How much protein should you eat? Muscle growth vs. IGF-1 longevity concerns | Rhonda Patrick
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There's a trade-off that occurs with aging and muscle growth. Whereas fasting turns off multiple pathways associated with aging, such as mTOR and IGF-1, eating for optimal fitness activates these important processes. The IGF-1 pathway, in particular, plays key roles in growth and is strongly associated with cancer. But it also participates in the repair of muscles and neurons and promotes brain health. Directing IGF-1 toward its more beneficial processes through exercise may offer protection from its deleterious effects. In this clip, Dr. Rhonda Patrick describes the dual nature of biochemical pathways involved in aging and explains how exercise tips the balance toward its beneficial properties.
- [Mike]: Let's talk about longevity because that's a lot of the reason that our audience and your audience, you know, is doing fasting.
So this is from Nina, "Can you elaborate on the growth longevity trade-off?" So you talked a little bit about that at the beginning with IGF-1 and longevity. So the growth, the longevity tradeoff. "By fasting, we down-regulate the aging pathways such as mTOR growth hormone and IGF-1." Clearly, Nina has done her homework and listened to you. "But in order to build muscle through resistance training, we need to eat protein and have these pathways activated in order to maintain, build muscle. Is there a way we can get the best of both worlds?" It's a great question. "Is the tradeoff overstated? How so? Thank you!" It's a meaty question, but it relates to a lot of what you talked about already.
[Dr. Patrick]: It does. And I think I will try to keep it as brief as possible. I think, you know, I do need to kind of just briefly explain, you know, the role of IGF-1, mTOR in, you know, aging, and then in the field of aging research. There have been many, many, many studies that have shown that higher IGF-1, particularly higher IGF-1, is associated with higher cancer incidence. And this has been shown, if you look in humans, you know, humans that have a mutation in genes that regulate IGF-1 that make them have like a higher IGF-1 level all the time, they kind of, they have actually higher cancer incidence than people that don't have those.
[Mike]: And the idea there is if your IGF-1 is high, it's a growth mechanism and is, could promote tumors to grow.
[Dr. Patrick]: Yes, exactly. So because IGF-1 is a growth signal, as you mentioned, it allows, basically, you know, when you have accumulated damage in your cells, whether that damage comes from the mitochondria and, you know, genomic damage, there are signaling pathways that are activated that say, "Look, the cells are too damaged to repair. I need to kill it. I need to get rid of it because I may acquire a very dangerous mutation that could allow cancer to survive." And so your body has this beautiful way of doing that. And it's called programmed cell death or apoptosis basically kill the cell.
But IGF-1, if IGF-1 is around and express at a high level, it's kind of around going, "No, no, no grow, grow, grow. You're cool. And you can stay. I'm here. "
[Mike]: Forget about the damaged cell. Let's just move on.
[Dr. Patrick]: Yeah, forget about. Yeah. So it basically overrides those checkpoints that says die. And so it can become very dangerous because then it can allow us one cell to then grow, which then replicates and makes more cells. And then you eventually get the formation of a tumor. Sometimes this takes several decades to happen. And then, of course, you know, it bypasses immune point, immune cells and things like that that are also involved in killing the cells.
But that is important way that IGF-1 plays a role in cancer. Humans that have more of it have a higher cancer incidence and the vice versa. So humans that have mutations that make less of it have less cancer incidence.
It's been shown in many, many animal studies. Dr. Valter Longo has shown this, and so many others that, you know, IGF-1 can override, you know, if you basically inject human tumor cells into a mouse and increase their IGF-1 by a variety of modalities, including high protein intake, you can actually allow the cancer cells to grow faster.
[Mike]: Yeah. And just real quick on the high protein intake, I mean the latest diet trend, I think it's waning, it's just been protein, protein, protein, right? And so, I mean, we have yet to see the impacts, you know, long term of all that protein uptake, which is I think interesting. I don't want to concern people, but I, you know, protein does upregulate IGF-1, correct?
[Dr. Patrick]: Yeah, it does. You know, and to address the good part of IGF-1, I mean, so, so we talked about this bad part where it is...
