diet, hormones, aging, immune function

[jimmylegs]

yeah i'm still in a fairly new-to-me learning curve, hunting up how modifiable lifestyle elements might contribute in the hormone department specifically.

even though i am not yet clear on all the nuances re progesterone, these interesting tidbits have influenced my plans around dried parsley use in cooking, and the frequency of tabbouleh consumption over the current growing season, too

Effects of progesterone administered after MPTP on dopaminergic neurons of male mice (2017)
https://www.sciencedirect.com/science/a ... 0817300527

Progesterone-based compounds affect immune responses and susceptibility to infections at diverse mucosal sites (2017)
https://www.nature.com/articles/mi201735

The Flavonoid Apigenin Is a Progesterone Receptor Modulator with In Vivo Activity in the Uterus (2018)
https://link.springer.com/article/10.10 ... 018-0333-x

Apigenin, a Natural Flavonoid, Attenuates EAE Severity Through the Modulation of Dendritic Cell and Other Immune Cell Functions (2016)
https://link.springer.com/article/10.10 ... 015-9617-x

https://en.wikipedia.org/wiki/Apigenin
"Apigenin is found in many fruits and vegetables, but parsley, celery, celeriac, and chamomile tea are the most common sources.[3] ... Dried parsley can contain about 45 mg/gram and dried chamomile flower about 3-5 mg/gram apigenin.[5] The apigenin content of fresh parsley is reportedly 215.5 mg/100 grams, which is much higher than the next highest food source, green celery hearts providing 19.1 mg/100 grams.[6]"

https://bit.ly/3vMzptn
"The average bunch of parsley contains 12 stems, weighs 55 grams and contains just over two cups of sprigs."

[Jaded]

Thanks Scott1 that's a very interesting discussion. It's always about the money, eh?!

And JL, thanks for the links. I will definitely be adding more parsley, celery and camomile (tea) to my diet. But you guys can have the celeriac ;)

On a serious note, I was a little worried reading that progestins can increase susceptibility to HSV. Quite how this happens isn't expained (well, I haven't read all the article yet, it's late and I need sleep!) but anything pro-viral is worrying

Thanks again

J

[jimmylegs]

np

i haven't really dug in much yet re the progestin x hsv connection. in the meantime, found this:

A Review on Flavonoid Apigenin: Dietary Intake, ADME, Antimicrobial Effects, and Interactions with Human Gut Microbiota (2019)
https://www.hindawi.com/journals/bmri/2019/7010467/
"8.2. Antiviral Activity
Apigenin has been reported to be able to inhibit multiple viruses, including enterovirus 71 (EV71), herpes simplex virus HSV-1 and HSV-2, hepatitis C virus, influenza virus..."

i haven't spent much time in that article yet, lots more to read!

[Jaded]

Many thanks - that's reassuring. There is always so much to read....

Thanks again
J

[jimmylegs]

interesting info, if not entirely from the (unmedicated) modifiable realm...

Roles of Progesterone, Testosterone and Their Nuclear Receptors in Central Nervous System Myelination and Remyelination (2020)
https://www.mdpi.com/1422-0067/21/9/3163/htm

" ... We summarize here a recent advancement in the field of myelin biology, to treat demyelinating disorders using the natural as well as synthetic analogs of progesterone and testosterone."

[jimmylegs]

still exploring

Evaluating sex hormone levels in reproductive age women with multiple sclerosis and their relationship with disease severity (2012)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3697216/

"... There is possibly a limitation of our study, it was better to calculate the progression index (PI) of patients and then obtain correlation between PI and sex hormone levels, but the duration of disease was not available for all patients.

It is concluded that the hormone-related modulation of disease severity supports the suggestion that sex hormones play a role in the inflammation and repair mechanisms. ..."

Zinc status and serum testosterone levels of healthy adults (1996)
https://pubmed.ncbi.nlm.nih.gov/8875519/

"... Dietary zinc restriction in normal young men was associated with a significant decrease in serum testosterone concentrations after 20 weeks of zinc restriction (baseline versus post-zinc restriction mean +/- SD, 39.9 +/- 7.1 versus 10.6 +/- 3.6 nmol/L, respectively; p = 0.005). Zinc supplementation of marginally zinc-deficient normal elderly men for six months resulted in an increase in serum testosterone from 8.3 +/- 6.3 to 16.0 +/- 4.4 nmol/L (p = 0.02). We conclude that zinc may play an important role in modulating serum testosterone levels in normal men."

