More Twists And Turns In The Beta-Carotene Story

The researchers who told us beta-carotene caused lung cancer are back. As explained in a previous issue they've refined their data, weighed the role of alcohol ... and, in my opinion, still fudged a few of the facts.

Lead investigator Gilbert S. Omenn, M.D., of the Fred Hutchinson Cancer Center, Seattle, took another look at the data he and his colleagues collected in the Beta-Carotene and Retinol Efficacy Trial (CARET), which they hastily ended in Dec. 1995. As you may remember, they had called a press conference last year to warn of the dangers of beta-carotene.

In the reanalysis, Omenn found that current, long-term smokers and workers exposed to asbestos--people at a very high risk of lung cancer--were 36 percent more likely to develop the disease if they took high doses of synthetic beta-carotene (30 mg/day) and vitamin A (25,000 IU/day). That's a slightly higher risk than the 28 percent increase Omenn originally reported. In addition, everyone taking synthetic beta-carotene and vitamin A in the CARET study had at least a 10 percent increase in lung cancer risk.

But there's more to the story.

Alcohol As The Significant Factor Smokers are often heavy drinkers, and the CARET subjects who consumed three or more alcoholic drinks daily (along with taking the synthetic beta-carotene and vitamin A) doubled their risk of cancer.¹ The reason wasn't exactly clear, but it is known that the combination of vitamin A and alcohol disrupts cell function and causes liver damage.² Such deleterious changes could be a prelude to cancer.

A fresh look at the Alpha-Tocopherol Beta-Carotene (ATBC) trial, generally known as the "Finnish study," shows similar findings. This study--which in 1994 first reported that beta-carotene supplements slightly increased the risk of cancer among current, long-term smokers--found that 20 mg of synthetic beta-carotene daily for five to eight years increased lung cancer risk by 16 percent, compared with the 18 percent originally reported.³

The 16 (or 18) percent increases are considered of only marginal statistical significance. They translate to less than one extra case of lung cancer in every thousand people. But, as in the CARET study, Finnish researchers found that adding alcohol (just under one drink a day) increased the risk of lung cancer to 35 percent.

However--and this is a major point--synthetic beta-carotene supplements created no appreciable risk of lung cancer when people smoked less than 20 cigarettes daily and drank little or no alcohol.

Lesson number one:
If you smoke less than a pack a day and drink moderately, beta-carotene shouldn't be a problem. (Smoking on its own, even less than a pack daily, is still an independent risk factor for lung cancer.)(empahsis added)

Natural Vs. Synthetic Beta-Carotene There's more. Since both the CARET and ATBC studies used synthetic beta-carotene, the supplements contained only the all-trans isomer. In contrast, natural beta-carotene supplements from algae (Dunaliella spp.) are roughly 50:50 all-trans and 9-cis isomers. ("Isomers" are different molecular arrangements of the same compound.)

What does all this mean? The body converts as much as 70 percent of the all-trans isomer to vitamin A, which functions primarily as a cell regulator and hormone, not as an antioxidant. In contrast, the 9-cis isomer of beta-carotene appears to be a powerful antioxidant, rapidly absorbed by tissues, and the more protective isomer in natural beta-carotene.
Omenn gave his subjects a combination of 30 mg of synthetic beta-carotene and 25,000 IU of vitamin A daily for an average of four years. Bearing in mind that the body converts most of the all-trans isomer to vitamin A, that's the equivalent of 60,000 IU of vitamin A, an enormous amount that is rarely recommended for any condition. And by giving synthetic beta-carotene, Omenn withheld what may be the more potent antioxidant, namely the 9-cis isomer.

Furthermore, when you consider that the combination of vitamin A and alcohol may be dangerous in nonsmokers, it was probably a time bomb in heavy smokers. All this vitamin A may have potentiated the risk of lung cancer under the oxidative stresses of smoking and alcohol, which may explain why people in the CARET study were at a high risk of cancer, particularly when compared with smokers in the Finnish study.

Lesson number two:
Take natural, not synthetic beta-carotene.

Slippery With The Beta-Carotene Facts And there's still more.
Having been criticized about the use of synthetic beta-carotene in the New England Journal of Medicine, Omenn decided to go on the offensive. He dismissed the differences between natural and synthetic beta-carotene, noting that foods contain mostly the all-trans isomer. He also stated that natural beta-carotene supplements from algae contain both the all-trans and 9-cis isomers, but that the isomers in human circulation resemble those from synthetic beta-carotene.

That's all correct if you ignore, as Omenn did, recent research conducted by Elizabeth Johnson, Ph.D., of Tufts University in Medford, Mass. Johnson showed that while the 9-cis isomer doesn't always show up in the blood, it does show up in tissues, which is more important. (Blood is the means of transport; tissues are where it's used.) Johnson reported that in lactating women given natural beta-carotene, the 9-cis isomer increases in breast milk but not in blood.⁴ This reservoir of 9-cis also hints at an important biological role for the natural isomer.

