Considerations for glutamine supplementation as it relates to gut health and cancer
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Glutamine supports the growth of cancer cells in petri dish studies. However, glutamine is therapeutic for the gut and can help reduce systemic inflammation. The majority of glutamine administered orally is taken up by the liver and gut, with little ending up in the bloodstream. Dr. D'Agostino discourages supplementing with glutamine for patients with cancers of the gastrointestinal tract and even recommends they avoid high glutamine containing foods. In this clip, Dr. Dominic D'Agostino discusses the importance of an individualized approach when considering glutamine supplementation.
Rhonda: You're talking about glutaminolysis and I have done a lot of research on this, and there are questions that I would love to be answered, but haven't been. So, since you're looking at this and you have resources, I'll just throw it out there. Obviously, you said this is well-known literature that glucose and glutamine are both source...cancer cells love them. It's like crack for cancer cells, both glucose and glutamine, and I've done a lot of studies on various types of cancer cells and these are in vitro. So this is not in an animal model where I can, I withdraw glucose and the cancer cells will proliferate slower, some will die, but if there's glutamine there...
Dom: What's your level of glutamine?
Rhonda: Two millimolar.
Dom: Two millimolar, yeah.
Rhonda: Yeah, so then I would start withdrawing the glutamine and glutamine withdrawal, this is all in vitro, though. Glutamine withdrawal would kill them within 24 hours, but.
Dom: Pretty lethal, yeah.
Rhonda: Very lethal, and has been shown at least some of the studies that were initially done by Ralph DeBarardinis when he was with Craig Thompson, and later when he established his own lab where he radiolabeled and showed that, actually, it was being used predominantly for macromolecular synthesis and not for which is...of course, that makes sense because a lot of tumor cells aren't using the mitochondria.
Dom: Making fatty acids, actually.
Rhonda: Making fatty acids, proteins, like, for new synthesis.
Dom: Like, cell membranes and stuff.
Rhonda: Right, so the question for you...the question that I have and this is... So that's one of the spectrum. Okay, glutamine seems bad when you're looking from an in vitro perspective and I did these studies, but many people have published on this. You're familiar with the literature. But then there's the other perspective where really glutamine really is believed, like, to gut, to cells, it's very, very healing and therapeutic for gut, and when you take glutamine orally, the gut takes it, it's not getting into your bloodstream, It's not being so...
Dom: The gut and the liver take its share and very little of it actually gets into the bloodstream.
Rhonda: Right, so that's what I'm getting at. The question is, if you have a mouse model of a solid tumor that's not gut-oriented, so it's not colon cancer, like let's say it's you got a pancreatic cancer or...
Dom: Brain tumor.
Rhonda: ...brain tumor, then you give the mouse glutamine, is that really is it really going to affect the tumor or is it just going to help the gut? I mean, of course, it can indirectly affect it, but the question for me, in my mind, is, well, yeah, if you had tumor in the gut, man, that's like crack for the tumor. Do not take glutamine, do not, you know... But on the other hand, if you've got gut issues, you know...
Dom: It can be helpful.
Rhonda: Right, do you see what I'm getting at?
Dom: This is something that I have thought about.
Rhonda: You have?
Dom: Yeah, I think about stuff like this, yeah.
Rhonda: I'm not alone, yeah, well, in vitro is very different because the way our bodies are working and the way glutamine when we take glutamine, it's affecting our gut, it's very important. I mean, it helped. It's helped me.
Dom: I used to take it.
Rhonda: It's helped me with gut, but then there's this whole, like, conflict in my head around...cancer cells love it, but the question is if I'm taking it orally, and I have some cancer cells, in my, I don't know, my liver or something, then I guess you said liver is one that does. it does use it, but, so the question is, is that harming me or is it helping me?
Dom: Should you take it or not? Yeah, I get that question a lot. For GI cancers and liver cancer, I would say do not supplement glutamine, and I would say under most conditions...I always say in those states, I actually tried to look up the glutamine content of food, and you might want to avoid it or minimize glutamine, high glutamine-containing foods. Otherwise, I wouldn't really pay too much attention. Some patients really stress out about it but I think if you just keep your protein low to moderate, or keep your protein at a level to ensure proper regeneration and just, kind of, replenishment of your normal cells, and prevent protein deficiency, and being in a state of ketosis will help with that to some extent, but glutamine is pretty low on...
Rhonda: The classical ketosis, right, where it's 10% protein?
