Breast cancer and dietary and plasma concentrations of carotenoids and vitamin A

A case-control study of breast cancer was conducted in Buffalo. Participants completed a food frequency questionnaire and donated a fasting blood sample before definitive workup for breast masses. Dietary and plasma concentrations of carotenoids and retinol for 83 women found to have breast cancer were compared with those of 113 women found to be free of breast cancer (control subjects). There were no case-control differences in dietary estimates of vitamin A intake or in plasma alpha-carotene and lycopene. However, subjects with breast cancer had lower concentrations of plasma beta-carotene than did control subjects (P = 0.02). There was no overall association between plasma retinol and breast cancer but a positive relationship was observed between retinol and breast cancer in the subgroup with low beta-carotene values. These results suggest that low plasma beta-carotene is associated with increased risk of breast cancer. Other studies will need to determine whether low carotene concentrations are a subtle effect of the disease or might be causally related to breast cancer.     

Optimal nutrition: vitamin A and the carotenoids.

There are two major dietary sources of vitamin A: easily absorbed retinyl palmitate in foods of animal origin, and poorly bioavailable carotenoids from plant foods. Plasma retinol is tightly controlled, probably by regulation of retinol-binding protein (RBP) formation in the liver, and only hormonal factors (e.g. oral contraceptives) and infection will alter the homeostasis. Delivery of retinol to the tissues is facilitated by the RBP-retinol complex; however, there is evidence that this mechanism can be bypassed when very high doses of vitamin A are given. Some retinyl ester may be released to tissues from chylomicrons when the latter bind to tissue lipoprotein receptors during their passage from the gut to the liver following a meal. High-dose vitamin A therapy is a means of rapidly improving vitamin A status in persons with sub-optimal vitamin A nutrition but there are dangers of toxic symptoms (e.g. teratogenicity) from excess vitamin A usage. Evidence is presented to suggest that the plasma retinol: RBP may be a guide to optimal vitamin A status, since values less than one frequently occur in less-developed countries and during infection. In contrast to plasma retinol, plasma carotenoids reflect the dietary intake of plant foods. However, absorption is limited by poor bioavailability and a saturable uptake mechanism in competition with other phytochemicals. Recent work on bioavailability suggests that the calculation of plant food vitamin A activity should be re-examined. Illness has little influence on plasma levels except by suppressing appetite. Carotenoids are generally regarded as non-toxic yet intervention studies with beta-carotene in smokers have been associated with increased lung cancer and heart disease. Some carotenoids are important as vitamin A precursors, but the physiological importance of their antioxidant properties is not known and consequently the amount needed for optimal nutrition is uncertain.     

Provitamin A function of carotenoids: the conversion of beta-carotene into vitamin A

Two pathways have been suggested for the conversion of carotenoids to vitamin A in mammals, central cleavage and excentric cleavage. An enzyme, beta-carotenoid-15,15'-dioxygenase (EC 1.13.11.21), has been partly purified from the intestines of several species and has been identified in several other organs and species. The enzyme, which converts beta-carotene into two molecules of retinal in good yield, requires molecular oxygen and is inhibited by sulfhydryl-binding and iron-binding reagents. Most provitamin A carotenoids, including the beta-apo-carotenals, are cleaved to retinal by this enzyme. Its maximal activity in the rabbit is approximately 200 times that required to meet nutritional needs but is less than 50% of that expected to produce signs of vitamin A toxicity. Excentric cleavage unquestionably occurs in plants and some microorganisms and might occur in mammals. Thus far, however, carotenoid dioxygenase with excentric bond specificity has been identified in mammals, the yield of beta-apo-carotenals from beta-carotene in vivo and in vitro is very low, and beta-apo-carotenals are formed nonbiologically from beta-carotene. To remain viable as an alternative pathway of vitamin A formation from carotenoids in mammals, the excentric cleavage hypothesis clearly requires unambiguous direct supporting evidence.     

Nutrigenomics, vitamin D and cancer prevention

Although there is growing epidemiological, preclinical and clinical evidence suggesting that low vitamin D intake, exposure and/or status is associated with an increased risk of various types of cancer, the optimum amount needed remains controversial. Furthermore, there is evidence that a U- or J-shaped response curve exist between 25(OH)D and certain cancers. Increasing information about the impact of genetic variation, especially polymorphisms that influence absorption, transport, metabolism and associated molecular targets, should help clarify inconsistencies in the data regarding vitamin D's effect on cancer risk. Rather than focusing on the main effects of a few variants of these genes alone, future studies need to consider gene-nutrient or environmental interactions. Nutrigenomics should clarify who might benefit and be placed at risk because of vitamin D exposure.     

