Serum Lutein and Zeaxanthin Are Inversely Associated with High-Sensitivity C-Reactive Protein in Non-Smokers: The Mikkabi Study.

Recent randomized controlled trials have demonstrated a protective association between carotenoids and inflammation; however, the basis of this association on lifestyle factors remains unclear. This study aimed to clarify the associations between carotenoids and inflammatory markers stratified by lifestyle factors, using baseline data from the Mikkabi Study. Serum carotenoid and high-sensitivity C-reactive protein (hs-CRP) levels were measured. Multivariable adjusted odds ratios (ORs) for a high hs-CRP level (≥2.0 mg/dL) were obtained using logistic regression analysis. The data of 882 individuals were analyzed; 11.7% had high hs-CRP levels. The highest tertile of lutein (OR: 0.44; 95% confidence interval [CI]: 0.25-0.76), zeaxanthin (OR: 0.36; 95% CI: 0.21-0.64), total carotenoid (OR: 0.57; 95% CI: 0.32-0.9997), and oxygenated carotenoid concentration (OR: 0.50; 95% CI: 0.28-0.90), with the lowest tertile as reference, was inversely associated with a high hs-CRP level. The interaction between lutein, but not other carotenoids, and current smoking was significant. The inverse association between lutein and a high hs-CRP level was significant in non-smokers (OR: 0.41; 95% CI: 0.22-0.76) but not in smokers. These results further support the anti-inflammatory effect of carotenoids; nevertheless, further studies should clarify the interaction of smoking with the association between lutein and inflammation.

ß-Cryptoxanthin Induces UCP-1 Expression via a RAR Pathway in Adipose Tissue.

While ß-cryptoxanthin is hypothesized to have a preventive effect on lifestyle-related diseases, its underlying mechanisms are unknown. We investigated the effect of ß-cryptoxanthin on energy metabolism in adipose tissues and its underlying mechanism. C57BL/6J mice were fed a high-fat diet (60% kcal fat) containing 0 or 0.05% ß-cryptoxanthin for 12 weeks. ß-cryptoxanthin treatment was found to reduce body fat gain and plasma glucose level, while increasing energy expenditure. The expression of uncoupling protein (UCP) 1 was elevated in adipose tissues in the treatment group. Furthermore, the in vivo assays showed that the Ucp1 mRNA expression was higher in the ß-cryptoxanthin treatment group, an effect that disappeared upon cotreatment with a retinoic acid receptor (RAR) antagonist. In conclusion, we report that ß-cryptoxanthin reduces body fat and body weight gain and that ß-cryptoxanthin increases the expression of UCP1 via the RAR pathway.

Amelioration of the Development of Osteoarthritis by Daily Intake of ß-Cryptoxanthin.

ß-Cryptoxanthin, which is primarily obtained from citrus fruits such as Satsuma mandarins, is a major carotenoid routinely found in human serum. Recently, we demonstrated that daily oral intake of ß-cryptoxanthin prevented ovariectomy-induced bone loss and ameliorated neuropathic pain in mice. Although ß-cryptoxanthin exerts preventive effects on various lifestyle-related diseases, there have been no studies on the effect of ß-cryptoxanthin on the development of osteoarthritis, the most common degenerative joint disease, which frequently leads to loss of ability and stiffness in the elderly. Here we showed that daily oral administration of ß-cryptoxanthin significantly prevented the development of osteoarthritis developed by surgically inducing knee joint instability in mice in vivo. Furthermore, in vitro experiments revealed that ß-cryptoxanthin markedly inhibited the expression of inflammatory cytokines and enzymes critical for the degradation of the extracellular matrix in primary chondrocytes. Our results suggest that oral supplementation of ß-cryptoxanthin would be beneficial for the maintenance of joint health and as prophylaxis against osteoarthritis.

ß-Cryptoxanthin exerts greater cardioprotective effects on cardiac ischemia-reperfusion injury than astaxanthin by attenuating mitochondrial dysfunction in mice.

