Rhonda Patrick and Tim Ferriss discuss metformin as a possible cancer prevention drug
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A growing body of evidence suggests that metformin, a drug commonly used for the treatment of type 2 diabetes, is associated with a reduced risk of developing or dying from several types of cancer in adults with diabetes. Metformin acts by decreasing the production of glucose in the liver, decreasing glucose uptake in the gut, and increasing overall glucose utilization by improving insulin sensitivity in skeletal muscle and fat tissue. Since the long-term consequences of metformin are unknown, a viable approach to depriving cancer cells of glucose, their preferred energy source, might be to limit dietary sugar intake. In this clip, Tim Ferriss and Dr. Rhonda Patrick discuss the anti-cancer properties of the diabetes drug metformin.
- Tim: I've been thinking about it also because cancer generally . . . by the time you're 40, we all have pre-cancerous little cells. But the question is do they grow? Do they then metastasize or become a problem, or do they just remain these little mutations that don't cause any particular harm among other things obviously? For me, I've become also interested in . . . I'd love to get your opinion on metformin. There are people who'd say, "Well, if you want to try to dodge that cancer bullet, we know that cancer cells, they love sustaining themselves anaerobically . . . or let me rephrase that, with glucose. They love glucose. So if we can dramatically lower, whether it's storage of glycogen, plasma, glucose, whatever it might be, then in theory, we should be able to lower the risk of cancer and limit cancer growth, cancer cell growth. What are your thoughts on metformin and why are you taking it or not taking it?
- Rhonda: I'm not taking it. The reason I'm not taking it . . . I think it has been shown, like you said, it can possibly prophylactically prevent cancer so far. I think the studies that have shown that have been pretty short-term. My concern with metformin is the feedback mechanisms that happen when you're taking this drug. How is that going to affect other cells and how they respond to glucose and things like that over the long-term, like 15 years down the line? I think that limiting your sugar intake is probably . . . if you haven't damaged yourself by eating a bunch of crap, a bunch of processed sugars and carbohydrates and things like that, then I think limiting your sugar intake is probably good, good enough. To a certain component, there's a certain component of cancer that there is a genetic component. What I mean by that is not that you're born with it but . . . so, downstream of a cell that's glycolytic, that's only using glucose to make ATP through this glycolysis pathway is inflammation again. I come back to it because it's just downstream of everything. And inflammation damages DNA and eventually you get it in the right gene that's saying, "Oh, this gene usually protects," whenever there's any damage, it kills a cell. It's called a tumor suppressor gene. You get it in that tumor suppressor gene, you're screwed. Now any time you get damaged, that pathway isn't activated to go, "Whoa, wait a minute, this is not good. I'm going to die. And it just keeps living."
- Tim: Yeah.
- Rhonda: If you look at, for example, our lymphocytes, our lymphocytes are glycolytic and they're not cancer. So it's not as simple as a glycolytic cell is going to give you cancer.
- Tim: No, no.
- Rhonda: But definitely starving . . . I think before you get to the point where you're starving a cancer cell, you can kill the damaged cell before it becomes to that point where it's shifted its metabolism.
- Tim: What do the lymphocytes do in a ketotic state?
- Rhonda: I don't know.
- Tim: Do they derive glucose form lactate or something?
- Rhonda: Yes. They do get it from lactate. Lactate is something that they do use. Yeah.
- Tim: Cool.
- Rhonda: It's interesting because lactate also is much like ketone bodies, energetically thermodynamically favorable. So it takes less energy to make energy.
- Tim: Yeah.
- Rhonda: So you're consuming less oxygen because you don't need as many ATP molecules to make ATP.
A highly branched chain of glucose molecules that serves as a reserve energy form in mammals. Glycogen is stored primarily in the liver and muscles, with smaller amounts stored in the kidneys, brain, and white blood cells. The amount stored is influenced by factors such as physical training, basal metabolic rate (BMR), and eating habits.
A series of enzyme-dependent reactions that breaks down glucose. Glycolysis converts glucose into pyruvate, releasing energy and producing ATP and NADH. In humans, glycolysis occurs in the cytosol and does not require oxygen.
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.
Molecules (often simply called “ketones”) produced by the liver during the breakdown of fatty acids. Ketone production occurs during periods of low food intake (fasting), carbohydrate restrictive diets, starvation, or prolonged intense exercise. There are three types of ketone bodies: acetoacetate, beta-hydroxybutyrate, and acetone. Ketone bodies are readily used as energy by a diverse array of cell types, including neurons.
Lactate is thought to participate in a sort of "lactate shuttle" where, after being produced in muscle from exercise, it is transported in to tissues like the heart, and brain, where it is used as an energy source. Lactate is one of many molecules that falls under a loose group of molecules referred to as exerkines, a broad group of exercise-induced hormonal-like factors. Evidence suggests that lactate is the preferred fuel of the brain. Additionally, rodent studies suggest that lactate mediates some of the benefits of exercise on learning and memory via inducing neuronal brain-derived neurotrophic factor (BDNF) expression.[1] In clinical studies, lactate shows promise as a treatment for inflammatory conditions including traumatic brain injury and as a means to deliver fuel to working muscles.
- ^ Helge, Jørn Wulff; Moritz, Thomas; Morville, Thomas; Clemmensen, Christoffer; Dela, Flemming (2020). Plasma Metabolome Profiling Of Resistance Exercise And Endurance Exercise In Humans Cell Reports 33, 13.
The thousands of biochemical processes that run all of the various cellular processes that produce energy. Since energy generation is so fundamental to all other processes, in some cases the word metabolism may refer more broadly to the sum of all chemical reactions in the cell.
Cancer that has spread from the part of the body where it started to other parts of the body. When cancer cells break away from a tumor, they can travel to other areas of the body through the bloodstream or the lymph system.
A drug commonly used for the treatment of type 2 diabetes. Metformin is in a class of antihyperglycemic drugs called biguanides. It works by decreasing gluconeogenesis in the liver, reducing the amount of sugar absorbed in the gut, and increasing insulin sensitivity. A growing body of evidence indicates that metformin modulates the aging processes to improve healthspan and extend lifespan. Furthermore, metformin may prevent genomic instability by scavenging reactive oxygen species, increasing the activities of antioxidant enzymes, inhibiting macrophage recruitment and inflammatory responses, and stimulating DNA damage responses and DNA repair.[1]
[1] Najafi, Masoud, et al. "Metformin: Prevention of genomic instability and cancer: A review." Mutation Research/Genetic Toxicology and Environmental Mutagenesis 827 (2018): 1-8.
A medication or treatment intended for the prevention of disease.
Genes that suppress cell division or growth. Tumor suppressor genes encode proteins involved in aspects of cell growth regulation such as cell cycle arrest and apoptosis. Loss of tumor suppressor gene function promotes uncontrolled cell division and growth, which are hallmarks of cancer.
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