A Neurosurgeon’s Take On Melatonin

New to Melatonin? Read my blog post on melatonin here.

The below is Neurosurgeon Jack Kruse‘s take on Melatonin. And he’s a super clever guy…

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Molly and Dylan said, “Consider the following: melatonin is made in the eye in the morning”.

But the common wisdom is that melatonin is made in the pineal gland at night.

What gives? Are we being bamboozled by the melatonin lobby? 

Not exactly. It’s a complicated story that has huge implications for one of the best circadian rhythm and sleep hacks you MUST DO every gosh-darn day on planet Earth.

First, you need to step your game up on your understanding of what melatonin is.

It is a hormone much like testosterone and cortisol. This means that melatonin is made and then has actions elsewhere… but also locally (we’ll get to that in a second!)

It is both soluble in fat and water. That means that melatonin will go through cell membranes (which have a lot of fat) and then into your blood (which is mainly water).

The implication of this is that as soon as melatonin is made is going to travel elsewhere like a 16-year-old with wanderlust. It ain’t sticking around where it was made UNLESS it is being used up locally.

That’s why it isn’t made in the eye in the morning per se… (but this statement is still accurate… more below)

First and foremost, melatonin is an anti-oxidant.

Long ago (like before your parents met) the Sun was increasing in strength and there was more oxygen on planet Earth.

This changed Earth from a relatively “mellow” primordial soup to a harsher environment. Things were getting oxidized left and right by oxygen and UV light. Life had to come up with a kick-butt anti-oxidant to offset this new environment.

As evolution would have it, melatonin was made to do the job. (1)

Melatonin is the Hulk of anti-oxidants. It smashes everything (that’s oxidizing you). Your mitochondria produce a poop-load of oxidants (that’s not cool man!).

It produces superoxide, hydrogen peroxide, hydroxyl radical, nitric oxide, and peroxynitrite. Yikes.

Luckily melatonin can control the “fire” caused by all these oxidants. (2) And, melatonin is far more effective than vitamin C, Vitamin A, Vitamin E, and glutathione as an anti-oxidant (3-5).

There are some major implications for what you just read. You make the optimal amount of melatonin when you get good sleep and have a circadian rhythm that helps you produce your own melatonin.

Thus, the best “anti-oxidant” you can take is 7-9 hours of AWESOME sleep.

Not some supplement Dr. McShmuck is trying to sell you.

The other implication of the relationship of melatonin and anti-oxidants is huge…
Like I’m talking enormous… giant… perhaps even ginormous.

You may have spotted an interesting relationship between melatonin and mitochondria.

1. When melatonin is made, it either travels somewhere else… or stays local and is used up.
2. Melatonin counterbalances acts inside the mitochondria (the powerhouse of oxidants).
3. So, is all the melatonin in mitochondria from the pineal gland? Or is it from somewhere else?
4. Ah, excellent question Circadian Jedi!

In 1958, an America Dermatologist was removing cow pineal glands (like any self-respecting dermatologist would) to see how melatonin levels would change.

Obviously, there should be no melatonin left anywhere in the body…

Melatonin was still present in the blood 😱 (6)

What 🤔 ?!?!?

Where is the melatonin coming from???

As life would have it… melatonin is EVERYWHERE.

Melatonin is made in your:

• Eye (lens, retina, and ciliary body, 7)
• Inner ear (8)
• Thymus (9)
• Immune cells (the highest concentration of any cell; 10)
• Gut (there is 400 times more melatonin in your gut than your pineal gland, 11)
• Microbiome (12)
• Ovaries and testes (13)
• Seriously, whatever organ you can name, melatonin has been found to be made there without the pineal gland present… (14)

Melatonin is not just from your pineal gland… so where is it from?

💣Melatonin Truth Bomb Time💣

Melatonin is made in your mitochondria! (15-17)

🤯🤯🤯🤯

That means if you have better mitochondria… then you make more melatonin! Not only do you stave off pretty much every disease known to man, you also get better sleep!