SCOPE: ß-Cryptoxanthin and astaxanthin are antioxidant carotenoid pigments that inhibit lipid peroxidation as potently as vitamin E. We hypothesized that acute treatment with ß-cryptoxanthin and astaxanthin causes similar reductions in the sizes of cardiac infarcts caused by ischemia-reperfusion (I/R) injury by attenuating oxidative stress and cardiac mitochondrial dysfunction. METHODS AND RESULTS: C57BL/6 mice (n = 36) were randomized to receive vehicle, ß-cryptoxanthin, astaxanthin, or vitamin E at 50 mg/kg by gavage feeding prior to I/R injury. Cardiac I/R was induced by left anterior descending coronary artery ligation followed by reperfusion. All treatments significantly reduced infarct sizes by 36-57%, attenuated apoptosis and also attenuated cardiac mitochondrial dysfunction in the treated groups compared to the control group. Although astaxanthin and vitamin E exhibited similar efficacy with respect to cardioprotection, ß-cryptoxanthin exhibited greater efficacy than its counterparts, as it reduced infarct sizes by 60%. ß-Cryptoxanthin was more effective than astaxanthin and vitamin E because it reduced cardiac mitochondrial swelling, mitochondrial depolarization, the Bax/Bcl-2 ratio, and plasma and cardiac thiobarbituric acid reactive substances levels more significantly than its counterparts. CONCLUSION: Acute ß-cryptoxanthin treatment exhibits greater cardioprotective efficacy against I/R injury than astaxanthin and vitamin E by reducing infarct sizes and attenuating apoptosis, oxidative stress, and mitochondrial dysfunction.

Daily oral intake of ß-cryptoxanthin ameliorates neuropathic pain.

ß-cryptoxanthin, a xanthophyll carotenoid, exerts preventive effects on various lifestyle-related diseases. Here, we found that daily oral administration of ß-cryptoxanthin significantly ameliorated the development of tactile allodynia following spinal nerve injury but was ineffective in mechanical allodynia in an inflammatory pain model in mice. Our results suggest that ß-cryptoxanthin supplementation would be beneficial for the prophylaxis of neuropathic pain.

High Vitamin C Intake with High Serum ß-Cryptoxanthin Associated with Lower Risk for Osteoporosis in Post-Menopausal Japanese Female Subjects: Mikkabi Cohort Study.

Recent epidemiological studies show that antioxidant vitamins and carotenoids might be beneficial to the maintenance of bone health. Recently, we found that serum carotenoids were inversely associated with the risk of developing osteoporosis in post-menopausal Japanese female subjects. However, little is known about the vitamin alone and/or the combination of the vitamin and carotenoid with the risk of osteoporosis. The objective of this study was to investigate longitudinally whether antioxidant vitamins and their combination with carotenoids are associated with the risk of developing of osteoporosis. We conducted a follow-up study on 187 post-menopausal female subjects from the Mikkabi prospective cohort study. Those who participated in previous bone mineral density (BMD) surveys and completed four years of follow-up were examined longitudinally. During a four-year follow-up, fifteen of the post-menopausal female subjects developed new-onset osteoporosis. After adjustment for confounders, the odds ratios (OR) for osteoporosis in the highest tertiles of vitamins C and E and retinol intakes against the lowest tertiles were 0.15 (95% confidence interval (CI): 0.02-0.99), 0.50 (CI: 0.08-3.23), and 1.49 (CI: 0.36-6.22), respectively. Furthermore, a significantly lower odds ratio was observed in the higher vitamin C intake group (169-625 mg/d) with higher serum ß-cryptoxanthin (1.88-10.53 µM) against the lower vitamin C intake group (47-168 mg/d) with lower serum ß-cryptoxanthin (0.24-1.84 µM) used for the reference group (p<0.05). The combination of ß-cryptoxanthin and vitamin C is inversely associated with the risk of developing osteoporosis in post-menopausal Japanese female subjects.

High serum carotenoids are associated with lower risk for developing elevated serum alanine aminotransferase among Japanese subjects: the Mikkabi cohort study.

