Lycopene: The redder the better

Subject: A literature review on the possible benefit of lycopene, a constituent of tomato products, in the prevention and treatment of prostate cancer, breast cancer, diabetes, and heart disease.

Lycopene

Poor Ronald Reagen was given a peck of grief years ago when as President, he had the audacity to suggest that ketchup should be counted as a vegetable in school lunch programs. Time has a way of giving us perspective and in hindsight Reagan's ketchup suggestion was one of his better ideas.

Ketchup and other cooked tomato products are one of the best sources of a chemical coumpound called lycopene. This chemical may have a crucial role in protecting us against cardiovascular disease, diabetes and cancer.

Lycopene gives the red color to tomatoes and is a prominent member of the carotenoid family. In plants, lycopene is similar to other carotenoids, serving as a light-absorbing pigment during photosynthesis and protecting cells against photosensitization.

More than 80% of lycopene consumed in the United States is derived from tomato products. Apricots, papaya, pink grapefruit, guava, and watermelon also contain smaller amounts of lycopene and contribute to our intake.

The lycopene content of tomatoes varies significantly, depending on type of tomato and ripening. A simple rule is the redder the better. In the reddest strains of tomatoes, lycopene concentration is close to 50 mg per kg compared with only 5 mg per kg in the yellow strains. Roma tomatoes have the highest concentration.
Lycopene is stable during cooking and food processing. Bioavailability of lycopene is influenced by heat and fats. Heating foods prior to eating can improve lycopene absorption in the body. Further, fat also seems to enhance lycopene absorption from the gastrointestinal tract. In other words, tomatoes simmered with olive oil into a sauce will provide more benefit than raw tomatoes in a salad.

Many of the reported health benefits of lycopene are attributed to its ability to protect cells against oxidative damage. Studies suggest that lycopene is a more potent scavenger of oxygen radicals than other major dietary carotenoids.

As a result lycopene may play a role in providing protection against all disease involving oxidative damage to the cells. Current research has focuses in several areas:
1. prostate cancer
2. breast cancer
3. diabetes
4. cardiovascular disease.

Food Serving Size Lycopene (mg/serving)
Spaghetti sauce ½ cup 28
Tomato juice 1 cup 25
Tomato ketchup 1 tablespoon 3
Tomato paste 2 tablespoon 14
Tomato sauce ¼ cup 9
Watermelon 1 cup 4

A review of the literature on lycopene:
1. Prostate Cancer
Lycopene has been shown to concentrate in prostate tissues.1 Of the carotenoids present in the prostate, lycopene levels appeared to be highest. Thus, it has been hypothesized that lycopene may lower the risk of prostate cancer. Studies at the University of Toronto found that prostate cancer patients have lower serum and prostate tissue lycopene levels compared to control subjects.2 In a cell culture study, lycopene, when combined with Vitamin E, prevented the growth of prostate cancer cells.3 These data provide further evidence that increased consumption of tomato products and other foods containing lycopene could lower the risk of prostate cancer.

One recent study evaluated how prostate levels of antioxidants relate to plasma levels and self-reported usual dietary intake.4 Levels were measured in 47 men undergoing radical prostatectomy or transurethral prostatectomy at Loyola University Medical Center in Chicago. The levels of tocopherols and carotenoids in the prostate were significantly correlated with plasma levels; the strongest correlations were associated with lycopene, beta-carotene, and gamma-tocopherol. The researchers note that this finding supports their potential to provide better estimates of internal dose, and thus target organ exposure, than reported intake.

In a study conducted on 65 patients with prostate cancer and 132 cancer-free controls, significant inverse relationships with prostate cancer were observed with plasma concentrations of lycopene. An 83% reduction of prostate cancer risk was observed in the group with the highest plasma concentration of lycopene in comparison with individuals with the lowest concentration. The strength of the association was directly related to dose; with increasing concentrations of plasma lycopene, the risk of prostate cancer was decreased.5

Studies suggest that lycopene from various tomato products is associated with the lowered risk of several other types of cancers.6

