Beta-Carotene

Beta-carotene is one of more than 600 carotenoids known to exist in nature. Carotenoids are yellow to red pigments that are widely distributed in plants. About 50 of these can potentially yield vitamin A activity and are thus referred to as provitamin A carotenoids. beta-carotene is the most abundant and most efficient provitamin A in our foods.

Theoretically, one molecule of beta-carotene can be cleaved into two molecules of vitamin A (Figure 2). However, inside the body, beta-carotene is only partially converted to vitamin A and the rest is stored as such. Furthermore, the proportion of beta-carotene converted to vitamin A in the body is controlled by the vitamin A status and thus it cannot cause vitamin A hypervitaminosis in humans. Currently available evidence suggests that in addition to being a safe source of vitamin A, beta-carotene plays many important biological roles that may be independent of its provitamin status.

The best sources of beta-carotene are deep yellow/orange vegetables and fruits and dark green leafy vegetables:

Yellow/orange vegetables - carrots, sweet potatoes, pumpkins, winter squash

Yellow/orange fruits - apricots, cantaloupes, papayas, mangoes, carambolas, nectarines, peaches

*Dark green leafy vegetables - spinach, broccoli, endive, kale, chicory, escarole, watercress and the greens of beet, turnip, mustard, dandelion other good vegetable and fruit sources - summer squash, asparagus, peas, sour cherries, prune plums.

The beta-carotene content of fruits and vegetables can vary depending on the season and degree of ripening. The bioavailability of beta-carotene from fruits and vegetables depends on the method of preparation before ingestion. Any indications concerning the beta-carotene content of foods are therefore only approximate values.

In the following short list the beta-carotene content is given per 100 g edible substance:

Vegetables: carrots (6.6 mg), watercress (5.6 mg), spinach (4.9 mg), broccoli (1.5 mg)

Fruits: mangoes (2.9 mg), melons (2.0 mg), apricots (1.6 mg), peaches (0.5 mg).

Bile salts are needed for the absorption of beta-carotene in the upper small intestine. Many factors in the diet, e.g. fat and protein, affect absorption.

Approximately 10-50% of the total beta-carotene consumed is absorbed in the gastrointestinal tract. The proportion of carotenoids absorbed decreases as dietary intake increases. Within the intestinal wall (mucosa), beta-carotene is partially converted into vitamin A

(retinol) by an enzyme, dioxygenase. This mechanism is regulated by the individual's vitamin A status. if the body has enough vitamin A, the conversion of beta-carotene decreases. Therefore, beta-carotene is a very safe source of vitamin A and high intakes will not lead to hypervitaminosis A.

Excess beta-carotene is predominantly stored in the fat tissues of the body. The adult's fat stores are often yellow from accumulated carotene while the infant's fat stores are white. Excessive intake of beta-carotene leads to yellowish skin, but this is quickly reversible upon cessation of intake.

Traditionally, vitamin A activity of beta-carotene has been expressed in International Units (IU; 1 IU = 0.60 µg of all-trans beta-carotene). However, this conversion factor does not take into account the poor bioavailability of carotenoids in humans. Thus, FAO/WHO Expert Committee proposed that vitamin A activity be expressed as retinol equivalent (RE).

1 RE = 1 µg retinol

1 RE = 6 µg beta-carotene

1 RE = 12 µg other provitamin A carotenoids

1 RE = 3.33 IU vitamin A activity from retinol

1 RE = 10 IU vitamin A activity from beta-carotene

Carotenoids can loose some of their activity in foods during storage, due to the action of enzymes and exposure to light and oxygen. Dehydration of vegetables and fruits may greatly reduce the biological activity of carotenoids. on the other hand, carotenoid stability is retained in frozen foods.

1. Singlet oxygen quenching
Beta-carotene can quench singlet oxygen, a reactive molecule that is generated, for instance in the skin by exposure to ultraviolet light and which can induce precancerous changes in cells. Singlet oxygen has the ability to trigger the generation of free radical chain reactions.

