Antioxidant Vitamin Combo Cuts Alzheimer’s Risk

Antioxidant Vitamin Combo
Cuts Alzheimer's Risk

Vitamins E and C are very effective—but only when used together
By Will Block

Cache Valley, Utah
buzzword in the business community is networking—you know, communicating with friends and associates for mutual assistance in finding a job or furthering your career. Underlying that concept is a deeper one called synergy, the interaction of two or more agents such that their combined effect is greater than the sum of their individual effects. It’s synergistic, for example, when the combined input from two people (such as your cousin Bernie’s accountant and your neighbor’s girlfriend, who’s a chemist) is unexpectedly productive and yields a desired result that might not have come from either one of them alone.

Synergy occurs all the time in our cells. A classic example is the role played by vitamins. Vitamins are indispensable mainly because they serve as cofactors (or the precursors to cofactors) to the enzymes that catalyze certain of the chemical reactions of life processes. The enzymes are “turned on” by the cofactors (which are also called coenzymes), thus enabling them to perform their appointed tasks. Not all enzymes require a cofactor, but those that do are inert without them—it takes the interaction between enzyme and cofactor to get the job done. (Just to spice things up, Mother Nature has made some vitamins and minerals act as cofactors for each other, i.e., a given vitamin may work well only in the presence of certain other vitamins or minerals.)

The Antioxidant Network Keeps Us Alive

Certain vitamins are also indispensable, however, because of their antioxidant properties—their ability to neutralize free radicals and other reactive oxygen species (ROS) that can damage our cells. This is especially important for neurons (brain cells), which are more vulnerable to oxidative stress than most other cells. Oxidative damage to neurons is believed to play a crucial role in the development of Alzheimer’s disease—indeed, it is has been suggested that oxidative damage is one of the earliest pathophysiological events in Alzheimer’s.1 All the more reason to minimize oxidative stress through the use of antioxidant supplements!

Many nutrients have antioxidant properties. Among the most potent are the fat-soluble vitamin E and the water-soluble vitamin C, whose benefits in this regard have been abundantly documented in the scientific literature. These vitamins exert their powerful antioxidant effects not just individually, however, but also—and perhaps more importantly—through their participation in the human body’s antioxidant network. This is a web of chemical reactions by which five crucial antioxidant compounds engage (synergistically) in each others’ regeneration from the spent state back to the active antioxidant state so that they can continue neutralizing free radicals and other ROS.*

*For more on this topic, see “Lipoic Acid, the ‘Antioxidant’s Antioxidant’” (July 2001) and “Lipoic Acid Helps Heart Health” (September 2001).

The five compounds in question are vitamin E, vitamin C, lipoic acid, coenzyme Q10, and glutathione (all can be taken as supplements except glutathione, which is destroyed in the digestive tract). If the protective action of these antioxidants against the torrents of free radicals that are generated constantly by the chemical reactions of cellular metabolism were suddenly to cease, we would die within an hour or two.

Certain features of the antioxidant network may help explain the results of a recent study showing that the risk for Alzheimer’s disease in elderly people can be sharply reduced with relatively large supplemental amounts of vitamins E and C—but only when they’re taken together! Before we examine the details, let’s review the risk factors for dementia.

The Risk Factors for Dementia

Being a woman is a significant risk factor for dementia, probably because women live longer than men, and age is the single greatest risk factor. The prevalence of dementia at age 65 is 1%, but by age 85 it’s 30–50%, and the incidence of new cases thereafter is 5–10% per year.2 Other risk factors include all the major ones that pertain to heart disease: lack of exercise, high cholesterol, high blood pressure, obesity, diabetes, and smoking. Low income, low educational level, and low intellect (all of which can be pretty closely related) are also factors, as are prior head injuries severe enough to have caused loss of consciousness.

Finally, there is a genetic factor: the presence of a gene called apolipoprotein E e4 allele (APOE e4) apparently predisposes one to Alzheimer’s, although having this gene will not necessarily lead to the disease, nor will lacking the gene provide protection from it.

