Dr. Mercola's comments:
Dr. William Grant provided this through review of Alzheimer's disease and, as mentioned in his bio below, he publishes the first paper linking diet to Alzheimer's disease and identifying the major dietary components that are risk and risk reduction factors.
Before you get into the article, I'd like to point out that one of the dietary recommendations that Dr. Grant mentions is fish. While fish would be an extremely healthy food, I would not recommend it eating it to reduce your risk of Alzheimer's because, unfortunately, most all fish is contaminated with mercury and other pollutants. Unless you can verify via lab testing that the fish you are eating is mercury-free, I would not eat it.
However, an excellent alternative to eating fish is taking high-quality fish oil or cod liver oil, either in the form of Carslon's liquid or Living Fuel Omega 3 and E. Eating plenty of fish oil is an important part of preventing Alzheimer's (and a host of other diseases as well).
Following are additional steps you can use to reduce your risk of Alzheimer's. These inexpensive and natural methods can be easily implemented by anyone, and you can keep them in mind as you read the article below:
And now Dr. Grant's Article:
Alzheimer’s disease (AD), first described in 1906 by German psychiatrist Alois Alzheimer, is a progressive brain disorder that causes a gradual and irreversible decline in memory, language skills, perception of time and space, emotional stability, pattern recognition, coordination, and, eventually, the ability to care for oneself 1. AD is associated with abnormal changes in the brain involving plaques, tangles, beta-amyloid protein, and free radicals 2.
The risk factors for AD include both genetic and environmental factors. The primary genetic risk factor is the presence of the apolipoprotein E epsilon4 (APOE e4) allele, which is more common among:
- Africans
- Inuits
- AmerIndians
- Northern Europeans than southern Europeans 3
This allele can be considered a "thrifty gene," one that helps store excess energy as fat, which is a survival factor for hunter-gatherer peoples 4.
The primary dietary risk factors are total energy and some types of fat, while the primary risk reduction factors are fish and some types of fat. Some studies have also reported that diets high in cereals and grains are associated with reduced rates of AD 5-7. Among fats, the good ones are 8,9:
- linoleic acid (found in safflower, sunflower, hemp, soybean, walnut, pumpkin, sesame, and flax seed oil 10)
- alpha-linolenic acid (found in fish, canola, flax, hemp seed, soy bean, and walnut oil and dark green leaves 10)
- docosahexanoic acid (DHA) and eicosapentanoic acid (EPA), largely found in fish oil
- olive oil
The bad ones are trans-fatty acids (found in many processed foods and labeled as partially-hydrogenated vegetable oils) 8,11,12.
Antioxidant vitamins C and E, as well as flavonoids, found in fruits and vegetables, and resveratrol, found in red wine, play a protective role. Obesity, smoking, cholesterol, and homocysteine are also risk factors, while exercise reduces the risk. Thus, even if one has a genetic predisposition for AD, there are many ways that one can reduce the risk.
For those who want to reduce their risk of AD, the most important thing appears to be to maintain a low body mass index by eating a diet low in total energy, low in bad fats, adequate in good fats, high in fruits, vegetables and antioxidants. Added sugars should also be avoided since they lead to obesity 13.
The traditional diet in the Mediterranean provides an example of a good diet 14. Adequate folate consumption, perhaps via supplements, should also be included. In addition, antioxidant and folate supplements would be beneficial. Finally, keeping both the mind and body active is very helpful.
An Introduction to Alzheimer’s Disease
AD is a disease in which the mind deteriorates to the point where one has no memory and a limited ability to function. It is one form of dementia. Another common type of dementia is called vascular dementia (VaD). However, the two types of dementia are sometimes present simultaneously, and both are sometimes considered to represent variations of the same disease 15.
The pathology of AD is linked to tangles and plaques in the brain, and these structures are associated with beta-amyloid protein. AD brain tissue contains higher levels of free radicals and oxidative stress. In the early 1990s, Alan Roses’ group discovered that the APOE e4 allele is closely associated with risk for AD 16-20. The APOE e4 allele was also found to be associated with oxidative insults to the brain 21. Those with higher risk of having the APOE e4 allele include those with African or American Indian ethnic backgrounds. Those with genetic roots in northern Europe have a somewhat lower probability than the first two ethnic groups, and the probability is lower among southern Europeans 3.
