Melatonin, Genes, and Weight Loss

Color TV has made us fat! Nope, not the commercials advertising fast food at night, nor the fact that we are lying on our couches watching those commercials. The flickering blue light pouring out of almost every window in the neighborhood each evening is fundamentally changing our biology.

My argument goes as follows: obesity started to rise right around 1980 in the US, which coincides with color TV’s being in the majority of homes in the US. Every good argument needs data to back it up, so here is a nice chart from the National Institute of Health webpage showing the increase in obesity and extreme obesity starting just before 1980 in the US:

Yes, I am being a bit sarcastic here with my broad, sweeping statements and reckless use of a chart, but stick with me as I explain how melatonin is made (including why MTHFR may affect melatonin production). I’ll also explain how artificial light at night decreases the production of melatonin — and how all of this ties into negative health consequences, including weight gain.

Table of Contents

Blue light at night negatively affects health

When you start looking at the increasingly strong evidence that blue light at night is messing us up, it starts to make sense that color television sets pouring blue light into our living rooms each night would affect the population as a whole. Currently, people’s exposure to more blue light at night than ever before comes from our phones, tablets, and CFL or LED lights.

There is actually quite a lot of evidence that light in the evening and at night, especially in the blue wavelengths, causes a disruption to our body’s natural circadian cycles. This disruption can cause weight gain as well as more serious metabolic issues. Here are just a few studies from the past couple of years:

A study of 100,000 women in the UK found exposure to light at night–even when addressing all confounding factors–to be associated with obesity.[ref]
A smaller study of elderly Japanese people came to the same conclusion: those exposed to light at night had almost twice the risk for dyslipidemia and obesity.[ref]
An animal study found that longer exposure to light (16 hours vs. 12 hours) significantly increased weight without a change in the amount the animal ate.[ref]
We can reverse obesity in animals by modifying the light period.[ref]
Melatonin modulates obesity by affecting the gut microbiome.[ref]
There is a big link between melatonin levels and type 2 diabetes (more below on the genes involved). A recent animal study reversed type 2 diabetes with a synthetic melatonin receptor agonist.[ref]

There has always been light at night from moonlight, candles, fire, or even incandescent light bulbs. But those light sources all have very little of the short wavelengths of blue light.

The blue wavelengths stop melatonin production for up to 2 hours, so exposure in the evening/night from TVs, tablets, and smartphones delays the onset of melatonin production.[ref] It takes a surprisingly short amount of exposure (15 seconds!) to bright light to delay the onset of melatonin production.[ref]

So what does melatonin do in the body?

Do you wonder why it is such a big deal for melatonin production to be delayed or decreased by light at night? It turns out that melatonin plays a role in several systems in the body.

Melatonin was first isolated from pineal glands in the late 1950s. Eventually, studies associated it with sleep and then followed synthetic melatonin’s first patent for its production as a sleep aid in 1995. Melatonin production is part of our body’s natural circadian rhythm: the level rises at bedtime, peaks around 3 am for most people, and then drops off sharply around 6 am.

Although most often thought of as the sleep hormone, melatonin has many more roles than “just” a good night’s sleep.

It acts as an antioxidant: “It achieves this action via a variety of means: direct detoxification of reactive oxygen and reactive nitrogen species and indirectly by stimulating antioxidant enzymes while suppressing the activity of pro-oxidant enzymes”.[ref]
Melatonin also chelates transition metals such as iron.[ref]
Melatonin plays a role in the circadian rhythms of insulin secretion. The pancreas has melatonin receptors to help insulin get down-regulated by melatonin at night.[ref]

A recent review sums it up “The reduction in melatonin production, as during aging, shift-work or illuminated environments during the night, induces insulin resistance, glucose intolerance, sleep disturbance, and metabolic circadian disorganization characterizing a state of chronodisruption leading to obesity.”[ref]

How is melatonin made?

Melatonin Biosynthesis (public domain, Wikimedia Commons)

The synthesis of melatonin occurs in the body in a four-step process. It starts with the amino acid l-tryptophan, which we can get from a variety of foods. (This is where we get the idea that Thanksgiving turkey (high in tryptophan) makes you sleepy.) Tryptophan goes through a couple of steps to become serotonin. The result of this process lets serotonin become available for use as a neurotransmitter, or it methylates to become melatonin.

