Carotenes
What is it?
Carotenes are a group of highly colored plant compounds, some of which can be converted into vitamin A in the intestinal wall and liver, as the body requires. They are also referred to as carotenoids. Beta carotene is the best known of the carotenes as it has high pro-vitamin A activity and is abundant in many foods. Other carotenoids include lutein, zeaxanthin, beta cryptoxanthin, lycopene and alpha carotene. Carotenoids interact with each other during intestinal absorption, metabolism, and clearance from the body.
What it does in the body
Antioxidant action
The beneficial effects of some carotenoids are partly due to their conversion to vitamin A. They also have potent activity of their own due to their ability to act as antioxidants and protect against free radical damage. This type of damage may lead to several medical problems, such as inflammatory damage and tissue injury after trauma; and chronic conditions, such as cardiovascular disease, eye disorders, autoimmune diseases and cancer. Carotenoids also affect cell growth regulation and gene expression.
Protection against cancer
High levels of dietary carotenoids have been linked to decreases in the risks of several types of cancer.
Colon cancer
In a small study of cancer patients done in 1997, Italian researchers assessed carotenoid levels in four healthy patients, seven patients with pre-cancerous lesions and seven patients with colon cancer. They found significantly lower carotenoid levels in the cancer patients.1
Breast cancer
In a study published in the Journal of the National Cancer Institute in 1996, researchers examined the links between dietary intake of carotenoids (including nonfood supplements) and premenopausal breast cancer risk. The study involved 297 premenopausal women 40 years of age or older who were diagnosed with breast cancer from November 1986 to April 1991.These were compared with 311 women without cancer. The results showed a reduction in risk associated with high intake of several nutrients including beta carotene, lutein and zeaxanthin.2
In a study published in 1998, researchers in Missouri examined blood levels of various nutrients in women who developed breast cancer after donating blood to a bank over a ten-year period. They then compared these levels to women who were free of cancer. They found lower levels of the carotenoids beta cryptoxanthin, lycopene, lutein and zeaxanthin in patients who developed breast cancer.3
In a 1997 study reported in the American Journal of Clinical Nutrition, researchers at Harvard School of Public Health compared carotenoid concentrations in the breast fat tissue from 46 cancer patients and 63 women with benign breast lumps. They found an increased risk in those with low levels of beta carotene, lycopene, lutein and zeaxanthin.4
Lung cancer
Several population studies have shown lower levels of carotenoids in lung cancer cases. In a study published in 1998, researchers at Johns Hopkins University measured nutrient levels in blood samples from 258 patients with lung cancer and compared these with those in samples from 515 people free of cancer. Blood concentrations of cryptoxanthin, beta carotene, lutein and zeaxanthin were significantly lower among the cancer patients. Small differences were noticed for alpha carotene and lycopene.5
Protection against cardiovascular disease
Population studies have shown that diets high in carotenoids can protect against cardiovascular diseases. They may do this by preventing the oxidation of LDL cholesterol and reducing free radical damage at sites of atherosclerotic plaque formation.
Researchers involved in the Massachusetts Health Care Panel Study examined the links between consumption of carotene-containing fruits and vegetables and death from cardiovascular disease among 1299 elderly people. The results of the study, which were published in the Annals of Epidemiology in 1995 showed that during the follow-up period of almost five years, there were 161 deaths from cardiovascular disease. The risk of death in the group who ate the most carotene-containing foods was almost half that of those people whose carotene consumption was low.6
In a 1996 study UK researchers compared blood levels of antioxidant vitamins in Belfast, Northern Ireland with those of people in Toulouse, France where the incidence of coronary heart disease is much lower. The results showed that levels of carotenoids such as lutein, cryptoxanthin and alpha carotene were much higher in people from Toulouse.7
Protection against eye disorders
Oxidative damage is also implicated in the development of eye disorders such as cataracts and macular degeneration.
