Quercetin and Vitamin C May Protect Brain Cells

Quercetin and Vitamin C Pack a One-Two Punch

Quercetin and Vitamin C
May Protect Brain Cells

Their antioxidant action, dramatically evident in the
laboratory, could be a weapon against Alzheimer’s
By Will Block

n apple a day keeps the doctor away. How often have you heard that old saw? Don’t you wish you had a dollar for every time you did? Another way to look at it is to wonder whether every apple you’ve ever eaten may have saved you a dollar in medical costs in the long run. Eating healthy foods (and avoiding unhealthy ones) is, after all, one of the best ways to ensure a long, healthy life without too many costly visits to the doctor’s office or hospital. And when it comes to healthy foods, few have such wholesome appeal as apples. They have enjoyed a special place in our culture ever since the Garden of Eden, when Eve took that first, fateful bite of the forbidden fruit from the tree of knowledge of good and evil.

Eating that apple imbued Adam and Eve with knowledge of sin—but it’s knowledge of science that concerns us here. What science has told us recently is that apples may be even better for our health—including our mental health—than we had thought, owing to a chemical compound called quercetin, which is prevalent in apple skins (especially the red ones). The primary medicinal use for quercetin is in the treatment of capillary fragility.1 Here’s what the respected PDR for Nutritional Supplements has to say about quercetin:2
Quercetin may have antioxidant, anti-inflammatory, antiviral, immunomodulatory, anticancer, and gastroprotective activities. It may also have antiallergy activity and activity in preventing secondary complications of diabetes.

A Good Reason for Supplementing with Quercetin

That gets your attention, doesn’t it? Let’s find out more about this remarkable compound. Quercetin (pronounced kwur´si-tin) is a flavonoid, a member of a class of polyphenolic compounds known for their strong antioxidant activity. It’s found not just in apples, but also in onions, red wine, green tea, and St. John’s wort, and it’s widely distributed throughout the plant kingdom in rinds and barks. The name comes, in fact, from the Latin quercetum, meaning oak forest (from quercus, oak).

So to get quercetin in our diet, we could chew bark, or we could eat apples or onions, or drink wine or tea. All but one of those sound delightful and are undeniably healthful for many reasons that go far beyond the benefits of quercetin. But there is, of course, another way to get quercetin, and that is through supplementation, which guarantees a reliable and optimal daily intake. One reason for wanting that is that quercetin may be beneficial in helping to prevent Alzheimer’s disease, according to researchers in the Department of Food Science and Technology at Cornell University.3*


*A supplement with proven efficacy in treating mild to moderate cases of Alzheimer’s, and probably in helping to prevent it in the first place, is galantamine. See the sidebars for some new information on this invaluable substance.


Galantamine Helps a Forgetful “Ferrari”

It’s unsettling to see a Ferrari running poorly because it needs a tune-up, but it’s not as though the car can’t still go pretty fast—it is, after all, a Ferrari. Similarly, when a person of exceptional intelligence suffers a mental slowdown, such as memory decline, the problem begins at a sufficiently lofty level that it may not even be noticeable for a long time, especially since the person may be skillful in compensating for it. Furthermore, tests of cognitive ability that are designed with folks of average intelligence in mind may not be adequate to discern the difference between a high level of function and a somewhat lower high level.

Sometimes the cognitive decline in such individuals goes unnoticed until some particularly upsetting event brings it to the fore in an unexpected manner. A dramatic example is an episode of transient global amnesia (TGA), which is a sudden inability to acquire new information. Things are happening, but they’re not registering in the person’s memory, so there’s no recollection of them immediately afterward. That’s upsetting!

And that’s what happened to a 74-year-old retired engineer (“Mr. A”) in California, as reported by one of his doctors.1 One morning in 2000, Mr. A went to pick up his car (the make was not specified, darn it) at an auto repair shop and got into a heated argument with the staff over their sloppy work. Later, when he got home, he had a headache and complained that he could remember nothing that had occurred after the verbal battle; he also had some difficulty recalling the events of the previous day.

