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23 Nov, 8 tweets, 2 min read
While anemia is a risk factor for hair loss, interestingly enough so is iron overload

One of the first symptoms of hereditary hemochromatosis is hair loss, and this even seems to occur via similar mechanisms to androgenic alopecia
Androgen receptor activation in the scalp seems to trigger hair loss either partially or primarily via a signaling cascade involving TGF-beta

I've found a number of studies linking androgen receptor activation and TGF-beta in general, and they seem to potentiate each other
My impression is that this depends on the tissue the receptor is present in, having more influence in scalp and prostate, but not as much in other tissues

It may even explain why AR activation promotes body hair growth by not scalp hair growth, though this is mostly speculation
Interestingly the higher levels of "free" iron in cases of iron overload are also associated with TGF-beta activation in various tissues, so in some cases hair loss may result from excess iron in the scalp potentiating androgenic effects
Then of course there's all sorts of structural changes in the hair follicles themselves that make hair loss difficult to reverse once it occurs, such as fibrosis that limits blood flow to the follicle, and follicle miniaturization

TGF-beta likely plays some role here as well
Role of TGF-β2 in the human hair cycle
sciencedirect.com/science/articl…
Dermal fibrosis in male pattern hair loss: a suggestive implication of mast cells
link.springer.com/article/10.100…
Iron deposition in skin of patients with haemochromatosis
sciencedirect.com/science/articl…

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More from @ck_eternity_

22 Nov
Alzheimer's disorder is often referred to as a metabolic disorder ("type III diabetes"), but I've come to view it as a circadian disorder

Disrupted circadian rhythm = rapid insulin resistance, combined with inability to clear amyloid plaques with glymphatic function impaired
This is in combination with other factors of course, neurodegeneration doesn't develop overnight

It does raise the question of how crucial of a role melatonin and sunlight play in the prevention of neurodegeneration, I'll link a few interesting articles below
Melatonin regulates Aβ production/clearance balance and Aβ neurotoxicity: A potential therapeutic molecule for Alzheimer's disease
pubmed.ncbi.nlm.nih.gov/33254429/
Read 5 tweets
16 Nov
Normally in undermethylation we see decreased levels of serotonin and dopamine activity at their receptors, since higher levels of DNA methylation can inhibit the reuptake of these neurotransmitters

This "mimics" the effects of SSRIs and DRIs to some extent

(thread)
However this can also be paired with more adrenaline and noradrenaline through a separate mechanism, where methyl groups are required to metabolize adrenaline

Because of this when methyl groups are depleted we see lower levels of metanephrine, an adrenaline metabolite
One of the main causes of niacin toxicity is the depletion of methyl groups, since niacin forms methyl-nicotinamide in the liver

This is paired with more adrenaline/noradrenaline, less betaine (a methyl donor in the liver), and high levels of homocysteine
nature.com/articles/hr201…
Read 13 tweets
16 Nov
Niacin deficieny causes tryptophan to be funneled away from serotonin production into endogenous niacin production

Some of the intermediates in the conversion are neurotoxic, especially quinolinic acid which imitates excess glutamate Image
This is often implicated in schizophrenia pathology

These intermediates are created due to lack of niacin stemming from dietary deficiency or higher demand to drive essential reactions like NAD+ creations
Reducing the formation of quinolinic and kynurenic acids is also one of the mechanisms through which niacin supplementation significantly improves some cases of schizophrenia

This seems to be especially useful in cases of overmethylation
Read 4 tweets
26 Oct
If we look at the structure of cytochrome C oxidase, the rate limiting protein in energy production in mitochondria, it becomes obvious why light is so important

The heme and copper cores act as chromophores absorbing light and using it to excite electron transfer
If we compare the structure of chlorophyll (left) with hemoglobin (right) there is a distinct similarity

Both contain similar structures that harness light to drive redox reactions, this works via the photoelectric effect where the energy of light is transferred into electrons
Cytochrome C oxidase is the last protein in the electron transport chain, which operates by using a current of electrons to drive ATP production

It's absorption peaks in the 630-670nm range, red light, which is the part of the spectrum that penetrates the farthest into the body
Read 6 tweets
25 Oct
It's important to note that with ideal digestion you only absorb something like 60% of the B12 RDI per servings

So for resolving deficiency, sublingual B12 may be necessary, and for maintenance 2-3 meals containing B12 are necessary to prevent deficiency
With bowel inflammation disorders like IBS, B12 absorption is even more impaired

It's also usually necessary to include a combination of oral methylfolate with sublingual B12 to avoid the methyl trap, especially with high doses
For sublingual B12 either the activated methylcobalamin or a combination of the methylated form with adenosylcobalamin works best

Methyl-B12 drives methylation, while adenosyl-B12 is used primarily in mitochondria
Read 4 tweets
15 Oct
Parvalbumin may be another reason for the added benefits from eating whole seafood rather than fish oil

It is produced endogenously, and plays a role in photoreceptor activity, neurogenesis, muscle contraction, memory formation, stress response, and neuroprotection
It does seem to be at least somewhat orally absorbed since it is one of the mediators of fish allergy (but not shellfish)

As long as you're not allergic to seafood however it may still be absorbed but instead may be redistributed into various tissues
Most parvalbumin is likely broken down into amino acids during digestion, similar to what occurs when you take a collagen supplement, but the benefit may be more in providing higher amounts of the same amino acids used specifically for parvalbumin synthesis
Read 5 tweets

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