AGEs, Antioxidants and Brain Health

We all know the ugly statistics. Deaths from Alzheimer’s disease (AD) have seen a steady increase over the last few decades and it is now the sixth leading cause of death in the US. Recent predictions are that the number of people worldwide afflicted with AD will double every 20 years to 42 million by 2020 and 81 million by 2040. Equally disturbing is that those aged 60 and older who have AD will experience 11.2% of years living with disability. This is more than for stroke (9.5%), musculoskeletal disorders (8.9%), cardiovascular disease (5%) and cancer (2.4%).

However, rates of AD have not had universally similar distributions. Age-adjusted rates tend to be significantly lower for Africans living in Nigeria, than for African Americans living in Indianapolis. It is also lower for Japanese living in Japan than those living in the US or Hawaii. This suggests that environmental rather than genetic factors are the underlying cause of this disease.

Actually, I should say “were” lower in Japan as this country has also seen rapid increases in AD rates in recent years. This increase has been attributed to a shift away from more traditional diets based on rice, vegetables and fish to higher intakes of meat and other animal-derived foods. Similar associations have been noted for China.

In one lifestyle and age-matched prospective study, subjects who ate meat (including poultry and fish) were more than twice as likely to become demented than their vegetarian counterparts (relative risk 2.18), and the longer people ate meat the discrepancy was further widened to three times the risk (relative risk 2.99).

While this disease is certainly complicated and multifaceted, the associations to meat consumption are quite strong. Thus, the question is, is it the meat per se that is the problem, or the associated decline in fruit and vegetable consumption?

Well, as it turns out, it could be both.

Oxidative stress has been blamed as playing a central role in AD. It has been estimated that every cell in our bodies suffers 10,000 attacks by free radicals every day (i.e. oxidative stress). Cells most susceptible to damage are the neurons in the brain. Factors such as eating fried foods, cigarette smoke, stress, alcohol and even exercise promote the production of free radicals or reactive oxygen species. (For a discussion on exercise and oxidative stress, see my blog post about fruit and veggie benefits for athletes).

To quote one research paper “...evidence indicates that a long ‘dormant period’ of gradual oxidative damage accumulation precedes and actually leads to the seemingly sudden appearance of clinical and pathological AD symptoms, including amyloid-b (Ab) deposition, neurofibrillary tangle (NFT) formation, metabolic dysfunction, and cognitive decline.” 

Two antioxidants that have been shown to protect our brain cells are Vitamins E and C. One study which followed 800 elders for four years found that vitamin E in food lowered risk of AD by 67%. Another study concluded that “various tocopherol forms rather than alpha-tocopherol alone may be important in the vitamin E protective association with Alzheimer disease.”

You will notice a couple of important points here. The first study refers to vitamin E from foods and the second to “various tocopherol forms.” This is important. Vitamin E is a family of tocopherols, including the alpha, beta, gamma and delta forms. These in turn also consist of different isomers. The synthetic form of vitamin E found in most supplements is alpha-tocopherol and only contains one of the eight isomers found in the natural alpha-tocopherol. Thus, most vitamin E supplements bear little or no resemblance to the vitamin E found in whole plant foods. The best vitamin E pills are sunflower seeds, walnuts and almonds! Animal foods (including fatty fish) are almost completely devoid of vitamin E. Nuts, seeds and avocados are among the best choices. Vitamin C works synergistically with vitamin E in protecting our neurons. Again, animal foods are devoid of this antioxidant. Fruits and vegetables are your best source of vitamin C.

There are three antioxidants that we produce internally which also defend us against free radicals. These are superoxide dismutase, glutathione peroxidase and coenzyme Q10. For information on how the diet can impact superoxide dismutase and glutathione peroxidase, see a previous blog post).

Coenzyme Q10 is found in foods like soybeans, peanuts, pistachio nuts and olives. But mostly you should be making it internally. Statin drugs interfere with its production, which could be why their use is associated with cognitive decline. Studies suggest that supplementation with coenzyme Q10 might be useful therapy for AD for some people.

The best bet, however, is to eat an antioxidant rich diet. Again, plant foods win the day. As I’ve often pointed out plant foods have on average 64x the ability to quench free radicals than do animal foods. Of the plant foods, beans, berries, walnuts, herbs, spices and dark leafy vegetables are among the most antioxidant rich foods. Numerous studies have found that diets high in these foods improve cognitive performance and significantly reduce risk for AD and age related cognitive decline.

Not only are animal foods devoid of free radical fighting nutrients, they also contain substances that are harmful to brain health. Saturated fat (mostly sourced from meat and dairy) and cholesterol (only found in meat and dairy) consumption have been shown to double one’s risk of AD. Elevated serum cholesterol in midlife was found to triple one’s risk later in life. This is similar to the risk posed by cigarette smoking. In a review paper by Dr Grant, total fat (mostly from animal sources) was most strongly associated with increased risk for AD while cereal or whole grain intake was inversely associated with risk. But when it comes to animal foods, their fat and cholesterol content, while troublesome, is really the least of your worries. AGEs pose another threat to brain health.

Advanced glycation end-products (AGEs) are cross linked proteins that damage neurons and increase oxidative stress and inflammation within the brain. They are also aptly called AGEs as they promote aging. In fact, scientists refer to them as gerontoxins, or aging toxins. Skin wrinkling is in part caused by AGEs that have built up in the collagen tissue. They can also damage kidneys, eyes, joints, bones and arteries.

AGEs can enter our bodies when we eat foods that contain them. They are formed when meats are cooked at high temperatures, such as frying, roasting or grilling. Cooking foods in water, or cooking foods with a high-water content limits their formation. Fresh plant foods, for example, contain very low amounts (if any). Boiling meat has been shown to limit their formation whereas broiling meat promotes their formation.

When it comes to AGE content, foods that top the list are roasted chicken, bacon, fried steak, and hamburgers--all foods that loom large in western diets. Just by way of comparison, a burger has almost 5,000 units, a Boca veggie burger has 20. Foods that contain carbohydrates, like beans, fruits, and vegetables, have very low AGE concentrations. Dairy products are also low unless you age the milk into cheese. Thus, cheeses contain significant amounts as well.

AGEs have been shown to be 2-3x higher in the brains of AD patients compared to normal patients. They were found specifically in the amyloid plaques and the tau tangles. AGEs wreak their havoc by increasing free radical damage and inflammation and have been implicated as being one of the causative factors in AD.

For a variety of reasons, it is best to limit your consumption of AGEs.

As a leader your brain is your most important asset. Eating nutrient rich and high fiber foods, not smoking, regular exercise and good sleep habits will go a long way toward improving cognitive performance, maintaining cognitive performance as you age and protecting you from AD and dementia. Take care of your brain and it will pay dividends both now and in the long-term. And the sooner you start the better the long-term outcomes!

(For a more thorough review of this information as well as other nutrients and herbs that can help protect your brain, I refer you to this presentation presentation by Dr. Steve Blake.) He has also authored a book called “A Nutritional Approach to Alzheimer’s Disease”).

PS What about coconut oil? Coconut oil can be converted to ketones. One of these is called beta-hydroxybutyrate. According to Dr. Blake, this ketone can become an alternate fuel for damaged brain cells. Thus, they may provide a temporary memory boost in some Alzheimer’s patients. However, it does not slow the progression of the disease. Coconut oil contains almost no antioxidants, is missing key minerals, is low in vitamin E and 70% of its fat are the artery clogging kind (myristic acid). Thus, this is not the magic bullet that it has been made out to be!