Recently we had a comment on our social media page, saying they had been told in another group (and I’m paraphrasing here) Salvestrols are phytoestrogens and are not good for estrogen/hormone-based cancers.

So, we thought it would be a good idea to discuss this concept and clarify the misconceptions about what Salvestrols are, the interaction between Salvestrol and oestrogen activity in cancer and briefly talk about phytoestrogens from foods.

 

A brief summary on Estrogens

First, let's briefly discuss estrogens in relation to the female body. Estrogens are a group of steroid hormones crucial for a number of bodily functions, including reproductive and non-reproductive systems. The primary forms of estrogens in the female body are:

1. Estradiol (E2): The most potent and prevalent form in premenopausal women.
2. Estrone (E1): Found mainly after menopause.
3. Estriol (E3): Primarily present during pregnancy.

Image from: www.freepik.com

 

These hormones play significant roles in regulating the menstrual cycle, maintaining pregnancy, and influencing bone density, skin health, and cardiovascular function.

Estradiol and estrone are the most dominant form of estrogen in women who are not pregnant. Estradiol or specifically 17-beta estradiol is metabolized into two major metabolites:

• 2-hydroxyestradiol and (2-OHE2)
• 4-hydroxyestradiol (4-OHE2).

The 4-OHE2 metabolite is known to be carcinogenic.

 

The enzyme CYP1B1, which is expressed in unhealthy, DNA-damaged cells, preferentially produces this carcinogenic estrogen metabolite. Important to note is that the production of the CYP1B1 enzyme occurs only after cancer has developed, research has shown the CYP1B1 enzyme is the only enzyme produced from the P450 gene that is produced in unhealthy cells all other P450 enzymes can be produced in both healthy and unhealthy cells. ^{7, 8}

 

So what are Salvestrols?

 

 

Phytoalexins are compounds produced by plants in response to stress or pathogen attack. These natural substances are thought to have significant health benefits, including anti-cancer properties. Salvestrols, in particular, have been identified for their potential to selectively target the CYP1B1 enzyme, which is overly expressed in DNA-damaged/cancer cells. ⁷

Read more about phytoalexins, nesems here

 

Salvestrols and the CYP1B1 Enzyme

Salvestrols are metabolized by the enzyme CYP1B1, which is overexpressed in cancer/DNA damaged cells. This CYP1B1 enzyme in DNA damaged cells metabolites Salvestrols creating metabolites that can induce apoptosis (cell death), sparing healthy cells. ⁷ The selectivity for DNA Damaged cells is a key feature making Salvestrols a unique option to support those with cancer.

 

What are Phytoestrogens?

Phytoestrogens are naturally occurring plant compounds that are structurally similar to estrogen specifically 17beta-estradiol.

Phytoestrogens are found in various vegetables and fruits – soybeans, legumes, cabbage, sprouts, garlic, onions etc. These compounds can bind to estrogenic receptors and have both estrogenic and anti-estrogenic effects. ^3,4

Image: From: Lephart, Edwin. (2021). Phytoestrogens (Resveratrol and Equol) for Estrogen-Deficient Skin—Controversies/Misinformation versus Anti-Aging In Vitro and Clinical Evidence via Nutraceutical-Cosmetics. International Journal of Molecular Sciences. 22. 11218. 10.3390/ijms222011218.

 

With phytoestrogens having the ability to be estrogenic and anti-estrogenic can we say phytoestrogens are inheritable bad for cancer cells or healthy cells?

 

The effects of phytoestrogens on individual health is complex and depends on individual response based on hormone levels, epigenetics, and the type and quantity of phytoestrogens being eaten. 

