VITAMINS & SUPPLEMENTS · GUIDE
High-Dose Antioxidants: Risks by Compound (A Reference Table)
A reference table of the risk signals found for high-dose antioxidant supplements, compound by compound, with the trial or official source, the population studied and the limits.
Content last updated . This page has not been medically reviewed.
Back to AntioxidantsQuick answer
"Antioxidant" does not mean "safe at any amount". The National Center for Complementary and Integrative Health (NCCIH, US) says antioxidants can have harmful effects when taken at high doses, and that large amounts may interfere with normal cell defenses and signaling. [1] This page lists the harm signals, compound by compound, with the people who were studied. It gives no personal limits: study amounts are study amounts, and a clinician or pharmacist decides what is right for a person.
How to read the table
Risk signals come from different kinds of evidence: randomized trials, pooled reviews, case reports and official safety statements. Each row says which. A signal in smokers, or in people with heart disease, does not automatically apply to healthy non-smokers, and the reverse is also true. Compounds are not interchangeable, so a signal for one form or compound should not be carried to another.Risks by compound
| Compound | Risk signal | Source | Population and amount |
|---|---|---|---|
| Beta-carotene (supplement) | Higher lung cancer incidence (18% higher; 95% CI 3 to 36%) and 8% higher total mortality [2] | ATBC trial, 1994 | 29,133 male smokers aged 50 to 69 in Finland; 20 mg a day (study amount) for 5 to 8 years [2] |
| Beta-carotene with retinol | Relative risk of lung cancer 1.28 and of death from any cause 1.17; trial stopped early [3] | CARET trial, 1996 | 18,314 smokers, former smokers and asbestos-exposed workers; abstract gives 30 mg beta-carotene plus 25,000 IU retinol a day (study amounts). The NCI table lists 15 mg beta-carotene [3][4] |
| Beta-carotene (former smokers) | Beta-carotene increased lung cancer risk among former smokers; lutein and zeaxanthin did not [1] | AREDS2 as summarized by NCCIH, 2023 | People at high risk of advanced age-related macular degeneration; current smokers were not given beta-carotene [1] |
| Vitamin A (retinol) | Higher doses of vitamin A seem to increase mortality (meta-regression) [5]; long-term intake above an average of 1.5 mg a day may affect bones [6] | Cochrane review, 2012; NHS (UK) | Adults in trials of mixed health [5]; NHS stresses older people, especially women at risk of osteoporosis [6] |
| Vitamin E (alpha-tocopherol and mixtures) | In trials of 400 IU a day or more, pooled extra deaths of 39 per 10,000 persons (95% CI 3 to 74) [7] | Meta-analysis, 2005 | 19 trials, often in people with chronic disease; the authors say generalizability to healthy adults is uncertain [7] |
| Vitamin E | 17% higher prostate cancer risk (hazard ratio 1.17); 1.6 extra cases per 1,000 person-years [8] | SELECT, 2011 | 35,533 men aged 50 or 55 and older; 400 IU a day of synthetic (all rac) alpha-tocopheryl acetate (study amount) [8] |
| Vitamin E | Higher risk of heart failure and heart-failure hospitalization [9]; more hemorrhagic stroke deaths in ATBC [2] | HOPE and HOPE-TOO, 2005; ATBC | People 55 or older with vascular disease or diabetes; 400 IU natural-source daily [9]; male smokers, 50 mg daily [2] |
| Vitamin E | May raise bleeding risk and interact with anticoagulant or antiplatelet medicines [1] | NCCIH, 2023 | High-dose supplements; no amount given on the page we read |
| Vitamin C | Diarrhea, nausea and stomach cramps at high doses [1]; may worsen iron overload in hemochromatosis [1] | NCCIH, 2023 | High-dose supplements; people with hemochromatosis |
| Selenium | Selenosis, which in its mildest form can cause hair and nail loss [10]; not significantly linked to mortality in the 2012 review [5] | NHS (UK); Cochrane review | UK general public; trial populations of mixed health |
| Coenzyme Q10 | Mild effects such as insomnia or digestive upset; may interact with warfarin and insulin [11] | NCCIH | Supplement users; see CoQ10 side effects |
| Alpha-lipoic acid | Case reports link it to insulin autoimmune syndrome, a rare cause of low blood sugar [12] | Narrative review, 2026 | Genetically susceptible people; case-based evidence only. See ALA cautions |
| Green tea extract | Uncommon liver injury, mainly with extracts in tablet or capsule form [13] | NCCIH, 2025 | Some people who used green tea products; the beverage was not linked to safety concerns in adults [13] |
| Curcumin (highly bioavailable forms) | May harm the liver [14] | NCCIH, 2025 | Users of highly bioavailable formulations. See curcumin supplements |
| Antioxidants during chemotherapy | Any antioxidant supplement use linked with higher breast cancer recurrence and death in one observational study [1] | NCCIH summary of a 2019 study | 1,134 women with breast cancer; the study may be biased because people chose their own supplements [1] |
Official upper levels
The NHS (UK), citing the Department of Health and Social Care on pages last reviewed in August 2020, gives these supplement levels as amounts unlikely to cause harm for the general public (the pages we read name no age group, apart from the vitamin A bone advice for older people): vitamin E, 540 mg (800 IU) a day or less [15]; vitamin C, less than 1,000 mg a day [16]; selenium, 350 mcg a day or less [10]; vitamin A, an average of 1.5 mg a day or less from food and supplements combined [6]. These are one country's guidance, not universal limits, and not a target. The NHS says there is not enough evidence to know what taking high doses of vitamin E each day might do. [15] The US NIH Office of Dietary Supplements page could not be read this session, so US upper limits are not stated here.Limits and uncertainty
- Several signals come from trials with a single form and a fixed amount. They do not show where a risk begins. The 2005 meta-analysis itself says it is difficult to estimate the threshold precisely. [7]
- Case reports and observational signals (ALA, chemotherapy) show a concern, not a proven cause.