Many recent studies have shown that antioxidant vitamins and/or carotenoids may reduce liver disease, but this association has not been well established with thorough longitudinal cohort studies. The objective of this study was to longitudinally investigate whether serum carotenoids at baseline are associated with the risk of developing elevated serum alanine aminotransferase (ALT) among Japanese subjects. We conducted a follow-up study of 1073 males and females aged between 30 and 79 years at baseline from the Mikkabi prospective cohort study. Those who participated in the baseline study and completed follow-up surveys were examined longitudinally. Exclusions included excessive alcohol consumption (≥60 g alcohol/d), hepatitis B and C and having a history of medication use for liver disease. A cohort of 213 males and 574 females free of elevated serum ALT (>30 IU/ml) at baseline was studied. Over a mean follow-up period of 7·4 (sd 3·1) years, thirty-one males and forty-nine females developed new elevated serum ALT. After adjustments for confounders, the hazard ratios for elevated serum ALT in the highest tertiles of basal serum ß-carotene, ß-cryptoxanthin and total provitamin A carotenoids against the lowest tertiles were 0·43 (95 % CI 0·22, 0·81), 0·51 (CI 0·27, 0·94) and 0·52 (CI 0·28, 0·97), respectively. For α-carotene and lycopene, borderline reduced risks were also observed; however, these were not significant. Our results further support the hypothesis that antioxidant carotenoids, especially provitamin A carotenoids, might help prevent earlier pathogenesis of non-alcoholic liver disease in Japanese subjects.

High-serum carotenoids associated with lower risk for developing type 2 diabetes among Japanese subjects: Mikkabi cohort study.

OBJECTIVE: Recent epidemiological studies show the association of antioxidant carotenoids with type 2 diabetes, but thorough longitudinal cohort studies regarding this association have not been well conducted. The objective of this study was to investigate longitudinally whether serum carotenoids are associated with the risk for developing type 2 diabetes among Japanese subjects. RESEARCH DESIGN AND METHODS: We conducted a follow-up study on 1073 males and females aged 30-79 years at the baseline from the Mikkabi prospective cohort study. Those who participated in the baseline and completed follow-up surveys were examined longitudinally. Over the 10-year period, 910 subjects (295 males and 615 females) took part in the follow-up survey at least one time. A cohort of 264 males and 600 females free of diabetes at baseline was studied. RESULTS: Over a mean follow-up period of 7.8 years (SD=2.9), 22 males and 33 females developed new type 2 diabetes. After adjustments for confounders, the HRs for type 2 diabetes in the highest tertiles of serum α-carotene, ß-cryptoxanthin, and total provitamin A carotenoids against the lowest tertiles were 0.35 (95% CI 0.15 to 0.82), 0.43 (CI 0.20 to 0.92) and 0.41 (CI 0.19 to 0.90), respectively. For ß-carotene and zeaxanthin, borderline reduced risks were also observed, but these were not significant. CONCLUSIONS: Our results further support the hypothesis that eating a diet rich in carotenoids, especially provitamin A carotenoids, might help prevent the development of type 2 diabetes in Japanese patients. TRIAL REGISTRATION NUMBER: NIFT-2013001.

Daily intake of ß-cryptoxanthin prevents bone loss by preferential disturbance of osteoclastic activation in ovariectomized mice.

Although ß-cryptoxanthin, a xanthophyll carotenoid, has been shown to exert an anabolic effect on bone calcification, little attention has been paid thus far to the precise mechanism of bone remodeling. Daily oral administration of ß-cryptoxanthin significantly inhibited osteoclastic activation as well as reduction of bone volume in ovariectomized mice. In vitro studies revealed that ß-cryptoxanthin inhibited differentiation and maturation of osteoclasts by repression of the nuclear factor-κB-dependent transcriptional pathway. Our results suggest that supplementation with ß-cryptoxanthin would be beneficial for prophylaxis and for therapy of metabolic bone diseases associated with abnormal osteoclast activation.

High serum carotenoids associated with lower risk for the metabolic syndrome and its components among Japanese subjects: Mikkabi cohort study.

