Vitamins, Dietary Supplements, and Cognition: Making Informed Decisions
Kelly A. Condefer, M.D.§
Visiting Clinical Research Fellow
Department of Care of the Elderly
University of Bristol, United Kingdom
I have been working in a British memory disorders clinic for six months, and it has become clear to me that dementia sufferers and those who care about them are intensely interested in the potential cognitive benefits of vitamins and herbal supplements. Even here in England, where the national pastimes of drinking, smoking, and eating fried food are still going strong (they revere their traditions here), a new health-consciousness seems to have arisen, especially in the aging populace. I would say that more than half of our patients either are taking supplements like ginkgo biloba and cod liver oil, or are interested in learning about their potential for improving cognition.
As a physician, of course I view safe forms of self-health promotion as positive things. I feel that in the case of memory loss and dementia especially, promoting self-care among older people is important, because it in effect puts the ball back into the ‘patient’s’ court. Receiving a diagnosis of Alzheimer’s (AD), or even of ‘Mild Cognitive Impairment’ which may lead to AD, can result in a feeling of helplessness at first, because the truth is, there is no cure. However, diet and nutrition are very personal things, and people experiencing memory loss or the beginning stages of AD sometimes find that by maximizing their nutritional state of health, they can gain some control over a process that might otherwise make them feel quite helpless.
For that reason, I’ve written the following synopsis of some of the most recent and relevant literature on vitamins, nutrition, and dementia. I hope that it will help healthy older adults, caregivers, and dementia sufferers alike to make informed choices about the types of dietary supplements they decide to include in their treatment regimen.
I would like to start with a disclaimer on the most important consideration about nutritional supplements of all kinds: their safety. As most people are aware, not every pill that is packaged and ready for the taking on the druggist's counter has undergone the strict safety and efficacy testing regulated by our FDA. Here in England, there are somewhat more stringent laws regulating dietary supplements, but in the US, anything can be bottled up and sold as a supplement of some kind. Unfortunately, Americans are not guaranteed the safety, dosage, or efficacy of anything classified as a "dietary supplement." Therefore, the consumer is somewhat at the mercy of the manufacturers’ claims.
The best piece of advice I can give is to ask your doctor before you begin taking any supplement. Unfortunately, most practitioners of Western medicine are not well versed in the compendium of herbal and nutritional treatments that are available. However, doctors are often aware of potential side effects and interactions of the more popular supplements, and will be able to advise on whether taking a specific supplement is safe for you in particular. It goes without saying that your physician should be made aware of each and every vitamin and supplement you are already taking.
After all, because the efficacy of many of these agents has not been proven in double-blind placebo-controlled clinical trials, the real issue is making sure that the potential benefit of the supplement far outweighs the risks. Sometimes, your own peace of mind can be therapeutic in itself! This is what you and your physician should consider when deciding whether ‘to use or not to use.’
Antioxidants: The neuroprotectors.
Perhaps the best known purveyors of nutritional health are the vitamins and other substances with antioxidant properties. These include Vitamins A, C, E, beta-carotene, selenium, and the polyphenols, which have been touted to do everything from, prevent cancer to slow the aging process. In the case of antioxidants, unlike many ‘fad’ supplements and herbs, the real benefits to both cardiovascular health and cognition do appear to far outweigh any potential risks.
The oxidation of lipids is one of the biochemical processes driving Alzheimer’s Disease, although its exact significance is not yet clear. In the brain, this process leads to neuronal cell death and thus the loss of memory and cognitive skills. In the rest of the body, oxidation contributes to the general wear and tear that could contribute to the eventual development of cancers cardiovascular disease.
Antioxidants scavenge free radicals, or unstable ions, that result from oxidation, and therefore tend to protect the tissues from damage by these ions. Though lipid oxidation is a natural process in the aging brain, some researchers have found that people with AD have lower defences against oxidation than the rest of us. Namely, AD sufferers seem to have lower levels of the antioxidants Vitamins E and C in their cerebrospinal fluid than do healthy elderly people. We might postulate from this that supplementation of these vitamins early on in the course of AD, or in any healthy older adult, can delay or prevent the onset of dementia. This theory has not been adequately tested yet, but Vitamin E supplementation is the only dietary supplement thus far to have shown objective memory improvement in mildly demented patients in a well-designed trial (Olson 2000).
