Natural Carotenoids

A. Cancer Prevention

• 1. Effect of retinoic acid and palm oil concentrate on oestrone sulphatase and oestradiol-17beta hydroxysteroid dehydrogenase activities in MCF-7 and MDA-MB-231 breast cancer cell lines

  Nesaretnam, K. et al. (2000). Effect of retinoic acid and palm oil carotenoids on oestrone sulphatase and oestradiol-17beta hydroxysteroid dehydrogenase activities in MCF-7 and MDA-MB-231 breast cancer cell lines.International Journal of Cancer. 88(1):135-8.

  Oestrogen is important in the development of breast cancer. Oestrogen receptor positive breast cancers are associated with a better prognosis than oestrogen-receptor negative breast cancers since they are more responsive to hormonal treatment. Oestrone sulphate acts as a huge reservoir for oestrogens in the breast. It is converted to the potent oestrogen, oestradiol (E(2)) by the enzymes oestrone sulphatase and oestradiol-17beta hydroxysteroid dehydrogenase (E(2)DH). Retinoic acid and carotenoids have been shown to have chemopreventive activity against some cancers. The aim of our study was to determine and compare the effects of retinoic acid and palm oil carotenoids on growth of and oestrone sulphatase and E(2)DH activities in the oestrogen receptor positive, MCF-7 and oestrogen receptor negative, MDA-MB-231 breast cancer cell lines. Retinoic acid and carotenoids inhibited MCF-7 cell growth but had no effect on MDA-MB-231 cell growth. Both retinoic acid and carotenoids stimulated oestrone sulphatase activity in the MCF-7 cell line. E(1) to E(2) conversion was inhibited by 10(-7) M carotenoids but was stimulated at 10(-6) M in the MCF-7 cell line. Retinoic acid had no effect on E(1) to E(2) conversion at 10(-7) M but stimulated E(1) to E(2) conversion at 10(-6) M. Retinoic acid and carotenoids had no effect on E(2) to E(1) conversion in the MCF-7 cell line. Retinoic acid stimulated E(1) to E(2) conversion in the MDA-MB-231 cell line but had no effect on oestrone sulphatase activity or E(2) to E(1) conversion in this cell line. Both oestrone sulphatase and E(2)DH activity were not affected by carotenoids in the MDA-MB-231 cell line. In conclusion, retinoic acid and carotenoids may prevent the development of hormone-dependent breast cancers since they inhibit the growth of the MCF-7 cell line.

• 2. Effect of a carotene concentrate on the growth of human breast cancer cells and pS2 gene expression.

  Nesaretnam, K. et al. (2000). Effect of a carotene concentrate on the growth of human breast cancer cells and pS2 gene expression. Toxicology. 151(1-3):117-26.

  Breast cancer is the most common cancer in women worldwide. The growth of breast cancer cells is either hormone-dependent or hormone-independent. Both types are represented in vitro by the estrogen-receptor positive (ER+) MCF-7 and the estrogen-receptor negative (ER-) MDA-MB-231 cell lines, respectively. The pS2 gene is an estrogen-regulated gene and serves as a marker for the ER+ tumours. Carotenoids are pigments with anti-cancer properties besides having pro-vitamin A, antioxidant and free-radical quenching effects. This study was designed firstly, to compare the effect of palm oil carotene concentrate with retinoic acid on the growth of the ER+ MCF-7 and the ER- MDA-MB-231 cells; and secondly to evaluate the effect of the palm oil carotene concentrate on the regulation of pS2 mRNA. The growth experiments were performed with monolayer cells seeded in phenol red free RPMI 1640 culture media and subsequently treated with varying concentrations of either retinoic acid or palm oil carotenoids. The cell numbers were determined at the start of each experiment and then at successive time intervals. The results showed that the palm oil carotene concentrate caused dose-dependent inhibition of estradiol-stimulated growth of MCF-7 cells but did not affect the proliferation of MDA-MB-231 cells. Retinoic acid caused similar, albeit more potent effects, as significant inhibition was observed at lower concentrations than the palm oil carotenoids. In the pS2 gene expression experiment, cell monolayers were treated with the carotene concentrate (10(-6) M), either with or without supplemented estradiol (10(-8) M), and subsequently the RNA was extracted. Northern blotting was performed and the regulation of pS2 mRNA determined using a 32P-labelled pS2 cDNA probe. The results showed that the palm oil carotene concentrate did not affect the expression of pS2 mRNA and are therefore independent of the estrogen-regulated pathway.