[Mike]: Yeah. And Nina is asking you know about that tradeoff.
[Dr. Patrick]: Exactly. And, you know, IGF-1, in addition to the cancer, it also deactivates a very important longevity pathway and gene in the body called FoxO which is really, really associated with...it regulates all sorts of genes that are involved in repair and stem cell production, autophagy. All those turns things.
[Mike]: IGF-1.
[Dr. Patrick]: Turns that off.
[Mike]: Turns that off.
[Dr. Patrick]: It turns off autophagy, all that stuff.
[Mike]: Interesting. Okay. She is speeding. No protein?
[Dr. Patrick]: No. So the tradeoff is that IGF-1 has a really good, it's also very important. I mean, obviously during development, it's part of the growth pathway. You need it to grow. But it's also an important grow pathway in muscle to repair muscles, to grow muscle, which is also important for longevity. I mean, there's multiple studies that have come out even recently showing that muscle mass is really important for lowering all-cause mortality and preventing frailty and things like that. It also gets into the brain as an important growth factor for neurons. It actually helps you grow new neurons that's called neurogenesis, and it actually helps prevent neurons from dying. So it allows the existing neurons to keep living. So it's an important signaling pathway in your brain and muscle.
I've seen a handful of studies in mice and in humans that have shown exercise, being physically active helps bring IGF-1 into the brain. So it crosses over the blood brain barrier and gets it into the brain where you want it and also gets into the muscle. So as opposed to having your IGF-1 around in your bloodstream, where then goes to other tissues, or it stays around and is being a growth signal for potentially damaged cells, you actually want it to get into your brain, into your muscle. So I think exercise and physical activity is a really good way to make sure that IGF-1 that you're getting is going to the right places.
[Mike]: Interesting.
[Dr. Patrick]: And in fact, there have been looking at protein intake and all-cause mortality that have shown that higher protein intake does increase all-cause mortality and cancer mortality as well. However, in people that have none of that unhealthy lifestyle factors that are looked at. For example, they're not obese, they are physically active, they don't smoke, they're not drinking excessive alcohol, and they still have high protein intake. They had the same mortality and cancer mortality rate as someone that has a lower protein.
[Mike]: That's a great recap. And I guess, intuitively, you know, if you're going to give your body all this fuel and growth, use it.
[Dr. Patrick]: Exactly. That makes sense.
[Mike]: Use it for what it's designed to do and then, but if you're giving you all that fuel and you're not using it, it can be left to do not so great things.
[Dr. Patrick]: Bad things. Yeah. But to sort of, I went on a tangent there to kind of get to the second part of her question, which was, you know...
[Mike]: Is there happy medium? What's the golden rule here?
[Dr. Patrick]: Where is the sweet spot? You know, for a long time it was thought, you know, this process what's known as calorie restriction, which does lower IGF-1, but you're doing it all the time. You're constantly eating like 30% less than what you would. And it's nice. You know, some people are kind of miserable doing it. You're chronically lowering your IGF-1. Is that good because you want IGF-1 for some things? And in fact, I had a conversation with Dr. Valter Longo, and he has even talked about the fact that, you know, the prolonged fast seemed to be a good sweet spot because you're doing a prolonged fast, you actually drop your IGF-1 during that fasting period. And that is what is critical for the apoptosis, the clearing away of the damaged cells. It's important to activate the stem cells.
But once you get to that point and you then refeed, you actually want IGF-1. You want IGF-1 because IGF-1 then allows the stem cells to grow and make more cells and replenish that population and regrow. So you, actually, there's this balance and it's like IGF-1 is important in that it plays an important, you want it lowered to get that whole clearing away and autophagy and apoptosis.
[Mike]: And the rebuilding.
[Dr. Patrick]: And then the rebuilding you wanted. So there's this nice sweet spot and I think that...