The likely reason for this variation with ethnicity is based on the role of the APOE alleles in regulating the metabolic process of food assimilation and generation of lipids, as well as other functions. The APOE e4 allele is associated with the storage of excess energy as fat, which is an important survival trait among hunter-gatherers or those who live in regions with harsh winters.
ApoE acts as a cholesterol transporter in the brain 22, and cholesterol is a risk factor for AD 23. Studies with cells found results consistent with APOEe4 forming a reactive molecular intermediate that avidly binds phospholipid and may insert into the lysosomal membrane, destabilizing it and causing lysosomal leakage and apoptosis in response to Abeta1-42 24. APOEe4 may also be a risk factor for increased transition metal (iron, mercury, zinc, etc.) and aluminum ion concentrations in the body and brain 25.
While the strong connection between genetics and AD is very important, it suffered a setback in terms of being the only important risk factor for AD in 1996 with the publication of a report from the Honolulu-Asia Aging Study showing that Japanese-American men living in Hawaii had 2.5 times the prevalence of AD of native Japanese 26.
At the time that I read the account of this finding, I was studying the adverse effects of ozone and acid rain on eastern oak and hickory forests and learned that acid deposition lowers the pH of the soil and, in doing so, dissolves some aluminum and transition metal oxides, thereby releasing these metal ions into the soil where trees and other plants can readily absorb them.
I was also aware that those diagnosed with AD had increased aluminum in their brains. I quickly reasoned that since the Japanese had the same genetic traits no matter where they lived, they had to have experienced some environmental factor in Hawaii that led to their AD. I also thought that the most important environmental factor in the broadest sense was the food they ate.
In my forest studies, I had developed a facility with the ecologic approach for studying links between environmental factors and disease outcomes. I reasoned that I should be able to apply the ecologic approach to examine the correlation of major dietary factors on AD prevalence by assembling data from a number of countries.
In the ecologic approach, populations defined geographically are treated as entities, and population average values for various factors are compared with disease outcomes in regression analyses. Armstrong and Doll 27 did this for cancer, thereby providing an example to follow. I didn’t realize until a few years later that the health research community had essentially discarded the ecologic approach after an influential paper by Doll and Peto 28 stated that it was not very reliable or useful in determining causal factors for disease.
Note that, more recently, the ecologic approach has largely been vindicated after case-control and cohort approaches confirmed the findings by Burkitt 29 and Armstrong and Doll 27 that dietary fiber reduces the risk of colorectal cancer and that meat and milk are risk factors for breast cancer 30.
Dietary Risks for Alzheimer’s Disease
I found AD prevalence data for 11 countries and obtained dietary data from the Food Balance Sheets 31. The linear regression results indicated that total energy and total fat were the primary risk factors, while cereals or grains and fish were the primary risk reduction factors. I gave a seminar on my findings to the AD group at the University of Kentucky in early 1997 and convinced them that I had an interesting finding. James Geddes accepted my manuscript for publication in the Alzheimer Disease Review, and it appeared in print on the Web on June 17, 1997 5.
The results were not immediately accepted, in part because I employed the largely abandoned ecologic approach, and in part because I was an independent researcher from a different field (atmospheric sciences).
A paper published shortly after mine found total fat as a risk factor for VaD and fish as a risk reduction factor for AD 12,32. Slowly, the interest of the rest of the AD research community was prodded 33,34, and, in 2002, a group at Columbia University confirmed three of the four dietary links to the development of AD (energy, fat, and an inverse association for cereals) 6, very likely inspired by a letter to the editor commenting on their earlier study 35 suggesting that dietary factors were likely involved 33.