Researchers at Harvard Medical School examined the link between cataract development and intake of various foods and antioxidant vitamins in over 50 000 women. The results of their studies showed that those with high beta carotene and vitamin A intakes were less likely to develop cataracts. Those whose diets contained spinach also seemed to have a lower risk. The researchers concluded that dietary carotenoids, although not necessarily beta carotene, can decrease the risk of cataracts severe enough to require extraction.8
Absorption and metabolism
Carotenoids need bile acids for absorption and unless they are converted to vitamin A in the wall of the small intestine, they are absorbed unchanged. Conversion appears to depend on several factors including protein, thyroid hormone action, zinc and vitamin C. Around 40 to 60 per cent of dietary beta carotene is absorbed, although this appears to be reduced in the presence of low stomach acid. Beta carotene can be stored in the lung, liver, kidneys, skin and fat.
Sources
Good sources of beta carotene include carrots, sweet potatoes, pumpkin and other orange winter squashes, cantaloupe, pink grapefruit, spinach, apricots, broccoli, and most dark green leafy vegetables. The more intense the green, yellow or orange color the more beta carotene the vegetable or fruit contains. These foods are also good sources of alpha carotene. Beta carotene is not destroyed by cooking which, in fact, may make it easier to absorb.
Good sources of lycopene include tomatoes, carrots, green peppers and apricots. Spinach, paprika, corn and fruits are high in zeaxanthin; and green plants, corn, potatoes, spinach, carrots and tomatoes are high in lutein.
Beta carotene
As an antioxidant, beta carotene has beneficial effects in protecting against oxidative damage including that caused by ultraviolet light.9 Beta carotene has been shown to stimulate and enhance many immune system processes. It increases the numbers of immune cells such as B and T lymphocytes and natural killer cells. T cells play a very important role in determining immune status and are produced by the thymus gland, which is particularly sensitive to free radical and oxidative damage. Beta carotene protect macrophages, white blood cells which engulf and destroy foreign substances. It also facilitates communication between immune cells and makes the stimulatory action of interferon on the immune system more powerful.
Protection against cancer
As with other carotenoids, research suggests that low levels of beta carotene increase the risk of certain types of cancer, including those of the lung, stomach, breast, prostate, colon, ovary and cervix. Several population studies have shown that cancer victims have lower dietary and/or blood beta carotene levels than healthy people. The evidence from these studies is strongest for lung cancer.
In a study done in Wellington, New Zealand researchers investigated the links between beta carotene and cancer. They compared levels in 389 people with cancer to those in 391 hospital patients without cancer. They also assessed the family members of the study participants to compensate for the fact that changes in beta carotene levels may have occurred after the cancer developed. Low levels of beta carotene were found in people with a number of cancers, including those of the lung, stomach, esophagus, small intestine, cervix, and uterus. Low levels were also found in the relatives of these cancer patients and the links were strongest in those with lung cancer. In this study patients with cancers of the breast, colon, prostate, and skin did not have lower levels of beta carotene and neither did their families. These results suggest that the cancer sites associated with beta carotene levels are, in general, sites for which smoking is a strong risk factor.10
Lung cancer
Researchers at Yale University School of Medicine compared diets in 413 nonsmokers suffering from lung cancer and compared these with 413 people without cancer. The results of the study, which were published in 1994, showed that high dietary intake of fruit and vegetables and beta carotene was linked to a decreased risk of lung cancer in both men and women.11
Breast cancer
In a study published in 1996, Italian researchers investigated the relationship between selected nutrients and breast cancer risk in 2569 women with the disease and 2588 women with no history of cancer. The results showed significantly less risk in women with high beta carotene intakes.12
In another recent study published in the British Journal of Cancer, West Australian researchers investigated the effect of increased intake of beta carotene on survival in breast cancer patients. Over a six-year period only one death occurred in the group with the highest consumption of beta carotene, while there were eight and 12 deaths in the intermediate and lowest groups of consumption respectively.13
Prostate cancer
Results from the Chicago Western Electric Study published in 1996, suggest that surviving prostate cancer is more likely in men with higher beta carotene intakes. The study involved 1899 middle-aged men who were followed for a total of 30 years. During that time 132 men developed prostate cancer and survival was found to be less likely in those with low beta carotene intakes.14
Cervical cancer
Research suggests that women with low beta carotene levels in their cervical tissues may be at increased risk of cervical cancer. Laboratory studies show that beta carotene can slow the growth of cervical cancer cells.15 Increasing intake of beta carotene may help to overcome this tissue-specific deficiency.16
Protection against heart disease and stroke
Several studies suggest high dietary beta carotene intake can protect against cardiovascular disease. As an antioxidant, beta carotene has been shown to inhibit oxidative damage to cholesterol and protect against atherosclerotic plaque formation.
