Oxidative Stress: Effects on Cognition

By Ram Rao, Ph.D., Principal Research Scientist for Apollo Health

One of my earlier articles focused on external stress and its effects on people’s lives, personal relationships, sleep patterns, eating habits, and the development of Alzheimer’s disease (AD). In addition to external stress internal cellular stress is termed oxidative stress, characterized by the abnormal accumulation of free radicals in the body, which trigger cell and tissue damage. Free radicals are atoms or molecules with unpaired electrons. They form when cellular oxygen interacts with certain molecules. Free radicals are highly reactive, unstable, and have a lifespan of only a fraction of a second. During that time they can damage DNA and trigger mutations that can lead to various diseases.

Free radicals are produced in several ways and may be generated from normal metabolic processes in the body or from exposure to environmental factors. Examples of free radicals include singlet oxygen, hydrogen peroxide, superoxides, and hydroxyl radical (HO•). Once they are generated, whether through external exposure or the normal metabolic processes, free radicals are free to do damage. Several factors contribute to oxidative stress and excess free radical production. These factors can include a poor diet, infections, disharmonious lifestyle, radiation, chemical carcinogens, or other environmental toxins (e.g., tobacco smoke, UV, and air pollutants).

Uncontrolled oxidative stress characterized by the abnormal accumulation of free radicals can accelerate the aging process and may contribute to the development of a number of chronic conditions. Such conditions include heart disease, cancer, diabetes, chronic inflammatory diseases, and neurodegenerative conditions, including Alzheimer’s disease (AD) and Parkinson’s disease (PD). The brain is particularly vulnerable to oxidative stress because brain cells require a substantial amount of oxygen. Research studies show that the brain consumes nearly 20 percent of the total amount of oxygen to fuel itself. The brain uses oxygen to perform intense metabolic activities that also result in the production of free radicals. Normally, these free radicals help support brain cell growth, neuroplasticity, and cognitive functioning, but during oxidative stress, the abnormal accumulation of free radicals and the body’s failure to neutralize the excess toxic radicals result in structural and functional damage to the brain. Research studies have shown that the brains of people with AD show lesions that are typically associated with oxidative stress. Research studies also indicate that those with the ApoE4 allele are likely to be more susceptible to oxidative stress than those without the E4 allele.

Free radical scavengers (FRS) or antioxidants (AOs) are compounds that bind to free radicals, neutralize their toxicity and reduce the damage they would cause in the body. They are produced by the body and can also be obtained from external sources. In general, the body is able to maintain a balance between cellular antioxidants and free radicals. When there is an abnormal accumulation of free radicals, and the body’s own antioxidant levels are not sufficient to neutralize the free radicals, it is necessary to get the protective antioxidants from external sources. Brains of people with AD appear to have higher levels of natural antioxidants responsible for ‘clearing up’ excess free radicals, suggesting that the body is trying to combat oxidative stress suggesting the therapeutic use of antioxidants. There are numerous different substances that can act as antioxidants. The most familiar ones are vitamin C, vitamin E, beta-carotene, other related carotenoids, phytoestrogens, glutathione, coenzyme Q10, lipoic acid, flavonoids, phenols, polyphenols, and minerals including selenium and manganese. Most are naturally occurring, and which is partly why a diet rich in vegetables and fruits has been linked with a lower risk of many oxidative stress-related diseases.

Research studies have shown that diets rich in antioxidants prevent the deleterious effects of oxidative stress, improve the levels of several neurotrophic factors and reverse cognitive impairment. Fruit and vegetables could also have protective effects against oxidative stress induced-stroke and vascular dementia. Epidemiological studies show that higher intakes of antioxidant-rich fruits, vegetables, and legumes are associated with a lower risk of chronic oxidative stress-related diseases and deaths from all causes. While most of the clinical trials have fundamental limitations, at the same time, the unanimous opinion is that eating fruits and vegetables— all rich in free radical scavengers and antioxidants — protects against age-associated health conditions and cognitive impairment.

Non-starchy vegetables and some resistant starches such as colored tubers and legumes are the best substitutes for whole grains to avoid inflammation and blood glucose spikes. We recommend that everyone on the protocol, prioritize vegetables that are below 35 on the glycemic index. Additionally, note the effect that higher glycemic fruits have on your blood sugar with one- and two-hour post-prandial checks. You may need to avoid some fruits entirely or at least until your blood sugar levels are optimal and sustained. For more refer to our Grocery Guide: Fruit.

The Bredesen Seven (or “B7”) involves seven distinct yet complementary strategies that optimize brain health. Each of the strategies alone can reduce the levels of free radicals and thereby suppress oxidative stress. Furthermore, adding Mindfulness to the B7 and practicing all eight strategies together creates a powerful synergy that prevents the deleterious effects of oxidative stress, allowing the brain to heal and be more resilient. The recent successful clinical trial, together with the several observational studies that showed remarkable benefits on human participants that incorporated these complementary strategies, serve as a testimony to the B7’s success in alleviating oxidative stress-induced degenerative changes in Alzheimer’s disease.