Alzheimer’s disease remains a debilitating and tragic disorder despite decades of scientific research attempting to find a cure. Even with the advent of new drugs designed to slow the progression of the disease, patients and doctors alike are still looking for ways to stave off its onset and reduce the severity of its cognitive effects. Patients may soon have reason to be hopeful, however. In the hunt for effective treatment, scientists are now on the verge of cracking the secrets of a new therapeutic molecule: quercetin.
Quercetin is a molecule produced by a variety of plants, including grains, onions, and leafy greens. It’s also a member of the bioactive flavonoid family of molecules. Like other flavonoids, quercetin is metabolized easily by humans and has a variety of physiological effects ranging from scavenging reactive oxygen species to reducing inflammation. Importantly, many flavonoids like quercetin have effects which suggest that they’re useful in protecting against dementia and improving cognition in those affected by neurodegenerative diseases.
These effects are documented in a seminal 2008 paper by Drs. David Vauzour, Katerina Vafeiadou, Ana Rodriguez-Mateos, Catarina Reneiro, and Jeremy Spencer from the University of Reading in the UK. The researchers’ collation of prior research into flavonoids is directly applicable to quercetin and is one of the few comprehensive summaries of flavonoids’ impact on cognition as portrayed in the scientific literature. The researchers’ analysis cites a handful of other studies on flavonoids sourced from many different plants, finding that the source of the flavonoid doesn’t seem to change their physiological effects. In the course of their research summary, the authors of the review tie together countless pieces of information which, taken together, indicate that if patients find the right sources of quercetin and other flavonoids, they can slow down the rate of cognitive decline caused by old age. Significantly, they’ll also increase the ability of their neurons to survive the ravages of dementia which are typical in Alzheimer’s disease.
How Do Flavonoids Work?
Flavonoids have a number of significant physiological effects, ranging from anti-inflammatory and anti-allergenic properties to supporting neuronal health. In their synthesis of the research on flavonoids, Dr Vauzour’s group approaches the neuroprotective properties of flavonoids as their primary point of inquiry. The researchers break the beneficial properties of flavonoids into three separate but related phenomena, as identified by several other studies examining flavonoid class molecules:
- Protection of the brain against neurotoxins
- Suppression of neuroinflammation
- Promotion of cognitive functioning and memory
While functionally discrete, each of these phenomena is caused by activation of the same physiological mechanisms. This means that any flavonoids consumed will be beneficial in all three cases.
The mechanisms of these beneficial effects are inhibition of cell death and the promotion of blood vessel formation. The former is particularly important, as inhibition of cell death occurs via flavonoids’ interaction with certain enzymes used in cell signaling; when cells are exposed to flavonoids, they can’t send each other chemical signals that trigger cell death, which means that cells destroy themselves less frequently. Additionally, the promotion of new blood vessel formation helps to increase the resiliency and functionality of tissues by allowing for greater oxygenation. Taken together, these effects may have a significant impact on symptoms of Alzheimer’s disease.
Quercetin And Cognition In Alzheimer’s
Of the mechanisms responsible for flavonoids’ protective effects in Alzheimer’s disease, their impact on cell death signals is potentially the most useful, as decreasing cell death signaling leads to increased neuronal survival. When glial cells responsible for supporting the brain’s neurons are exposed to flavonoids, their production of the cell death signal protein tumor necrosis factor alpha (TNFa) is inhibited. TNFa is also linked to inflammatory states in the brain, which means that its inhibition reduces inflammation. Increasing levels of inflammation are linked to worsening Alzheimer’s symptoms. These combined effects mean flavonoid supplementation may cause neurons to self-destruction less frequently and perform more efficiently than they would in an inflamed state.
Neuronal persistence is particularly critical for Alzheimer’s disease patients. As part of the main pathology of Alzheimer’s, clumps or “plaques” of a harmful protein called beta-amyloid accumulate inside neurons and inhibit their function, eventually killing them. As more neurons die, cognitive functions, memory consolidation, and memory recall are hampered. The researchers optimistically discuss flavonoids’ ability to reduce the cellular death caused by exposure to beta-amyloid plaques, as observed in several validated in vitro studies.