Fish and Fish Oil Reduce AD Risk
The role of fish in reducing the risk of AD was further discussed in 36 and confirmed by a French team 37, as well as by a team at the Rush Alzheimer's Disease Center in Chicago 9,38. The French team extended their work on fish and AD, finding that those who ate fish at least once a week had a relative risk of AD of about 0.7 compared to those who didn't 39. Fish consumption was found inversely correlated with cognitive impairment among middle-aged Dutch, while cholesterol was positively associated 40. The benefits of the primary n-3 fish oils, DHA and EPA, appear to include providing the lipids required for proper brain development and maintenance 41,42 and reducing inflammation 43.
Fatty Acids and AD
It should be noted that one of the first signs of impending AD is what is called cognitive impairment (CI). Thus, studies of dietary links to CI are useful regarding AD, and, indeed, they find much the same results as the AD studies e.g., 11,12. Such results, as well as some for AD, indicate that there are good fats and bad fats, as mentioned above.
However, the ratio of n-6 to n-3 fatty acids is also important, with a ratio of LA to ALA (n-6 to n-3) of about 4:1 being optimal 44,45. This value is nearer to the 1:1 or 2:1 ratio found in the diet of our ancestors than the 10:1 to 25:1 found in present day Western diets 46.
Also, extra virgin olive oil, with its strong antioxidant properties, is a good choice. Virgin olive oil should be considered a risk reduction factor for AD since it has plenty of phenols with high antioxidant capabilities 47. These compounds have been suggested to be very useful when free transition metal ions are involved in oxidation processes 47, as is the case in AD (see discussion below).
Obesity Increases Risk of AD
In addition, there has been further support of the finding that total energy consumption is a risk factor for AD 48,49. Mark Mattson has long championed the idea of caloric restriction for reducing the risk of AD 50, and a recent paper identified obesity as a risk factor for AD 51 with the comment that it was likely related to diet 52. The epidemic of obesity in the United States aa ppears to be linked to increased consumption of convenience food, which is energy-dense 13. These foods are rich in sweeteners (fructose and sucrose), other refined carbohydrates, and animal products high in fat. Sugar is also implicated as a risk factor for AD through the finding that type 2 diabetes mellitus is associated with increased risk of AD 53,54.
Wine Consumption
Two recent studies reported that risk of AD decreased markedly with wine consumption for mild and moderate drinkers 39,55. The risk ratio for AD for moderate drinkers was 0.53 (95% C.I. 0.30-0.95) compared to non-drinkers 39.
Very similar results were found for up to three glasses of wine per day, but not for other alcohol beverages in another study 55. Also, these results were limited to those who did not have the APOEe4 allele.
It is likely the antioxidants in wine that were responsible for this result. Wine has been proposed as an explanation for the "French paradox" regarding coronary heart disease 56. However, another possibility for the brain is that resveratrol in red wine is responsible. A recent paper reported that resveratrol was able to significantly induce heme oxygenase 1, thereby reducing the oxidative stress on neurons 57. Resveratrol also exerts an anti-oxidative action by enhancing the intracellular free-radical scavenger glutathione 58. Resveratrol is also available from grape juice, but is not as readily absorbed as from wine 59,60.
Why Antioxidants are Useful for Alzheimer's Disease
Since AD is to some extent a disease of oxidative stress, it would be expected that antioxidants would reduce the risk of developing AD. That is indeed the case. One prospective study found that a high intake of flavonoids found in tea, fruits, and vegetables reduced the risk of AD by about half 61. A prospective cohort study in Rotterdam found that high consumption of vitamins C and E reduced the risk of AD by 20 percent to 40 percent, with the most pronounced benefit found for smokers 62. Antioxidants are, of course, useful in reducing the risk of a large number of degenerative diseases 63.
An observational study found peripheral levels and activities of all antioxidants reduced in those with mild cognitive impairment and AD 64. A recent study reported that those taking large amounts of vitamins C and E in combination had one-quarter to one-third the risk for AD as those not taking the vitamin supplements 65.
Cholesterol and AD
Cholesterol has been a known risk factor for AD since the early 1990s 23. Cholesterol is often elevated by a diet high in fats 66 and/or high in sugars 67. The role of cholesterol in the etiology of AD was recently reviewed 68,69. The mechanisms are still under review 70,71.
