#032 Does Meat Consumption Cause Cancer?

Meat cancer link disappears in healthy people

Patrick breaks down a landmark JAMA study showing that the association between meat consumption and cancer mortality only holds for people with other unhealthy lifestyle factors like obesity, smoking, or inactivity - healthy meat eaters showed no increased risk.

"This pattern only held up for participants with at least one other factor associated with an unhealthy lifestyle, like being obese or being a heavy consumer of alcohol or having a history of smoking or being physically inactive."

IGF-1 the double-edged sword of growth and cancer

Patrick explains how IGF-1 from protein/meat consumption is essential for muscle, brain health, and neurogenesis, but also promotes cancer cell survival - and how periodic fasting can reduce IGF-1 to offset cancer risk while still getting its benefits.

"Hello, ladies and gents. Today is a brief topic-focused podcast centralizing on one question. Does eating meat cause cancer? Question mark, exclamation point, question mark, exclamation point. Or put another way, does avoiding meat help prevent cancer? I have heard this question in some form now, probably close to a couple hundred times. Meat is a bit of a polarizing topic. If you aren't already savvy to the topic, this may sound a bit more absurd than it should. Here's why. There have been many, many, many correlative studies that have found that higher meat consumption is associated with a significantly higher risk of cancer and also cancer mortality. With such a relationship showing up not once, but multiple times across multiple studies, it's actually a legitimate concern. Sure, the data is correlative, but it does at least become a bit harder to dismiss the relationship out of hand altogether when it keeps popping up over and over. So where do we go from here? If we're ever to get a real hold on what's going on, we need to start asking ourselves what the mechanism is. Noticing a pattern is just the beginning. The next step is to try to figure out what is actually driving the relationship. In 2016, a study came out in JAMA Internal Medicine entitled Association of Animal and Plant Protein Intake with All-Cause and Cause-Specific Mortality. This study was the largest population study to date. And while it still held with the pattern mentioned a moment ago, specifically finding that a high intake of meat from animal sources was associated with a higher mortality rate and cancer mortality rate, a more careful analysis within the paper revealed something interesting. This pattern only held up for participants with at least one other factor associated with an unhealthy lifestyle, like being obese or being a heavy consumer of alcohol or having a history of smoking or being physically inactive. Meat consumers that were healthy by not having any of these aforementioned unhealthy lifestyle factors did not have a higher mortality rate or higher cancer mortality rate. I have some general thoughts on why this might be the case, but in order for me to explain them, it helps to have a quick biology lesson. First on cancer initiation, and then secondly, on a very important pathway known as the IGF-1 or the insulin-like growth factor 1 pathway. What causes a normal cell to become a malignant cell is damage. At the most basic level, just by being alive, our cells are churning out damaging products known as reactive oxygen species as a byproduct of our cell's energy production known as respiration. So our cells can naturally mitigate that in a variety of ways. But we can increase that rate of ongoing damage by introducing more environmentally, perhaps by making poor lifestyle choices that cause us to produce more damaging molecules and compromise our ability to repair DNA. But no matter what, some amount of damage still happens. When some of that damage makes it through, the good news is that the cell just often dies. I know that sounds like bad news, but it's good news. Bear with me. The reason that happens is because our cells expect some degree of damage and have programs in place in the form of tumor suppressor genes and other genes involved in programmed cell death, known as apoptosis, that ensure cells self-destruct or at the very least stop these cells from dividing, known as cell cycle arrest, before they get too weird. But what happens if that cell's DNA experiences damage that just happens to strike and disable the very program that ensures this process of self-destruction, known as apoptosis, occurs? Well, that'd be pretty unlucky, but it might mean that the cell would just go on living when it should have died. Then most likely, it would eventually give rise to daughter cells. And in an environment where there's a high rate of DNA damage, these cells too would experience DNA damage, which knocks out even more tumor suppressor genes. And then after a few generations, some of the genes involved in growth and proliferation become mutated, making them constantly active. And once this happens, these genes become known as oncogenes. Then maybe genes involved in cell adhesion become affected by DNA damage and mutate, and this leads to metastasis. What you have then is a sort of evolution, literally descent with modification going on that just happens to be disadvantageous for the rest of the organism. That's cancer. And that's because of DNA damage. And it's why we want to reduce DNA damage in our lives if we can. Obesity, smoking, heavy alcohol consumption, and physical inactivity have all been shown to increase mortality risk independent of meat consumption. And all of these unhealthy lifestyle factors have also been shown to cause inflammation and DNA damage, both which are well-known