In an aim to extend cognitive functioning into old age, and reduce the costs of care in late life, a greater focus has been put on understanding what factors may accelerate cognitive decline. One such factor is oxidative stress - an imbalance between pro-oxidant and antioxidant states, which tilts more toward pro-oxidant metabolism. Such metabolic stress may contribute to neurodegenerative diseases such as Alzheimer’s disease (AD), and other age-related conditions such as cardiovascular disease and cancer.
Reactive Oxygen Species (ROS) can accumulate because of DNA repair impairment with age. The brain may be particularly vulnerable to ROS because it accounts for about 20% of all bodily oxygen consumption. Therefore exposure can trigger unfavorable DNA oxidative modifications within the brain.
Oxidative stress refers to the imbalance due to excess ROS or oxidants over the capability of the cell to mount an effective antioxidant response. Dietary intake of antioxidants has been shown to reduce lipid peroxidation, the production of ROS, apoptosis, and protein and DNA oxidative damage. Epidemiological evidence from observational studies also suggests that antioxidants in the diet, supplements, and serum may play a neuroprotective role.
There is also evidence of biological synergism between some carotenoids and other antioxidants, whereby increased intake of carotenoid β-carotene may reduce blood levels of vitamin E.
The authors of the current study therefore hypothesised that dietary antioxidants might slow the pace of cognitive decline among middle-aged adults, thus delaying the onset of AD and other forms of dementia in older age. They also aimed to uncover any synergism between antioxidants.
Researchers used the longitudinal data from a large bi-racial study of urban middle-aged adults (The Healthy Aging in Neighborhoods of Diversity across the Life Span, HANDLS, ongoing prospective cohort study initiated in 2004), to examine adjusted associations among several dietary antioxidants (specifically vitamins A, C, and E and carotenoids such as α-carotene, β-carotene, lutein + zeaxanthin, β-cryptoxanthin, and lycopene) and cognitive performance change over time.
They report consistent synergism between total (and individual) carotenoids and vitamin E in relation to baseline cognitive performance in verbal memory, verbal fluency, attention, working memory, and executive function.
Vitamin E was associated with greater verbal memory performance in the uppermost tertile of carotenoids, an association largely driven by lycopene intake. Within the uppermost tertile of total carotenoids, vitamin A was associated with faster decline on a test of visual memory and visuo-constructive ability, an association that was driven by β-carotene and lutein + zeaxanthin.However, both vitamins A and C showed inconsistent interactions with carotenoids with respect to both baseline cognitive performance and change in cognitive test scores over time.
While no antagonism was found between β-carotene and vitamin E, there was some evidence of synergism between α-carotene and vitamin E in relation to performance in multiple domains of cognition.
The report concludes: "The clinical interpretation and implications of this study are that a diet rich in vitamin E and carotenoids, including lycopene, may reduce the likelihood of cognitive decrements in the short term, particularly in the domain of verbal memory.
"Time-dependent changes in dietary and plasma levels of antioxidants need to be linked with changes in cognitive performance over time in future cohort studies, in a lagged manner, to ensure temporality of the associations and to incorporate supplemental sources of antioxidants. Pending such studies, randomized trials examining synergism between carotenoids and vitamin E in relation to cognitive performance and decline are needed."
The authors do also note that within the total population, and after correction for multiple testing, there was limited evidence of an association between each of these antioxidants and cognitive performance or decline.
This study is believed to be the first to examine the potential synergistic associations of carotenoids and other antioxidants in relation to cognitive performance and change in a prospective cohort study of a large bi-racial sample of urban middle-aged adults.
The initial cohort of HANDLS consisted of 3720 participants (aged 30–65) who underwent fasting blood draw, a complete physical examination, a dual-energy X-ray absorptiometry scan, an electrocardiogram, a cognitive assessment, and a second 24-h dietary recall.
During the period of 2009–2013, a first follow-up visit (v2) was conducted and consisted primarily of an MRV in-depth examination visit that assessed the cognitive performance in a similar manner as in the first visit (v1). Among the 2468 participants who completed v2, the mean ± SD follow-up time was estimated at 4.66 ± 0.93 years.
Largely protective findings were reported when cognitive decline or incident cognitive impairment were among the main outcomes of interest and the exposures were dietary intakes of antioxidants [1,2,3]. Other studies have concluded that certain forms of tocopherols not found only in foods, not supplements, may be at play [4, 5].
At least four cohort studies found no association between intake of vitamins E and C and dementia incidence [6,7,8,9]. Numerous cross-sectional studies have also found that dietary carotenoids, vitamins A, C, and E were associated with better cognitive performance, while others could not detect such associations [10,11].
Among the individual carotenoids, lycopene in plasma, directly reflecting dietary intakes, has generally been linked to better cognitive performance and reduced rate of cognitive decline.
Independent cohort studies have found only borderline or little evidence of a cognitive benefit from use of antioxidant supplements, particularly vitamins C and E, [12,13,14]. Nevertheless, at least a few randomized controlled trials (RCTs) have indicated a benefit from supplementation with vitamin C, or from a combination of various antioxidants while other RCTs that focused on vitamin E supplementation failed to do so.
An inverse association between plasma vitamin E and poor cognitive outcomes was found in at least five cross-sectional studies [15,16,17,18,19]. Moreover, among studies that examined the influence of plasma carotenoids, several have detected a significant potential protective effect against cognitive impairment.
Zonderman. A. B., et al
Association of Antioxidant Vitamins A, C, E and Carotenoids with Cognitive Performance over Time: A Cohort Study of Middle-Aged Adults
https://doi.org/10.3390/nu12113558 (registering DOI)