The relationship between intake of dietary antioxidants and risk of stroke was investigated as part of the Chicago Western Electric Study. The researchers found a moderately reduced risk in those with high beta carotene intakes.17
In a 1997 study, researchers in Italy investigated the relationship between non-fatal heart attacks and dietary intake of beta carotene. The study involved 433 heart attack patients and 869 women without cardiovascular disease. The results showed that women with high beta carotene intakes had around half the risk of heart attack of those with low intakes.18
Autoimmune diseases
Free radical damage may also contribute to the development of autoimmune diseases such as arthritis. Increasing dietary levels of antioxidants may help to prevent this damage. Researchers at Johns Hopkins University examined the links between dietary intake of beta carotene and rheumatoid arthritis and systemic lupus erythematosus. The study involved people with the disorders that developed two to 15 years after donating blood for a serum bank in 1974. The results showed that disease sufferers had significantly lower blood concentrations of beta carotene than those without the disorders.19
Wound-healing
Oxidative stress is linked to inflammation and may contribute to secondary tissue damage and impaired immune function after burns and other kinds of injuries. As beta carotene has antioxidant and anti-inflammatory properties it may help to promote wound-healing.
Eyes
Free radical damage is implicated in the formation of cataracts and as an antioxidant, beta carotene may exert protective effects by reducing this damage. It may also act as a filter and protect against light-induced damage to the fiber portion of the eye lens. Beta carotene may also protect against macular degeneration, a disease of the retina to which older people are particularly susceptible.
Finnish researchers recently compared the differences between beta carotene levels in patients admitted to eye wards for senile cataract with those without eye disorders. The results showed that those with low concentrations of beta carotene were 1.7 times as likely to suffer from cataract.20
Mental function
In a study reported in 1996, Dutch researchers looking at the effect of foods rich in beta carotene on memory impairment and mental function found that these had protective effects. The researchers studied 5182 people aged 55 to 95 from 1990 to 1993. They found that those with intakes of less than 0.9 milligrams of beta carotene per day were almost twice as likely to have impaired memory, disorientation and problem solving difficulty as those with intakes of 2.1 milligrams of beta carotene.21
Researchers involved in a 1997 Swiss study found similar results. The study which was reported in the Journal of the American Geriatrics Society, involved 442 men and women, aged from 65 to 94 in 1993. Antioxidant levels were originally tested in 1971 and then again in 1993, when the participants were also given memory related tests. Higher vitamin C and beta carotene levels were associated with higher scores on free recall, recognition and vocabulary tests.22
Candidiasis
Lower levels of beta carotene have been seen in the cells of women with vaginal candidiasis (thrush). In an American study done in 1994, researchers compared beta carotene levels in vaginal cells from women with candidiasis to those in women without the infection. They found significantly lower levels in women with candidiasis. Women are more susceptible to candida infection when the immune response is suppressed and as beta carotene has been shown to boost immune response the high levels may protect against the overgrowth of candida.23
Lycopene
Lycopene is the carotenoid which gives tomatoes their red color and is one of the major carotenoids in the diet of North Americans and Europeans. It is found in high concentration in testes, adrenal gland and prostate. Levels of lycopene seem to decrease with age. Several studies suggest that lycopene may help to prevent cardiovascular disease and cancers of the prostate, pancreas and gastrointestinal tract.38 According to the results of a 1997 study done in Germany, lycopene from tomato paste is more bio-available than lycopene from fresh tomatoes.39
Prostate cancer
Tomato-based foods, which are rich in lycopene, seem to be linked with a lower risk of prostate cancer. In a study published in 1995, researchers at Harvard Medical School assessed the links between diet during a one-year period and prostate cancer in almost 48 000 men taking part in the Health Professionals Follow-up Study. They found that men who ate more foods such as tomatoes, pizza and tomato sauce which are high in lycopene, were less likely to be at risk of prostate cancer.40
Heart attack
Researchers involved in the EURAMIC study assessed the links between antioxidants and heart attacks. They studied people from ten European countries and analyzed for levels of carotenoids in those who had suffered heart attacks and those who had not. They found protective effects of alpha carotene, beta carotene, and lycopene. Lycopene was particularly protective with those in the highest intake group, having around half the risk of heart attack of those in the lowest intake group.41
Lutein
Like the other carotenoids, lutein has been shown to have antioxidant effects. Lutein and zeaxanthin are constituents of the pigment of the eye. A low density of this pigment in the macula of the eye may increase the risk of the disorder macular degeneration, possibly because it permits greater blue light damage.
