An Orange a Day Keeps Stroke Away

By Crystal Phend, Senior Staff Writer, MedPage Today

Published: February 23, 2012

Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner

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Action Points

• In this large study in women, total flavonoid intake was not inversely associated with risk of stroke; however, increased intake of the flavanone subclass was associated with a reduction in the risk of ischemic stroke.
• Citrus fruits/juices are the main dietary source of flavanones, and in this study they tended to be associated with a reduced risk for ischemic stroke, but the association did not reach significance.

A compound found in oranges, grapefruit, and other citrus fruit may modestly reduce stroke risk among women, an observational study determined.

Women with the highest levels of flavanone in their diet were 19% less likely to have an ischemic stroke during 14 years of follow-up than those with the least flavanone intake (P=0.04), Aedín Cassidy, PhD, of the University of East Anglia in Norwich, England, and colleagues found.

As the main source of these antioxidants, citrus fruit and juice showed a similar trend (relative risk 0.90, 95% CI 0.77 to 1.05), they reported in the April issue of Stroke: Journal of the American Heart Association.

Vitamin C has gotten most of the praise for the protective effect of citrus found in prior stroke studies, but in Cassidy's analysis of the Nurses' Health Study, the vitamin didn't correlate with total or ischemic stroke or attenuate the link to flavanones.

Most of the flavanones consumed by women in the study came from orange and grapefruit juice (63%). But eating the whole fruit would likely be a better way to boost intake, the researchers suggested.

"Given the higher flavanone content of citrus fruits and the sugar content of commercial fruit juices, public health recommendations should focus on increasing citrus fruit intake," they recommended in the paper.

Flavanones are one of six types of commonly consumed flavonoids, which various studies have linked individually to different benefits -- hypertension risk reduction with anthocyanins, lower stroke risk in some studies of flavonols -- but never looked at all simultaneously.

Cassidy's group broke down food frequency data from nearly 70,000 women participating in the Nurses' Health Study for total flavonoid intake and for each component.

With dietary reports every four years over a total 14 years of follow-up, the researchers found big variations in total flavonoid intake, ranging from an average 761 mg per day in the top quintile to 97 mg per day in the bottom quintile.

Tea was the biggest contributor to those levels, followed by apples and oranges or orange juice.

However, total flavonoid intake didn't predict ischemic stroke risk in the multivariate-adjusted model (P=0.36 for trend).

These results suggested "that flavanones may be another important cardioprotective constituent of citrus fruits," Cassidy's group wrote. "However, in a population-based study like ours, it is impossible to disentangle the relative influence of all the constituents of citrus fruits."

An impact from flavanones is plausible, they noted, pointing to experimental evidence that two flavanones, naringenin and hesperetin, act on neuroprotective pathways with effects on nitric oxide release. Naringenin was the strongest anti-inflammatory of all the flavonoids tested in one study.

A trend appeared for the flavones at the highest intake level of more than 3 mg per day compared with the lowest at less than 1 mg per day, but the difference wasn't statistically significant (adjusted relative risk 0.88, 95% CI 0.72 to 1.08).

The same was true for anthocyanins (blueberries were the main source) and flavan-3-ols (predominantly consumed from tea).

None of the compounds impacted hemorrhagic stroke risk.

Individual flavonoids are likely to differ in benefits because of different mechanisms through their specific structural characteristics, the researchers noted.

They cautioned that residual or unmeasured confounding was possible despite the detailed adjustment used in the study.

Another limitation is that the actual flavonoid content in foods consumed may have differed from levels recorded because of wide variability based on where the food was grown and during what season and how it was cultivated and processed.

Randomized trials are needed to test flavanone and citrus foods for reduction of ischemic stroke risk, the group concluded.

The study was supported by grants from the National Institutes of Health.

Cassidy and a co-author reported having received funding from Unilever Research and GlaxoSmithKline to conduct trials and experimental studies on flavonoid-rich foods in the past.

From the American Heart Association:

• Diet and Lifestyle Recommendations

Primary source: Stroke: Journal of the American Heart Association
Source reference:
Cassidy A, et al "Dietary flavonoids and risk of stroke in women" Stroke 2012; DOI: 10.1161/STROKEAHA.111.637835.