Jouni Karppi

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.

Simultaneous measurement of retinol, α-tocopherol and six carotenoids in human plasma by using an isocratic reversed-phase HPLC method

A simple and sensitive isocratic reversed-phase high-performance liquid chromatography (HPLC) method for simultaneous determination of retinol, alpha-tocopherol and six carotenoids in human plasma was described. Sample preparation of the earlier published method was further developed by addition of ultrapure water, which enabled aqueous layer to freeze facilitating phase separation without pipetting thus also improving precision of the method. Developed method appeared to be less laborious and time consuming compared to the traditional extraction methods, which require removal of organic layer by pipetting. The recoveries (absolute and relative) were between 80% and 103%. The intra-assay CVs were 1.1-4.0% (normal level) and 3.3-9.0% (low level). Inter-assay CVs were 5.3-8.8%. Reference method for all these analytes was not available, but a comparison with another published method was carried out. The results of the comparison matched satisfactorily. The method is used routinely in our laboratory in a large population-based study.

Serum lycopene decreases the risk of stroke in men A population-based follow-up study

Objective: Intake of fruits and vegetables and levels of serum carotenoids have been associated with decreased risk of stroke, but the results have been inconsistent. The aim of the present study was to examine whether serum concentrations of major carotenoids, α-tocopherol and retinol, are related to any stroke and ischemic stroke in men. Methods: The study population consisted of 1,031 Finnish men aged 46−65 years in the Kuopio Ischaemic Heart Disease Risk Factor cohort. Serum concentrations of carotenoids retinol and α-tocopherol were measured by high-performance liquid chromatography. The association between the serum concentrations of lycopene α-carotene, β-carotene, α-tocopherol, and retinol and the risk of strokes was studied by using Cox proportional hazards models. Results: A total of 67 strokes occurred, and 50 of these were ischemic strokes during a median of 12.1 follow-up years. After adjustment for age, examination year, BMI, systolic blood pressure, smoking, serum low-density lipoprotein cholesterol, diabetes, and history of stroke, men in the highest quartile of serum lycopene concentrations had 59% and 55% lower risks of ischemic stroke and any stroke, compared with men in the lowest quartile (hazard ratio [HR] = 0.45, 95% confidence interval [CI] 0.25−0.95, p = 0.036 for any stroke and HR = 0.41; 95% CI 0.17−0.97, p = 0.042 for ischemic stroke). α-Carotene, β-carotene, α-tocopherol, and retinol were not related to the risk of strokes. Conclusions: This prospective study shows that high serum concentrations of lycopene, as a marker of intake of tomatoes and tomato-based products, decrease the risk of any stroke and ischemic stroke in men.

Serum β-carotene concentrations and the risk of congestive heart failure in men: A population-based study

BACKGROUND Fruit and vegetable intake has been associated with lower risk for cardiovascular diseases, but data on congestive heart failure (CHF) are inconsistent. The association of serum carotenoids, biomarkers reflecting fruit and vegetable intake, with the risk of CHF has not been well documented in previous studies. We therefore examined the association between carotenoid levels and the risk of CHF. METHODS Data were available for 1031 males aged 46 to 65 years participating in the Kuopio Ischaemic Heart Disease Risk Factor Study (Finland). Baseline data for the present study were collected between 1991 and 1993. The association between serum concentrations of carotenoids and the risk of CHF was examined by using Cox proportional hazard models. RESULTS During the median of 17.8 follow-up years, CHF occurred in 72 patients. Age and examination year adjusted risk (hazard ratio, HR) for CHF among men within the lowest quartile of serum β-carotene was 4.08 (95% CI, 1.90-8.78, p<0.001) as compared to men in the highest quartile of serum β-carotene. After further adjustment for many potential confounders, men with the lowest quartile of β-carotene had almost 3-fold increased risk of CHF (HR=2.78, 95% CI, 1.23-6.25, p=0.014). However, serum concentrations of lycopene and α-carotene were not related to the risk of CHF. CONCLUSIONS The present study suggests that low concentrations of serum β-carotene may be associated with an increased risk of CHF.

Impaired Fasting Plasma Glucose and Type 2 Diabetes Are Related to the Risk of Out-of-Hospital Sudden Cardiac Death and All-Cause Mortality

OBJECTIVE The aim of the study was to determine whether impaired fasting plasma glucose (FPG) and type 2 diabetes may be risk factors for sudden cardiac death (SCD). RESEARCH DESIGN AND METHODS This prospective study was based on 2,641 middle-aged men 42–60 years of age at baseline. Impaired FPG level (≥5.6 mmol/L) among nondiabetic subjects (501 men) was defined according to the established guidelines, and the group with type 2 diabetes included subjects (159 men) who were treated with oral hypoglycemic agents, insulin therapy, and/or diet. RESULTS During the 19-year follow-up, a total of 190 SCDs occurred. The relative risk (RR) for SCD was 1.51-fold (95% CI 1.07–2.14, P = 0.020) for nondiabetic men with impaired FPG and 2.86-fold (1.87–4.38, P < 0.001) for men with type 2 diabetes as compared with men with normal FPG levels, after adjustment for age, BMI, systolic blood pressure, serum LDL cholesterol, smoking, prevalent coronary heart disease (CHD), and family history of CHD. The respective RRs for out-of-hospital SCDs (157 deaths) were 1.79-fold (1.24–2.58, P = 0.001) for nondiabetic men with impaired FPG and 2.26-fold (1.34–3.77, P < 0.001) for men with type 2 diabetes. Impaired FPG and type 2 diabetes were associated with the risk of all-cause death. As a continuous variable, a 1 mmol/L increment in FPG was related to an increase of 10% in the risk of SCD (1.10 [1.04–1.20], P = 0.001). CONCLUSIONS Impaired FPG and type 2 diabetes represent risk factors for SCD.

