Analysis of Repeated Measurements of Serum Carotenoid Levels and All-Cause and Cause-Specific Mortality in Japan

Fujii, Ryosuke; Tsuboi, Yoshiki; Maeda, Keisuke; Ishihara, Yuya; Suzuki, Kôji

doi:10.1001/jamanetworkopen.2021.13369

Cited by 13 publications

(10 citation statements)

References 55 publications

(118 reference statements)

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“…Previous observational studies have examined the relationship between plasma or serum carotenoids and the risk of all‐cause and cardiovascular mortality. 8 , 9 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 56 Despite inconsistent results, most of these studies found that different types of higher plasma or serum carotenoid concentrations were associated with a reduced risk of mortality. 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 Among them, lycopene, α‐carotene, and β‐carotene have been extensively studied as major antioxidants that exert a variety of bioactive effects on humans.…”

Section: Discussionmentioning

confidence: 99%

“… 11 Observational epidemiological studies have shown that higher dietary carotenoid intake levels or serum carotenoid concentrations are linked with a lower incidence of cardiovascular disease (CVD) 12 , 13 and hypertension, 14 and a lower risk of mortality. 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 Furthermore, a meta‐analysis of longitudinal studies that examined the relationships between plasma or serum concentrations of several different types of carotenoids and mortality found that total carotene, α‐carotene, β‐carotene, and lycopene concentrations were inversely linked with the risk of all‐cause mortality. 26 Carotenoids are thought to have protective effects against CVD and may reduce cardiovascular mortality because of their antioxidant stress effect.…”

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confidence: 99%

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Associations of Serum Carotenoids With Risk of All‐Cause and Cardiovascular Mortality in Hypertensive Adults

Zhu

Cheang

Tang

et al. 2023

JAHA

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Background Systemic oxidative stress is involved in the development of hypertension, whereas carotenoids are a group of natural antioxidants. Our study aims to evaluate the relationships between the serum concentrations of major carotenoids and mortality in hypertensive adults. Methods and Results Data on 5 serum carotenoids from the National Health and Nutrition Examination Survey (NHANES) III and NHANES 2001–2006 were included. Outcome measures (all‐cause and cardiovascular mortality) were identified from the National Death Index through December 31, 2019. Multiple Cox proportional hazards regression and restricted cubic spline analyses were performed to determine the association between carotenoid levels and outcomes. A total of 8390 hypertensive adults were included in the analysis. At a median follow‐up duration of 16.6 years, all‐cause and cardiovascular mortality occurred in 4005 (47.74%) and 1205 (14.36%) participants, respectively. Compared with the lowest quartiles, the highest quartiles of 5 major serum carotenoids were associated with lower risk of all‐cause mortality, with multivariable‐adjusted hazard ratios (HRs) of 0.63 (95% CI, 0.56–0.71) for α‐carotene, 0.70 (95% CI, 0.61–0.80); for β‐carotene, 0.67 (95% CI, 0.58–0.76); for β‐cryptoxanthin, 0.74 (95% CI, 0.64–0.86) for lycopene; and 0.72 (95% CI, 0.63–0.83) for lutein/zeaxanthin. For cause‐specific mortality, this association with the fourth quartile of serum carotenoids was evident for a reduced rate of cardiovascular mortality, with a 32% reduction for α‐carotene (HR, 0.68 [95% CI, 0.55–0.86]), a 29% reduction for β‐cryptoxanthin (HR, 0.71 [95% CI, 0.56–0.89]), and a 26% reduction for lycopene (HR, 0.74 [95% CI, 0.59–0.94]), but not for β‐carotene and lutein/zeaxanthin. In addition, we found that serum α‐carotene, β‐carotene, β‐cryptoxanthin, and lutein/zeaxanthin levels were nonlinearly related to all‐cause mortality with inflection points of 2.43, 8.49, 5.12, and 14.17 μg/dL, respectively. Serum α‐carotene, β‐cryptoxanthin, and lutein/zeaxanthin concentrations showed nonlinear associations with cardiovascular mortality with inflection points of 2.31, 5.26, and 15.40 μg/dL, respectively. Conclusions Findings suggest that higher serum carotenoid concentrations were associated with lower risks of all‐cause and cardiovascular mortality in hypertensive adults.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Associations of Serum Carotenoids With Risk of All‐Cause and Cardiovascular Mortality in Hypertensive Adults

Zhu

Cheang

Tang

et al. 2023

JAHA

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“…This study further explored the relationship between total carotenoids and individual carotenoids and all–cause mortality, as serum carotenoid levels are thought to reflect the intake of vegetables and fruits in an individual's diet ( 28 , 30 ). Previous studies have found a negative association between serum total carotenoid, alpha–carotene, beta–carotene, lycopene, lutein/zeaxanthin, and beta–cryptoxanthin and all–cause mortality ( 24 , 31 , 32 ). Lycopene, a non–provitamin A carotenoid, has been shown to have direct anti–inflammatory effects ( 33 , 34 ).…”

Section: Discussionmentioning

confidence: 90%

“…A positive association between the number of times per month that total fruits and vegetables were consumed and serum vitamin C was also observed in this study. Carotenoids are sources of various immune–protective substances and they are reported to have the protective effects on human health ( 24 ). Although studies of the individual carotenoids have given inconsistent results ( 6 , 25 ).…”

Section: Discussionmentioning

confidence: 99%

Associations of Serum Biomarkers of Fruit and Vegetable Intake With the Risk of Cause–Specific Mortality and All–Cause Mortality: A National Prospective Cohort Study

Zhang

Wang

et al. 2022

Front. Nutr.