In a study published in 1997, researchers at Florida International University in Miami tested the effects of 30 mg of lutein on eye pigment in two people for a period of 140 days.The results showed that 20 to 40 days after the people started taking the lutein supplement, the density of the pigment in their eyes started to increase. This amount of blue light reaching the vulnerable eye tissues that are damaged in macular degeneration was reduced by around 30 to 40 per cent.42
Oxidative damage to the lens of the eye is also implicated in the development of cataract, in which the eye lens becomes clouded. (See page 603 for more information.) In a 1997 study, researchers at Arizona State University assessed the relationship between carotenoid pigments in the retina of the eye and the density of clouding in the lens. The study involved younger people (ages 24 to 36 years) and older people (aged 48 to 82 years). The results showed that lens density increased with age, and that the increase was related to lower macular pigment carotenoids. These findings open up the possibility that lutein and zeaxanthin may be used to slow down age-related increases in lens density.43
Recommended dietary allowances (RDA)
There is no RDA for beta carotene. An intake of 6 mg beta carotene is needed in order to meet the vitamin A RDA of 1000 mcg RE. 1 RE is equivalent to 6 mcg beta carotene. Some experts recommend a daily intake of 10 to 30 mg.
The RDA for vitamin A for women who are breastfeeding increases from 800 mcg RE to 1300 mcg RE. This can be met by increasing the intake of beta carotene-rich foods.
Supplements
Beta carotene supplements are available in various forms, including synthetic forms and those extracted from algae and palm oil. Some studies suggest that those extracted from palm oil are absorbed more efficiently. Natural beta carotene may have greater beneficial effects than synthetic forms.24
Toxic effects of excess intake
Unlike vitamin A, beta carotene is not toxic in large amounts although it may cause the skin of the hands, feet and face to become yellow. This disappears when large intakes are stopped and does not appear to have any ill effects. Research in animals suggests the possibility of menstrual problems with long-term excessive intake.
Therapeutic uses of supplements
Beta carotene supplements have been used in cancer and cardiovascular disease prevention trials, including the Finnish Alpha Tocopherol Beta Carotene Cancer (ATBC) Prevention Study, the US Carotene and Retinol Efficacy Trial (CARET) and the US Physicians Health Study. In 1996, these studies reported results which received wide publicity.
ATBC study
The ATBC Prevention group studied 29 000 men who smoked and drank alcohol. The results showed an 18 per cent increase in lung cancer deaths and an 11 per cent increase in ischemic heart disease deaths in men who took daily supplements of 20 mg beta carotene.25
CARET study
The CARET study was stopped 21 months early. This study was examining the effect of beta carotene (30 mg daily) and retinol (7500 mcg RE daily) supplementation on the prevention of cancer and heart disease in over 18 000 smokers and people who had been exposed to asbestos. The trial was stopped when the results showed a 28 per cent increased risk of lung cancer, a 26 per cent increase in the risk of death from cardiovascular disease, and a 17 per cent increase in overall deaths in the group receiving the supplements.26
Physicians Health Study
This study examined the effect on over 22 000 male doctors of 50 mg beta carotene taken every other day for 12 years. The results suggest that beta carotene has no effect, either positive or negative, on the risk of cardiovascular disease or cancer. Analysis of a subgroup of 333 men in the study with a prior history of heart disease suggested that beta carotene supplements reduced the risk of heart attacks and death by a small amount.27
There are a number of possible explanations for the adverse effects of beta carotene supplements found in these studies and for the failure of supplements to show the protective effects suggested by epidemiological studies.
Beta carotene is susceptible to oxidative damage from alcohol and the gases in cigarette smoke which may lead to the formation of harmful by-products.28 Beta carotene may be dependent on other antioxidants, such as vitamins C and E to exert protective effects. An individual's total dietary intake of antioxidants may therefore need to be considered when assessing protection by beta carotene.
