By Sue Klapholz, MD, PhD — VP of Nutrition & Health, Impossible Foods.
Glutamates are a natural and abundant part of our diet.¹ Yet, glutamates, and particularly monosodium glutamate or MSG, have gotten a bad rap since the late 1960s when MSG was posited to be the cause of a complex of symptoms that includes numbness and heart palpitations (see further below).² Some grocery stores still place MSG and other glutamates on their lists of “not allowed” ingredients. Is there a rational basis for concern? This blog explores the facts and fallacies surrounding glutamates.
Proteins are composed of 20 amino acids, in various proportions.³ And virtually all foods that contain protein contain the amino acid glutamic acid. In fact, glutamic acid is often the most abundant amino acid present in protein.³ ⁴ When protein is digested in our bodies, glutamic acid and other free amino acids are released. Glutamic acid is the “acid form” of glutamate, meaning it has an extra hydrogen (Figure 1). Physiologic conditions (e.g., those found in the human digestive tract) favor the conversion of glutamic acid to glutamate, making glutamate the form that is normally found in our bodies.
Figure 1: Under physiologic conditions, glutamic acid loses a hydrogen ion (H+) to yield glutamate.
Glutamic acid is absolutely essential for life. It is a building block for new protein synthesis, an excitatory neurotransmitter (see further below) and a precursor of another neurotransmitter, gamma-aminobutyric acid (GABA).⁴ ⁵ It plays a key role in the removal of excess nitrogen from the body, in the synthesis of glutathione — an important antioxidant, and in the synthesis of many other amino acids, including glutamine, arginine and proline.⁴ ⁵ 95% of dietary glutamate is metabolized by cells in the intestine, where it serves as an important source of energy for these cells.³ ⁶
Natural sources of glutamate in our diet: During digestion, protein is broken down into amino acids, making dietary protein by far the largest contributor to free glutamate in the gut.³ Certain foods, for example, ripe tomatoes, contain an abundance of free glutamate — glutamate that is not part of protein.⁷ Some other common natural sources of free glutamate in our diet are grape juice, potatoes, broccoli, fish, parmesan cheese, and mushrooms.⁸ ⁹ ¹⁰ ¹¹ Fermented foods, such as soy sauce and miso, are particularly rich in free glutamate.⁸ ¹¹Yeast extract, an ingredient in which the proteins are physically or chemically broken down (e.g., by hydrolysis), is another plentiful source of free glutamate.¹ ¹¹Human breast milk contains a substantial amount of free amino acids, of which glutamate is the most abundant.¹² ¹³ In fact, glutamate concentration in breast milk increases significantly during the first three months of lactation.¹² ¹³
Glutamate salts: Sometimes free glutamate or glutamate salts are added to food to enhance umami (savory) flavor.¹¹ ¹⁴ MSG is the sodium salt of glutamate, meaning that it has an added sodium (Na) ion that readily separates from glutamate when it dissolves in water (Figure 2). Likewise, monopotassium glutamate (MPG) is the potassium salt of glutamate. Other glutamate salts include: calcium glutamate, magnesium glutamate and monoammonium glutamate.¹¹ Commercially manufactured glutamate salts are products of microbial fermentation.¹⁵ ¹⁶ As with glutamic acid, all glutamate salts are converted to glutamate in our bodies, and all glutamate molecules that enter our bloodstream from the gastrointestinal tract are structurally identical.⁹ ¹⁷
Bottom line: Regardless of the source, glutamate is glutamate — there is no difference between the glutamate in your body that was derived from MSG, hydrolyzed yeast extract, tomatoes or pea protein.
Figure 2: Glutamate is derived from glutamic acid from digested proteins, free glutamic acid, and glutamate salts such as MSG and MPG.
How much glutamate do we consume?
MSG is what many people think of when considering glutamate consumption. But the average daily intake of MSG that has been added to food is estimated at 0.55 g in the US and 0.4 g in Europe.¹ ¹⁸ To put these typical Western dietary levels of MSG in perspective, one cup of dried tomatoes contain between 0.35 and 0.62 g of free glutamate.⁸ In Asian countries, consumption of MSG is substantially higher — ranging from 1.5 to 4.6 g per day. ¹⁹
According to the US Food and Drug Administration (FDA), the average American adult consumes 13 g of glutamate per day from protein in food.¹ In European countries, the total daily intake of glutamate occurring naturally in food ranges from 5 to 12 g per day, with about 10 g from protein and 1 g as free glutamate.¹⁸ Glutamates in the Impossible Burger come from protein and free glutamates. Per 4-oz serving, the Impossible Burger has 4.5 g of total glutamate, in between the amount of total glutamate found in lean ground beef (3.5 g)²¹ and sharp Cheddar cheese (6.4 g).²¹
Bottom line: Relative to the total glutamate intake from all dietary sources, free glutamic acid and glutamate salts make a relatively small contribution.
How much glutamate is safe to consume?