• 3. Cancer prevention by natural carotenoids

  Nishino, H. et al.(2000). Cancer prevention by natural carotenoids. Biofactors. 13(1-4):89-94.
  

  Various natural carotenoids were proven to have anticarcinogenic activity. Epidemiological investigations have shown that cancer risk is inversely related to the consumption of green and yellow vegetables and fruits. Since beta-carotene is present in abundance in these vegetables and fruits, it has been investigated extensively as possible cancer preventive agent. However, various carotenoids which co-exist with beta-carotene in vegetables and fruits also have anti-carcinogenic activity. And some of them, such as alpha-carotene, showed higher potency than beta-carotene to suppress experimental carcinogenesis. Thus, we have carried out more extensive studies on cancer preventive activities of natural carotenoids in foods; i.e., lutein, lycopene, zeaxanthin and beta-cryptoxanthin. Analysis of the action mechanism of these natural carotenoids is now in progress, and some interesting results have already obtained; for example, beta-cryptoxanthin was suggested to stimulate the expression of RB gene, an anti-oncogene, and p73 gene, which is known as one of the p53-related genes. Based on these results, multi-carotenoids (mixture of natural carotenoids) seems to be of interest to evaluate its usefulness for practice in human cancer prevention.

• 4. Dietary carotenoids and risk of gastric cancer: A case-control study in Uruguay

  Boffetta, P. et al. (2000). Dietary carotenoids and risk of gastric cancer: a case-control study in Uruguay. European Journal of Cancer Prevention. 9(5):329-34

  In the period 1997-1999, 120 incident and histologically verified cases of stomach cancer were frequency matched on age, sex, residence and urban/rural status with 360 controls in order to study the role of diet in gastric cancer in Uruguay. Our attention was focused on the role of carotenoids in gastric carcinogenesis, after controlling for major confounders. According to the results, vitamin A, alpha-carotene and lycopene were associated with strong inverse relationships with stomach cancer (OR of stomach cancer for high alpha-carotene intake 0.34, 95% CI 0.17-0.65). Joint exposure to high intakes of alpha-carotene and vitamin C intakes were associated with a strong reduction in risk (OR 0.11, 95% CI 0.03-0.36). It was also suggested that high lycopene intake explained most of the reduction in risk of gastric cancer associated with vegetable intake, whereas no such effect was observed for fruit intake.

• 5. Intake of specific carotenoids and risk of lung cancer in 2 prospective US cohorts

  Giovannucci, E. et al.(2002). Intake of specific carotenoids and risk of lung cancer in 2 prospective US cohorts”, Am . J. Clin .Nutr. 72(4):990-7.

  During a 10-y follow-up period, 275 new cases of lung cancer were diagnosed in 46924 men; during a 12-y follow-up period, 519 new cases were diagnosed in 77283 women. Carotenoid intakes were derived from the reported consumption of fruit and vegetables on food-frequency questionnaires administered at baseline and during follow-up. The data were analyzed separately for each cohort and the results were pooled to compute overall relative risks (RRs). In the pooled analyses, α-carotene and lycopene intakes were significantly associated with a lower risk of lung cancer; the association with β-carotene, lutein, and β-cryptoxanthin intakes were inverse but not significant. Lung cancer risk was significantly lower in subjects who consumed a diet high in a variety of carotenoids (RR: 0.68; 95% CI: 0.49, 0.94 for highest compared with lowest total carotenoid score category). Inverse associations were strongest after a 4–8-y lag between dietary assessment and date of diagnosis. In subjects who never smoked, a 63% lower incidence of lung cancer was observed for the top compared with the bottom quintile of α-carotene intake (RR: 0.37; 95% CI: 0.18, 0.77).