2. Antioxidant
Beta-carotene may also have antioxidant properties that help neutralize free radicals, reactive and highly energized molecules which are- formed through certain normal biochemical reactions (e.g. in the immune response, prostaglandin synthesis), or through exogenous sources such as air pollution or cigarette smoke. Free radicals can damage lipids in cell membranes as well as the genetic material in cells, and the resulting damage may lead to the development of cancer.

The consumption of fruits and vegetables rich in beta-carotene is associated with a protective effect against the development of certain cancers and a high intake/status of this nutrient has been related to a decreased incidence of certain cancers and cardiovascular events. Findings in laboratory studies show that beta-carotene acts in synergy with vitamins E and C.

Although the US population on the average does not consume enough beta-carotene, certain groups of people are particularly at risk for inadequacy of beta-carotene. For example, low blood levels of beta-carotene have been reported in smokers, alcohol drinkers and in users of certain drugs (oral contraceptives, hypotensive drugs).

Dietary intakes for beta-carotene have up to now been expressed as part of the RDA for vitamin A. The RDA for males (11+ years) is 1000  RE, equivalent to 1000 µg of retinol or 6 mg of beta-carotene, while the RDA for females (11+ years) is slightly lower: 800 RE, equivalent to 800 µg of retinol or 4.8 mg of beta-carotene. There are additional requirements during pregnancy and lactation, 200 RE and 400 RE, respectively. Infants and small children up to three years of age need about 400  RE and children (4-10 years) require 500-700 RE. Up to 40-60% of the vitamin A in the average US diet comes from beta-carotene. If dietary guidelines of the US National Cancer Institute (NCI) are followed the ratio beta-carotene/vitamin A in the diet would be about 9:1. Apart from its provitamin A function, data continue to accumulate supporting a role for beta-carotene as an important micronutrient in its own right. Consumption of foods rich in beta-carotene is being recommended by scientific and government organizations such as the US National Cancer Institute (NCI) and the US Department of Agriculture (USDA).

If these dietary guidelines are followed, dietary intake of beta-carotene (about 6 mg) would be several times the average amount consumed in the US (about 1.5 mg daily).

Beta-carotene is available in hard and soft gelatin capsules, in multivitamin tablets, and in antioxidant vitamin formulas.

Immune system
In a number of animal and human studies beta-carotene supplementation was found to enhance certain immune responses.

Cancer/Cardiovascular
Epidemiological studies consistently indicate that as consumption of beta-carotene-rich fruits and vegetables increases, the incidence of certain cancers (i.e. lung, stomach) and cardiovascular disease decreases. Additionally, animal experiments have shown that beta-carotene acts as a cancer preventive agent. This is further supported by studies using biomarkers for development of certain cancers. However, results from recent clinical intervention studies did not confirm these findings. Thus the accumulated overall evidence is promising but the hypothesis is still unproven. Similar results were observed in studies on a potential of beta-carotene in the reduction of cardiovascular events.

Skin
Recent evidence points to a role of beta-carotene in protecting skin from sun damage and maintaining immune response and collagen integrity.

Photosensitivity disorders
Many studies have been performed in patients with abnormal skin reactions to sunlight, called photosensitivity disorders (i.e. erythropoietic protoporphyria). Beta-Carotene in large doses up to 180 mg has been shown to exert a photoprotective effect in these individuals.

Due to the regulated conversion of beta-carotene into vitamin A, overconsumption does not produce hypervitaminosis A. Excessive intakes of carotenoids in certain disease conditions (hyperlipidaemia, diabetes mellitus, nephrotic syndrome or hyperthyroidism) may cause hypercarotenodermia which manifests itself in a yellowish tint of the skin, mainly in the palms and soles. The yellow colour disappears when carotenoid consumption is reduced or stopped.