Further analyses of results from the ATBC trial support the suggestion that smoking and alcohol consumption may contribute to the adverse effects of beta carotene. The adverse effects appeared stronger in men who drank alcohol and in those who smoked 20 cigarettes a day than in those who smoked less. This is confirmed by the CARET results which showed greater risk in current smokers than former smokers and also in those who drank alcohol.
Another aspect to be considered is the fact that beta carotene exists in many possible forms and some research suggests that the specific form chosen for use in these clinical trials was not the most active. A mixture of various forms of beta carotene, similar to that which occurs naturally, may have the most beneficial effect. It is also possible that the large dose of the particular form of beta carotene used in the trials competed with other, possibly more beneficial forms at vital sites in the body.
The results of these trials point to the importance of considering total diet and a balanced mixture of nutrients when studying protection against cancer risk. High blood levels of carotene seem to predict lower risk and these high blood levels of beta carotene may be accompanied by high levels of other carotenoids, and even other nutrients, which may also play a vital part in cancer protection. Both the ATBC and CARET studies found that those with higher blood beta carotene levels on entering the trials had a lower risk of lung cancer.
Laboratory research suggests that vitamin C protects against the harmful effects of beta carotene in smokers. Smokers tend to have low levels of vitamin C and this may allow a build-up of a harmful form of beta carotene called the carotene free radical which is formed when beta carotene acts to regenerate vitamin E. These results suggest that in smokers, dietary vitamin C supplementation should accompany beta carotene supplementation.29
Double-blind placebo-controlled studies may be more useful for evaluating a specific drug for one condition in one population group and less suitable for investigating multifactorial agents in complex, mixed population studies. These studies do not invalidate hundreds of other studies showing that diets high in fruits and vegetables protect against a variety of diseases.
Immune system support
In a 1997 double-blind, placebo-controlled study done in the UK, researchers tested the effects of daily doses of 15 mg of beta carotene in 25 healthy, adult male nonsmokers. Their findings showed improvement in function in various parts of the immune system, including white blood cells known as monocytes which are involved in surveillance of tumors.30
Large doses of beta carotene may boost immune function in AIDS patients. In a Yale University study done in 1995, researchers found that daily supplements of 60 mg beta carotene given to seven AIDS patients for a period of four weeks increased CD4+ lymphocyte cell counts.31
Other uses
In addition to exerting protective effects against a wide range of diseases, beta carotene may slow the rate of aging in the skin and other organs by protecting against free radical damage caused by smoking, pollution, ultraviolet light and other chemicals. Beta carotene is also used to treat oral leukoplakia, a pre-cancerous condition of mucous membranes.
Beta carotene may also be beneficial in pre-eclampsia.32 Other results from the CARET study suggest that beta carotene supplements can help to improve lung function in men that have been exposed to asbestos.33
Beta carotene is used to decrease light sensitivity reactions in sufferers of the disease, erythropoietic protoporphyria. Beta carotene supplements have been shown to have beneficial effects in cystic fibrosis by decreasing harmful lipid peroxidation. Fibrocystic breast disease, a painful cystic swelling of the breast which affects 20 to 40 per cent of premenopausal women, may be helped by vitamin A and beta carotene.
Interactions
With other nutrients
The conversion of beta carotene to vitamin A depends on vitamin C, zinc and thyroid hormones. The function of beta carotene is enhanced by the levels of the other antioxidants, vitamin C, vitamin E and selenium. Large doses of beta carotene may increase the requirements for vitamin E. Beta carotene improves iron absorption.34
With drugs
Oral contraceptive use may decrease beta carotene levels.35 Drinking large amounts of alcohol and smoking lowers blood levels of carotenoids.36
Cautions
People with hypothyroidism or liver disease have trouble converting beta carotene to vitamin A and should not rely solely on beta carotene to meet their vitamin A requirements. Diabetics may also have trouble converting beta carotene to vitamin A, although recent research suggests that this may not be the case.37
Large doses of beta carotene may increase the risk of cancer in those who drink alcohol and smoke heavily. Vitamin C supplements may be useful in protecting against the damaging effects of large doses of beta carotene.