Updated on April 7, 2023
As people become more health-conscious and increasingly seek natural alternatives to pharmaceutical drugs, those with a wide variety of health conditions are expressing interest in the benefits of antioxidant supplementation. There is good reason for this; in the body, antioxidant molecules scavenge the free radicals that are produced by oxidative processes, which otherwise have the potential to cause significant cell and tissue damage.
Indeed, a growing body of research indicates that in both foods and in nutritional supplements, antioxidant-containing compounds can provide nutritional support for a broad range of physical and mental health conditions, from cardiovascular disease to autism spectrum disorder (ASD).* For many patients, families, and practitioners looking to manage conditions like these, antioxidants pose an appealing alternative to traditional pharmacotherapy, given that they are often derived from all-natural sources.
The appeal of antioxidants also hinges on the notion they are generally less likely to have side effects than standard pharmaceutical treatments. However, this view has been called into question over the years, and many are increasingly expressing concerns about the safety of antioxidant use. Upon consideration of the reported side effects of dietary supplementation, there is no clear connection between a compound’s antioxidants and its potential side effects.
In fact, most side effects are relatively mild, and they have been reported in only a minority of users. Therefore, it’s best to approach the use of antioxidant-containing compounds for health purposes on a case-by-case basis. By examining the evidence more closely, you can determine whether antioxidant supplementation is right for you.
One of the first instances in which the safety of antioxidants was called into question was that of beta-carotene, a carotenoid found in many fruits and vegetables. In the late 1990s and early 2000s, there were several clinical studies in which higher mortality rates were observed in patients who were taking beta-carotene supplements. Although these studies naturally raised concerns in the research community, follow-up studies were unable to confirm a direct connection between beta-carotene and disease or mortality risk.
As early as 1999, scientists pointed out that the concerns about the side effects of antioxidants like carotenoids were limited to highly specific clinical circumstances. Indeed, according to a review in the Journal of the American College of Nutrition, the antioxidant activities of carotenoids “promote health when taken at dietary levels,” and adverse health effects are only observed when the compounds are “taken in a high dose by subjects who have smoked or who have been exposed to asbestos.”
More recently, comprehensive studies on beta-carotene have also failed to demonstrate an association between this antioxidant-containing nutrient and potential long-term side effects. In 2013, the data from a meta-analysis of six randomized controlled trials (which included more than 40,500 patients) indicated the link between beta-carotene and cancer risk was tenuous at best, even in high-risk populations; the authors of the study found the incidence of cancer was not significantly higher among healthy patients who took beta-carotene supplements, and the risk was only “marginally increased” among cancer patients.
This lack of long-term side effects of beta-carotene was verified in a broader 2016 meta-analysis. In this review, the researchers probed seven studies for evidence of a link between beta-carotene and all-cause mortality—not just deaths from cancer. Not only was beta-carotene not associated with a higher risk of mortality, the data indicated that supplementation with beta-carotene actually led to a significantly lower risk of all-cause mortality, directly contradicting what had been found in the earlier studies.
As more evidence accumulates, it now appears the potential long-term side effects of beta-carotene are outweighed by its beneficial antioxidant activities and other likely health benefits.
Beta-carotene is not the only compound with significant antioxidant activity. In recent years, researchers have explored a wide range of all-natural, plant-based phytochemicals with antioxidant effects. Most of the human and animal studies on the efficacy of these compounds for various health issues have included evaluations of potential side effects. On the whole, the side effects of antioxidants tend to be minimal or nonexistent. Consider the following findings for several of the antioxidant-containing compounds that have recently shown particular promise for various physical and mental health conditions:
Within the clinical and research communities, curcumin has a well-established safety record. Both the Joint United Nations and World Health Organization Expert Committee on Food Additives (JECFA) and the European Food Safety Authority (EFSA) have established an allowable daily intake of curcumin at 0-3 mg/kg of body weight. While the participants in some studies reported minor side effects—such as nausea, diarrhea, headache, and rash—these were most often observed when curcumin was being taken at an unusually high dosage of 500 to 12,000 mg per day. Considering that curcumin supplements are now provided in highly bioavailable forms, individuals usually do not need to take such high doses to see therapeutic results.
