Category:Antioxidants

An antioxidant is a medicine or nutrient that prevents or reduces oxidative damage to biological molecules by scavenging reactive oxygen species (free radicals), by reducing already-oxidised species back to their reduced state, by chelating transition metals that catalyse oxidative reactions, or by replenishing the body's own antioxidant defences. The category includes the vitamin C (ascorbate) and vitamin E (tocopherol) of physiological antioxidant defence, the dietary supplements marketed for "oxidative stress" with varying evidence (coenzyme Q10, alpha-lipoic acid, the polyphenolic plant extracts), the glutathione precursor N-acetylcysteine, the iron chelators used in transfusion-dependent thalassemia and selected other indications, and the specific neuroprotective antioxidant medicines (edaravone, idebenone, omaveloxolone) approved for selected neurodegenerative indications.

The pharmacological-history significance of the antioxidants is dominated by the "oxidative stress" hypothesis of disease, the proposal advanced through the 1950s by Denham Harman of the University of Nebraska that cellular damage from reactive oxygen species was a fundamental cause of aging, of cardiovascular disease, of cancer, of neurodegenerative disease, and of many other chronic conditions.^[1] The corollary that exogenous antioxidants would slow or prevent these diseases was tested in many large randomised trials between 1990 and 2010, with broadly disappointing results: vitamin E supplementation in the HOPE, HOPE-TOO, and HPS trials did not reduce cardiovascular events and in some meta-analyses produced a small but consistent excess of all-cause mortality; beta-carotene supplementation in the CARET and ATBC trials increased lung cancer in smokers and was abandoned; high-dose vitamin C for cancer (the Linus Pauling proposals of the 1970s) has not survived Cochrane review; vitamin E in Alzheimer's disease showed mixed results in the early trials and was downgraded in subsequent meta-analyses. The simple oxidative-stress hypothesis has not survived the controlled-trial evidence as a generic justification for routine antioxidant supplementation.

Several antioxidant medicines retain specific clinical roles. N-acetylcysteine (NAC) is the antidote for paracetamol overdose (replenishing the hepatic glutathione consumed by the reactive metabolite NAPQI; described under acetaminophen); it is also used as a mucolytic (described under mucolytics) and has small-evidence-base use in idiopathic pulmonary fibrosis (the PANTHER-IPF trial subgroups) and as an adjunct in selected psychiatric conditions (trichotillomania, skin-picking, obsessive-compulsive disorder; the evidence is preliminary). Iron chelation in transfusion-dependent thalassemia and in iron-overload of selected acquired conditions (deferasirox, deferiprone, deferoxamine) is mechanistically an antioxidant strategy as well as an iron-removal one, because iron is a transition metal catalyst of the Fenton reaction that generates the most damaging hydroxyl radicals.

The specific neuroprotective antioxidants have produced selected approvals. Edaravone (Radicava, Mitsubishi Tanabe 2017 in the U.S.) is a free-radical scavenger approved for amyotrophic lateral sclerosis on the basis of the MCI186-19 trial showing slower ALSFRS-R decline in a defined patient subset; the medicine has substantial commercial cost and modest clinical effect. Omaveloxolone (Skyclarys, Reata 2023) activates the Nrf2 antioxidant-response pathway and is approved for Friedreich ataxia on the basis of the MOXIe trial. Idebenone (Raxone, Santhera 2015 in Europe) is a coenzyme-Q10 analogue approved for Leber hereditary optic neuropathy.

The coenzyme Q10 (ubiquinone, the endogenous mitochondrial electron-transport antioxidant) supplementation has trial evidence for migraine prophylaxis (100-300 mg/day for prophylaxis; modest effect; described under migraine prophylaxis) and mixed evidence for statin-associated muscle symptoms (the LIPID-NET-ARI trial of 2018 did not show benefit, but smaller trials and clinical practice retain some use). Alpha-lipoic acid is a dietary supplement with small-trial evidence for diabetic peripheral neuropathy (the SYDNEY, SYDNEY 2, and ALADIN trials of intravenous alpha-lipoic acid showed symptom reduction in painful diabetic neuropathy; the oral preparation has weaker but extant evidence). Selenium is required at trace levels for the antioxidant glutathione-peroxidase system, but routine supplementation has not shown benefit and the SELECT trial of high-dose selenium and vitamin E was stopped in 2008 for an excess of prostate cancer in the active arm.

The plant-derived antioxidants (the polyphenols of green tea, the resveratrol of grape skin and red wine, the curcumin of turmeric, the quercetin of fruit and vegetables, the anthocyanins of berries) have substantial in-vitro antioxidant activity and an enormous popular-supplement market but limited clinical-trial evidence for specific medical indication beyond general dietary recommendation. Their listing under herbal medicines when used in specific therapeutic preparations is appropriate; their categorisation here as systemic "antioxidants" reflects the supplement-market framing rather than evidence-based clinical pharmacology.

By chemistry or clinical use:

• Glutathione and thiol antioxidants:
  • N-acetylcysteine (Mucomyst, Acetadote, Cetylev; mucolytic, paracetamol antidote, IPF adjunct)
  • Glutathione (intravenous in selected indications)
  • Methionine (oral, historical paracetamol antidote)
• Antioxidant vitamins (cross-indexed under vitamins):
  • Vitamin E (alpha-tocopherol)
  • Vitamin C (ascorbic acid)
  • Beta-carotene and other carotenoids
• Coenzymes and cofactors:
  • Coenzyme Q10 (ubiquinone, ubiquinol; migraine prophylaxis, statin-associated muscle symptoms)
  • Alpha-lipoic acid (diabetic neuropathy)
  • Idebenone (Raxone; Leber hereditary optic neuropathy)
• Iron chelators:
  • Deferoxamine (Desferal; intravenous, subcutaneous)
  • Deferasirox (Exjade, Jadenu; oral)
  • Deferiprone (Ferriprox; oral)
• Specific neuroprotective antioxidants:
  • Edaravone (Radicava; ALS)
  • Omaveloxolone (Skyclarys; Friedreich ataxia)
• Plant-derived polyphenols and flavonoids (cross-indexed under herbal medicines where used as specific preparations):
  • Resveratrol
  • Curcumin (from turmeric)
  • Green tea catechins (EGCG)
  • Quercetin
• Other:
  • Selenium (trace element, antioxidant cofactor)
  • Allopurinol (xanthine oxidase inhibitor; sometimes used as antioxidant in selected non-gout indications including reperfusion injury)

The boundary of this category is "medicine that reduces oxidative damage to biological tissues by free-radical scavenging or related mechanism." The dietary supplements with antioxidant claims but limited clinical-trial evidence (multi-vitamin antioxidant cocktails, the various commercial "antioxidant" preparations) are listed under vitamins or herbal medicines as appropriate to their composition. The antioxidant-related ophthalmologic supplements (the AREDS and AREDS2 formulations for macular degeneration, the combinations of vitamins C and E with zinc and lutein and zeaxanthin and selected polyphenols) have specific approved indications and are listed under their primary indication. The antioxidant component of medicines whose primary mechanism is something else (the 5-aminosalicylates in inflammatory bowel disease, the NSAIDs' minor antioxidant component, the calcium channel blockers' minor calcium-cycling stabilisation) are listed under the primary mechanism.

This category page is an encyclopedia article about its subject. The actual index of medicines belonging to the category is generated automatically by the wiki engine, from category-membership declarations on the individual medicine pages, and appears at the foot of the page below the references.