Immunological role of vitamin A and its related substances in prevention of cancer

The antitumor effects of vitamin A and its related substances, vitamin E, vitamin K, ß‐carotene, ubiquinone, phytol, and sgualene, were examined using a syngeneic murine tumor system. Intraperitoneal administration of these substances (0.19 μmol/mouse/day) slightly suppressed the growth of Meth A fibrosarcoma cells inoculated s.c. into Balb/c mice. Administration of all test substances except ß‐carotene significantly suppressed the growth of Meth A fibrosarcoma cells rechallenged in Meth A‐primed mice on day 10, but did not influence the growth of Meth 1 fibrosarcoma cells (another syngeneic tumor of Balb/c origin) rechallenged in Meth A‐primed mice on day 10. The growth of Meth A tumor cells was suppressed when Meth A was inoculated together with lymph node cells obtained from the Meth A‐primed Balb/c mice treated with vitamin A, vitamin E, phytol, or squalene. Our findings suggest that certain constituents in green‐yellow vegetables may contribute to the prevention of cancer by augmenting an immunological response against tumor cells in the early stages of carcinogenesis.     

The role of vitamin D in cancer prevention

Vitamin D status differs by latitude and race, with residents of the northeastern United States and individuals with more skin pigmentation being at increased risk of deficiency. A PubMed database search yielded 63 observational studies of vitamin D status in relation to cancer risk, including 30 of colon, 13 of breast, 26 of prostate, and 7 of ovarian cancer, and several that assessed the association of vitamin D receptor genotype with cancer risk.The majority of studies found a protective relationship between sufficient vitamin D status and lower risk of cancer. The evidence suggests that efforts to improve vitamin D status, for example by vitamin D supplementation, could reduce cancer incidence and mortality at low cost, with few or no adverse effects.     

Bioconversion of plant carotenoids to vitamin A in Filipino school-aged children varies inversely with vitamin A status

BACKGROUND: It is important to understand the factors affecting strategies to improve the vitamin A status of populations. We reported previously that a 3-d deuterated-retinol-dilution (DRD) procedure might be used to indicate total body stores of vitamin A. OBJECTIVE: We studied the ability of 3-d DRD to detect changes in the body pool size of vitamin A and the effect of vitamin A status on the bioconversion of plant carotenoids to vitamin A. DESIGN: Two separate, unrelated studies were conducted in 7-13-y-old children with poor or marginal serum retinol concentrations (0.32-0.93 micromol/L) by feeding them controlled diets daily for 5 d/wk for 12 wk, after treatment with an anthelmintic drug. In school 1 (n = 27), lunch and 2 snacks that were provided at school contained 2258 retinol equivalents/d (mostly from orange fruit and vegetables) and 5.3 MJ/d from 33 g fat, 37 g protein, and 209 g carbohydrates; in school 2 (n = 25), 2 snacks provided 2.5 MJ/d from 9.4 g fat, 9.6 g protein, and 119 g carbohydrates, but no carotenes. RESULTS: In school 1, mean serum beta-carotene increased from 0.12 to 0.62 micromol/L (P = 0.0001) and serum retinol increased from 0.68 to 1. 06 micromol/L (P = 0.0001). In school 2, serum beta-carotene increased from 0.06 to 0.11 micromol/L (P = 0.0001) and serum retinol increased from 0.66 to 0.86 micromol/L (P = 0.0001). In school 1, but not school 2, improvement in serum retinol varied inversely with baseline retinol (r = -0.38, P = 0.048). In both schools, 3-d DRD showed reductions in the ratio of serum deuterated to nondeuterated retinol (D:H retinol) postintervention, denoting improvements in vitamin A status; the higher D:H retinol (ie, the poorer the status) at baseline, the greater the reduction in D:H retinol postintervention (school 1: r = -0.99, P = 0.0001; school 2: r = -0.89, P = 0.0001). CONCLUSIONS: Three-day DRD can detect changes in the body pool size of vitamin A, although a predictive equation to quantitate total body stores of vitamin A with the use of 3-d data needs to be developed. Bioconversion of plant carotenoids to vitamin A varies inversely with vitamin A status; improvement in status after dietary interventions is strongly influenced by total body stores of vitamin A and is influenced little or not at all by serum retinol.     

补充富含类胡萝卜素的蔬菜对儿童维生素A营养状况的影响

于１９９６年９月～１２月在山东省泰安市某幼儿园的两个班使用富含类胡萝卜素的蔬菜进行了干预试验。所选择两个班４１名儿童的平均年龄为５．３～６．５岁,其中３９％的儿童血清视黄醇低于０．３０ｍｇ／Ｌ,处于边缘缺乏状态。分为２个组：对照组,不改变日常膳食,平均每日每人摄入１９３ｇ浅色蔬菜（圆白菜、大白菜、土豆、黄瓜、菜花和白萝卜等）和５６ｇ黄绿色蔬菜（菠菜、空心菜、胡萝卜和红心红薯等）;试验组,平均每日每人摄入２３８ｇ黄绿色蔬菜和３４ｇ浅色蔬菜。结果表明膳食中黄绿色蔬菜对改善学龄前儿童的维生素Ａ营养有重要影响,且安全、廉价。     

