The role of carotenoids in disease prevention

Many studies have linked the regular consumption of carotenoid-rich foodstuffs to a reduced risk for the incidence of a number of diseases. Under discussion as basic mechanisms for this protective effect are the antioxidant activity of carotenoids and their biochemical ability to influence signal transmission in cells. A sufficient intake of carotenoids to support the body’s own antioxidative network could therefore combat the development of diseases that are stimulated by oxidative damage to cell constituents. Since these micronutrients are fat-soluble they act mainly in cell membranes and lipoproteins to protect against excessive oxidation. There they can help prevent cell mutation – and therefore the development of cancer – and the formation of atherosclerosis, which is a cause of cardiovascular disease.

Among the best investigated carotenoids are beta-carotene, lycopene and lutein and zeaxanthin, which are found in numerous kinds of fruit and vegetables and usually need to be made accessible and available to the body by unlocking them mechani- cally during food preparation (e.g., by cooking or juicing). In addition to its antioxi- dant properties, beta-carotene, the most common efficient vitamin A precursor, plays an important part in ensuring an adequate supply of this vitamin to the body. More- over, beta-carotene appears to help protect the skin against ultraviolet irradiation. Lutein and zeaxanthin are present mainly in the retina, where they can protect the eye against damage caused by UV light. Several studies have found an association between the antioxidant activity of lycopene, which occurs primarily in tomatoes, and a reduction in the risk of developing cancer or coronary and vascular diseases.

Carotenoids in the prevention of

Cancer

The term “cancer” is applied to any malignant growth of tissue (tumor), in which the body’s own cells divide autonomously, progressively and excessively. Malignant cells grow in a random fashion. They are often un- differentiated and mutate rapidly. Cancer cells invade surrounding tissue, destroying and replacing it. They can also form colonies (metastases) in other tissues and organs. It is thought that cancer generally alters the genome (DNA) of a cell. While many factors are known to be potentially involved in the occurrence of a tu- mor, they by no means play a role in all forms of the disease. In addition to some chemicals, ionizing radia- tion and certain viruses, genetic disposition and many factors relating to individual lifestyle, like diet, excess weight, tobacco and alcohol consumption, can contribute to the occurrence of cancer. Some of these factors lead to an increase in the formation of free radicals in the body. In high concentrations (oxidative stress), these free radicals could damage cell constituents (membranes, proteins and DNA) and contribute to the incidence of diseases like cancer. Antioxidant substances that the body produces for itself (some enzymes), or which can be ingested, can function as free radical antagonists. The antioxidants that can be ingested include micronutrients such as some vitamins (C and E) and carotenoids. A sufficient intake of such anti- oxidant nutrients can, for instance, help protect the DNA against oxidative damage and hence combat the occurrence of cancer cells.

The carotenoids are among the most potent of the micronutrient antioxidants. Beta-carotene and lycopene, in particular, have been investigated for their possible cancer-preventing activity. Lycopene is considered one of the carotenoids with the strongest antioxidant effect. It also exhibits anti-inflammatory activity (1). Further, lycopene appears to be involved in the modulation of signal transmission between cells and the ex- pression of genes that control cell growth and division (2). This carotenoid is of particular interest in pros- tate cancer research (3). Many observational studies provided evidence that a diet rich in lycopene, espe- cially with tomatoes and tomato products, could reduce the risk of developing prostate carcinoma (4, 5). The results from a prospective cohort study with over 49,000 men over a period of 23 years indicate that a diet rich in lycopene could combat the development of aggressive prostate cancer with a fatal outcome, as well as the formation of new blood vessels (angiogenesis) that encourage cancer growth (6). This findings have been confirmed by initial randomized controlled studies in which subjects were specifically given 15–30 mg lycopene daily (5, 7).