The Role of Zinc in Selected Female Reproductive System Disorders (2020)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468694/

"... In summary, zinc is important in both the male and female reproductive system. It plays a critical role in the functioning of this system by serving a protective function, e.g., as an antioxidant. ..."

[jimmylegs]

MRI in multiple sclerosis during the menstrual cycle: Relationship with sex hormone patterns (1999)
https://n.neurology.org/content/53/3/622.short

"... The ratio of progesterone/17-beta-estradiol during the luteal phase was significantly associated with both number (r = 0.6, p = 0.03) and volume (r = 0.7, p = 0.009) of enhancing lesions, providing support for a role of these hormones as immunomodulatory factors in MS. ..."

yep, definitely outside the research comfort zone these days. not used to 'news' being over 20 yrs old lol

[jimmylegs]

The neural androgen receptor: a therapeutic target for myelin repair in chronic demyelination
https://academic.oup.com/brain/article/136/1/132/431168

[jimmylegs]

Impact of Estrogen Therapy on Lymphocyte Homeostasis and the Response to Seasonal Influenza Vaccine in Post-Menopausal Women (2016)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4747494/

"... the numbers of circulating CD4 and CD20 B cells were reduced in the post-menopausal group receiving ET, we also detected a better preservation of naïve B cells, decreased CD4 T cell inflammatory cytokine production, and slightly lower circulating levels of the pro-inflammatory cytokine IL-6. Following vaccination, young adult women generated more robust antibody and T cell responses than both post-menopausal groups. Despite similar vaccine responses between the two post-menopausal groups, we observed a direct correlation between plasma 17β estradiol (E2) levels and fold increase in IgG titers within the ET group. These findings suggest that ET affects immune homeostasis and that higher plasma E2 levels may enhance humoral responses in post-menopausal women."

[jimmylegs]

Relationship between Carotenoids, Retinol, and Estradiol Levels in Older Women (2015)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4555135/

"... During aging there are significant reductions in retinol and carotenoid concentrations, whereas estradiol levels decline during menopause and progressively increase from the age of 65. ... Conclusions: In older women, β-carotene levels are independently and inversely associated with E2.
...
Given the limited studies on this topic, the underlying mechanisms contributing to the relationship between β-carotene and E2 need to be investigated. Several lines of evidence suggest that β-carotene might induce regulation of ER expression and antagonize estrogen binding to nuclear estrogen receptors [13]. However, other reports suggest that β-carotene does not necessarily play a role in estrogen-regulated pathways and its beneficial effect in hormone-dependent cancers might be realized through a steroid hormone-related mechanism, by diffusing through the cell membrane, serving as ligands for nuclear carotenoid-specific receptors (with or without first binding to cellular transport proteins) [32].
...
The potential mechanisms underlying the modulation of E2 levels as well as the therapeutic role of these phyto-nutrients in estrogen-dependent cancer targets need to be evaluated in large-scale clinical trials."

ok so if i'm understanding this properly, the takeaway point could be: keep your intake of beta carotene foods high, and if serum estradiol still goes higher than it should be at that stage of life, add more!

based on my limited understanding today, i think i will be keeping a (tbd) upper limit in mind for serum estradiol.

[jimmylegs]

17β-Estradiol Inhibits Iron Hormone Hepcidin Through an Estrogen Responsive Element Half-Site (2012)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3380311/

" ... We have previously observed that although levels of 17β-estradiol (E2) are high in young women, levels of iron in the form of ferritin are low (Supplemental Fig. 1, ... http://endo.endojournals.org) (4). In older postmenopausal women, the reverse is true, with low E2 and high iron levels. These concurrent but inverse changes in E2 and iron levels during menopausal transition prompted us to investigate whether changes in E2 levels could lead to changes in iron levels. In the present study, we investigated whether E2, the most active form of estrogens, affects expression of hepcidin, a key iron regulatory hormone, and, thus, may alter body iron homeostasis.
...
At the systemic level, an interaction of estrogen with iron has long been suspected. This is exemplified by a concurrent but inverse change in estrogen and iron levels during menopausal transition, with high estrogen and low iron in young women but low estrogen and high iron in older postmenopausal women (4). Furthermore, a time-dependent increase in iron stores has been shown in oral contraceptive users when compared with nonusers (34–36). The increased iron stores are said to be attributable primarily to reduced volume in menstrual blood loss. However, this cannot explain the animal data showing a significant rise in body iron stores and uptake in estrogen-treated ovariectomized rats, because rats do not have menses (37, 38). Clearly, there is a direct link between estrogen and systemic iron metabolism, although the molecular mechanism remains unclear. ..."

[jimmylegs]

i've always avoided taking meds and hormones at least in part to keep the downstream as clean as possible..