Recent epidemiological studies show the association of carotenoids with the metabolic syndrome (MetS), but thorough longitudinal cohort studies regarding this association have not been well conducted. The objective of this study was to investigate longitudinally whether serum carotenoids are associated with the risk of developing the MetS and its components in Japanese subjects. We conducted a follow-up study on 1073 men and women aged 30-79 years at the baseline from the Mikkabi prospective cohort study. Those who participated in the baseline and completed follow-up surveys were examined longitudinally. Over the 10-year period, 910 subjects (295 men and 615 women) took part in the follow-up survey at least once. Over a mean follow-up period of 7·8 (sd 2·9) years, thirty-six men and thirty-one women developed new MetS. After adjustments for confounders, the hazard ratio (HR) for the MetS in the highest tertile of serum ß-carotene against the lowest tertile was 0·47 (95 % CI 0·23, 0·95). On the other hand, significantly lower risks for dyslipidaemia were observed in the highest tertiles of serum α- and ß-carotene and ß-cryptoxanthin (HR 0·66; 95 % CI 0·46, 0·96; HR, 0·54; 95 % CI 0·37, 0·79; and HR 0·66; 95 % CI 0·44, 0·99, respectively). Other significant associations between the risks for obesity, high blood pressure and hyperglycaemia with serum carotenoids were not observed. Our results further support the hypothesis that eating a diet rich in carotenoids might help prevent the development of the MetS and its complications in Japanese subjects.

[ß-Cryptoxanthin and the risk for lifestyle-related disease: findings from recent nutritional epidemiologic studies].

  Antioxidant micronutrients, such as vitamins and carotenoids, exist in abundance in fruits and vegetables and have been known to contribute to the body's defense against reactive oxygen species. Numerous recent epidemiologic studies have demonstrated that a high dietary consumption of fruit and vegetables rich in carotenoids or with high serum carotenoid concentrations results in lower risks of certain cancers, diabetes, and cardiovascular disease. These epidemiologic studies have suggested that antioxidant carotenoids may have a protective effect against several lifestyle-related diseases. ß-Cryptoxanthin is a carotenoid pigment found in Japanese mandarin (Citrus unshiu MARC.) fruit, which is mainly produced in Japan. Our nutritional epidemiologic survey, the Mikkabi Study, utilized data derived from health examinations of inhabitants performed in the town of Mikkabi in Shizuoka, Japan. In this survey, we measured serum ß-cryptoxanthin as a specific biomarker to estimate the consumption of Japanese mandarin fruit. From the cross-sectional analyses from the Mikkabi Study, we found inverse associations of serum ß-cryptoxanthin with the risks for atherosclerosis, insulin resistance, liver dysfunction, metabolic syndrome, low bone mineral density, and oxidative stress. In this review, recent epidemiologic studies about the associations between serum ß-cryptoxanthin with the risk for several lifestyle-related diseases were reviewed.

Prevention and reversal of lipotoxicity-induced hepatic insulin resistance and steatohepatitis in mice by an antioxidant carotenoid, ß-cryptoxanthin.

Excessive hepatic lipid accumulation promotes macrophages/Kupffer cells activation, resulting in exacerbation of insulin resistance and progression of nonalcoholic steatohepatitis (NASH). However, few promising treatment modalities target lipotoxicity-mediated hepatic activation/polarization of macrophages for NASH. Recent epidemiological surveys showed that serum ß-cryptoxanthin, an antioxidant carotenoid, was inversely associated with the risks of insulin resistance and liver dysfunction. In the present study, we first showed that ß-cryptoxanthin administration ameliorated hepatic steatosis in high-fat diet-induced obese mice. Next, we investigated the preventative and therapeutic effects of ß-cryptoxanthin using a lipotoxic model of NASH: mice fed a high-cholesterol and high-fat (CL) diet. After 12 weeks of CL diet feeding, ß-cryptoxanthin administration attenuated insulin resistance and excessive hepatic lipid accumulation and peroxidation, with increases in M1-type macrophages/Kupffer cells and activated stellate cells, and fibrosis in CL diet-induced NASH. Comprehensive gene expression analysis showed that ß-cryptoxanthin down-regulated macrophage activation signal-related genes significantly without affecting most lipid metabolism-related genes in the liver. Importantly, flow cytometry analysis revealed that, on a CL diet, ß-cryptoxanthin caused a predominance of M2 over M1 macrophage populations, in addition to reducing total hepatic macrophage and T-cell contents. In parallel, ß-cryptoxanthin decreased lipopolysaccharide-induced M1 marker mRNA expression in peritoneal macrophages, whereas it augmented IL-4-induced M2 marker mRNA expression, in a dose-dependent manner. Moreover, ß-cryptoxanthin reversed steatosis, inflammation, and fibrosis progression in preexisting NASH in mice. In conclusion, ß-cryptoxanthin prevents and reverses insulin resistance and steatohepatitis, at least in part, through an M2-dominant shift in macrophages/Kupffer cells in a lipotoxic model of NASH.