A year after the researchers substantiated the connection between the entire class of flavonoid molecules and resistance against beta-amyloid-induced cellular death, another group of researchers from the University of Kentucky published a paper documenting their results examining quercetin specifically. This research cohort performed extensive in vitro investigations of quercetin’s impact on cultured neurons that were exposed to beta-amyloid. The results were compelling: neurons treated with small quantities with quercetin experienced lower cytotoxicity, lower oxidative stress, and 33% less cell death when exposed to beta-amyloid plaques in comparison to cells which weren’t treated. The samples treated with quercetin also exhibited 75% fewer proteins associated with Alzheimer’s induced cellular damage.
Quercetin was not uniformly helpful, however. When the researchers tested the impact of extremely high concentrations of quercetin, they found that the protective effect disappeared. However, reaching these concentrations would be impossible by consuming quercetin in foods alone due to the speed at which it is metabolized, which means that patients are unlikely to encounter this effect. The researchers’ findings were promising, though the fact that their experiments were limited to cell cultures prevented them from speculating about any in vivo effects. Their work has recently been confirmed by numerous other researchers.
The Potential of Quercetin in the Treatment of Other Neurological Diseases
Although Dr. Vauzour’s primary area of interest was Alzheimer’s disease, literature review also makes a compelling case for applications of flavonoids in the treatment of other neurological diseases. Dr. Vauzour’s group discussed several studies linking flavonoid consumption to improved patient outcomes in dementia, Parkinson’s disease, and even depression. Significantly, several of these studies were in vivo investigations with large cohorts of patients.
One notable example cited by Dr. Vauzour’s review examined 1640 subjects who were healthy and without dementia. The study followed the subjects for 10 years, performing cognitive testing and surveying the subjects’ diets frequently along the way. With a very high degree of confidence, the results showed that those with higher flavonoid intake exhibited better cognitive performance than those with lower flavonoid intake. This effect was exaggerated when the researchers compared the group with the lowest self-reported flavonoid intake with the group who reported the highest. Earlier research had found the same relationship.
At the conclusion of the study, the researchers found that the difference in cognitive performance between the groups was nearly a full point on the Mini-Mental State Examination. The Mini-Mental State Examination is used as a tool to aid in the diagnosis of dementia and is scored out of 30 points. After controlling for all potential confounding variables, the benefit of flavonoids persisted in the data; the high flavonoid intake group scored on average 0.9 points better than the low flavonoid intake group. This means that while flavonoids can decrease the damage caused by Alzheimer’s disease, it can also help patients maintain a greater degree of cognition in the course of normal aging. Other studies with large cohorts of patients have since confirmed this phenomenon. Dr. Vauzour’s group was enthusiastic about the safety and potential of flavonoid therapeutics, but they did outline one catch: “In order for flavonoids to access the brain, they must first cross the blood brain barrier, which controls entry of xenobiotics into the brain.” In short, the research group was concerned about the flavonoids’ bioavailability. After examining relevant research, the authors subsequently conclude that “flavonoids traverse the blood brain barrier and are able to localize in the brain, suggesting that they are candidates for direct neuroprotective and neuromodulatory actions.”
Improving Quercetin Efficacy
Flavonoids like quercetin are an exciting new frontier for Alzheimer’s patients and doctors alike, and they could hold the key to slowing the disease’s progression. As the researchers note, flavonoids are surprisingly ideal for therapeutic use because, unlike most pharmaceutical molecules, they can easily cross the blood-brain barrier without being modified. However, flavonoids can’t be reliably stored or distributed in the body, as they are metabolized by multiple organs at an extremely high speed; although some of the metabolites are bioactive, they are broken down quickly.
Due to the rapid and comprehensive way the body breaks down quercetin and other flavonoids, their physiological impact is limited. This problem is deepened by the fact that most foods that contain flavonoids have far fewer flavonoid molecules than the quantities necessary to produce beneficial effects in in vitro studies. As such, supplementation will be necessary for patients who want to add quercetin to their treatment regimes and these supplements must be formulated to compensate for the metabolic barriers of the molecule and ensure bioavailability.
The picture created by Dr. Vauzour’s group is clear: if flavonoids such as quercetin can be formulated to be bioavailable, it will be much easier for patients with Alzheimer’s, dementia, and other neurological conditions to access their benefits. Already, scientists are developing advanced new delivery systems which can survive first-pass metabolism and control the distribution of quercetin to achieve therapeutic concentrations. If patients want an extra edge against Alzheimer’s that spans multiple aspects of the disease’s impact, finding a highly bioavailable quercetin supplement is thus an excellent place to start.
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