Effects of 17β-estradiol (E2) on aqueous organisms and its treatment problem: a review (2016)
https://www.degruyter.com/document/doi/ ... -0040/html

"The most direct and clear evidence has been found in male fish swimming downstream from estrogen-impacted water sources exposed to estrogens (EE2-E2) even at low-dose concentrations (1–2 ng/L). Specifically, these fish have been found to have sexual characteristics of both male and female, such as partially developed eggs or ova in their testes (23).
...
Table 8:
The concentration of E2 and other estrogen compounds in surface waters, sediments and drinking water.
...
USA, drinking water E2 .... 17 ng/L :O (bit of an outlier i think)
...
Concerning water, at least regarding this review, surely it can be stated that it is contaminated by E2 at high levels in most areas. ..."

yikes. LOTS more info in that one.

well, looks like i will be having a think about whether estradiol is really going to do me enough personal good to be worth contributing to downstream impacts. definitely have some more reading to do! and a couple questions for the local WWTP, see what's up in the local effluent.

[jimmylegs]

Environmental impact of estrogens on human, animal and plant life: A critical review (2017)
https://www.sciencedirect.com/science/a ... 2016304494

"Conclusions
There is published evidence to establish a causal relationship between estrogens in the environment and breast cancer. However, there are serious gaps in our knowledge about estrogen levels in the environment and a call is required for a world wide effort to provide more data on many more samples sites. Of the data available, the synthetic estrogen, ethinyl estradiol, is more persistent in the environment than natural estrogens and may be a greater cause for environmental concern. Finally, we believe that there is an urgent requirement for inter-disciplinary studies of estrogens in order to better understand their ecological and environmental impact."

note to self. at the very least, avoid ethinyl estradiol.

[jimmylegs]

The occurrence of steroidal estrogens in south-eastern Ontario wastewater treatment plants (2012)
https://pubmed.ncbi.nlm.nih.gov/22634558/

" ... Estrone (E1), 17β-estradiol (E2) and 17α-ethinylestradiol (EE2) were found at maximum concentrations in raw sewage (RS), at 104, 66.9 and 5.7 ng L(-1), respectively. ... estrogenic potency, as determined by a sensitive in vitro reporter gene assay, did not decrease during the water treatment process, suggesting that many estrogenic chemicals are conserved in FE (final effluent). E1 and EE2 were found in river water, both upstream and downstream of the WWTPs, and at much lower concentrations than in FE. Our study demonstrates the persistence of steroidal estrogens and estrogenic potency in Ontario WWTP effluents and surface waters, and has uncovered temporal patterns of release that may be used to help predict risks to aquatic organisms in these environments."

Distribution of estrogens, 17β-estradiol and estrone, in Canadian municipal wastewater treatment plants (2016)
https://www.sciencedirect.com/science/a ... 9704004565

"...In conventional activated sludge and lagoon treatment systems, the mean concentrations of 17β-estradiol and estrone in influent were 15.6 ng/l (range 2.4–26 ng/l) and 49 ng/l (19–78 ng/l). In final effluents, the mean concentrations of both 17β-estradiol and estrone were reduced to 1.8 ng/l (0.2–14.7 ng/l) and 17 ng/l (1–96 ng/l), respectively. 17β-estradiol was removed effectively, >75% and as high as 98%, in most of the conventional mechanical treatment systems with secondary treatment. The removal of estrone was much more complex with removal varying from 98% to situations where the concentrations in the effluent were elevated above that detected in the influent...."

Status of hormones and painkillers in wastewater effluents across several European states—considerations for the EU watch list concerning estradiols and diclofenac (2016)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4912981/

"... combinations of different conventional and advanced technologies including biological and plant-based strategies seem to be most promising to solve the burning problem of polluting our environment with hazardous emerging xenobiotics."

[jimmylegs]

ok so back to exploring food based options, then...

The pros and cons of phytoestrogens
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3074428/

"...Older individuals, especially those with high cholesterol, may experience modest benefits including improved bone and cardiovascular health, and perhaps a decreased risk of carcinogenesis. Moderation is likely key and the incorporation of real foods, as opposed to supplements or processed foods to which soy protein is added, is probably essential for maximizing health benefits. Finally, the relative importance of the soy protein itself, compared to the isoflavones, on health outcomes such as lipid levels, reduced risk of carcinogenesis, and fracture risk must be resolved. If something other than the isoflavone phytoestrogens is producing the mild but measurable health benefits of soy foods, this would considerably help shape the development of dietary guidelines for both adults and children."