Human blood contains vitamin E, an antioxidant that breaks down chains and is fat soluble. Vitamin E's primary job as a free radical scavenger is to eliminate peroxide free radicals. As a result, it guards against oxidation and damage to long-chain polyunsaturated fatty acids, which are found in cell membranes and LDL cholesterol. Since α-tocopherol inhibits lipid peroxidation by converting to oxidized α-tocopherol radicals, which then undergo redox reactions, its association with vitamin C has significant pathophysiological significance [1]. The active reagent is reduced and regenerates into α-tocopherol. Alpha-tocopherol has the ability to prevent eosinophil and lymphocyte recruitment [1].

To longitudinally compare vitamin E status (assessed by α- and γ-tocopherol measured in red blood cell membranes) with inflammatory status and oxidative stress (assessed by total antioxidant capacity of plasma and lipid peroxidation biomarkers) association, and assess its relationship to hard disease. long-term outcomes (e.g., total and cause-specific graft and recipient losses), and the capacity to consider liver, lung, and heart transplant recipients equally [1].

Absorption, Distribution and Excretion
Tocopherol absorption in the digestive tract requires the presence of lipids. The bioavailability of tocopherol is highly dependent on the type of isoform administered, with α-tocopherol achieving a bioavailability of up to 36%. This isoform specificity also determines intestinal permeability, with γ-tocopherol exhibiting extremely low permeability. Following oral administration, the Cmax values for δ-tocopherol, γ-tocopherol, β-tocopherol, and α-tocopherol were 1353.79 ng/ml, 547.45 ng/ml, 704.16 ng/ml, and 2754.36 ng/ml, respectively. The time to peak concentration (Tmax) for δ-tocopherol, γ-tocopherol, and β-tocopherol was 3 to 4 hours, while that for α-tocopherol was approximately 6 hours. The pharmacokinetic characteristics of tocopherol indicate that it has a longer excretion time compared to tocotrienols. Different conjugated metabolites are excreted via urine or feces, depending on their side chain length. Due to its polarity, medium-chain and short-chain metabolites are excreted in urine as glucosinolate conjugates. A mixture of all metabolites and their precursors can be detected in feces. Long-chain metabolites account for more than 60% of total metabolites in feces. It is estimated that fecal excretion accounts for as much as 80% of the administered dose. The apparent volume of distribution for δ-tocopherol is 0.284 ± 0.021 mL, for γ-tocopherol it is 0.799 ± 0.047 mL, and for β-tocopherol it is 0.556 ± 0.046 mL. The clearance rates of δ-tocopherol, γ-tocopherol, and β-tocopherol range from 0.081 to 0.190 L/h. Excess tocopherol is converted to its corresponding carboxyethyl hydroxychromium (CEHC) according to its isomer. More specifically, tocopherol metabolism begins in the liver, a process dominated by CYP4F2/CYP3A4-dependent side-chain ω-hydroxylation, yielding 13'-carboxychromol. The metabolic pathway then proceeds through five β-oxidation cycles. These β-oxidation cycles function by shortening the side chain; the first cycle yields carboxydimethyldecylhydroxychromol, followed by carboxymethyloctylhydroxychromol. These two metabolites are long-chain metabolites and are not excreted in urine. Some intermediate-chain metabolites are products of two rounds of β-oxidation, such as carboxymethylhexylhydroxychromol and carboxymethylbutylhydroxychromol. These intermediate-chain metabolites can be detected in human feces and urine. As previously mentioned, the final catabolite of tocopherol is CEHC, which is primarily found in urine and feces. Two novel metabolites were detected in human and mouse feces: 12'-hydroxychromol and 11'-hydroxychromol. Due to their chemical properties, these metabolites are thought to be evidence of ω-1 and ω-2 hydroxylation, which leads to impaired 12'-OH oxidation and consequently, side chain truncation.
Liver.

---

Biological Half-Life
The elimination half-lives of δ-tocopherol, γ-tocopherol, and β-tocopherol are 2.44 to 3.02 hours.

