Resveratrol’s Link to Slowing Alzheimer’s
August 08, 2016 | 14,035 views
By Dr. Mercola
What do pomegranates, grape skin and raw cacao have in common? If your first thought was that they're all plant-based foods, you'd be right, but if you also knew they all contain a powerful antioxidant called resveratrol, you'd get a gold star!
Resveratrol is a polyphenol released by plants to help them resist damage from things like bacteria, excess ultraviolet light or injury, say, by aphids or other microorganisms.
The amazing thing is when you eat foods containing this compound, you, too, may experience similar benefits.
Resveratrol has been the object of scrutiny by scientists all over the world in relation to its effect on Alzheimer's disease, which currently hits someone in the U.S. every 66 seconds and affects 5 million Americans annually.1
Alzheimer's Disease Is on the Rise in the US
Most people know Alzheimer's as a disease that causes memory loss. In its earliest stages, it manifests itself in small ways, such as forgetting important dates or where things are; later, checkbook balancing becomes an increasingly frustrating challenge.
More progressed Alzheimer's patients confuse what day it is and where they are, and find words and distances difficult to discern. Following a conversation may become difficult for them. Progressively, their moods and personalities change. An Alzheimer's Association report reveals:
"The number of Americans living with Alzheimer's disease is growing — and growing fast … Of the 5.4 million Americans with Alzheimer's, an estimated 5.2 million people are age 65 and older, and approximately 200,000 individuals are under age 65 (younger-onset Alzheimer's)." 2
How and why it happens has been hypothesized about for years, but medicine has only been able to treat the systems rather than nailing down the root cause.
One of the downsides in humans, too, was that when it's taken in, resveratrol quickly metabolizes and is eliminated, which prevents your body from gaining much benefit.3 The Alzheimer's Association website also states:
"Alzheimer's is the only disease among the top 10 causes of death in America that cannot be prevented, cured or even slowed."
But in recent scientific findings, high doses of resveratrol given to individuals with mild to moderate Alzheimer's appeared to either slow the symptoms or stop them completely.
The results were presented at the Alzheimer's Association International Conference in Toronto in July 2016, providing a "bigger picture" of how resveratrol might work.
Initial Study: High-Dose Resveratrol May Hold Promise for Alzheimer's Patients
In 2015, the journal Neurology published a year-long study4 — the largest clinical trial in the U.S. on high-dosage resveratrol — on 119 subjects with mild to moderate Alzheimer's. Principal investigator Dr. R. Scott Turner said one of the objectives was to see if high doses of resveratrol might be safe in the long term.
Half of the study subjects were given a placebo; the other, resveratrol, starting with 500 milligrams (mg) per day and ending with two doses of 1,000 mg per day.
Scientists already knew that age-related diseases in animals could be decreased by caloric restriction and that resveratrol could imitate caloric restriction by means of releasing the same sirtuin proteins thought to play a role in the regulation of skeletal muscle mitochondrial function.
Restricting caloric intake is known to alter genes related to longevity by slowing the aging process in worms, rats and fish, but there's evidence it has the same effect on humans. As reported by Georgetown University Medical Center (GUMC), where the research took place:
"The researchers studied resveratrol because it activates proteins called sirtuins, the same proteins activated by caloric restriction.
The biggest risk factor for developing Alzheimer's is aging, and studies with animals found that most age-related diseases — including Alzheimer's — can be prevented or delayed by long-term caloric restriction (consuming two-thirds the normal caloric intake)."5
As dementia increases, a protein known as amyloid-beta40 (Abeta40) weakens. Researchers found the resveratrol group showed higher levels of amyloid-beta proteins in their spinal fluid, and their brain volume loss was increased by resveratrol treatment compared to placebo.6 According to a CNN report:
"Although accumulation of amyloid-beta in the brain is a hallmark of Alzheimer's disease, patients actually have lower levels of this protein outside of the brain. The study finding suggests that resveratrol could help change the balance from amyloid-beta buildup in the brain to circulating protein in the body."7
So when the scientists examined brain MRIs on the patients both before and after the study, they discovered that those in the resveratrol group lost more brain volume than those in the placebo group. Their supposition was that the treatments reduced the brain swelling common with Alzheimer's sufferers.8
Those findings were called "paradoxical" and "puzzling," providing a segway for a follow-up study.
New Findings: Inflammation Versus Resveratrol
Turner was lead investigator in the second trial on resveratrol, working with Dr. Charbel Moussa, scientific and clinical research director at GUMC. In the new clinical trial, 19 subjects received high doses of resveratrol, equal to 1,000 bottles of red wine, and another 19 received a placebo.
