Which Vitamin E Provides the Best Protection for Blood Vessels?
The best-known and most frequently researched vitamin E form is alpha-tocopherol. Inexpensive vitamin preparations bought in the supermarket usually contain alpha-tocopherol.
However, there are additional, important vitamin E forms with significant biological activity. According to latest research findings, these include mainly alpha and beta tocotrienols.
Unfortunately, to date only alpha-tocopherol is offered as vitamin E.
Tocotrienols, however, have particularly valuable properties which tocopherols do not or do only contain in small amounts. The fact that tocopherols have bioactive sub-fractions must also be taken into account. [1]
A review study from 1999, published in the Clinical Biochemistry Journal (authors: Theriault et al), concluded that in many situations tocotrienols are superior to alpha-tocopherol.
According to recent studies, tocotrienol has better antioxidant properties than tocopherol. Quote from the authors: “From a pharmacological point of view, the use of conventional vitamin E, which mainly contains alpha-tocopherol, is questionable.” [2]
This is especially important in connection with vascular health. A test tube study (in vitro) with biological membranes in 1991, published in the Free Radical Biology Medicine Journal (authors: Serbinova et al.) shows a 40 to 60-fold higher anti-oxidative activity of tocotrienols against dangerous lipid peroxidation (cell-damaging oxidation of fats) than with ordinary alpha-tocopherols. Thus, for example, only oxidized cholesterol is harmful, whereas none-oxidized cholesterol is not. [3]
In an animal study in 2016, the effects on the lipid metabolism of alpha-tocopherols were compared to tocotrienols. Effects of the two vitamin E-forms on cholesterol and triglyceride levels were investigated.
Alpha-tocopherol did not show lipid-lowering effects.
However, alpha-tocopherol even inhibited the lipid-lowering effects of tocotrienols. [4]
The study leads to the conclusion that alpha-tocopherol (negatively) affects the naturally-contained tocotrienol in the diet.
This may be one reason why certain studies do not attribute positive effects to vitamin E (in the form of alpha-tocopherol). This is also a good example that natural vitamins can be superior to isolated synthetically produced ones.
Inhibition of HMG-CoA Reductase
Is natural vitamin E with tocotrienols the new statin? To lower cholesterol levels, statins (lipid-lowering agents) are used in conventional medicine. Statins inhibit the enzyme HMG-CoA reductase. However, they also do lower Q10 levels in the body. Therefore, coenzyme Q10 should always be used in statin-therapy to prevent statin-induced mitochondrial dysfunction. [5]
Natural vitamin E, or to be more precise, the gamma and delta-tocotrienol portions and the gamma-tocopherol portions also have an inhibitory effect on the very important enzyme HMG-CoA reductase.
Delta and gamma-tocotrienols reduce the activity of the enzyme HMG-CoA reductase in humans and animals. Thus, the BH4 regeneration is promoted. BH4 is essential as a cofactor for the enzyme NO synthase.
Tocotrienols regulate cholesterol formation in mammalian cells by post-transcriptional inhibition of HMG-CoA reductase. [6]
Delta and gamma tocotrienols stimulate the degradation of HMG-CoA reductase. [7]
The inhibition of the enzyme HMG-CoA reductase is regarded as the most important vascular protective effect of statins. An inhibition of cholesterol synthesis is thus pursued. However, the positive effect on the coupling status of the NO synthases by inhibition of the peroxinitrite formation and the promotion of the BH4 regeneration rate is another very important effect for vascular health. Statins and vitamin E have a common factor in that both of them have these important effects on blood vessels.
Gamma-tocopherol as well as delta and gamma-tocotrienol have a positive influence on the NO synthases and the formation of bioactive NO (nitric oxide).
NO synthases not only perform a central function in the vessels, but also in the whole body (for example pathogen defense, maintenance of nerve health, regulation of programmed cell death, etc.).
The end product, which is so essential for the body, is ultimately the small and volatile nitric oxide molecule formed by the NO synthases.
The following NO-mediated effects are of great importance for vascular health:
NO is the key molecule for regulation of blood pressure.
It is not without reason that the Nobel Prize was awarded for the discovery of NO in 1998.
Until then NO was unknown and there was talk about a mysterious substance called EDRF. EDRF is the abbreviation for endothelial derived relaxing factor; that is a substance which comes from the vascular wall possessing relaxing properties.
NO (nitric oxide) reduces the formation of adhesion molecules on endothelial cells. The adhesion of leukocytes indicates the beginning of developing arteriosclerosis. NO prevents arteriosclerosis at the time of its onset.
Furthermore, the formation of harmful oxidized LDL cholesterol and the platelet aggregation, i.e. the clumping of blood platelets, are inhibited by the small nitrogen molecule.
If the vessels are already “diseased” a so-called endothelial dysfunction exists.
