I've been digging more into the connections between the "big three" sex hormones (testosterone, estrogen, and progesterone), and glutamatergic disorders like epilepsy
Interestingly, androgens like testosterone and DHT are actually anticonvulsant, which seems counterintuitive since they increase force production

This seems to result from their conversion into the neurosteroids androsterone and 3a-androstenediol which increase GABA sensitivity
Progesterone is also anticonvulsant as a result increased neurosteroid production, most notably allopregnanolone, but to lesser extent other dihydroprogesterone derivatives
Much to my surprise, estrogen is actually glutamatergic in excess despite its ability to increase serotonin, which is generally acts as an inhibitory neurotransmitter
That said, I think it's safe to extrapolate that the effects of chronically low estrogen are equally glutamate-driven given the reports of side effects like anxiety during heavy aromatase inhibitor use and hypogonadism

In general it seems to work best in balance
There's also an interesting interplay between progesterone and estrogen where progesterone seems to increase estrogen receptor sensitivity and downstream effects

This does not seem to be enough to cancel out its own anticonvulsant effects from what I've seen though

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More from @ck_eternity_

11 Oct
The idea that free radicals = bad and antioxidants = good is a major oversimplification

When we talk about redox state it's not just about maintaining as little oxidation as possible, but rather keeping an appropriate balance in place between reduction and oxidation

Chemistry 101:

Put simply, oxidation refers to any chemical reaction involving the loss of an electron, when something is oxidized it just means that one of its electrons is transferred to another molecule
Reduction is the inverse of this, a molecule or atom gaining an electron from another molecule or atom

As you can see, it's impossible for reduction to occur without oxidation, and vice versa, hence the shorthand "redox" refers to this category of reactions
Read 16 tweets
9 Oct
The idea of a "debate" around CICO is pretty ridiculous, in the sense that the role that thermodynamics plays in metabolism is well-established and agreed on by everyone

What we're actually seeing is a shift in emphasis away from calories in and more towards calories out
What I mean by this is that more and more nutritionists seems to be recognizing the error in the initial premise of the amount of calories eaten being the only significant factor in weight gain/loss

This is obvious in cases like hypothyroidism, etc, where metabolism is impaired
This isn't a new idea or mutually exclusive with CICO, just a shift in emphasis from one side of the equation to the other

I think most everyone would agree that the amount of food you eat matters, but also that lack of exercise, hormone imbalance, etc, can impair weight loss
Read 8 tweets
7 Oct
If I had a few million $ to allocate towards developing an herb into a medical therapy, conducting clinical trials on it, etc, I would choose bacopa

Specifically, the possible role of bacopa extracts in improving epilepsy long term
I've reviewed hundreds of rodent and human studies on various herbs and the potential benefits of bacopa in epilepsy have always stood out to me as being some of the most promising, yet the relevant human data seems to be totally lacking
When we consider the role that GABA/glutamate imbalances play in nearly every mental illness and neurodegenerative disorder, the potential applications of these herbs is extensive
Read 4 tweets
3 Oct
N-acetylserotonin, the chemical byproduct of serotonin and precursor to melatonin, acts as an agonist of the TrkB receptor (the same receptor that BDNF activates)

This is another interesting pathway by which MAO inhibition may enhance the actions of neurotrophic factors
Increasing serotonin is also known to raise BDNF levels itself via activation of various serotonin receptors, we see this in SSRI's and other serotonergic supplements/drugs

This pathway could replicate a portion of these effects even if serotonin is not increased significantly
Mostly I find this interesting in the context of beta-carboline containing herbs which act as mild reversible MAO inhibitors, like ginseng or polygala

Most herbs with these properties behave well in rodent metrics of increasing neurogenesis
Read 5 tweets
2 Oct
I think I've found the mechanism behind the reports psychedelics reversing anosmia in some cases, I'll post the studies below

There's a strong association in rodent studies between the neurogenesis growth factors NGF and BDNF in creating new olfactory neurons
Psychedelics are known to increase these growth factors to what seems to be a remarkable degree, perhaps even lasting months after exposure

It seems that the elevated level of these growth factors improves healing of this segment of the nervous system
Hypothetically you could use foods and herbs which are also known to increase BDNF and NGF instead if you aren't comfortable or able to use psychedelics

If anyone has tried this I'd love to hear your experience so far
Read 8 tweets
2 Oct
Yep, though it is possible to reverse this

I had a client recently that mentioned he would feel sick for 2-3 days if he ate junk food after just a few months following my dietary framework, when he before used to eat these foods daily
The key is cutting out hyper-palatable processed foods

These include fried foods, processed grains, iron-fortified foods, and foods with a lot of added sugar

For some individuals cutting out (cow) dairy may be necessary as well
Interestingly I've seen kefir have a significant impact on both reversing food sensitivity and helping individuals rebalance after cutting out problem foods

I believe this has something to do with the interaction of probiotics like L. casei with regulatory T cells
Read 4 tweets

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