[Mike]: It's the beautiful machine of our body that it goes through modalities of cleansing. And it's the reason that I think fasting has become rightly very...intermittent fasting and caloric restriction has become so popular because you know, that's kind of how ancestrally, we were brought up. I mean, we didn't have, you know, 711's and supermarkets and cupboards full of food all the time or constantly eating. We had these natural breaks where we were hunting for food or gathering for food, and we weren't eating all the time. Our bodies were repairing. And then we got to refeed when we, you know, caught the deer and ate it. And then, you know, brought ourselves to that rebuilding phase.
[Dr. Patrick]: Exactly.
[Mike]: Replicating what for millennia we've been as humans designed to do.
[Dr. Patrick]: Exactly.
The death rate from all causes of death for a population in a given time period.
Programmed cell death. Apoptosis is a type of cellular self-destruct mechanism that rids the body of damaged or aged cells. Unlike necrosis, a process in which cells that die as a result of acute injury swell and burst, spilling their contents over their neighbors and causing a potentially damaging inflammatory response, a cell that undergoes apoptosis dies in a neat and orderly fashion – shrinking and condensing, without damaging its neighbors. The process of apoptosis is often blocked or impaired in cancer cells. (May be pronounced “AY-pop-TOE-sis” OR “AP-oh-TOE-sis”.)
An intracellular degradation system involved in the disassembly and recycling of unnecessary or dysfunctional cellular components. Autophagy participates in cell death, a process known as autophagic dell death. Prolonged fasting is a robust initiator of autophagy and may help protect against cancer and even aging by reducing the burden of abnormal cells.
The relationship between autophagy and cancer is complex, however. Autophagy may prevent the survival of pre-malignant cells, but can also be hijacked as a malignant adaptation by cancer, providing a useful means to scavenge resources needed for further growth.
The practice of long-term restriction of dietary intake, typically characterized by a 20 to 50 percent reduction in energy intake below habitual levels. Caloric restriction has been shown to extend lifespan and delay the onset of age-related chronic diseases in a variety of species, including rats, mice, fish, flies, worms, and yeast.
A naturally occurring substance capable of stimulating cellular growth, proliferation, healing, and differentiation. Growth factors typically act as signaling molecules between cells. Examples include cytokines and hormones that bind to specific receptors on the surface of their target cells.
A broad term that describes periods of voluntary abstention from food and (non-water) drinks, lasting several hours to days. Depending on the length of the fasting period and a variety of other factors, intermittent fasting may promote certain beneficial metabolic processes, such as the increased production of ketones due to the use of stored fat as an energy source. The phrase “intermittent fasting” may refer to any of the following:
- Time-restricted eating
- Alternate-day fasting
- Periodic fasting (multi-day)
An enzyme that participates in genetic pathways that sense amino acid concentrations and regulate cell growth, cell proliferation, cell motility, cell survival, protein synthesis, autophagy, and transcription. mTOR integrates other pathways including insulin, growth factors (such as IGF-1), and amino acids. It plays key roles in mammalian metabolism and physiology, with important roles in the function of tissues including liver, muscle, white and brown adipose tissue, and the brain. It is dysregulated in many human diseases, such as diabetes, obesity, depression, and certain cancers. mTOR has two subunits, mTORC1 and mTORC2. Also referred to as “mammalian” target of rapamycin.
Rapamycin, the drug for which this pathway is named (and the anti-aging properties of which are the subject of many studies), was discovered in the 1970s and is used as an immunosuppressant in organ donor recipients.
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.
The process of forming new neurons. Neurogenesis is essential during embryonic development, but also continues in certain brain regions throughout human lifespan.
A cell that has the potential to develop into different types of cells in the body. Stem cells are undifferentiated, so they cannot do specific functions in the body. Instead, they have the potential to become specialized cells, such as muscle cells, blood cells, and brain cells. As such, they serve as a repair system for the body. Stem cells can divide and renew themselves over a long time. In 2006, scientists reverted somatic cells into stem cells by introducing Oct4, Sox2, Klf4, and cMyc (OSKM), known as Yamanaka factors.[1]
- ^ Takahashi, Kazutoshi; Yamanaka, Shinya (2006). Induction Of Pluripotent Stem Cells From Mouse Embryonic And Adult Fibroblast Cultures By Defined Factors Cell 126, 4.
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