Most everyone has heard of the dreaded monosodium glutamate, or “MSG” for short (remember the word glutamate in that phrase).
The stereotype is that MSG is an additive in many restaurant dishes, and so it’s easily avoided, but it’s actually much more common than you might think.
What if I told you that a common ingredient in many dietary supplements, L-glutamic acid, was almost identical to MSG in terms of what it does in the body?
When ingested, both MSG and L-glutamic acid produce glutamate, which is the “bad guy ingredient” in MSG.
MSG is just a form of L-glutamic acid where the glutamate is bound to a sodium atom.
MSG’s sodium / glutamate combination dissolves much more quickly than does L-glutamic acid, which is why MSG is often used as a food additive, it dissolves quickly in the mouth releasing loads of glutamate to stimulate our tastebuds.
However, whether you eat MSG or L-glutamic acid, you are ingesting glutamate, and as we’ll discuss, some people are sensitive to high levels of glutamate.
What is glutamate?
In the brain, GABA is a calming neurotransmitter, and glutamate is an excitatory neurotransmitter. You can think of GABA as the break, it slows you down and chills you out.
By contrast, glutamate is the gas, it speeds you up and gets you going.
Glutamate sends signals between neurons, it is essential for learning and memory, but too much glutamate, especially when paired with high levels of calcium, can become what’s called an excitotoxin. 1
The process of excitotoxicity is marked by a necessary neurotransmitter, glutamate, becoming dangerous as it exceeds healthy levels. This Stanford paper does a nice job of explaining the two primary ways glutamate causes problems for some people:
First, there can be too much glutamate around; abnormally high concentrations of glutamate can lead to overexcitation of the receiving nerve cell. Second, the receptors for glutamate on the receiving nerve cell can be oversensitive, such that less glutamate molecules are necessary to excite that cell.
When glutamate runs amuck, as it does in both of the scenarios listed above, it kills neurons in the brain. In fact, there are a number of neurodegenerative diseases that are linked to excess glutamate. 2
And here’s the problem: glutamate is common in the world of supplements, and it’s also found in high concentrations in some of the foods we love.
For example, the popular gut repair supplement Restore used to list glutamic acid as an ingredient. It’s not clear from current labeling if this is still an additive.
L-glutamic acid vs. MSG
As we’ve established, there is very little difference at the molecular level between L-glutamic acid and MSG.
For the chemists among us, MSG is a salt of L-glutamic acid, where one of the hydrogen ions is replaced by a sodium. The benefit of this change is that MSG dissolves much more quickly and easily than L-glutamic acid in the body.
So while both can convert into glutamate, MSG does it much faster.
Note: if you want to avoid MSG, you can also be on the lookout for these names in ingredient lists as well: monoammonium glutamate, monopotassium glutamate, natrium glutamate, magnesium glutamate, calcium glutamate.
What is the difference between glutamate and glutamic acid vs. glutamine?
Now that glutamate is on your radar, you might be wondering about supplements made with glutamine.
Is glutamine the same thing as glutamate?
As you can see from the photo above, Vega Sport protein powder lists 6g of glutamine per serving (although confusingly, the ingredients list breaks this out as glutamic acid).
But what’s glutamine got to do with glutamate and glutamic acid?
Is Vega Sport listing an equivalent ingredient, or pulling the wool over consumers’ eyes here?
Well, first it’s important to note that glutamine and glutamate aren’t the same thing, they are independent amino acids with quite different functions, so it’s strange that they seem to be lumped together in several supplements. But, they are linked. Enzymes in the body convert glutamate into glutamine in a two step process shown below.
This can go the other way as well with glutamine converting back into glutamate, in a process which is likely regulated by what your body needs at that moment. Interestingly, glutamine has been shown to help protect the gut from damage by maintaining the integrity of the intestinal lining. So glutamine, as opposed to glutamate, may be of interest to those with gut issues such as Crohn’s disease or IBD/IBS. 3
So, the bottom line here is that glutamic acid and glutamine are two separate amino acids with different functions in the body, but supplement manufacturers don’t seem to get this, and in the case of Vega Sport, they advertise glutamine, but make their product with glutamic acid.
Many popular foods are also high in what is known as “free glutamate.”
Foods that contain free glutamate
Processing proteins, like when a soybean becomes tofu, “unbinds” the naturally occurring glutamate amino acid in that food and “sets it free.” The glutamate molecules that were “bound,” become free floating, allowing them to bind to the glutamate receptors in your tongue and elsewhere. 4 As a general rule of thumb, most processed proteins have high amounts of free glutamate. Bone broth and collagen supplements are a major source. Cow dairy, tofu, vinegar, and many other foods you wouldn’t suspect, all contain glutamate.
It is important to note: a normal dietary intake of glutamate, or even MSG, is not conclusively linked with any adverse effects in the general population. High intake (over 3g per day without food) however was, and there are continuous reports of sensitive individuals. The kicker is we don’t know what drives this individual response. Long term readers will know that this is a great marker of some genetic differences driving the effect, which fort some, is quite severe.
Problems associated with too much glutamate
For starters, it probably comes as no surprise that MSG has been linked to anxiety, both anecdotally and in animal models. 5
However, aside from the list of chronic diseases that are linked to glutamate excitotoxcity over long periods of time, build up of glutamate can contribute to sleep issues as well. 6 In the body, glutamate is actually converted into GABA in one of the many metabolic circles that comprise our molecular physiology.
SNPs in the GAD1 gene have been associated with a decreased ability to convert glutamate into GABA, and therefore greater anxiety and trouble sleeping. For example, one of the reasons why theanine is so calming for some people is because it is a glutamate antagonist, it works to block glutamate receptors. Most anti-anxiety drugs target the GABA receptors, however, there is an emerging belief that glutamatergic agents can cause anxiety disorders and drugs should be developed that target the glutamate receptor as well. 6
The science is still new, and to date, there is nothing conclusive linking glutamate in food to GAD1 SNPs, however, when reviewing your genetic data, GAD1 SNPs are an important place to look when trying to diagnose anxiety issues. Regardless of whether glutamate in food is the issue, an inability, or reduced ability, to recycle glutamate back to GABA will leave you prone to sleep and anxiety issues.
Genetics – GAD1, AOC1, VDR
I mention the GAD1 gene above because that is a logical place to begin, however, there are a few genetic polymorphisms to keep in mind when thinking about glutamate.
Certain VDR Fokl genotypes are associated with greater calcium uptake from the gut. When this SNP is paired with mutations in the GAD1 genes, there may be potential for greater issues with glutamate, especially over a period of years, because calcium is likely to be elevated. Remember, it is the combination of calcium and glutamate, and not glutamate alone, that causes cell death in cases of excitotoxicity.
More glutamate reading
For more, see our GAD1 page.
Pharmason Labs also offers a neuro endocrine panel where you can measure the levels of glutamate in your brain.