Selenium (L-selenomethionine) — The Essential Antioxidant Mineral
Selenium is an essential trace mineral that functions as a key component of antioxidant enzymes like glutathione peroxidase. While it plays a crucial role in redox balance and thyroid function, its impact on longevity is complex, with evidence suggesting that supplementation may only be beneficial in deficient populations and could be harmful in excess.
Mechanism of Action
Selenium is incorporated into selenoproteins, such as glutathione peroxidases (GPx) and thioredoxin reductases (TrxR), which are critical for cellular antioxidant defence and redox regulation. In animal models, selenium supplementation has been shown to inhibit IGF-1 signalling, conferring metabolic benefits similar to methionine restriction. This reduction in IGF-1 signalling and enhancement of antioxidant capacity can protect against oxidative stress and modulate inflammatory pathways. However, the longevity benefits appear to follow a U-shaped curve, where both deficiency and excess are detrimental.
Human Trial Evidence
Human trials on selenium for longevity are mixed and highly dependent on baseline status. The SELECT trial found no benefit of 200 mcg/day L-selenomethionine for prostate cancer prevention. Furthermore, a randomised controlled trial by Rayman et al. (2018) showed that long-term supplementation (300 mcg/day for 5 years) in a population with moderately low baseline status actually increased all-cause mortality 10 years later. Thus, routine high-dose supplementation is not recommended for longevity in selenium-replete individuals.
Dosing Protocol
The standard supplemental dose is 50–200 mcg/day of L-selenomethionine. Doses exceeding 400 mcg/day are not recommended due to the risk of selenosis. It is best taken with food. In clinical trials, 200 mcg/day is frequently used for autoimmune thyroiditis and general supplementation.
Safety & Contraindications
Selenium has a narrow therapeutic index. Chronic intake above 400 mcg/day can lead to selenosis, characterised by garlic-like breath, hair and nail brittleness, gastrointestinal disturbances, and neurological symptoms. High-dose supplementation has also been associated with an increased risk of type 2 diabetes and all-cause mortality in some populations. It should be avoided in individuals who already have adequate or high dietary selenium intake.