• 6. Serum micronutrients and upper aerodigestive cancer

  Craft, N.E. et al. (1997). Serum micronutrients and upper aerodigestive cancer”, Cancer Epidemiol. Biomakers Prev. 6(6):407-12.

  Numerous dietary studies have found that vegetables and fruits protect against upper aerodigestive tract cancer. To evaluate the role of beta-carotene and other specific carotenoids, a nested case-control study using prediagnostic serum was conducted among 6832 American men of Japanese ancestry examined from 1971 to 1975. During a surveillance period of 20 years, the study identified 28 esophageal, 23 laryngeal, and 16 oral-pharyngeal cancer cases in this cohort. The 69 cases were matched to 138 controls. A liquid chromatography technique, designed to optimize recovery and separation of the individual carotenoids, was used to measure serum levels of lutein, zeaxanthin, beta-cryptoxanthin, lycopene, alpha-carotene, beta-carotene, retinol, retinyl palmitate, and alpha-, delta-, and gamma-tocopherol. With adjustment for cigarette smoking and alcohol intake, we found that alpha-carotene, beta-carotene, beta-cryptoxanthin, total carotenoids and gamma-tocopherol levels were significantly lower in the 69 upper aerodigestive tract cancer patients than in their controls. Trends in risk by tertile of serum level were significant for these five micronutrients. These significant trends persisted in cases diagnosed 10 or more years after phlebotomy for the three individual carotenoids and total carotenoid measurements. The odds ratios for the highest tertile were 0.19 (95% confidence interval, 0.05-0.75) for alpha-carotene, 0.10 (0.02-0.46) for beta-carotene, 0.25 (0.06-1.04) for beta-cryptoxanthin, and 0.22 (0.05-0.88) for total carotenoids. When the cases were separated into esophageal, laryngeal, and oral-pharyngeal cancer, both alpha-carotene and beta-carotene were consistently and strongly associated with reduced risk at each site. The findings suggest that alpha-carotene and other carotenoids, as well as beta-carotene, may be involved in the etiology of upper aerodigestive tract cancer.

• 7. Cancer prevention by natural carotenoids

  Nishino, H. et al (2000). Cancer prevention by natural carotenoids. Biofactor. 13(1-4):89-94.

  Epidemiological investigations have shown that cancer risk is inversely related to the consumption of green and yellow vegetables and fruits. Since beta-carotene is present in abundance in these vegetables and fruits, it has been investigated extensively as a possible cancer preventive agent. However, various carotenoids that coexist with beta-carotene in vegetables and fruits also have anticarcinogenic activity. Some of them, such as alpha-carotene, showed higher potency than beta-carotene in suppressing experimental carcinogenesis. Thus, we have carried out more extensive studies on cancer-preventive activities of natural carotenoids, which found that lycopene and lutein had potent anticarcinogenic activity. In the present study, the cancer-preventive activity of phytoene was also confirmed biotechnologically when mammalian cells producing phytoene were resistant to H-ras-induced cell transformation. Further studies on various natural carotenoids besides beta-carotene should be continued to obtain more information about the potential of natural carotenoids in the field of cancer prevention.

• 8. Potent preventive action of alpha-carotene against carcinogenesis: Spontaneous liver carcinogenesis and promoting stage of lung and skin carcinogenesis in mice are suppressed more effectively by alpha-carotene than beta-carotene

  Murakoshi, M. et al.(1992). Potent preventive action of alpha-carotene against carcinogenesis: Spontaneous liver carcinogenesis and promoting stage of lung and skin carcinogenesis in mice are suppressed more effectively by alpha-carotene than beta-carotene. Cancer Research. 52(23):6583-7.