Comparison of bioavailability between ß-cryptoxanthin and ß-carotene and tissue distribution in its intact form in rats.

The bioavailability of two intact carotenoids in several tissues of ß-cryptoxanthin- and ß-carotene-fed rats (20 mg/kg of diet) was investigated. Although metabolites of provitamin A are not included in our study, ß-cryptoxanthin was found at higher concentrations in majority of the tissues. The results show that the bioavailability of intact ß-cryptoxanthin seemed to be higher than that of ß-carotene.

ß-Cryptoxanthin alleviates diet-induced nonalcoholic steatohepatitis by suppressing inflammatory gene expression in mice.

Recent nutritional epidemiological surveys showed that serum ß-cryptoxanthin inversely associates with the risks for insulin resistance and liver dysfunction. Consumption of ß-cryptoxanthin possibly prevents nonalcoholic steatohepatitis (NASH), which is suggested to be caused by insulin resistance and oxidative stress from nonalcoholic fatty liver disease. To evaluate the effect of ß-cryptoxanthin on diet-induced NASH, we fed a high-cholesterol and high-fat diet (CL diet) with or without 0.003% ß-cryptoxanthin to C56BL/6J mice for 12 weeks. After feeding, ß-cryptoxanthin attenuated fat accumulation, increases in Kupffer and activated stellate cells, and fibrosis in CL diet-induced NASH in the mice. Comprehensive gene expression analysis showed that although ß-cryptoxanthin histochemically reduced steatosis, it was more effective in inhibiting inflammatory gene expression change in NASH. ß-Cryptoxanthin reduced the alteration of expression of genes associated with cell death, inflammatory responses, infiltration and activation of macrophages and other leukocytes, quantity of T cells, and free radical scavenging. However, it showed little effect on the expression of genes related to cholesterol and other lipid metabolism. The expression of markers of M1 and M2 macrophages, T helper cells, and cytotoxic T cells was significantly induced in NASH and reduced by ß-cryptoxanthin. ß-Cryptoxanthin suppressed the expression of lipopolysaccharide (LPS)-inducible and/or TNFα-inducible genes in NASH. Increased levels of the oxidative stress marker thiobarbituric acid reactive substances (TBARS) were reduced by ß-cryptoxanthin in NASH. Thus, ß-cryptoxanthin suppresses inflammation and the resulting fibrosis probably by primarily suppressing the increase and activation of macrophages and other immune cells. Reducing oxidative stress is likely to be a major mechanism of inflammation and injury suppression in the livers of mice with NASH.

The protective effects of ß-cryptoxanthin on inflammatory bone resorption in a mouse experimental model of periodontitis.

We examined the effects of ß-cryptoxanthin, a typical carotenoid, on inflammatory periodontitis. ß-Cryptoxanthin suppressed lipopolysaccharide (LPS)-induced osteoclast formation in co-cultures of bone marrow cells and osteoblasts. In a mouse model of periodontitis, it suppressed bone resorption in the mandibular alveolar bone in vitro and restored alveolar bone loss induced by LPS in vivo. ß-Cryptoxanthin might protect against periodontal disease.

Absorption, storage and distribution of ß-cryptoxanthin in rat after chronic administration of Satsuma mandarin (Citrus unshiu MARC.) juice.

