This week I’m going to continue our conversation about phytoestrogens with a new spotlight. And, I also want to provide you more context around phytoestrogens by offering you some education on estrogen itself. As I mentioned last week, this is a big topic, and what I’m giving you is a bite-sized piece (hopefully a delicious one!), but do keep in mind that it’s not the whole story.

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1. An interesting bite of an underestimated hormone

My renewed interest in estrogen began a few years ago when in one of my graduate courses we were given an article summarizing case studies of patients treated for cognitive decline by Dr. Dale Bredesen. I noticed that part of the lengthy protocol for one postmenopausal patient involved estrogen replacement therapy. And so I asked my instructor what the consensus was on this: should estrogen be considered a standard of care for women experiencing cognitive decline? Disappointingly, my instructor admitted that she did not know well enough to give me a definitive answer, but my curiosity was piqued about this hormone I had previously relegated to topics of fertility and the menstrual cycle.

Even though we tend to categorize estrogen as a reproductive hormone, both women and men have estrogen receptors throughout our bodies, and they do surprising things for us that we were never taught about in high school biology! One important role of estrogen in the brain is to regulate energy balance by binding to its receptors on the hypothalamus, which is the area of the brain producing hormones which control our hunger, body temperature, and heart rate, among many other things¹. Among the amazing effects stemming from estrogen binding to its receptors on the hypothalamus are decreased food intake, increased energy expenditure, and blood glucose regulation. Studies²’³ in both male and female mice have shown that either deletion of estrogen receptors in the hypothalamus or estrogen deficiency leads to accumulation of visceral fat, which is the dangerous type of fat stored around our organs and is associated with blood sugar dysregulation, increased blood pressure, and lipid abnormalities–a cluster of signs which you may have heard referred to as “metabolic syndrome” and which paves the way for type 2 diabetes, heart disease, and stroke. Summary: estrogen is a friend of men and women alike.

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2. Phytoestrogen spotlight: flaxseed!

Although myths about male feminization by phytoestrogens are persistent, research has shown that the effects of phytoestrogens in the body are modulatory rather than stimulatory. This is to say that in cases of excess estrogen, these compounds can reduce the effects of this excess by binding in place of estrogen and exerting only a weak effect. In cases of low estrogen, phytoestrogens can help by producing an estrogen-like effect, although it will not be as potent as estrogen itself. Lack of estrogen, or ineffective/insufficient estrogen receptors, contributes to blood glucose dysregulation and visceral fat accumulation in men as it does in postmenopausal women⁴.

Among Western populations, plant lignans (rather than soy, which I touched on last week) are a primary source of phytoestrogens. Like soy isoflavones, lignans are polyphenols found in a variety of plant foods, but flaxseeds are considered one of the richest sources. Lignans such as flaxseed are being explored for their potential role in preventing or reversing the dysfunctions of metabolic syndrome which contribute so heavily to our chronic disease burden.

In one 12-week randomized controlled trial, patients with metabolic syndrome receiving a daily combination of flaxseed and hesperidin (another phytoestrogen derived from citrus fruits) experienced significant improvements in triglyceride level, blood glucose, and systolic blood pressure compared to the placebo group⁵.

These same researchers conducted another study in which prediabetic patients received either a lifestyle intervention (exercise + healthy eating guidance) or a lifestyle intervention plus flaxseed and hesperidin. The group receiving the phytoestrogens experienced significantly greater improvements in blood pressure, lipid profile, glucose control, and inflammatory biomarkers than those in the lifestyle-only group⁶. Disappointingly, this study does not provide details of the lifestyle intervention used. Nevertheless, I wanted to share it as a good example of the use of lifestyle medicine in combination with phytoestrogen supplementation to reduce disease risk.

Let us not underestimate the power of plants! It doesn’t get much simpler than the humble flaxseed.

Wishing you a beautiful and healthful week,

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References

1. Xu, Y., & López, M. (2018). Central regulation of energy metabolism by estrogens. Molecular metabolism, 15, 104–115. https://doi.org/10.1016/j.molmet.2018.05.012 ​https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6066788/​
2. Musatov, S., Chen, W., Pfaff, D. W., Mobbs, C. V., Yang, X. J., Clegg, D. J., Kaplitt, M. G., & Ogawa, S. (2007). Silencing of estrogen receptor alpha in the ventromedial nucleus of hypothalamus leads to metabolic syndrome. Proceedings of the National Academy of Sciences of the United States of America, 104(7), 2501–2506. https://doi.org/10.1073/pnas.0610787104 https://pubmed.ncbi.nlm.nih.gov/17284595/​
3. Jones, M. E., Thorburn, A. W., Britt, K. L., Hewitt, K. N., Wreford, N. G., Proietto, J., Oz, O. K., Leury, B. J., Robertson, K. M., Yao, S., & Simpson, E. R. (2000). Aromatase-deficient (ArKO) mice have a phenotype of increased adiposity. Proceedings of the National Academy of Sciences of the United States of America, 97(23), 12735–12740. https://doi.org/10.1073/pnas.97.23.12735 https://pubmed.ncbi.nlm.nih.gov/11070087/​
4. Gupte, A. A., Pownall, H. J., & Hamilton, D. J. (2015). Estrogen: an emerging regulator of insulin action and mitochondrial function. Journal of diabetes research, 2015, 916585. https://doi.org/10.1155/2015/916585 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4391691/​
5. Yari, Z., Cheraghpour, M., & Hekmatdoost, A. (2021). Flaxseed and/or hesperidin supplementation in metabolic syndrome: an open-labeled randomized controlled trial. European journal of nutrition, 60(1), 287–298. https://doi.org/10.1007/s00394-020-02246-9​https://pubmed.ncbi.nlm.nih.gov/32296931/​
6. Yari, Z., Naser-Nakhaee, Z., Karimi-Shahrbabak, E., Cheraghpour, M., Hedayati, M., Mohaghegh, S. M., Ommi, S., & Hekmatdoost, A. (2021b). Combination therapy of flaxseed and hesperidin enhances the effectiveness of lifestyle modification in cardiovascular risk control in prediabetes: a randomized controlled trial. Diabetology & metabolic syndrome, 13(1), 3. https://doi.org/10.1186/s13098-020-00619-y https://pubmed.ncbi.nlm.nih.gov/33402222/