  Although beta-carotene has been considered to be a key cancer preventive agent in green and yellow vegetables, other types of carotenoids, such as alpha-carotene, may also contribute to anticarcinogenic action, since these carotenoids usually coexist with beta-carotene and are detectable in human blood and tissues. In this study, we compared the inhibitory effect of natural alpha-carotene, obtained from palm oil, with that of beta-carotene on spontaneous liver carcinogenesis in C3H/He male mice. The mean number of hepatomas per mouse was significantly decreased by alpha-carotene supplementation (per os administration in drinking water at a concentration of 0.05%, ad libitum) as compared with that in the control group (P < 0.001, Student's t test). On the other hand, beta-carotene, at the same dose as alpha-carotene, did not show any such significant difference from the control group. Furthermore, we also compared the antitumor-promoting activity of alpha-carotene with that of beta-carotene against two-stage mouse lung carcinogenesis (initiator, 4-nitroquinoline 1-oxide; promoter, glycerol). alpha-Carotene, but not beta-carotene, reduced the number of lung tumors per mouse to about 30% of that in the control group (P < 0.001, Student's t test). The higher potency of the antitumor-promoting action of alpha-carotene compared to beta-carotene was confirmed in other experimental systems; e.g., alpha-carotene was also found to have a stronger effect than beta-carotene in suppressing the promoting activity of 12-O-tetradecanoylphorbol-13-acetate on skin carcinogenesis in 7,12-dimethylbenz[a]anthracene-initiated mice. These results suggest that not only beta-carotene, but also other types of carotenoids, such as alpha-carotene, may play an important role in cancer prevention.

• 9. Anticarcinogenesis activity of natural carotenes

  Imanishi, J. et al. (1989). Anticarcinogenesis activity of natural carotenes. C.R.Seances Soc. Biol. Fil.183(1):85-9.

  Natural carotene sample obtained from palm oil was proved to suppress the promoting stage of two-stage carcinogenesis of mouse skin, and also inhibit the proliferation of human malignant tumor cells, such as neuroblastoma GOTO cells, stomach cancer HGC-27 cells, and pancreatic cancer PANC-I cells. Among the major constituents of palm carotene, alpha-carotene showed stronger anti-proliferative effect than beta-carotene. The present results indicate that further investigation for not only beta-carotene but also other kinds of natural carotenes, such as alpha-carotene, should be carried out.

• 10. Selected micronutrients and colectal cancer : A case control study from Canton of Vaud, Switzerland

  Levi, F. et al. (2000). Selected micronutrients and colectal cancer : A case control study from Canton of Vaud, Switzerland. Eur. J. of Cancer. 36(16):2115-9.

  The association between dietary intake of various micronutrients and colorectal cancer risk was analysed using data from a case-control study conducted between 1992 and 1997 in the Swiss Canton of Vaud. Cases were 223 subjects (142 (64%) males, 81 (36%) females; median age 63 years) with incident, histologically confirmed colon (n=119; 53%) or rectal (n=104; 47%) cancer, and controls were 491 subjects (211 (43%) males, 280 (57%) females; median age 58 years; range 27-74) admitted to the same university hospital for a wide spectrum of acute non-neoplastic conditions, unrelated to long-term modifications of diet. Dietary habits were investigated using a validated food frequency questionnaire (FFQ). Odds ratios (OR) were obtained after allowance for age, sex, education, smoking, alcohol, body mass index, physical activity, and total energy and fibre intake. No significant association was observed for calcium, retinol, folate, vitamin D or E. The risk of colorectal cancer was directly associated with measures of iron intake (OR=2.43 for the highest tertile, 95% confidence interval (CI): 1.2-5.1) and inversely associated with vitamin C (OR=0.45; 95% CI: 0.3-0.8), and non-significantly with total carotenoids (OR=0.66, 95% CI: 0.4-1.1). Among various individual carotenoids considered, inverse associations were observed for alpha-carotene, beta-carotene and lutein/zeaxanthin. These findings were consistent across the strata of gender and age, and support the hypothesis that selected micronutrients have a favourable effect on colorectal carcinogenesis.

• 11. Inhibitory effects of alpha-carotene an proliferation of the human neuroblastoma cell line GOTO

  Murakoshi, M. et al. (1989). Inhibitory effects of alpha-carotene an proliferation of the human neuroblastoma cell line GOTO. Journal of the national Cancer Institute. 81(21):1649-52.

