A Brief History of Carotenoids
In 1913, McCollum and Davis showed that ft
soluble factor in butter, later characterized s
vitamin A, stimulated the growth of rats fed
an incomplete diet. The belief that some
coloured plant extracts with similar effects,
later known as carotenoids, might be
biologically converted to vitamin A was
confirmed by Moore in 1930.
Originally carotenoids were considered .
More recently, there has been significant
interest in evaluation of carotenoids for re
that are unrelated to their conversion to
vitamin A.
Beta-carotene was the primary research
of earlier studies evaluating the role of
carotenoids in disease prevention probably
because it was the best known antioxidant
of the carotenoids and due to its potential
vitamin A activity. Other carotenoids in
addition to beta-carotene have functions which
are important in diseases prevention and
with the availability of data on individual
carotenoids, a number of studies have been
evaluating the protective effects of various
carotenoids, rather than beta-carotene alone.
Carotenoids are effective quenchers of
singlet oxygen, with lycopene
exhibiting the highest singlet oxygen
quenching activity. Carotenoids
function as chain-breaking
antioxidants, protecting cell and other
body components from free radical
attack. Oxidative damage resulting
from free radical attack has been linked
to the onset of premature aging, cancer,
atherosclerosis, cataracts, age-related
macular degeneration and an array of
degenerative diseases.
Carotenoids enhance the immune
response. In animals, carotenoids
stimulate a number of immune
function. Studies in humans have also
shown enhancement of immune
parameters by carotenoids. Carotenoids
also protect the skin from redness and
damage following exposure to UV
radiation.
Lutein and zeaxanthin are the only
carotenoids present in the macular
region of the retina and are linked to
normal function of the macula, which
is responsible for sharp and detailed
vision.
These carotenoids are believed to serve as
filters for harmful blue light in the macula and
as scavengers of singlet oxygen in retinal
tissues.
Certain carotenoids (including lycopene and
beta- carotene) have the ability to increase
communication of growth regulatory signals
between cells. Increased communication
between growth-inhibited normal cells and
cells which have been damaged by chemical
carcinogens prevents these damaged cells
from becoming malignant.
Carotenoids have been shown to inhibit
proliferation of various types of cancer cells. In
different cell lines, different carotenoids are
more effective in tumor suppression. Specific
carotenoids have also been found to be
protective against specific cancer types in
animal and human, epidemiologic studies. For
example, decreased risk of various cancers is
associated with certain carotenoids: lycopene
with prostate cancer, lutein, zeaxanthin,
alpha-carotene and beta-carotene with oral
cancers, and cryptoxanthin with cervical
cancer. Thus, a number of carotenoids can
work together to prevent generation of free
radicals and also quench free radical
reactions and limit free radical/oxidative
damage.
What is the role of antioxidants/
Micronutrients in precancerous
Conditions ?
Krishnaswamy et al undertook a study in
Srikakulam district of Andhra Pradesh,
where reverse smoking of tobacco where
the burning end inside the oral cavity is in
vogue. In more than 30 per cent of such
reverse smokers, precancerous oral
lesions are encountered which eventually
lead to the development of oral cancers in a
good proportion. The study was designed
to assess the impact of a cocktail of
micronutrients, viz. Vitamin A, riboflavin,
zinc and selenium in oral precancerous
lesions. After one year of such
supplementation, it became evident that
subjects with precancerous lesions
receiving nutrient supplement exhibited a
much higher regression of lesions (57 %)
than the control unsupplemented group (8
%). Biomarkers, namely micronuclei, and
DNA adducts, which were monitored both
in the supplemented and unsupplemented
group, showed a significant fall in the
former (60-98%) and no fall in the later.
What is the relationship between
Carotenoid levels and cancer ?
Epidemiologic and in vitro studies have
Indicated inverse correlation between
Intake and/or blood concentrations of
Different carotenoids, retinol, and alpha-
tocopherol with different chronic disorders
including cancer. Olmedilla et al
determined carotenoid and fat-soluble
vitamins in men with recently diagnosed
cancer of larynx who had undergone total
or partial laryngectomy and compared
them with those of an age- and sex-
matched control group. The levels of all
Carotenoids, retinol and alpha-tocopherol
were significantly lower in men with
laryngeal cancer than in the control
group.
How does one conclude that
Carotenoids will help reduce the
Risk of aerodigestive tract cancer ?
Numerous dietary studies have found thal
vegetables and fruits protect againsi
upper aerodigestive tract cancer. A case-
control study using prediagnostic serum
was conducted among 6832 Americar
men of Japanese ancestry. During c
surveillance of 20 years, the stud)
identified 28 esophageal, 23 laryngeal
and 16 oral-pharyngeal cancer cases ir
this cohort. The 69 cases were matched to
138 controls. Serum levels of lutein
zeaxanthin, beta-cryptoxanthin, lycopene
alpha-carotene, beta-carotene, and others
substances were measured. With-
adjustment for cigarette smoking and
alcohol intake, it was found that alpha-carotene,
beta-carotene, beta-cryptoxanthin,
total Carotenoids and gamma-tocopherol levels were
significantly lower in the 69 upper
aerodigestive tract cancer patients than in
their controls. When the cases were
separated into esophageal, laryngeal, and
oral-pharyngeal cancer, both alpha-
carotene and beta-carotene were
consistently and strongly associated with
reduced risk at each site. The findings
suggest that low levels of alpha-carotene
and other Carotenoids, as well as beta-
carotene, may be involved in the etiology of
aerodigestive tract cancer.
