Lycopene: Clinical Use. Dosage

The clinical effects of lycopene are studied in relation to dietary intake and oral supplementation. It should be noted that the assessment of dietary lycopene intake varies with the method used to collect dietary information and the food composition databases used to estimate nutritional content.

CANCER PREVENTION

Lycopene is often included as an ingredient in antioxidant combination supplements and is thought to contribute to risk reduction for cancer. Some studies have investigated the effects of lycopene on risk of disease, although many consider it as part of the carotenoid group and study its effects in this way.

Total cancer risk

A 2002 Japanese study involving 2444 people who were followed for 9 years found that high serum levels of lycopene, total carotenes and carotenoids were significantly and inversely associated with subsequent mortality from all causes and cancers of all sites after adjusting for gender, age and serum levels of total cholesterol, alpha-tocopherol and retinol.

In particular, there is some evidence that lycopene levels are inversely proportional to cancers of the prostate, stomach and cervix.

Prostate cancer

A review of 1 5 epidemiological studies concluded that although results are not yet definitive, overall the data suggest that increased consumption of lycopene from tomatoes and tomato-based products may be prudent in order to reduce the risk of prostate cancer. More specifically, five studies found a 30-40% reduction in prostate cancer risk associated with high tomato or lycopene consumption, three found a non-significant 30% reduction in risk, and seven were not supportive of an association. The largest epidemiological study was conducted by the Harvard Medical School, which assessed the diets of 47,894 volunteers and identified several foods as significantly associated with lower prostate cancer risk. They were tomato sauce, tomatoes and pizza, which are primary sources of lycopene. Additionally, consumption of more than 10 servings per week was required for protective effects to be observed.

Besides the epidemiological data on primary prevention, there are some reports of short- to medium-term clinical intervention trials with lycopene supplement or tomatoes. A small study of men with high-grade prostate intraepithelial neoplasia (HGPIN), a precursor of prostate cancer, showed that supplementation with 4 mg lycopene twice daily for 1 year had a chemopreventative effect, preventing progression of HGPIN to prostate cancer. Three of four studies found that either lycopene or tomatoes significantly reduces serum levels of prostate-specific antigen (PSA). Kucuk et al conducted a randomised study involving 26 men, which found that taking a tomato oleoresin extract containing 30 mg lycopene for 3 weeks resulted in smaller prostate tumours, less involvement of surgical margins and/or extra-prostatic tissues with the cancer and less diffuse involvement of the prostate by high-grade prostatic intraepithelial neoplasia compared with controls. Additionally, plasma PSA levels were reduced. Another study, by Bowen et al (2002), involving 32 patients with localised prostate cancer found that consuming tomato sauce-based pasta dishes for 3 weeks (providing 30 mg lycopene/day) reduced serum PSA levels by 17.5% and, overall, significantly reduced DNA damage in both leukocyte and prostate tissue. A lycopene supplement (Lycored softules) for 3 months in 20 patients with metastatic hormone refractive prostate cancer (HRPC) significantly reduced PSA levels and provided relief in bone pain and lower urinary tract symptoms. HRPC was defined as an increase in PSA levels of more than twice the normal value (0-4 ng/mL) confirmed in two consecutive determinations at 2-week intervals in the presence of castrate levels of testosterone. In contrast, no effect on PSA levels was observed in a dose-escalating study of 36 men, which tested high doses of lycopene in biochemically relapsed prostate cancer. The doses studied were 15, 30, 45, 60, 90, and 120 mg/day taken for 1 year and significant elevations of plasma lycopene were noted at 3 months and then appeared to plateau for all six dose levels.

Stomach

Although mixed results were previously obtained from case-control studies, recent evidence is supportive of lycopene as a protective agent in stomach cancer.

The relationship between pre-diagnostic serum levels of carotenoids and risk of gastric cancer was determined in a study involving 761 middle-aged or older men in Shanghai, China, with a follow-up of 12 years. High serum levels of alpha-and beta-carotenes and lycopene were significantly associated with reduced risk of developing gastric cancer (all P values for trend <0.05) whereas no statistically significant relationships among the serum levels of beta-cryptoxanthin, lutein/zeaxanthin, retinol, alpha-tocopherol and gamma-tocopherol were identified with gastric cancer risk.

