Inflammation May Explain Association of Dementia with Constipation

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Ten thousad people attended the Alzheimer’s Association International Conference (AAIC) in Amsterdam on July 19, 2023, which featured more than 3,000 scientific presentations. Much of this conference dealt with amyloid plaques and the drugs associated with them. The U.S. Food and Drug Administration (FDA) has approved anti-amyloid drugs Lecanemab (Leqembi, Eisai) and Aducanumab (Aduhelm TM), and fast-tracked a third drug, Aducanumab. These drugs may help to slow brain damage caused by amyloid plaques that deposit in and damage the brain as much as 20 years before a person suffers loss of mental function. However, once amyloid damages the brain and a person loses mental function, the drugs are not useful because the brain damage appears not to be reversible. This suggests that efforts to avoid dementia may need to begin very early in life.

Dementia Associated with Constipation
Several of the studies presented at AAIC showed that chronic constipation (less than one bowel movement every three days) is associated with decreased mental function. Dr. Chaoran Ma and his large team evaluated three prospective cohort studies from Harvard of more than 110,000 people in the Nurses’ Health Study, the Nurses’ Health Study II, and the Health Professionals Follow-up Study. They evaluated brain functions and constipation in 12,696 people. Having a bowel movement frequency of three days or less was associated with a 73 percent higher odds of loss of mental function. Those who were constipated had a greater cognitive decline that could be explained by finding fewer intestinal bacteria that convert the soluble fiber found only in plants into short chain fatty acids (SCFAs). SCFAs are absorbed into the bloodstream to lower high blood pressure, high insulin levels and high cholesterol and reduce an overactive immunity called inflammation. Other studies showed that adults over 50 who had reduced mental function and/or increased amyloid brain plaques associated with Alzheimer’s disease had low intestinal levels of the bacteria that make SCFAs.

Inflammation and Gut Bacteria
These studies cumulatively suggest that inflammation may be the common factor linking dementia and constipation. The association between constipation and loss of mental function may be explained by a decreased number of the colon bacteria that convert soluble fiber into SCFAs. Your colon is loaded with more than a hundred trillion bacteria. Most of these bacteria are good for you and help in many different ways. They help you to digest and absorb nutrients from the food that you eat, and to eliminate waste products.

Germs are not supposed to invade your cells, but when they do, your immune system recognizes that the germs’ sugar-proteins are different from the sugar-proteins on your own cells. Your immune system then produces proteins called antibodies that attach to and try to kill the invading bacteria or virus, lymphocytes that literally eat the invading germs, and cytokines that marshal your entire immune system to destroy harmful germs that are trying to invade your body. The visible signs of inflammation — redness, swelling, soreness, fever — tell you that your immune system is working to combat an infection or an injury.

As soon as an infection is gone or a wound is healed, your immune system is supposed to dampen down and stop making large amounts of these cells and cytokines. If your immune system does not stop making excessive amounts of cells and proteins to kill germs, these same cells and proteins can attack you to damage:
• your brain to cause dementia
• your arteries to cause plaques to form and break off, leading to heart attacks and strokes
• your DNA in cells to block apoptosis that can lead to cancer
• your liver to cause diabetes
• your own immune system itself, leading to auto-immune diseases such as rheumatoid arthritis

Anti-Inflammatory Foods
What you eat determines the proportions of good and bad bacteria in your colon. The good bacteria are happy to eat the same food that you eat, while the bad bacteria are not happy with your food supply and try to enter your colon cells, which keep your immune system turned on to cause excessive inflammation. You can improve the colony of good bacteria in your colon by:
• Eating lots of the anti-inflammatory foods: vegetables, whole grains, beans, seeds, nuts, fruits, and seafood (non-fried)
• Restricting the pro-inflammatory foods such as red meat, processed meats, fried foods, foods with added sugar and all drinks with sugar in them including fruit juices and alcohol.

The pro-inflammatory foods turn on your immune system to cause these cells and proteins to attack and damage your own normal cells, while the anti-inflammatory foods dampen down this response to protect your cells from damage from an overactive immune system. Chronic inflammation increases risk for obesity, heart disease, diabetes, Alzheimer’s disease, certain cancers, and many other diseases. The more pro-inflammatory foods you eat, the greater your risk for these conditions. The more anti-inflammatory foods you eat, the greater your protection from chronic inflammation and the diseases associated with inflammation (Alzheimer’s and Dementia, Dec 2021;17(12):1914-1922; Stroke, Mar 15, 2021:52(6A);52:e295-e308).

Which Foods are Healthful?
Many people are confused about a healthful diet because food companies spend so much money advertising that their products are healthful when they are not. Most ultra-processed foods are pro-inflammatory even if they are promoted and packaged to appear “healthful.” Ultra-processed foods usually lack protein, dietary fiber, and micronutrients and also often contain contaminants from industrial processing and packaging. An estimated 75 percent of the U.S. food supply is ultra-processed and usually contains unhealthful ingredients such as sugar, salt, fat, artificial colors, preservatives, flavorings, sweeteners, and emulsifiers. Ultra-processed foods include soft drinks and “fruit” drinks, frozen meals, hot dogs, cold cuts, most fast foods, sweet or savory packaged snacks, energy bars and drinks, and so forth. Several studies suggest that ultra-processed foods are associated with dementia and decreased mental functioning (JAMA Neurology, Dec. 5, 2022).

My Recommendations
Dementia is not just a disease of the brain. Research is showing that it is a disease of inflammation. Constipation is just another marker for inflammation that can damage and destroy every type of cell throughout your body. Lifestyle factors to help prevent dementia include:
• Develop good sleep habits (Nature Communications, April 20, 2021)
• Try to exercise daily (JAMA Netw Open, July 22, 2023;6(7):e2324465)
• Use hearing aids if you have hearing loss (The Lancet Public Health, May 2023;8(5):e329-e338)
• Eat mostly anti-inflammatory foods with lots of soluble fiber: vegetables, whole grains, beans, fruits, nuts and other seeds (Int J Mol Sci, 2022 Dec;23(23):14924)
• Restrict pro-inflammatory foods: meat from mammals and processed meats (Nutrients, 2020 May; 12(5): 1528), sugar added foods and drinks (Int J Mol Sci, Dec 2022;23(23):14924), fried foods and many highly processed foods
• Socialize (Neurology, August 23, 2022;99 (8)) and participate in lots of different activities (Epidemiol Psychiatr Sci, Jan 11, 2022;31:e5)
See my report on Anti-Inflammatory Lifestyle to Help Prevent Dementia as You Age