Low Total Plasma Carotenoids are Independent Predictors of Mortality Among Older Persons: the InCHIANTI Study
Epidemiologic studies suggest that a diet high in fruit and vegetable intake is protective against cardiovascular disease, stroke, and cancer. Fruits and vegetables are high in bioactive compounds such as carotenoids, flavonoids, and other plant polyphenols. Carotenoids are powerful antioxidants and have been shown to protect against damage caused by oxidative stress. The reduction in oxidative damage is related to the decreased risk of all-cause, cancer, and cardiovascular disease mortality. Carotenoids act as free radical scavengers, modulate immune responses, and play an important role in the redox regulation involved in inflammation. Carotenoids (alphacarotene, beta-carotene, beta-cryptoxanthin, lutein, zeaxanthin, and lycopene) occur in a wide variety of fruits and vegetables. Plasma carotenoids can be reliable quantified and are considered a valid biological marker for vegetable and fruit intake.
The relationship between plasma carotenoids and mortality has not been well characterized.
We hypothesized that low plasma carotenoid concentrations were associated with increased mortality in older adults. In order to address this hypothesis, we examined the Relationship between plasma carotenoid levels and mortality in the InCHIANTI study, a population-based cohort of older adults living in the community in Tuscany, Italy.
The study participants consisted of men and women, aged 65 and older, who participated in the Invecchiare in Chianti, “Aging in the Chianti Area” (InCHIANTI) study, conducted in two small towns in Tuscany, Italy. Briefly, in August 1998, 1270 people aged 65 years and older were randomly selected from the population registry of Greve in Chianti (pop. 11,709) and Bagno a Ripoli (pop. 4,704).
Of 1256 eligible subjects, 1155 (90.1%) agreed to participate, and 1043 (90.3%) participated in the blood drawing. At the end of the field data collection, we collected data on mortality of the original InCHIANTI cohort, using data from the Mortality General Registry maintained by the Tuscany Region. During the eight-years of follow-up study, 310 participants died. Blood samples were collected in the morning after a 12-h fast. Aliquots of serum and plasma were immediately obtained and stored at -80° C. Aliquots of plasma were shipped on dry ice to Dr. Semba’s laboratory for measurements of plasma carotenoids. Carotenoids were measured using high performance liquid chromatography (HPLC). Total carotenoids were calculated as the sum of alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein, zeaxanthin, and lycopene in Ìmol/L.
Mean total carotenoid concentration was 1.80 (0.69) Ìmol/L. The mean plasma level of total carotenoids is significantly lower with aging (P for trend=0.0004) . During the eight years of follow-up, 310 (29.7%) of participants died. From the highest to the lowest tertile of total carotenoids, respectively, 74 (21.2%), 105 (30.2%) and 131 (37.8%) participants died after eight years of follow-up.
In Cox Hazards Models adjusted for age and sex, participants with the highest tertile of plasma carotenoids at enrollment had lower mortality compared to those in the lowest tertile (Hazards Ratio = 0.63; 95% CI: 0.47-0.84; P=0.002). After adjusting for all covariates, adults in the highest tertile of plasma carotenoids at enrollment had lower mortality compared to those in the lowest tertile, although the association was slightly attenuated (Hazards Ratio obtained by considering carotenoids level as an ordinal variable = 0.81; 95% CI: 0.65-0.99; P for trend=0.046) .
The present study suggests that low total plasma carotenoids, a marker for fruit and vegetable intake, are an independent predictor of eight year, all-cause mortality among older persons. This work further shows the important relationship between antioxidant nutrients and mortality among older persons. Further work is needed to identify the sub-groups in the population which might be helped by interventions that reduce mortality in older populations.