Longevity in Cache County, Utah

A team of American Alzheimer’s researchers from several institutions has undertaken an extensive study of the elderly residents of Cache County in northern Utah, who are known for their extraordinary longevity.3 The researchers chose this region so as to be able to study large numbers of people who live well into their nineties and beyond.* The Cache County Study was an investigation of the prevalence and incidence of Alzheimer’s disease and other dementias in relation to genetic and environmental factors (including diet, of course). Prevalence refers to the proportion of individuals who were already demented at the outset of the study, and incidence refers to the proportion of individuals who became demented during the course of the study.

*The 92,000 residents of Cache County are not representative of the population at large. They are better educated, mostly Caucasian, relatively homogeneous, and overwhelmingly Mormon (91%). That’s significant because they typically adhere to a healthy lifestyle (including abstinence from tobacco and alcohol) that reflects the teachings of their church. It’s probably no coincidence that they’re exceptionally long-lived. For more on this interesting population, see the sidebar “To Avoid Alzheimer’s, Get Really Old” in the article “Galantamine Can Sharpen Your Mental Edge,” April 2002.

Low Antioxidants = Increased Risk for Dementia

The importance of dietary antioxidants can hardly be overemphasized, considering that oxidative stress—the damage caused by free radicals and other reactive oxygen species—is believed to be a major factor in the development of many diseases, and in the aging process itself. And if the antioxidant vitamins E and C can reduce the risk for Alzheimer’s disease (AD), it seems most likely that they can do the same for mild cognitive impairment (MCI), the common “precursor” condition to Alzheimer’s.

Researchers in Italy and Germany published a study in which they evaluated 144 elderly Italians (25 with MCI, 63 with AD, and 56 healthy controls) for 13 different antioxidants in their blood—including, of course, vitamins E and C.1 The results showed that, compared with the controls, the MCI patients had significantly reduced levels of 10 of the 13 antioxidants, and the AD patients had significantly reduced levels of 11 of them (in both groups, the levels of vitamins E and C were below normal).

These results are consistent with those of epidemiological studies showing a direct relationship between high plasma antioxidant levels and good cognitive performance, as well as between high plasma levels of markers of lipid peroxidation (the result of free-radical attacks on blood lipids) and cognitive decline. The authors stated:

. . . a diet containing high levels of antioxidants may prevent or delay cognitive deterioration. Furthermore, dietary antioxidants may be used to correct an antioxidant imbalance, and an increased intake of antioxidants in subjects with MCI could be helpful in lowering the risk of conversion to dementia.
  1. Rinaldi P, Polidori MC, Metastasio A, Mariani E, Mattioli P, Cherubini A, Catani M, Cecchetti R, Senin U, Mecocci P. Plasma antioxidants are similarly depleted in mild cognitive impairment and in Alzheimer’s disease. Neurobiol Aging 2003;24:915-9.

The study encompassed 4740 individuals who were 65 or older. They were assessed during the period 1995–1997 for prevalence of dementia, and again during the period 1998–2000 (i.e., 3 years later in each individual case) for incidence of dementia. The assessments were based on a number of standardized tests for memory and other aspects of cognitive function, as well as on questionnaires and interviews with individuals (and their caregivers) who were unable to take the tests.

Classes of Vitamin Users

The genetic factor the investigators were looking for (using DNA testing) was the presence of APOE e4. The environmental factors that were considered included sociodemographic factors such as education, occupational history, medical history, tobacco and alcohol use, use of prescription or over-the-counter medications, and use of nutritional supplements. In reference to supplements, the subjects were categorized as follows:

  • Vitamin E users – Those who took an individual vitamin E supplement or a multivitamin formulation containing more than 400 IU of vitamin E. (IU, or international unit, is a measure of vitamin E biological activity regardless of which chemical form the vitamin E is in: alpha-tocopherol, alpha-tocopheryl acetate, etc.)
  • Vitamin C users – Those who took an individual vitamin C supplement or a multivitamin formulation containing at least 500 mg of ascorbic acid (vitamin C). Ascorbic acid is specified to ensure that the full measure of vitamin C biological activity is accounted for. (When ascorbic acid derivatives such as calcium ascorbate or ascorbyl palmitate are used in product formulations, one must include proportionally greater weights of these compounds to obtain the equivalent biological activity of the desired amount of pure ascorbic acid.)
  • Multivitamin users – Those who took a multivitamin formulation containing lower amounts of vitamins E or C than those specified above.
  • Vitamin B users – Those who took an individual vitamin B-complex supplement formulation (presumably with or without other supplements—the authors did not specify). Note that the B-vitamins are not antioxidants.

