Why Consumption of Dietary Antioxidant Supplements May Not Work?

by Chang Sui Kiat

There have been accumulating evidences that suggest the consumption of large doses of dietary antioxidant supplements does not have significant medicinal effect and could be harmful in some cases. This is because the effect of free radicals in the development of various chronic diseases is still unclear. Furthermore, the natural antioxidant capacity and the immune system of the human body could counteract the actions of dietary antioxidants. The dosage of antioxidant in dietary supplements may also be inappropriate. The consumption of food naturally rich in antioxidants, such as fruits, vegetables and grains should be promoted instead of the consumption of dietary supplements.

Antioxidant supplementation, either in tablets or in food per se, is based on the notion that reactive oxygen species (ROS) and other free radicals contribute to many human diseases by causing oxidative damage, and that decreasing oxidative damage will help to prevent those diseases [1]. Therefore, the notion that ‘antioxidant is good – the more antioxidants we take, the better our health will be’ is common among the general public. The supplements and nutraceutical industries use these concepts to market their products, often portraying them as safe, health-providing molecules to be eaten as mega-dose supplements. Hence, antioxidant-enriched food, drinks (typically rich in sugars and colouring agents), cosmetics and supplements are being advertised and marketed extensively.

Over-consumption of antioxidants may down-regulate important endogenous antioxidants and depress parts of the immune system

Scientists are now baffled by latest research findings advising against routine consumption of antioxidant or dietary supplements. Numerous human clinical trials showed no beneficial effect of multivitamin or multi-mineral supplements, folic acid and vitamin B supplements on all-cause mortality, cancer, cardiovascular diseases and cognitive impairment [2-5]. Moreover, it was found that β-carotene, vitamin E and vitamin A supplements may be associated with higher all-cause mortality [6]. This happens because β-carotene, vitamin E and vitamin A may exert pro-oxidant activities in human body, especially when consumed in large doses [7]. Furthermore, most supplements do not prevent non-communicable diseases (NCDs) or death [8]. This statement is especially true for healthy general population with no obvious evidence of nutrient deficiencies [7, 9, 10]. Therefore, consumption of antioxidant supplements appears to be redundant.

(i) Moderate levels of ROS are essential for health

A common misconception from the general public is that free radicals or ROS are bad, whereas antioxidants must be good. Indeed, ROS are bad as they contribute to ageing, cancer and neurodegenerative diseases such as dementia and Alzheimer’s disease [7, 9, 10]. There are several reasons why these antioxidants fail to show benefits in humans.

Firstly, ROS may not be the main causes in some NCDs. We have a well-balanced pool of ROS and antioxidants that allows some ROS to perform their useful physiological functions while minimising oxidative damage (Figure 1). This can be exemplified by the role of ROS in killing pathogens as part of the human innate immune system [10, 11]. In addition, it has been reported that stem cells need some ROS to function properly, but excessive amount of ROS can impair their function [12].

The  overall antioxidant defense in our body depends heavily on endogenously-synthesised antioxidant enzymes such as reduced glutathione (GSH), catalase and superoxide dismutase (SOD) instead of diet-derived antioxidants (Figure 1) [10, 11]. Therefore, it will be more effective if the antioxidant defense system is stimulated with some weak or mild pro-oxidants or ROS, which will in turn stimulate the level of our own antioxidants, such as GSH to fight infections[1, 7, 9]. In relation to that, ROS is the culprit for the development of cancer; however ROS sometimes can help to cure cancer [13]. In the same vein, exercise is well known to be beneficial for humans because it is a mild pro-oxidant challenge that stimulates beneficial adaptation in skeletal muscles [14].

Figure 1: Balance of antioxidants and reactive species (RS) in vivo. Adapted from [12] with permission from Elsevier.
Figure 1: Balance of antioxidants and reactive species (RS) in vivo. Adapted from [12] with permission from Elsevier.
Therefore, basal levels of pro-oxidants could be better for our health than huge amounts of antioxidants. Over-consumption of antioxidants may down-regulate important endogenous antioxidants and depress parts of the immune system or the normal cellular protective responses to oxidative stress.

(ii) Physiological sensitivity to dietary antioxidant

It is possible that only patients with high levels of oxidative damage or those whose diet and lifestyle are in poor conditions will respond to antioxidant supplementation [11]. It is also important to note that those antioxidants are more efficient in decreasing oxidative damage in animal models like mice or rabbits than in human patients [1, 9-11]. It seems that human antioxidant defense system resists modulation by dietary antioxidants, while the laboratory rats and rabbits appear more sensitive to administered dietary antioxidants.

