Thanks to Nutrition Science News for permission to reproduce this article!
By Jack Challem
Research shows that eating ample amounts of lycopene-rich tomatoes greatly reduces the risk of prostate cancer. Lycopene is the most potent carotenoid antioxidant,
followed by beta-carotene, cryptoxanthin, lutein and zeaxanthin.
in beta-carotene, long considered a leading antioxidant, has been
shaken during the past few years by negative studies that showed
it can increase the risk of lung cancer and coronary heart
disease. But a review of published research during this time
shows far more positive than negative findings.
Several important themes have emerged. One, natural beta-carotene
(from Dunaliella salina algae) is different and apparently
better than the synthetic form, which was used in the studies
with negative results. Two, related carotenoids, particularly
lutein and lycopene, look promising as antioxidants and cancer
fighters and should be among the mix of supplemental carotenoids.
Three, there is a synergism among carotenoids and other
antioxidants, such as vitamins E and C, and the sum effect may be
greater than the parts.
Debunking The Criticism
The beta-carotene controversy began in 1996 after two
studies--the Finnish Alpha-Tocopherol Beta-Carotene (ATBC) and
the Beta-Carotene and Retinol Efficacy Trial
(CARET)--unexpectedly determined that supplements of this
nutrient increased the risk of lung cancer among people who were
either smokers or exposed to asbestos, a known carcinogen. Some
researchers, such as Lester Packer, Ph.D., of the University of
California, Berkeley, questioned the validity of these studies,
in part because they were contradicted by hundreds of others.
When researchers reexamined the data for the ATBC study, they
found that beta-carotene supplements did not increase lung cancer
risk unless the subjects smoked more than a pack of cigarettes
and consumed one or more alcoholic drinks daily.  In
the CARET study, smokers and heavy drinkers had twice the lung
cancer risk if they also took high doses of beta-carotene. But
when alcohol consumption was factored out, the increase in lung
cancer associated with beta-carotene was not statistically
significant among people who smoked less than a pack a day.
Furthermore, former smokers had a decreased risk of lung cancer
if they took beta-carotene supplements. [2,3] (For more
information on these studies, please see NSN, 1(1): 4,
1996; 2(1): 7, 1997; 2(3): 100, 1997.)
Why would beta-carotene increase the risk of lung cancer under
any circumstances? It is possible that high doses of
beta-carotene or vitamin A (to which some beta-carotene is
converted), when combined with tobacco smoke, are susceptible to
free radical oxidation. Without other antioxidants to quench
beta-carotene or vitamin A free radicals, these free radicals
might cause cell damage and lead to cancerous
Indeed, another team of researchers suggested the unexpected
increase in lung cancer among smokers taking beta-carotene was
related to just that--the lack of other supplemental
antioxidants. T. George Truscott, Ph.D., of Keele University,
England, reported that antioxidants work together to neutralize
free radicals, such as those associated with tobacco smoke.
In experiments, Truscott determined that vitamin E was the first
antioxidant to quench free radicals from tobacco smoke. The
chemical reaction turned vitamin E into a weak free radical, but
beta-carotene recycled this free radical back to vitamin E. In
the process, beta-carotene became a free radical, but it could be
restored with vitamin C. The bottom line: Smokers need a mix of
antioxidants, not just beta-carotene. 
In another analysis of the CARET data, John R. Balmes, M.D., of
the University of California, San Francisco, looked at the
relationship between lung capacity and beta-carotene intake,
regardless of whether the nutrient was a synthetic supplement or
was obtained from foods. Balmes reported that higher intake of
beta-carotene was associated with better lung capacity--in
essence, stronger lungs--even if the subjects smoked or were
exposed to asbestos.  Although increased lung capacity
appeared inconsistent with lung cancer, Balmes could not bring
himself to recommend beta-carotene supplements to increase lung
capacity, because he was afraid the supplements could increase
the risk of cancer.
Natural Vs. Synthetic
It also turned out that the negative studies used synthetic
beta-carotene, which is different in chemical structure from
natural beta-carotene. Does that mean natural beta-carotene is
better? Research has not yet directly compared natural to
synthetic beta-carotene on lung cancer risk. However, Ami
Ben-Amotz, Ph.D., a carotenoid researcher at the National
Institute of Oceanography, Israel, has stressed the differences
between natural beta-carotene derived from dunaliella algae and
the synthetic version.
Natural beta-carotene consists of two isomers; that is, two
different structures of the same molecule. One is the all-trans
and the other is the 9-cis; each contains the same atoms but in
different arrangements. However, synthetic beta-carotene consists
of only the all-trans form.  In experiments, Ben-Amotz
found that the natural 9-cis is a potent antioxidant that rapidly
quenches free radicals. If that's the case, it would give natural
beta-carotene a powerful advantage over the synthetic.