One of the scientists' main goals was to investigate levels of matrix metalloproteinase-9 (MMP-9) molecules in Alzheimer's patients' cerebrospinal fluid (CSF). Sure enough, tests showed the number decreased by 50 percent in comparison with the placebo group. Medical News Today noted:
"This is significant because MMP-9 is reduced when sirtuin1 (one of the proteins linked to caloric restriction) is activated. Higher levels of MMP-9 are known to cause a breakdown of the blood-brain barrier — a blockade that normally prevents proteins and other molecules from entering the brain.
Additionally, the team found that resveratrol increased levels of compounds linked to a long-term 'adaptive' immune response; this suggests an involvement of inflammatory cells that are resident in the brain. This type of reaction degrades and removes neurotoxic proteins."9
Besides brain inflammation, Alzheimer's patients are often further compromised by nervous tissue inflammation, linked to degraded neurons and subsequent cognitive decline, caused by the MMP-9 molecules. However, resveratrol seems to act as a sort of gatekeeper, keeping the harmful immune molecules from entering your brain.
Scientists said similar decreased brain inflammation has been noted by scientists in drugs used for patients with multiple sclerosis, another brain disease characterized by too much inflammation.
While the high resveratrol doses caused some of the study participants to experience nausea, diarrhea and either slight weight gain or weight loss, researchers said the supplements caused no other side effects.
Besides finding a more significant role that inflammation may play in causing Alzheimer's, scientists expressed excitement about resveratrol's measurable anti-inflammatory effects and plan further investigation.
Resveratrol Mitochondrial Benefits
A number of reviews have described other health benefits from resveratrol. The journal Nature said resveratrol improves the health and survival rate of mice on a high-calorie diet, possibly revealing a treatment option for obesity-related disorders and diseases of aging.10
Another showed resveratrol improved mitrochondria, the tiny, vital engines in nearly all your cells producing more than 90 percent of the energy currents in your body, and protected against metabolic disease, diet-induced obesity and insulin resistance.11 Mitochondrial protection via resveratrol was discussed in another study, which noted:
"Age-specific mortality rates from heart disease, stroke, complications of diabetes, Alzheimer disease and cancer increase exponentially with age …
The evidence (supports) the hypothesis that mitochondrial protective effects of resveratrol underlie its anti-aging action that can prevent/delay the development of age-related diseases in the cardiovascular system and other organs."12
Resveratrol has been shown to improve mitochondrial function and protect against metabolic disease by its ability to activate SIRT1 and PGC-1alpha, the primary driver for mitochondrial biogenesis. Science Direct13 noted resveratrol's potential anti-aging and anti-diabetic properties via Sirt1, essentially recharging your mitochondria. According to a review of pre-clinical studies for human cancer prevention:
"Resveratrol is known to have potent anti-inflammatory and anti-oxidant effects and to inhibit platelet aggregation and the growth of a variety of cancer cells.
Its potential chemopreventive and chemotherapeutic activities have been demonstrated in all three stages of carcinogenesis (initiation, promotion and progression), in both chemically and UVB-induced skin carcinogenesis in mice, as well as in various murine models of human cancers.
Evidence from numerous in vitro and in vivo studies has confirmed its ability to modulate various targets and signaling pathways."14 Still another study used mice to show that PGC-1α prevents the formation and accumulation of lactate in the muscles.15
Caveats in Regard to Obtaining Resveratrol From Your Diet
One little known but powerful source of resveratrol is itadori tea,16 a traditional herbal remedy used in Japan and China for heart disease and stroke. Both itadori tea and red wine contain high concentrations of resveratrol. But while you may be thinking of upping your red wine intake to glean the resveratrol benefits, keep in mind that alcohol can damage your brain and other organs, so it's counterintuitive to drink it in order to help your brain.
Because resveratrol is most concentrated in the skin of grapes, and muscadine grapes are thick-skinned, this would be a better source. However, grapes are high in sugar (fructose) and should only be eaten in moderation, making it difficult to obtain therapeutic quantities of resveratrol.
Excess fructose consumption has been linked to metabolic syndrome, adverse endocrine effects, kidney damage and pancreatic cancer, to name a few problems.
My recommendation for fructose consumption is an average of around 25 grams per day, including from whole fruits. However, if you have a problem with insulin resistance, high blood pressure, cardiovascular disease or cancer, your fructose intake should be cut down to 15 grams.
Understand, too, that the long arm of Monsanto has reached even into grapes used to make organic wine. Studies also show that wine may contain high levels of arsenic and carcinogens. Even without those factors, it stresses your liver and increases your insulin levels, which altogether can lead to a wide array of health problems and serious illness.
Even Turner, who helped author the study, conceded that one glass of red wine a day could help with mild Alzheimer's, but he cautioned: "No more than that."17