Endogenous Antioxidants in Metabolic Diseases

Oxidative stress is a condition where the antioxidants in the body are not plentiful enough to combat free radicals, unstable molecules that cause cell and tissue damage that can lead to degenerative disease. This typically occurs when the body is exposed to a high amount of environmental attacks, such as tobacco smoke, alcohol, high-fat diet, chemicals and insecticides, and radiation. Free radicals are attacked by two types of antioxidants – those that are made within the body, called endogenous antioxidants, and those that we consume in the diet from fruits and vegetables (exogenous antioxidants).

Metabolic conditions, such as dyslipidemia, particularly elevated low density lipoprotein (LDL) cholesterol levels, are linked to oxidative stress. Free radicals trigger the process of atherosclerosis which leads to cardiovascular disease. Other conditions related to free radical attacks include Alzheimer’s disease, Parkinson’s disease, diabetes and rheumatoid arthritis.


Glutathione is synthesized in the liver from three amino acids – L-cysteine, L-glutamic acid and glycine. The antioxidant directly neutralizes free radicals as well as assists exogenous antioxidants, such as vitamin C and E. Glutathione also detoxifies carcinogens and other harmful substances, is essential to the immune system, and plays a fundamental role in many metabolic processes.

Coenzyme Q

Coenzyme Q, also known as ubiquinol, is made through the mevalonate pathway which also regulates cholesterol levels in the body. CoQ10 is also essential to the energy production cycle and is found in high quantities in the heart and the liver.  Although the body makes CoQ10, aging causes a reduction in the organs. Exposure to ultraviolet (UV) light also reduces Coenzyme Q.

Superoxide Dismutase (SOD)

Of the three superoxide dismutase enzymes in the body, SOD1 is the most important to the antioxidant process. It reduces free radicals into hydrogen peroxide, which is less harmful and eventually broken down–with the assistance of an enzyme called catalase–into water and oxygen. Lack of SOD1 may lead to a wide range of disease states, including hepatocellular (liver) cancer, an acceleration of age-related muscle mass loss, and a reduced lifespan. Some studies have also linked SOD1 to Amyotrophic lateral sclerosis (ALS, or Lou Gehrig’s Disease).


Melatonin is a naturally occurring compound in both plants and animals. While it is best known for regulating the sleep-wake cycle, it is also a powerful antioxidant. Melatonin is produced in the brain, the skin, the eyes and the GI tract. In some animal studies, melatonin has been shown to prevent the DNA damage caused by some carcinogens. It may also reduce the damage caused by Parkinson’s disease, enhance the immune system, and could inhibit the accumulation of amyloid proteins that cause the neuron tangles in Alzheimer’s Disease.

Interaction with Exogenous Antioxidants

While the body can help defend itself against free radical damage and oxidative stress, exogenous nutrients are needed to assist with the process. Glutathione, for example, works with Vitamins C and E to reduce them into usable compounds for the body. Minerals such as copper and zinc are needed to produce SOD1. Most experts agree, however, that exogenous nutrients should be provided by an overall healthy diet and not through supplements. Overuse of supplements can actually damage some of the metabolic processes that are needed for antioxidant protection.


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