May 8, 2017

Preventing Alzheimer's disease through diet

William B. Grant, Ph.D.,

The most important risk-modifying factor for Alzheimer's disease is diet.

The first published paper linking diet to risk of Alzheimer's disease (AD) came from the Adventist's study in 1993 [Giem, 1993]. Most Adventists are vegans with small amounts of eggs or dairy, very little meat. However, those Adventists who ate meat over a long period had three times the risk of dementia as those who did not. In the U.S., AD accounts for about two-thirds of dementia, so this result is primarily for AD.

I started studying dietary risk factors for Alzheimer's in 1996. I had been studying the effects of acid rain on eastern hardwood forests. I learned two things that led to my work on AD: one was how to conduct "ecological studies". Ecological studies treat populations as individuals, averaging health outcomes/disease rates geographically such as by state or country, then using averaged risk-modifying factors for each population to look at correlations. The other thing was that oak forests declined slowly over periods of decades due to acid rain, and the basic cause was that the trace minerals they took up from the soil solution slowly had fewer beneficial minerals, calcium, magnesium, and potassium, and more harmful minerals such as aluminum, copper, iron, mercury, manganese, and zinc. As a result, when the trees went to make various cells, they used what they had and if it wasn't the right mineral, the cells were defective and the trees went into slow decline.

When I read in October 1996 that Japanese-American men in Hawaii had 2.5 times the rate of AD as native Japanese, I recalled that people with AD had higher concentrations of aluminum in their brains than those without AD, just like the trees in forests affected by acid rain. I immediately thought that the reason had to be the American diet and that by using the ecological approach, I could determine which aspects of the diet were to blame. I obtained AD prevalence data for 11 countries as well as the dietary supply values for the larger dietary components from the Food and Agriculture Organization of the U.N. It did not take long to find that total dietary fat supply and total energy (calorie) supply were highly correlated with AD prevalence, that fish supply was associated with a slight decrease in risk, and that countries with rice-based diets had very low AD rates. The University of Kentucky had done studies on the trace mineral composition of those with AD and found it to be very similar to that of forest soils affected by acid rain. The University of Kentucky accepted my paper [Grant, 1997] and I had a press conference in the National Press Club in Washington, DC on June 17, 1997. The story was covered on national TV by Dan Rather (in 45 words) and CNN.

I have continued my research on dietary links to AD. The three most important recent papers are described here briefly.

One published in 2014 found that the rise in AD rates for the elderly in Japan, which rose from 1% in 1985 to 7% in 2008, were preceded by about 20-25 years by their nutrition transition from the traditional Japanese diet to the Western diet. The traditional Japanese diet obtained about 15% of its energy (calories) from animal products, mostly seafood, and 42% from rice. Meat consumption increased by a factor of 6, while rice consumption dropped by 50%. Japan used to have the longest healthy life expectancy in the world. On the other hand, the Japanese were short. Now the Japanese have rates of cancer that are comparable to those in the U.S. and Europe, and younger Japanese are about as tall as Westerners. Also in this paper, published results for AD risk with respect to mid-life factors were tabulated. AD takes many years to develop, so it seems worthwhile to adopt an anti-AD diet in mid-life.

In a paper published in 2015 with Dr. Lorena Perrone, we reported that advanced glycation end products (AGEs) were strongly linked to AD rates based on national diets. AGEs are combinations of proteins and glucose, and can be produced by cooking or by a chemical reaction in the body. AGEs are formed during cooking meat at high temperatures in a dry environment such as by frying, baking, or Bar-B-Que. AGEs are also risk factors for diabetes mellitus type 2 and some types of cancer. One of the mechanisms whereby AGEs increase risk of AD is through production of free radicals, which can destroy neurons.

My most recent paper on AD compared AD prevalence rates in 10 countries with national diets 5-25 years prior to the rate data. Per capita dietary meat supply had the highest correlation with AD rates. The three countries with the highest per capital meat supply, Brazil, Mongolia, and the U.S., had the highest AD rates while the four countries with the lowest meat supply, Egypt, India, Nigeria, and Sri Lanka, had the lowest AD rates. Similar results were found for meat plus eggs plus fish. Milk did not seem to affect risk of AD, but cheese did. Some fish are protective against AD, those that contain omega-3 fatty acids and vitamin D, such as cold water ocean fish. However, other fish are not protective. The Mediterranean diet, often touted as a diet associated with half the AD rate as the Western diet, was associated with half the maximum AD rate.

There are genetic risk factors for AD such as the apolipoprotein E epsilon 4 (APOEε4) allele. This allele (genetic variation) is most common in peoples who go from feast to famine and back such as hunter gatherers (Africans, Melanesians, Polynesians) or those who live at high northern latitudes (Inuit). APOEε4 increases cholesterol production in the liver and insulin production in the pancreas in order to help store all excess food as fat so that people survive from one feast through famine to the next feast. These people living in their ancestral homelands and eating as their ancestors did do not have high rates of AD. However, when they migrate to a land where food is plentiful, they often become obese and develop high rates of AD as is the case for African-Americans. I have often considered the relative roles of genes and environment in risk of chronic disease such as AD and many types of cancer. My conclusion is that genetics may be a risk factor, but environment is generally much more important. Those with genetic risks just have to work a bit harder on the environmental factors such as diet.

References

Giem P, Beeson WL,Fraser GE. The incidence of dementia and intake of animal products: preliminary findings from the Adventist Health Study. Neuroepidemiology.1993;12(1):28-36.

My papers on Alzheimer's disease:

Grant WB. Dietary links to Alzheimer's disease. Alz Dis Rev 1997;2:42-55.

Grant WB. The APOE-epsilon4 allele and Alzheimer disease among African Americans, Hispanics, and Whites, JAMA, letter. 1998;280:162-3.

Grant WB. Dietary links to Alzheimer’s disease: 1999 update. J Alz Dis. 1999;1197-201.

Grant WB, Campbell A, Itzhaki RF, Savory J, The significance of environmental factors in the etiology of Alzheimer’s disease. J Alz Dis (Debates from Challenging Views of Alzheimer Disease) 2002;4:179-89.

Grant WB. Does vitamin D reduce the risk of dementia?J Alz Dis. 2009 May;17(1):151-9.

Grant WB. Trends in diet and Alzheimer’s disease during the nutrition transition in Japan and developing countries. J Alz Dis. 2014 Jan 1;38(3):611-20.

Wu YT , Grant WB, Prina AM, Lee HY, Brayne C. Nutrition and the prevalence of dementia in mainland China, Hong Kong and Taiwan: an ecological study. J Alz Dis. 2015 Jan 1;44(4):1099-106.

Perrone L, Grant WB. Observational and ecological studies of dietary advanced glycation end products in national diets and Alzheimer’sdisease incidence andprevalence. J Alz Dis. 2015;45: 965–79.

Grant WB. Using Multicountry Ecological and Observational Studies to Determine Dietary Risk Factors for Alzheimer’s Disease. J Am Coll Nutr, 2016;35(5):476–489.

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