Fruits and vegetables contain numerous antioxidants, such as carotenoids. Recent epidemiologic studies have demonstrated that a high dietary consumption of fruit and vegetables rich in carotenoids or with high serum carotenoid concentrations results in lower risks of certain cancers, diabetes, and cardiovascular disease. These results indicate that absorbed carotenoids are stored in various organs. Previously, we found that ß-cryptoxanthin, found especially in Satsuma mandarin (Citrus unshiu MARC.), is easily absorbed and can also survive for a relatively long time in the human body; however, little is known about the absorption, storage, and tissue distribution of ß-cryptoxanthin. In this study, we measured serum and the content of ß-cryptoxanthin in several rat tissues after chronic ingestion of Satsuma mandarin extract rich in ß-cryptoxanthin. Rats were fed a standard commercial diet containing Satsuma mandarin extract (containing ß-cryptoxanthin at 11.7 mg/kg diet) for eight weeks. After 3 h of fasting, serum, liver, spleen, kidney, lung, heart, testis, brain, and epididymal fat were collected. The concentrations of ß-cryptoxanthin in serum and tissues were evaluated by high-performance liquid chromatography. There was a wide range in the tissue levels of ß-cryptoxanthin; liver had the greatest value, with 1265.3 ng/g tissue, followed by spleen, kidney, lung, heart, brain, and testis. Epididymal fat had the lowest value, with 6.99 ng/g tissue. ß-Cryptoxanthin was also detected in serum in a concentration of 5.76 ng/mL. These results indicate that ß-cryptoxanthin is easily absorbed and accumulated in several organs.

High serum carotenoids associated with lower risk for bone loss and osteoporosis in post-menopausal Japanese female subjects: prospective cohort study.

INTRODUCTION: Recent epidemiological studies show that high intakes of carotenoids might be useful to maintain bone health, but little is known about the association of serum carotenoids with change of bone mineral density (BMD). The objective of this study was to investigate longitudinally whether serum carotenoids are associated with bone loss. METHODS: We conducted a follow-up on 146 male and 99 pre- and 212 post-menopausal female subjects from the Mikkabi study. Those who participated in previous BMD surveys and completed four years of follow-up were examined longitudinally. RESULTS: During a 4-year follow-up, 15 of the post-menopausal female subjects developed new-onset osteoporosis. In contrast, none of the male and pre-menopausal female subjects did. In male and pre-menopausal female subjects, the six serum carotenoids at the baseline were not associated with bone loss. On the other hand, in post-menopausal female subjects, the 4-year bone loss of radius was inversely associated with the serum carotenoid concentrations, especially in ß-carotene. After adjustments for confounders, the odds ratios (OR) for osteoporosis in the highest tertiles of serum ß-carotene and ß-cryptoxanthin against the lowest tertiles were 0.24 (95% confidence interval 0.05-1.21) and 0.07 (CI: 0.01-0.88), respectively. Serum ß-cryptoxanthin was also inversely associated with the risk for osteopenia and/or osteoporosis (P for trend, 0.037). In addition, our retrospective analysis revealed that subjects who developed osteoporosis and/or osteopenia during the survey period had significantly lower serum concentrations of ß-cryptoxanthin and ß-carotene at the baseline than those in the normal group. CONCLUSIONS: Antioxidant carotenoids, especially ß-cryptoxanthin and ß-carotene, are inversely associated with the change of radial BMD in post-menopausal female subjects.

Beta-cryptoxanthin, plentiful in Japanese mandarin orange, prevents age-related cognitive dysfunction and oxidative damage in senescence-accelerated mouse brain.

