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In 1968, Robert Ho Man Kwok, MD, penned a letter to the New England Journal of Medicine. He described a host of symptoms he experienced after eating at a Chinese restaurant: “numbness at the back of the neck,” he wrote, “gradually radiating to both arms and the back, general weakness and palpitation.”

In the letter, Kwok proposed to his colleagues that some research ought to be conducted to better understand these mysterious symptoms. Kwok himself was unsure of the cause. Perhaps it was the soy sauce, he mused. It might have been the cooking wine. Maybe, he wrote, it was the presence of monosodium glutamate (MSG).

The following year, John Olney, PhD, conducted a study in which he injected newborn mice with large doses of MSG. He reported a wide range of effects, including brain lesions, obesity, stunted growth, and reproductive issues.

Of course, humans are not baby mice. We don’t ingest MSG through direct injection. And the amounts of MSG used in this study — up to 4 grams per kilogram of body weight — were many times the amount of MSG that the average person eats over the course of a week, let alone in a single meal. Yet Olney’s research became something of a springboard for widespread skepticism around MSG.

Subsequent studies have failed to reproduce the effects he witnessed or to demonstrate a causal relationship between MSG consumption and anecdotal reports of adverse reactions to it, including headaches, chest pain, nausea, heart palpitations, and more — a constellation of responses known as MSG symptom complex. “MSG’s bad reputation is not upheld by the research,” explains Ellie Krieger, RD.

Still, 50 years after Kwok’s letter, four in 10 Americans say they actively avoid eating it. Restaurants and food manufacturers still advertise that they do not use MSG — and plenty who have experienced MSG symptom complex report finding relief after cutting out foods that contain it.

The question is, why?

A Brief History of MSG

MSG is a mixture of water, sodium, and glutamate, one of the most abundant amino acids. It was first developed in 1908 after Japanese chemist Kikunae Ikeda isolated it from seaweed, in an effort to replicate the flavor of his wife’s homemade dashi, a soup stock.

Ikeda found that the glutamates in the kombu were responsible for a taste he called umami, loosely translated as “deliciousness” — the rich, savory taste that the dried seaweed imparted to his wife’s soup. He mixed the acid with some water and salt to stabilize the compound, and the rest is history.

“Adding MSG to foods has been a common practice over the years because it enhances flavor,” says Brigid Titgemeier, RDN, LD, IFNCP. You’ll often find MSG in processed foods because it makes them extra palatable, and it’s sometimes added to restaurant cuisine to improve the taste.

You can even use it in your home kitchen. Food writer Laurie Woolever, who calls MSG “the cook’s little helper,” often adds about a half teaspoon to a pan of greens or a pot of soup, or sprinkles it like finishing salt over a dish prior to serving.

“It contains less sodium than table salt,” Krieger explains, “so it may help those who want to lower sodium content in their cooking but keep the flavor.”

MSG also occurs naturally in plenty of whole foods. If you enjoy eating cheese, tomatoes, grapes, or walnuts, it’s partly because of their glutamates. “MSG gives food more body and depth,” says Krieger. “It gives it a sense of mouthwatering deliciousness.”

That layer of flavor is an indispensable element of many beloved culinary experiences. It’s why your risotto tastes even better with a shower of Parmesan grated on top. It’s why mushrooms are often included in vegetarian dishes — because those glutamates stimulate the same taste receptors on your tongue as a piece of chicken.

Behind the Symptoms

Your body processes the glutamates in whole foods differently than the ones in, for instance, a bag of Doritos.

“The main difference is that naturally occurring glutamate comes with other nutrients, like fiber and other proteins,” explains Maggie Ward, MS, RD, LDN, nutrition director at the UltraWellness Center in Lenox, Mass. “So the body may be able to better regulate the levels of glutamate.” (For more on why that matters, see the sidebar below.)

Titgemeier notes that it’s important to distinguish between two forms of glutamate: bound and free. “When bound, it’s delivered in an unmodified protein source that the body is able to digest and absorb at its natural pace,” she says. “When glutamate is free, as with added MSG, it can lead to faster increases in glutamate absorption.”

Still, free glutamate also occurs in foods like aged cheeses, soy sauce, and bone broth — and people don’t usually experience MSG symptom complex after sipping a mug of bone broth.

Of course, that bag of Doritos also contains a host of other ingredients that could be triggering a headache or nausea. “The worst thing about MSG is the company it keeps,” Krieger says. “But there’s this unnecessary culture of fear around it. If you see a product advertising ‘No MSG’ with a slash mark through it, even if you’d never thought about MSG before, you’d probably think you should be avoiding it.”

That fear itself — what’s known medically as the nocebo effect — could spark adverse reactions to eating something known to contain MSG. It’s like the flip side of the placebo effect, when a patient’s knowledge of a drug’s potential side effects is enough to bring about negative symptoms, even if the drug in question is a sugar pill.

Whether those symptoms are a result of MSG or the power of suggestion, they’re very real to those experiencing them. And though the research doesn’t link MSG to those adverse effects, experts acknowledge that some people do suffer from MSG intolerance.

“There are some individuals who are incredibly sensitive to it, especially if it’s consumed in larger doses of more than 3 grams,” Titgemeier says. “Removing processed foods from the diet is one of the easiest ways to lower a person’s unnecessary consumption.”

But for the majority of the popu­lation, Krieger says, MSG is analogous to table salt — a little is fine, but too much could throw off the flavor of your meal and, if eaten in excess, potentially undermine your health.

“I don’t think it needs to inspire so much fear,” she explains. “I’d rather people think of MSG in a balanced way as a potential tool in the flavor toolbox.”

Glutamate and the Goldilocks Principle

Glutamate is a nonessential amino acid, meaning the body produces it without needing to ingest it through food. One of the body’s most abundant amino acids, it plays a vital role in muscle function, cellular metabolism, immune response, and more.

It is also the most prevalent neurotransmitter in the entire nervous system, responsible for up to 40 percent of the brain’s synaptic function.

“Glutamate activates brain cells and is responsible for neuronal communication,” says Brigid Titgemeier, RDN, LD, IFNCP. “That can lead to stimulating the cells, which is why it’s called an excitatory neurotransmitter.”

That cell stimulation allows glutamate to communicate signals to the brain and throughout the body, supporting cognition, memory, and other vital brain functions.

Glutamate also follows the Goldilocks Principle, which means that to function optimally, the brain needs just the right levels of glutamate. An overabundance can lead to excitotoxicity, which has been linked to neurodegenerative diseases like Parkinson’s and Alzheimer’s.

Glutamate deficiency, on the other hand, can cause symptoms like brain fog, exhaustion, and memory problems.

But eating glutamate in food doesn’t necessarily have an effect on that delicate balance. That’s thanks to a protective layer of cells called the blood–brain barrier, which keeps substances like glutamate in the blood from passing into the central nervous system.

“Research has shown that MSG cannot cross the blood–brain barrier unless it is accompanied by a receptor, which controls the amount that enters at one time,” explains Titgemeier.

“The concern is for those who have a leaky gut, which may allow for higher levels of glutamate to enter the brain at once. This hasn’t been demonstrated in research, but it makes sense from a mechanistic perspective and may explain why some are more sensitive than others.”

(For more on how your gut microbiome heals and protects your brain, see “Healthy Gut, Healthy Brain”.)

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