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Antioxidants lower stroke risk

Eating a diet high in antioxidants may protect against ischemic stroke, an Italian cohort study showed.

People who had a diet high in total antioxidant capacity — an index that takes into account several different antioxidants and their interactions — had a 59% reduced relative risk of ischemic stroke (HR 0.41, 95% CI 0.23 to 0.74), according to Nicoletta Pellegrini, PhD, of the University of Parma in Italy, and colleagues. But there was no such relationship with hemorrhagic stroke, they reported in the January issue of the Journal of Nutrition. In fact, the highest intake of the antioxidant vitamin E was associated with a greater risk of hemorrhagic stroke (HR 2.94, 95% CI 1.13 to 7.62).
Considering evidence suggesting that oxidative stress and systemic inflammation are involved in the pathogenesis of ischemic stroke, the researchers noted that “a high-total antioxidant capacity diet could be protective as a consequence of its ability to deliver compounds with antioxidant activity and with a demonstrated anti-inflammatory effect.” But, they acknowledged that the mechanism for such activity was unclear may “go beyond the antioxidant activity of the numerous total antioxidant capacity contributors present in foods and beverages.”

Pellegrini and her colleagues set out to explore the relationship between dietary total antioxidant capacity and the risk of stroke among 41,620 people participating in EPICOR, the Italian segment of the European Prospective Investigation into Cancer and Nutrition (EPIC). None had a history of stroke or MI at baseline. Dietary intake was assessed with a food frequency questionnaire. In the study population, more than half of the total antioxidants consumed came from coffee, wine, and fruit. Through a mean follow-up of 7.9 years, there were 112 ischemic strokes, 48 hemorrhagic strokes, and 34 other types of strokes. After adjustment for energy intake, hypertension, smoking status, education, nonalcoholic energy intake at recruitment, alcohol intake, waist circumference, body mass index, and total physical activity, individuals eating a diet in the highest tertile of total antioxidant capacity had a reduced risk of ischemic — but not hemorrhagic — stroke.

Looking at individual antioxidants, the researchers found that participants consuming the highest amounts of vitamin C had a reduced risk of ischemic stroke (HR 0.58, 95% CI 0.34 to 0.99). Controlling for vitamin C intake did not negate the overall association between antioxidants and ischemic stroke, which ruled out the nutrient as the sole driver of the relationship. High intake of vitamin E, on the other hand, was associated with nearly triple the relative risk of hemorrhagic stroke. However, “it must be stressed that the small number of cases observed in this population strongly limits the validity of statistical observations on hemorrhagic stroke,” noted the researchers, who called for further studies.

Aside from anti-inflammatory effects, it is possible that the association between antioxidants and ischemic stroke risk can be explained by the interaction between polyphenols — the major contributors to total antioxidant capacity — and the generation of nitric oxide from the vascular endothelium. That interaction leads to the vasodilation and expression of genes that may be protective for the vascular system, according to the researchers. In addition, coffee — the main source of antioxidants in the study population — reduces blood pressure, which is a recognized risk factor for ischemic stroke, the researchers wrote.

They noted some limitations of the study, including the low numbers of cases when different types of stroke were analyzed, the measurement of total antioxidant capacity at baseline only, and the inability to rule out confounding effects of other dietary components, like sodium and potassium.

Source: Del Rio D, et al “Total antioxidant capacity of the diet is associated with lower risk of ischemic stroke in a large Italian cohort” J Nutr 2011; 141: 118-123.

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Low vitamin D common in lung disease

Kinder and his colleagues assessed the prevalence of vitamin D deficiency in a cohort of patients with interstitial lung disease, who are often treated with corticosteroids. The detrimental effect of chronic use of corticosteroids on bone health has been well established, according to the researchers. Of the patients included in the study, 51 had interstitial lung disease and 67 had other forms of interstitial lung disease related to autoimmune connective tissue diseases.

A vitamin D insufficiency was defined as a serum level of less than 30 ng/mL. A level of less than 20 ng/mL was considered deficient. Both insufficient and deficient levels were prevalent in the study. In the overall sample, lower vitamin D levels were associated with reduced forced vital capacity (P=0.01). When the analysis was restricted to patients with connective tissue disease, both forced vital capacity and diffusing capacity of lung for carbon monoxide — a measure of the lung’s ability to transfer gases from the air to the blood — were significantly reduced (P<0.05 for both). After adjustment for several potential confounders — including age, corticosteroid use, race, and season, the presence of connective lung disease was a strong predictor of vitamin D insufficiency (OR 11.8, 95% CI 3.5 to 40.6).

According to the researchers, a pathogenic role of low vitamin D in the development of autoimmune diseases such as interstitial lung disease is plausible because of the immunoregulatory role of the biologically active form of vitamin D, 1,25-(OH)2D. “All cells of the adaptive immune system express vitamin D receptors and are sensitive to the action of 1,25-(OH)2D,” they wrote. “High levels of 1,25-(OH)2D are potent inhibitors of dendritic cell maturation with lower expression of major histocompatibility complex class II molecules, down-regulation of costimulatory molecules, and lower production of proinflammatory cytokines.” “A common theme in the immunomodulatory functions of vitamin D is that higher levels are immunosuppressive,” they continued, “which is consistent with a potential role for hypovitaminosis D in the pathogenesis of autoimmune disorders.”

In a statement, Len Horovitz, MD, a pulmonary specialist at Lenox Hill Hospital in New York City, commented that “vitamin D is known to promote wound healing, and to benefit the immune system. So it is not surprising to find that patients with immune lung disorders are vitamin D deficient.” He said that all of his patients are screened and treated for vitamin D deficiency with supplements. The study authors noted that further research is needed to determine whether supplementation is associated with improved outcomes. The study was limited, Kinder and his colleagues wrote, by its use of patients from a single center in Cincinnati.

In addition, the cross-sectional design of the study did not evaluate whether vitamin D supplementation is associated with any improved clinical outcomes. To examine that issue, the team called for prospective controlled interventional studies to determine whether vitamin D7 supplements can ameliorate symptoms and improve outcomes in connective tissue disease-related interstitial lung disease.

Source reference: Hagaman J, et al “Vitamin D deficiency and reduced lung function in connective tissue-associated interstitial lung diseases” Chest 2011; DOI: 10.1378/chest.10-0968.

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