Paradoxically, however, it may be the high-density lipoprotein (HDL) rather than the low-density lipoprotein (LDL) cholesterol that is the bad actor 72, the reverse of the case for heart disease. In heart disease, LDL can clog the arteries, and oxidized LDL can break off the arterial walls and block blood flow to the heart. Thus, use of statins, which act primarily to reduce LDL cholesterol, may not reduce the risk of developing AD 73.
Since cholesterol is implicated as a risk factor for AD, statins, which reduce serum cholesterol levels, especially the LDL fraction, may be useful in reducing the risk of AD 74. Some studies support this hypothesis e.g., 75 and others are underway 76.
Homocysteine Increases the Risk of Alzheimer's
Homocysteine is another risk factor for AD. Homocysteine was first identified as a risk factor for arteriosclerosis from autopsy studies by Kilmer McCully 77. For his important pioneering work, he was dismissed from Harvard and black-listed for several years. Homocysteine levels are elevated when there are deficiencies of vitamin B6, folate, and vitamin B12 78,79. A prospective study found that elevated homocysteine levels were associated independently with increased risk for AD 80.
Conversely, patients with AD have been found to have elevated levels of homocysteine 81,82. Also, patients with stroke and VaD have elevated levels of homocysteine 81.
The Role of Metal Ions Including Aluminum
Metal ions are also involved in the pathology of AD. It is well known that aluminum is elevated in the brains of AD patients 83. Less well known, but well documented, is that transition metal ions (e.g., copper, iron, and zinc) are also elevated, while base cations (e.g., calcium and magnesium) are at lower concentrations 83.
I have attributed this phenomenon to a high consumption of acid-forming foods, such as animal products, which are high in protein (amino acids) and fat (fatty acids). These acids may dissolve the aluminum or transition metal oxides in the food we eat and, thus, permit the ions to be absorbed into the blood 49,84.
There is also the possibility that aluminum from aluminum soft drink cans can be ingested, since carbonated drinks are highly acidic and can leach out aluminum 85. In addition, some soft drinks also contain moderate levels of fluoride, and, in combination with aluminum, can be a risk factor for AD 86.
These transition metal ions and aluminum ions increase the production of free radicals such as hydroxyl 87, both in the body and in the brain, and, thus, are involved in oxidative damage to the brain 88-95. It has been suggested that the transition metal ions can be removed from the body by chelation in a manner that reduces the oxidative damage to the brain 96; a clinical intervention using clioquinol, a metal-protein-attenuating compound (MPAC) that inhibits zinc and copper ions from binding to beta-amyloid, thereby promoting beta-amyloid dissolution and diminishing its toxic properties.
Inflammation and NSAIDs
Inflammation appears to be one of the risk factors for AD, and is related to free radicals and oxidative stress from beta-amyloid 98 or, transition metal ions 99. One of the ways that fish oil may reduce the risk of AD is by reducing inflammation in the brain.
The use of non-steroidal anti-inflammatory drugs (NSAIDs) to reduce the risk of AD has been studied 100,101 following the finding that those with rheumatoid arthritis had a reduced risk of AD 102. The reader is cautioned that use of NSAIDs including aspirin and COX-2 inhibitors carries the significant risk of gastrointestinal bleeding 103-106.
A recent paper reports that those with H. pylori increase their risk of gastrointestinal tract bleeding by a factor of two to four times 107, so anyone planning to take NSAIDs on a regular basis should be checked for H. pylori. A better policy is to eat in a manner so as to reduce the risk of oxidative stress in the first place, rather than have to treat it later.
Dietary Recommendations
AD is rare in Africa 108 and India 7, but Africans generally consume far fewer calories than would be tolerated in the United States, and Indians are generally vegetarians with high rates of diabetes and heart disease due to large fractions of carbohydrates in their diets. The Mediterranean diet 14,109-115 is associated with a risk of cognitive impairment and AD intermediate between those of Southeast Asia and the United States.
In addition to diet, additional risk reduction can be achieved by taking antioxidant and B-vitamin supplements as well as a few other substances that one can find described in the literature.
