What Blood Testing Data Reveals About Runners' Health

I used to think running was a panacea. "If the furnace is hot enough, anything will burn, even Big Macs," as the fictional miler Quenton Cassidy once said. Then, about a decade ago, there was a big surge of doubt about the health effects of running. Most prominent was the suggestion that even modest amounts of running might damage your heart-"One Running Shoe in the Grave," as the Wall Street Journal put it-but running was also accused of broader sins like promoting inflammation, causing muscle loss, and wreaking havoc on blood sugar levels.

As a runner and a journalist, I spent a lot of time trying to understand these claims, and reevaluating my own understanding of running's health effects-a process that continues to this day. Part of that process involved going back to the original research that led us to believe that running is healthy. And to be honest, the evidence wasn't as clear as I'd assumed. Does running (or aerobic exercise more generally) really improve health markers, or is it just that healthy people are more likely to choose to run? Do the benefits max out after a few minutes per day, or do they keep growing? Can you outrun a bad diet?

I have opinions about all these questions, but I no longer assume that the answers are obvious. So I'm always interested in new data, like a recent study in PLoS ONE from the science team at InsideTracker, a company that sells personalized blood testing to track various health biomarkers. The paper offers a peek at the aggregated results of more than 23,000 customers who report various levels of running, divided into three groups: low volume (less than three hours of running per week), medium volume (three to ten hours per week), and high volume (more than ten hours per week). For comparison, they also include results from 4,400 sedentary non-runners, and at the opposite end of the spectrum, 82 professional distance runners.

There are two important caveats to point out before diving into the data. First, this is observational data, not a randomized trial. That makes it hard to determine whether running causes any of the patterns in the data (though, as we'll see below, there are some ways to test our assumptions about causation). Second, this is a self-selected cohort. Even the sedentary group is made up of people who are interested enough in their health that they've decided to spring for a service that starts at $699 for a single battery of blood tests. Since this control group is already fairly healthy, detecting any improvements will be more challenging.

The Raw Data

The journal article (which is free to read online) presents data on 27 different biomarkers that were significantly different between runners and non-runners. I'm just going to pick out a few categories that are particularly interesting.

First, here's HDL (i.e. "good") cholesterol levels, for females (f) and males (m) in each of the five groups: pro runners, high-, medium-, and low-volume amateurs (HVAM, MVAM, and LVAM, respectively), and sedentary people. 

The biggest difference is between runners and non-runners: runners have clearly higher levels, which is good. And among the runners, the trend is that more running is associated with higher levels. Similar patterns are seen for LDL ("bad") cholesterol and triglycerides: running is good, and more running is better.

Here are the fasting glucose (i.e. blood sugar) levels:

The pattern here is much less pronounced. There's still a significant difference between runners and non-runners, but the dose-response effect of more mileage is smaller in men and non-existent for women. The same is true when looking at HgbA1c levels, which offer an estimate of long-term average blood sugar levels rather than a single snapshot. In that case, there's a more pronounced difference between runners and non-runners, but no dose-response response effect. For blood sugar, then, running is good but more running isn't necessarily better.

One key point: the sedentary control group has remarkably good blood sugar levels, with an average below the prediabetes cutoff. Given that 98 million Americans have prediabetes, this confirms that the control group is already pretty healthy. If you were to compare runners to the average population, you'd probably see a bigger effect.

Another group of biomarkers is associated with chronic low-grade inflammation. The pattern here is a little more complicated, but data on C-reactive protein, white blood cell count, and ferritin collectively suggest that greater volumes of running are associated with lower levels of inflammation. The fact that ferritin is considered a marker of inflammation was a surprise to me, since I think of it as an indicator of iron levels in endurance athletes. But it turns out ferritin levels can mean different things in different contexts.

For most of the biomarkers, there's a fairly smooth trend from sedentary to pro runners. But there are a few examples where the pro runners are noticeably different from everyone else, even the amateurs who claim they're running more than ten hours a week. Most notably, the pro runners tended to have low magnesium levels-an observation that mirrors earlier data from British Olympic track athletes. The British study also found that athletes with a history of tendon problems were most likely to have low magnesium levels, which suggests that it's something to watch for if you're training hard.

Is It All About BMI?

All the results I mentioned above were statistically adjusted for body-mass index, age, and sex. That's important, because there were significant differences in BMI among the groups. Here's that data:

Now, I look at this graph and think, "Yep, all else being equal, the more you run the less you weigh." This used to strike me as a painfully obvious statement. The current scientific consensus, on the other hand, is that exercise is ineffective for weight loss. And it's true that lots of studies have assigned people to exercise, sometimes quite vigorously, and have seen underwhelming results for weight loss. This is a complex topic whose nuances I'll leave for another day, but suffice to say that the new data agrees with my feeling that, if you're running more than an hour a day, you very likely weigh less than you would if you weren't running.

You can get another level of insight by adding in some of the genetic data that InsideTracker also collects from some of its customers. There are a large number of separate gene variants that are associated with higher BMI; by checking which of these variants a given individual has, the researchers calculated a "polygenic risk score" for obesity. In the sedentary group, those with higher risk scores tended to have higher BMI. Among the high-volume and pro runners, in contrast, that trend was flattened: those with higher risk scores had similar BMI to those with lower scores. Though the sample size was too small to draw definitive conclusions (since relatively few customers opted to get genetic testing), the results suggest that running counteracted the gene variants associated with obesity.

The BMI data raises another important question: are all the other apparent health benefits of running just secondary effects of lower BMI? Here they use a cool technique called Mendelian randomization (which I wrote about in another context earlier this year). It's a way of turning a large observational study into a randomized trial. The randomization occurs at birth: as noted above, some people have gene variants that predispose them to have a higher BMI. These variants are randomly distributed, so if people with the low-BMI versions tend to also have better cholesterol scores (for example) regardless of whether or not they run, it suggests that BMI is what's driving the cholesterol scores.

The results of the Mendelian randomization-again limited by low sample numbers-are somewhere in the middle. It does appear that BMI explains much of the group's difference in cholesterol and inflammation levels, for example-but not all of it. For example, gene variants didn't predict LDL levels, suggesting that it's an independent effect of running.

But the closer you look, the blurrier the line between genes and behavior gets. Some of the genes associated with exercise are also associated with motivation and self-control; people who exercise a lot are also more highly motivated to eat healthily; and so on. We're back to the challenge I mentioned at the top: teasing out the independent health effects of going for a run is really hard. The InsideTracker researchers conclude that "a holistic wellness lifestyle approach is in practice the most likely to be most effective toward preventing cardiometabolic disease." That borders on tautological, but their data adds another small brick to the pile of evidence suggesting that endurance exercise, even or perhaps especially in large quantities, is a useful part of that holistic wellness lifestyle.

posted Saturday January 27th