Alpha-tocopherol is the form of vitamin E that is one of the most important lipid-soluble antioxidants in the blood — it is the most biologically active and the most abundant form of vitamin E in the human body, and it is the primary defence against the oxidative modification of the LDL (low-density lipoprotein) particles, which is the initiating event in the atherosclerosis and in the development of the cardiovascular disease. Alpha-tocopherol is a chain-breaking antioxidant that interrupts the lipid peroxidation chain reaction in the LDL particle — it reacts with the lipid peroxyl radicals faster than they can react with the fatty acid side chains of the LDL phospholipids, and it thereby prevents the propagation of the lipid peroxidation and the formation of the oxidised LDL, which is the most atherogenic and most pro-inflammatory form of the LDL. Without adequate alpha-tocopherol and antioxidant protection in the blood, the LDL particles are oxidatively modified, they are taken up by the macrophages in the arterial wall (through the scavenger receptor pathway), and they form the foam cells that are the hallmark of the early atherosclerotic lesion. The oxidative modification of the LDL is the initiating event in the atherosclerosis, and it is the primary reason why the LDL is so atherogenic when it is oxidised — the oxidised LDL is internalised by the macrophages at a rate that is 10-50 times higher than the native LDL, and it therefore rapidly leads to the foam cell formation, the fatty streak development, and the progression of the atherosclerotic plaque. The alpha-tocopherol is therefore one of the most important and most specific preventers of the atherosclerosis known — and it explains why the alpha-tocopherol supplementation has been shown to reduce the cardiovascular events in multiple large clinical trials, particularly in the populations with the low dietary vitamin E intake and with the elevated oxidative stress.
Alpha-Tocopherol and the Cardiovascular Protection
Alpha-tocopherol supports the cardiovascular protection primarily through its inhibition of the LDL oxidation and through its anti-inflammatory effects on the endothelial cells and the macrophages — these are the two primary mechanisms by which the alpha-tocopherol prevents the atherosclerosis and reduces the cardiovascular events. The inhibition of the LDL oxidation is the most important and most specific mechanism — the alpha-tocopherol intercepts the lipid peroxyl radicals in the LDL particle and prevents the oxidative modification of the LDL, thereby preventing the foam cell formation and the atherosclerotic plaque initiation. The anti-inflammatory effects of the alpha-tocopherol are secondary to the antioxidant effect — by reducing the oxidative stress in the arterial wall, the alpha-tocopherol reduces the endothelial activation, the monocyte adhesion, and the inflammatory cytokine production, and it thereby slows the progression of the atherosclerotic plaque and reduces the risk of the plaque rupture and the acute cardiovascular events (heart attack, stroke). The combination of the antioxidant effect and the anti-inflammatory effect makes the alpha-tocopherol one of the most effective and most comprehensive cardiovascular protective nutrients known — and it explains why the alpha-tocopherol supplementation has been shown to reduce the cardiovascular events by 20-40% in the populations with the low vitamin E intake and with the elevated oxidative stress.
The clinical importance of the alpha-tocopherol for the cardiovascular health is underscored by the Cambridge Heart Antioxidant Study (CHAOS) — a study in 2002 patients with the angiographically proven coronary artery disease found that the alpha-tocopherol supplementation at 400-800 IU daily significantly reduced the risk of the cardiovascular events (by 47%) and the risk of the myocardial infarction (by 77%) — demonstrating the potent and clinically meaningful cardiovascular protective effect of the alpha-tocopherol in humans with the established coronary artery disease.
Practical Application
For general alpha-tocopherol supplementation for the cardiovascular protection and for the LDL oxidation prevention, the evidence-based approach is to supplement with 200-400 IU of alpha-tocopherol daily (as the natural d-alpha-tocopherol, which is more bioavailable than the synthetic dl-alpha-tocopherol). The alpha-tocopherol should be taken with the gamma-tocopherol (which is the other major form of vitamin E in the diet and which has complementary effects on the inflammatory and the antioxidant response — the combination of the alpha-tocopherol and the gamma-tocopherol is more effective than the alpha-tocopherol alone for the comprehensive cardiovascular protection and for the prevention of the atherosclerosis). The alpha-tocopherol is generally well-tolerated with no significant adverse effects at the doses that are used for the cardiovascular protection (up to 1000 IU daily), though the very high doses (above 1000 IU daily) may increase the bleeding risk by inhibiting the platelet aggregation and the vitamin K-dependent clotting factors — people who are taking the anticoagulant medications (warfarin, clopidogrel, aspirin) should use the alpha-tocopherol with caution and under the supervision of a qualified healthcare practitioner. For comprehensive LDL oxidation prevention and cardiovascular protection, alpha-tocopherol pairs well with the vitamin C (which is a water-soluble antioxidant that works synergistically with the alpha-tocopherol for the protection of the LDL particles from the oxidative modification — the vitamin C regenerates the alpha-tocopherol from its radical form and thereby recycling it and extending its antioxidant activity — the combination of the alpha-tocopherol and the vitamin C is one of the most effective and most evidence-based antioxidant combinations for the prevention of the LDL oxidation and for the cardiovascular protection), with the gamma-tocopherol (which is the other major form of vitamin E and which works synergistically with the alpha-tocopherol for the comprehensive cardiovascular protection and for the reduction of the inflammatory response in the arterial wall — the combination of the alpha-tocopherol and the gamma-tocopherol is one of the most effective approaches for the prevention of the atherosclerosis and for the reduction of the cardiovascular events), with the carotenoids (lutein, zeaxanthin, lycopene — which are lipid-soluble antioxidants that work synergistically with the alpha-tocopherol for the protection of the LDL particles from the oxidative modification and for the prevention of the atherosclerosis — the combination of the alpha-tocopherol and the carotenoids is one of the most effective combinations for the comprehensive cardiovascular protection), and with the omega-3 fatty acids (which have complementary effects on the triglycerides, the inflammation, and the plaque stability, and which work synergistically with the alpha-tocopherol for the comprehensive cardiovascular risk reduction — the combination of the alpha-tocopherol and the omega-3 fatty acids is one of the most effective combinations for the prevention of the cardiovascular events and for the maintenance of the cardiovascular health).
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