cancer initiators, as I just explained. As a matter of fact, inflammation also produces damaging products known as reactive nitrogen species, which, similar to reactive oxygen species, also damage DNA. But it's not enough to have one or two malignant cells sitting around. To really get things going, we need something more. We need growth signals. This is where IGF-1 enters. IGF-1 is a growth factor that plays a very important role during early growth and development, and also is important in promoting and maintaining muscle mass and neuronal function. There are many positive benefits to IGF-1, but there is also a trade-off, as there so often is in biology. IGF-1 is a very potent growth factor that allows cells that have been damaged to survive when they otherwise would die. In other words, if we take our hypothetical damaged cell, which maybe a few tumor suppressor genes are knocked out and mutated in a cellular environment absent that IGF-1, it might actually still self-destruct or undergo apoptosis. Biology tends to create resilient, redundant systems in that way. But then if we throw a bunch of IGF-1 at it, that outcome becomes less likely. Instead, it's more likely to live on passing the normal cell cycle checkpoints and will continue to give rise to new daughter cells and even increasing the proliferation rate. As a pathway for this reason, IGF-1 is actually of great interest in both cancer and longevity research. We know from animal evidence that growth hormone and IGF-1 deficient mice are resistant to cancer. Interestingly, this evidence isn't limited to animal research. Some humans also have polymorphisms in the gene that encodes for the IGF-1 receptor, which leads to a decrease in IGF-1 activity in these individuals. Similar to animal research, we see a decrease incidence in cancer and also longer lifespans in these people. Human evidence also exists for the exact opposite. People that have genetic polymorphisms that cause them to have increased IGF-1 also have an increased cancer risk. If we get away from the genetic polymorphisms and just look at people with higher circulating IGF-1 in their serum, something that can be quantified, this has also been associated with an increased risk of several common cancers, including breast, colon, and prostate cancer. So high IGF-1, higher cancer risk, low IGF-1, reduced cancer risk, and even longevity. Got it? This is where meat comes in. Meat, unlike plants, is of course extremely rich in protein. And protein, particularly the essential amino acids found in protein, directly affect our IGF-1 levels by increasing them. Moreover, essential amino acids, which are disproportionately found in meat, have more of an effect on increasing serum IGF-1 compared to non-essential amino acids. And in terms of essential amino acids that have the most potent effect on IGF-1, the branched-chain amino acid leucine, often supplemented by bodybuilders, is especially effective at increasing IGF-1 activity. With this new understanding of the relationship of meat consumption to IGF-1 production and IGF-1's relationship with cancer and longevity, where it even inhibits the longevity gene FOXO3, it would be very tempting and very easy to take an absolutist position and never touch meat again, putting aside all of the other reasons why someone might make such a choice. In fact, with gene engineering on the horizon, we might even opt to swap out our IGF-1 receptors for the less active ones found in human populations. The problem is that IGF-1 has been shown to increase lean muscle mass and reduce adipose tissue simultaneously. It acts as a neurotrophic factor, increasing the growth of new brain cells. It prevents brain cells from dying. Age-related decline in IGF-1 is associated with muscle atrophy, neuronal loss, skin thinning, growth hormone replacement, the activities of which are mediated mostly through IGF-1, has also been shown to maintain muscle mass, decrease fat, boost executive function and verbal memory. Moreover, folks with IGF-1 polymorphisms that reduce activity actually suffer from a type of dwarfism. I think knowing all of this, if we assume that IGF-1 is the mediating factor in these studies, showing an association with meat consumption and cancer, it makes the choice a little bit trickier. It's pretty clear that I actually want some IGF-1 activity. But if we separate this process of cancer development and consider that we need both cancer to be initiated and then for it to thrive, we can come to some conclusions. The first is that we need to avoid cancer initiation events. We must adhere to a lifestyle that, as much as possible, mitigates DNA damage and maximizes DNA repair processes. In a big way, that's a part of my lifestyle philosophy that I try to share with the wider world. There are so many factors that we know of that are unhealthy and can increase DNA damage. We've talked about quite a few today, but there are many more out there that we're finding all the time. Here's another example, excess consumption of refined sugar. Healthy men that were given 20 ounces of a sugar-sweetened beverage, which is essentially refined sugar, to drink daily for three weeks experienced an increase in the biomarker of inflammation called C-reactive protein by as much as 60% to 100% over their baseline levels. If we increase our inflammation, we increase our DNA damage. Moreover, if we lack magnesium, which is found at the center of a chlorophyll molecule and richly found in green leafy plants, our ability to repair our DNA is impaired because these enzymes require magnesium. The other conclusion that we can come to based on this information is that in the context of IGF-1, maybe we should seek balance and consider