Studies have been conducted in humans to evaluate the safety of beta-carotene. Studies performed in patients with light sensitivity such as erythropoietic protoporphyria have shown no adverse effect from ingestion of 50-200  mg/day of beta-carotene for several years.

The observation of an apparent increase of lung cancer in chronic heavy smokers with intakes of more than 20 mg/day over several years is a matter of debate, and only the long-term follow-up of the participants in the clinical intervention studies is to be awaited to clearly establish whether this finding may be a causal adverse effect of beta-carotene.

Isler and co-workers developed a method to synthesize beta-carotene, and it has been commercially available in a crystalline form since 1954.

Margarine and fruit drinks are often fortified with beta-carotene. In 1941, the US Food and Drug Administration (FDA) established a standard of identity for the addition of vitamin A to margarine; in the meantime, however, vitamin A has been partly replaced by beta-carotene which additionally imparts an attractive yellowish colour to this product. Due to its high safety margin, beta-carotene has been recognized to be more suitable for fortification purposes than vitamin A.

1831: Wackenroder discovers orange,/yellow pigments in carrots and coins the term 'carotene'  

1847: Zeise provides a more detailed description of carotene  

1866: Carotene is classified as hydrocarbon by Arnaud and coworkers  

1887: Arnaud describes the widespread presence of carotenes in plants  

1907: Willstatter and Mieg establish the molecular formula for carotene, a molecule consisting of 40 carbon and 56 hydrogen atoms  

1914: Palmer and Eckles discover the existence of carotene and xanthophylls in human blood plasma  

1919: Steenbock (University of Wisconsin) suggests a relationship between yellow plant pigments (beta-carotene) and vitamin A  

1929: Moore demonstrates that beta-carotene is converted into the colourless form of vitamin A in the liver  

1931: Karrer and coworkers (Switzerland) determine the structures of beta-carotene and vitamin  

1939: Wagner and coworkers suggest that the conversion of beta-carotene into vitamin A occurs within the intestinal mucosa  

1950: Isler and colleagues develop a method for synthesizing beta-carotene  

1966: beta-Carotene is found acceptable to use in foods by the joint FAO/ WHO Expert Committee on Food Additives  

1972: Specifications for beta-carotene use in foods is established by the U.S. Food Chemicals Codex  

1979: Carotene is established as 'GRAS', which means that the ingredient is 'Generally Recognized As Safe' and can be used as a dietary supplement or in food fortification  

1981-1982: beta-Carotene/carotenoids are recognised as important factors (independent of their provitamin A activity) in potentially reducing the risk of certain cancers. R. Doll and R. Peto: "Can Dietary beta-Carotene Materially Reduce Human Cancer Rates?" (in: Nature, 1981; 290:201-208) R. Shekelle et al: "Dietary Vitamin A and Risk of cancer in the Western Electric Study" (in: Lancet, 1981: 1185-1190) "Diet, Nutrition and Cancer" (1982): Review of the U.S. National Academy of Sciences showing that intake of carotenoid-rich foods is associated with reduced risk of certain cancers.  

1982: Krinsky and Deneke show the interaction between oxygen and oxyradicals with carotenoids  

1983: The US National Cancer Institute (NCI) launches large-scale clinical intervention trials using beta-carotene supplements alone and in combination with other nutrients  

1984: beta-Carotene is demonstrated to be an effective antioxidant in vitro  

1988: Due to the large number of epidemiological studies that demonstrate the potential reduction of cancer incidence with increased consumption of dietary beta-carotene, the US National Cancer Institute (NCI) issues dietary guidelines advising Americans to include a variety of vegetables and fruits in the daily diet  

1993-1994: Results from several large-scale clinical intervention trials using beta-carotene alone or in various other combinations became available  

1997: Evidence indicates beta-carotene to act synergistically with vitamins C and E  

1997-2001: Clinical intervention studies are under way(WACS, BHPS) to evaluate the combination of antioxidant vitamins (beta-carotene and vitamins C and E)