2. Studies reviewing lycopene and the incidence of breast cancer
In cell culture studies, lycopene's activities in inhibiting breast cancer tumors were compared with those of alpha and beta-carotene.7 The cell cultures that were enhanced with lycopene showed that it inhibited the growth of breast cancer cells (MCF-7), and that alpha and beta-carotene were far less effective than lycopene in inhibiting the cell growth. When lycopene was fed to mice genetically susceptible to developing breast tumors8 , it was found that lycopene-fed mice had suppressed and delayed tumors. Another study showed that rats injected with lycopene developed fewer and smaller size carcinogen-induced tumors than rats without lycopene injections.9 Beta-carotene didn't provide any protection against breast tumors in this study.
Several studies have shown insignificant or no association between either lycopene from the diet10 and concentrated lycopene11 and breast cancer risk, however others have found a relationship between breast tissue lycopene and breast cancer risk.12

A study of samples taken from The Breast Cancer Serum Bank in Columbia, Missouri were analyzed to evaluate the relationship of levels of carotenoids (including lycopene), selenium and retinol with breast cancer.13 Only lycopene was found to reduce the risk for developing breast cancer. Other carotenoids were not found to be associated with reduced breast cancer risk.

3. Diabetes and Lycopene
Research on the role lycopene may play with diabetes is less clear cut than in other areas. There are confliciting reports, some suggesting benefit others showing no benefit. Recent studies have found free radicals to cause disruption in insulin action and mitigate glucose-intolerant states.14 Because lycopene is one of the best antioxidants among carotenoids, as evidenced by its singlet oxygen-quenching ability, it may play a vital role in reducing the on-set of this disease.
Olemedilla et al. studied the fat soluble antioxidant status in IDDM patients. Using 450 controls and 123 Type I diabetic patients, the team examined and compared concentrations of serum retinol, tocopherol, and main carotenoids. Lycopene and ß-carotene were the only nutrients positively associated with the disease, while retinol was the only nutrient that indicated a significant negative association with diabetes. 15

Conflicting results were reported by Granado et al., comparing the antioxidant status of 54 Type I diabetic patients, 214 non-diabetic first degree relatives and 236 unrelated controls. The study found no significant differences in serum vitamin E, lutein, or lycopene between controls and patients with IDDM. In fact the investigators observed serum fat-soluble antioxidant levels equal to or higher than those in controls, and concluded that supplementation with fat-soluble antioxidants is not necessary for patients with diabetes.16

Ford et al., recently analyzed the data from Phase I of the Third National and Nutrition Examination Survey (1988-1991) to examine carotenoids concentration in 40 to 70 year old subjects with normal glucose tolerance (1010 subjects), impaired glucose tolerance (277 subjects) and newly diagnosed diabetic cases (148 subjects). All serum carotenoids were found to be inversely associated with the fasting serum insulin levels. Moreover, serum lycopene and ß-carotene levels in the diabetic patients were significantly lower compared to levels in persons with impaired glucose tolerance and was also found to be lower than the levels in subjects with normal glucose tolerance. 17

Diabetic Asian Indian physicians living in USA were found to have lower lycopene compared to their non-diabetic counterparts.18 Similarly elderly subjects with Type II diabetes were reported to have significantly lower levels of plasma antioxidants including lycopene, compared to matched controls.19 In a clinical trial , tomato juice supplementation in Type II diabetic patients resulted in nearly 3 fold increase plasma levels of lycopene and significant protection from LDL oxidation20 , a risk factor in CVD.21

