Melatonin: the master antioxidant

I want take some time here to delve into what I consider to be the single most important antioxidant in the human body, that's right... melatonin. For those that don't know, antioxidants are a type of binding agent crucial for detox to occur in the body. They bind a group of small yet highly-reactive molecules known as reactive oxygen species (ROS, free radicals). ROS are mostly formed when stray electrons are lost during electron chain transport, a process where a series of proteins carry a current of electrons across the surface of mitochondria to power ATP production. Put simply, antioxidants clean up waste from cell metabolism. There are dozens of antioxidants in the body, even including some nutrients like vitamins C and E. Glutathione is often called the "master antioxidant," but the true master antioxidant is melatonin.

Most people talk about melatonin in the context of sleep, but in reality its effects extend far beyond that. Essentially, there are two different kinds of melatonin use in the body. The first is what most people refer to when they talk about it, pineal melatonin. The pineal gland connects to the eye and is the part of the hormone master regulation system that responds to light (the SCN/PVN/Pineal axis). The second is mitochondrial melatonin. While melatonin produced in the pineal gland is stored, released, then circulated through the bloodstream, mitochondrial melatonin lacks a releasing mechanism and can be synthesized at any time. Researchers used to think that melatonin entered mitochondria from the bloodstream, but recently it was discovered that mitochondria contain all the enzymes needed to synthesize it themselves!

It seems like melatonin and mitochondria go hand in hand. The theory is that originally mitochondria existed as independent bacteria that were absorbed into larger cells and formed a symbiotic relationship with them. Melatonin synthesis likely predates multi-celled life, it is estimated to be more than 2.5 billion years old! It is also found in bacteria, plants, fungi, and animals. Chloroplasts, the organelles in plant cells that photosynthesize, even produce melatonin for the same reason mitochondria do.

You're probably wondering, what makes melatonin so special? There are actually a few things.:

First off it's an extremely simple molecule. The amino acid tryptophan is converted into serotonin, then serotonin is converted into melatonin. I already mentioned that melatonin is an antioxidant, but it's also unique in the fact that it creates what's called an "antioxidant cascade." Basically this means that when melatonin binds to ROS, the compound that's formed as a result is also an antioxidant. When the resulting compound binds up ROS it forms yet another antioxidant, and so on. This means that melatonin can be used as a binder multiple times in a row. Lastly melatonin is amphiphillic, which means that it can travel through both water and lipids. Other antioxidants are either only fat soluble (vitamin E), or only water soluble (vitamin C, glutathione).

Melatonin is produced within the mitochondria so it's constantly on-hand, it diffuses into every part of the cell and mitochondria, and it last longer than any other antioxidant, which (under the right conditions) gives the cell time to synthesize more before it runs out.

But melatonin has other benefits besides being an antioxidant. For one, it actually increases the mitochondria's ability to produce energy. Mitochondria need a state of constant negative charge (redox potential) to function. This essentially works as a storage of excess electrons to fuel the electron transport chain, which the mitochondria uses to pump out protons (positive charge) to create a proton gradient, which powers the synthesis of ATP. Free radicals form when a stable compound has an uneven number of electrons, it seeks to fill it's orbit and binds up electrons, or larger structures like proteins, fats, or DNA. More free radicals = less negative charge. More melatonin = greater redox potential!

Melatonin activates AMPK, a "longevity" factor that may protect against insulin resistance and protect DNA. This same pathway is thought to play a role in some of the benefits of fasting and caloric restriction. This is why you may have seen me say before that carbs themselves aren't toxic, it's when carbs are consumed in excess, especially in the wrong light environment, that they become a problem, but we'll get to that shortly.

Throughout the body, melatonin is also one of the master regulators of the hormone system. Specifically it increases DHEA, the most abundant hormone in the body which is associated with anti-aging benefits by stimulating creation of new mitochondria. Melatonin also downregulates NF-kB, the gene transcription pathway that is the master regulator of inflammation. More melatonin = less inflammation throughout the body.

It even stimulates factors that trigger apoptosis (programmed cell death). Many studies show that higher levels of melatonin are correlated with lower risk of cancer. Melatonin is also one of the most potent protectors against neurodegeneration. It breaks oxidative waste more potently than any other antioxidant in the body by weight, and helps reduce over activation of calcium channels in cell signaling cascades. It's also involved in maintaining proper levels of beta-endorphin and other inhibitory neurotransmitters like GABA released during sleep.

Without proper melatonin release at night, the body has less ability to go through a full sleep cycle, and cerebrospinal fluid detox through the brain's lymphatic system (the glymphatic system) is impaired.