Interestingly it has recently been suggested that a person’s Apo E4 status may influence their cognitive responsiveness to antioxidants. Apo E4 is a gene mutation that is now known to increase a carrier’s risk of developing AD. Dreon and colleagues suggested that Apo E4 carriers are more likely to respond dramatically to antioxidant therapy than non-carriers (Dreon 2001). This could provide a therapeutic relevance to knowing one’s Apo E4 status, lending some usefulness to genetic testing, but this needs more work as well.
One general thing to keep in mind is that AD and cardiovascular disease seem to share some common risk factors, though their exact relationship is still unclear. Since antioxidant use on the whole has been found to be safe and effective as a cardiovascular protector, it is probably safe to assume that these beneficial effects apply to the mind as well. Therefore, despite the fact that information regarding antioxidant benefits in dementia is just emerging, any vitamin or nutrient that is good for the heart is likely to be good for the mind as well.
Antioxidants are hard to avoid if you eat a well balanced diet. Citrus fruits, berries, broccoli and potatoes are full of them. Vitamin E in particular is easy to find in olive and safflower oils, nuts, wheat germ, and lima beans. Green tea is an excellent source of polyphenols and vitamin E, and selenium can be found in shellfish, swordfish, sunflower seeds, tuna, cracked wheat bread, egg noodles, breakfast cereal, eggs, and ham. Fish oils also have the distinct benefit of containing omega-3 fatty acids, which help to lower cholesterol. My mother may have been right to say, "eat fish—it makes you smart."
Memory nutrients: The B vitamins.
Deficiencies in the B vitamins B12, B6, folate, and thiamine (B1) have long been recognized as contributors to cognitive decline. In the evaluation of dementia and memory disorders, deficiencies in these vitamins, if present, are always treated first before drugs like cholinesterase inhibitors are instated. Patients with these deficiencies often respond favorably to vitamin replacement, showing improved short-term memory and language abilities. Furthermore, it is now thought that people with even slightly lower levels of these vitamins go on to develop Alzheimer’s more often than people with normal levels (Wang 2001).
But if replacing these vitamins in deficient individuals improves cognitive function, then does supplementation with these vitamins in people with normal levels necessarily improve memory and cognition? Or should we stick to the old adage, "if it ain’t broken, don’t fix it."
There is very little information out there regarding the usefulness of supplementing B vitamins in people with normal levels of the vitamins. For instance, one recent study found that there is simply not enough evidence to warrant thiamine (B1) supplementation in dementia unless the person is severely thiamine deficient (most often seen with chronic alcoholism) (Rodriguiez-Martin 2001).
Many dementia sufferers, however, are subclinically or mildly deficient in either B12 or folate, and can derive a cognitive benefit from replacement (Calvaresi 2001). It seems that a certain subset of patients with a subclinical deficiency in these nutrients derive particular benefit. Nilsson and colleagues in Sweden recently found that patients with elevated blood homocysteine levels showed a greater improvement in cognitive function on B12 and folate supplements than did patients with normal homocysteine levels (Nilsson 2001). Elevated homocysteine, which can be measured in the blood, is thought to represent a cardiovascular risk. More work needs to be done, but it appears that measuring a person’s homocysteine level may be a way of predicting how their memory might respond to B12 or folate supplements.
All in all, researchers seem to agree that a healthy diet high in the B vitamins and folate is at least protective against cognitive decline (McDowell 2001).
Trace elements and heavy metals: Can’t live with or without them.
The toxic buildup of the heavy metal elements cadmium, iron, zinc, and manganese occurs naturally in the brain and other organs as we age. The resulting overabundance of these metals tends to hyperactivate destructive "scavenger" cells called macrophages, and this can lead to cellular damage. Unfortunately, there is not much a person can do to prevent this particular process from occurring.
