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Seemingly Straightforward Study on Cardiorespiratory Fitness and Mortality Raises New Questions About Cholesterol

A recent study published in JAMA Network Open presents a lot of food for thought. The study, “Association of Cardiorespiratory Fitness With Long-term Mortality Among Adults Undergoing Exercise Treadmill Testing,” showed an inverse correlation between subjects’ level of cardiorespiratory fitness and risk for all-cause mortality: the more fit people were, the less likely they were to die. Of course, so far as we know in the human race, the risk for mortality in all of us is 100%. No one’s getting out of this alive! So in this case, reduced all-cause mortality means simply that the better someone’s cardiorespiratory fitness, the less likely they are to die of anything other than a nice, happy old age.

The study assessed fitness via estimated metabolic equivalents (METs) on a treadmill test and found that cardiorespiratory fitness classified as “extreme” (≥ 2 standard deviations above the mean for age and sex) was associated with the lowest risk-adjusted all-cause mortality compared to all other fitness level groups.

The increase in all-cause mortality associated with low cardiorespiratory fitness was comparable to or greater than the increases associated with traditional clinical risk factors including coronary artery disease, smoking, and diabetes. In other words, in this study, it appears that having a low level of cardiorespiratory fitness is worse for mortality risk than smoking, or having diabetes or coronary artery disease. As level of fitness increased, the percentage of subjects with certain health conditions decreased: the elite fitness quintile had the lowest percentages of subjects with diabetes, hypertension, coronary artery disease, end-stage renal disease, or a coronary artery bypass graft. The fittest quintile also had the lowest BMI, but since BMI takes into account body weight only, and not body fat percentage or body composition, we can’t hang our hats there too much, except to say that the fittest quintile had the lowest percentage of subjects who were overweight or obese.

This isn’t exactly earthshattering news. People who are more physically fit tend to live longer. The questions the study raises have less to do with an elite level of fitness and more to do with how that fitness was achieved. More exercise isn’t always better. This paper included no data on subjects’ habitual exercise regimens, so we have no way of knowing what these people did to get fit. Just because their fitness was “extreme” doesn’t mean they were performing “extreme” amounts or intensity of physical feats every day in order to get there. Running marathons doesn’t guarantee good health. In this sense, it’s a bit misleading for researchers to have written, “Cardiorespiratory fitness is inversely associated with long-term mortality with no observed upper limit of benefit.” Yes, the level of fitness had “no upper limit of benefit,” but the efforts some people might conclude are required to get there can have an upper limit and reach a point of diminishing returns.

Mark Sisson, former elite triathlete, creator of The Primal Blueprint, and curator of the wildly popular site Mark’s Daily Apple, addressed this issue nicely in a blog post: This study determined that the level of fitness—not necessarily the total amount of time spent exercising nor the degree of intensity—is correlated to reduced mortality. So, fitness is a huge influence on longevity, but how that fitness is attained and maintained matters.

Intense exercise regimens are not automatically good for health. Just like with water, oxygen, or any vitamin or mineral, just because some is good doesn’t always mean more is better. In the case of exercise, things can go awry and actively work against health when recovery and nutritional replenishment are not properly addressed. The female athlete triad is one example of exercise being taken to extremes in the context of inadequate nourishment and rest. Depressed immune function, mood disturbances, GI problems, and increased susceptibility to upper respiratory infections among athletes is another. It may be possible to achieve excellent fitness without grinding oneself into dust on a daily basis.

Another interesting point the study raises—although you have to look closely at the data to see it—is that the fittest quintile had the highest percentage of subjects with hyperlipidemia. In the quintile with the lowest fitness. 25.1% of subjects were hyperlipidemic, compared to 31.6% in the fittest quintile. Now that is an interesting tidbit. In the fittest group, more people had high cholesterol compared to the least fit group. They also had the lowest BMI: 24.5 (±3.4) compared to 31.7 (±7.3) for the least fit quintile. This seems like a paradox…until

Within the low-carb and ketogenic community, there’s increasing recognition of a phenomenon being called the “lean mass hyper-responder.” These are individuals who are very lean, fit, and highly athletic, mostly engaged in endurance activities like running or cycling. They follow a very low carb diet, and they have very high cholesterol—sometimes well above 300 mg/dL, with LDL above 200 mg/dL. They’re a cardiologist’s worst nightmare, until their other metabolic markers are looked at: they typically have low triglycerides and high HDL (> 80 mg/dL), low fasting insulin, glucose, and A1c, and very low inflammatory markers. A paper recently explored a similar phenomenon in elite ultra-runners and found that highly trained athletes consuming a low-carb, high-fat diet had substantially higher LDL than their high-carb consuming counterparts, but they also had higher HDL, fewer “small, dense” LDL particles (which are believed to be more atherogenic than the “large, buoyant” particles), and overall profiles that suggested better insulin sensitivity.

The study correlating better cardiorespiratory fitness with reduced all-cause mortality revealed no data regarding subjects’ diets, and we certainly can’t assume that all—or any—of them were following low-carb or ketogenic diets. But one thing that does seem to be emerging is that highly fit people appear to have higher cholesterol, including LDL, and this may not automatically be cause for alarm. There’s a great deal of controversy about cholesterol, including whether LDL is even a cause of cardiovascular disease at all.

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