- Proper evidence not found here for a safe amount of any antioxidant that applies to everyone; we looked in the NCCIH and NCI summaries, the NHS pages and the trials above.
Who should ask a clinician first
Smokers and people exposed to asbestos (beta-carotene), people having cancer treatment, people on blood thinners, diabetes medicines or cholesterol medicines, people with liver, kidney or bleeding conditions, and anyone before surgery. In pregnancy or for a child, the NCCIH says it is especially important to consult a health care provider. [1] Never stop a prescribed medicine without asking your prescriber. Product quality varies: see quality testing and certifications. Medicine details are on antioxidants and medicines and general guidance on medication interactions.Related
Antioxidant safety and marketing claims · Vitamin EFrequently asked questions
Can you overdose on antioxidants?
High doses of some antioxidants have caused harm in studies, for example beta-carotene in smokers, but there is no single amount that applies to everyone. [1][2]
Is high-dose vitamin E risky?
A 2005 meta-analysis of high-dose trials found extra deaths, often in people with chronic disease, and SELECT found more prostate cancer in healthy men. [7][8]
Which antioxidant is most clearly linked to harm?
Beta-carotene supplements in smokers and asbestos-exposed people, where two large trials found more lung cancer. [2][3]
Are water-soluble antioxidants like vitamin C harmless?
No. High doses can cause stomach upset, and vitamin C may interact with cancer treatment or worsen iron overload in hemochromatosis. [1]
Do the NHS levels mean a safe daily amount for me?
No. They are UK guidance for the general public, not personal advice. [15] A clinician or pharmacist can say what suits your health and medicines.
References
- Antioxidant Supplements: What You Need To Know. National Center for Complementary and Integrative Health (US), last updated July 2023. Read 2026-10-23.
- The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. N Engl J Med 1994. Read 2026-10-23.
- Omenn GS, et al. Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. N Engl J Med 1996 (CARET). Read 2026-10-23.
- Antioxidants and Cancer Prevention. National Cancer Institute (US). Read 2026-10-23.
- Bjelakovic G, et al. Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. Cochrane Database Syst Rev 2012. Read 2026-10-23.
- Vitamin A. NHS (UK), page last reviewed 3 August 2020 (next review was due 2023). Read 2026-10-23.
- Miller ER 3rd, et al. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med 2005. Read 2026-10-23.
- Klein EA, et al. Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA 2011. Read 2026-10-23.
- Lonn E, et al. Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial. JAMA 2005 (HOPE and HOPE-TOO). Read 2026-10-23.
- Vitamins and minerals: Others (includes selenium). NHS (UK), page last reviewed 3 August 2020 (next review was due 2023). Read 2026-10-23.
- Coenzyme Q10. National Center for Complementary and Integrative Health (US). Read 2026-10-23.
- Vallianou NG, et al. Alpha-lipoic acid as a trigger of insulin autoimmune syndrome. Metabol Open 2026. Read 2026-10-23.
- Green Tea: Usefulness and Safety. National Center for Complementary and Integrative Health (US), last updated February 2025. Read 2026-10-23.
- Turmeric: Usefulness and Safety. National Center for Complementary and Integrative Health (US), last updated April 2025. Read 2026-10-23.
- Vitamin E. NHS (UK), page last reviewed 3 August 2020 (next review was due 2023). Read 2026-10-23.
- Vitamin C. NHS (UK), page last reviewed 3 August 2020 (next review was due 2023). Read 2026-10-23.
Education, not medical advice. This page is for general information. It does not diagnose or treat any condition and is not a substitute for care from a qualified health professional. Natural does not automatically mean safe. Ask a clinician or pharmacist before changing your care, especially if you take medication, are pregnant or breastfeeding, or have a health condition.