Is vitamin E antiangiogenic?

January 9, 2026 •

4 min read

Recent research has revealed that not all forms of vitamin E are created equal when it comes to inhibiting new blood vessel formation. This discovery prompts a more nuanced investigation into the question: Is vitamin E antiangiogenic? The answer depends largely on the specific isoform of this complex nutrient.

Quick Summary

The antiangiogenic properties of vitamin E differ significantly between its isoforms; tocotrienols show potent inhibition, while alpha-tocopherol can weaken these effects.

Key Points

Not all forms are equal: The antiangiogenic effects of vitamin E are primarily linked to tocotrienols, not tocopherols.
Tocotrienols inhibit angiogenesis: These isomers, especially delta-tocotrienol, block endothelial cell growth, migration, and tube formation.
Alpha-tocopherol can interfere: High concentrations of alpha-tocopherol may antagonize the antiangiogenic benefits of tocotrienols.
Mechanism involves apoptosis: Synthetic vitamin E analogues and tocotrienols induce selective cell death in proliferating angiogenic cells.
VEGF is a key target: Delta-tocotrienol suppresses the signaling of Vascular Endothelial Growth Factor receptor 2, a crucial step in vessel formation.
Clinical evidence exists: Some human studies, such as one involving PCOS patients, have shown reduced angiogenic markers with vitamin E supplementation.

The Complex Relationship Between Vitamin E and Angiogenesis

Angiogenesis is the physiological process involving the growth of new blood vessels from pre-existing ones. While crucial for normal growth and wound healing, it can also play a detrimental role in diseases like cancer, where it supports tumor growth. The scientific community has long explored natural compounds for their potential to modulate this process. Vitamin E, a fat-soluble vitamin and powerful antioxidant, has been a key focus of this research, but findings have been complex and at times contradictory, largely due to the eight different forms it comprises: four tocopherols and four tocotrienols.

Tocotrienols: The Potent Antiangiogenic Isoforms

Research shows that the antiangiogenic effect of vitamin E is most prominently associated with its tocotrienol (T3) family, particularly delta-tocotrienol (δ-T3). Unlike the more common tocopherols, tocotrienols have a different chemical structure that contributes to their unique biological activities. Numerous studies have confirmed the antiangiogenic potency of tocotrienols both in vitro and in vivo.

Delta-Tocotrienol's Mechanism: Research has demonstrated that δ-T3 inhibits the proliferation, migration, and tube formation of endothelial cells, which are critical steps in the creation of new blood vessels. It does this by suppressing the signaling of Vascular Endothelial Growth Factor receptor 2 (VEGFR-2), a key pathway in angiogenesis. Furthermore, studies have shown that tocotrienols can trigger apoptosis (programmed cell death) specifically in proliferating endothelial cells, thereby suppressing vessel growth.
In Vivo Evidence: In mouse models, orally administered tocotrienols have been shown to inhibit tumor-induced angiogenesis. In contrast, the much more common alpha-tocopherol (Toc) demonstrated very weak inhibitory effects in the same studies. This highlights a crucial difference in the biological effects of these two forms.

Tocopherols: A Complicating Factor?

While tocotrienols have been shown to suppress angiogenesis, tocopherols, especially the prevalent alpha-tocopherol (α-Toc), have been found to have a more ambiguous or even counterproductive role. The bias towards studying α-Toc in early research due to its higher concentration in human tissues often led to inconsistent results. Later studies revealed a potential conflict between the two vitamin E families.

Antagonistic Effects: A significant finding showed that α-Toc can actually suppress the antiangiogenic effects of δ-T3 when administered together. This is attributed to α-Toc interfering with the cell signaling pathways (like the Akt pathway) that δ-T3 targets to induce apoptosis. This suggests that supplementation with high doses of α-Toc, which is common in many over-the-counter formulas, may hinder the beneficial effects of tocotrienols.
Analogue Studies: Interestingly, synthetic vitamin E analogues, such as alpha-tocopheryl succinate (α-TOS), have shown potent antiangiogenic effects in cancer models by inducing apoptosis in angiogenic endothelial cells. This indicates that specific structural modifications can unlock powerful antiangiogenic properties, but the effects are distinct from the natural isoforms.

Clinical and Health Implications

Research findings extend beyond laboratory settings, hinting at potential therapeutic applications, though further studies are needed. For example, a placebo-controlled trial on women with polycystic ovary syndrome (PCOS), a condition often linked to angiogenesis disturbances, found that eight weeks of vitamin E supplementation significantly reduced levels of pro-angiogenic factors like Vascular Endothelial Growth Factor (VEGF). This provides a real-world example of its antiangiogenic influence in a disease context. However, the precise mechanisms and long-term implications, especially regarding the interaction between different vitamin E forms, require more comprehensive investigation.

Comparing Antiangiogenic Effects: Tocotrienols vs. Tocopherols


Feature	Tocotrienols (esp. delta-T3)	Tocopherols (esp. alpha-Toc)
Potency	Strong antiangiogenic properties	Weak or no antiangiogenic properties
Mechanism	Inhibits endothelial cell proliferation, migration, and tube formation; triggers apoptosis	No significant direct inhibitory effect on angiogenesis at similar doses
VEGF Pathway	Suppresses VEGF receptor 2 (VEGFR-2) signaling	May interfere with or counteract tocotrienol signaling pathways
Interaction	Effects can be inhibited by co-administration of alpha-tocopherol	Can antagonize the antiangiogenic effects of tocotrienols
Structure	Unsaturated side chain	Saturated side chain

Conclusion

In conclusion, the question of whether is vitamin E antiangiogenic cannot be answered with a simple yes or no. The antiangiogenic properties are highly dependent on the specific isoform. Evidence strongly supports that tocotrienols, particularly delta-tocotrienol, are potent inhibitors of angiogenesis by targeting key pathways and inducing endothelial cell apoptosis. Conversely, the more common alpha-tocopherol appears to have little to no antiangiogenic effect and may even inhibit the benefits of tocotrienols when combined. This nuanced understanding is critical for ongoing research into therapeutic applications for conditions involving abnormal angiogenesis, such as cancer and PCOS. For those interested in a deeper dive, the National Institutes of Health offers extensive resources on vitamin E research. [^NIH_VitaminE]

[^NIH_VitaminE]: National Institutes of Health Office of Dietary Supplements. Vitamin E: Fact Sheet for Health Professionals. https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/

Frequently Asked Questions

The most antiangiogenic forms of vitamin E are the tocotrienols, particularly the delta- and gamma-tocotrienol isomers, which have shown potency in laboratory studies.

Standard vitamin E supplements are often rich in alpha-tocopherol. High doses of this form have not demonstrated potent antiangiogenic effects and can even counteract the beneficial actions of tocotrienols.

Tocotrienols inhibit angiogenesis by targeting the VEGF signaling pathway and promoting apoptosis (cell death) in proliferating endothelial cells, which are necessary for forming new blood vessels.

Yes, research on vitamin E's antiangiogenic properties is particularly relevant to cancer, as new blood vessel growth supports tumor development. Studies have explored how tocotrienols suppress tumor angiogenesis and growth in animal models.

Tocopherols and tocotrienols have different chemical structures; tocotrienols have an unsaturated side chain, which contributes to their unique biological activities, including stronger antiangiogenic potential.

While research is promising, especially for tocotrienols, more clinical trials are needed. Current evidence suggests a potential role, but it is not yet established as a standard therapeutic approach.

Tocotrienols are abundant in certain food sources, such as palm oil, annatto, and rice bran, in contrast to tocopherols, which are more common in vegetable oils, nuts, and seeds.