Dom: Yeah, yeah, and I think that will lower your blood glutamine levels, just being on a ketogenic diet will do that. And then, you could further lower it by selecting protein food sources that are lower on the end of, are glutamine. I'm not for avoiding protein types of supplements, avoiding glutamine supplementation all together. And you may be able to further suppress glutamine by taking a supplement that's like high branched-chain amino acids, high essential amino acids. So taking a supplement that is formulated in a way that, kind of, gives you essential amino acids, excluding glutamate, of course. Glutamine is not an essential amino acid. It's conditionally essential. But then you...I don't think you'll run the risk of being deficient in glutamine in any way, but I would avoid, I would pay attention to it if you have a GI cancer or liver cancer, and then if...
Rhonda: The liver, I didn't know, but yeah, GI was...
Dom: So if you have, say, for example, like, a brain tumor and you're taking a drug that can impair systemically, you're taking something that impairs your GI function, and it may be helpful to take a little bit of glutamine because I don't...I really don't think...the gut's going to be very greedy when it comes to glutamine.
Rhonda: It's very greedy.
Dom: So I think just maybe even 5, 10 grams of glutamine to help repair your gut. We know that if your gut permeability is impaired, that can wreak havoc in your body as far as systemic inflammation. So try to...and there's other ways to repair your gut, too, but I think glutamine may be a factor in helping to ensure proper gut.
Rhonda: Yeah, there's definitely other ways. I mean, I think that you know, like I was saying, fiber, good diet, and things like that.
Dom: Exactly. But glutamine has been used in oncology. So, yeah, glutamine is for helping people with chemo combating the issues with chemo. And then glutamine has almost been like a staple, you know...
Rhonda: So they give it to chemo patients, kind of...
Dom: Help them recover part of the immune system, too.
Rhonda: Because your gut regulates the Immune systems well.
Dom: Your gut is, like, what, 70%, 80% of your immune system, right? So it's huge. So we want to keep your gut as healthy as possible. And there are many drugs out there that really impair gut mobil-, or...
Rhonda: And diets, too.
An amino acid having aliphatic side-chains with a branch (a central carbon atom bound to three or more carbon atoms). Among the proteinogenic amino acids, there are three BCAAs: leucine, isoleucine and valine.
Amino acids that cannot be synthesized by the organism, but must be supplied via diet. The nine amino acids humans cannot synthesize are phenylalanine, valine, threonine, tryptophan, methionine, leucine, isoleucine, lysine, and histidine.
A molecule composed of carboxylic acid with a long hydrocarbon chain that is either saturated or unsaturated. Fatty acids are important components of cell membranes and are key sources of fuel because they yield large quantities of ATP when metabolized. Most cells can use either glucose or fatty acids for this purpose.
An amino acid found in high concentration in every part of the body. In the nervous system, glutamate is by a wide margin the most abundant neurotransmitter in humans. It is used by every major excitatory information-transmitting pathway in the vertebrate brain, accounting in total for well over 90% of the synaptic connections in the human brain.
One of the most abundant non-essential amino acids in the human body. Glutamine plays key roles in several metabolic functions, including protein and glutathione synthesis, energy production, antioxidant status, and immune function. In addition, it regulates the expression of several genes. Although the body can typically produce all the glutamine it needs, during periods of metabolic stress it must rely on dietary sources of glutamine such as meats, fish, legumes, fruits, and vegetables.
A critical element of the body’s immune response. Inflammation occurs when the body is exposed to harmful stimuli, such as pathogens, damaged cells, or irritants. It is a protective response that involves immune cells, cell-signaling proteins, and pro-inflammatory factors. Acute inflammation occurs after minor injuries or infections and is characterized by local redness, swelling, or fever. Chronic inflammation occurs on the cellular level in response to toxins or other stressors and is often “invisible.” It plays a key role in the development of many chronic diseases, including cancer, cardiovascular disease, and diabetes.
Experiments that are performed using cells or microorganisms outside of their normal biological context and are often done in a test tube or petri dish.
A diet that causes the body to oxidize fat to produce ketones for energy. A ketogenic diet is low in carbohydrates and high in proteins and fats. For many years, the ketogenic diet has been used in the clinical setting to reduce seizures in children. It is currently being investigated for the treatment of traumatic brain injury, Alzheimer's disease, weight loss, and cancer.
A class of proteins present in many edible plants, such as grains or legumes. Lectins are carbohydrate-binding molecules. They have been referred to as antinutrients for their ability to impair absorption of some nutrients. Many lectins possess hemagglutinin properties, which means they can bind to blood cells and cause them to aggregate. Cooking typically denatures lectins in foods.
Tiny organelles inside cells that produce energy in the presence of oxygen. Mitochondria are referred to as the "powerhouses of the cell" because of their role in the production of ATP (adenosine triphosphate). Mitochondria are continuously undergoing a process of self-renewal known as mitophagy in order to repair damage that occurs during their energy-generating activities.
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