Clinical trials of vitamin and mineral supplements for cancer prevention

Approximately 20-30% of Americans consume multivitamin supplements daily, indicating high public interest in the prevention of cancer and other chronic diseases through a nutrition-based approach. Although several bioactive food components, including vitamins and minerals, have been investigated for their ability to affect cancer risk, few large, randomized, placebo-controlled clinical trials of multivitamins with cancer as the primary endpoint have been performed. The results of most large-scale trials of multivitamin supplements (combinations of > or = 2 vitamins and minerals) to prevent cancer have been mixed. The Linxian General Population and Dysplasia trials found a decreased risk of cancer, particularly stomach cancer, for participants taking a multivitamin supplement, but this was in a borderline-deficient population in China. Two trials, the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study and the beta-Carotene and Retinol Efficacy Trial, found an increased risk of lung cancer among male cigarette smokers or asbestos-exposed persons taking beta-carotene-a surprising result, considering that most epidemiologic studies have suggested that consumption of fruit and vegetables appears to lower cancer risk. To clarify the effects of multivitamin supplements, several large randomized clinical trials are underway, including the Physicians' Health Study II, the Selenium and Vitamin E Cancer Prevention Trial, and a European study, Supplémentation en Vitamines et Minéraux Antioxydants (SU.VI. MAX). Because epidemiologic studies generally evaluate foods rather than specific bioactive food components, a systematic approach to determining how combinations of vitamins and minerals may interact to ameliorate cancer risk is necessary to further our understanding of the potential benefits and risks of supplement use.     

Dietary sources of vitamin C, vitamin E and specific carotenoids in Spain

A cross-sectional study was conducted within the Spanish cohort of the European Prospective Investigation in Cancer and Nutrition to assess the principal food sources of vitamin C, vitamin E, alpha-carotene, beta-carotene, lycopene, lutein, beta-cryptoxanthin and zeaxanthin in an adult Spanish population. The study included 41446 healthy volunteers (25812 women and 15634 men), aged 29-69 years, from three Spanish regions in the north (Asturias, Navarra and Guipúzcoa) and two in the south (Murcia and Granada). Usual food intake was estimated by personal interview through a computerized version of a dietary history questionnaire. Foods that provided at least two-thirds of the studied nutrients were: fruits (mainly oranges) (51 %) and fruiting vegetables (mainly tomato and sweet pepper) (20 %) for vitamin C; vegetable oils (sunflower and olive) (40 %), non-citrus fruits (10 %), and nuts and seeds (8 %) for vitamin E; root vegetables (carrots) (82 %) for alpha-carotene; green leafy (28 %), root (24 %) and fruiting vegetables (22 %) for beta-carotene; fruiting vegetables (fresh tomato) (72 %) for lycopene; green leafy vegetables (64 %) for lutein; citrus fruits (68 %) for beta-cryptoxanthin; citrus fruits (43 %) and green leafy vegetables (20 %) for zeaxanthin. In conclusion, the main food sources of nutrients with redox properties have been identified in a Mediterranean country. This could provide an insight into the interpretation of epidemiological studies investigating the role of diet in health and disease.     

Retinol equivalence of carotenoids can be evaluated by hepatic vitamin A content

The present study demonstrates a new method to evaluate the bioavailability of carotenoids based on the calculation of the hepatic retinol contents. Weaning male rats of Wistar strain were divided into 5 groups. Each group respectively received retinol acetate (2000-10,000 IU per kg diet), alpha-carotene (2400-6000 micrograms per kg diet), beta-carotene (2400-6000 micrograms per kg diet), mixture of alpha- and beta-carotenes in the ratio of 1:2 (2400 and 4800 micrograms per kg dit), and palm-carotene oil (2400-6000 micrograms per kg diet). The derived retinol equivalences of each carotenoid calculated according to the hepatic retinol contents were almost constant regardless of the volume of respective intake (alpha-carotene: 1.25 micrograms per IU; beta-carotene: 0.59 microgram per IU; mixture of alpha- and beta-carotene in the ratio of 1:2: 0.96 microgram per IU; Palm-carotene oil: 1.23 micrograms per IU). The results suggest that the hepatic retinol contents can be used as a new measure to evaluate the vitamin A bioavailability of carotenoids.     

Prostate cancer and dietary carotenoids

This population-based case-control study investigated associations between prostate cancer risk and dietary intake of the carotenoids beta-carotene and lycopene and their major plant food sources, including carrots, green leafy vegetables, and tomato-based foods. The study was carried out in Auckland, New Zealand, during 1996-1997 and recruited 317 prostate cancer cases and 480 controls. The authors found that dietary intake of beta-carotene and its main vegetable sources was largely unassociated with prostate cancer risk, whereas intake of lycopene and tomato-based foods was weakly associated with a reduced risk. These results suggest that in contrast to the findings regarding many types of cancers, vegetables rich in beta-carotene are not protective against prostate cancer. However, lycopene from tomato-based foods was found to be associated with a small reduction in risk.