So there are quite a few processes in the body that can play a role in your melatonin levels, including eating adequate protein (tryptophan), producing the right amount of enzymes needed in the synthesis, and having adequate methyl groups available for the final step. When all of the processes work optimally, the lack of light at night initiates the final role in melatonin production.

Melatonin Genotype Report:

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Genes involved in melatonin levels:

Some people may be more affected by blue light in the evenings or low levels of light at night — depending on their genes. There is both a genetic component to the amount of melatonin created as well as the interaction with the environmental cues from light.

Period 2 (PER2) and PER3 gene:

A small recent study looked at haplotypes (groups of variants) for the PER2 gene and found that the ancestral haplotype had less suppression of melatonin when exposed to bright light at night.[ref] For this study, 23andMe doesn’t include in their data most of the variants in the haplotype. Interestingly, only those with variants different than the ancestral type were affected by the bright light.

Another study looked at the PER3 gene and found a similar effect.[ref] Those with a longer version of the gene (PER3 5/5) had a significantly greater suppression of melatonin from blue light, while those without the insertion had less of an effect. Those with the PER3 5/5 genotype also were more likely to be morning types. Again, 23andMe data doesn’t cover this variation.

One PER3 variation covered in the 23andMe data is rs228697. The G allele is tied to an evening preference, and the C allele is associated with morning preference. While you might speculate that the C allele here is similar to the PER3 5/5 (morning type, greater suppression of melatonin by blue light at night), there haven’t been any studies that I can find to confirm that.

Check your genetic data for rs228697 (23andMe data v4, v5):

G/G: may prefer to stay up late[ref][ref]
C/G: may prefer to stay up late
C/C: may be more of a morning person

Members: Your genotype for rs228697 is —.

Methylation cycle genes:

The final step in melatonin synthesis involves methylating serotonin. For serotonin to be converted into melatonin, it needs a methyl group. MTHFR plays a big role in the methylation cycle and the production of methyl groups. If you have impairments in the methylation cycle, consider starting there to optimize your ability to create methyl groups. The MTHFR C677T variant decreases the ability to convert folate for use in the methylation cycle. If you carry that variant, you may find that increasing folate in your diet or adding methyl folate supplements would help with melatonin creation. Check your MTHFR variants here.

Melatonin Receptor (MTNR1B):

Melatonin signals through its receptors to downregulate insulin production at night, so it makes sense that a genetic variation in the melatonin receptor would be linked to the risk of insulin-related problems.

rs10830963 (G is the risk allele) linked to a higher risk of type 2 diabetes, gestational diabetes, and fasting glucose levels.[ref][ref] A study published in Cell Metabolism explains that this variant confers “increased expression of MTNR1B mRNA in human islets”.[ref] There is an excellent article on this variant at Dan’s Plan blog. One study notes: ” it is intriguing that we and others have found that a variant of the MTNR1B gene is associated with elevated plasma glucose levels, a reduction of the early insulin response to both oral and intravenous glucose, a faster deterioration of insulin secretion over time, and increased future risk of T2D”.[ref]

A recent randomized, cross-over trial found that “The concurrence of meal timing with elevated endogenous melatonin concentrations resulted in impaired glucose tolerance. This effect was stronger in MTNR1B risk carriers than in non-carriers.[ref] Furthermore, eating late significantly impaired glucose tolerance only in risk carriers and not in the non-risk carriers.”

Another recent study that looked at different types of diets (high fat/low carb, low fat, high protein, etc.) found that for those in the low-fat group, carriers of the rs10830963 G allele had a greater total reduction of cholesterol (LDL) levels.[ref]

Check your genetic data for rs10830963 (23andMe data for v4, v5):

G/G: linked to a higher risk of diabetes, increased fasting glucose – don’t eat dinner late
C/G: linked to a higher risk of diabetes, increased fasting glucose – don’t eat dinner late
C/C: typical

Members: Your genotype for rs10830963 is —.

AANAT gene:

The alkylamine N-acetyltransferase (AANAT) gene controls the rhythmic production of melatonin by the pineal gland.

rs28936679 (A is the risk allele) -A rare variant that causes delayed phase sleep disorder (Japanese study)[ref]

Check your genetic data for rs28936679 (23andMe data for v4 only):

A/G: may cause delayed phase sleep disorder
G/G: typical

Members: Your genotype for rs28936679 is —.

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Color TV has made us fat: melatonin, genetics, and light at night