Flavonoid in Strawberries May Limit Diabetes Complications

The research, suggests that fisetin may reduce diabetes complications by protecting nerve cells from toxic insults and by direct effects of antioxidant and anti-inflammatory activity. 

Significantly, the study found that oral fisetin reduced methylglyoxal-protein glycation in the kidney, brain, and blood of diabetic mice, lending support to the hypothesis that complications of diabetes share common pathogenic mechanisms, the study authors say.

Fisetin, or a synthetic version of it, might eventually be used to treat patients with diabetes, said corresponding author, Pamela Maher, PhD, senior staff scientist at The Salk Institute for Biological Studies.

"A compound that could reduce some or all of these complications has a real potential for improving quality of life for people with diabetes," Dr. Maher said.

For their experiments, the researchers used Akita mice, which, because of a mutation in the insulin gene, develop the pathologic characteristics of type 1 diabetes, including diabetic nephropathy and elevated anxiety symptoms. Male Akita mice develop hyperglycemia by 4 weeks of age.

The researchers added the equivalent of about 25 to 40 mg/kg of fisetin daily to the food of the Akita mice and of wild-type control mice and tested blood glucose levels at 12 and 24 weeks. Fisetin had no effect on blood glucose in either the Akita or control mice.

At baseline, the kidneys of the Akita mice were significantly heavier than those of controls, consistent with hypertrophy associated with diabetic nephropathy. Their kidneys were significantly reduced in size by fisetin, which had no effect on the kidneys of control mice.

Urine analysis also showed significant albuminuria in the Akita mice that was almost completely eliminated by dietary fisetin. Fisetin had no effect on the albumin:creatinine ratio in control mice.

The researchers also found that oxidative markers were elevated in the kidneys of Akita mice but not in the control animals and that this was prevented by feeding the animals fisetin.

Interestingly, the study authors noted that a recent epidemiologic study found kidney disease is a marker for brain dysfunction in people with type 1 diabetes.

As for markers of inflammation associated with diabetes, the researchers found that C-reactive protein (CRP) was significantly increased in the plasma of Akita mice and that this increase, too, was attenuated by the fisetin-rich diet.

Flavonoids are thought to protect the leaves and fruit of plants against the sun and insects. They're an integral part of the healthy "Mediterranean" diet that is rich in fruits and vegetables and includes red wine, which contains flavonoids called polyphenols.

The fisetin flavonoid is found in highest quantities (160 μg/g) in strawberries, but even that isn't very much. To consume the equivalent of what the mice ate in the study, an average 150-lb person would have to down 37 strawberries every day, said Dr. Maher. Fisetin is more soluble in fat than water, so consuming strawberries with something like cream might aid absorption, although "there are obviously concerns about eating too much cream," she said.

Fisetin is also found, although in 5- to 10-fold lower levels, in apples and persimmons and even smaller amounts in kiwi fruit, peaches, grapes, tomatoes, onions, and cucumbers.

Supplements containing fisetin are apparently available over the Internet but in doses substantially lower than those used in this study.

The study adds to the growing body of evidence of the health benefits of flavonoids, said Dr. Chelimsky. "Beyond just talking about diabetes, this research adds to growing information that flavonoids are good for you."

PLoS ONE, Published online June 27, 2011