There are dozens more benefits, but now I want to go over how to increase melatonin:

This is actually fairly simple... get as much sunlight as possible, and avoid artificial light.

Red and infrared light stimulate melatonin production. Sunlight averages about 40% red light throughout the day. In the morning and evening the percentage is higher, and it is lowest around noon. One little known fact is that melatonin production actually starts in the morning, in both the brain and mitochondria. In the pineal, melatonin is produced but it is mostly stored until the end of the circadian cycle when it's released in response to the red light from the sunset. In the mitochondria melatonin is produced more in the morning and evening, while production naturally drops slightly in the middle of the day. This drop is small, and creates a manageable amount of oxidative stress which has a hormetic effect on cell function, actually increasing the synthesis of new mitochondria!

Unfortunately for us, artificial light on the other hand contains almost no red light. When lightbulbs were created they were designed to produce the most light with the least electricity required. Over time this has resulted in all our light falling mostly under the blue portion of the visible light spectrum. In nature, blue light is only present paired with red and infrared light in sunlight. Noon is when blue light is highest and even then it's only about 25% of overall light!

Blue light is essentially the antithesis melatonin. It blocks the electron transport chain, while also elevating oxidative stress to the point of damaging mitochondria. The negative effects we see more and more with high carb consumption are a result of the fact that we're eating carbs under blue light, which means the energy can't be managed properly whatsoever. Blue light is a toxic stimulus unless it's paired with red light.

Here's what you can do to protect yourself:

1. Spend as much time as possible outside in the sun. The most important time to get sunlight is first thing in the morning for at least 10-30 minutes. If possible, never miss a sunrise or sunset. There are many benefits of UV light so getting sunlight in the middle of the day is important too. Basically just get outside throughout the day. And yes, even on a cloudy day 30+% of the light still gets through which is more than enough.

2. Start wearing blue blocking glasses when using your computer or phone. Make sure you get a high quality pair, as some of the cheaper options are largely ineffective. They even sell prescription blue blockers for those that wear glasses. Blue light filtering programs can also be used, though just make sure you select a good one (such as F.lux or Iris).

3. Minimize use of glasses outside. All glass (except quartz) blocks almost all beneficial UV and infrared light, reducing it to little more than artificial light. This is why you can't get vitamin D from sitting inside by your window. You need light to touch your skin and enter your eyes, so if you're outside take off your glasses if you wear them. Sunglasses are even worse and ideally should never be worn. If you're driving you can always crack the window or sunroof to let some light in. As we've seen in the double-slit experiment, light is actually non-linear so as long as some full spectrum light gets in, it will be beneficial. You can also wear as little clothing as possible when you're out in the sun for maximum skin exposure.

4. Don't use artificial light at night. Ideally you could spend all day out in the sun, then go to bed shortly after sunset, but if you have to work late or live too far north there are a few different solutions. The best light to use after sunset is firelight, candles, a fireplace, or a homemade oil lamp. All are easy to use and work wonders here. Firelight is primarily red and infrared light, so it stimulates healthy of melatonin production. Your next best option after firelight is a blue light filtered LED (there are many good options on Amazon), or even a combination of blacklight and incandescent bulbs. Incandescents are mostly red light as well, though not quite as much as firelight. Blacklights put off purple and low-level UV light, mildly stimulating beta-endorphin production without impairing melatonin, which also helps you sleep.

If you're dealing with a more severe illness and can't get out of your blue light filled environment, red light therapy is one last option to consider. Red light therapy has been well-studied, and shows tremendous benefits to numerous conditions. Just be aware that red light in this form is essentially a drug and should be treated as such. Everyone will have a sweet spot where they get maximum benefit, but going to far above that may result in negative effects. Each condition has different light requirements, so research carefully before using and if possible consult with a medical practitioner that uses light therapy beforehand. The average usage seems to be around 10-30 minutes upon waking and shortly before bed. Don't overdo it, as too much red light (especially at night) has the paradoxical effect of actually breaking down melatonin!

Note: I don't recommend supplementing melatonin. Some studies suggest that melatonin increases the eye's sensitivity to blue light, so the combination of blue light and melatonin may cause circadian rhythm issues. Supplementing melatonin may also lead to greater levels of serotonin oxidation, which creates more oxidative stress in the nervous system.

While melatonin supplements don't produce tolerance or decrease natural production, they also don't produce the same effect as melatonin produces endogenously in mitochondria, as they aren't able to effectively penetrate every cell in the body.

There are also certain specific disease conditions where high-dose melatonin may be beneficial, but in general it's better to minimize its use and optimize circadian rhythm if possible instead. Weigh the risk/benefit of the disease and decide whether to supplement or not from there.