How Glutamine Supports Gut and Immune Cell Metabolism
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In this clip from Dr. Rhonda Patrick's appearance on Huberman Lab, she describes glutamine as a versatile amino acid that can supply carbon and nitrogen for cellular metabolism. Intestinal epithelial cells and activated immune cells can use glutamine during periods of high demand, linking it to gut-barrier maintenance, immune-cell growth, and biosynthesis. [1] [2]
Human studies provide early, context-dependent signals. Meta-analytic evidence suggests that glutamine can improve selected intestinal-permeability measures in some populations, although results vary by dose, duration, and health status. Exercise studies also show that prolonged endurance work can lower circulating glutamine and alter immune measures, which helps explain interest in supplementation during heavy training. [3] [4]
One older study reported fewer self-reported infections after marathon or ultramarathon events among athletes who received glutamine. Dr. Patrick presents her own use as an experiment rather than a prescription and notes that placebo or other supplements could contribute to her experience. The evidence supports glutamine's metabolic role and continued study, not a guarantee that it prevents illness. [5]
This clip is excerpted, with permission, from Dr. Rhonda Patrick's appearance on Huberman Lab. Thank you to Huberman Lab for allowing us to share it.
- ^ 10.3892/etm.2016.3799
- ^ 10.1080/15502783.2023.2300259
- ^ 10.12965/jer.1835154.577
- ^ Rohde T; Asp S; MacLean DA; Pedersen BK (1998). Competitive sustained exercise in humans, lymphokine activated killer cell activity, and glutamine--an intervention study. Eur J Appl Physiol Occup Physiol 78, 5.
- ^ Castell LM; Poortmans JR; Newsholme EA (1996). Does glutamine have a role in reducing infections in athletes? Eur J Appl Physiol Occup Physiol 73, 5.
Dr. Andrew Huberman: Lately, you've posted a bit about glutamine as a potential tool to perhaps buffer the immune system under times of stress. I've also been interested in L-glutamine as a way to reinforce tight junctions in the gut. I don't know if that literature is robust or not. I have to say I started taking L-glutamine years ago in times when I was working a lot and not sleeping enough because someone told me it would help me not get sick. And indeed, I didn't get sick as much as the imaginary control experiment that I never got to do. Meaning, I don't know if it helped or not, but I continue to take L-glutamine when I'm feeling run down.
I take a couple of other things, too, but could you tell us about how or if or how L-glutamine is important for gut health and if and how L-glutamine might be helpful for reinforcing the immune system.
Dr. Rhonda Patrick: There's not a ton of evidence in terms of what's in the scientific literature supporting these statements, but there is some, and it's enough to go, "Well, I'm going to try to maybe experiment with it." So, I first became interested in glutamine because when I was doing my graduate research, I was doing a lot of cancer metabolism studies and I would do nutrient withdrawal. I would remove glucose from cancer cells and see what happens.
I would remove glucose from lymphoma cancer cells in a petri dish, and many of them would die, but not all of them. I wondered why. It turned out that glutamine was present and was enough to sustain them. Glutamine is an amino acid that can also be converted into intermediates in the Krebs cycle, which mitochondria use to make energy.
And glutamine can be converted into glutamate. Neurotransmitter. So, there's a lot of pathways and different fates for glutamine. So, I became interested in that because it was like, "Oh, glutamine's important for the survival of these cancer cells." then I was doing a lot of activating immune cell studies as my graduate advisor is an immunologist by training and so, I was also doing that. Turns out glutamine was essential for the activation of immune cells. So, that was always in the back of my mind.
And then in my post-doc, I did my post-doc with Dr. Bruce Ames and my colleague Dr. Mark Shigenaga was doing a lot of gut work and this is why I know a lot about the LPS in the gut, it's from him. Like brilliant guy, he's now a photographer, like not in science at all, but brilliant guy and did a lot of really amazing experiments looking at, gut permeability and things that can help buffer, gut permeability and one of those things were glutamine. So, glutamine can get converted into these intermediates that are used by mitochondria in the gut epithelial cells and so, that's like an easy source of energy as well for the gut. Now, these are all animal studies.
Take it with a grain of salt. In my opinion, animal studies are important for understanding mechanisms, and we also need human studies. Looking at the totality of evidence is important. Human evidence is limited, especially for gut health.
I found the human evidence on glutamine and the immune system more compelling. Endurance athletes who train for marathons throughout the year put high energetic demands on their bodies and can be more prone to respiratory infections. A few studies reported a lower incidence of respiratory tract infections when these athletes took a higher dose of glutamine, around 30 grams, compared with when they did not.
And then I went back to my, "Oh, I know that glutamine's really important for T-cell activation." And I was like, "I'm going to take this because being a mom and having a child that's bringing everything home like a vector, you're like desperate."
Dr. Andrew Huberman: You're the experiment.
Dr. Rhonda Patrick: Exactly. I never used to get sick and then all of a sudden I was getting sick like three times a year and I was like, "Do I have cancer? What's going on?" I literally was worried. And then I started taking glutamine. Now, I take 5 g on a daily basis, but if my son's sick, if there's any exposure, if it's during the season, if I'm traveling, I go up to 15, I go up to 20.
Dr. Andrew Huberman: Because it can be a little hard on the gut all at once, right?
Dr. Rhonda Patrick: Not all at once. I usually divide it into five-gram doses. I do 5 grams, 5 grams, and 5 grams. I have to add the caveat that I also take a lot of creatine, so I do not know which one helps, or whether both help, but I really do not get sick. Even if something is brought home, I do not get sick. Maybe it is a placebo, and I am okay with that because the placebo effect is real.
As long as I'm not getting sick, I think glutamine is worth experimenting with. I would not say that there is overwhelming evidence that it improves gut health or immunity. It can provide energy to immune cells when they are activated after exposure to a pathogen. Someone with colon cancer might have more reason for concern because cancer cells can use many of the same nutrients that support normal cells.
Folate, if you don't have enough folate, you can cause double-stranded breaks to your DNA, which lead to mutations that lead to cancer, but if you have cancer and you take a bunch of folate, you need folate to make new DNA and so, they like the folate. So, it's like
Dr. Andrew Huberman: It's in that normal growth. So, anything that's associated with drugs, mTOR. I saw the recent study on taurine, which scared a lot of people because taurine's in a lot of energy drinks, but that was an in vitro study. Yes, I was going to ask, is there increased cancer risk if you're supplementing with glutamine because cancer cells like glutamine?
Dr. Rhonda Patrick: My personal opinion, and I am not a medical physician, is that this is not a prescription. It is only my opinion.
I personally am not scared of getting cancer from taking glutamine. If I had a colon tumor in a tumor in my colon, the first site that the glutamine is seen, maybe the liver as well since that's also the next step, but barring like having a tumor already in my liver or in my colon, those would be the only, types of situations that I would be worried about taking glutamine. I don't think it's going to cause cancer. Now, I guess the question is what if you don't know you have Well, hopefully the cost will come down on whole body MRIs. Actually, the cost is coming down on whole body MRIs and hopefully more people are able to get those. It's not just such a high-end exclusive thing in the near future.
It may become more like blood draws. In the past, people received blood-test panels only when they really needed them. Now, the cost of blood draws is low.
Dr. Andrew Huberman: Right.
Dr. Rhonda Patrick: So, hopefully people will be more aware.
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