In fact, in a recent article in Nutrition Review, Luigi M. De Luca, Ph.D., and Sharon A. Ross, Ph.D., of the National Cancer Institute, hinted that Omenn and the Finnish researchers put the cart in front of the horse. Apparently, no previous studies in peer-reviewed journals ever showed that beta-carotene could prevent lung cancer.⁵ That means Omenn and the Finns initiated their studies without much evidence or prior claims that beta-carotene is useful in combating lung cancer.

Now, after having presided over a disastrous study that may have been doomed to fail from the start, Omenn seems to be digging in his heels. He's arguing that beta-carotene is a carcinogen and has asked FDA to prohibit companies from calling it an antioxidant.⁶

But in his anti-beta-carotene crusade, Omenn downplays a salient point in his own research: former smokers taking beta-carotene--yes, even the synthetic forms-- and vitamin A had a 20 percent reduction in lung cancer risk.

Lesson number three:
Stop smoking, go easy on the alcohol, and take natural beta-carotene.

Other Beta-Carotene Notes Aside from its antioxidant properties, beta-carotene may protect against cancer by stimulating activity of natural-killer (NK) cells. These cells, produced by the immune system, circulate in the body and kill cancer cells and virus-infected cells.

Simin N. Meydani, D.V.M., Ph.D., of the U.S.D.A. Human Nutrition Research Center, Tufts University, Boston, recently investigated what happened when elderly men took 50 mg--83,000 IU--of synthetic beta-carotene every other day. Beta-carotene increased activity of NK cells in the men. Elderly men not taking beta-carotene had much lower levels of NK cells.⁷

If someone has low stomach acid, though, they'll have trouble absorbing beta-carotene from the diet or supplements. Thirty percent of people over 60 years of age suffer from atrophic gastritis, an inflammatory condition in which the stomach produces little or no stomach acid. The lack of acid is known to interfere with nutrient absorption, and it aggravates the malnutrition common among elderly persons.

In a recent experiment, Guangwen Tang, Ph.D., also of Tufts University, found that a lack of stomach acid prevented the absorption of beta-carotene. Tang gave 12 healthy subjects a 120 mg beta-carotene supplement under either normal conditions or after giving them a drug that temporarily stops stomach acid secretion (to mimic atrophic gastritis).

Beta-carotene levels in the blood rose impressively after Tang's subjects took beta-carotene. But only about half of the beta-carotene was absorbed after the subjects took the stomach acid-blocking drug.⁸

Think about the implications. A lack of stomach acid also would interfere with other fat-soluble nutrients such as vitamins D, E and K. And millions of people are reducing their stomach acid every day when they pop over-the-counter antacids. That's enough to give a person heartburn.

Jack Challem is based in Aloha, Oregon, and has been writing for health magazines for 20 years. He also publishes his own newsletter, The Nutrition Reporter, which summarizes recent medical journal articles on vitamins.

REFERENCES
1. Omenn G.S., Goodman G.E., Thornquist M.D., Balmes J., Cullen M.R., Glass A., et al. "Risk factors for lung cancer and for intervention effects in CARET, the beta-carotene and retinol efficacy trial." Journal of the National Cancer Institute, 88: 1550-1559, 1996.

2. Bland J. The beta-carotene controversy in perspective. Journal of Applied Nutrition, 48: 42-45, 1996.

3. Albanes D., Heinonen O.P., Taylor P.R., Virtamo J., Edwards B.K., Rautalahti M., et al. "Alpha-tocopherol and beta-carotene supplements and lung cancer incidence in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention study: effects of baseline characteristics and study compliance." Journal of the National Cancer Institute, 88: 1560-1570, 1996.

4. Johnson E., Krinsky N.I., and Russell R.M. "Bioavailability of all-trans and 9-cis isomers of beta-carotene in humans." Agricultural Research Service Report No. 37595, United States Department of Agriculture, 1996.

5. De Luca L.M., and Ross S.H. "Beta-carotene increases lung cancer incidence in cigarette smokers." Nutrition Reviews, 54: 178-180, 1995.

6. Hathcock J., Nutrition and Health Perspectives, Council for Responsible Nutrition News, July 1996.

7. Santos M.S., Meydani S.N., Leka L., et al. "Natural killer cell activity in elderly men is enhanced by beta-carotene supplementation," American Journal of Clinical Nutrition, 64: 772-777, Nov 1996.

8. Tang G., Serfaty-Lacrosniere C., Camilo M.E., et al. "Gastric acidity influences the blood response to a beta-carotene dose in humans," Journal of Clinical Nutrition, 64: 622-6, 1996

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