Increased oxidative stress is known to accelerate age-related pathologies. Beta-cryptoxanthin (ß-CRX, (3R)-ß,ß-caroten-3-ol) is a potent antioxidant that is highly rich in Satsuma mandarin orange (mandarin), which is the most popular fruit in Japan. We investigated the antioxidative and anti-aging effects of ß-CRX and mandarin using senescence-accelerated mice (SAMP10), which were characterized by a short lifespan, high generation of superoxide anions in the brain and poor learning ability with aging. ß-CRX (0.5-5.0 µg/ml) or mandarin juice (3.8-38.0%) was added to drinking water of SAMP10 one to 12 months of age. ß-CRX was dose-dependently incorporated into the cerebral cortex and the contents were similar to the concentration of ß-CRX in the human frontal lobe. These mice also had higher learning ability. The level of DNA oxidative damage was significantly lower in the cerebral cortex of mice that ingested ß-CRX and mandarin than control mice. In addition, the mice that ingested ß-CRX (>1.5 µg/ml) and mandarin (>11.3%) exhibited a higher survival when 12 month-old, the presenile age of SAMP10, than control mice. These results suggest that ß-CRX is incorporated into the brain and has an important antioxidative role and anti-aging effect.

Synergistic interaction of cigarette smoking and alcohol drinking with serum carotenoid concentrations: findings from a middle-aged Japanese population.

Previous studies have indicated low serum carotenoid concentrations among cigarette smokers and/or alcohol drinkers, but little is known about the interaction of smoking and drinking with serum carotenoids. We tested the hypothesis that smoking and drinking reduce serum carotenoid concentrations synergistically. A total of 1073 subjects (357 male and 716 female) who had received health examinations in the town of Mikkabi, Shizuoka Prefecture, Japan, participated in the study. The subjects were divided into six groups according to alcohol intake (non-drinkers, < 1 g/d; light drinkers, > or = 1, < 25 g/d; moderate-to-heavy drinkers, > or = 25 g/d) and smoking status (non-smokers and current smokers). The dietary intakes and serum concentrations of six carotenoids (lycopene, alpha-carotene, beta-carotene, lutein, beta-cryptoxanthin and zeaxanthin) within each group were evaluated cross-sectionally. The dietary intakes of all carotenoids did not differ in the six groups after adjusting for age and sex. The multivariate-adjusted means of the serum carotenoid concentrations in non-drinkers did not differ between non-smokers and current smokers. In contrast, the adjusted means of serum alpha-carotene, beta-carotene and beta-cryptoxanthin were significantly lower than those with increased alcohol intake, and these lower serum carotenoids among alcohol drinkers were more evident in current smokers than in non-smokers. Serum lycopene of moderate-to-heavy drinkers was significantly lower than that of non-drinkers, but it was not influenced by smoking. Neither smoking nor drinking was associated with the serum concentrations of lutein and zeaxanthin. These results suggest that smoking and drinking may reduce the serum alpha-carotene, beta-carotene and beta-cryptoxanthin concentrations in a synergistic manner.

Associations of serum carotenoid concentrations with the metabolic syndrome: interaction with smoking.

Recent epidemiological studies show the associations of serum antioxidant status with the metabolic syndrome. Oxidative stress may play an important role in the pathogenesis of diabetes and CVD. Actually, smoking is a potent oxidative stressor in man, but little is known about the interaction of serum carotenoids and the metabolic syndrome with smoking status. In this study, the associations of the serum carotenoids with the metabolic syndrome stratified by smoking habit were evaluated cross-sectionally. A total of 1073 subjects (357 male and 716 female) who had received health examinations in the town of Mikkabi, Shizuoka Prefecture, Japan, participated in the study. Among total subjects, the OR for the metabolic syndrome in the highest tertile of serum beta-carotene was 0.41 (95 % CI 0.18, 0.92) after adjusting confounders. In current smokers, significantly lower OR were observed in the middle (OR 0.10; 95 % CI 0.01, 0.72) and highest (OR 0.06; 95 % CI 0.01, 0.73) tertiles of serum beta-carotene. Furthermore, lower OR were observed in accordance with tertiles of serum alpha-carotene and beta-cryptoxanthin in current smokers (P for trend 0.042 and 0.036, respectively). In contrast, in non-smokers, a significantly lower OR was observed in the highest tertile of serum beta-carotene (OR 0.30; 95 % CI 0.10, 0.89) after multiple adjustment. Inverse associations of serum carotenoids with the metabolic syndrome were more evident among current smokers than non-smokers. These results support that antioxidant carotenoids may have a protective effect against development of the metabolic syndrome, especially in current smokers who are exposed to a potent oxidative stress.