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What is the relationship between 16-OH E1 and low vitamin D levels?

16-OH E1 is a genotoxic tumorigenic estrogen metabolite. However, there doesn’t appear to be significant evidence that it is specifically associated with low vitamin D levels.

E1 is estrone, one of the three major forms of estrogen produced in the body. Though some E1 is produced by the ovaries, it is primarily synthesized peripherally from androstenedione. The E1 form is the dominant form of estrogen in women after menopause (Pagana 2021).

Estrone can also be synthesized from estradiol (E2), and vice versa, though the conversion of E2 to E1 is favored, and tissue levels of E1 are higher than those of E2 (Zhu 2005).

As with all estrogens, E1 must undergo biotransformation/detoxification via cytochrome P450 enzymes to eliminate it from the body. One of the detoxification pathways produces 16-alpha-OH-E1, a genotoxic and tumorigenic metabolite (Chabi 2022, Stanczyk 2020).

There doesn’t appear to be significant research in humans connecting the 16-alpha-OH-E1 metabolite to vitamin D levels.

References

Chabi, Kahina, and Lekha Sleno. “Estradiol, Estrone and Ethinyl Estradiol Metabolism Studied by High Resolution LC-MS/MS Using Stable Isotope Labeling and Trapping of Reactive Metabolites.” Metabolites vol. 12,10 931. 30 Sep. 2022, doi:10.3390/metabo12100931

Pagana, Kathleen Deska, et al. Mosby's Diagnostic and Laboratory Test Reference. 15th ed., Mosby, 2021.

Stanczyk, Frank Z. “The 2-/16α-Hydroxylated Estrogen Ratio-Breast Cancer Risk Hypothesis: Insufficient Evidence for its Support.” The Journal of steroid biochemistry and molecular biology vol. 201 (2020): 105685. doi:10.1016/j.jsbmb.2020.105685

Zhu, Bao Ting, and Anthony J Lee. “NADPH-dependent metabolism of 17beta-estradiol and estrone to polar and nonpolar metabolites by human tissues and cytochrome P450 isoforms.” Steroids vol. 70,4 (2005): 225-44. doi:10.1016/j.steroids.2005.01.002