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ObjectiveThe purpose of this study was to evaluate the associations of serum biomarkers of fruit and vegetable intake (vitamin C and carotenoids) with cause–specific mortality and all–cause mortality in a nationally representative sample of US adults.MethodsWe analyzed data from 12,530 participants from the National Health and Nutrition Examination Survey III (1988–1994). The Cox proportional hazards models with restricted cubic spline were used for the analysis.ResultsDuring 246,027 person–years of follow–up, 4,511 deaths occurred, including 1,395 deaths from cardiovascular disease, 1,072 deaths from heart disease, 323 deaths from cerebral disease, and 954 deaths from cancer. The serum vitamin C was significantly associated with the cancer and all–cause mortality, with hazard ratios (HRs) (95% CIs) for each one SD of 0.80 (0.71–0.91) and 0.91 (0.86–0.96). The serum alpha–carotene was significantly associated with the cancer mortality, with HRs (95% CIs) of 0.70 (0.54–0.90), 0.68 (0.48–0.95), 0.64 (0.43–0.95), and 0.44 (0.33–0.60) for comparisons of groups 2–5 with group 1 in model 2, respectively. The change for each one SD in the composite biomarker score, equivalent to a 0.483 times/month difference in total fruits and vegetables intake, gave an HR of 0.79 (0.69–0.90) for cancer mortality.ConclusionInverse associations were found between serum vitamin C, carotenoids, and composite biomarker score and outcomes expect for cerebral disease, heart disease, and cardiovascular disease mortality. This finding supports an increase in dietary fruit and vegetable intake as a primary prevention strategy for cancer and all–cause mortality.

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“…Early atherosclerosis patients had lower serum concentrations of lutein and zeaxanthin than healthy subjects [ 108 ]. In a cohort study conducted on 3116 Japanese patients, higher levels of serum carotenoid were associated with lower risks of all-cause, cancer, and cardiovascular disease mortality in Japanese patients [ 109 ]. Diabetic patients with higher serum carotenoid concentrations had fewer vascular complications [ 110 ].…”

Section: Properties Of Carotenoidsmentioning

confidence: 99%

Effect of Carotenoids on Paraoxonase-1 Activity and Gene Expression

Otocka-Kmiecik

2022

Nutrients

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Paraoxonase 1 (PON1) is an antioxidant enzyme attached to HDL with an anti-atherogenic potential. It protects LDL and HDL from lipid peroxidation. The enzyme is sensitive to various modulating factors, such as genetic polymorphisms as well as pharmacological, dietary (including carotenoids), and lifestyle interventions. Carotenoids are nutritional pigments with antioxidant activity. The aim of this review was to gather evidence on their effect on the modulation of PON1 activity and gene expression. Carotenoids administered as naturally occurring nutritional mixtures may present a synergistic beneficial effect on PON1 status. The effect of carotenoids on the enzyme depends on age, ethnicity, gender, diet, and PON1 genetic variation. Carotenoids, especially astaxanthin, β-carotene, and lycopene, increase PON1 activity. This effect may be explained by their ability to quench singlet oxygen and scavenge free radicals. β-carotene and lycopene were additionally shown to upregulate PON1 gene expression. The putative mechanisms of such regulation involve PON1 CpG-rich region methylation, Ca(2+)/calmodulin-dependent kinase II (CaMKKII) pathway induction, and upregulation via steroid regulatory element-binding protein-2 (SREBP-2). More detailed and extensive research on the mechanisms of PON1 modulation by carotenoids may lead to the development of new targeted therapies for cardiovascular diseases.

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Analysis of Repeated Measurements of Serum Carotenoid Levels and All-Cause and Cause-Specific Mortality in Japan

Abstract: This cohort study investigates the association of serum carotenoid levels found using repeated measurements with all-cause, cancer, and cardiovascular disease mortality in Japanese adults.

Cited by 13 publications

References 55 publications

Associations of Serum Carotenoids With Risk of All‐Cause and Cardiovascular Mortality in Hypertensive Adults

Associations of Serum Carotenoids With Risk of All‐Cause and Cardiovascular Mortality in Hypertensive Adults

Associations of Serum Biomarkers of Fruit and Vegetable Intake With the Risk of Cause–Specific Mortality and All–Cause Mortality: A National Prospective Cohort Study

Effect of Carotenoids on Paraoxonase-1 Activity and Gene Expression

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