Post-prandial inflammation and fasting as a method to counteract it. | Charles Raison
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Eating food is hard on the gut as it involves the ingestion of foreign substances. The gut lining becomes slightly compromised with each meal, and the immune system is activated. Humans may have evolved strategies to counteract these risks. For example, the inflammatory response that is triggered after a meal contributes to a less hospitable environment for foodborne pathogens. Furthermore, diet-induced thermogenesis, a rise in body temperature that occurs after eating, may also serve an antibiotic role. Periods of fasting have a powerful anti-inflammatory effect. In this clip, Dr. Charles Raison describes strategies that have evolved to offset the risks associated with eating, such as inflammation and the antibiotic effects of hyperthermia.
- Rhonda: I think you had even published some studies, or a study, talking about the effects of exercise on, what was very interesting to me, what you had called the inflammatory response that was induced post-prandial, so after you eat a meal.
- Charles: Oh, yes. That’s a big...
- Rhonda: It is. What’s interesting to me is I’ve only really, I’ve heard one other person, one of a colleague of mine who’s brilliant, his name is Mark Shigenaga. He is a gut expert, so he studies the gut, gut health, microbiome. He talks about how this postprandial inflammatory response occurs, because food is hard on the gut and...
- Charles: It’s a foreign substance, the risk. I mean, thousands of people die every year from eating out in the United States.
- Rhonda: Yeah, that’s true. But even in addition to that, in addition to the bacteria that can, you know, come along with eating some bad food, is that just that the gut itself, the gut barrier is sort of to some degree, gets compromised with every meal, you’re releasing a little bit of endotoxin in the bloodstream, because your immune system is activated.
- Charles: Leaky gut.
- Rhonda: Yeah, and so there is an inflammatory response that occurs, insulin, you know, in itself, the insulin response and all that. So I thought it was very interesting that you were looking specifically at that, and the effects of exercise, that exercise had on that.
- Charles: No, I don’t think that that... But we’ve written about this phenomena.
- Rhonda: Oh, you’ve written about it? Okay.
- Charles: Well, you know, and the other thing is when you eat, it kind of gives you fever. Do you know about diet-induced thermogenesis? So every time you eat, your body temperature elevates. It’s why people sweat after they eat, you know, because it’s not a fever per se, because I don’t think it is... I don’t know whether upper regular is a thermal related set point, but we’ve known for years that, and again you think about well why, partly because you’ve got to burn off the energy, but it may also be that again hyperthermia has antibiotic effects, right? So it is true that when you, it is, you know, any time a foreign substance comes in contact with a vulnerable entry point into the body, there’s a risk of infection and death, right? There’s a risk of infection and death, there’s a risk of pathogen manipulation, there’s all sorts of things. So it shouldn’t be surprising that that happens, nor should it be surprising that fasting has a powerful anti-inflammatory effect. There’s some beautiful data in animals, but also beautiful data in human too. There was a study in 19 normal volunteers, and they looked at the effect of a, like a 24-hour fast on something called the NLRP3 inflammasome. It’s the intercellular thing that connects up and it activates inflammation, turns on this thing called IL1 Beta. So you fast, and that the expression, the gene expression for that complex, just goes down, down, down, down, down. Then they let the people eat again, it goes up, up, up, up, up. And they look at sort of leaky gut, and you find that eating sort of opens the gut up to leakiness too. Which may be just a bummer, that may just be that we can’t be built better than that. Or it may be an evolved adaptive mechanism to kind of activate a little bit of inflammation, you know, that when you kind of get things kicked up in your body, you look around. I think the core idea here, and we’re talking about this in terms of the evolution of depression, is nature is really smart. It’s a compromise, it’s not perfect. But, you know, you go, “Geez man, that’s bad. You get a leaky gut when you eat.” Well yeah, but across millions of years, if that was so bad, the gut would have figured out a way not to do that. It probably is an evolved strategy that every time you are exposed to death by an infection, the body responds with a little bit of pre potent inflammatory response, just to get everything kicked up and to deal with it, you know. And of course, yeah, you pay a little bit of a price in terms of tissue damage, but it’s a smoke alarm principle. That little bit of damage is more than outweighed for the one time you don’t do it then you die.
- Rhonda: Yeah, right. So it totally makes sense, because the gut is what is exposed, the internal environment, I mean. So that’s...
- Charles: I mean, when you think about it, that’s the big one, right?
- Rhonda: Right.