Toxicity Summary
While all forms of vitamin E possess antioxidant activity, the known antioxidant activity of vitamin E is insufficient to explain its full biological activity. The anti-atherosclerotic activity of vitamin E involves inhibiting the oxidation of low-density lipoprotein (LDL) and the accumulation of oxidized low-density lipoprotein (oxLDL) in the arterial wall. It also appears to reduce oxLDL-induced apoptosis in human endothelial cells. LDL oxidation is a key early step in the development of atherosclerosis, as it triggers a series of events that ultimately lead to the formation of atherosclerotic plaques. Furthermore, vitamin E inhibits the activity of protein kinase C (PKC). PKC plays a role in smooth muscle cell proliferation; therefore, inhibition of PKC leads to suppression of smooth muscle cell proliferation, which is closely related to the development of atherosclerosis. The antithrombotic and anticoagulant activities of vitamin E involve downregulating the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), thereby reducing the adhesion of blood components to endothelial cells. Furthermore, vitamin E upregulates the expression of cytosolic phospholipase A2 and cyclooxygenase-1 (COX-1), thereby enhancing the release of prostacyclin. Prostacyclin is a vasodilator and an inhibitor of platelet aggregation and release. Platelet aggregation is known to be mediated by the binding of fibrinogen to the platelet glycoprotein IIb/IIIa (GPIIb/IIIa) complex. GPIIb/IIIa is a major membrane receptor protein that plays a crucial role in platelet aggregation. GPIIb is the α subunit of this platelet membrane protein. α-Tocopherol downregulates GPIIb promoter activity, thereby reducing GPIIb protein expression and decreasing platelet aggregation. In vitro culture studies have also shown that vitamin E reduces the production of thrombin in plasma, a protein that binds to platelets and induces their aggregation. A metabolite of vitamin E, called vitamin E quinone or α-tocopherol quinone (TQ), is a potent anticoagulant. This metabolite can inhibit vitamin K-dependent carboxylase, a major enzyme in the coagulation cascade. The neuroprotective effect of vitamin E is related to its antioxidant activity. Many neurological diseases are caused by oxidative stress. Vitamin E can counteract this stress, thereby protecting the nervous system. In vitro experiments have confirmed that vitamin E has immunomodulatory effects, with α-tocopherol enhancing the mitotic response of T lymphocytes in aged mice. The mechanism of this response of vitamin E is not fully understood, but studies suggest that vitamin E itself may possess cell-promoting activity independent of its antioxidant activity. Finally, the antiviral effect of vitamin E (primarily against HIV-1) is related to its antioxidant activity. Vitamin E can reduce oxidative stress, which is considered to be involved in the pathogenesis of HIV-1 and other viral infections. Vitamin E also affects cell membrane integrity and fluidity. Since HIV-1 is a membrane-bound virus, altering the cell membrane fluidity of HIV-1 may interfere with its ability to bind to cell receptors, thereby reducing its infectivity.

---

Effects during pregnancy and lactation
◉ Overview of medication use during lactation
Vitamin E is a normal component of breast milk. Maternal obesity, smoking, and preterm birth (premature delivery before 37 weeks of gestation) are all associated with reduced vitamin E levels in breast milk. Breastfeeding mothers may need to supplement with vitamin E to reach the recommended daily intake of 19 mg. Compared to not supplementing with vitamin E, taking a multivitamin supplement during pregnancy can safely and moderately increase vitamin E levels in breast milk and improve vitamin E status in breastfed infants. Higher daily doses have not been studied.
◉ Effects on breastfed infants
No published information found as of the revision date.
◉ Effects on lactation and breast milk
No published information found as of the revision date.

---

Protein binding
No specific plasma transporter for tocopherol has been identified, but it is believed to bind highly to lipoproteins such as very low-density lipoprotein (VLDL), high-density lipoprotein (HDL), and chylomicrons.

[1]. Plasma versus Erythrocyte Vitamin E in Renal Transplant Recipients, and Duality of Tocopherol Species. Nutrients. 2019 Nov 19;11(11). pii: E2821.

Pharmacodynamics
The antioxidant effects of tocopherol can be translated into various pharmacodynamic changes. In vitro studies have shown that this antioxidant activity can alter the activity of protein kinase C (PKC), thereby inhibiting cell death. Other derivative effects of tocopherol include its anti-inflammatory properties, which may be related to the regulation of cytokines or prostaglandins, prostaglandins, and thromboxanes.

C29H50O2

430.7061

430.381

2074-53-5

α-Vitamin E;59-02-9

14985

Light yellow to yellow ointment

0.9±0.1 g/cm3

485.9±0.0 °C at 760 mmHg

3ºC

210.2±24.4 °C

0.0±1.2 mmHg at 25°C

1.495

11.9

1

2

12

31

503

3

CC(CCCC(CCCC(CCCC1(CCC2=C(C(=C(C(C)=C2O1)C)O)C)C)C)C)C

GVJHHUAWPYXKBD-IEOSBIPESA-N

InChI=1S/C29H50O2/c1-20(2)12-9-13-21(3)14-10-15-22(4)16-11-18-29(8)19-17-26-25(7)27(30)23(5)24(6)28(26)31-29/h20-22,30H,9-19H2,1-8H3/t21-,22-,29-/m1/s1

(2R)-2,5,7,8-tetramethyl-2-[(4R,8R)-4,8,12-trimethyltridecyl]-3,4-dihydrochromen-6-ol

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Ethanol : ~50 mg/mL (~116.09 mM)
DMSO : ~16.11 mg/mL (~37.40 mM)
H2O : < 0.1 mg/mL

Solubility in Formulation 1: ≥ 1.61 mg/mL (3.74 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 16.1 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

---

Solubility in Formulation 2: ≥ 1.61 mg/mL (3.74 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 16.1 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

---

 (Please use freshly prepared in vivo formulations for optimal results.)