Like curcumin, resveratrol is generally considered to be safe and well-tolerated by almost all users. In a 2017 review in the journal Oxidative Medicine and Cellular Longevity, researchers examined clinical studies in which resveratrol supplements were taken in doses ranging from 20 mg per day to 2 g per day, and they found that almost all subjects reported no side effects.
Only when healthy subjects were taking 2 mg to 5 mg per day did side effects become more frequent, and they were still limited to mild gastrointestinal complaints: flatulence, nausea, stomach pain, and/or diarrhea. Similarly, studies in animal models have reported no adverse short-term or long-term side effects of resveratrol supplementation.
A 2018 review in the journal Molecular Nutrition and Food Research examined the safety profile of quercetin, another phytochemical with beneficial antioxidant activity.* According to the researchers, in human research studies, negative side effects “have rarely been reported, and any such effects were mild in nature.” Indeed, since the late 1990s and early 2000s, studies have consistently shown that quercetin has “very small side effects,” even at dosages as high as four grams per day. Although the authors did report on animal studies suggesting possible interactions between quercetin and common pharmaceutical drugs, this issue must be considered when trying any nutritional supplement, not just an antioxidant.
Another antioxidant-containing compound that has recently risen to prominence for addressing various health conditions is glutathione (GSH). As the most abundant endogenous antioxidant in the body, glutathione’s activity is considered essential to a wide range of cellular processes.
In a recent randomized, placedbo-controlled trial, research showed, for the first time, that daily supplementation with glutathione can significantly increase how the body’s stores of GSH, which otherwise declines with age.* Moreover, no serious side effects were reported by participants in the study, which further adds to glutathione’s promise as a nutritional supplement.
This result mirrors earlier findings. In a 2011 clinical study involving GSH supplementation, only eight of the 40 participants reported adverse effects: Five noted increased flatulence and loose stools, two said they experienced flushing, and one said they had gained weight. Therefore, in regard to safety, the researchers concluded that, “it is not an apparent barrier to continued clinical trials” on GSH supplementation. This conclusion was further verified in a 2015 study comparing oral and sublingual glutathione supplementation.
Although the 2015 study was relatively small in scale—only 20 participants—no adverse events were reported by any participants, regardless of the GSH supplementation method. Considered in the context of the other research on the topic, these findings suggest it is unlikely for patients to experience adverse symptoms from using GSH. Even if they do, the side effects of this antioxidant-containing compound are likely to be far more mild than those often reported for the most common pharmaceutical drugs on the market.
Ultimately, when considering the existing body of scholarly literature, it appears unwise to draw a broad conclusion about the side effects of antioxidants because they vary so widely. Based on the results of studies on beta-carotene, other common phytochemicals, and glutathione, there are three major factors that affect the potential for an antioxidant-containing compound to produce side effects: the dosage, the user’s unique physiology, and the nature of the compound itself. Because there are no clear connections between the side effects observed for different antioxidants, it does not seem like the antioxidant activity of these compounds is directly responsible for any adverse effects.
That’s good news for consumers and practitioners both, because it leaves lots of room for experimentation. For instance, if a consumer experiences mild gastrointestinal discomfort when they increase their intake of a particular antioxidant (either through nutritional supplementation or dietary changes), they might still be able to reap the health benefits of antioxidant intake by trying a different dosage or a different antioxidant compound that has been shown to exert a similar physiological effect.
Further research into the efficacy of these compounds will likely shed more light on the reasons some individuals experience adverse effects and others do not. For now, consumers and practitioners can take comfort in the knowledge that most antioxidants are generally considered safe and pose a low risk of side effects, especially compared to the pharmaceutical drugs that might otherwise be used to address important health concerns. Individuals who want to optimize potential benefits while reducing the possibility of side effects further should consider supplements formulated with advanced delivery methods, such as those produced by Tesseract Medical Research.
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