Vitamin E (not specified).

When alpha-tocopherol quenches a lipid peroxyl radical it becomes a tocopheryl radical sitting at the membrane surface. Ascorbate in the adjacent aqueous phase donates an electron and returns it to the active form. This is textbook chemistry measured in model membranes and it is why the two are so often formulated together. It describes radical handling, not any clinical outcome.

Selenium is required for glutathione peroxidase, which removes lipid hydroperoxides once they have formed. Vitamin E works one step earlier by intercepting the chain-propagating radical. Deficiency in one raises the demand on the other, which is why classic deficiency syndromes in livestock respond to either. The two cover different points on the same sequence.

Glutathione sits downstream of ascorbate in the chain that regenerates oxidised vitamin E, either directly or through ascorbate recycling. Low glutathione status leaves tocopheryl radicals in circulation longer. The relationship is well characterised in cell systems.

Dihydrolipoic acid reduces both ascorbate and, indirectly, the tocopheryl radical, so it feeds the same regeneration cycle from the aqueous side. It is unusual among antioxidants in working in both lipid and water phases. The pairing is mechanistic and measured in vitro.

Reduced ubiquinol sits inside the same lipid bilayer as alpha-tocopherol and can regenerate the tocopheryl radical without needing an aqueous partner. Both also share the mixed micelle route into the enterocyte. Coenzyme Q10 is one of the few antioxidants able to reach vitamin E where it actually sits.

High-dose alpha-tocopherol and its quinone metabolite interfere with vitamin K recycling and can extend clotting time in people with marginal vitamin K status. The effect is dose-dependent and appears at supplemental rather than dietary intakes. It is the main reason high-dose vitamin E is stopped before surgery.

The interference described for vitamin K applies to the menaquinone forms as well, since they pass through the same reductase cycle. Long-chain MK7 has a long half-life, which buffers the effect somewhat. The interaction is mechanistic and dose-dependent.

Each additional double bond in a membrane fatty acid raises its susceptibility to peroxidation, so a high intake of long-chain polyunsaturates raises tocopherol requirement. Fish oil products are routinely formulated with tocopherol for exactly this reason, both in the capsule and in the body. The added tocopherol in an oil capsule is usually a preservative dose, not a nutritional one.

EPA and DHA carry five and six double bonds respectively and are the most oxidation-prone fatty acids in a typical diet. Raising their membrane content raises the tocopherol needed to protect them. The pairing is standard formulation practice as well as physiology.

Vitamin E absorption depends on bile-driven micelle formation, which in turn depends on fat arriving in the same meal. Taking a tocopherol capsule with a fat-free meal lowers uptake substantially. Any lipid vehicle serves, and medium-chain triglyceride is a common carrier in softgels.

Retinol, tocopherol and the carotenoids all partition into the same mixed micelles and compete for a limited micellar carrying capacity at high single doses. At dietary intakes the competition is negligible. It becomes measurable when one is given in a large bolus.

Large tocopherol doses lower the fraction of beta carotene taken up from the same meal, and the same is true in the other direction. Both are fat-soluble and both need micellar space. Splitting large doses across meals sidesteps most of it.

The hepatic alpha-tocopherol transfer protein preferentially loads the alpha form into lipoproteins, so high-dose alpha-tocopherol supplementation lowers circulating gamma-tocopherol. Gamma-tocopherol has its own chemistry, in particular quenching reactive nitrogen species. This displacement is the single strongest argument for reading the isoform on a label rather than the total.

The alpha-tocopherol transfer protein has low affinity for tocotrienols, and co-dosing with alpha-tocopherol lowers tocotrienol appearance in plasma. Products that carry both often instruct separate timing for this reason. The competition is at distribution, not at absorption.

Free ferrous iron drives Fenton chemistry and generates the very lipid radicals tocopherol is there to intercept, consuming it in the process. Iron salts and tocopherol in the same capsule shorten the shelf life of both. Separating them is a formulation convention as much as a physiological one.

Astaxanthin spans the bilayer while tocopherol sits with its head at the surface, so the two intercept radicals at different depths. Their coverage overlaps only partly. This is structural chemistry, not evidence of an outcome.

Zinc is a structural cofactor for copper-zinc superoxide dismutase, which handles superoxide before it can initiate lipid peroxidation. Vitamin E acts after initiation has begun. They occupy different steps rather than duplicating each other.