Serum lycopene and the risk of cancer: the Kuopio Ischaemic Heart Disease Risk Factor (KIHD) study.

PURPOSE: Lycopene is thought to decrease the risk of cancers, although previous epidemiologic studies have produced inconsistent results. The aim of the present study was to evaluate the protective effect of lycopene against the risk of cancer. METHODS: The study population consisted of 997 middle-aged Finnish men in the Kuopio Ischaemic Heart Disease Risk Factor (KIHD) cohort. During the mean follow-up time of 12.6 years, a total of 141 cancer cases appeared, of which 55 were prostate cancers. The association between the serum concentrations of lycopene and the risk of cancer was studied using the Cox proportional hazard models. RESULTS: An inverse association was observed between serum lycopene and overall cancer incidence. The adjusted risk ratio (RR) in the highest tertile of serum lycopene was 0.55 (95% confidence interval [CI], 0.34-0.89; p=0.015) compared with the lowest serum lycopene group. No association was observed between the lycopene concentrations and a prostate cancer risk. RR for other cancers was 0.43 (95% CI, 0.23-0.79; p=0.007). CONCLUSIONS: These findings suggest that in middle-aged men, the higher circulating concentrations of lycopene may contribute to the lower risk of cancer, with the exception of prostate cancer.

Effects of astaxanthin supplementation on lipid peroxidation.

Astaxanthin, the main carotenoid pigment in aquatic animals, has greater antioxidant activity in vitro (protecting against lipid peroxidation) and a more polar configuration than other carotenoids. We investigated the effect of three-month astaxanthin supplementation on lipid peroxidation in healthy non-smoking Finnish men, aged 19-33 years by using a randomized double-blind study design. Also absorption of astaxanthin from capsules into bloodstream and its safety were evaluated. The intervention group received two 4-mg astaxanthin (Astaxin) capsules daily, and the control group two identical-looking placebo capsules. Astaxanthin supplementation elevated plasma astaxanthin levels to 0.032 pmol/L (p < 0.001 for the change compared with the placebo group). We observed that levels of plasma 12- and 15-hydroxy fatty acids were reduced statistically significantly in the astaxanthin group (p = 0.048 and p = 0.047 respectively) during supplementation, but not in the placebo group and the change of 15-hydroxy fatty acid was almost significantly greater (p = 0.056) in the astaxanthin group, as compared with the placebo group. The present study suggests that intestinal absorption of astaxanthin delivered as capsules is adequate, and well tolerated. Supplementation with astaxanthin may decrease in vivo oxidation of fatty acids in healthy men.

Carotenoids and cardiovascular health.

Cardiovascular disease (CVD) is the main cause of death in Western countries. Nutrition has a significant role in the prevention of many chronic diseases such as CVD, cancers, and degenerative brain diseases. The major risk and protective factors in the diet are well recognized, but interesting new candidates continue to appear. It is well known that a greater intake of fruit and vegetables can help prevent heart diseases and mortality. Because fruit, berries, and vegetables are chemically complex foods, it is difficult to pinpoint any single nutrient that contributes the most to the cardioprotective effects. Several potential components that are found in fruit, berries, and vegetables are probably involved in the protective effects against CVD. Potential beneficial substances include antioxidant vitamins, folate, fiber, and potassium. Antioxidant compounds found in fruit and vegetables, such as vitamin C, carotenoids, and flavonoids, may influence the risk of CVD by preventing the oxidation of cholesterol in arteries. In this review, the role of main dietary carotenoids, ie, lycopene, beta-carotene, alpha-carotene, beta-cryptoxanthin, lutein, and zeaxanthin, in the prevention of heart diseases is discussed. Although it is clear that a higher intake of fruit and vegetables can help prevent the morbidity and mortality associated with heart diseases, more information is needed to ascertain the association between the intake of single nutrients, such as carotenoids, and the risk of CVD. Currently, the consumption of carotenoids in pharmaceutical forms for the treatment or prevention of heart diseases cannot be recommended.

Serum homocysteine, folate and risk of stroke: Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study.

BACKGROUND: Homocysteine and folate have been suggested to have opposite effects on the risk of stroke, although the results are controversial. DESIGN AND METHODS: The purpose of this study was to assess the effects of serum total homocysteine (tHcy) and serum folate levels on the risk of stroke in a prospective cohort study. The subjects were 1015 men aged 46-64 years and free of prior stroke, examined in 1991-1993 in the Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study. RESULTS: At baseline the mean serum tHcy concentration was 10.9 micromol/l (SD 3.4). During an average follow-up time of 9.6 years, 49 men experienced a stroke, of which 34 were ischaemic. In Cox proportional hazards models, men in the highest tHcy third had a risk factor-adjusted hazard rate ratio (RR) of 2.77 [95% confidence interval (CI): 1.23-6.24] for any stroke and 2.61 (95% CI: 1.02-6.71) for ischaemic stroke, compared with men in the lowest third. The mean baseline serum folate concentration was 10.4 nmol/l (SD 4.1). Men in the highest third of serum folate (>11.2 nmol/l) had an adjusted RR for any stroke of 0.35 (95% CI: 0.14-0.87) and for ischaemic stroke of 0.40 (95% CI: 0.15-1.09), compared with men in the lowest third. CONCLUSION: Elevated serum tHcy is associated with increased risk of all strokes and ischaemic strokes in middle-aged eastern Finnish men free of prior stroke. On the other hand, high serum folate concentration may protect against stroke.

