Updated on March 23, 2023
There’s no denying that the currently available therapies for Alzheimer’s disease are suboptimal. As practitioners, patients, and families grow frustrated with the limited results of pharmacological approaches, researchers have begun exploring all-natural alternatives, including polyphenolic compounds derived from plant extracts.
For years, polyphenolic compounds have been recognized for their antioxidant properties and ability to support the body’s natural inflammatory response.* They also support cardiovascular function, which is important for Alzheimer’s patients because there is evidence suggesting a link between cardiovascular health and Alzheimer’s progression.* Because of the well-known bioactivity of polyphenols, researchers have begun to seriously consider polyphenols as an alternative therapy to utilize with Alzheimer’s patients. In preclinical studies, two of the polyphenols that have shown particular promise are Epigallocatechin-3-gallate (ECGC) and quercetin.
ECGC is a polyphenolic compound best known as the most abundant polyphenolic extract in green tea. Although in vitro studies show that ECGC can play a role in a variety of biological processes, there are three ways it might particularly benefit Alzheimer’s patients:
According to a model based on existing laboratory research, these activities should inhibit enlargement of the ventricles and the atrophy of the cerebral cortex and hippocampus, all of which are key structural changes observed in the brains of Alzheimer’s patients.
A 2017 preclinical animal study provides strong support for this proposed model. Researchers at Xi’an University in China demonstrated that in a mouse model of Alzheimer’s disease, oral supplementation with ECGC inhibited structural changes in the brain. Without supplementation, the mouse model displayed abnormalities in synaptic protein levels in both the frontal cortex and the hippocampus. The study showed that long-term ECGC therapy (15 mg/kg per day) could restore these levels, as measured by the reversal of the decreases in two different synaptic protein biomarkers. Moreover, the structural changes were coupled with notable behavioral effects; the mice treated with ECGC performed significantly better on maze tests that measured memory and spatial learning ability.
There is also pre-clinical evidence that ECGC supplementation can be even more effective when coupled with exercise, an exciting finding for patients interested in activity-based alternative therapies for Alzheimer’s disease. In 2015, researchers at the University of Missouri subjected mouse models to four months of wheel-running exercises combined with daily supplementation of ECGC (50 mg/kg per day). The supplementation led to a significant drop in amyloid beta plaque buildup (a hallmark of Alzheimer’s disease) in the cortex and hippocampus. The combination of ECGC and exercise also had positive behavioral impacts: the mouse models that received the intervention did not demonstrate the same behavioral deficits as the untreated Alzheimer’s mouse models in maze tests (which measured memory) and nest-building tests (which measured anxiety levels).
Not only do these results suggest that ECGC can directly address symptoms of Alzheimer’s disease, it also supports the hypothesis that the cardiovascular effects of ECGC might further contribute to its impacts. Exercise is a known mediator of cardiac function, so its effectiveness for addressing Alzheimer’s disease symptoms suggests that the cardiovascular benefits of ECGC could be indirectly supporting reductions in Alzheimer’s disease progression. This means that ECGC might help Alzheimer’s patients in two ways: through direct effects on the brain and through indirect effects on the cardiovascular system.
Like ECGC, quercetin is a polyphenolic compound that has shown considerable promise as an alternative therapy for Alzheimer’s patients in pre-clinical studies. Again, the potential of quercetin supplementation is underpinned by evidence of structural changes in mouse brains and corresponding behavioral changes. In a study from 2015, researchers treated a mouse model of Alzheimer’s disease with quercetin (25 mg/kg per day for three months). Extensive histological studies (studies of changes in mouse brain tissues) indicated that supplementation led to beneficial impacts on certain brain structures and declines in the presence of certain Alzheimer’s disease-associated proteins.* These effects were observed alongside improvements on behavioral tests of both cognitive and emotional function, which would make quercetin a promising alternative therapy for Alzheimer’s patients and practitioners looking for a more comprehensive treatment regimen.
Although there is broad speculation that antioxidant effects are at the core of quercetin’s effectiveness as a polyphenol, it might also be working through other molecular pathways. A 2016 study suggests that quercetin supplementation modulates levels of Apolipoprotein E (ApoE), a cholesterol carrier protein, and high cholesterol is a known risk factor for Alzheimer’s disease. The researchers propose that improving cholesterol metabolism is a novel mechanism through which quercetin can address an Alzheimer’s risk factor. The findings provide further evidence of a beneficial link between polyphenol supplementation, cardiovascular health, and the cognitive decline observed in Alzheimer’s patients.* In addition, polyphenolic compounds like quercetin could indirectly benefit Alzheimer’s patients by supporting heart health (in addition to their direct actions in the nervous system), thus being more effective than options that only target the brain.*
There are no major clinical studies that support the effectiveness of ECGC or quercetin in Alzheimer’s patients. Although there is one double-blind, placebo-controlled study on resveratrol, a similar polyphenolic compound that has shown promise in preclinical studies, preliminary clinical results are inconclusive. Researchers have determined that both supplements are safe and well-tolerated, but more research is necessary before researchers can confirm their efficacy.
In the future, it will be important to conduct rigorous clinical trials on both ECGC and quercetin while continuing to probe their mechanisms of action. But given the frustrating outcomes of conventional therapies and the promising laboratory evidence of polyphenolic supplements, patients and practitioners might want to consider integrating supplements now.
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