Low Vitamin D in Diet Linked to Increased Stroke

Megan Brooks

June 20, 2012

June 20, 2012 — New data from the Honolulu Heart Program show that low dietary vitamin D at baseline was independently associated with higher risk of stroke over the next 34 years.

"Increasing dietary vitamin D intake might be beneficial for stroke prevention," first author Gotaro Kojima, MD, from the John A. Burns School of Medicine, University of Hawaii, Department of Geriatric Medicine in Honolulu, told Medscape Medical News.

Dr. Gotaro Kojima

Although some other studies have found an association between vitamin D deficiency and incident stroke, most of these studies looked at serum vitamin D levels. Less is known about the association between dietary vitamin D intake and risk of stroke.

There was only one study "which demonstrated that higher vitamin D intake was associated with lower stroke incidence. Our study's findings were consistent with this previous study. However, we had a 10-fold larger population size and a 3-fold longer follow-up period," Dr. Kojima said.

The findings of Dr. Kojima and colleagues were published online May 24, 2012, in Stroke.

The Honolulu Heart Program

Study participants included 7385 Japanese-American men who enrolled in the Honolulu Heart Program, a long-running, prospective, population-based observational study, between 1965 and 1968. They were 45 and 68 years old at the baseline examination and were followed through 1999 for stroke.

At baseline, the men's average intake of dietary vitamin D was 3.62 µg/day (range, 0.00 - 211.60 µg/day). During 34 years of follow-up, incident stroke occurred in 960 men. There were 651 (68%) thromboembolic strokes, 269 (28%) hemorrhagic strokes, and 40 (4%) strokes of unknown type.

Age-adjusted rates of stroke were significantly higher in the lowest dietary vitamin D quartile (0 - 1.12 µg/day) compared with the highest quartile (4.13 - 211.60 µg/day).

Table: Age-Adjusted Incidence Rates of Stroke (Per 1000 Person-Years Follow-up)

Stroke Type

Quartile 1

Quartile 4


All stroke




Thromboembolic stroke




Hemorrhagic stroke




Using Cox regression and adjusting for age, total caloric intake, body mass index, hypertension, diabetes, pack-years of smoking, physical activity, cholesterol level, and alcohol intake, patients in the lowest quartile of dietary vitamin D intake had a significantly increased risk of incidence of any stroke and thromboembolic stroke but not hemorrhagic stroke, relative to those in the highest quartile.

Table: Risk for Incident Stroke for Highest vs Lowest Quartile of Dietary Vitamin D


Adjusted Hazard Ratio (95% Confidence Interval)


P Value

All stroke

1.22 (1.01 - 1.47)


Thromboembolic stroke

1.27 (1.01 - 1.59)


Hemorrhagic stroke

0.97 (0.68 - 1.38)


Interpret Cautiously

In comments to Medscape Medical News, JoAnn E. Manson, chief of preventive medicine at Brigham and Women's Hospital, and professor at Harvard Medical School in Boston, cautioned that this is an observational study and "association does not prove causation."

"The association was modest, and the problem is that there are many potential confounding factors in these studies," Dr. Manson told Medscape Medical News. "Dietary factors often correlate with many other lifestyle factors that can be linked to heart disease and can confound the association."

"There may be a cause-and-effect relationship, but we certainly cannot determine that from this type of study. The only way to understand for sure whether higher dietary intake of vitamin D prevents cardiovascular disease and other health outcomes is randomized clinical trials that will balance out equally these other factors," added Dr. Manson, who was not involved in the study.

Dr. Manson is principal investigator of the Vitamin D and Omega-3 Trial, or the VITAL trial. Launched in 2010, VITAL is the first large, randomized clinical trial undertaken to study whether daily dietary supplements of vitamin D3 or omega-3 fatty acids reduce the risk of developing heart disease, stroke, and cancer in people who do not have a history of these illnesses.

She is coauthor of another recent article, published in the June issue of Stroke, looking at 25-hydroxyvitamin D levels and stroke risk in women participating in the observational Nurses' Health Study. These results show a "modest" correlation between vitamin D levels and subsequent stroke. Investigators carried out a meta-analysis using data from 6 other prospective trials that also suggest a relationship.

The current study was supported by the National Heart, Lung, and Blood Institute; the National Institute on Aging; and the Office of Research and Development, Department of Veterans Affairs. The authors and Dr. Manson have disclosed no relevant financial relationships.

Stroke. Published online May 24, 2012. Abstract



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