During many processes throughout the body, tiny molecules called free radicals are naturally produced that collide & react with other molecules & change their properties. These free radicals serve some purpose but also react with DNA, RNA & oxidative substances causing damage & metabolic ageing. There is a balance between production & accumulation of these free radicals & organism’s capacity to manage those endogenous & exogenous antioxidants. Disturbance in this balance is called Oxidative Stress. The amount of oxidative stress determines whether it will lead to good or bad response.
High levels of oxidative stress can lead to excessive production of these free radicals in the absence of natural defences resulting in damage to protein, lipids & DNA. This damage is said to be the starting point for the onset of diseases such as obesity, diabetes & some cardiovascular diseases.
Exogenous antioxidants obtained from diet, mainly Vitamin C, Vitamin E, Zinc, Selenium & carotenoids have an important role to play in oxidative stress & DNA damage. Individual genetic variations can impact the components involved in maintaining oxidative balance. These variations can impact proteins involved in uptake, utilization & metabolism of dietary antioxidants. It may alter their serum levels & lead to modulation of oxidative stress. Interaction between genetic variation & antioxidant can help in evaluating if an individual can benefit from diet intervention & antioxidant supplementation. A greater understanding of which antioxidant could promote protection & increase DNA repair would go a long way in minimising chances of chronic disease.
Superoxide, hydroxyl, hydro peroxide, nitric oxide and nitrogen dioxide are examples of free radicals, which can cause DNA damage or oxidize lipids and proteins. The excess of these free radicals can be produced by exogenous factors such as pollution, smoking, drinking alcohol & inadequate nutrition. For this reason, our body needs a complete defense system to protect the damage caused by excess production of free radicals /reactive oxygen species. When the production or accumulation of these species exceeds the organism’s ability to neutralize them, oxidative stress arises. Besides directly damaging biological molecules & tissues, these excess free radicals also lead to production of cytokines & inflammation.
The excess of free radicals are neutralised by antioxidants produced by organisms (endogenous) & those acquired through diet (exogenous). Let us discuss in detail about antioxidants & how it helps in DNA repair.
Antioxidants act at different levels for protection of organisms. The first protection against free radicals is to prevent their formation through inhibition of chain reaction with iron & copper. Besides, antioxidants can intercept free radicals produced by cellular metabolism or exogenous sources, thereby preventing attack on lipids, amino acids, double bonds of polyunsaturated fatty acids & DNA basis
The primary antioxidant defense system includes the enzymes superoxide dismutase, glutathione peroxidase and catalase. These substances can remove oxygen or highly reactive compounds reacting with the oxidizing compounds and protect cells and tissues from oxidative stress.
Some nutrients & bioactive compounds acquired through diet play an important role in preventing oxidative stress. These antioxidants work by preventing formation of free radicals, neutralizing already formed & repairing the damage caused by highly reactive molecules. Moreover, exogenous antioxidants combine with those produced by organisms to enhance antioxidant capacity. Let us discuss sources of exogenous antioxidants & its genetic determinants in detail:
- Vitamin C: Vitamin C is a vital nutrient & is primary hydrophilic antioxidant in plasma. Besides neutralising free radicals, it also acts in regeneration of α-tocopherol which also has antioxidant action. Vitamin C (ascorbic acid) is a white, crystalline, water-soluble and stable material in dry form. Around 85% of vitamin C in the human diet is provided by citrus fruits & vegetables. Vitamin C consumed is absorbed in the small intestine by active transportation by vitamin C transporter type 1 which is encoded by SLC23A1 gene. The sodium dependent vitamin C transporter type 2, encoded by the SLC23A2 gene is found in several tissues including brain, lung, liver and skeletal muscle. There is large interindividual variability when it comes to circulating concentration of ascorbic acid as well as response to Vitamin C from the diet. Genetic variation between individuals explains this difference. Environmental factors play only a partial role in this variability. Several variations to the status of Vitamin C have been found in various genes. Polymorphisms in the SLC23A1 gene and changes in the glutathione S-transferase (GST) gene were also associated with the concentrations of ascorbic acid.
- Vitamin E: Vitamin E is an essential micronutrient consumed regularly in a diet consisting of vegetable oil & derivatives such as margarine. Other dietary sources of Vitamin E include meat & animal fat, whole grain, nuts & seeds. Vitamin E has several functions in the organism, including membrane stabilization and regulation of the signaling cascade of gene expression, in addition to its known antioxidant properties. There are large variations among individuals in circulating levels of Vitamin E. Around 22% these variations were attributed to difference in key genes.Genetic variants affecting the transport and metabolism of lipids are also important in determining the status of vitamin E. Genetic variations can also be used to identify patients who would benefit from vitamin E supplementation in a specific population.
- Carotenoids: Carotenoids are a large group of lipophilic substances. Only 60 of these Carotenoids are normally found in our diet & a small number comes from human blood & tissue.The most abundant forms found in human plasma include α-carotene, β-carotene, Lycopene and lutein. Carotenoids print their characteristic color to many fruits & vegetables such as carrots, oranges & red tomatoes. These can also be found in plants of dark green leaves. The bioavailability of some carotenoids is further enhanced by boiling & addition of dietary fat. The antioxidant properties of carotenoids are important in protecting lipids & DNA against the action of free radicals and driving repair mechanisms. Variability in individuals was found in absorption, circulating concentration and response to supplementation of carotenoids explained by genetic variation. Two variations of the BCMO1 gene were associated with circulating concentrations of β-carotene and the ability of this enzyme to convert β-carotene to vitamin A.
Key takeaways
Oxidative stress has been responsible for development of chronic diseases. Diet with high consumption of fruits & vegetables is inversely related to development of chronic diseases. Genetic variations involving uptake, distribution, metabolism & transport of dietary antioxidants were associated with circulating concentration of antioxidants & hence different individual responses to supplementation. Besides, genetic variations modulate relationships with endogenous antioxidant systems & environmental factors such as antioxidants required through diet.
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