Missing From the Databases: Glutamine

Why are the USDA, NCCDB, Cronometer, and all databases missing the glutamine content of foods?

It’s my birthday today!

My present to myself is to finish this article :)

Glutamine is considered “conditionally essential” because it can be synthesized from glutamate when total protein is adequate, yet it can become depleted to dangerous levels that require supplementation during illness, injury, and surgery.

As I will cover in more detail in the future, glutamine should be considered a major fuel for people who have major impairments in complex I of the respiratory chain, or who take complex I inhibitors like metformin and berberine, or who thrive on low-carb diets where glutamine becomes an alternative to carbohydrate for fueling the citric acid cycle through anaplerosis.

The USDA database has no data on the glutamine content of any foods, with the sole exception of five “branded foods,” all of which are sports drinks.

The reason why is found in the documentation: all amino acids besides tryptophan and sulfur amino acids are determined by acid hydrolysis and high-performance liquid chromatography (HPLC). Acid hydrolysis removes the nitrogen from the side groups of glutamine and asparagine, converting them to glutamate and aspartate.

This means that the data for glutamate and aspartate are false, because the value for glutamate is actually the sum of glutamate and glutamine, and the value for aspartate is actually the sum of the of aspartate and asparagine.

This feeds forward into every other major nutritional database, such as NCCDB, and into all values tracked in apps like Cronometer.

In fact, no one ever cared to measure these amino acids in meat until 2016, when Wu and colleagues reported, “this is the first study to determine aspartate, asparagine, glutamate, and glutamine in meat proteins of any animal species.”

The reason they were able to measure these was because they used enzymatic hydrolysis rather than acid hydrolysis to break apart the amino acids of food proteins.

It’s not like this was invented in 2016. After Schulze and Bossahard found free glutamine in beet juice in 1883, E. Fischer documented that acid hydrolysis destroyed glutamine in 1904 and Domodaran and colleagues isolated glutamine from enzymatic hydrolysis of wheat gliadin in 1932.

Rather, it was easier not to measure glutamine and asparagine, and to get completely inaccurate results for glutamate and aspartate, and no one cared.

Authors tended to assume the glutamine content of protein is constant. For example, Shao and Hathcock wrote in 2008, “[Glutamine] content of protein from food sources is estimated to be approximately 4–5% (Lowe et al., 1990; Kuhn et al., 1996), suggesting that typical daily intake of [glutamine] from food by most adults is approximately 5 g (1.5 g protein/kg body weight in 70 kg adult).”

Lowe, 1990 asserted that “glutamine accounts for only 4-5% of the amino acids found in commonly used food protein” and provided no reference.

Kuhn, 1996 looked at the glutamine content of 14 commercial hospital formulas and no actual foods. They used acid hydrolysis, but they treated the proteins prior to the hydrolysis in a way that made the glutamine acid-stable. They concluded all of these diets would provide 6 to 8 grams per day of glutamine if based on milk or whey protein, and only 1 to 5 grams per day if based on partially hydrolyzed milk, soy, or meat protein, and that all of them fell short of the 10-20 grams per day called for under conditions of critical illness, which they considered possibly “deleterious, adversely affecting the course of recovery.”

The actual range of glutamine was 1.3-8.1% of total protein, and they didn’t measure any natural foods. As such, the data do not support the statement that glutamine is generally 4-5% of total protein, nor are the data useful to determine the typical proportion of glutamine in proteins in the first place.

I will be writing up the results of my self-experiments with time, but I will say for now that I believe glutamine, glutamate, and alpha-ketoglutarate can be summed together and that it likely takes 1-2 grams of the sum to replace each gram of carbohydrate for fueling the citric acid cycle. The biochemistry of this is laid out in my lesson, Anaplerosis: Why Carbs Spare Protein In Ways That Fat Can’t. The quantification is based on the fat that each glucose can fuel two turns of the citric acid cycle while each glutamine, glutamate, or alpha-ketoglutarate can only fuel one turn, and then is adjusted for molar mass, which suggests each gram of glucose is worth 1.6 grams of glutamine. 

Putting together several resources (here, here, here, here, and here), we can say the following about the glutamate and glutamine content of foods:

• The glutamine content of plant proteins ranges from 2.98% (sweet potato) to 29% (wheat flour) of total protein, but the total protein of plant foods is rather low. For example, despite the high proportion of protein, you would need to eat close to 500 grams of wheat flour to get 20 grams of glutamine, which would provide 1700 Calories, which would take up most of the room in the average person’s diet.