Both the FDA and the Food and Agriculture Organization of the United Nations (FAO)/ World Health Organization (WHO) have concluded that the levels of glutamic acid and glutamate salts typically consumed pose no risk to public health or safety¹ ²² ²³, and neither organization has set an upper limit for glutamate intake. The European Food Safety Authority (EFSA), on the other hand, proposed an acceptable daily intake (ADI) for free glutamate and glutamate salts of 30 mg per kg-body weight.¹⁵ For a 150-lb person, this would be about 2 g per day. This ADI has been criticized for being much lower than scientific evidence would indicate is warranted .²⁴ For example, it has been demonstrated that breast-fed infants consume 4.5 times more free glutamate than the EFSA’s ADI.¹³ Finally, it has been pointed out that free glutamate and glutamate salts make only a “marginal contribution” to total dietary glutamate intake.¹⁰ While not all regulatory authorities agree on whether free glutamates should be limited, human studies have shown that extremely high levels of free glutamic acid (137 g per day) can be ingested for 30 days or longer with no ill effect.²⁵ This is because our bodies are great at regulating the amount of glutamate in our blood. When glutamate is consumed at higher levels than the body needs, it is metabolized in the intestines and converted to carbon dioxide or other amino acids, keeping the level of glutamate in the blood remarkably constant, between 50 and 100 µM.⁵ ¹⁵ ²⁶
Bottom line: The metabolism of glutamate and its physiological effects have been extensively studied. These studies provide abundant evidence for its safety at doses far exceeding what any human encounters in the diet.
Are some people sensitive to MSG (and other glutamates)?
In a letter to the New England Journal of Medicine in 1968, Dr. Ho Man Kwok described experiencing numbness, weakness and palpitations about 15–20 minutes after eating Chinese restaurant food.² He suggested some possible causes, such as an ingredient in the soy sauce or cooking wine or MSG. Others have gone on to attribute symptoms of headache, asthma, hives, runny nose, muscle twitching and chest pain to MSG ingestion.⁹ ²⁷ However, well-controlled scientific studies have failed to produce consistent evidence that MSG causes these symptoms in the general population or even in people who self-identify as MSG-sensitive.²³ ²⁷ ²⁸ A 2016 paper reviewed the connection between MSG and headache; the authors separated studies into two groups: those in which MSG or placebo was taken with a meal and those in which MSG or placebo was taken (in a strongly flavored beverage or broth) on an empty stomach.²⁸ In the former, the typical amount of MSG was 3 g, in the latter it was 5 g. In all studies, the doses were substantially higher than the 0.4–0.55 g of MSG consumed daily in the average Western diet. When MSG was taken with food, four of five studies showed no significant difference between placebo and MSG, and a fifth study only showed significantly more headaches in female, but not male, participants. When taken on an empty stomach, results were mixed: some studies showed no significant differences between response to MSG vs. placebo, while others showed more headache symptoms after ingesting MSG. However, a much repeated criticism of studies of MSG taken without food is that the characteristic strong flavor of MSG is difficult to mask, unblinding the subjects to its identity and potentially leading to bias.²⁹ Even in people who self-identify as MSG sensitive, studies have failed to provide reproducible evidence of an MSG effect.¹⁸ ²⁷ ²⁹ ³⁰ ³¹ The authors of the largest and most comprehensive of such studies concluded that “…large doses of MSG given without food may elicit more symptoms than a placebo in individuals who believe that they react adversely to MSG. However, the frequency of the responses was low and the responses reported were inconsistent and were not reproducible.”¹⁷ ²⁷ In other words, they did not pass the basic test of scientific credibility — reproducibility. Furthermore, the same test subjects failed to respond when MSG was given with food.¹⁷ ²⁷ A systematic review of over 60 studies that purported to examine the effects of MSG ingestion on asthma failed to demonstrate a link, however only two studies met the reviewers’ rigorous inclusion criteria.³² A recent placebo-controlled study of individuals who self-reported an irregular heartbeat, atrial fibrillation (AF), in association with MSG consumption, demonstrated no association between AF and doses of 3 g of MSG.³¹
Bottom line: There is no reproducible scientific evidence that the general population or even self-identified MSG-sensitive individuals, are adversely affected by ingestion of MSG with food or on an empty stomach. There is also no evidence that MSG should be avoided in asthmatics or in individuals with AF.
Does MSG cause neuroexcitation or neurotoxicity?
In addition to being an amino acid, glutamate is a neurotransmitter³³, the major excitatory neurotransmitter of the vertebrate central nervous system.⁴ ³⁴ Glutamate in the brain is either synthesized in the brain or obtained from the recycling of brain proteins.²⁶ ³⁵ Levels of glutamate in the brain (10,000–12,000 µM) are at least 100 times higher than circulating blood levels (50–100 µM).²⁶ Because of the blood-brain barrier (which prevents many substances in the bloodstream from entering the brain), levels of glutamate in the blood do not affect levels of glutamate in the brain.²⁶ ³⁵ Under certain pathological conditions (e.g., ischemic stroke), release of glutamate from brain cells can occur, leading to extreme excitation of nerve cells. However, in these cases, the excess glutamate comes from within the brain itself, not from the diet.²⁶ ³⁵ There is no evidence of brain damage in humans resulting from dietary glutamate.³⁴
Bottom line: Glutamate in the brain is synthesized in the brain. Dietary glutamate does not influence levels of glutamate in the brain, nor does it play a role in neuroexcitation due to pathological conditions such as stroke.
Glutamate is essential for life and is ubiquitous in food. Extensive scientific studies of the effects of dietary glutamate have found no evidence for harmful effects of any kind, even at implausibly high doses.
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