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Bryce Hanna Profile picture
@photobiogenesis
Mar 6, 2021 • 12 tweets • 3 min read • Read on X
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Melatonin research (thread):

Melatonin is my favorite molecule in the body, it regulates circadian rhythm, the immune system, and gene expression, and acts as a antioxidant within both cells and mitochondria
This is a collection of a few of my favorite studies on melatonin, specifically focused on endogenous function and production

I'll be adding more over time
Mitochondria: Central Organelles for Melatonin′s Antioxidant and Anti-Aging Actions
ncbi.nlm.nih.gov/pmc/articles/P…
Melatonin: A Versatile Protector against Oxidative DNA Damage
ncbi.nlm.nih.gov/pmc/articles/P…
Melatonin, a Full Service Anti-Cancer Agent: Inhibition of Initiation, Progression and Metastasis
ncbi.nlm.nih.gov/pmc/articles/P…
Aging, Melatonin, and the Pro- and Anti-Inflammatory Networks
ncbi.nlm.nih.gov/pmc/articles/P…
Melatonin: Buffering the Immune System
ncbi.nlm.nih.gov/pmc/articles/P…
Immune‐pineal axis – acute inflammatory responses coordinate melatonin synthesis by pinealocytes and phagocytes
ncbi.nlm.nih.gov/pmc/articles/P…
Melatonin in Medicinal and Food Plants: Occurrence, Bioavailability, and Health Potential for Humans
ncbi.nlm.nih.gov/pmc/articles/P…
Melatonin: a possible link between the presence of artificial light at night and reductions in biological fitness
ncbi.nlm.nih.gov/pmc/articles/P…
Melatonin, mitochondria, and the skin
ncbi.nlm.nih.gov/pmc/articles/P…
Melatonin and the Optics of the Human Body
melatonin-research.net/index.php/MR/a…

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More from @photobiogenesis

Bryce Hanna Profile picture
Mar 5
The idea of digestion affecting mental state is reaching a point of being common knowledge

However the gut's neural network is not a "second brain" but a "third brain," as after the CNS the heart and circulatory system have the second most neurons

So in the same way that the gut microbiome and its metabolites alter brain activity, circulation issues can as well

(thread)Image
One of the best examples of this is "biofeedback"

Anxiety involves increased heart rate, but artificially elevating heart rate can also lead to the perception of anxiety

This isn't just the brain noting the heart rate but instead the fact that the same factors that regulate heart rate are those that regulate anxiety

Adrenaline, noradrenaline, glutamate, and elevated calcium are all involved here
These factors seem to be communicated directly between the heart/circulation and brain at all times

Beyond that, blockages in circulation intimately affect the brain

Calcification, arterial plaque, and amyloid fibrils all impact cognitive function by changing blood flow
Read 16 tweets
Bryce Hanna Profile picture
Sep 13, 2024
Idebenone is an interesting quinone that may be useful in Parkinson's disease

It's an analog of CoQ10 (another quinone) but while CoQ10 binds to complex I to transfer electrons to complex III idebenone can bypass CI and move directly to CIII

It's also a membrane antioxidant Image
Complex I blockage is one of the main underlying drivers of Parkinson's disease

It creates metabolic issues in dopaminergic neurons and has been shown to to elevate neurotoxic dopamine wastes

The main downside is that idebenone does not unblock complex I itself
Quinones in general do have some ability to improve complex I through the enzyme NQO1

As both pro-oxidants and antioxidants quinones activate a suite of antioxidant enzymes by stimulating Nrf2

This include NQO1 or quinone reductase
Read 6 tweets
Bryce Hanna Profile picture
Sep 11, 2024
GDNF is a brain growth factor that regulates growth of various neurons, but is particularly targeted toward dopamine

It's considered promising for the treatment of addiction and Parkinson's disease

Let's look at a few ways to stimulate it Image
In addiction, things that increase dopamine have a tendency to increase GDNF in the short term while downregulating it during withdrawal

This is true for alcohol, nicotine, drugs, etc

The psychedelic ibogaine, used in addiction therapy, may work partially by increasing GDNF
I think in general neurogenesis tends to be downregulated in drug withdrawal and mental health disorders, and supporting it can help alleviate symptoms

GDNF also promotes differentiation of kidney and pancreas cells, and may regulate fertility in men

Beyond dopamine it also promotes development of noradrenergic, cholinergic, GABAergic, and motor neurons in certain brain regions
Read 9 tweets
Bryce Hanna Profile picture
Sep 8, 2024
Brain normally runs on glucose (more than 50%), under cognitive exertion energy demands outpace oxygen availability and lactate shuttled into neurons from glia becomes the dominant energy source (50-60%)

Lactate also represents the point of "high cognitive load" and fatigue
Now while I don't believe lactate is responsible for exercise-induced fatigue on its own, it does play a role in cognitive fatigue


The point where anaerobic metabolism is reached "indicates that a cognitive task has reached the limits of complexity for a given individual"


Beyond that, it's been suggested that one of the main features of intelligence is better use of glucose by the brain
ncbi.nlm.nih.gov/pmc/articles/P…
sciencedirect.com/science/articl…
static1.squarespace.com/static/538634a…
Now this doesn't mean that lactate is necessarily toxic, this depends more on glial activity (inflammatory vs. stabilizing)

However lactate is one of the main stimuli for long term potentiation (formation of new connection) and neurogenesis (brain growth/repair)
Read 6 tweets
Bryce Hanna Profile picture
Sep 6, 2024
I have a theory that a LOT of sleep issues in babies and young kids are a result of bright artificial light before bed and in the middle of the night (when nursing, etc)

I plan to avoid night-lights and artificial light at night with my children as much as possible
I think there's a spectrum to this, and I'd rather use a dim night-light than turn on overhead lights, but neither is ideal

Blue-light filtered bulbs could be used as well

There's a growing body of research that supports the idea that artificial light at night harms children
Sensitivity of the circadian system to evening bright light in preschool‐age children


This study found a ~90% drop in melatonin for 20-50 minutes after exposure to bright light in the evening, though they didn't use complete darkness afterward ncbi.nlm.nih.gov/pmc/articles/P…
Image
Read 7 tweets
Bryce Hanna Profile picture
Sep 6, 2024
Black walnut is one of the most common ingredients in "candida cleanses" and blends meant to reverse SIBO

Similar to black seed oil, it also contains an active quinones, in this case the compound juglone, lawsone, and plumbagin

Quinones are pro-oxidants that break down biofilms and have toxic effects on pathogens, while promoting antioxidant pathways and chelating heavy metals in humans and higher animalsImage
Thymoquinone, juglone, and other quinones all cross the blood brain barrier

They break down amyloid and tau aggregates in animal models of Alzheimer's, likely through their intercalation into the protein, and the removal of free iron and copper that trigger aggregation
I believe quinones are our best bet at beating neurodegeneration as they target it at multiple levels:

- reducing gut dysbiosis and killing endotoxin-producing bacteria
- stimulating endogenous antioxidant release via the Nrf2 pathway
- by crossing the blood brain barrier and binding and removing free iron
- by shifting NAD+/NADH ratio through activating the NQO1 enzyme
Read 4 tweets

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