All-rac-alpha-tocopherol

BRAND NAMES

All-rac-alpha-tocopherol is the synthetic form of Vitamin E and is most commonly labeled as "dl-alpha-tocopherol" on product packaging. Many brands sell generic Vitamin E supplements, so the specific product name will vary depending on the retailer. 

MECHANISM OF ACTION

All-rac-alpha-tocopherol, a synthetic form of vitamin E, acts through its function as a powerful lipid-soluble antioxidant and by influencing cellular signaling and gene expression. In the body, all-rac-alpha-tocopherol (also known as dl-alpha-tocopherol) is a mixture of eight stereoisomers, four of which have significant biological activity. After de-esterification in the gut, these isomers are absorbed and enter circulation, with the body preferentially retaining the naturally occurring RRR-alpha-tocopherol form.

PHARMACOKINETICS:

Absorption

All-rac-α-tocopherol is absorbed in the small intestine, and its uptake relies on being dissolved in dietary fats and properly emulsified during digestion. In humans, esterified forms such as all-rac-α-tocopheryl acetate are efficiently hydrolyzed and absorbed, with some studies reporting absorption rates between 72% and 77.5%.

Distribution

The distribution of all-rac-α-tocopherol is greatly influenced by its origin and the body's metabolic activity. It tends to accumulate more in the liver than RRR-α-tocopherol, whereas RRR-α-tocopherol remains in the body longer and is more selectively released into the plasma and other tissues.

Metabolism

The metabolism of all-rac-alpha-tocopherol, the synthetic form of vitamin E, differs significantly from the naturally occurring RRR-alpha-tocopherol, resulting in lower overall retention in the body. The synthetic form contains eight stereoisomers, only four of which are efficiently utilized by the body. This process involves uptake, discrimination by the liver, extensive breakdown, and excretion through urine and bile.

Excretion

All-rac-α-tocopherol is mainly excreted in the urine as a metabolite known as α-CEHC, particularly when consumed in excess. A smaller portion is also eliminated via the feces, consisting of both unabsorbed and metabolized forms of vitamin E.

PHARMACODYNAMICS

All-rac-α-tocopherol functions as a chain-breaking antioxidant, neutralizing lipid peroxyl radicals to protect cell membranes from oxidative damage. Its pharmacodynamic properties are affected by the fact that it consists of eight stereoisomers, but only the four 2R-isomers are biologically active, while the 2S-isomers lack significant activity.

ADMINISTRATION

All-rac-α-tocopherol is typically taken orally, commonly as its more stable acetate ester form, all-rac-α-tocopheryl acetate. It can be consumed with meals or mixed into foods such as cereal or juice. For general adult supplementation, the recommended daily intake is 15 mg, with 1 mg of RRR-α-tocopherol considered equivalent to 2 mg of all-rac-α-tocopherol.

DOSAGE AND STRENGTH

All-rac-alpha-tocopherol is the synthetic form of vitamin E, also known as dl-alpha-tocopherol. Its biological activity is approximately half that of the natural form, RRR-alpha-tocopherol. This difference in activity means that a higher amount of the synthetic form is generally needed to achieve an equivalent effect to the natural form. 

The activity of vitamin E is often expressed in International Units (IU) or milligrams (mg). The conversion between IU and mg for synthetic vitamin E (all-rac-alpha-tocopherol) is approximately 1 IU being equivalent to 0.45 mg of alpha-tocopherol. 

Various strengths of synthetic vitamin E supplements are available in forms like capsules and tablets, including common strengths such as 200 IU, 400 IU, 600 IU, and 1,000 IU. 

DRUG INTERACTIONS

High doses of all-rac-α-tocopherol (greater than 300 mg per day) can interact with certain medications, such as blood thinners like aspirin and warfarin, by enhancing their anticoagulant effects. It may also decrease the effectiveness of drugs like tamoxifen and cyclosporine A by reducing their concentration in the bloodstream. Although vitamin E is generally considered safe when taken at recommended dietary levels, excessive intake may interfere with these medications and could potentially impact cancer treatments, including chemotherapy and radiation therapy.

FOOD INTERACTIONS

All-rac-alpha-tocopherol, the synthetic form of vitamin E, has a key interaction with fats, which are necessary for its absorption. Otherwise, dietary interactions are minimal, unlike the potential risks of high-dose vitamin E supplements interacting with medications.

CONTRAINDICATIONS

Contraindications for all-rac-α-tocopherol (synthetic vitamin E) and other vitamin E supplements include known hypersensitivity, a heightened risk of bleeding, and potential interactions with specific medical conditions or medications. The likelihood of adverse effects increases with high-dose supplementation.

SIDE EFFECTS

Common side effects
When taken at high doses, generally exceeding 400 IU per day, common side effects can include:

• Gastrointestinal problems: nausea, diarrhea, stomach cramps, and indigestion.

• Neurological symptoms: fatigue, headaches, and blurred vision.

• Skin reactions: rashes or irritation, particularly with topical use.

OVER DOSE

An overdose of all-rac-α-tocopherol (synthetic vitamin E) can disrupt blood clotting and raise the risk of severe, potentially life-threatening bleeding. Although mild symptoms might appear with lower doses, the most significant dangers are linked to high-dose supplementation rather than vitamin E obtained from food.

TOXICITY

All-rac-α-tocopherol is generally regarded as safe when used as intended in animal feed, posing no significant risks to consumers or the environment at approved levels. However, very high doses can be toxic to animals, leading to negative effects such as weight loss and immune suppression in mice. In humans, although toxicity is typically low, very high supplemental doses may elevate the risk of bleeding.