Protein, Especially Fish, Linked to Reduced Stroke

Pauline Anderson

June 12, 2014

Intake of protein, especially fish, is associated with a decreased risk for stroke, results of a new meta-analysis show.

"Our findings suggest that moderate dietary protein intake may lower the risk of stroke," study author Xinfeng Liu, MD, PhD, professor and chairman, Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, Jiangsu Province, China, told Medscape Medical News.

The primary protein driver was fish intake, while animal protein appeared to be associated with increased risk. "These results indicated that stroke risk may be reduced by replacing red meat with other protein sources such as fish," write the authors.

The study is published online June 11 in Neurology.

Major Contributor

Researchers searched PubMed and Embase for studies with a prospective design that investigated intake of protein — including total protein, animal protein, and vegetable protein — and included the outcome of stroke and stroke subtype.

The analysis included 7 studies (4 from the United States, 2 from Japan, and 1 from Sweden) with a total of 254,489 participants. The length of follow-up ranged from 10.4 to 18 years, with a median of 14 years. Four studies assessed the dietary protein intake by food-frequency questionnaires and 3 by 24-hour dietary recall.

Researchers pooled the relative risk (RR) for stroke for the highest dietary protein intake compared with the lowest. Overall, compared with participants in the lowest category, the RR among those with the highest was 0.80 (95% confidence interval [CI], 0.66 - 0.99).

According to the results, animal protein intake could decrease risk for stroke by 29% while vegetable protein could decrease it by 12%. This may be due to a narrower range between the highest and lowest intake for vegetable protein, said the authors.

The results suggest that protein from fish is a major contributor to stroke protection while red meat was associated with an increased risk. Two Japanese studies and 1 study in which fish was the primary source of animal protein observed a decreased stroke risk.

The association between protein intake and risk for stroke was stronger in women than men. "This may be due to the fact that the male subgroup only contained 1 study, which may have insufficient statistical power to detect a slight effect or may have generated a fluctuated risk estimate," explained Dr. Liu.

A dose-response analysis found that the risk for stroke decreased by 26% (RR, 0.74; 95% CI, 0.65 - 0.84) for every 20-g per day increment in total protein intake, the study found. "This risk reduction would be translated into a reduction of 1,482,000 stroke deaths every year worldwide and is expected to produce overall health benefits by decreasing the level of disability," write the authors.

Likely Mechanism

The protective effect of protein could be due to its lowering of blood pressure, triglycerides, total cholesterol, or non–high-density lipoprotein or through a substitution effect, where patients replace potentially harmful foods with high-protein ones, However, said Dr. Liu, "in my opinion, lowering of blood pressure is the most likely" explanation, he said.

This is supported by the analysis by stroke type, in which the protective effect was found in intracerebral hemorrhage. "Hypertension is a very crucial risk factor for intracerebral hemorrhage," noted Dr. Liu.

The research team acknowledged that other factors may account for the observed association. For example, dietary protein tends to be associated with nutrients, such as potassium, magnesium, and dietary fiber, that may also prevent stroke. However, the stroke risk persisted after they confined the analysis to studies that adjusted for these risk factors.

"I think protein has a similar role as other nutrients in protecting against stroke," commented Dr. Liu.

Dietary protein intake may also have been misclassified because most studies assessed diet only at baseline and did not update it during follow-up, the authors note.

A randomized trial to test a high- versus a low-protein diet with stroke as an outcome "is anticipated," Dr. Liu said.

More Data Needed?

In an accompanying editorial, Arturo Tamayo, MD, Brandon General Health Center and Winnipeg Health Sciences Center, and Luis Castilla-Guerra, MD, PhD, Stroke Clinics, Section Neurology, University of Manitoba, Canada, and Department of Internal Medicine, Hospital de la Merced, Spain, say the study results should be reviewed cautiously.

While more benefits were found with animal protein sources than with grains, the grain study population was small; this could have been a factor for the inconsistent results, they write. "Therefore, labeling animal protein completely as beneficial is not helpful until more data are available."

The finding that patients who consumed fish had a stroke benefit corroborates the results of multiple studies, the editorialists note. The protective impact, they say, is due to the favorable effects of certain polyunsaturated fatty acids on blood pressure, lipid profiles, platelet activity, and endothelial function.

Another interesting result of the study was that it corroborates that red meat has a negative role in stroke prevention, they note.

However, it seems "invalid" to focus exclusively on protein when it comes to diets that prevent stroke, the editorial writers conclude. "It is paramount to promote diets low in sodium and higher in potassium, magnesium and calcium," they write, adding that more recently the importance of folate and vitamin B12 has been emphasized.

The study was supported by the National Natural Science Foundation of China and the Natural Science Foundation of Jinling Hospital.The authors and editorialists have disclosed no relevant financial relationships.

Neurology. Published online June 11, 2014. Abstract Editorial

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