  Alpha-Carotene inhibited the proliferation of the human neuroblastoma cell line GOTO in a dose- and time-dependent manner. In addition, it was about 10 times more inhibitory than beta-carotene. Northern blot analysis indicated that alpha-carotene caused maximum suppression of the level of the N-myc messenger RNA of GOTO cells. This suppression occurred within 18 hours of alpha-carotene treatment, after which the level of the N-myc messenger RNA gradually recovered to the basal level. Analysis by flow cytometry indicated that when GOTO cells were exposed to alpha-carotene, they were arrested in the G0-G1 phase of their cell cycle. However, as the level of the N-myc messenger RNA was recovering, these cells resumed normal cycling. These results indicate that the reduction in the level of the N-myc messenger RNA caused by alpha-carotene is closely linked with G0-G1 arrest.

• 12. Mutagenicity studies with palm fruit carotene

  Nakamura, T. et al. (1995). Mutagenicity studies with palm fruit carotene. Journal Toxicological Science. 20(5):619-27.

  The mutagenicity of palm fruit carotene was examined using the reverse mutation test with bacteria, the chromosomal aberration test with mammalian cells and the micronucleus test in mice. The carotene induced neither reverse mutation in Salmonella typhimurium TA98, TA1537, TA100, TA1535 and in Escherichia coli WP2uvrA, nor structural and numerical (polyploidy) chromosomal aberrations in the Chinese hamster fibroblast cell line (CHL). In addition, no increase in micronucleated polychromatic erythrocytes was elicited in the micronucleus test in CD-1(ICR) male mice. It is concluded that palm fruit carotene had no mutagenic activity in these in vitro and in vivo tests.

• 13. Serum carotenoids and vitamins and risk of cervical dysplasia from a case control study in Japan

  Kawana, T. et al. (1999). Serum carotenoids and vitamins and risk of cervical dysplasia from a case control study in Japan. Br. J . Cancer. 81(7): 1234–1237.

  The relationships between risk of cervical dysplasia and dietary and serum carotenoids and vitamins were investigated in a case–control study. Cases were 156 women who attended Papanicolaou test screening in nine institutes affiliated with Japan Study Group of Human Papillomavirus (HPV) and Cervical Cancer and had cervical dysplasia newly histologically confirmed. Age-matched controls were selected from women with normal cervical cytology attending the same clinic. Blood sample and cervical exfoliated cells were obtained for measuring serum retinol, α-carotene, β-carotene, zeaxanthin/lutein, cryptoxanthin, lycopene and α-tocopherol and for HPV detection. Higher serum level of α-carotene was significantly associated with decreased risk of cervical dysplasia after controlling for HPV infection and smoking status (odds ratio (OR) = 0.16, 95% confidence interval (CI) 0.04–0.62 for the highest as compared with the lowest tertile). Decreased risk for the highest tertile of serum lycopene (OR = 0.28) was marginally significant. Decreased risks observed for the highest tertiles of β-carotene (OR = 0.65) and zeaxanthin/lutein (OR = 0.53), were not statistically significant. © 1999 Cancer Research Campaign

• 14. Carotenoids, antioxidants and ovarian cancer risk in pre- and postmenopausal women

  Cramer, DW. et al. (2001). Carotenoids, antioxidants and ovarian cancer rish in pre- and postmenopausal women. International Journal of Cancer. 94(1):128-34.

  An inverse association between ovarian cancer risk, carotenoids and antioxidant vitamins has been suggested by several epidemiologic studies and 1 experimental trial of a vitamin A analogue. From a population-based study of 549 cases of ovarian cancer and 516 controls, we estimated the consumption of the antioxidant vitamins A, C, D and E and various carotenoids, including alpha- and beta-carotene and lycopene, using a validated dietary questionnaire. Multivariate logistic regression was used to calculate the exposure odds ratios adjusted for established ovarian cancer risk factors. Intakes of carotene, especially alpha-carotene, from food and supplements were significantly and inversely associated with risk for ovarian cancer, predominantly in postmenopausal women. Intake of lycopene was significantly and inversely associated with risk for ovarian cancer, predominantly in premenopausal women. Food items most strongly related to decreased risk for ovarian cancer were raw carrots and tomato sauce. Consumption of fruits, vegetables and food items high in carotene and lycopene may reduce the risk of ovarian cancer.

