This is a tale of two chemicals — one excites, while the other relaxes our brain.
Our brain has so many types of neurotransmitters floating about, all signalling our neurons to do something here or there.
Glutamate is no stranger to neurotransmission — it is an amino acid that we can obtain from proteins in our diet, or from the popular flavouring condiment that we know as monosodium glutamate (MSG). In fact, glutamate is an excitatory neurotransmitter, and as this article states,
glutamate has excitatory effects on nerve cells, and that it can excite cells to their death in a process now referred to as “excitotoxicity”. This effect is due to glutamate receptors present on the surface of brain cells. Powerful uptake systems (glutamate transporters) prevent excessive activation of these receptors by continuously removing glutamate from the extracellular fluid in the brain. Further, the blood–brain barrier shields the brain from glutamate in the blood. The highest concentrations of glutamate are found in synaptic vesicles in nerve terminals from where it can be released by exocytosis. In fact, glutamate is the major excitatory neurotransmitter in the mammalian central nervous system.
Glutamate binds onto glutamate receptors on the surfaces of brain cells to excite them. In this way, our brain cells are able to operate better when we’re awake and in an “excited” state with the aid of glutamate.
However, we don’t want that much glutamate in our brain at night.
Because an excited brain makes it difficult to go to sleep.
I don’t know about you, but I’ve experienced sleepness nights where my brain was in overdrive thinking about something, and those niggling thoughts just wouldn’t go away. The neurons were firing and I was finding it difficult to sleep.
The balancing effect on glutamate
Interestingly though, our brain is able to regulate a healthy balance between wakefulness and restfulness by fiddling around with the levels of glutamate in our brain. Our brain cells do have the ability to synthesise glutamate decarboxylase (GAD) enzymes, which are capable of converting glutamate to γ-aminobutyric acid (GABA). A necessary cofactor, pyridoxal-5-phosphate (also known as Vitamin B6) supports the conversion of glutamate to GABA.
GABA is a neural inhibitor — where glutamate excites the brain, GABA helps to calm down the brain. Hence, some people who do experience sleeping difficulties may turn to GABA supplements as an option to get better sleep.
But really, what we’re looking at is a BALANCE, as always.
In my previous articles on inflammation and osteoporosis/osteoarthritis, I keep stressing on the concept that we’re supposed to be balancing out both sides of the equation.
In the case of glutamate and GABA, we’re looking at balancing out their concentrations in the brain properly, so that we can sleep and rest our brain when we ought to sleep and rest our brain, or that we can be awake and using our brain when we’re supposed to be awake and using our brain.
The balance therefore hinges on the ability of the brain’s GAD enzymes to do a proper conversion of glutamate to GABA. If we aren’t able to sleep properly, then what’s going on with the glutamate to GABA conversion?
Perhaps we’re consuming too much MSG in our diet?
Perhaps we’re not consuming sufficient Vitamin B6?
Perhaps we have insufficient GAD activity?
Or… could there be something else, even?
It’s highly possible.
As I do explore in How Does A Lack Of Sleep Affect Our Ability To Function?:
This article summarises the biochemistry in our body as we sleep:
In the dark, norepinephrine is released by the superior cervical ganglion to stimulate the pineal gland in the brain to release melatonin into the blood. The pineal gland synthesises melatonin sequentially from the amino acid tryptophan, which is converted into serotonin as an intermediate. All of this activity (and our circadian rhythm) is regulated by the suprachiasmatic nucleus in the brain.
When this circadian rhythm is not well regulated, as mentioned in this article:
Disruptions of circadian rhythms are associated with mood disorders and serotonin has been implicated in their pathophysiology.
When serotonin is implicated, the subsequent synthesis of melatonin will be affected too.
Could it be a problem with melatonin production? Yes it could, hence melatonin supplements are also considered for people who are experiencing sleeping difficulties.
The crucial thing to note here is…
Our sleep quality is dependent on multiple factors. As I also did discuss in How Does A Lack Of Sleep Affect Our Ability To Function?:
In the presence of an injury, where there is acute inflammation, the pineal gland (PG) releases less melatonin, the neuro-modulator that contributes to our ability to sleep — and that is one of the reasons why we find it more difficult to sleep properly when we are injured or sick. The immune cells are stimulated to release their own melatonin into the tissues, as melatonin is both a potent antioxidant and anti-inflammatory. When the inflammation signal is resolved, the PG starts producing melatonin again.
However, in the case of sleep deprivation, one faces an accumulation of pro-inflammatory cytokines in their blood. The problem with this accumulation of the pro-inflammatory cytokines is that it will affect our immune system’s response to a viral infection. The problem, also, then, is that a case of chronic sleep deprivation will cause an existing sleep problem to worsen.
Because we need the pineal gland to release melatonin into our blood so that we can sleep properly.
When the concentrations of the pro-inflammatory cytokines in our blood are higher, the immune cells will release their own melatonin to counteract the effects of the inflammation — and the immune cells will continue producing melatonin daily (while shutting out the pineal gland’s production of melatonin) when the inflammation signal is stronger than usual.
Our ability to sleep hinges on our cells’ capabilities to produce sufficient melatonin, convert sufficient glutamate to GABA, and our immune system’s capability in regulating the inflammation response in our body (which means that we do need to make good lifestyle choices with regards to sleeping, exercise, stress management and diet, as I explore in Four Ways That Our Lifestyle Affects Our Immune System).
Perhaps, in one person’s case, they are unable to convert sufficient glutamate to GABA prior to bedtime.
Another person might not be able to synthesise sufficient melatonin to aid sleeping.
These 2 probable reasons may result in the same visible symptom of sleep deprivation, but the treatment methods are completely different. We don’t want to treat that symptom, we want to find out why we aren’t able to sleep properly. Hence, a GABA supplement may work for one person, while another might need melatonin, for instance.
Once we understand how we can balance out all these different cell activities, the endpoint should be a much easier target to achieve, isn’t it?
Do check out Dr J's nutritional recommendations for stress busting or for a good night's rest!
This article was originally published in Medium.