- Charles: I mean, the skin is a much more robust protector against... Any membrane that’s wet, it’s just bad news in that way. But it has to be for us to survive to eat, and it’s sort of the compromise that we’ve evolved.
A mood disorder characterized by profound sadness, fatigue, altered sleep and appetite, as well as feelings of guilt or low self-worth. Depression is often accompanied by perturbations in metabolic, hormonal, and immune function. A critical element in the pathophysiology of depression is inflammation. As a result, elevated biomarkers of inflammation, including the proinflammatory cytokines interleukin-6 and tumor necrosis factor-alpha, are commonly observed in depressed people. Although selective serotonin reuptake inhibitors and cognitive behavioral therapy typically form the first line of treatment for people who have depression, several non-pharmacological adjunct therapies have demonstrated effectiveness in modulating depressive symptoms, including exercise, dietary modification (especially interventions that capitalize on circadian rhythms), meditation, sauna use, and light therapy, among others.
A type of toxin released when bacteria die. Endotoxins can leak through the intestinal wall and pass directly into the bloodstream. The most common endotoxin is lipopolysaccharide (LPS), a major component of the cell membrane of gram-negative bacteria. If LPS leaks into the bloodstream, it can trigger an acute inflammatory reaction. LPS has been linked with a number of chronic diseases, including Alzheimer’s disease, inflammatory bowel disease (Crohn’s disease or ulcerative colitis), cardiovascular disease, diabetes, obesity, autoimmune disorders (celiac disease, multiple sclerosis, and type 1 diabetes), and psychiatric disorders (anxiety and depression).
The process in which information stored in DNA is converted into instructions for making proteins or other molecules. Gene expression is highly regulated. It allows a cell to respond to factors in its environment and involves two processes: transcription and translation. Gene expression can be turned on or off, or it can simply be increased or decreased.
A component of the innate immune system. The inflammasome is expressed in the myeloid cells and promotes the maturation of the pro-inflammatory cytokines IL-1B and IL-18. It is responsible for activation of inflammatory processes.
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.
A peptide hormone secreted by the beta cells of the pancreatic islets cells. Insulin maintains normal blood glucose levels by facilitating the uptake of glucose into cells; regulating carbohydrate, lipid, and protein metabolism; and promoting cell division and growth. Insulin resistance, a characteristic of type 2 diabetes, is a condition in which normal insulin levels do not produce a biological response, which can lead to high blood glucose levels.
A proinflammatory cytokine produced by macrophages. IL-1 beta is an important mediator of the body’s inflammatory response. It is involved in a variety of cellular activities, including cell proliferation, differentiation, and apoptosis.
Otherwise known as intestinal permeability – a condition in which gaps form between the tight junctions of the endothelial cells that line the gut. These gaps allow pathogens like bacteria or endotoxins – toxins that are released when bacteria die – to leak through the intestinal wall and pass directly into the bloodstream. The most common endotoxin is lipopolysaccharide (LPS), a major component of the cell membrane of gram-negative bacteria. If LPS leaks into the bloodstream, it can trigger an acute inflammatory reaction. LPS has been linked with a number of chronic diseases, including Alzheimer’s disease and cardiovascular disease.
The collection of genomes of the microorganisms in a given niche. The human microbiome plays key roles in development, immunity, and nutrition. Microbiome dysfunction is associated with the pathology of several conditions, including obesity, depression, and autoimmune disorders such as type 1 diabetes, rheumatoid arthritis, muscular dystrophy, multiple sclerosis, and fibromyalgia.
In general, anything that can produce disease. Typically, the term is used to describe an infectious agent such as a virus, bacterium, prion, fungus, or other microorganism.
Relating to the period after eating. Postprandial biomarkers are indicators of metabolic function. For example, postprandial hyperglycemia is an early sign of abnormal glucose homeostasis associated with type 2 diabetes and is markedly high in people with poorly controlled diabetes.
A physiological process that results in the production of heat. There are two types of thermogenesis: shivering and nonshivering. Shivering thermogenesis, as its name implies, involves shivering to produce heat. During shivering, skeletal muscles undergo repeated, rapid contractions that produce little net movement and instead, produce heat. Nonshivering thermogenesis generates heat in the absence of shivering by unique mechanisms in both skeletal muscle and adipose (fat) tissue depots. These processes involve uncoupling electron transport from ATP synthesis and repetitive, non-productive transport of ions across the adipose cell membrane.
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