If you look for research on the health effects of phytoestrogens you will find both positive and negative research in this area, which causes a lot of confusion. ^1,2,3,4,5,6

When looking at the research on this, in general, eating phytoestrogens found in natural unprocessed foods like vegetables, fruits, seeds and nuts have positive impacts on health including associations with decrease cell proliferation in breast cancer. It's indicated that when we start consuming highly processed phytoestrogens in large quantities, particularly when our current/previous diet has not included these phytoestrogens, we can see negative consequences for health. ⁶

 

Salvestrols, when taken in therapeutic amounts, selectively bind to the CYP1B1 binding sites, preventing the binding of estradiol and its subsequent metabolism into 4-OHE2. As Salvestrols have an affinity for CYP1B1, they can outcompete other compounds for these binding sites when taken in therapeutic doses. Once bound, Salvestrols are metabolized creating metabolites that initiates apoptosis and prevents estradiol metabolism within the cell. ⁷

The dual action of Salvestrols addresses two issues in hormone-related cancers such as breast cancer: Preventing the metabolism of estradiol by CYP1B1 and creating metabolites that initiate apoptosis. ^{7, 8}

 

Activity of Phytoestrogens vs Salvestrols

Phytoestrogens are plant-derived compounds that can mimic or modulate the activity of estrogen in the body by binding to estrogen receptors and influencing estrogen-related pathways. Salvestrols, on the other hand are specific secondary plant metabolites, nesem, which target the CYP1B1 enzyme to exert their effects, making their mechanisms of action distinct from those of phytoestrogens. 7, 8

Salvestrols and phytoestrogens represent fascinating areas of research in the realm of natural compounds and their potential health benefits.

Salvestrols have the unique ability to selectively target the CYP1B1 enzyme and when taken in therapeutic amounts can out competing other compounds that bind to the CYP1B1 enzyme such as estradiol. Highlighting the benefits in modulating DNA damaged cells and providing support in those with cancer. 7, 8

 

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1. Ahlin R, Nørskov NP, Nybacka S, Landberg R, Skokic V, Stranne J, Josefsson A, Steineck G, Hedelin M. Effects on Serum Hormone Concentrations after a Dietary Phytoestrogen Intervention in Patients with Prostate Cancer: A Randomized Controlled Trial. Nutrients. 2023 Apr 6;15(7):1792. doi: 10.3390/nu15071792. PMID: 37049632; PMCID: PMC10097251.

2. Domínguez-López I, Yago-Aragón M, Salas-Huetos A, Tresserra-Rimbau A, Hurtado-Barroso S. Effects of Dietary Phytoestrogens on Hormones throughout a Human Lifespan: A Review. Nutrients. 2020 Aug 15;12(8):2456. doi: 10.3390/nu12082456. PMID: 32824177; PMCID: PMC7468963.

3. Desmawati D, Sulastri D. Phytoestrogens and Their Health Effect. Open Access Maced J Med Sci. 2019 Feb 14;7(3):495-499. doi: 10.3889/oamjms.2019.044. PMID: 30834024; PMCID: PMC6390141.

4. Bacciottini L, Falchetti A, Pampaloni B, Bartolini E, Carossino AM, Brandi ML. Phytoestrogens: food or drug? Clin Cases Miner Bone Metab. 2007 May;4(2):123-30. PMID: 22461212; PMCID: PMC2781234.

5. Patisaul HB, Jefferson W. The pros and cons of phytoestrogens. Front Neuroendocrinol. 2010 Oct;31(4):400-19. doi: 10.1016/j.yfrne.2010.03.003. Epub 2010 Mar 27. PMID: 20347861; PMCID: PMC3074428.

6. https://www.bcpp.org/resource/phytoestrogens/

7. Schaefer, B.A. (2012). Salvestrols, Natures Defence Against Cancer: Linking Diet & Cancer. Clinical Intelligence Corp, Canada

8. Bapi Gorain, Subrat Kumar Bhattamishra, Hira Choudhury, Utpal Nandi, Manisha Pandey, Prashant Kesharwani, Chapter 3 - Overexpressed Receptors and Proteins in Lung Cancer, Editor(s): Prashant Kesharwani, Nanotechnology-Based Targeted Drug Delivery Systems for Lung Cancer, Academic Press,2019,Pages 39-75,ISBN 9780128157206, https://doi.org/10.1016/B978-0-12-815720-6.00003-4. (https://www.sciencedirect.com/science/article/pii/B9780128157206000034)