Physical Exercise Reduces Risk
Regular physical exercise is another way to reduce the risk of AD. A study in Canada found that those who engaged in high levels of physical activity had half the risk of developing AD of those who did not 116.
Smoking Doubles AD Risk
Smoking was associated with double the normal risk for AD in a cohort study in Hawaii 117. Since those in the United States who smoke generally have poorer dietary habits than those who don't, it could be that dietary factors explain some of the risk. However, since smoking reduces the body's stores of antioxidants, it could well be a direct effect.
Ethnic Differences in AD Prevalence
It is noteworthy that African Americans have the highest AD rate of any ethnic group in the United States 108,118 while Japanese Americans have the lowest 26,119. This result is probably a combination of both genetic and dietary factors. African Americans have a higher frequency of APOE e4 than European Americans, who, in turn, have a higher frequency than Asians.
In addition, there are very likely ethnic differences in diet, with Asian Americans eating less total energy and animal products and more vegetable products than European Americans. Black Americans may eat more convenience foods and fewer fruits and vegetables than European Americans 120, 121. A predisposing gene combined with poor diet is the worst combination in terms of risk for AD.
Prevalence of AD in the United States
Hebert et al. estimated that of the number of people with AD in the United States in 2000 was 4.5 million 122. According to the authors, by 2050 this number will increase by almost three-fold, to 13.2 million.
I have criticized both estimates 123.
The 4.5-million estimate was based on incidence rates in a biracial community, with African Americans making up about 40 percent of the sampled population. The authors used education level to extrapolate the results to the entire United States.
As shown in 124, ethnic origin is a much better way, especially since African Americans have a frequency of APOE e4 that is two to three times that for European Americans. In addition, Hebert et al. seemed to classify nearly everyone with dementia as having AD. That classification is not consistent with what is normally found in Western developed countries 125. In Asian countries, VaD rates are about the same as AD rates since VaD is more related to hypertension, and hypertension is more related to dietary sodium than to dietary fat, and Asian diets are different from Western Developed Country diets.
As for the 2050 estimate, it is likely high as well. If Americans find a way to reverse the obesity epidemic that is sweeping the country, the numbers need not reach that high.
Other studies have also estimated AD prevalence in the United States. The East Boston Study, which estimated 4 million with AD 126, was criticized in 127, who found 2.3 million in 1997, for having incidence values much higher than any other U.S. study. The ecologic study 5 gave an estimate of about 2.1 million with AD in the early 1990s. In my opinion, some prevalence estimates are intentionally inflated in order to persuade Congress to appropriate more funding for AD research.
Diet and Lifestyle Play an Important Role
While genetics plays a role in the risk of developing Alzheimer's disease, diet and lifestyle also play important roles. Since genetics can't be changed, those who would like to reduce their risk of Alzheimer's disease should make lifestyle choices.
For those who want to reduce their risk of AD, the most important thing appears to be related to dietary factors, including fruits, vegetables and moderate intake of fatty fish (or fish oil). Olive oil also appears to be beneficial. In addition, antioxidant and folate supplements would be beneficial. The red wine ingredient resveratrol is also helpful. Finally, keeping body mass index low and keeping both the mind and body active are very helpful.
William B. Grant has a Ph.D. in physics from U.C. Berkeley and has worked at the level of senior research scientist in the fields of optical and laser remote sensing of the atmosphere and atmospheric sciences at SRI International, the Jet Propulsion Laboratory, and the NASA Langley Research Center. He is the author or coauthor of over 60 physics, instrument development, and atmospheric sciences articles in peer-reviewed journals, has edited two books of reprints, and contributed half a dozen chapters to other books.
He published the first paper linking diet to Alzheimer's disease and identifying the major dietary components that are risk and risk reduction factors. He has also studied the links between dietary sugars and heart disease and obesity, diet and breast, colon and prostate cancer, and UVB/vitamin D and cancer and autoimmune diseases. He recently retired from NASA and founded Sunlight, Nutrition and Health Research Center (SUNARC) (www.sunarc.org), where he will continue and extend his health research and educational efforts.
Source: mercol.com
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