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Oestrogen Metabolism Bioactives II | Research

Certain plants and nutrients may encourage the production of the enzymes involved in oestrogen metabolism and may support a healthy oestrobolome. This week we will focus on rosemary, selenium and methylation support.

Certain plants and nutrients may encourage the production of the enzymes involved in oestrogen metabolism and may support a healthy oestrobolome.

Many of the enzymes required for oestrogen biotransformation are also used in the clearance of xenoestrogens and other toxins. This week we will focus on rosemary, selenium and methylation support.

Rosemary extract
Rosemary is well-established for its anti-microbial, anti-inflammatory and antioxidant properties from the phytochemicals rosmarinic and carnosic acid.

Rosemary induces Nrf2, which signals to the cell nucleus to increase the production of intracellular REDOX capacity and phase II detoxification enzymes. It also increases the expression of genes involved in glutathione synthesis and transport and increases reduced glutathione (GSH) and superoxide dismutase (SOD) levels (1).

In addition, rosemary has been shown to upregulate anti-inflammatory genes, inhibit COX-2 formation, and decrease IL-6 production (2,3). Rosemary reduced the expression of oestrogen and androgen receptors in prostate cancer cell lines and reduced the proliferation of ovarian cancer cell lines (3-6). It also has potent anti-microbial properties, especially to multi-drug-resistant E. coli (7).

Selenium
Selenium is an essential micronutrient, which plays a major role in twenty-five selenoproteins essential for many enzyme systems in the body. These enzymes play a large role in detoxification, anti-inflammatory, and antioxidant-systems (8).

Figure 1 (9): CDP-Cho, cytidine diphoshocholine; PCho, phosphocholine; PtdEtn, phosphatidylethanomine; AdoHcy, S-adeno-sylhomocysteine; AdoMet, S-adenosylmethionine; B12, vitamin B12

Methylation support: betaine, choline, riboflavin
Some individuals may have epigenetic variants in their enzymes that contribute to inadequate production of methylation co-factors, which may be why some individuals are more prone to the toxic metabolic by-products of oestrogen (10,11).

The enzyme Catechol-O-methyltransferase (COMT) catalyses the methylation of the catechol oestrogens to methoxy oestrogens, which simultaneously lowers the potential for DNA damage and increases the concentration of 2-methoxyestradiol which is an anti-proliferative metabolite (11).

Betaine (trimethylglycine/TMG) is primarily found in seafood, wheat germ and spinach. Inadequate dietary intake of methyl groups can lead to hypomethylation in many important pathways, such as decreasing methionine concentrations and production of S-Adenosyl methionine (SAMe) which is a principle co-factor for many methylation reactions.

Dietary intake of choline can modulate methylation via betaine homocysteine methyltransferase (BHMT), this nutrient (and its metabolite, betaine) regulate the concentrations of S-Adenosylhomocysteine (SAH) and SAMe, which are the main methyl donors for methylation reactions (12,13).

References
  1. Pérez-Sánchez A, Sánchez-Marzo N, Herranz-López M, Barrajón-Catalán E, Micol V. Rosemary ( Rosmarinus officinalis L ) extract increases ROS and modulates Nrf2 pathway in human colon cancer cell lines. Free Radic Biol Med [Internet]. 2017;108:S79. Available from: http://dx.doi.org/10.1016/j.freeradbiomed.2017.04.263.
  2. Petiwala SM, Johnson JJ. Diterpenes from rosemary (Rosmarinus officinalis): Defining their potential for anti-cancer activity. Cancer Lett [Internet]. 2015;367(2):93–102. Available from: http://dx.doi.org/10.1016/j.canlet.2015.07.005.
  3. Petiwala SM, Berhe S, Li G, Puthenveetil AG, Rahman O, Nonn L, et al. Rosemary (Rosmarinus officinalis) extract modulates CHOP/GADD153 to promote androgen receptor degradation and decreases xenograft tumor growth. PLoS One. 2014;9(3).
  4. Johnson JJ, Syed DN, Suh Y, Heren CR, Saleem M, Siddiqui IA, et al. Disruption of androgen and estrogen receptor activity in prostate cancer by a novel dietary diterpene carnosol: Implications for chemoprevention. Cancer Prev Res. 2010;3(9):1112–23.
  5. Lee WH, Chen HM, Yang SF, Liang C, Peng CY, Lin FM, et al. Bacterial alterations in salivary microbiota and their association in oral cancer. Sci Rep [Internet]. 2017;7(1):1–11. Available from: http://dx.doi.org/10.1038/s41598-017-16418-x
  6. Tai J, Cheung S, Wu M, Hasman D. Antiproliferation effect of Rosemary (Rosmarinus officinalis) on human ovarian cancer cells in vitro. Phytomedicine [Internet]. 2012;19(5):436–43. Available from: http://dx.doi.org/10.1016/j.phymed.2011.12.012
  7. Sienkiewicz M, Łysakowska M, Pastuszka M, Bienias W, Kowalczyk E. The potential of use basil and rosemary essential oils as effective antibacterial agents. Molecules. 2013;18(8):9334–51.
  8. Rayman MP. Selenium and human health. Lancet [Internet]. 2012;379(9822):1256–68. Available from: http://dx.doi.org/10.1016/ S0140-6736(11)61452-9.
  9. Zeisel SH, Blusztajn JK. Choline and Human Nutrition. Annu Rev Nutr. 2003;14(1):269–96.
  10. Yager JD. Mechanisms of Estrogen Carcinogenesis: The Role of E2/E1- Quinone Metabolites Suggests New Approaches to Preventive Intervention – A Review. Steroids. 2015;99(0 0):56–60.
  11. Dawling S, Roodi N, Mernaugh RL, Wang X, Parl FF. Catechol-O-methyltransferase (COMT)-mediated metabolism of catechol estrogens: Comparison of wild-type and variant COMT isoforms. Cancer Res. 2001;61(18):6716–22.
  12. Zeisel, Steven H. and da Costa K-A. Choline: An Essential Nutrient for Public Health. Nutr Rev. 2009;67(11):615–23.
  13. Fischer LM, Costa K, Kwock L, Galanko J, Zeisel SH. Dietary choline requirements of women : effects of estrogen and. Clin Lab. 2010;(C):1–7.

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