Newsletter #228 - Hard Exercise, Immunity, and Fighting Cancer 💪🏻
A new study, published this month, found that the incidence of early-onset cancers (meaning those diagnosed before the age of 50) has risen substantially worldwide. Interestingly, the data showed a birth cohort effect. As one of the authors stated, "We found that this risk is increasing with each generation. For instance, people born in 1960 experienced higher cancer risk before they turn 50 than people born in 1950 and we predict that this risk level will continue to climb in successive generations."
Why is this happening? Well, improvements in early detection and screening programs are obviously part of the picture, but that doesn’t fully explain this increase. The researchers noted that the rise in early-onset cancer was tightly correlated with various lifestyle trends that started around the mid-twentieth century. One such lifestyle factor, of course, is exercise.
Now, exercise influences cancer in a few different ways. It may do so indirectly, by lowering body fatness, which itself is independently associated with cancer. Furthermore, there are an array of chronic systemic effects of regular exercise, like lowered inflammation and reproductive hormones, which in turn would reduce risk of some cancers. However, some relatively new research suggests that exercise might also help fight cancer through transient shifts in various metabolites and signaling factors in the blood These changes are fairly short-lived, usually returning to baseline within an hour or two following the exercise bout, but could add up over time through repeated exposure. And the biggest payoff, in this context, comes from more intense exercise.
Why does strenuous exercise, specifically, have this effect? And what metabolites are responsible for the reduction in cancer risk? To get the answers to these questions, scroll on down!
This Week's Research Highlights
🚴♀️ Elite athletes are much less likely to die from cancer, compared to the general population.
Researchers in Paris analyzed data from 2814 French Olympians from 1912-2012 (more than a century of followup!). They found that these athletes lived, on average, 6 and a half years longer than comparable individuals in the general population. The impressive longevity advantage enjoyed by Olympic athletes was mainly attributable to lower risk of cancer, and secondarily to reduced cardiovascular risk (much as you would expect). This finding is further supported by a meta-analysis of ten cohort studies, including mortality data from a total of 42,807 professional/elite athletes, which found that top athletes had a 27% lower risk of cardiovascular death and a 40% lower risk of dying from cancer. In other words, members of the population who arguably engage in the largest number of bouts of strenuous exercise seem to be remarkably protected from cancer.
🩸 Metabolites generated during exercise improve the anti-tumor efficacy of immune cells.
To gain insight into some of the molecular mechanisms that underlie the relationship between physical activity and mortality, researchers in Sweden conducted a series of experiments using a special strain of mice that 1) are susceptible to developing cancer and 2) love to run. (Obviously a convenient combo of attributes for answering this question.) When the animals were provided a running wheel, they experienced reduced tumor growth and lived longer than counterparts that weren’t able to exercise, and this appeared to be due to alterations in cytotoxic T cells, the immune cells that attack and kill cancer. To isolate these effects, the scientists extracted T cells from mice that had been training on the exercise wheel, and transplanted them into sedentary rodents that had melanoma. Sure enough, these mice fared significantly better than controls that got T-cells from sedentary donors. But how exactly does exercise do this? The researchers put mice (and human volunteers) through an exhaustive exercise test, and then harvested plasma from them. When they analyzed the samples, they found changes in a host of metabolites. But the biggest change was an increase in lactate, which makes sense; lactate rises exponentially when you hit the anaerobic threshold, increasing up to 100-fold in muscle and 10-fold in plasma. Finally, to see if lactate was driving these positive changes in immune cells, the researchers infused mice with sodium L-lactate at doses that resulted in plasma lactate levels close to what is seen through bouts of intense exercise. And indeed, tumor growth was significantly attenuated.
🏃♂️ Lactate specifically rejuvenates T-cells, making them better at fighting cancer.
Interested in better understanding how exactly lactate improves the ability of T-cells to infiltrate tumors, researchers injected either glucose or lactate directly into mice that had tumors transplanted into their bodies. Glucose, as expected, did not do anything, but the lactate suppressed tumor growth substantially. When the scientists extracted tumor tissue from rodents that had been treated with lactate, and compared them to controls, they observed that more cytotoxic T cells had infiltrated the tumors, much as we saw in the previous experiments. When they looked a little closer at the T cells that were being boosted in these tumors, they noticed that stem-like T cells were increasing the most. Stem-like T cells are, in effect, youthful, and still able to respond to stimulation to become highly specific cancer-fighting cells, so this is definitely a good thing. They also noted that lactate treatment increased expression of a transcription factor (TCF1) which regulates the function of T cells, promoting proliferation and stemness. TCF1 is considered to be a critical determinant of success in immunotherapy.
Random Trivia & Weird News
🧬 Due to their limited numbers, genetic diversity among cheetahs is so low that they can readily accept skin grafts from ostensibly unrelated individuals.
As you probably know, it is quite difficult to transplant organs and successfully maintain them because our adaptive immune system is able to identify differences in the proteins on the cells of the transplanted tissue and reject them as being “non-self.” In humans, it is fairly rare to find a perfect match in the most critical antigens, outside of identical twins.
However, cheetahs are so genetically similar to one another that they can accept such transplants with little risk of rejection, almost as though they were clones of one another. This is partly attributed to historical bottleneck events from thousands of years ago, which led to inbreeding, as well as the obvious recent reduction in their numbers due to climate change and habitat infringement.
Podcasts We Loved This Week
- Stuart Phillips: Bacterially synthesized whey, plant vs. animal proteins, muscle & extended fasts, & much more. Via Sigma Nutrition Radio.
- Seirian Sumner: Why you should thank your local wasp. Via Science Friday.
Products We Are Enjoying
One big drawback to training hard enough to generate substantial amounts of lactate is that it’s really freaking hard. This is where LactiGo can help.
When you exercise strenuously, lactic acid is generated, which is subsequently broken down into lactate and hydrogen ions. This causes cellular pH to drop, producing the well-known burning sensation and making it hard to maintain force production. However, carnosine has long been known to act as a pH buffer, and higher levels of carnosine in muscle can help prevent accumulation of hydrogen ions during high-intensity exercise. This increases the power you can produce during a workout, and potentially aiding recovery, while still enabling you to reap the benefits of lactate-generating activity. Pretty cool!
To learn more about how it works, and how it could enhance your own training, check out our past interview with Brad Dieter, LactiGo’s lead scientist.
humanOS Catalog Feature of the Week
How-to Guide - Ergogenic Aids (Athletic Enhancers)
An ergogenic aid is simply a supplement that enhances physical performance. Dietary intake of these substances can, in theory, affect training adaptations in a couple of different ways. They can achieve this by simply increasing the exercise stimulus from a single training bout - basically just enabling an athlete to train longer or harder, or reducing perceived exertion. But they may also be able to affect gains in endurance by altering cellular responses to exercise-induced stress.
Importantly, these changes in cell signaling may not be universally beneficial from the standpoint of adaptation. For example, it is theoretically possible that a supplement could simultaneously make it easier for an athlete to exercise hard, but also have effects on cellular signaling that actually have a long-term negative impact on the adaptive response to training.
In this guide, we review some of the most rigorously researched supplements (including LactiGo), discuss how best to use them, and talk about why some supplements that sound like a good idea may actually not be helpful at all. If you are looking for a quick reference sheet of the latest evidence-based guidance on supplements to maximize your performance and adaptations, check it out! 👀
Thanks for reading, enjoy the weekend, and we'll see y'all next week!