I omitted to mention that this is not the first time that the...

I omitted to mention that this is not the first time that the potent anti-inflammatory properties of tocopheryl phosphate has been reported in the literature.

In the 2022 study I referenced, the Japanese researchers cite the previous published findings of POH/AVE scientists which showed that TPM diminished expression of the inflammatory cytokines IL-6 and TNF-α in animal studies.

And previously, in a 2015 review of the literature on α- tocopheryl phosphate, British and Iranian researchers cited the findings of POH/AVE researchers regarding the impact of TPM on an even broader range of proinflammatory cytokines and markers

α-TP treatment was associated with decreased plasma levels of several key proinflammatory cytokines and markers including interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor-α (TNF-α, C-reactive protein (CRP), plasminogen activator inhibitor-1 (PAI-1). The effects observed for α-TP were significantly greater than those exerted by α-T succinate. (1)

Various forms of Vitamin E have also been reported in the literature to differ in their level of antioxidant activity. In 2004, Dutch scientists published a paper on Vitamin E phosphate in which they noted that Vitamin E phosphate has a potent antioxidant effect of its own in contrast to Vitamin E acetate and Vitamin E succinate.(2)

Additionally, various forms of Vitamin E have been reported to differ in apoptopic (programmed cell killing) effect. In a 2007 study by the same Dutch scientists, alpha tocopheryl phosphate was compared with alpha tocopherol and alpha tocopheryl succinate for its ability to inhibit osteosarcoma cell proliferation and induce cell death and apoptosis. At that time, alpha-tocopheryl succinate was already well known as a potent and selective apoptotic agent. The researchers found that α-tocopheryl phosphate induced cell death in a dose dependent manner and was more potent than α-tocopheryl succinate in inhibiting osteosarcoma cell proliferation and inducing apoptosis.(3)

A further difference in activity between Vitamin E forms was reported in a 2011 study by French researchers. Both α-tocopherol and α-tocopheryl phosphate were found to have direct, but opposite action on synaptic transmission in the rat hippocampus, an effect mediated by cannabinoid receptors.

These compounds had opposite actions on both glutamatergic and **Aergic transmission: whereas α-TOH potentiated these transmissions, α-TP inhibited them. Interestingly, these effects were both mediated by cannabinoid receptors (CB1Rs), because they were blocked by the CB1R antagonist AM251. (4)

Clearly, all forms of Vitamin E do not act in the same way.

Returning to the 2022 Japanese preclinical study, improvement was seen in the symptoms of rheumatoid arthritis in mice after dosing with tocopheryl phosphate. Tocopheryl phosphate (on which TPM is based), but not α-tocopherol or tocopheryl succinate, was found to inhibit the mRNA expression of IL-6, TNF-α, MMP-3, and MMP-13. Previously, TPM has also been found to reduce the levels of (IL)-1β and IL-8. (5)

This is notable because in a 2020 study of the effects of CBD on rheumatoid arthritis (using synovial fibroblasts taken from 40 patients with rheumatoid arthritis), it was found that CBD also inhibited IL-6,IL-8 and MMP-3 production. The authors concluded

Thus, CBD possesses anti-arthritic activity and might ameliorate arthritis via targeting synovial fibroblasts under inflammatory conditions. (6)




(1) Majid Ghayour-Mobarhan, Zahra Saghiri, Gordon Ferns & Amirhossein Sahebkar (2015) α-Tocopheryl Phosphate as a Bioactive Derivative of Vitamin E: A Review of the Literature, Journal of Dietary Supplements, 12:4, 359-372, DOI: 10.3109/19390211.2014.952859

(2) Rezk BM, Haenen GR, Van Der Vijgh WJ, Bast A. The extraordinary antioxidant activity of vitamin E phosphate. Biochimica et Biophysica Acta. 2004 Jul;1683(1-3):16-21. DOI: 10.1016/j.bbalip.2004.03.005. PMID: 15238215.

(3) Bashir M. Rezk, Wim J.F. van der Vijgh, Aalt Bast, Guido R.M.M. Haenen. Alpha-tocopheryl phosphate is a novel apoptotic agent. Front. Biosci. (Landmark Ed) 2007, 12(6), 2013–2019. https://doi.org/10.2741/2206

(4) Crouzin N., Ferreira M.-C.D.J., Cohen-Solal C., M’Kadmi C., Bernad N., Martinez J., Barbanel G., Vignes M., Guiramand J. α-Tocopherol and α-tocopheryl phosphate interact with the cannabinoid system in the rodent hippocampus. Free Radic. Biol. Med. 2011;51:1643–1655. doi: 10.1016/j.freeradbiomed.2011.07.012.

(5) Hama S, Kirimura N, Obara A, Takatsu H, Kogure K. Tocopheryl Phosphate Inhibits Rheumatoid Arthritis-Related Gene Expression In Vitro and Ameliorates Arthritic Symptoms in Mice. Molecules. 2022 Feb 20;27(4):1425. doi: 10.3390/molecules27041425. PMID: 35209214; PMCID: PMC8880618.

(6) Lowin, T., Tingting, R., Zurmahr, J. et al. Cannabidiol (CBD): a killer for inflammatory rheumatoid arthritis synovial fibroblasts. Cell Death Dis 11, 714 (2020). https://doi.org/10.1038/s41419-020-02892-1