4. Studies reviewing lycopene and the incidence of heart disease
Cardiovascular diseases are one of the leading causes of death in North America. Scientific evidence indicates that oxidation of low-density lipoproteins, which carry cholesterol into the blood stream, plays an important role in the development of atherosclerosis - the underlying disorder leading to heart attacks and ischemic strokes. 22 Antioxidants are believed to slow the progression of atherosclerosis because of their ability to inhibit cell-damaging oxidation23 Studies indicate that consuming the antioxidant lycopene, contained in tomatoes and tomato products, can reduce the risk of heart diseases.
Scientists at Johns Hopkins University report that smokers with low levels of carotenoids are at an increased risk for heart disease.24 Lower blood lycopene levels are also associated with increased risk of coronary heart disease according to studies with Lithuanian and Swedish people.25 Another study of people from 10 different European countries, measured the relationship between antioxidant levels and acute heart disease.26 It was found that the consumption of lycopene in fruits and vegetables may reduce the likelihood of developing heart disease.
Lycopene is a lipid soluble antioxidant that is transported in the blood through lipoproteins. The absorption of lycopene and other carotenoids, including beta-carotene and vitamin E, has been shown to prevent the oxidation of LDL (or bad) cholesterol.27 A University of Toronto study investigated the effects of tomato lycopene on LDL oxidation. People consumed one-to-two servings per day of tomato juice, spaghetti sauce and concentrated lycopene for one week. Blood samples were collected and analyzed for lycopene, blood cholesterol and oxidized LDL. Lycopene levels were doubled by the consumption of tomato juice, spaghetti and concentrated lycopene. Although there was no change in cholesterol levels, the level of oxidized LDL was significantly lowered as a result of lycopene consumption.28 The study results suggest that consumption of tomato products inhibits oxidative damage of LDL cholesterol, and thus may be helpful in reducing the risk of heart disease. The consumption levels from this study are consistent with current dietary guidelines for healthy eating.
A glass of tomato juice, a serving of tomato soup or four tablespoons of ketchup can be part of the recommended daily consumption of fruits and vegetables.

This article was something of an accident. I started in looking for recipes to make homemade ketchup and came up with this instead. Ketchup recipes will follow at a later date.

