Table 1.

Main studies considered in our review.

Source	Year	Design	Aims	Results
Ito et al. [43]	2006	New analysis of a cohort from the Lipid Research Clinics Coronary Primary Prevention Trial and follow-up study.	To examine the relationship between total serum carotenoid levels and the risk of subsequent coronary heart disease events.	Higher serum carotenoid levels were associated with a decreased risk of incidence of coronary heart disease. This finding was stronger among men who never smoked.
Shaish et al. [44]	2006	Prospective and cross sectional-study.	To assess the relationship between plasma levels of carotenoids (α- and β-carotene, lutein, lycopene, zeaxanthin, and beta-cryptoxanthin), vitamins A and E, and atherosclerosis in the carotid and femoral arteries.	α- and β-carotene plasma levels were inversely associated with the prevalence of atherosclerosis in the carotid and femoral arteries (P = 0.004) and with the 5-year incidence of atherosclerotic lesions in the carotid arteries (P = 0.04).
Street et al. [45]	1994	Observational study (study cohort consisted of 26 593 male smokers, aged 50 to 69 years, without a history of stroke, during a 6.1-year followup).	Association between dietary antioxidants and subtypes of stroke	The dietary intake of β-carotene was inversely associated with the risk for cerebral infarction, lutein plus zeaxanthin with risk for subarachnoid hemorrhage, and lycopene with risks of cerebral infarction and intracerebral hemorrhage.
Street et al. [46]	1994	Observational epidemiologic study.	To examine the association between lycopene and acute coronary events and stroke in middle-aged men previously free of these events.	Low serum level of lycopene is associated with an increased risk of atherosclerotic vascular events.
Karppi et al. [47]	2013	Meta-analysis (seven randomised trials of vitamin E treatment and eight of β-carotene one).	To assess the effect of α-tocopherol (vitamin E), β-carotene, or both on long-term cardiovascular mortality and morbidity.	Vitamin E did not provide benefit in mortality or significantly decrease risk of cardiovascular death or cerebrovascular accident (p:ns). β-carotene led to a small but significant increase in all-cause mortality (P = 0.003) and cardiovascular death (P = 0.003).
Shaish et al. [48]	2006	Prospective study (73 286 female nurses followed for 12 years for the development of incident CAD).	Dietary intakes of specific carotenoids and risk of CAD in women.	Higher intakes of foods rich in α-carotene or β-carotene are associated with a reduction in risk of CAD.
Schürks et al. [49]	2010	Prospective, nested case control analysis.	Plasma lycopene and risk of CVD in middle-aged and elderly women.	Higher plasma lycopene concentrations are associated with a lower risk of CVD in women.
Sesso et al. [50]	2004	Observational epidemiologic study (3061 subjects aged 39 to 80 years).	Serum carotenoids and CVD mortality risk.	High serum levels of total carotene, comprising α- and β-carotenes and lycopene, may reduce the risk for CVD mortality.
Howard et al. [51]	1996	A case-control study (760 patients with nonfatal AMI and 682 controls patients)	The intake of selected carotenoids and retinol and risk of AMI.	The risk of AMI decreased with increasing intake of α-carotene (OR = 0.71, 95%, CI 0.51–0.98, for the highest versus the lowest quartile of intake), β-carotene (OR = 0.71, 95% CI 0.50–1.01), and β-cryptoxanthin (OR = 0.64, 95% CI 0.46–0.88). No associations emerged for total carotenoids, lycopene, lutein plus zeaxanthin, and retinol.
Bjelakovic et al. [52]	2008	Systematic review and meta-analysis of randomised, placebo-controlled trials published until January 2010.	To evaluate the effect of vitamin E supplementation on incident total, ischaemic, and haemorrhagic stroke.	Vitamin E increased the risk for haemorrhagic stroke by 22% and reduced the risk of ischaemic stroke by 10%.
Myung et al. [53]	2013	A meta-analysis of 13 randomised controlled trials.	To evaluate the role of vitamin E supplementation in the prevention of stroke.	There is no statistically significant or clinically important benefit of vitamin E supplementation in the prevention of stroke.
Bin et al. [54]	2011	Review (The Cochrane Library, MEDLINE, EMBASE, LILACS, the Science Citation Index Expanded, and Conference Proceedings Citation Index-Science to February 2011).	To assess the beneficial and harmful effects of antioxidant supplements for prevention of mortality in adults.	Results show no evidence to support antioxidant supplements for primary or secondary prevention. β-carotene and vitamin E seem to increase mortality and so may higher doses of vitamin A.
Hirvonen et al. [55]	2000	Observational study (1031 Eastern Finnish men aged 46–65 years, follow-up period of 15.9 years).	Relations between the concentrations of serum carotenoids and CVD mortality among Eastern Finnish men.	Low serum concentrations of β-carotene were strongly related to an increased CVD mortality risk after adjustment for confounders.
Karppi et al. [56]	2012	Observational study (1031 Finnish men aged 46–65 years, follow-up period of 15.9 years).	To examine whether serum concentrations of carotenoids are related to the risk of sudden cardiac death in middle-aged men	Low serum β-carotene concentrations increased the risk of sudden cardiac death, CVD, and total mortality.
Karppi et al. [57]	2013	Observational study (1031 males aged 46 to 65 years followed for 17.8 years).	To examine the association of serum carotenoids with the risk of congestive heart failure.	Low serum β-carotene concentrations were associated with 3-fold increased risk of congestive heart failure.

CAD: coronary artery disease. CVD: cardiovascular disease. AMI: acute myocardial infarction.