At the same time, as we age, we also tend to become less efficient at absorbing the other metals copper, zinc, and magnesium from our diets, and we may end up with relative deficiencies of these nutrients. Deficiencies in these metals can cause oxidative damage in our brains by preventing some key protective enzymes from operating to their fullest extent, thereby resulting in damage and cell loss.
However, selenium, vitamin B6, and vitamin D all aid in the absorption of magnesium, which may help to fend off a deficiency (Johnson 2001). Furthermore, vitamin E helps to minimize the damage resulting from too much or too little of the heavy metals. Therefore, we aren’t completely helpless in this department after all.
Herbal therapies are the subject of great interest on the part of the public and therefore the medical profession alike. Perhaps the idea that many of the popular herbal remedies each represent ‘one-off’ therapies for a variety of ailments makes them attractive to us. Naturally, people have always been intrigued by cure-alls, and those of us concerned about our memory are no exception. Herbal medications also have the advantage of being "natural," unlike manufactured medicines, and therefore are felt to be "good for us" in some general way.
However, we mustn’t get carried away with our preconceived ideas, both positive and negative, about herbal therapies. In order to safely derive benefit from these preparations, we must view them as drugs like any other medication. They can have dose-related side effects, drug-drug interactions, and overdose potential just like other medications. Some of them also happen to be effective to a degree, as an added bonus.
There are so many popular herbs that I won’t discuss them all here. I will focus on ginkgo, which is the one herb whose effect on memory and cognition has been studied fairly extensively. Ginkgo is quickly becoming the most popular herb used by people with memory disorders both in Europe and the US. Luckily, there have been clinical trials on ginkgo both in healthy populations, and demented groups.
Overall ginkgo does appear to be effective at improving memory, concentration, fatigue, anxiety, and depressed mood (Ernst 2002). It seems to act through a complex mechanism that results in neuroprotection, or prevention of nerve cell damage. It does seem to have a beneficial effect in Alzheimer’s patients, but how long that effect can last, and how well that effect compares to drugs like cholinesterase inhibitors remain to be seen. Its benefits and risks need to be studied more.
An important note of caution: Ginkgo is not totally benign, and you should consult your doctor before you take it. Long term use of ginkgo has been associated with spontaneous bleeding in the brain, especially in people who are taking aspirin or other blood thinners. Ginkgo also appears to interact with the very common medications digoxin, phenelzine, and warfarin (Coumadin) (Boniel 2001). If you are taking any blood thinning, blood pressure, or heart medications, you should probably not use ginkgo.
Can fatty foods promote health? The emerging story of choline
This discussion must be taken with a grain of salt—a very small one in fact, because controlling vascular risk factors like cholesterol, your weight, triglycerides, and blood pressure should always take precedence over eating fatty foods just for their potential cognitive benefits.
That said, choline is a component of fatty food that is most abundant in milk, liver, eggs, and peanuts. It is a molecule in the brain that encourages the communication between neurons and accelerates the synthesis and release of acetylcholine, the neurotransmitter that is in short supply in Alzheimer’s. There have been no trials of choline supplementation in humans as yet, so the safety or effect of the dietary choline supplements that are already available cannot be guaranteed.
However, some preliminary reports, mostly in mice models of Alzheimer’s, suggest that choline supplementation significantly improves cognitive function (Kopf 2001). Whether we can extrapolate these findings to humans remains to be seen. Choline, however, is well known to promote neurologic development in neonates, and has been shown in a pilot study to improve verbal and visual memory in critically ill patients requiring parenteral nutrition (Buchman 2001).
Though choline’s application in dementia is not defined as yet, we may hear more about the usefulness and safety of this fatty food component in the near future.
Like mother always said-- Eat your Brussels sprouts! Supplements vs. good old fashioned healthy eating.
To conclude, I’d like to reinforce the simple point that no combination or amount of supplements can provide the same value as eating a healthy, varied diet. Of course, this becomes more and more difficult to do as we age—we begin to lose our sense of taste and our appetites, and sufferers of dementia are not always able to choose the correct foods for themselves. Though fresh vegetables and fruit are always best, not everyone can get to the store every day. Fresh frozen ones are OK too. For people with restricted diets by necessity, the correct supplements are an excellent second choice.