Mr. A wound up in the hospital, where lab tests were negative. An MRI scan, however, showed some abnormalities, including a blocked right vertebral artery (which ascends through the spinal column into the brain). Meanwhile, his memory began to return—a typically benign outcome for this odd disorder. He was unnerved by the experience, however, and with time he began noticing other symptoms of cognitive impairment, such as a tendency to transpose numbers and to have difficulty visualizing things in three dimensions.

Neuropsychological testing of Mr. A in 2002 (he was then 76) revealed short-term verbal memory impairment that was out of proportion to the rest of his cognitive function. Although his scores on many cognitive tests were high for a man of his age, they were deemed to have been reduced (a judgment call) relative to his previous level of functioning. Based on his memory impairment and his self-reported problems with numbers and 3-D visualization, the diagnosis was one of early dementia (probably of the Alzheimer type) rather than its common precursor, mild cognitive impairment. Nonetheless, he was still functioning pretty well by most standards—a testament to his “Ferrari” intellect.

And now, the punch line: Mr. A was treated with galantamine (24 mg/day), and he and his family noticed an improvement in his cognitive functioning (no details were given in the report), which had apparently been sustained for 18 months with galantamine therapy when the report was written. Galantamine is well known for its ability to stabilize and even to improve (for a period of months) the condition of patients with mild to moderate Alzheimer’s disease, and this appears to be another success story of that kind.

Of course, there is no proof in this case (as the author admits) that galantamine caused the improvement in Mr. A’s condition, but it seems likely that it did, because in placebo-controlled studies with galantamine, the condition of the patients taking the placebo typically continues to deteriorate, while the condition of the patients taking galantamine typically stabilizes or improves.

  1. Daniel ES. Early diagnosis and treatment of dementia presenting as transient global amnesia in a 76-year-old man. Prim Care Companion J Clin Psychiatry 2004;6:248-51.

Galantamine Helps the Brain-Injured

With good reason, people fear brain injury more than almost any other kind. Fortunately, thanks to our well-designed skulls, our brains are generally well protected—but accidents will happen. It is estimated that in Europe and North America there are at least 19 million people living with a permanent disability of one kind or another caused by traumatic brain injury (as opposed to brain injury caused by disease), or TBI.1

The four main consequences of TBI are fatigue, poor memory, attention deficits, and diminished initiative ability, and psychiatric symptoms caused by the injury are also common in such patients. Sadly, however, there are practically no effective therapies available.

Well, perhaps there are after all, according to Dr. Olli Tenovuo, a neurologist at the University of Turku in Finland, who notes that the brain functions that are defective in TBI (regulation of vigilance, attention, and memory) are at least partly mediated by cholinergic neurons, i.e., those whose principal neurotransmitter is acetylcholine.1 Collectively, these neurons constitute the cholinergic system of the brain. Impaired cholinergic function caused by diminished acetylcholine activity is one of the hallmarks of Alzheimer’s disease and is found in some other forms of dementia as well.

The standard treatment for Alzheimer’s is with agents called acetylcholinesterase inhibitors, of which the three most commonly used are the nutritional supplement galantamine (which is also sold as a prescription drug) and the prescription drugs donepezil and rivastigmine. What if … ?

Dr. Tenovuo’s medical practice at the university’s outpatient clinic includes hundreds of patients with TBI annually. Following up on suggestive evidence from studies by other researchers, he started in 2001 to treat some of these patients with the three agents mentioned above to see if their condition could be improved (most patients received just one of the agents, but some tried two or even all three). There were 111 adult patients in all (average age 40), most of whom were men, which is typical for TBI. The injuries, which ranged in severity from mild to extremely severe, had occurred 6 years earlier, on average, and had been caused mainly by traffic accidents and falls.