(iii) Doses of dietary antioxidant matter

Thirdly, the doses of administered dietary antioxidant may be incorrect. The dosages of nutrients in the form of supplements often exceeded the recommended daily allowances (RDA) [15]. There is evidence that lower doses and/or mixtures of antioxidants demonstrated more benefits than higher doses of single agents [10]. For example, consumption of foods rich in vitamin C was shown to decrease oxidative damage physiologically whereas the intake of vitamin C alone did not [16].

Antioxidants from organic sources

Consumption of fruits, vegetables and grains help maintain good health and delay disease occurrence. The intake of 3-5 servings of fruits and vegetables daily would protect against NCDs like heart disease, cancer and diabetes. This happens because fruits and vegetables are chemically complex, where the health benefits could arise from the additive effects of many compounds or mixtures of components present, including vitamins, minerals, fibre, phenolic compounds and flavonoids [15, 16, 18]. This mechanism is called synergistic actions where nothing happens in isolation in complex biological systems [7].

Isolating individual nutrients making them into quantity for human consumption to imitate the nutritional benefits from whole foods might not be a good idea after all. This is because the isolated nutrient may either lose its bioactivity or may not behave the same way as the same compound in whole food [18]. More importantly, plant foods like fruits and vegetables are low in ‘calories’, the term of which the people is most concerned about. So, why not take more fruits and vegetables for our good health?

An understanding of why dietary antioxidant supplements do not completely benefit human health remains a target of research in the scientific field. In conclusion, consumption of natural foods containing antioxidants, such as fruits, vegetables and grains, coupled with regular exercise are suffice to maintain good health and prevent the onset of NCDs. 

Note: Find out more about various types of dietary supplements on http://fnic.nal.usda.gov/dietary-supplements, the website of Food and Nutrition Information Center, USDA.

Facts & Figures

In 2014, Japanese was listed at the top of the overall life expectancy (84.6 years old) worldwide according to World Health Organization. Earlier this year, Office for National Statistics (UK) reported that Japanese diet rich in vegetables, green tea and raw fish as some of the keys to longevity.

The Japanese Food Guide Spinning Top was introduced in 2005 by the Japanese Ministry of Health, Labor, and Welfare and the Ministry of Agriculture, Forestry, and Fishery to promote healthy diet as follows (Source: www.mhlw.go.jp):




[1] Halliwell (2012) Nutr Rev 70:257-265
[2] Briancon et al. (2011) Intl J Epidemiology 40:1605-1616
[3] Fortmann et al. (2013) Ann Intern Med 159:824-834
[4] Kesse-Guyot et al. (2011) Am J Clin Nutr 94:892-899
[5] Lamas et al. (2013) Ann Intern Med 159:797-804
[6] Bjelakovic et al. (2013) J Am Med Assoc 310:1178-1179
[7] Halliwell (2009) Free Radical Bio Med 46:531-542
[8] Gahche et al. (2011) Natl Center for Health Statistics
[9] Halliwell (2012) Brit J Clin Pharmaco 75:637-644
[10] Halliwell (2011) Trends Pharmacol Sci 32:125-130
[11] Gutteridge et al. (2010) Biochem Bioph Res Co
[12] Juntilla et al. (2010) Blood 115:4030-4038
[13] Halliwell (2007) Biochem J 401:1-11
[14] Jackson (2011) Antioxid Redox Signal 15:2477-2486
[15] USDA & HHS (2010) Dietary Guidelines for Americans
[16] Halliwell et al. (2005) Am J Clin Nutr 81:268S-276S
[17] John et al. (2002) Lancet 359:1969-1974
[18] Liu (2003) Am J Clin Nutr 78:517S-520S

About the Author

CHANG SUI KIAT (SHAWN) is a PhD candidate (Nutritional Sciences) who have submitted his PhD thesis under the sponsorship of Biasiswa Yang Di-Pertuan Agong. His research interests include bioactive food components and nutritive qualities of food that advance and impact the understanding of human health. As a graduate nutritionist and a life member of Nutrition Society of Malaysia (NSM), he is involved in the health promotion and screening programs, such as Nutrition Month of Malaysia and World Digestive Health Day organised by NSM and Ministry of Health annually. Find out more about Sui Kiat at http://www.scientificmalaysian.com/members/suikiatchang/

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