By Melanie Haiken
March 31, 2014
Fisetin, a flavonol found in strawberries, mangoes, cucumber, and other fruits and vegetables, may protect the brain against Alzheimer’s, dementia, and age-related memory loss, according to research just out from the Salk Institute for Biological Studies.
Mice that had been genetically programmed to develop Alzheimer’s retained their normal cognitive skills when they were fed fisetin, found a team led by Salk Institute Senior Staff Scientist Pamela Maher, who’s been studying the potential of fisetin to protect brain health for more than a decade.
In the study,which was published in Aging Cell, researchers gave Alzheimer’s-fated mice water supplemented with fisetin, then compared them with mice who did not receive fisetin, as well as with normal mice without the Alzheimer’s genes. Within nine months, the Alzheimer’s mice began to lose their cognitive abilities, losing their way in a water maze. Meanwhile, the cognitive abilities of the fisetin-supplemented mice remained similar to those of genetically normal mice. At the one-year mark, follow-up tests showed the Alzheimer’s-wired fisetin-fed mice still showed no sign of decline.
Maher calls fisetin a “groundbreaking” preventative strategy with strong potential to protect the brain from Alzheimer’s, dementia, and age-related memory loss. ”We had already shown that in normal animals, fisetin can improve memory,” she says, adding, ”What we showed here is that it also can have an effect on animals prone to Alzheimer’s.”
In previous studies, Maher and her team at Salk’s Cellular Neurobiology Laboratory have identified numerous ways in which fisetin works on metabolic pathways to age-proof the brain. In a 2009 paper summarizing her research, Maher called fisetin a “novel neuroprotective and cognitione-enhancing molecule and cited fisetin’s “wide range of actions” to keep the brain humming along.
It’s important to point out that the bulk of the fisetin studies that have been conducted to date are in vitro or in animals, rather than in humans. Therefore, we don’t know for certain that fisetin will have the same potent effects on human brain health; the scientific literature is littered with promising antioxidants that did not hold up in human trials.
In the current study, Maher’s team collaborated with scientists from the University of California, San Diego, to examine the mice’s brains for evidence of changes associated with fisetin supplementation.
What they discovered was fascinating: In the brains of the mice genetically modified to develop Alzheimer’s, pathways associated with inflammation at the cellular level were activated. But in the brains of fisetin-treated mice, the scientists found anti-inflammatory molecules that quieted the inflammation. More specifically, the scientists said, fisetin appeared to affect a protein known as p35 that’s been implicated in turning on inflammatory pathways.
What is Fisetin?
Never heard of fisetin? That’s because it was only identified a little more than a decade ago when scientists isolated plant flavonols with the ability to protect brain cells from degeneration. Like the similar flavonol quercetin, it’s a sirtuin-activating compound that mimics many of the natural effects of calorie restriction, a well-studied anti-aging strategy.
Scientists studying fisetin (also called flavonoid 3,7,3′,4′-tetrahydroxyflavone) say it has positive effects on a number of cellular signalng pathways associated with brain aging. Research shows that fisetin protects nerve cells from age-related damage, including damage from stroke. Fisetin works via specific pathways to boost production of glutathione, an antioxidant that studies have shown prevents oxidative damage to brain and nerve cells. Fisetin also preserves mitochondrial production and reduces levels of peroxynitrite, a free radical that damages neurons.
While there have not yet been clinical trials of fisetin for brain health, fisetin has been studied for it’s anti-cancer and diabetes benefits and shows serious potential.
The Alzheimer’s Drug Discovery Foundation, in its overview of fisetin, says it’s possible fisetin can prevent dementia but there is as of yet very limited evidence. (Worried you might be at risk for Alzheimer’s? Take this test here.)
How Do I Get More Fisetin?
Unfortunately, fisetin is not a common antioxidant, and is present in only very small quantities in certain fruits and vegetables. Strawberries are the best source of fisetin, but scientists colloquially suggest you’d need to eat 37 strawberries to get an adequate dose. The next best sources of fisetin are mangoes and cucumber with the skin left on; it can also be obtained from apples, persimmons, kiwi, peaches, grapes, tomatoes, and onions.
The amount of fisetin in fruits and vegetables is so small that unless you really like strawberries (and can get them all year long), it would be difficult to get the amount used in the studies from diet alone. Hence researchers are looking into the creation of fisetin supplements.
Luckily, many other plant sources are higher in the compound, including acacia trees, the honey locust, and the Japansees wax shrub. Therefore there are plenty of sources from which to derive supplements. Fisetin is already turning up in many anti-aging supplements directed at preserving brain health, many with cute names like 37 Strawberries and Brain-Retain.
In 2011 The Salk Institute received a patent on a fisetin supplement of its own, cleverly titled Cognisetin, which it licensed to Cyvex Nutrition with exclusive distribution rights. Cyvex in turn sells Cognisetin to supplement manufacturers such as Doctor’s Best.
Stay tuned for actual human trials of fisetin to see if it really works.