Free radicals are highly reactive and dangerous molecules that damage DNA, proteins and cellular membranes. Free radicals can be created in our bodies due to certain environment exposures such as air pollution, smoking or UV light. However, free radicals can also be produced by our body in natural processes such as inflammation and as a normal by-product in metabolism when producing energy.
Anti-oxidants are free radical scavengers that interact with the free radical to ensure it is no longer a reactive molecule. The balance between oxidation and antioxidation is believed to be critical in maintaining healthy biological systems.
Anti-oxidants are found naturally in the body in the form of enzymes but can also be consumed in a wide variety of foods, especially vegetables and fruits, as well as green tea and red wine. Examples of dietary anti-oxidants are vitamin C, vitamin E, carotenoids and polyphenols. A low consumption of fruit and vegetables has been linked with an increased risk for a variety of illnesses, attributed to the build-up of damaging free radicals.
Oxidative Stress Explained
To understand oxidative stress better it is helpful to understand the chemistry of a free radical.
Atoms are surrounded by electrons that orbit the atom in layers called shells. Each shell needs to be filled by a set number of electrons. If the outer shell of an atom is not full, it is unstable and called a free radical. Atoms want to have a full outer shell so the free radicals react quickly with other substances to try attain another electron.
There are many types of free radicals, but the ones of most concern in biological systems are derived from oxygen, and these free radicals are known collectively as reactive oxygen species (ROS).
Oxygen has two unpaired electrons, one in each of the two outer shells. This structure makes oxygen especially susceptible to radical formation. Reactive oxygen species (ROS) are reactive forms of a standard oxygen molecule. High levels of ROS cause damage to cellular structures that leads to the process of oxidative stress.
Oxidative stress can damage the body’s cells, leading to a range of diseases and causes symptoms of aging, such as wrinkles.
Reactive Species Effects
Some of the ways that ROS in the body cause damage is by peroxidation of membrane lipids (phospholipids). This leads to numerous effects such as:
- increased membrane rigidity
- decreased activity of membrane-bound enzymes (e.g. sodium pumps)
- altered activity of membrane receptors
- altered permeability
In addition to effects on phospholipids, radicals can also directly attack membrane proteins.
Examples of reactive oxygen and nitrogen species
Three groups of enzymes play significant roles in protecting cells from oxidant stress. These are explained more in detail below.
- Superoxide dismutases (SOD) – three forms exist, SOD1 (Intracellular), SOD2/MnSOD (Mitochondrial), SOD3 (Extracellular)
- Catalase (CAT)
- Glutathione peroxidase (GPx)
In addition to these enzymes, glutathione transferase, ceruloplasmin, hemoxygenase and possibly several other enzymes may participate in enzymatic control of oxygen radicals and their products.
Oxygen molecules in the body sometimes have an electron removed from its shell which makes it reactive species superoxide. Superoxide can be managed in a few ways.
- One way is that a SOD enzyme changes superoxide to hydrogen peroxide and oxygen which is less reactive but still potentially harmful. Hydrogen peroxide is then neutralised by either GPx or CAT enzymes.
CAT enzyme converts the harmful hydrogen peroxide to neutral water and oxygen using iron as a cofactor.
GPx enzyme converts mildly harmful hydrogen peroxide to neutral water and oxygen using selenium and glutathione as a cofactor. During this process glutathione (GSH) is converted to glutathione disulfide (GSSG). The body wants more GSH to help convert more hydrogen peroxide so it needs to convert the GSSG back to GSH. Glutathione reductase enzyme converts GSSG back to GSH using vitamin B2 and NADPH.
2. Superoxide is sometimes also converted to other reactive species such as hydroxides. Metal ions are used as cofactors during this reaction. This is why one wants SOD enzymes to be working effectively to start the process of neutralising superoxides.
Four prominent non-enzymatic antioxidants one should note are:
- Vitamin E is a fat-soluble antioxidant, and it reduces oxidative stress by protecting membranes from oxidative damage as it traps peroxy radicals in cellular membranes.
- Vitamin C is a water-soluble antioxidant that can reduce radicals from a variety of sources and assists in recycling vitamin E radicals. Unfortunately, vitamin C can also be a pro-oxidant under certain circumstances.
- The carotenoids are fat- soluble antioxidants and may be important in the protection against lipid peroxidation. Food sources of carotenoids are orange and red vegetables and fruits (carrots, tomatoes, apricots, plums) and green leafy vegetables (spinach, kale).
4. Glutathione may well be the most important intracellular defence against damage by reactive oxygen species. It is made up of 3 amino acids (glutamic acid, cysteine and glycine). The cysteine provides an exposed free sulphydryl group (SH) that is very reactive, providing an abundant target for radical attack. Reaction with radicals oxidizes glutathione, but the reduced form is regenerated in a redox cycle involving glutathione reductase and the electron acceptor NADPH.
- The glutathione molecule is often confused with two types of enzymes; glutathione peroxidase (GPx) and glutathione-s-transferase (GST).
- GPx enzyme uses glutathione in the process where it converts harmful hydrogen peroxide to safe water and oxygen.
- GST enzyme requires glutathione in the detoxification process where harmful intermediate compounds are converted to water soluble molecules that can be easily excreted.
There are other small molecules that function as antioxidants besides these three such as bilrubin, uric acid, flavonoids and carotenoids.
Exogenous Verses Endogenous Antioxidants
Antioxidants can be made by the body (endogenous) or need to be consumed through the diet (exogenous) as the body cannot make them.
- Vitamin C
- Vitamin E
- Superoxide dismutase (SOD)
- Catalase (CAT)
- Glutathione peroxidase (GPx)
- Glutathione S -transferase (GST)
- Lipoic acid
- Uric acid
Interventions below may vary depending on which genes in the oxidative stress panel are impacted.
- Ensure a polyphenol-rich diet by increasing dietary intake of vegetables and fruit and ensure adequate antioxidant intake from food.
- Engage in regular moderate intensity physical activity.
- Decrease dietary and environmental toxin exposure, from pollution, pesticides, smoked foods, heavy metals and nitrates used as a food preservative.
- Cessation of smoking should be strongly encouraged.
- It is important to moderate alcohol consumption, and to rather drink red wine (due to higher resveratrol levels) as the alcohol of choice. Excessive alcohol intake can reduce glutathione levels and increase oxidative stress.
- Increase intake of omega 3 fatty acids.
- Increase intake of foods such as spinach and beetroot that contain nitrates and are converted naturally in the body to nitric oxide.
- Ensure adequate intake of manganese, the cofactor for SOD2.
- As GPx1 uses selenium as a co-factor it is helpful to ensure adequate selenium intake. Brazil nuts are a rich source of selenium, and a regular intake has been shown to significantly increase the activity of the GPx1 enzyme in C allele carriers. One brazil nut contains approximately 70mcg of selenium, (providing over 100% RDA). Include brazil nuts in the diet and other food-rich sources of selenium, such as sardines and turkey. If selenium intake from food is poor, consider supplementation.
- Provide adequate intake of glutathione precursors to support glutathione production. A diet should provide sulphur and building block amino acids. Eating beef, chicken and fish should supply adequate sulphur containing amino acids. For vegetarians and vegans the following may provide some sulphur but in smaller amounts: garlic, onion, broccoli, Brussels sprouts, cauliflower, kale, watercress and mustard greens. Some foods naturally contain glutathione however, it is poorly absorbed. Examples are spinach, avocados, and asparagus.
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