Do carotenoids help reduce the risk
Of Ca-breast ?
To evaluate relationships of serum
Carotenoids (and other substances) with
breast cancer prospectively, a case-control
study was conducted of cohorts from the
Breast Cancer Serum Bank in Columbia,
Missouri (United States). Women free of
cancer donated blood to this bank in 1977-
87. During the follow-up (9.5 years,
median = 2.7 years), 105 cases of
histologically confirmed breast cancer
were diagnosed. For each case, two
women alive and free of cancer at the age
of the case's diagnosis and matched on age
and date of blood collection were selected
as controls. Serum lycopene was associated
inversely with risk, and among
women who donated blood at least two
years before diagnosis, a significant
gradient of decreasing breast cancer risk
with increasing lycopene concentration
was evident. A marginally significant
gradient of decreasing risk with increasing
serum lutein / zeaxanthin also was
apparent among these women. Results of
this study suggest that the Carotenoids
beta-cryptoxanthin, lycopene, and
lutein/zeaxanthin may protect against
breast cancer.
Why is it believed that Carotenoids
May reduce the risk of cervical
Cancer in women ?
Paired blood (collected after an overnight
fast) and cervical tissue (cancerous,
precancerous, and noncancerous)
samples were obtained from 87 patients
(age, 21-86 years) who had a hysterectomy
or biopsy due to cervical cancer, precancer
(cervical intraepithelial neoplasia I, II, and
III), or noncancerous diseases. The
samples were analyzed for lutein,
zeaxanthin, beta-cryptoxanthin,
lycopene, alpha-carotene, beta-carotene,
cis-beta-carotene, and others. The results
indicated that among the three patient
groups, the mean plasma concentrations
of all micronutrients except gamma-
tocopherol were lowest in the cancer
patients; the mean tissue concentrations of
the two tocopherols and certain
Carotenoids were highest in the cancerous
tissue; among the 10 micronutrien+s, only
the concentrations of beta-carotene and
cis-beta-carotene were lower in both the
plasma and tissue of cancer and precancer
patients than in those of noncancer
controls. The results suggest that not all of
the micronutrients concentrations in
plasma reflect the micronutrients
concentrations in cervical tissue; it may be
necessary to measure the tissue
micronutrients concentrations to define the
role of the micronutrients in cervical
carcinogenesis; maintaining an adequate
plasma and tissue concentration of beta-
carotene may be necessary for the
prevention of cervical cancer and
precancer.
Why is it believed that lycopene may
Play a role in reducing the risk of
Prostate cancer ?
An evaluation of the Health Professional
follow-up Study to define thi
concentrations of lycopene, other
Carotenoids, and retinol in paired benigi
and malignant prostate tissue from 25
men, ages 53 to 74, undergoing
prostatectomyfor localized prostate cancer
detected a lower porstate cancer risk
associated with greater consumption of
lycopene containing food items like
tomato . All-trans lycopene accounted for
only 121021% and cis isomers for 79 to
88% of total lycopene in benign or
malignant prostate tissues. The study
concluded that the presence of lycopene in
the prostate at concentrations that are
biologically active in laboratory studies
supports the hypothesis that lycopene may
have direct effects within the prostate and
contribute to the reduced prostate cancer
risk associated with the consumption of
tomato-based foods.
How do we know that Carotenoids
Intake may reduce the risk of
Lung cancer ?
Hankin and others looked into intake of
specific Carotenoids and lung cancer risk.
The authors reanalyzed a population-
based case-control study of diet and lung
cancer conducted in Hawaii in 1983-1985.
A previously validated quantitative diet
history assessed the usual intake of foods
rich in Carotenoids. After adjusting to
smoking and other covariates, no
association was found with lung cancer risk
for dietary lycopene or beta-cryptoxanthin
intake, whereas dose-dependent invers
associations of comparable magnitude
were found for dietary beta-carotene,
alpha-carotene, and lutein. When subjects
were cross-classified by their joint intakes of
the latter three Carotenoids, those who
had a high intake (> median) for all three
had the lowest risk for lung cancer. In a
similar two-way interaction analysis, the
previously reported inverse association of
lung cancer with vegetable consumption in
these data was found to be stronger than
that with intake of these three Carotenoids.
The analysis provides further evidence for a
protective effect of certain Carotenoids
against lung cancer and for the greater
protection afforded by consuming a variety
of vegetables compared to only foods rich
in a particular carotenoid.