The patients reported their responses to Dr. Tenovuo personally, and his conclusions were based solely on these subjective descriptions. Overall, 61% of the patients had a marked positive response (which typically began immediately) to at least one of the agents, but there was no statistically significant difference among the agents—all three were about equally effective. (The dosage of galantamine used was a fairly low 10 mg/day.) The clearest and most prevalent benefit was increased vigilance, together with improved attention and initiation, which added up to a generally higher level of functioning in everyday life. As a result, some patients were able to return to work or to their studies. Dr. Tenovuo reported that no other treatment had hitherto given comparable results in his practice.

A surprising result was that some patients remained at a higher level of functional ability for weeks or even months after discontinuing the treatment (because of financial problems, e.g.). This is strikingly different from clinical experience with Alzheimer’s patients, who tend to begin declining promptly if treatment is discontinued. (In Alzheimer’s, galantamine is generally more effective than donepezil or rivastigmine in its ability, often, to improve the patient’s condition for a period of months rather than merely holding it steady for some months before the inevitable decline resumes.)

Although Dr. Tenovuo’s study was not a randomized, double-blind, placebo-controlled trial (the “gold standard”), the results are intriguing and are probably not, in his opinion, due to the placebo effect. They strongly suggest that formal trials are needed to pursue this fascinating new insight into the capabilities of galantamine and its pharmaceutical brethren.

  1. Tenovuo O. Central acetylcholinesterase inhibitors in the treatment of chronic traumatic brain injury—clinical experience in 111 patients. Prog Neuropsychopharmacol Biol Psychiatry 2005;29:61-7.

Your Cells Produce Natural Toxins

In previous work, the Cornell researchers had demonstrated that phenolic compounds found in apples have strong antioxidative and antiproliferative activities and that vitamin C has strong antioxidative and anticarcinogenic activities. Because there had been little work, however, on the activities of these two compounds with regard to neurodegenerative disorders, such as Alzheimer’s and Parkinson’s diseases, they decided to investigate the potential protective effects on neurons (nerve cells) that were exposed to a toxic substance implicated in such disorders.

The toxin they chose for their experiments was hydrogen peroxide (H2O2), one of the most common of the so-called reactive oxygen species (ROS) that are produced as unwanted byproducts of cellular energy metabolism. That’s the process by which fuel molecules (primarily glucose) are “burned” in the mitochondria of our cells to produce the chemical energy needed for all life processes.

Meet Hydrogen Peroxide—Carefully

Most ROS consist of the notorious free radicals, highly reactive molecules whose collective chemical assaults on the lipids, proteins, and nucleic acids in our cells are called oxidative stress. Some non-free radical molecules also participate in this demolition derby, however, and the most prevalent of these is H2O2, which is lethal to neurons.*


*The H2O2 in our cells is extremely dilute, which is a good thing. Pure H2O2 is a colorless, syrupy liquid that is highly corrosive and explosive: it decomposes violently (to water and oxygen) when heated. It’s such a powerful oxidizing agent that it can react explosively with many combustible materials. Even a 30% aqueous solution of H2O2, which is widely used in industry, is dangerous. The 3% solution you buy at the drugstore for use as an antiseptic or bleach, however, is not dangerous, except to bacteria and pigments.


Among the tissues most vulnerable to oxidative stress is the brain, whose delicate cell membranes are rich in polyunsaturated fatty acids—an easy target for ROS. The process by which these lipids (fatty substances) are degraded by ROS, called lipid peroxidation, is the same as that which degrades LDL-cholesterol in our blood, causing it to form atherosclerotic plaques in our arteries.

Quercetin and Vitamin C Protect Cells from H2O2

For their experiments with quercetin and vitamin C, the Cornell researchers used cells called PC12, which is a well characterized cell line derived from a rat pheochromocytoma, a benign tumor of the adrenal medulla (the inner portion of an adrenal gland). PC12 cells have properties that make them desirable for cellular toxicity research, and the results obtained are thought to be applicable to normal cells.