Polyphenol-rich phloem enhances the resistance of total serum lipids to oxidation in men.

In humans, polyphenol supplementation studies have resulted in inconsistent findings in lipid peroxidation. Our aim was to investigate the effects of a 4-week consumption of polyphenol-rich phloem on serum lipids and lipid peroxidation in the hydrophilic fraction of serum and on isolated lipoproteins. We conducted a randomized double-blind supplementation study consisting of 75 nonsmoking hypercholesterolemic men. Participants consumed 70 g daily of either rye bread (placebo) or phloem-fortified rye bread containing 31 mg (low polyphenol, LP) or 62 mg (high polyphenol, HP) of catechins. The ex vivo susceptibility of total serum lipids and VLDL and LDL to oxidation after copper induction was measured as a lag time to the maximal oxidation rate at the baseline and after the supplementation. In the HP group, an increase in the oxidation resistance of total serum lipids was observed (11.4%), while no effect was seen in the LP group (-0.8%) or in the placebo group (-1.0%) (p = 0.007). No differences were observed in the oxidation resistance of VLDL and LDL between the study groups. The phloem also increased in vitro oxidation resistance of serum lipids and radical scavenging activity (DPPH.) in a dose-dependent manner. Our results suggest that polyphenols may inhibit lipid peroxidation in the hydrophilic fraction of serum.

Dark chocolate consumption increases HDL cholesterol concentration and chocolate fatty acids may inhibit lipid peroxidation in healthy humans.

Cocoa powder is rich in polyphenols and, thus, may contribute to the reduction of lipid peroxidation. Our aim was to study the effects of long-term ingestion of chocolate, with differing amounts of polyphenols, on serum lipids and lipid peroxidation ex vivo and in vivo. We conducted a 3 week clinical supplementation trial of 45 nonsmoking, healthy volunteers. Participants consumed 75 g daily of either white chocolate (white chocolate, WC group), dark chocolate (dark chocolate, DC group), or dark chocolate enriched with cocoa polyphenols (high-polyphenol chocolate, HPC group). In the DC and HPC groups, an increase in serum HDL cholesterol was observed (11.4% and 13.7%, respectively), whereas in the WC group there was a small decrease (-2.9%, p < 0.001). The concentration of serum LDL diene conjugates, a marker of lipid peroxidation in vivo, decreased 11.9% in all three study groups. No changes were seen in the total antioxidant capacity of plasma, in the oxidation susceptibility of serum lipids or VLDL + LDL, or in the concentration of plasma F2-isoprostanes or hydroxy fatty acids. Cocoa polyphenols may increase the concentration of HDL cholesterol, whereas chocolate fatty acids may modify the fatty acid composition of LDL and make it more resistant to oxidative damage.

Serum linoleic and total polyunsaturated fatty acids in relation to prostate and other cancers: a population-based cohort study.

Dietary and serum fatty acid composition has been implicated in the pathogenesis of prostate and other cancers, but findings have been conflicting. Cohort studies reporting serum fatty acid composition are lacking. We assessed the association of fatty acid composition determined from dietary records and serum with incident cancer of the prostate and any site in a population-based cohort of 2,002 middle-aged Finnish men who were free of cancer at baseline and during the first 4 years of follow-up. During 12.6 years of follow-up, 46 men developed prostate cancer and 151 any cancer. Men with proportions of serum nonesterified [risk ratio (RR) 0.28; 95% confidence intervals (CI) 0.12-0.66] and esterified linoleic acid (RR 0.37; 95% CI = 0.16-0.86) and total polyunsaturated fatty acids (RR 0.30; 95% CI = 0.12-0.71) in the upper third were less than 1/3 as likely to develop prostate cancer during follow-up. Adjustment for possible confounders like socioeconomic status, physical activity, obesity and insulin concentrations did not attenuate the association. Similar but weaker associations with any cancer were found. Dietary linoleic acid intake also tended to be inversely associated with incident prostate cancer (age-adjusted RR for the upper vs. lower third 0.55; 95% CI = 0.26-1.14, p for the trend 0.097). Substitution of linoleic acid for saturated fat in middle-aged men consuming a high saturated-fat diet may decrease the risk of prostate and other cancers, although it is possible that some of the effect may be mediated by nutrients closely associated with vegetable fats.