Plasma lutein and zeaxanthin and the risk of age-related nuclear cataract among the elderly Finnish population.

Oxidative stress plays an important role in cataractogenesis. Previous studies have shown that long-term dietary intake of antioxidants (lutein and zeaxanthin) may decrease the risk of age-related cataracts. The aim of the present study was to examine whether plasma concentrations of lutein and zeaxanthin are related to age-related nuclear cataract in the elderly population. Subjects were participants in the Kuopio Ischaemic Heart Disease Risk Factor Study and they were classified into tertiles according to plasma concentrations of lutein and zeaxanthin. The association of plasma lutein and zeaxanthin concentrations with age-related nuclear cataract in 1689 elderly subjects (aged 61-80 years) was investigated in the present cross-sectional study by using the Cox proportional hazards model. A total of 113 cases of incident age-related cataracts were confirmed, of which 108 cases were nuclear cataracts. After adjustment for age, examination year, sex, BMI, smoking, alcohol consumption, serum LDL-cholesterol, serum HDL-cholesterol, years of education, use of oral corticosteroids, history of diabetes and history of hypertension with current use of antihypertensive medication, subjects in the highest tertiles of plasma concentrations of lutein and zeaxanthin had 42 and 41 % lower risks of nuclear cataract, respectively, compared with those in the lowest tertiles (relative risk (RR) = 0·58, 95 % CI 0·35, 0·98; P = 0·041 for lutein and RR = 0·59, 95 % CI 0·35, 0·99; P = 0·046 for zeaxanthin). In conclusion, we suggest that high plasma concentrations of lutein and zeaxanthin were associated with a decreased risk of age-related nuclear cataract in the elderly population.

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.

Lycopene, lutein and β-carotene as determinants of LDL conjugated dienes in serum

Oxidative modification of low-density lipoprotein (LDL) in the vascular endothelium is considered to be important in the development of early atherosclerosis. The aim of this study was to investigate the main determinants of serum LDL conjugated dienes in women (n=124) and men (n=225). We focused on the influence of fat-soluble vitamins and carotenoids on the concentration of conjugated dienes in LDL. In multivariate linear regression models, including age, body mass index, diastolic blood pressure, symptomatic ischaemic heart disease (IHD) or IHD history, statin medication, leukocytes and serum triglycerides as covariates, plasma lycopene (standardized beta=-0.33; P=0.002) and lutein (standardized beta=-0.22; P=0.027) concentrations were the strongest determinants of serum LDL conjugated dienes in women, whereas plasma beta-carotene (standardized beta=-0.23; P=0.002) was the most important factor in men. Furthermore, statin medication, diastolic blood pressure, age and serum triglycerides were significant determinants of LDL conjugated dienes. The regression model with lycopene contributed to 29% in women and 15% in men with beta-carotene of the variation of serum LDL conjugated dienes. Results of the present study suggest that plasma lycopene, lutein and beta-carotene are the most powerful antioxidants for explaining the content of in vivo oxidatively modified LDL in serum.

Serum β-carotene and the risk of sudden cardiac death in men: A population-based follow-up study

OBJECTIVES To examine whether serum concentrations of carotenoids are related to the risk of sudden cardiac death (SCD) in middle-aged men. METHODS The study population consisted of 1031 Finnish men aged 46-65 years of the Kuopio Ischemic Heart Disease Risk Factor (KIHD) cohort. Serum concentrations of carotenoids were measured by high-performance liquid chromatography. The hazard ratios (HR) of serum β-carotene, lycopene and α-carotene were estimated by using the Cox proportional hazard model after adjusting for age and other potential confounding factors. RESULTS During a median follow-up of 15.9 years a total of 59 incidents of SCD occurred. After controlling for age, systolic blood pressure, waist circumference, smoking, alcohol consumption, years of education, serum LDL cholesterol, serum hs-CRP, diabetes, prevalent coronary heart disease (CHD) and congestive heart failure (CHF), men in the lowest tertile of serum concentrations of β-carotene had a 2-fold increased risk of SCD (HR=2.15, 95% CI: 1.02-4.51; p=0.044) as compared to those in the highest tertile. The risk of SCD was borderline significant for lycopene. In addition, low serum β-carotene concentrations increased the risk of cardiovascular disease (CVD) and total mortality. Lycopene and α-carotene were not related to the risk of SCD. CONCLUSIONS Our findings suggest that low serum β-carotene concentrations may increase the risk of SCD in middle-aged Finnish men. Furthermore, low serum β-carotene concentrations may be related to the risk of CVD and total mortality.

Plasma carotenoids are related to intima--media thickness of the carotid artery wall in men from eastern Finland.

Abstract.  Karppi J, Kurl S, Laukkanen JA, Rissanen TH, Kauhanen J (Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio; Lapland Central Hospital, Rovaniemi; Finland). Plasma carotenoids are related to intima – media thickness of the carotid artery wall in men from eastern Finland. J Intern Med 2011; 270: 478–485.