A central problem exists due to elevated levels of the vessel toxic superoxide radical.
Superoxide is produced in many ways. Decoupling (uncoupling) of the enzyme NO synthase can be a significant source of superoxide.
Uncoupled NO synthases are “diseased” and produce the cell-damaging superoxide instead of the implied important nitric oxide (NO).
A fast reaction with the important NO molecule occurs. Consequently, the even more harmful peroxinitrite is produced.
Gamma-tocopherol prevents the oxidation of BH4 (tetrahydrobiopterin). BH4 is an important substance for the function of NO synthase. A lack of non-oxidized BH4 leads to the so-called uncoupling of the NO synthase, which ultimately leads to less formation of NO and to increased peroxinitrite formation.
In addition, BH4 is a direct scavenger of peroxinitrite. [8] [9]
The cofactor BH4 (tetrahydrobiopterin), which is so important for NO synthase, is therefore increasingly oxidized to BH2 by peroxinitrite, leading to uncoupling. The uncoupled enzyme provides superoxide instead of nitric oxide (NO). Superoxide can react with the available nitric oxide (NO) to form peroxynitrite.
Thus the fatal vicious circle is completed. Tocotrienols and gamma-tocopherols (vitamin E) can precisely break this vicious circle.
It is still questionable whether or to what extent vitamin E can be used as a lipid-lowering agent. For this purpose, further large-scale human studies would have to be carried out.
The problem with statins is, unfortunately, that they can lead to Q10 depletion in the cell.
Coenzyme Q10 is essential for cell respiration in the power plants of the cell. An unwanted and dreaded side effect of statins is statin-induced muscle pain.
Reason for this is the feared acquired mitochondrial dysfunction. [10]
Statins inhibit the formation of mevalonic acid, which is needed for cholesterol formation. However, since mevalonic acid is also a precursor of coenzyme Q10, Q10 levels in the body are reduced.
Q10 depletion by tocotrienols or gamma tocopherols in contrast to the known Q10 depletion by statins has not been published yet.
Conclusion
VAbove all, tocotrienols are important for vascular health by positively affecting lipid metabolism.
Antioxidant protection against lipid peroxidation on cell membranes is 40 – 60 times higher by tocotrienols than by tocopherols.
The mechanisms include inhibition of HMG-CoA reductase, the rate-determining enzyme of cholesterol biosynthesis.
However, gamma-tocopherols also have positive effects by protecting against decoupling of the endothelial NO synthase and simultaneously scavenging peroxinitrite.
[1] Mark F. McCarty
Gamma-tocopherol may promote effective no synthase function by protecting tetrahydrobiopterin from peroxynitrite
Med Hypotheses, September 2007
[2] Andre Theriault, Jun-Tzu Chao, Qi Wang, Abdul Gapor, Khosrow Adeli
Tocotrienol: a review of its therapeutic potential
Clinical Biochemistry, July 1999
[3] Serbinova1,V. Kagan, D. Han, L. Packer
Free radical recycling and intramembrane mobility in the antioxidant properties of alpha-tocopherol and alpha-tocotrienol.
Free Radical Biology & Medicine – Journal, 1991
[4] Akira Shibata, Yuki Kawakami, Toshiyuki Kimura, Teruo Miyazawa, Kiyotaka Nakagawa
α-Tocopherol Attenuates the Triglyceride- and Cholesterol-Lowering Effects of Rice Bran Tocotrienol in Rats Fed a Western Diet
Journal of Agricultural and Food Chemitry, June 2016
[5] Richard Deichmann, Carl Lavie, Samuel Andrews
Coenzyme Q10 and Statin-Induced Mitochondrial Dysfunction
The Ochsner Journal, 2010
[6] Rex A. Parker, Bradley C. Pearce, Ronald W. Clark, David A. Gordon, J. J. Kim Wright
Tocotrienols regulate cholesterol production in mammalian cells by post-transcriptional suppression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase.
Journal of Biological Chemisty, 1993
[7] Bao-Liang Song, Russell A. DeBose-Boyd
Insig-dependent Ubiquitination and Degradation of 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase Stimulated by δ- and γ-Tocotrienols*
Journal of Biological Chemisty, July 2006
[8] Maaike Berbée, Qiang Fu, K. Sree Kumar, Martin Hauer-Jensen
Novel Strategies to Ameliorate Radiation Injury: A Possible Role for Tetrahydrobiopterin
Curr Drug Targets, November 2010
[9] Mark F. McCarty
Gamma-tocopherol may promote effective no synthase function by protecting tetrahydrobiopterin from peroxynitrite
Med Hypotheses, September 2007
[10] Richard Deichmann, Carl Lavie, Samuel Andrews
Coenzyme Q10 and Statin-Induced Mitochondrial Dysfunction
The Ochsner Journal, 2010