References:
1. Clinton SK, Emenhiser C, Schwartz SJ, Bostwick DG, Williams AW, Moore BJ, Erdman JW Jr. Cis-trans lycopene isomers, carotenoids, and retinol in the human prostate. Cancer Epidemiology, Biomarkers & Prevention 1996; 5:823-833
2. Rao AV, Fleshner N, Agarwal S. Serum and tissue lycopene and biomarkers of oxidation in prostate cancer patients: a case-control study. Nutrition and Cancer 1999; 32:159-164
3. Pastori M, Pfander H, Boscoboinik D, Azzi A. Lycopene in association with alpha-tocopherol inhibits at physiological concentrations proliferation of prostate carcinoma cells. Biochemical and Biophysical Research Communications 1998; 250:582-585
4. Freeman VL, Mohsen M, Yong S, Pyle J, Wan Y, Arvizu-Durazo R, Liao Y. Prostatic Levels of Tocopherols, Carotenoids, and Retinol in Relation to Plasma Levels and Self-Reported Usual Dietary Intake, Am. J. Epidemiology, Vol 151(2):109-118, January 15, 2000
5. Lu Q-Y, Hung J-C, Heber D, Go VLW, Reuter VE, Cordon-Cardo C, Scher HI, Marshall JR, and Zhang Z-F. Cancer Epidemiology Biomarkers & Prevention Vol. 10, 749-756, July 2001
6. Giovannucci E. Tomatoes, tomato-based products, lycopene and cancer: review of the epidemiological literature. Journal of the National Cancer Institute 1999; 91:317-331
7. Levy J, Bosin E, Feldman B, Giat Y, Miinster, Danilenko M, Sharoni Y. Lycopene is more potent inhibitor of human cancer cell proliferation than either A-carotene or beta-carotene. Nutr Cancer 1995; 24:257-266
8. Nagasawa H, Mitamura T, Sakamoto S, Yamamoto K. Effects of lycopene on spontaneous mammary tumor development in SHN virgin mice. Anticancer Res 1995; 15:1173-1178
9. Sharoni Y, Giron E, Rise M, Levy J. Effects of lycopene-enriched tomato oleoresin on 7, 12-dimethyl-benz(a)anthracene-induced rat mammary tumors. Cancer Detect Preven 1997; 21:118-123
10. Freudenheim JL, Marshall JR, Vena JE, Laughlin R, Brasure JR, Swanson MK, Nemoto T, Graham S. Premenopausal breast cancer risk and intake of vegetables, fruits and related nutrients. J Natl Cancer Inst 1996; 88:340-348
11. London SJ, Stein EA, Henderson IC, Stampfer MJ, Wood WC, Remine S, Dmochowski JR, Robert NJ, Willett WC. Carotenoids, retinol and vitamin e and risk of proliferative benign breast disease and breast cancer. Cancer Causes Control 1992; 3:503-512
12. Zhang S, Tang G, Russell RM, Mayzel KA, Stampfer MJ, Willett WC, Hunter DJ. Measurement of retinoids and carotenoids in breast adipose tissue and a comparison of concentrations in breast cancer cases and control subjects. Am J Clin Nutru 1997; 66:626-632
13. Dorgan JF, Sowell A, Swanson CA, Potischman N, Miller R, Schussler N, Stephenson HEJr. Relationships of serum carotenoids, retinol, a-tocorpherol and selenium with breast cancer risk: results from a prospective study in Columbia, Missouri (United States). Cancer Causes Control 1998; 9:89-97
14. Ford et al. Diabetes mellitus and serum carotenoids findings from the Third National and Nutrition Examination Survey. Am J Epidemiol 149:168-176, 1999
15. Olmedilla et al. Reference values fro retinol, tocopherol and main carotenoids in serum of control and insulin dependant diabetic Spanish subjects. Clin Chem 43:1066-1071, 1997
16. Granado et al. Carotenoids, retinol and tocopherols in patients with insulin dependant diabetes mellitus and their immediate relatives. Clin Sci (Colch) 94:189-195, 1998
17. Ford et al. Diabetes mellitus and serum carotenoids findings from the Third National and Nutrition Examination Survey. Am J Epidemiol 149:168-176, 1999
18. Chuang et al. Risk factors for coronary artery disease and levels of lipoprotein (a) and fat soluble antioxidant vitamins in Asian Indians of USA. Indian Heart J 50:285-291, 1998
19. Polidori et al. Plasma levels of lipophilic antioxidants in very old patients with type 2 diabetes. Diabetes Metab Res Rev 16:15-19, 2000
20. Upritchard et al. Effects of supplementation with tomato juice, vitamin E, and vitamin C on LDL oxidation and products of inflammatory activity in type 2 diabetes. Diabetes Care 23:733-738, 2000
21. Chuang et al. Risk factors for coronary artery disease and levels of lipoprotein (a) and fat soluble antioxidant vitamins in Asian Indians of USA. Indian Heart J 50:285-291, 1998
22. Steinberg D., Parthasarathy S., Care T.E., Khoo J.C., Witztum J.L. Beyond cholesterol: Modifications of low-density lipoprotein that increases its atherogenicity. N Engl J Med 1989: 320:915-924.
23. Parthasarathy S. Mechanisms by which dietary antioxidants may prevent cardiovascular diseases. J Medicinal Food 1998; 1:45-51.
24. Street D.A., Comstock G.W., Salkeld R.M., Schuep W., Klag M.J. Serum antioxidants and myocardial infarction. Are levels of carotenoids and alpha-tocopherol risk factors for myocardial infarction? Circulation 1994; 90:1154-1161.
25. Kristenson M., Zieden B., Kucinaskiene Z., Elinder L.S., Bergdahl B., Elwing B., Abaravicius A., Razinkoviene L., Calkauskas H., Olsson A. Antioxidant State and Mortality from Coronary Heart Disease in Lithuanian and Swedish Men: Concomitant Cross Sectional Study of Men Aged 50. BMJ 1997; 314:629-633.
26. Kohlmeir L., Kark J.D., Gomez-Garcia E., Martin B.C., Steck S.E., Kardinaal A.F.M., Ringstad J., Thamm M., Masaev V., Riemersma R., Martin-Moreno J.M., Huttunen J.K., Kok F.J. Lycopene and myocardial infarction risk in the EURAMIC study. Am J Epidemiol 1997; 146:618-626.
27. Linseisen J., Hoffmann J., Riedl J., Wolfram G. Effect of a single dose of antioxidant mixture (vitamin E, carotenoids) on the formation of cholesterol oxidation products after ex vivo LDL oxidation in humans. Eur J Med Res 1998; 3:5-12.
28. Agarwal S., Rao A.V. Tomato lycopene and low-density lipoprotein oxidation: a human dietary intervention study. Lipids 1998; 33:981-984.