Introduction:
Resveratrol is a plant compound similar to flavonoids. It is found in low levels in the skin of red grapes, red wine, cocoa powder, baking chocolate, dark chocolate, peanuts, and mulberry. Red wine is perhaps the most recognized source of resveratrol, however, red wine contains at the very most only one milligram per glass. Most resveratrol supplements use Japanese knotweed (Polygonum cuspidatum) as the source with dosage recommendations often 500 mg of resveratrol up to four times daily. So it would take several thousands glasses of wine to provide the level of reservatrol that is provided through supplementation.
There has been a great deal of hype regarding resveratrol supplements, but there have also been some positive clinical studies showing positive results in improving memory and brain function in elderly subjects. A new study from Georgetown University’s Department of Neurology and researchers from 21 medical centers across the United States shows that reservatrol supplements may offer significant protection against Alzheimer’s disease.
Background Data:
Resveratrol has received a lot of attention as a longevity aid, but its scientific basis relies primarily on test tube and animal studies. There is only a handful of published human studies at this time, but the results are very encouraging.
Resveratrol activates an enzyme known as sirtuin 1 which plays an important role in the regulation of cellular life spans; it also promotes improved insulin sensitivity. Either of these two effects might explain its ability to extend lifespan.
In terms of brain health, a 2010 clinical study in humans showed that resveratrol supplementation at a single dosage of 250 or 500 mg could improve blood flow to the brain, but it had no effect on mental function in this study. In a 2014 study conducted in Germany, the use of a resveratrol supplement resulted in a significant impact on the ability to remember words compared with placebo. Resveratrol users also showed a significant increase in functional connectivity of the hippocampus – the area of the brain involved with the formation, organization, and storage of memory.
New Data:
A randomized, placebo-controlled, double-blind, multicenter study was conducted to examine the safety and effectiveness of resveratrol in 119 individuals with mild to moderate Alzheimer disease (AD).
The patients were randomized to receive either a placebo or resveratrol capsules. The initial dosage was 500 mg orally once daily, with dose escalation by 500-mg increments every 13 weeks until the final dosage of 1,000 mg twice daily was achieved. Brain MRI and cerebrospinal fluid (CSF) collection were performed at baseline and after 52 weeks of treatment.
Resveratrol and its major metabolites were measurable in the blood (plasma) and CSF in the subjects in the resveratrol treated group. The researchers looked at several biomarkers of Alzheimer’s including the level of beta-amyloid in the CSF. When beta-amyloid accumulates, it leads to significant damage to brain cells and the characteristic lesions of AD. Interestingly, although accumulation of amyloid-beta in the brain is a hallmark of AD, these patients actually have lower levels of this protein in the CSF. When the researchers look at the level of beta-amyloid in the CSF in the patients in the study, they found that subjects in the resveratrol group had higher levels of beta-amyloid proteins in their spinal fluid than those in the placebo group. The results suggest that resveratrol apparently helps prevent beta-amyloid accumulating in the brain and promotes its transport out of the brain so that it can be effectively broken down.
Resveratrol and its major metabolites clearly penetrated the blood-brain barrier as they were found in the CSF. An additional finding of interest was that the patients taking resveratrol lost about two pounds during the one-year study, while the placebo group gained about 1 pound. The brain MRI results showed that the resveratrol group had a smaller brain volume than the placebo group. The explanation being that the inflammation within the brain linked to AD can cause swelling and a larger brain volume. So, a smaller brain volume in this case (AD) is a positive sign.
These results clearly indicate a potential role of resveratrol supplementation in preventing AD.
Commentary:
Over the past few months and years I have featured several newsletters highlighting studies that reflect nutritional approaches for improving brain health, memory, and/or the prevention of age-related mental decline or AD. There are a lot of natural products to choose from, but the basic underlying goals and effects are quite similar. You have to reduce inflammation, control blood sugar levels, provide necessary building blocks with super nutrition, and protect the brain from damage by consuming antioxidants from the diet and through supplementation.
While resveratrol shows some compelling data as detailed above, my feeling is that it can’t do the job well enough by acting alone. It needs to be part of bigger approach that focuses on diet, lifestyle, and proper supplementation. In regards to diet, the Mediterranean or New Nordic Diet look very helpful. In regards to supplementation, there are four primary recommendations I make to people to help them design a foundation nutritional supplement program that also, not surprisingly are very important in preventing AD:
#1. Take a high quality multiple vitamin and mineral supplement providing at least the recommended dietary intake for all vitamins and minerals.
#2. Take enough vitamin D3 (typically 2,000-4,000 IU daily) to elevate your blood levels to the optimal range (50-80 ng/ml).
#3. Take extra plant-based antioxidants like flavonoid-rich extracts like grapeseed or pine bark extract; curcumin (Theracurmin); a “greens drink” product; resveratrol; or some other broad-spectrum antioxidant.
#3. Take a high quality fish oil product to provide 1,000 mg EPA+DHA daily for general health or up to 3,000 mg EPA+DHA if you have an inflammatory condition, cardiovascular disease, depression, ADHD, multiple sclerosis, or any other brain or nerve disorder; or any of the 60+ health conditions shown to respond or be prevented by fish oils.
Also, realize that in the study described above, benefits to the brain in these patients may have been secondary to improvements in blood sugar control as resveratrol has also been shown to improve insulin action. This potential link highlights the importance of using PGX, which I think is the most important supplement in North America today given its effects in supporting proper blood sugar control and weight loss. Some researchers have referred to AD as “diabetes of the brain.”
Reference:
Turner RS, Thomas RG, Craft S, et al. A randomized, double-blind, placebo-controlled trial of resveratrol for Alzheimer disease. Neurology. 2015 Sep 11. [Epub ahead of print]
Dr. Michael Murray
9/15/15