Because of its properties as an antioxidant, its role as signal transmission modulator in the context of cell growth and reproduction, and its anti-inflammatory potential, beta-carotene has been linked to a possible protective effect against various types of cancer. With regard to the prevention of colon cancer, in the first instance observation and case control studies into the consumption of beta-carotene in the diet indicate a possible preventive potential (8, 9). According to one retrospective cohort study, beta-carotene appears to be able to suppress the growth of certain cancer precursor lesions (adenomas) in the bowel, especially in combination with other carotenoids (10). Increasingly, indications from observation studies and clinical studies are that beta-carotene can combat the incidence of cancer of the mouth and throat (pharynx), the voice box (larynx) and the gullet (esophagus) (11). The best documented evidence is for the possible pro- tective effect of a diet that includes fruit and vegetables, which are generally rich in carotenoids (12). This type of diet could also help to prevent breast cancer (13).

Studies into the prevention of lung cancer in high-risk groups (heavy smokers and asbestos workers) have indicated that long-term consumption of large amounts of beta-carotene could increase the risk of lung can- cer (14). One possible explanation for this is that the strongly oxidative environment in the lung caused by tobacco smoke or exposure to asbestos stimulates the formation of abnormal decomposition products of beta-carotene that could play a role in the development of cancer (15). In 2012 the European Food Safety Authority (EFSA) declared that epidemiological studies had come to the conclusion that heavy smokers who took beta-carotene in the form of dietary supplements in doses of 6 to 15 mg a day over a period of 5 to
7 years did not appear to have an increased incidence of lung cancer (16). According to EFSA, consumption of under 15 mg of beta-carotene a day as food additives or food supplements does not give rise to concerns about adverse health effects in the general population, including heavy smokers.

Cardiovascular diseases

Broadly speaking, the cardiovascular diseases include all diseases of the heart and the vascular system. High blood pressure, together with other risk factors such as diabetes or disorders of the lipid metabolism, encou- rages the occurrence of atherosclerosis. In the course of this vascular disease, cholesterol and other fats, as well as calcium, are deposited as plaque on the lining of the blood vessels (endothelium), where free radicals and/or oxidative stress can accelerate the development of chronic inflammatory processes. In consequence, the vessels become constricted and the blood can no longer flow freely through the arteries. Organs like the heart, brain and kidneys no longer receive sufficient blood and can suffer damage. The causes of cardiovas- cular disease are extremely complex. In addition to genetic disposition and the natural aging process, dia- betes, high cholesterol levels and smoking are all factors. Overweight and stress also appear to play a part. Preventive measures include avoiding nicotine, taking sufficient exercise and consuming a low-fat diet with plenty of fruit and vegetables. A varied selection of fruit and vegetables will include many carotenoids, whose antioxidant and anti-inflammatory properties could help maintain vascular health (17, 18).

The clearest indications of vascular protection by carotenoids overall were provided by epidemiological stu- dies which were able to show a connection between a diet rich in carotenoids from fruit and vegetables and a reduction in the risk of developing cardiovascular disease (11). Results from clinical studies with targeted administration of beta-carotene were, however, ambiguous (18). The results of a prospective cohort study indicate that too low concentrations of plasma beta-carotene could represent a risk factor for congestive heart failure (19), atrial fibrillation (20), sudden cardiac death (21), and increased mortality due to cardio- vascular events (22).

Skin damage

Ultraviolet rays of sunlight (UV radiation) damage the skin, lead to premature skin aging and can trigger skin diseases. UV radiation (100-400 nm) can be divided into short-wave (strong) UVC, middle-range UVB and long-wave (soft) UVA. Whilst UVC from the sun is almost completely absorbed by the ozone layer, UVA (90%) and UVB (10%) reach the skin. UVA penetrates deep into the skin and can cause oxidative damage in skin cell DNA. UVA rays can therefore accelerate light-induced skin aging (photoaging), leading to dryness, thickening of the epidermis, pigmentation and wrinkles. UVB rays only reach the superficial layers of the skin, but are capable of damaging skin-cell DNA and permanently damaging the skin. UVB radiation is also thought to be one of the main causes of skin cancer (11). (See also Micronutrients in human development – Part 3).