This also explain how people with conventionally defined mitochondrial diseases have poor sleep (18). This would imply that “high heteroplasmy rates” (aka a lot of bad mitochondria) lead to poor sleep.

So, if you do things for your mitochondria… you’re doing big things for sleep!

Another implication of this relationship between melatonin as an antioxidant is that being under oxidative stress would enhance melatonin production.

The most important example being ultraviolet (UV) light that triggers the eventual production of melatonin by triggering anti-oxidant defense mechanisms (19).

This brings us to the 2nd role of melatonin, a conductor of the circadian rhythm trained by UV light in the eye.

Melatonin not only resets your oxidation status, it also resets the “clocks” throughout your body. Long story short, it acts on genes and proteins involved in your molecular circadian clocks (20). Melatonin is controlled by the original clock: the SUN!

UV light in your eye determines your circadian rhythm and your production of melatonin!!!

Look at the biochem chart below:

Melatonin production starts with tryptophan.

The more energy tryptophan has, the faster it can make it to melatonin.
UV light gives tryptophan more energy. (21)

UV light also sets the “rhythm” to produce melatonin via neuropsin (OPN5) (22).

In the short term, this leads to more serotonin available (tryptophan goes to serotonin before melatonin) (23). In fact, natural light exposure in someone’s eye increases serotonin by itself likely for this mechanism.

Altogether, these set the stage of your “nighttime melatonin casserole.”
UV light in your eye helps you make a bunch of serotonin (the ingredients) and set the circadian rhythm (set the temperature and time on the oven).

The result is that at night time, your melatonin making enzymes in your pineal gland turn on and this allows for the massive conversion of serotonin to melatonin!

Hence, melatonin is “made” in your eye in the morning via UV light.

That’s why you must get UV light on your eyeballs every single day to make the most melatonin possible.

It’s simple.

Go outside between 9AM and Noon (if you want to be fancy, UV light is available as soon as the UV index = 1

Exposure your naked eye to unfiltered sunlight (no glasses, contacts, windows, cats, etc.)

Get at least 3 minutes.

Note: you don’t need to stare at the Sun, just being outside will do the trick!

Congrats, you’re now a melatonin expert!

References:

1. Tan DX, Hardeland R, Manchester LC, et al. The changing biological roles of melatonin during evolution: from an antioxidant to signals of darkness, sexual selection and fitness. Biol Rev Camb Philos Soc. 2010;85(3):607-23.
2. Reiter RJ, Rosales-corral S, Tan DX, Jou MJ, Galano A, Xu B. Melatonin as a mitochondria-targeted antioxidant: one of evolution’s best ideas. Cell Mol Life Sci. 2017;74(21):3863-3881.
3. Lopez-Burillo, S., Tan, D. X., Mayo, J. C., Sainz, R. M., Manchester, L. C., and Reiter, R. J. Melatonin, xanthurenic acid, resveratrol, EGCG, vitamin C and alpha-lipoic acid differentially reduce oxidative DNA damage induced by Fenton reagents: a study of their individual and synergistic actions. J Pineal Res 2003;34(4):269-277.
4. Montilla-Lopez P, Munoz-Agueda, MC, Lopez M, et al. Comparison of melatonin versus vitamin C on oxidative stress and antioxidant enzyme activity in Alzheimer’s disease induced by okadaic acid in neuroblastoma cells. Eur J Pharmacol. 9-20-2002;451(3):237-243.
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17. Sakaguchi K, Itoh MT, Takahashi N, Tarumi W, Ishizuka B (2013) The rat oocyte synthesizes melatonin. Reprod Fertil Rev 25:674–682
18. Ramezani RJ, Stacpoole PW. Sleep disorders associated with primary mitochondrial diseases. J Clin Sleep Med. 2014;10(11):1233-9.
19. Kleszczyński K, Hardkop LH, Fischer TW. Differential effects of melatonin as a broad range UV-damage preventive dermato-endocrine regulator. Dermatoendocrinol. 2011;3(1):27-31.
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