Ben-Amotz believes that the all-trans form found in synthetic
beta-carotene is not an antioxidant at all and is in fact a
"pro-oxidant," which is why it damages cells and leads to cancer.
But there may be different explanations. Part of the
beta-carotene we consume is converted to vitamin A. Vitamin A has
hormonelike effects that control cell growth and differentiation.
The all-trans is converted to vitamin A much more efficiently
than the 9-cis form, so it is quite conceivable that all-trans'
effects may be related more to its vitamin A activity than to
whether it is a pro-oxidant.
Recent Beta-Carotene Research
Despite the controversy surrounding beta-carotene, research on
this nutrient looks exceptionally promising. Highlights of the
more recent findings include:
Immune enhancement: In an article in the Journal of
Laboratory and Clinical Medicine, David A. Hughes, Ph.D., and
colleagues explained that monocytes, a type of white blood cell,
contain surface proteins that distinguish cancer cells from
normal ones. When these proteins, called MHC II, identify cancer
cells, they signal the immune system to attack them.
Hughes, a researcher at the Institute of Food Research, Norwich,
England, found that monocytes don't identify cancer cells if they
don't have enough MHC II proteins. After giving 25 apparently
healthy men beta-carotene supplements, Hughes found that the
number of MHC II proteins on their monocytes increased. The
beta-carotene also increased the subjects' production of tumor
necrosis factor alpha (TNF-a), which helps kill cancerous and
virus-infected cells. 
Mental functioning: Several other recent studies
demonstrate beta-carotene's broad roles in maintaining health. In
an epidemiological study of 5,182 middle-age and elderly people,
Dutch researchers saw a strong correlation between beta-carotene
intake and mental functioning. L.J. Launer, Ph.D., of Erasmus
University, Netherlands, reported that people who ate less than
0.9 mg of dietary beta-carotene daily were more than twice as
likely to suffer from poor memory, difficulty in solving problems
and disorientation, compared with people who eat more than 2.1
mg/day of the nutrient. 
Arthritis: Beta-carotene may also slow the progression
of rheumatoid arthritis. George W. Comstock, M.D., of the Johns
Hopkins University School of Hygiene and Public Health,
Baltimore, analyzed levels of beta-carotene, vitamin E and
vitamin A from blood samples obtained in 1974. He then studied
how levels of these nutrients correlated with illness the blood
donors developed in subsequent years.
Comstock found low blood levels of these antioxidant nutrients
were associated with the subsequent development of rheumatoid
arthritis and lupus erythematosus. However, the only
statistically significant relationship was between low
beta-carotene and the development of rheumatoid arthritis. People
who developed this type of arthritis had blood levels of
beta-carotene averaging 29 percent less than those of healthy
Prostate cancer: Beta-carotene supplements may also
reduce the risk of prostate cancer, according to a study led by
Harvard University researcher Meir Stampfer, M.D. In analyzing
the risk of prostate cancer among more than 3,000 physicians,
Stampfer noted several important trends. One, men who did not eat
enough fruits and vegetables and did not take beta-carotene
supplements were 36 percent more likely to develop prostate
cancer than their counterparts who did. Two, men with diets high
in beta-carotene had a 36 percent lower risk of developing
prostate cancer. Three, men who ate few fruits and vegetables but
took beta-carotene supplements had a similar low risk of prostate
cancer--the supplements appeared to compensate for the lack of
produce in the diet. Finally, men who ate a lot of fruits and
vegetables, and took beta-carotene supplements, had a slight
increase in risk, suggesting that there is an optimal range for
beta-carotene consumption, whether from diet or
Skin protection: In what may be one of the more unusual
uses of beta-carotene, a team of German and Israeli researchers
discovered that beta-carotene supplements--taken
internally--protect against sunburn. In a controlled experiment,
researchers asked 20 young women to use either a combination of
topical sunscreens and beta-carotene supplements (30 mg daily) or
a sunscreen alone for 10 weeks. By measuring skin redness and
inflammation, the researchers found that supplementation with
beta-carotene before sun exposure, combined with sunscreens, was
more protective than sunscreens alone.  (For more
information on sun protection, see related article, "A Holistic
Approach To Skin Protection," on p. 204.)
Lutein And Lycopene
Many studies have demonstrated a link between low intake of
lutein and zeaxanthin--the body converts some lutein to
zeaxanthin--and macular degeneration, the leading cause of
blindness among the elderly. These two carotenoids filter out
harmful blue light and quench free radicals that can damage the
macula, the part of the eye responsible for sharp and detailed
By all measures, macular degeneration is not reversible. However,
lutein supplements might slow its progression and provide a
protective effect. In studies at Florida International
University, Miami, John T. Landrum, Ph.D., gave healthy human
subjects 30 mg of lutein daily for several months. The macular
pigment increased by as much as 39 percent, decreasing by 30 to
40 percent the amount of blue light reaching receptors in the
Lutein may also play a role in cancer prevention, though research
is still at an early stage. In a small study conducted at
Washington State University, Pullman, researchers injected
laboratory mice with breast cancer cells, leading to solid
cancers in 60 to 70 percent of the mice. Some of the mice were
also given diets that included various percentages of lutein.