Cervix

Results from two case-control studies have found an association between low serum lycopene levels and existing cervical cancer, but it is uncertain whether this can be interpreted as a risk factor because depleted levels may be a result of tumour usage, the increased burden of oxidative stress or both.

PREVENTION OF CARDIOVASCULAR DISEASE

Recent epidemiological studies have shown an inverse relationship between tissue and serum levels of lycopene and risk of acute coronary event or stroke and degree of IMT of the common carotid artery.

Strong population-based evidence comes from the large Women’s Health Study (n = 39,875), the European Community Multicenter Study on Antioxidants, Myocardial Infarction and Breast Cancer (EURAMIC) study and the Kuopio Ischaemic Heart Disease Risk Factor study.

In the Women’s Health Study, higher plasma lycopene concentrations were associated with a lower risk of cardiovascular disease. Specifically, for cardiovascular disease, exclusive of angina, women in the upper three quartiles had a significant multivariate risk reduction of 50% compared with those in the lowest quartile. For the EURAMIC study, 1379 individuals (552 patients, 717 controls) from 10 European countries were recruited. Needle aspiration biopsy samples of adipose tissue were taken shortly after myocardial infarction, and levels of alpha- and beta-carotenes, lycopene, and alpha-tocopherol were measured. After adjusting forage, body mass index, socioeconomic status, smoking, hypertension, and maternal and paternal history of heart disease, only lycopene levels were found to be protective. The effect also appeared to be dose-dependent.

In the Kuopio Ischaemic Heart Disease Risk Factor study, 1028 middle-aged men (aged 45-54 years) from Finland were examined and classified into quartiles according to their serum lycopene concentration. The men in the lowest quartile had a significantly higher mean IMT of the common carotid artery (CCA-IMT) and maximal CCA-IMT than the others. Once again, a dose-dependent effect was observed as the mean and maximal CCA-IMT increased linearly across the quarters of serum lycopene concentration. This particular finding is important because increased IMT of the CCA has been shown to predict coronary events.

REDUCING RISK OF MACULAR DEGENERATION

Lycopene supplements are sometimes used to reduce the risk of developing macular degeneration and generally support eye health. In general, it is taken in combination with other carotenoids, such as zeaxanthin and lutein, for this indication for which there is supportive evidence. Few studies are available to determine whether lycopene as a sole agent exerts clinically significant protective effects. One cohort study of 1 59 older people found no inverse association between lycopene intake and 5-year incidence of early age-related macular degeneration (ARMD). Alternatively, a recent study comparing 34 patients with ARMD to 21 control subjects found that of the serum carotenoid concentrations measured, only lycopene was decreased significantly in the serum LDL and HDL fractions (P< 0.05).

CATARACT PREVENTION

Studies have identified protective effects for lycopene against oxidative changes in human lens epithelial cells in vitro and reduced incidence and grading of cataract in test animals. A cross-sectional survey of 372 older volunteers also produced positive results, finding the risk of cortical cataract was lowest in people with the highest plasma concentrations of lycopene.

PROTECTION AGAINST UV-INDUCED PHOTODAMAGE

Oral ingestion

Increasing lycopene intake to 16 mg/day (using tomato paste) over a 10-week period has been shown to provide significant protection against erythema formation following UV irradiation, compared with placebo. The protective effects appear to develop slowly, as tests conducted at 4 weeks found no significant changes. Protective effects were also seen in another study that compared the synthetic lycopene with concentrated tomato extract (Lyc-o-mato). The daily dose of lycopene was approximately 10 mg/day, which was lower in than the previous study. Again, 12 weeks were required to detect significant protective effects against UV-induced erythema and the effect was more pronounced in the group using a natural lycopene source.

Topical use Results from an experimental model show that topical lycopene also has protective effects against acute UV-induced photodamage. Furthermore, it may act as a preventative agent via inhibition of epidermal ornithine decarboxylase activity, reducing inflammatory responses, maintaining normal cell proliferation, and possibly preventing DNA damage, as indicated by blocking the necessitating step of apoptosis following UVB injury.

Lycopene: Other Uses

General antioxidant nutrient.

Lycopene: Dosage Range

BASED ON AVAILABLE EVIDENCE

• Hypercholesterolaemia: 60 mg/day.

• One large study on lycopene and prostate cancer suggested that a daily intake of approximately 6.5 mg was protective.

• Sunburn protection: 10-16 mg/day.