It is true that one can never be sure of the ‘dose’ of nutrients they are getting through food. But it is well accepted that eating healthy foods is a healthier way of getting your nutrients than through supplements. Fruits and vegetables are very likely to contain beneficial substances that have yet to be identified, and they contain large enough amounts of vitamins and minerals. Plus, there is little chance of overdosing while eating vegetables!
With memory loss, cognitive decline, and dementia, like so many other chronic health problems, there is no quick fix or cure-all. But there are steps that individuals can take on their own, or with the help of their caregivers, to maximize the memory and thinking skills they do have.
Words of general advice on diet are:
As yet, we have no cure for dementia or memory loss in their various forms. But new treatments are always being developed, and many of the available medications do help. Perhaps the most important thing for a dementia sufferer or carer to feel is that they have some control over the process, however small it may seem. Putting thought and care into one’s diet is one of the best ways to gain that control.
Boniel T, Dannon P. The safety of herbal medicines in the psychiatric practice. [Hebrew]. Harefuah Vol 140(8) (pp 780-783+805), 2001.
Buchman AL, Sohel M, Brown M, Jenden DJ, Ahn C, Roch M, Brawley TL. Verbal and visual memory improve after choline supplementation in long-term total parenteral nutrition: A pilot study. Journal of Parenteral & Enteral Nutrition Vol 25(1) (pp 30-35), 2001.
Calvaresi E, Bryan J. B vitamins, cognition, and aging: A review. Journals of Gerontology Series B-Psychological Sciences & Social Sciences Vol 56(6) (pp P327-P339), 2001.
Dreon DM, Peroutkal SJ. Medical Utility of APOE Allele Determination in Assessing the Need for Antioxidant Therapy. Med Hypotheses. Vol 56 (pp357-359), 2001.
Ernst E. The Risk-Benefit Profile of Commonly Used Herbal Therapies: Ginkgo, St. John's Wort, Ginseng, Echinacea, Saw Palmetto, and Kava. Annals of Internal Medicine. Vol 136(1) (pp 42-53), 2002.
Johnson S. Gradual Micronutrient Accumulation and Depletion in Alzheimer's Disease. Med Hypotheses. Vol 56 (pp 595-597), 2001.
Kopf SR, Buchholzer ML, Hilgert M, Loeffelholz K, Klein J. Glucose plus choline improve passive avoidance behaviour and increase hippocampal acetylcholine release in mice. Neuroscience Vol 103(2) (pp 365-371), 2001.
McDowell I. Alzheimer's Disease: Insights From Epidemiology. Aging. Vol 13 (pp 143-162), 2001.
Nilsson K, Gustafson L, Hultberg B. Improvement of cognitive functions after cobalamin/folate supplementation in elderly patients with dementia and elevated plasma homocysteine. International Journal of Geriatric Psychiatry Vol 16(6) (pp 609-614), 2001.
Olson DA, Masaki KH, White LR, et al. Association of vitamin E and C supplement use with cognitive function and dementia in elderly men. Neurology. Vol 55(6) (pp 901-902), 2000.
Rodriguez-Martin JL. Qizilbash N. Lopez-Arrieta JM. Thiamine for Alzheimer's disease (Cochrane Review). Cochrane Database Syst Rev. 2:CD001498, 2001.
Wang HX, Wahlin A, Basun H, et al. Vitamin B(12) and Folate in Relation to the Development of Alzheimer's Disease. Neurology. Vol 56 (pp 1188-1194), 2001.
FOR AN INFORMATIVE AND PERSONAL ARTICLE ON PRACTICAL SUGGESTIONS WHEN SELECTING A NURSING HOME SEE OUR ARTICLE "HOW TO SELECT A NURSING HOME"
Kelly A. Condefer, M.D.§
Visiting Clinical Research Fellow
Department of Care of the Elderly
University of Bristol, United Kingdom
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