New York /PSA Rising/ September 30, 2004 — Researchers from the world's largest chemical company, BASF Germany, hired Dutch doctors recently to test BASF's brand of synethetic lycopene and vitamin E on prostate tumors implanted in mice.

They shared their findings in Geneva last week at the 16th annual meeting on "Molecular targets and Cancer Therapeutics," sponsored by European and US cancer research organizations EORTC, NCI and AACR.

What attracts BASF, bigger than Dow and DuPont, to an ingredient found in home-cooked tomato paste? Why did they call in Dutch urologists to demonstrate that lycopene mixed with an oil (in this case Vitamin E) is better absorbed in mice prostates than lycopene alone — a fact known for almost a decade.

According to Yahoo, BASF has more than 100 major manufacturing facilities worldwide in five business segments: plastics (including polyolefins and polystyrene), performance products (value-added chemicals, coatings, and dyes), basic chemicals (plasticizers, catalysts, solvents), oil and gas exploration and production (through subsidiary Wintershall AG), and agricultural products and nutrition (additives, herbicides, and fertilizers).

BASF plans to sell their brand of synthetic lycopene, LycoVit®, as an additive for virtually every kind of manufactured food.

Like other supplement manufacturers — including DSM Nutritional Products of Switzerland; Argus International Inc , PA; TNO Nutrition and Food Research, Netherlands and The Burdock Group, FL. — BASF has has been dosing rats, mice and humans with lycopene product and publishing the results. So far BASF claims that:

• rats fed LycoVit® for 13 weeks show no ill-effects (except for red staining of gut and feces)
• Men and women dosed either with LycoVit® or with a natural tomato-lycopene product ( Lyc-O-Mato from LycoRed Natural Products, Israel) absorb the lycopene into the bloodstream equally
• and now, in the study presented by a Dutch urologist at the conference in Geneva — lycopene lowers PSA in mice implanted with prostate cancer, slows tumor growth, and does so especially effectively when mixed with vitamin E.

This made health-section headlines. Yet we already know that men with prostate cancer who agree to take lycopene pills or add tomato sauce to their diet for several weeks before undergoing surgery show measurable benefit. So is it really necessary to keep on implanting tumors in mice, taking their PSA tests and subjecting their tiny prostates to MRIs?

Well, it is if the aim is to put brand-name synthetic lycopene in just about anything a junk food addict might buy. BASF has invested in synthetic lycopene for a decade. Applying to the U.S. Food and Drug Administration (FDA) for a Generally Recognized As Safe (GRAS) label for their synthetic lycopene, they said they plan to use their product as a "food ingredient in breakfast cereals (ready-to-eat and cooked), drinks (juice drinks, energy drinks, and dairy fruit drinks), instant soup, low fat dressings, meal replacements, meatless meat products, nutrient bars, salty snacks, crackers and yogurt at levels ranging from 0.5 percent to 7.0 percent. "

Instead of reaching for a tomato, reach for those cereal and salty snacks — and pile on more calories. The industry doesn't see any downside to this.

But last year came reports of a 14 month study in Illinois, which found that powder from whole tomatoes is more effective than lycopene, and calorie restriction more effective than either (see Lycopene's Anti-cancer Effect Linked To Other Tomato Components).

John Erdman at the University of Illinois, lead author on that earlier study, said, "It has been unclear whether lycopene itself is protective.... lycopene is one factor involved in reducing the risk of prostate cancer. This also suggests that taking lycopene as a dietary supplement is not as effective as eating whole tomatoes. We believe people should consume whole tomato products — in pastas, in salads, in tomato juice and even on pizza."

BASF officials steer clear of this type of evidence. "Scientific evidence is beginning to indicate that lycopene may reduce the risk of many types of cancers and cardiovascular disease," Mike Doyle, Director, Human Nutrition, BASF Corporation, said last year. "We will continue to support our customers in incorporating this potent nutritional antioxidant into their products that will benefit consumers."

Natural sources of lycopene include many vegetables, especially tomatoes and red peppers, and fruits such as watermelon, pink grapefruit and apricots. But according to Dr. Herbert Woolf, Technical Manager, Nutraceuticals, BASF, "people would have to eat massive quantities to provide the concentration recommended by researchers."

"For example," Woolf said, "vegetarians, who have a low incidence of prostate cancer, consume about 14 milligrams of lycopene daily. In contrast, the average American diet provides about 7 milligrams of lycopene daily. For many Americans not consuming a balanced diet, the next best way to get the benefits of lycopene is to consume a lycopene supplement or processed foods fortified with lycopene," he said. I

This implies that quantity is key, Yet the latest BASF-Dutch test on mice shows, in fact, the opposite.

"We found that low dose lycopene suppressed the growth of the human prostate tumors by over half (at day 42 of the study)," Dutch research scientist Dr. Jacqueline Limpens, who is a urologist at the Erasmus Medical Center in Rotterdam, said when she presented results at the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Geneva.