• 15. Serum carotenoids and breast cancer

  Toniolo, P. et al. (2001). Serum carotenoids and breast cancer. American Journal of Epidemiology. 153(12):1142-7.

  The consumption of vegetables and fruit may protect against many types of cancer, but research evidence is not compelling for breast cancer. Carotenoids are pigments that are present in most plants and have known antioxidant properties. Blood concentrations of carotenoids have been proposed as integrated biochemical markers of vegetable, fruit, and synthetic supplements consumed. In a case-control study (270 cases, 270 controls) nested within a cohort in New York during 1985-1994, the carotenoids lutein, zeaxanthin, beta-cryptoxanthin, lycopene, alpha-carotene, and beta-carotene were measured in archived serum samples using liquid chromatography. There was an evident increase in the risk of breast cancer for decreasing beta-carotene, lutein, alpha-carotene, and beta-cryptoxanthin. The risk of breast cancer approximately doubled among subjects with blood levels of beta-carotene at the lowest quartile, as compared with those at the highest quartile (odds ratio = 2.21; 95% confidence interval (CI): 1.29, 3.79). The risk associated with the other carotenoids was similar, varying between 2.08 (95% CI: 1.11, 3.90) for lutein and 1.68 (95% CI: 0.99, 2.86) for beta-cryptoxanthin. The odds ratio for the lower quartile of total carotenoids was 2.31 (95% CI: 1.35, 3.96). These observations offer evidence that a low intake of carotenoids, through poor diet and/or lack of vitamin supplementation, may be associated with increased risk of breast cancer and may have public health relevance for people with markedly low intakes.

• 16. A study on serum carotenoid levels in breast cancer patients of Indian women in Chenai, India

  Shanta, V. et al. (1999). A study on serum carotenoid levels in breast cancer patients of Indian women in Chenai, India. Journal of Epidermiology. 9(5):306-14.

  Two-hundred and six breast cancer cases were histologically confirmed breast cancer diagnoses at the Cancer Institute in Chennai (Madras), India. One-hundred and fifty hospital controls were patients who had cancer at any site other than breast and gynecological organs, and 61 healthy controls were persons accompanying patients in the Cancer Institute. Serum levels of carotenoids such as beta-carotene, lycopene, cryptoxanthin, and zeaxanthin & lutein were determined by HPLC. Serum levels of total carotenes and total carotenoids including beta-carotene, which reflects food intake of colored vegetables and fruits and has a protective role for certain sites of cancer, were significantly lower among breast cancer cases and hospital controls compared to healthy controls, especially in post-menopausal women. Serum carotenoid levels appeared to change with menopausal status. Serum beta-carotene levels tended to be lower among breast cancer cases than among hospital controls in premenopausal women. Serum xanthophyll levels were significantly lower among breast cancer cases than among healthy controls in post-menopausal women, but not in premenopausal women. Serum levels of retinol and alpha-tocopherol among breast cancer cases were not significantly different from those in post-menopausal healthy controls, but were higher than those in hospital controls. Serum estrone levels were significantly higher among breast cancer cases than among healthy controls, but serum levels of estradiol and estriol were not. In conclusion, Indian women with cancer of breast or of other sites might have low intake of green-yellow vegetables rich in fiber and carotenoids such as beta-carotene and zeaxanthin & lutein.

• 17. Prospective study of carotenoids, tocopherols and retenoid concentrations and the risk of breast cancer

  Sato, R. et al. (2002). Prospective study of carotenoids, tocopherols and retenoid concentrations and the risk of breast cancer. Cancer Epidemiol Biomarkers Prevention.11(5):451-7.

