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Bryce Hanna

@photobiogenesis

Mar 29

Sleep is perhaps the most reducing (or antioxidant) process in the body

The glymphatic system uses CSF flow to detox oxidative neurotransmitter waste, homocysteine, oxidized lipids, amyloid plaques, lactate, excess glutamate, etc

This is paired with a diffusion of melatonin that stabilizes redox and energy metabolism pathways

Melatonin has two properties that make it uniquely important compared to other antioxidants released during sleep

It is amphiphilic, meaning it is soluble in both lipids and water, allowing it to operate in both membranes and cytosol

It also generates an "antioxidant cascade" where byproducts of its oxidation act as antioxidants themselves, giving it a unique ability to work as a multi-use antioxidant or electron donor

Both glymphatic detox and melatonin release are coordinated by light

THREAD //

Blue and green light (which are predominant in "cool" energy-efficient LED and fluorescent lights) are the frequencies that are most suppressive of melatonin release

The ideal way to promote healthy melatonin release is avoiding bright artificial light after sunset, your light environment should be as dark or dim as possible

You can also use selective modulation like blue-blocking glasses or blue-blocking LED bulbs, but these are secondary to darkness and a low-stim environment

What you do during the day matters as well

Bright light in the morning will shift circadian hormone peaks like cortisol and testosterone forward, leading to melatonin being released earlier as well

Perhaps the most underrated aspect of glymphatic system function is the impact of breathing on it

If we look at how waste in the cerebrospinal fluid is actually removed from the brain, it travels into a combination of lymphatic drainage and the bloodstream

CSF is cleared along the carotid artery, within the perineural space of vagal and olfactory nerves, and into the dense lymphatic network of the nasal submucosa

This means that blood flow to the brain, oxygen tension, and breathing all impact CSF drainage

Specifically nasal breathing is ideal, as it creates higher oxygen tension and increases CO2 levels in the blood and brain

Read 13 tweets

Bryce Hanna

@photobiogenesis

Mar 17

I've had a renewed interest in creatine recently, it's one of only a handful of supplements I've been taking

Both creatine and thiamine have the ability to support the ATP/ADP ratio by donating extra phosphate groups to turn ADP back into ATP

This means creatine acts as a "phosphate sink" where at any given time 60% of it is in the creatine phosphate form

When ATP levels begin to fall in cell stress, hypoxia, and high metabolic demand creatine opposes the loss of ATP

The interesting thing is that some of the benefits of taking glycine may actually be a result of its role in creatine synthesis

Animal research shows that higher glcyine intake produces higher creatine levels in tissue, and it almost certainly works the same in humans

Glycine is converted into guanidinoacetate, which is then methylated into creatine

This intersection with methylation is extremely important

The enzyme GAMT is the single biggest consumer of the cardinal methyl donor SAMe, so if methylation is impaired creatine synthesis is too

Read 7 tweets

Bryce Hanna

@photobiogenesis

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)

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

@photobiogenesis

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

https://twitter.com/photobiogenesis/status/1823130259287392382

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

https://twitter.com/photobiogenesis/status/1823130259287392382

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

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Bryce Hanna

@photobiogenesis

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

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

@photobiogenesis

Sep 8, 2024

https://twitter.com/hezerminator/status/1832895070439080308

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

https://twitter.com/hezerminator/status/1832895070439080308

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)

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