Healthy Skeptics Newsletter 
By Stephen Cherniske

“If people knew better, they’d do better.”

What you need to know about DHEA and Brain aging.

I’m going to try a different approach with this newsletter. Instead of the normal instructional narrative, I want to try a logic path, starting with established facts, then leading to a reasonable hypothesis. As always, each step will be supported by one or more references from the biomedical literature.

1. DHEA, testosterone, estradiol, progesterone and allopregnanolone) are known as sex steroids. Note: estradiol and estrone are two of the three classes of estrogen. 

2. These hormones are responsible for protecting and repairing the brain and peripheral nervous system.

3. The brain synthesizes DHEA and has a number of critical effects that are considered both neuro-protective and neuro-regenerative. In fact, DHEA is the only molecule that, when added to a cell culture, can cause brain stem cells to differentiate into fully-functioning neurons: [1]

4. DHEA is considered to be the primary neurosteroid, because, aside from its molecular activity, DHEA can be converted to other neurosteroids including testosterone, estradiol and estrone. For women after menopause, DHEA is the only source of these critical hormones.

5. The synthesis of all neurosteroids declines with advancing age. Importantly, the downward curve becomes steeper with every decade after age 30. The average 70 year-old produces only 15% of the DHEA they produced at age 25.

6. Considering the obvious adverse consequences of declining neurosteroid production, conventional medicine ignored DHEA and instead, turned to supplementing with estrogen and synthetic progestogens. Hormone replacement therapy (HRT) was embarked upon in the 1990‘s with the goal of helping women maintain bone density, cardiovascular health and neurosteroid levels.

7. In 2002, evidence from the Women’s Health Initiative (WHI) suggested that HRT increased a woman’s risk for blood clots, stroke and breast cancer. The knee-jerk reaction (STOP HRT!) sent panic throughout the world, leaving more than a million women and their doctors looking for guidance. It never came. Even today, women face a baffling array of conflicting advice regarding HRT, most of it falling in the category of “You were never intended to live this long, so learn to live with rapidly declining health after age 50. Sorry Hon.”
8. Do we know why HRT might have increased risk for breast cancer, stroke and blood clots? One important consideration is that the drugs, including synthetic progestogens, (not bioidentical progesterone) raised systemic levels of “bad” estrogens, which stimulated cell proliferation in tissues with estrogen receptors, including the breast and endometrium.[2]

9. So, what about using DHEA, a 100% natural hormone replacement that does NOT raise systemic levels of any sex steroid? This option was never widely considered. Why? As a natural molecule, DHEA cannot be patented. Thus no billion dollar profits. Thus a conspiracy of silence that continues to this day.

10. I know that’s a lot to take in. If you discuss this with your conventional doctor, be prepared to hear them say that DHEA carries the same risk as HRT. It does not. How do we know? Studies with human volunteers show that a 50 mg daily dose of DHEA does not elevate systemic or blood levels of estradiol.[3]

So when DHEA is consumed at a physiological dose (10 to 50 mg/d for women), there is no worrisome increase in cell proliferation in her breasts, uterus or endometrium.[4] [5]

In other words, we now know that conversion of DHEA to sex steroids takes place in tissues with high repair needs (eg brain, bones), on an as-needed basis, through an inherent self-regulating activity.

I’m going to say this again. The repair and regenerate benefits of DHEA come from local (or peripheral) anabolic activity such as was recently demonstrated in the journal, Mechanisms of Ageing and Development. This important study utilized genomic technology to reveal that DHEA improves bone density, not by raising systemic levels of estradiol, but through local conversion to estrone by osteoblasts. Again, DHEA is converted by repair cells in the bone to estrone… which does not promote cancer, while leaving estradiol levels in the breast and uterus unchanged.[6]

Tying it all together:

1. Women have roughly twice the incidence of Alzheimer’s disease compared to men. You now know why, even though your doctor probably doesn’t.[7]

1. You also know one important step that you can take to maintain youthful levels of neurosteroids for the protection and regeneration of your brain.[8]

1. You can monitor your DHEA level with a simple blood test. Tell (do not ask) your doctor to include serum DHEA Sulfate (DHEAS) in your annual blood chemistry. You can also have this tested without the need of a doctor’s requisition. Here are two easy-to-use options.

* https://www.lifeextension.com/lab-testing/hormones

* https://www.anylabtestnow.com/

Note 1: Your goal is to stay in the optimum range. For women, you’re looking for a DHEAS level from 200 to 350 mcg/dL. For men, optimum DHEAS is 350 to 500 mcg/dL.

Note 2: Do not take any DHEA for 12 hours before the blood draw. 

1. DHEA is not a magic bullet. Diet and lifestyle are critical co-factors, but it is reasonable to say that no diet, supplement program or exercise will effectively reduce your risk for dementia if your DHEA levels are declining.

And finally, is there an optimal DHEA formulation?

Natalie and I created Synergized DHEA for Men and Synergized DHEA for Women, based on the latest research showing remarkable benefits from DIM (diindolylmethane) and alpha lipoic acid. The Women’s formula also provides Chaste Tree Berry extract. Details on these companion ingredients can be found here: https://my2048.com/alpha-lipoic-acid-ala/

References:

1. Shiri EH, Mehrjardi NZ, Tavallaei M, Ashtiani SK, Baharvand H. “Neurogenic and mitotic effects of dehydroepiandrosterone on neuronal-competent marrow mesenchymal stem cells.” Int J Dev Biol. 2009;53(4):579-84.
2. Cagnacci A, Venier M. “The Controversial History of Hormone Replacement Therapy.” Medicina (Kaunas). 2019 Sep; 55(9): 602. doi: 10.3390/medicina55090602
3. Arlt W, Callies F, van Vlijmen JC, et al. “Dehydroepiandrosterone Replacement in Women with Adrenal Insufficiency.” N Engl J Med 1999;341:1013-20.
4. Baulieu EE, Thomas G, Legrain S et al. “Dehydroepiandrosterone (DHEA), DHEA sulfate, and aging: contribution of the DHEAge Study to a sociobiomedical issue.” Proc Natl Acad Sci U S A. 2000 Apr 11;97(8):4279-84.
5. Nair KS, Rizza RA, et al. “DHEA in elderly women and DHEA or testosterone in elderly men.” N Engl J Med. 2006 Oct 19;355(16):1647-59.
6. Takayanagi R, et al. “DHEA as a possible source for estrogen formation in bone cells: correlation between bone mineral density and serum DHEA-sulfate concentration in postmenopausal women, and the presence of aromatase to be enhanced by 1.25-dihydroxyvitamin D3 in human osteoblasts.” Mech Ageing Dev 2002; 123:1107-14.
7. https://www.alzheimers.org.uk/blog/why-dementia-different-women#:~:text=Women%20have%20a%20greater%20risk,risk%20factor%20for%20this%20disease.
8. Maninger N, Wolkowitz OM, Reus VI, Epel ES, Mellon SH. “Neurobiological and neuropsychiatric effects of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS).” Frontiers in Neuroendocrinology Volume 30, Issue 1, January 2009, Pages 65-91.