Limpens' team tested one low and one high dose of synthetic lycopene alone, one low and one high dose of synthetic vitamin E alone and a combination of low dose synthetic lycopene and vitamin E or a placebo. The researchers injected human tumour cells into the prostate of mice to see what effect the lycopene and vitamin supplements would have on the tumour growth and PSA (prostate specific antigen) and to compare any effects against the placebo.

Lycopene alone extended the tumor doubling time, "while all other single treatments had no significant effect. "

Further, Limpens says, "the combination of low-dose lycopene and vitamin E produced the greatest tumor inhibition — 73% (at day 42)." The effect on doubling time was matched by tumor responses.

"What was particularly marked was that it was the low dose of both lycopene and vitamin E that was the most effective, demonstrating that 'more does not necessarily equal better'. Many pharmacological agents and natural compounds follow a bell-shaped dose response curve, which means that very low or high doses may not work and that there is an optimal dose between the two extremes."

So it is problably false to suggest (as BASF's manager Herbert Woolf does) that people would have to eat unmanageable amounts of fruits and vegetables to protect themselves without synthetic lycopene obtained from manufactured snack foods.

The big picture remains complex. Numerous tests have shown that lycopene shrinks prostate cancer tumors in mice. The Illinois test claims that (for prostate cancer in rats) whole tomato is more effective. Several studies of what large groups or populations of people eat have found that intake of foods containing lycopene is associated with reduced prostate cancer risk, but some studies have found no connection.

A negative example, from Milan this year, found no meaningful association and no appreciable protective effect for lycopene compared with a "weak" effect of some other carotene nutrients (Bosseti C, Int J Cancer. 2004 Nov 20;112(4):689). By contrast, an Australian study of men in China has found that "prostate cancer risk declined with increasing consumption of lycopene, alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein and zeaxanthin. Tomatoes, pumpkin, spinach, watermelon and citrus intake were also inversely related to the risk of prostate cancer" (Asia Pac J Clin Nutr. 2004;13(Suppl):S117).

In Holland, a study of 58,279 men ages 55-69 found that "For intake of retinol, vitamins C and E and other carotenoids (alpha-carotene, beta-carotene, lycopene, and lutein/zeaxanthin) no effect on overall prostate cancer risk was found" (Cancer Causes Control. 2002 Aug;13(6):573-82).

At least one clinical study of the effect of lycopene on men with existing prostate cancer has been done in a way from which a firm conclusion can be drawn (although it would be desirable to have this study repeated).

To give the closing word to Dr. Limpens -- she says it is still too early to say whether lycopene and vitamin E could ever be used to prevent prostate cancer in healthy individuals.

"However, our data fit in with the general picture that lycopene and vitamin E may have chemopreventative effects on prostate cancer. Therefore we would certainly recommend that all men regularly eat lycopene and vitamin E-rich foods: for example, all kinds of processed tomato products, papayas, pink grapefruit and watermelon, wheat germs, whole grains, mangoes, leafy green vegetables, nuts and olive oils. Of course, this needs to be part of an all-round healthy lifestyle and diet with plenty of vegetables and other healthy foods. Regular consumption of supplements and fortified foods may help to obtain adequate amounts of lycopene and vitamin E, which may otherwise be difficult to obtain while maintaining a balanced diet."

Abstracts of the 14th EORTC-NCI-AACR Symposium on "Molecular Targets and Cancer Therapeutics" are searchable online at http://ex2.excerptamedica.com/ciw-04ena/index.cfm

The story above refers to Abstract no: 581
Lycopene, alone or combined with vitamin E, reduces orthotopic growth and plasma PSA release of PC346C prostate tumors Limpens J et al.

Selected earlier studies

Effects of lycopene supplementation in patients with localized prostate cancer. Kucuk O, et al. Division of Hematology and Oncology, 3990 John R, Barbara Ann Karmanos Cancer Institute, Wayne State University, 5 Hudson, Detroit, MI. Exp Biol Med (Maywood). 2002 Nov;227(10):881-5.

Plasma levels of six carotenoids in nine European countries: report from the European Prospective Investigation into Cancer and Nutrition (EPIC). Public Health Nutr. 2004 Sep;7(6):713-722.

Plasma and dietary carotenoids, and the risk of prostate cancer: a nested case-control study. Cancer Epidemiol Biomarkers Prev. 2004 Feb;13(2):260-9.
Wu K, Erdman JW Jr, Schwartz SJ, Platz EA, Leitzmann M, Clinton SK, DeGroff V, Willett WC, Giovannucci E.
Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts,, USA.

"We found a statistically significant inverse association between higher plasma lycopene concentrations and lower risk of prostate cancer, which was restricted to older participants and those without a family history of prostate cancer. This observation suggests that tomato products may exhibit more potent protection against sporadic prostate cancer rather than those with a stronger familial or hereditary component. In addition, our findings also suggest that among younger men, diets rich in beta-carotene may also play a protective role in prostate carcinogenesis."

Dietary sources of vitamin C, vitamin E and specific carotenoids in Spain. Br J Nutr. 2004 Jun;91(6):1005-11.

Last updated Oct 6, 2004.