Brunswick Labs knows antioxidants. Here’s some knowledge sharing on the science, history, types, and function of antioxidants.
Antioxidants: Mechanisms of Action and Effectiveness
The first connection between the protective role of antioxidants against age and disease-induced damage to cells and biological molecules, DNAs, lipids and proteins, was made in the late 1980s and early 1990s. Since then, numerous research studies have focused on elucidating the mechanism(s) of action of these molecules and identifying the factors that influence their effectiveness.
The human body utilizes both endogenous antioxidants as well molecules ingested through diet, as its defense mechanism. Examples of endogenous antioxidants include enzymes and small molecules such as glutathione peroxidase and glutathione, while vitamins, carotenoids and polyphenolics are representative of dietary antioxidants. In general, antioxidants belong to several categories, they are either: i) enzymes, such as superoxide dismutase, glutathione peroxidase, and catalase; (ii) hormones (melatonin for example); (iii) proteins (albumin, ferritin, etc.); or (iv) small molecules (phenolic compounds, carotenoids, glutathione, uric acid, tocopherol).1
The Institute of Medicine defines dietary antioxidants as “a substance in foods that significantly decreases the adverse effects of reactive species, such as reactive oxygen and nitrogen species, on normal physiological function in humans”.2 They can have either sacrificial or preventive role. Sacrificial action refers to their ability to scavenge reactive oxygen/nitrogen species (ROS/RNS) to stop radical chain reactions, while preventive role reflects their potential to inhibit the formation of reactive oxidants.1 Let’s take a look at how antioxidants exert their effects in molecular interactions.
Antioxidants exert their effects via several basic mechanisms, which include: scavenging the species that initiate peroxidation, quenching singlet oxygen, chelating metals, breaking free radical chain reactions, and reducing the concentration of O2.3 Antioxidant molecules are not all equally powerful in reacting according to these varied mechanisms. For example, phenolic acids are effective in trapping free radicals but not as good at chelating metals, while flavonoids can do both efficiently – scavenge free radicals and chelate metals.4 Because antioxidants employ several mechanisms, a single assay cannot account for all the different modes of action. As a consequence, over the years, the researchers have developed many antioxidant assays which are often used in conjunction to assess the overall antioxidant potency.
Intrinsic factors influencing the effectiveness of dietary antioxidants
Antioxidant effectiveness depends on several important intrinsic factors: activation energy, rate constants, molecular stability (volatility and heat susceptibility), oxidation–reduction potential, and solubility.5 These factors are in turn closely related to the antioxidant molecular structure.
Those antioxidants capable of interrupting the free radical chain reaction are usually the most effective.4 They are characterized by aromatic or phenolic rings and act by donating a hydrogen atom to free radicals formed during oxidation. In the process, they transition into a radical form themselves, however, these radical intermediates are stable due to resonance delocalization of the extra electron within the aromatic ring and subsequent formation of stable quinones.5 The most effective phenolic antioxidants have low oxidation-reduction potentials and OH groups in the ortho-position on the B phenolic ring. In addition, phenolics with more than one hydroxyl group, such as catechin, are more effective than those with only one.4 As an added benefit, many phenolic compounds are not susceptible to molecular oxygen attack.
Extrinsic factors influencing the effectiveness of dietary antioxidants
There are several important considerations to take into account in assessing the effectiveness of dietary antioxidants. They exert their effects according to the mentioned varied mechanisms and include radical chain reaction inhibitors, metal chelators, proteins/enzymes, and antioxidant enzyme cofactors.
The efficacy of dietary antioxidants is largely dependent on their bioavailability, which is, in turn, influenced by digestion and complex metabolic reactions taking place in the gut. In addition, the food matrix effects and interactions, both synergistic and antagonistic, occurring between food ingredients also play a role in antioxidant effectiveness.4 Clinical studies have confirmed the health protective effects of certain dietary patterns rich in plant foods and antioxidants, but researchers were not able to attribute these effects to one or more specific ingredients or compounds. For example, positive effects of the Mediterranean diet on heart health and cardiovascular disease prevention cannot be attributed to high intakes of olive oil alone, or to specific active constituents from olive oil. Rather, the overall effect is a result of complex interactions between food ingredients and their effects at the molecular, cellular and tissue levels.
Beyond antioxidant function
Although the term ‘’antioxidant’’ clearly implies a molecule’s function, antioxidant action is not the only function of these molecules have in the human body. Recent research suggests that the mechanism of action of antioxidants and their role in disease onset or progression delve deep into cellular signaling processes and control of gene expression.6 In the larger scheme of things, antioxidants and ROS co-exist in a finely tuned balance that ensures normal functioning of the human body. Nutrigenomics is a rapidly emerging area of epigenomics focused on studying the heritable changes in gene expression induced by diet, as well as interactions between the genome and the diet. With advances in this field, it will be exciting to learn more about the role that bioactive dietary compounds have in regulation of epigenetic modifications that result in significant health benefits.
- 1. Huang D, Ou B, Prior RL. The Chemistry behind Antioxidant Capacity Assays. J Agric Food Chem. 2005; 53:1841-1856.
- 2. Panel on Dietary Antioxidants and Related Compounds, Standing Committee on the Scientific Evaluation of Dietary Reference Intakes, Food and Nutrition Board Vitamin C, Vitamin E, Selenium, and â-Carotene and Other Carotenoids: Overview, Antioxidant Definition, and Relationship to Chronic Disease. In Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids; National Academy of Science: Washington, DC, 2000; pp 35-
- 3. Badarinath AV, Rao KM, Chetty CMS, Ramkanth S, Rajan TVS, Gnanaprakash K. A Review on In-vitro Antioxidant Methods: Comparisons, Correlations and Considerations. 2010; 2(2): 1276-1285.
- 4. Brewer MS. Natural antioxidants: Sources, compounds, mechanisms of action, and potential applications. Comp Rev Food Sci F. 2011;10:221-247.
- 5. Nawar WF. Lipids. In: Fennema O, ed. Food chemistry. 3rd New York, NY: Marcel Dekker; 1996: 225–320.
- 6. Wachtel-Galor S, Benzie IFF. Series Preface. In: Benzie IFF, Wachtel-Galor S, eds. Herbal Medicine Biomolecular and Clinical Aspects. 2nd Boca Raton, FL: CRC Press; 2011:1-10.
Author Jasenka Piljac Zegarac is a scientist and freelance writer. She holds a PhD in biology and a BS degree in biochemistry, and contributes on a regular basis to several health and science blogs. Her research articles have gathered more than 1200 citations. She may be contacted for assistance with a variety of science and medical writing projects. Find JasenkaLinkedIn.