Weightlifting study gives a genetic explanation for uneven gains
The uneven effects of weight training result from a complicated mix of factors.
Hello! Welcome to Leg Day Observer, an exploratory look at fitness, the companion to GQ.com’s Snake America vintage column, and a home for all things Leg Day.
One thing about lifting weights that stinks, besides changing clothes and sweating, is that it works better for some people than for others. The workout partner who’s never lifted before and is, within two months, squatting two plates is as classic a gym experience as a missing dumbbell. And while that variance is usually explained by diet, sleep, and stress levels, it’s not always the case that work done outside the gym makes up the difference in results.
It can sometimes feel like an off-kilter distribution of innate performance, with world-class athletes like Chad Ochocinco and Ryan Lochte turning McDonald’s-only diets into results at the highest level at one end of the spectrum and the rest of us at the other. Some people will excel at athletics — or working out, or putting on muscle — even when ignoring traditional inputs. That sort of variance in putting on muscle is explained, a little bit, in a new study by researchers at McMaster University.
The study, published in August in the life sciences journal Cell Reports, focused on a group of young men who exercised one leg and not the other over a 10-week period and wore a brace on the non-exercised leg for the final two weeks.
By isolating results between legs, the researchers created a control within their subjects, enabling them to more successfully pinpoint the direct effects of exercise. The researchers found that muscle gains in the active leg ranged between 1 and 15 percent, with an average of 8 percent, over the 10-week span, with muscle losses in the immobilized leg ranging between 1 and 18 percent, with an average of 9 percent, over a two-week period.
The study team notes that nutrition was kept pretty constant, with subjects maintaining a diet “sufficient to fully support muscular hypertrophy” throughout the 10-week period, with protein respectably high, and cycled at different ratios on workout and rest days. Subjects worked out their legs with leg extensions and leg press, eschewing upper-body exercises, and were pulled from what Stuart Phillips, the corresponding author and a professor at McMaster University, tells me is “a kinesiology and health sciences side of things:” fairly healthy young men who might play pickup basketball or work out occasionally but are not considered athletes. (Women were excluded from the study; a small note at the end of the paper mentions “a differing abundance of genes involved in fatty acid oxidation,” that might explain the exclusion.)
At first blush, the study seems big, explicitly stating some old ideas that we might already know but have not been able to prove. Most immediate is the size and degree of muscle atrophy in subjects, which occurred at a five-times faster rate than muscle growth, and the variability in muscle growth between subjects, with some gaining muscle at a rate of one percent, and some at 15.
The key scientific finding seems to be a genetic explanation for the variance: muscle protein synthesis, the body’s innate ability to use dietary protein to repair torn muscles into bigger ones, and muscle growth, which depends on this synthesis, are controlled by a set of 141 genes. Lifting, it seems, is both transitory — 10-week gains on one leg being wiped in two weeks — and complicated by biological factors. How do muscles disappear so quickly? And are gains just a matter of genes?
The muscle loss in the study is not something active people are likely to experience and is more due to atrophy than skipping workouts. The final two weeks had subjects’ legs in a brace that bent at about 35 to 40 degrees, suspending the leg in the air, Phillips tells me.
"The regulation of muscle growth is very complex."
But what about the eight other weeks? Phillips said the research team scanned subjects’ untrained legs before administering the brace — the study involved taking muscle tissue biopsies to get all the intense cell data — and leg mass “didn’t change.” Subjects’ non-worked out legs were not measurably different than before after eight weeks of skipping workouts, showing the difference in degree, if not in glory, between rendering a leg immobile and unsupportive and walking around on it so it holds up half the weight of a human body. Rapid muscle loss is, in active individuals, less a surprise than a nosedive: It’s what happens when your leg is in a cast, or worse.
The genetic factors limiting muscle growth are a bit of a work in progress. A critical part of the study is a dense conversation about mRNA and functional RNA and coding exons and 30 to 50 untranslated regions — not exactly the kind of stuff that immediately springs to mind when leg extensions are involved. But reading the study shows how difficult and complicated muscles are, and how many variables go into something as immediately observable as pushing a leg press on Monday and being bigger and stronger on Tuesday.
“The regulation of muscle growth is very complex,” says Phillips. “It’s not as simple as you do X and Y and then it’ll happen.”
Only a person as complex as Ryan Lochte can explain it: It’s not just that his 141 maxed-out genes let him turn McDonald's pancakes into gold medals. It's also his lifetime of training and mental preparation, luck, privilege, and genetic factors relating to swimming technique.
Enter: the exercise pill — Phillips and his colleagues also suggest in the study that “119 drugs that could either mimic or oppose” the lean mass 141-gene signature, hypothesizing a down-the-line drug that could stimulate muscle growth and prevent muscle loss, which could replace the need for exercise.
Such a drug is possible, says Phillips. Researchers could “experimentally develop and refine [an existing drug] a little bit,” and “recapitulate what you’re seeing in a weightlifting leg.” However, “there’s nothing out there drug wise” currently that mimics the muscle-growing environment short of a steroid, and he wouldn’t hold his breath for a non-steroid pill to replace exercise any time soon.
There’s reason to believe this sort of pill could help the elderly and those unable to physically exercise, which is reason alone to keep the progress moving. But it’s up for debate if that pill would be beneficial if you’re lucky enough to exercise and get stronger. Not having to work out seems less a reprieve than a punishment, and, just as with food, benefits from the real thing are almost always more substantial, and deeper.
It's true that genes might be limiting: we might likely be average at best, condemned to only see muscle growth at a 1 percent rate over two months. But lifting is less about hitting a number on a wall than making progress and changing. Phillips says the crux of the Cell Reports study is that “not everybody gains muscle and not everybody loses a lot of muscle,” which mostly means that more studies are coming and that they’ll be more specific. But he also says his output at McMaster — a dozen or so studies over the past 23 years — are united by a common thread: “everyone gets stronger when they lift and everybody gets weaker when they don’t.”
What it all means is that anyone lucky enough to train without incident has been dealt a good hand, and that beating a non-Lochtean genetic profile is both a real achievement and the better part of strength training. Marathon finish lines are lousy with people who never thought they’d be able to run one, and gyms in the winter are — or were — full of people who, in spring, could not get to parallel with bodyweight on their shoulders. Lifting works, the results say, even if it’s just a gain of 1 percent.