Risk of cardiovascular disease-related and all-cause death according to serum concentrations of enterolactone: Kuopio Ischaemic Heart Disease Risk Factor Study.

BACKGROUND: Enterolactone is a plant-derived compound that has been associated with a reduced risk of acute coronary events and cancer. Several studies have suggested that serum enterolactone concentration may play a role as a biomarker of a diet high in fiber and vegetables. Owing to its phenolic structure, enterolactone and its plant lignan precursors, which are converted by intestinal bacteria to enterolactone, are potential antioxidants. METHODS: The associations between serum enterolactone level and the risk of coronary heart disease (CHD)-related, cardiovascular disease (CVD)-related, and all-cause mortality were investigated in the Kuopio Ischaemic Heart Disease Risk Factor Study, which is a prospective population-based study of middle-aged Finnish men. The serum enterolactone concentration and cardiovascular risk factors were determined in 1889 men aged 42 to 60 years. In an average follow-up of 12.2 years, 70 CHD-related, 103 CVD-related, and 242 all-cause deaths occurred in participants free of prior CVD. RESULTS: Multivariate analyses showed significant associations between elevated serum enterolactone concentration and reduced risk of CHD- and CVD-related mortality, but weaker associations in relation to all-cause mortality. In the Cox proportional hazards regression model adjusting for the most potent confounding factors, the risk of CHD-related (P =.03 for trend) and CVD-related (P =.04 for trend) death decreased linearly across quartiles of serum enterolactone concentration. CONCLUSIONS: Our data suggest that a high serum enterolactone level is associated with reduced CHD- and CVD-related mortality in middle-aged Finnish men. These results add to the evidence supporting the importance of whole grain foods, fruits, and vegetables in the prevention of premature death from CVD.

Six-year effect of combined vitamin C and E supplementation on atherosclerotic progression: the Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) Study.

BACKGROUND: Self-selected supplementation of vitamin E has been associated with reduced coronary events and atherosclerotic progression, but the evidence from clinical trials is controversial. In the first 3 years of the ASAP trial, the supplementation with 136 IU of vitamin E plus 250 mg of slow-release vitamin C twice daily slowed down the progression of carotid atherosclerosis in men but not women. This article examines the 6-year effect of supplementation on common carotid artery (CCA) intima-media thickness (IMT). METHODS AND RESULTS: The subjects were 520 smoking and nonsmoking men and postmenopausal women aged 45 to 69 years with serum cholesterol > or =5.0 mmol/L (193 mg/dL), 440 (84.6%) of whom completed the study. Atherosclerotic progression was assessed ultrasonographically. In covariance analysis in both sexes, supplementation reduced the main study outcome, the slope of mean CCA-IMT, by 26% (95% CI, 5 to 46, P=0.014), in men by 33% (95% CI, 4 to 62, P=0.024) and in women by 14% (not significant). In both sexes combined, the average annual increase of the mean CCA-IMT was 0.014 mm in the unsupplemented and 0.010 mm in the supplemented group (25% treatment effect, 95% CI, 2 to 49, P=0.034). In men, this treatment effect was 37% (95 CI, 4 to 69, P=0.028). The effect was larger in subjects with either low baseline plasma vitamin C levels or CCA plaques. Vitamin E had no effect on HDL cholesterol. CONCLUSIONS: These data replicate our 3-year findings confirming that the supplementation with combination of vitamin E and slow-release vitamin C slows down atherosclerotic progression in hypercholesterolemic persons.

Low intake of fruits, berries and vegetables is associated with excess mortality in men: the Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study.

Diets rich in fruits and vegetables have been of interest because of their potential health benefits against chronic diseases such as cardiovascular disease (CVD) and cancer. The aim of this work was to assess the association of the dietary intake of a food group that includes fruits, berries and vegetables with all-cause, CVD-related and non-CVD-related mortality. The subjects were Finnish men aged 42-60 y examined in 1984-1989 in the prospective Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study. Dietary intakes were assessed by 4-d food intake record during the baseline phase of the KIHD Study. The risk of all-cause and non-CVD-related deaths was studied in 2641 men and the risk of CVD-related death in 1950 men who had no history of CVD at baseline. During a mean follow-up time of 12.8 y, cardiovascular as well as noncardiovascular and all-cause mortality were lower among men with the highest consumption of fruits, berries and vegetables. After adjustment for the major CVD risk factors, the relative risk for men in the highest fifth of fruit, berry and vegetable intake for all-cause death, CVD-related and non-CVD-related death was 0.66 [95% confidence interval (CI) 0.50-0.88], 0.59 (0.33-1.06), and 0.68 (0.46-1.00), respectively, compared with men in the lowest fifth. These data show that a high fruit, berry and vegetable intake is associated with reduced risk of mortality in middle-aged Finnish men. Consequently, the findings of this work indicate that diets that are rich in plant-derived foods can promote longevity.