The multivitamin and vitamin B users were included in the statistical evaluation of the data as “controls” to enable the researchers to correct for certain factors that could otherwise skew the results.

Vitamins E and C Provide Strong Protection Against Alzheimer’s

Of the 4740 subjects, 97% provided sufficiently detailed data for their use of supplements to be classified in one of the groups. Of these, 824 (17%) turned out to be vitamin E or vitamin C users; compared with the rest, they were significantly more likely to be female and to report better general health. Another 967 (20%) of the subjects were classified as multivitamin users; these individuals were also more likely to be female, but they reported poorer general health.

The results of the study were striking. In the prevalence analysis, there was a strong inverse correlation between the risk for Alzheimer’s disease and the use of both vitamin E and vitamin C, with or without the concomitant use of multivitamins, i.e., the vitamin E + C combination was strongly protective, reducing the risk by 78%. There was no statistically significant inverse correlation with either of these vitamins alone, or with a vitamin C + multivitamin combination, and there was no correlation whatever with vitamin B complex. There was a “significant, if relatively modest” inverse correlation with multivitamins alone, and a somewhat stronger one with a vitamin E + multivitamin combination.

In the incidence analysis, the results were similar (except for there being no correlation with the use of multivitamins alone): the vitamin E + C combination was again strongly protective, reducing the risk by 64%. Within the population studied, no significant differences were found in the data across different strata of age, sex, or genetic type (with respect to APOE e4).

High Levels of Vitamins E and C Are Needed

These results provide dramatic evidence for the synergistic efficacy of vitamins E and C in reducing the risk for Alzheimer’s disease. The authors’ interpretation of the data was that vitamin E provides the stronger effect, but only in conjunction with vitamin C (with the latter taken either alone or in the form of a multivitamin formulation). They stated:

Our findings suggest that vitamins E and C may offer protection against Alzheimer’s disease when taken together in the higher doses available from individual supplements.
In outlining the strengths and weaknesses of their study, the authors also discussed numerous similar studies of the relationship between antioxidant vitamins and the risk for Alzheimer’s disease. Most (but not all) of these studies showed beneficial effects, primarily from vitamin E, either alone or in combination with vitamin C. (For a discussion of a study on the positive effects of vitamin E alone, see “Vitamin E Keeps Your Brain Razor-Sharp” in Life Enhancement, November 2002.)

Are Your Neurons Protected?

There is no question that vitamin E—preferably, if not necessarily, in combination with vitamin C—is of great value in protecting cell membranes from oxidative damage caused by free radicals and other reactive oxygen species. And of all the cell membranes in our body, those of our neurons are among the most in need, and the most deserving, of such protection. If your neurons are working properly, they’re probably, right now, forming the thought, “Better take plenty of vitamins E and C.”


  1. Nunomura A, Perry G, Aliev G, Hirai K, Takeda A, Balraj EK, et al. Oxidative damage is the earliest event in Alzheimer’s disease. J Neuropathol Exp Neurol 2001;60(8):759-67.
  2. Goodwin L. Underwriting dementia and memory loss. The Messenger (Transamerica Reinsurance Risk Management newsletter), June 2000, pp 1-12.
  3. Zandi PP, Anthony JC, Khachaturian AS, Stone SV, Gustafson D, Tschanz JT, Norton MC, Welsh-Bohmer KA, Breitner JCS, for the Cache County Study Group. Reduced risk of Alzheimer disease in users of antioxidant vitamin supplements. Arch Neurol 2004 Jan;61:82-8.

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

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