When the researchers exposed these cells to a very dilute solution of H2O2 for 2 hours, cell viability was decreased by 44%, i.e., only 56% of the cells survived. The H2O2 concentration was 400 micromoles per liter, or 3175 times more dilute than the drugstore variety, which is 1.27 moles per liter. [A mole is a fundamental unit of measure in chemistry; it’s the number of grams of a compound that’s equal to its molecular weight (the molecular weight of H2O2 is 34)].

Next the researchers pretreated some PC12 cells with very dilute solutions (at concentrations ranging from 10 to 100 micromoles per liter) of either quercetin or vitamin C for 10 minutes and then exposed them to the same H2O2 solution for 2 hours. The results were very different: both quercetin and vitamin C protected the cells in a dose-dependent manner, i.e., the higher the concentration of the antioxidant solution, the greater the protective effect. At all but the highest concentration, quercetin provided greater protection than vitamin C. This jibed with the researchers’ previous studies showing that quercetin has stronger antioxidant activity than vitamin C. Further cell-based experiments in the current study also led to the same conclusion.

Protection Against Alzheimer’s?

An intriguing speculation in the current study is that the cell protection provided by quercetin and vitamin C may be due in part to an effect on the cells’ mitochondria, the tiny “powerhouses” where cellular respiration takes place and where, as a consequence, most of the free radicals and other reactive oxygen species in our bodies are generated. It had been suggested by another researcher in 1992 that mitochondrial defects might be involved in the development of Alzheimer’s disease.4 Thus, it could be that, by protecting the mitochondria (if indeed they do), quercetin and vitamin C might also be helping to prevent Alzheimer’s disease (if indeed it’s caused in part by mitochondrial defects).

There are a lot of if’s here, not the least of which is whether or not results similar to those described above would be seen in living rats, let alone in living humans—the ultimate objective. Nonetheless, they are consistent with what scientists do know about the health benefits of antioxidants in humans, and they point the way to further research that will shed more light on this subject. Meanwhile, it’s a good idea to take antioxidant supplements and keep those hydrogen peroxide molecules out of your brain as best you can.

Quercetin Has Other Angles Too

Quercetin may also help to preserve and protect brain function by inhibiting the formation of fibrillated amyloid-beta, the senile plaque found in Alzheimer’s brains. For information on this, see the Durk Pearson & Sandy Shaw® Life Extension News item entitled “Red Wine Polyphenols” on page 22 of the November 2004 issue of Life Enhancement. And for yet another intriguing angle on this remarkable compound, see that same issue’s cover story, “Mulberry Helps Control Blood Sugar, and More.”

References

  1. Lininger SW Jr., Gaby AR, Austin S, Brown DJ, Wright JV, Duncan A. The Natural Pharmacy, 2nd ed., p. 328. Prima Publishing, Rocklin, CA, 1999.
  2. PDR for Nutritional Supplements, p. 391. Medical Economics Co., Montvale, NJ, 2001.
  3. Heo HJ, Lee Y. Protective effects of quercetin and vitamin C against oxidative stress-induced neurodegeneration. J Agric Food Chem 2004;52:7514-7.
  4. Wallace DC. Mitochondrial genetics: a paradigm for aging and degenerative disease? Science 1992;256:628-32.

Dual-Action Galantamine

Galantamine provides a heralded dual-mode action for boosting cholinergic function: it inhibits the enzyme acetylcholinesterase, thereby boosting brain levels of acetylcholine, and it modulates the brain's nicotinic receptors so as to maintain their function. The recommended daily serving ranges from a low of 4 to 8 mg of galantamine to begin with to a maximum of 24 mg, depending on the individual's response.

For an added measure of benefit, it is a good idea to take choline, the precursor molecule to acetylcholine, as well as pantothenic acid (vitamin B5), an important cofactor for choline. Thus it is possible to cover all bases in providing the means to enhance the levels and effectiveness of your acetylcholine.


Will Block is the publisher and editorial director of Life Enhancement magazine.

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