With their antioxidant and anti-inflammatory properties and their ability to influence cell growth and division, carotenoids can help protect the skin against photo-damage and prevent skin diseases (23). The systemic protective effect of beta-carotene against sunburn (erythema) has been intensively investigated. A meta- analysis of several studies showed that targeted consumption of beta-carotene was best able to unfold its preventive effect over a period of at least 10 months (24). Positive outcomes in relation to sunburn were delivered by clinical studies which also focused on high intakes of lycopene in fruit and vegetables (25, 26). In general, systemic ingestion of carotenoids should only be used as protection against UV radiation in con- junction with topical sun protection products, since it is considerably less effective than sunscreens. Studies that investigated a possible association between increased consumption of carotenoids and a reduction in the risk for skin cancer have as yet not furnished clear results (11). Equally inconsistent are current findings on the systemic effect of carotenoids on light-induced skin aging.

Some studies gave indications that the administration of high-dose beta-carotene products could support the treatment of abnormally light-sensitive skin. Regular administration of beta-carotene was found to help redu- ce skin damage in cases of both polymorphous photodermatosis, which is mainly triggered by UVA sunlight and can be accompanied by very itchy inflammation and blisters (23), and erythropoietic protoporphyria, a rare inherited disease that is characterized by extreme skin sensitivity to light (27).

Eye diseases

The eyes, too, can suffer from exposure to energy-rich UV radiation and the scattering of visible light. This can lead to acute and chronic dama- ge to the eye. Looking at the sun without eye protection can cause damage to the retina after only a few seconds or minutes and even permanent loss of sight. The cornea of the eye primarily absorbs UVC and UVB radiation, while the lens absorbs UVB and UVA rays. Other types of ray reach the retina, especially the point of most acute vision, the Macula lutea or yellow spot, almost unim- peded. In young people, visible blue light also penetrates as far as the retina and, together with energy-rich UV radiation, is an important factor in the occurrence of changes to the lens and retina. Depending on the energy dose, incident light triggers light-induced oxidative damage in the optic lens which can lead to clouding (cataract) and hence poor vision, to increased sensitivity to glare and to blurred vision (see also Micronutrients and eye health). In the long term, the action of sunlight on the eyes contributes to the development of age-related macular degeneration (AMD), a multi-factorial degenerative condition of the retina in the region of the macula. In the course of the lifetime, cellular waste deposits (lipofuscin deposits) collect in the retina and cause retinal cells to die. Lipofuscin absorbs large amounts of light energy and is implicated in cell-damaging oxidative processes. The consequence is a loss of visual acuity, reduced perception of contrast and color and increased sensitivity to glare. High concentrations of macular pigment (lutein and zeaxanthin) are found in the macular region, which together with melanin have a strong antioxidant effect that protects against these oxidative processes (28).

Various epidemiological and randomized controlled studies indicate that increasing the intake of antioxidant carotenoids, in particular beta-carotene (29) and lutein and zeaxanthin, could prevent the occurrence
of cataract or at least slow its progress (30, 31). Currently, the most promising carotenoids for protection against AMD are lutein and zeaxanthin, which in high concentrations in the macula function as natural light filters. In the course of a lifetime they become exhausted. The loss of this protection from destructive oxi- dative processes in the macula is a gradual process. In the early (“dry”) stage, macular degeneration is untreatable. Only the later, more severe (“wet”) form can be treated. This makes it even more important to prevent AMD or slow its progress. A number of studies, including randomized controlled studies like the LUTEGA study, have shown that re-stocking the pigments lutein and zeaxanthin in the macula by increasing the intake of carotenoid-rich fruit and vegetables could combat the onset and advance of AMD (32). A delay in the development of AMD could also be demonstrated after targeted administration of lutein and zeaxanthin as dietary supplements (33–35).

Neurodegenerative disease

The structures of cells and tissue in the brain and nervous system can be damaged or destroyed by high concentrations of free radicals resulting from chronic inflammatory processes or environmental influences. The progressive loss of nerve cells leads to various neurological diseases of the brain, like dementia (e.g., Alzheimer’s disease) or motor function disorders (e.g., Parkinson’s disease) (see also Micronutrients and mental energy). A sufficient supply of antioxidant nutrients to the body could help protect the brain against oxidative stress and hence against an (age-related) loss of cognitive performance or the development of neurodegenerative disease. Preliminary study results that indicate blood levels of carotenoids to be lower in Alzheimer’s sufferers (36) or show a possible preventive effect of targeted administration of beta-carotene on the development of dementia (37, 38) should be substantiated by further, in particular randomized controlled studies.