Glycine is an amino aid with some pretty interesting effects in the body.  To me, the most interesting effect of glycine is it’s potential for lifespan extension through maintaining flux through the methionine cycle.  In fact, it’s the principal reason I take glycine.

But there are other potential uses for glycine, and one that’s gained quite a bit of interest in the last few years is the ability of glycine to improve sleep.  Two human studies have been done, and both showed taking glycine right before bedtime improves both subjective and objective measures of sleep.

The effect of glycine on sleep is due to its function as an inhibitory neurotransmitter and modulator of N-methyl-D-aspartate(NMDA) receptors.  Decreasing glycine in mice causes a disruption in circadian rhythms and recent evidence indicates that at least part of this effect is due to changes in core body temperature due to NMDA receptor modulation.

There is really no doubt that adequate glycine, through both endogenous synthesis and intake from food, is necessary for circadian synchronization, and thus, high quality sleep.  But there may be a significant drawback to taking it right before bed: An increased risk for certain types of Cancer.

Glycine and Cancer

Serine and glycine are interchangeably converted to one another via the enzyme Serine Hydroxymethyltransferase(SHMT).  Both play a role in providing the basic building blocks for DNA and cellular components required for cellular replication as well as antioxidant defense in healthy and cancerous cells.

Since cancer cells are rapidly replicating cells, many upregulate SHMT activity in the mitochondria to support their speedy growth.  Healthy cells on the other hand, are completely capable of providing themselves with enough glycine to promote replication, they just don’t replicate as much so their glycine needs are lower.

This is such a critical aspect of cancer metabolism that research has focused on selectively inhibiting SHMT in cancer cells.  Inhibition of SHMT decreases cancer cell proliferation and viability in many types of cancer cells, particularly ones that can’t import glycine from the diet.

But not all cancer cells are capable of upregualting SHMT, and those that can’t are more dangerous when dietary intake of glycine and serine are high.  A recent study in mice found that dietary glycine and serine restriction reduced the growth of lymphoma and intestinal cancer cells.

But does this mean a healthy person should restrict glycine from their diet?  I don’t believe so, but I do believe taking glycine at night nay increase the risk of some types of Cancer.

Circadian rhythms, the cell cycle, and glycine

Cellular metabolism and the cell cycle follow a circadian rhythm in healthy human cells.  Cellular replication needs to be separated from cellular metabolism because mitochondrial energy metabolism generates reactive oxygen species that can damage DNA during replication.  Mitochondrial energy metabolism generates more than 90% of the energy for healthy human cells.

This isn’t as much of a problem for cancer cells as they primarily utilize a different type of metabolism called Warburg metabolism.  In Warburg metabolism, energy is generated predominantly through glycolysis in the cytosol and the generation of lactate.  This allows cancer cells to replicate more rapidly.

Cancer cells also inhibit the circadian clock by keeping levels of the clock gene Bmal1 low.  They do this by upregulating the unfolded protein response to suppress BMAL1, which in healthy cells oscillates between high and low to help generate your circadian rhythm with another circadian gene, CLOCK.  Studies have shown that upregulation of BMAL1 suppresses cancer cell growth and proliferation.

This combination of altered metabolism and circadian clock inhibition gives cancer cells a competitive advantage against healthy human cells during certain times of the day.  At some point during the day, your healthy cells want to go offline for maintenance.  But cancer cells just want to grow, and in order to do so they need a constant supply of energy.

This is where I question the use of glycine at night.  One of the primary drivers of circadian rhythms in peripheral tissues is the feeding/fasting cycle.  A 10-12 hour feeding period followed by a 12-14 hour fasting period seems to convey some pretty good medtabolic health benefits, primarily through the regulation of circadian rhythms.  Consuming 3-5g of glycine right before bed may be a bad idea if it’s out of your feeding window as it will extend the window.

Hypothetically, consuming glycine during the day will cause both healthy and cancerous cells to compete for dietary glycine.  However, consuming it right before bed could be problematic if it’s out of the normal feeding window.  For this reason, I recommend glycine be consumed during the day rather than right before bed.

Conclusion

Glycine is an important amino acid with some interesting beneficial effects.  Unfortunately, many people probably don’t consume much of it in their diet, so supplementation may be necessary.

Recent evidence has indicated that taking 3-5g of glycine before bed may help induce sleep.  This effect is mediated by the ability of glycine to function as a neurotransmitter and neuromodulator of NMDA receptors.  However, there may be significant drawback to consuming glycine right before bed, particularly if it’s outside a 12 hour feeding window, due to the potential for increasing cancer growth.

Of course, the cancer data comes from mice while the sleep data comes from humans, so we can’t say for sure whether glycine restriction OR confining glycine consumption to the feeding window reduces cancer risk in healthy humans.  However, it certainly warrants caution in people with a history of Cancer or with known tumors.

That said, people still need to get adequate glycine in their diet.  In my opinion, the best practice for doing that involves consuming glycine earlier in the day, just in case.