the context in which we encourage IGF-1 activity. If we're not physically active, which itself mitigates some degree of cancer risk, then maybe we don't need quite as many essential amino acids in our lives. A more plant-based diet with less, if any, meat may be more ideal for the sort of person who might be loosely characterized as Joe Sixpack or Johnny Smoker, the sort of people that probably do not have much intention on implementing other healthy lifestyle changes. But conversely, maybe for someone that's hitting the weights hard five to six times a week, it isn't as bad of a situation, especially when the consumption of these amino acids is actually correlated in time with the exercise activity. In fact, while high circulating IGF-1 is what has been specifically correlated to cancer risk, we do have another way of reducing serum IGF-1. By exercising, whether we're talking about aerobic or resistance training, both have been shown to lower serum IGF-1. Exercise causes our muscles to take up IGF-1. Additionally, IGF-1 has been shown in rat studies to cross the blood-brain barrier in response to exercise, and it's thought that this may be one of the important mechanisms by which exercise actually increases neurogenesis because of the effects IGF-1 has on increasing the expression of brain-derived neurotrophic factor, which is one of the most important growth factors fundamental to fueling new brain cell growth, a process known as neurogenesis. Finally, we have one more possibility that's worth at least a mention. Instead of engineering a lifestyle in which we either commit to a diet that leads us to having diminished IGF-1 levels at the cost of some of the benefits that we might receive from having more, or having higher IGF-1 levels at the cost of having an increased risk of cancer or reduced longevity, we might also consider having periodic episodes of deprivation as a way of hedging our bets. If you listen to my podcast with Dr. Valter Longo or some of the other podcasts that I've covered on this topic, you might know where I'm going with this. Fasting. Specifically, prolonged fasting on the order of four to five days in particular has been demonstrated to induce a cellular cleanup mechanism known as autophagy, along with a concomitant reduction in IGF-1 that happens even as early as the first 24 hours of the fast, and indeed even improves biomarkers of longevity. Autophagy is your body's way of cleaning up damage or dysfunctional cells it may have sitting around. It may be possible that by introducing cycles characterized by periods of breaking down and then renewal, we may also be offsetting the risk we might introduce by also benefiting from periodically boosting our IGF-1 production. Only future research, however, will let us know for sure. So there you have it. We've gone from the macro to the micro and back again. We've made a case for why associations between cancer and meat consumption may exist. We've talked about some of the interesting confounders shown in one of the largest associative studies to date. We've talked about one of the most important pathways to cancer and longevity, and some of the choices we're faced with having this knowledge. We've also talked about certain strategies that might help us get the best of both worlds. The one thing that I haven't actually talked about is what I do. In practice, I walk the middle path. I try to view plants, usually as the main course, with meat as a side item. When eating meat, I often emphasize wild Alaskan salmon in order to get a dietary source of marine omega-3 fatty acids, which would be challenging to get dietarily otherwise. I also tried to time the consumption of meat with my bouts of exercise, and in general, try to stay especially physically active. Okay folks, time for our wrap-up. If you enjoyed this podcast more than a hound dog loves a milk bone, make sure to tell a friend or two about it and tell them to jump on my email newsletter found at my website. That's one of the best ways you can show all found my fitness a little bit of love and support. And it's free and anyone can do it. The next best way is to kick a few bucks in the can. I'm always striving to bring bigger and better things to you guys, including interviews with amazing scientists, informational videos, in-depth articles, and so much more. And as time goes on, I want to keep just making them better. This by necessity means more human energy as an input. You can learn more about making a pay what you can monthly page by heading over to foundmyfitness.com forward slash crowd sponsor. That's foundmyfitness.com forward slash C-R-O-W-D-S-P-O-N-S-O-R, crowd sponsor. Finally, if this IGF-1 is totally your bag, make sure to check out my podcast interview with the director of the Longevity Institute at the University of Southern California, Dr. Walter Longo. We talk about fasting, IGF-1, cancer, and so much more. And if you watch it on YouTube, I even add in helpful visual annotations to help make the conversation easier to follow. Get that conversation here on iTunes or on YouTube by going to youtube.com forward slash foundmyfitness. Once again, that's youtube.com forward slash foundmyfitness. Until next time, thanks for listening. Dr. Rhonda Patrick over and out."

Exercise lowers serum IGF-1 and drives neurogenesis

Both aerobic and resistance training lower circulating IGF-1 by driving muscles to absorb it, and exercise causes IGF-1 to cross the blood-brain barrier where it increases brain-derived neurotrophic factor and fuels new brain cell growth.

"By exercising, whether we're talking about aerobic or resistance training, both have been shown to lower serum IGF-1. Exercise causes our muscles to take up IGF-1."