  Previous prospective studies have raised the possibility that the antioxidantproperties of carotenoids and vitamin E (alpha-tocopherol) and the role of vitamin A (retinol) in cellular differentiation may be associated with a reduced risk of subsequent breast cancer. To investigate the association between serum and plasma concentrations of retinol, retinyl palmitate, alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein, lycopene, total-carotenoids, alpha-tocopherol, and gamma-tocopherol with subsequent development of breast cancer, a nested case control study was conducted among female residents of Washington County, Maryland, who had donated blood for a serum bank in 1974 or 1989. Cases (n = 295) and controls (n = 295) were matched on age, race, menopausal status, and date of blood donation, and the analyses were stratified by cohort participation. Median concentrations of beta-carotene, lycopene, and total carotene were significantly lower in cases compared with controls in the 1974 cohort (13.1, 12.5, and 7.9% difference; P = 0.01, 0.04, and 0.04, respectively) and for lutein in the 1989 cohort (6.7% difference; P = 0.02). The risk of developing breast cancer in the highest fifth was approximately half of that of women in the lowest fifth for beta-carotene [odds ratio (OR) = 0.41; 95% confidence interval (CI) 0.22-0.79; P trend = 0.007], lycopene (OR = 0.55; 95% CI 0.29-1.06; P trend = 0.04), and total carotene (OR = 0.55; 95% CI 0.29-1.03; P trend = 0.02) in the 1974 cohort. There was generally a protective association for other micronutrients in both cohorts, although none reached statistical significance. The results suggest that carotenoids may protect against the development of breast cancer.

• 18. Plasma antioxidant vitamins and carotenoids in five Japanese populations with varied mortality from gastric cancer

  Tsubono, Y. et al.(1999). Plasma antioxidant vitamins and carotenoids in five Japanese populations with varied mortality from gastric cancer. Nutrition and Cancer. 34(1):56-61.

  To examine the geographic associations between plasma antioxidant levels and gastric cancer risk, we conducted an ecological study in five regions of Japan representing the threefold variation in the disease mortality within the country. Subjects were 634 men aged 40-49 years sampled randomly from the five regions with 72% response rates. Plasma concentrations of five carotenoids (beta-carotene, alpha-carotene, lycopene, lutein, and zeaxanthin), alpha-tocopherol, and ascorbic acid were measured, and the mean levels were correlated with age-adjusted mortality rates from gastric cancer. beta-Carotene and alpha-tocopherol were inversely correlated with gastric cancer rates (r = -0.31 and -0.89, respectively). alpha-Carotene and lycopene showed stronger inverse correlation than did beta-carotene (r = -0.67 and -0.56, respectively), but these relations disappeared after the exclusion of one outlying region in Okinawa with the lowest mortality. In contrast, ascorbic acid revealed a negative correlation with the exclusion of this outlier (r = -0.61). Lutein and zeaxanthin were not inversely associated with risk. The results suggest that plasma levels of beta-carotene and alpha-tocopherol, and possibly alpha-carotene, lycopene, and ascorbic acid, may partly account for the regional difference in gastric cancer mortality in Japan.

• 19. Inhibitory effects of natural carotenoids, alpha carotene, beta carotene, lycopene and lutein, on colonic aberrant crypt foci formation in rat

  Narisawa, T. et al. (1996). Inhibitory effects of natural carotenoids, alpha carotene, beta carotene, lycopene and lutein, on colonic aberrant crypt foci formation in rat. Cancer letters. 107(1):137-42.

  Inhibitory effect of four carotenoids prevalent in human blood and tissues against the formation of colonic aberrant crypt foci was examined in Sprague-Dawley rats. They received three intrarectal doses of N-methylnitrosourea in weak 1, and a daily gavage of de-escalated doses of carotenoids during weeks 2 and 5. Lycopene, lutein, alpha-carotene and palm carotenes (a mixture of alpha-carotene, beta-carotene and lycopene) inhibited the development of aberrant crypt foci quantitated at week 6, but beta-carotene did not. The results suggested that lycopene and lutein in small doses may potentially prevent colon carcinogenesis.