Even very small quantities of lutein--about two-thousandths of a
percent (0.002) of the diet--decreased the incidence, appearance
and growth of tumors.  Other research, as yet
unpublished, indicates that human breast and cervix cells retain
higher levels of lutein than do other tissues. This suggests that
lutein plays a normal biological role in these cells.
Two years ago, Edward Giovannucci, M.D., and colleagues at the
Harvard University School of Public Health in Boston, reported
that high intake of tomatoes, rich in the carotenoid lycopene,
reduced the risk of prostate cancer by 45 percent. 
Two subsequent analyses of other groups of men found the same
benefit. It turns out that lycopene is a major antioxidant and
may protect against other forms of cancer as well.
Catherine A. Rice-Evans, Ph.D., of Guy's Hospital, London, tested
carotenoids for their antioxidant properties and found that
lycopene was the most potent, followed by beta-carotene and
cryptoxanthin, and then by lutein and zeaxanthin. 
Several Japanese cell-culture and animal studies also have
revealed that lycopene can inhibit the growth of cancers. It
works at least in part by blocking the activity of transforming
growth factor alpha (TGF-a), which is known to promote cancer,
according to a report by researchers at Japan's Meiji
University.  The carotenoid also increases the number
of immune T4 cells and normalizes the T4:T8 ratio, a sign of
improved immune function. 
In other cell-culture experiments, Joseph Levy, Ph.D., and his
colleagues at the Ben-Gurion University, Israel, found that
lycopene inhibited the growth of endometrial, breast and lung
cancers. The lycopene inhibited the cancer growth in just 24
hours, and it was substantially more potent than alpha-carotene
or beta-carotene. 
In an interview, Michael Aviram, D.Sc., a carotenoid researcher
currently working at the University of Michigan, Ann Arbor, sized
up the carotenoids this way: 9-cis (natural) beta-carotene is
better than all-trans (synthetic) beta-carotene--but lycopene is
better than either of them.
Not surprisingly, a mix of natural carotenoids, similar to what
is in a diet rich in fruits and vegetables, may offer the
greatest health benefits. Carotenoids are found in all fruits and
vegetables. A well-rounded selection might include broccoli,
carrots, citrus fruits, red and yellow peppers, spinach, sweet
potatoes and tomatoes. Diversity is really the key here.
Unfortunately, most Americans eat few fruits and vegetables, and
when they do, the choices are generally very limited.
In one study, Tim R. Kramer, Ph.D., and Betty J. Burri, Ph.D., of
the USDA Agricultural Research Service in Washington, D.C., asked
nine women to eat a low-carotene diet--few fruits, vegetables and
juices--for four months. At first, five of the women took a
low-dose beta-carotene supplement for two months, while the
remaining four women were given placebos.
By measuring the activity of lymphocytes, such as T4 cells,
Kramer and Burri found that a low-carotene diet compromised
immune function, and low-dose beta-carotene supplements did not
improve lymphocyte activity. However, when they gave the women a
mixed-carotenoid supplement--containing higher amounts of
beta-carotene as well as alpha-carotene, lutein, cryptoxanthin,
zeaxanthin and lycopene--immune function returned to
There's also compelling evidence that the carotenoids work best
with other antioxidants, and not just to reduce lung cancer risk.
In a study at the University of Nebraska, Lincoln, Judy A.
Driskell, Ph.D., fed rabbits a high-cholesterol diet. She gave
some of the rabbits beta-carotene, vitamin E, or both. The
beta-carotene lowered cholesterol levels, while vitamin E
prevented its oxidation--both important steps in lowering
cholesterol.  Taken together, the combination both
lowered cholesterol and prevented its oxidation. Why would
beta-carotene lower cholesterol? In a recent paper, Aviram
pointed out that the carotenoids and cholesterol share a common
metabolic pathway, and high intake of carotenoids blocks
cholesterol synthesis. 
While most scientific researchers have a "reductionist" view of
nutrition, looking for the single effective ingredient, a
wholesome diet consists of a multitude of beneficial nutrients
that work together and provide collective benefits. Applying the
same principle in supplementation--using multiple instead of
single nutrients--would appear to be sound. When it comes to
carotenoids, a mix of natural beta-carotene and other carotenoids
may be the best way to go. NSN
Jack Challem is based in Aloha, Ore. He has been writing about
vitamin research for more than 20 years and publishes The Nutrition
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