• The glutamine content of animal proteins is low in eggs (4.65%), organ meats (5.51% in a blend of “chicken byproducts”), beef loin (6.61%) and chicken breast (6.11%); it is intermediate in dairy proteins (9.4% in cow milk, 9.1% in whey protein, 11.3% in casein); and it is high in the leg meat of chicken and pork (22.5% in chicken gastrocnemius and 21.12% in pig gastrocnemius). The gastrocnemius is part of the drumstick in chicken and the hindshank in pigs.

• The fact that glutamine is low in chicken breast and high in the gastrocnemius of chicken and pork would suggest that heavily used muscles in the legs have high stores of glutamine to use for energy. However, this is not replicated in cattle. The gastrocnemius is part of the heel round, and the glutamine content of loin, round, and chuck are nearly identical. I believe this needs more research with other cuts from the legs like shank, and a specific analysis of the heel part of the round rather than the round in general, and that we need to look at sedentary animals in feedlots versus pastured animals, since the feedlot animals may not experience the need to fuel the leg muscles as much as typical chickens or pigs.

• The proportion of glutamine in human (8.3%), cow (9.4%), and pig (10.2%) milk is quite similar, suggesting that all dairy proteins are “intermediate” across the board.

• Thus, proteins can generally be ranked as low (about 5% or less), intermediate (close to 10%), or high (over 20%).

• The ratio of glutamate to glutamine in food proteins is wide: among animal proteins, this ranges from 0.33 in chicken gastrocnemius to 1.84 in chicken eggs; among plant proteins, this is even more variable, from 0.06 in wheat flour to 2.48 in sweet potato.

Since the nutrient databases rely on acid hydrolysis that converts all of the glutamine to glutamate, they are reliable indicators of the sum of these two amino acids.

Since the ratio of glutamate to glutamine is so wildly variable in foods, however, they are worthless in estimating the actual glutamine content.

Is this important?

On the one hand, the total anaplerotic value (the ability to fuel turns of the citric acid cycle) is really dependent on the sum of the two.

However, the specific complex I-avoidant anaplerotic value that would be valuable in conditions of complex I impairment, medicating with complex I inhibitors, or general benefit of carbohydrate restriction is maximized with glutamine, because the removal of the glutamine nitrogen will encourage oxaloacetate to leave the citric acid cycle to enter the urea cycle as aspartate, which will then maximize the amount of complex II-feeding FADH2 that is generated at the level of succinate dehydrogenase compared to the activity of the NADH-generating reactions of the cycle.

Further, the nitrogen of glutamine is used by the enzyme tissue transglutaminase to cross-link tissues during the healing process.

Thus, there is value to actually maximizing glutamine.

If shooting for total anaplerotic value, simply track your food in Cronometer and use the glutamic acid value to indicate the sum of these two amino acids.

If trying to maximize glutamine, then emphasis should be put on the hind legs of pigs and chicken with intermediate emphasis on dairy products.

My suspicion is that pastured animals who use their hind legs a lot have hind leg muscles with the richest glutamine content.

If vegan, wheat flour (29%) and white potatoes (17.95%) have high proportions of glutamine, other grains and legumes are intermediate (white rice 9.38%, soybean 8.26%, pistachio nut 11.64%, peanut 9.9%, corn 11.06%), and sweet potatoes (2.98%) are low.

As I was researching this, I discovered that Huberman’s list of glutamine-rich foods dominates the rankings on Google and lists cabbage, spinach, and parsley. For example, this list, which comes from this video, where Huberman states the following:

So people will supplement with glutamine, or people can get glutamine from foods. Foods that contain a lot of glutamine are things like cottage cheese. There are also other sources of glutamine. Glutamine is rich in protein rich foods, things like beef, chicken, fish, dairy products, eggs. But also, for you non-animal food-consuming people out there, vegetables, including beans, cabbage, once again, spinach, parsley, things of that sort."

While beans will make a contribution, it would take a kilogram of cabbage to reach a 2.9-gram glutamic acid value in Cronometer; it would take a kilogram of spinach to reach 3.4 grams; and it would take a kilogram of parsley to hit 2.5 grams. These foods cannot be considered high in glutamine.

As a general rule of thumb I would say that if one is opting for a lower-carb diet, one should aim to get 20-30 grams of glutamate and glutamine combined from whole foods, and the best way to hit this is to track your diet in Cronometer and look at the glutamic acid value in the protein section of the nutrition report. If trying to support tissue healing or complex I impairment, aim for foods higher in glutamine itself, where the superfoods appear to be the hind legs of active animals (or just chicken and pigs?), and the good foods are dairy proteins.

The best plant foods for glutamine are wheat flour and white potatoes, followed by grains and legumes. Just keep in mind the plant foods are much lower in total protein, so the high glutamine as a proportion of protein will not be as effective in yielding a high total intake of glutamine when compared to the animal foods.