amounts of an antioxidant called “rosmarinic acid” (RA). Antioxidants prevent cell damage caused by free radical reactions — reactions that are thought to be involved in inflammation, degenerative arthritis and the aging process in general. RA is a strong antioxidant (stronger than vitamin E), a fact which explains why RA-containing plants have long been used for treating inflammatory ailments — for example, drinking rosemary tea to treat arthritis is an American folk remedy.

Why do these plants produce rosmarinic acid? Certainly not in order to help humans. Rather, the plants probably use RA as a defense compound against pathogens and herbivores. While humans may like the taste of, say, rosemary and thyme, many other plant-eaters don’t — cattle and horses, for example, hate them. The same is probably true for deer and other undomesticated herbivores.

Current RA production methods involve extraction and purification of essential oils either from crushed leaves or from plant cells grown in culture media. Yields are less than optimal, and this makes the product expensive. But programs are underway in several countries to breed or engineer plant varieties or cell lines that produce rosmarinic acid in very high yields.

Rosmarinic acid: usages

A list of common usages for rosmarinic acid is available online. Beyond what is said there, several iffy areas should be mentioned:

Rosmarinic acid is widely considered to be an antimicrobial agent, active against certain bacteria and fungi, although the medical literature has rather little to say about this idea. While RA-containing plants have been used to treat certain microbial diseases such as cholera, it is not clear that the antimicrobial properties of rosmarinic acid were involved — what was being sought (and obtained) was the symptomatic relief provided by the extracts as a whole. A handful of modern studies have shown RA to have some antimicrobial activity in vitro, but until the subject is more thoroughly studied, it would be unwise to rely on it for treating infections.

Rosemary has been used since ancient times as a memory enhancer. In 1998 researchers at the University of Miami School of Medicine tested the effects on cognition of inhaling the aroma of rosemary. This aroma treatment was found to put test subjects in a relaxed and alert state of mind and to enable them to complete math computations more quickly. Was rosmarinic acid responsible? It seems doubtful, since RA does not vaporize easily. But we cannot be certain until this experiment is repeated using RA alone.

Another claim often made about rosmarinic acid is that it inhibits the growth of cancer cells. While the medical literature is somewhat vague about which component of rosemary extract is responsible for this effect, it does seem likely that rosmarinic acid’s antioxidant properties play a significant role. At any rate, rosemary extracts produce dramatic reductions in experimentally induced tumor formation in experimental animals. Topical application reduced skin tumors by as much as 99% in mice, and dietary supplementation at high doses reduced mammary tumor incidence by 47%.

Now let’s take a look at lycopene.

Lycopene: its nature and sources

Lycopene is the substance responsible for the red color in tomatoes, guava, watermelon, pink grapefruit, and other fruits. Chemically it is a “carotenoid” and has antioxidant properties. For a given level of lycopene consumption, lycopene levels in the body decline with age, with higher body weight, and with smoking.

Until recently, all lycopene supplements were made from lycopene extracted from tomato products. More recently the Roche pharmaceutical company developed a method for synthesizing high-purity lycopene for about one-fifth the cost of lycopene extracted from tomatoes. Meanwhile, other researchers are working to improve lycopene production by extraction techniques. Transgenic tomatoes having greatly increased lycopene content were developed recently by the US Department of Agriculture. (As an added bonus, this strain of tomatoes also turned out to have “prolonged vine life, and enhanced fruit juice quality”, according to the report.)

For more information on lycopene see Lycopene.org

Lycopene: usages

Epidemiological studies show a positive correlation between high-lycopene diets and a low incidence of certain cancers. For example, the low rate of digestive-tract cancer in Italy is usually attributed to a high consumption of tomato products. Recent research suggests that lycopene reduces the risk of cancers of the lung, digestive tract, bladder, prostate, cervix and skin.

Lycopene reduces the body’s production of IGF-1 (Insulin-like Growth Factor) — a substance that regulates the growth of many kinds of tissue. Lycopene’s anticancer properties are probably due in part to this suppression of IGF-1. On the negative side, in suppressing IGF-1, lycopene might also reduce the desired growth of non-cancerous tissues. For example, a high-lycopene diet might counteract a dietary or hormonal breast-enhancement treatment, or it could interfere with the growth or maintenance of muscle tissue.

Higher lycopene consumption also correlates with lower rates of macular degeneration (loss of detailed vision), according to a 1995 study, and with a lower incidence of cardiovascular disease. A study of American and European men showed that those who had low levels of lycopene were twice as likely to have a heart attack as those with high levels.

Rosmarinic acid + Lycopene for atherosclerosis

Atherosclerosis is the deposition of cholesterol-rich plaques in the artery walls. A key inducer of the process is the oxidation of LDL (low density lipoprotein) in the blood. Rosmarinic acid can prevent this oxidation. Furthermore, RA’s ability to inhibit LDL oxidation is enhanced synergistically by combining RA with lycopene. Israeli researchers recently showed that a combination of rosmarinic acid and lycopene was a far better LDL-oxidation inhibitor (in vitro, at least) than either of the individual supplements — in fact, 3 times better than RA alone.

How much of these two supplements would one need in order to produce this effect? For lycopene the answer is 30 mg/day: the dosage used successfully in clinical studies. For rosmarinic acid the answer is less clear, since no clinical studies have been done on RA itself. One approach would be to determine the amount of RA that would be present in dried rosemary leaves when consumed at the highest level recommended for any medical reason. That turns out to give a RA dose of about 240 mg/day. Doses higher than that can be considered terra incognita — not necessarily unsafe, but requiring caution. One would begin at lower doses and work upward, being on the look-out for side effects.

Enlarging the cocktail

Numerous herbs and nutritional supplements have some degree of action against high cholesterol levels, LDL levels, or cardiovascular disease in general. How far should one go in adding ingredients to one’s personal cocktail? That depends on how anxious one is about one’s medical condition, how much trust one wants to put into combinations of substances that have not all been studied together, and on how much money one wants to spend.

For those who would like to add a second combination of two supplements which have been studied together and which show promise in preventing atherosclerosis, a good case could be made for the combination of grape seed extract plus chromium. A clinical study published in 2000 showed that this combination reduced LDL levels by an average of 20%. The dosage used was: 100 mg Grape Seed Extract + 200 mcg Chromium Polynicotinate, twice per day. (See this press release.) Note: 200 mcg chromium polynicotinate provides the same amount of chromium as 125 mcg chromium picolinate (the most readily available chromium supplement).

To summarize

A reasonable combination of supplements aimed at reducing or preventing the buildup of arterial plaques (i.e., hardening of the arteries) would consist of:
30 mg/day Lycopene
240 mg/day Rosmarinic Acid
100 mg/day Grape Seed Extract
125 mg/day chromium picolinate.

The cost of the 4-component combination would be about $2.65/day. The cost of the 2-component combination, RA+Lycopene, would be only slightly less, since these two ingredients are far more expensive than the other two. The only source of Rosmarinic Acid the author could find on the Internet was LifeLink’s product, which happens to have Grape Seed Extract included in the formulation. The chromium picolinate can be added for a mere 5 cents per day.

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