Study reveals the “true magnitude” of how exercise influences metabolism

Only 12 percent of Americans over the age of 20 are metabolically healthy. This generally means they have ideal levels of blood sugar, blood pressure, and cholesterol, and do not take medications for these risk factors.

New research and decades of existing evidence, suggest working out helps keep these factors in check. Researchers reveal that exercise sets off a cascade of metabolic changes and reprograms the way our body burns fuel.

It's well known that exercise is good for you. However, the effects of exercise on metabolism are more profound than previously reported and emphasize exercise as a critical health choice, suggests this carefully designed study.

"By virtue of having such a well-controlled study that mitigated interference from age, gender, environment, and other factors, we uncovered both the true magnitude of the key changes, along with the true range of effects across many different pathways, of metabolic adaptation to exercise," John F. O'Sullivan, senior author on the study and researcher at the University of Sydney, Australia, tells Inverse.

This research was published Wednesday in the journal Cardiovascular Research.

Measuring metabolism — O'Sullivan and his team recruited 52 healthy soldiers newly enlisted to the Australian army. All the soldiers were around 26-years-old with healthy body mass indexes, or healthy weights relative to height.

With this unique cohort, researchers got the chance to control potential confounding factors — elements that might sway the results like diet, stress levels, and work environment. All the soldiers ate the same food, kept the same sleep patterns, lived together, and performed the same daily activities.

"By removing the 'noise' from the signal, the magnitude of changes seen were far greater than any previously reported," O'Sullivan says.

The soldiers each completed the same mixed aerobic and strength exercise program for 80 days. They also completed strength and endurance workouts, as well as traditional occupational activities related to the military like marching. The researchers took blood samples before and after the participants completed the exercise program.

"The magnitude of changes seen were far greater than any previously reported."

The group averaged about 1.3 hours of physical activity per day. Sixty-eight percent of the activity was moderate intensity, while 32 percent was high intensity.

How exercise affects metabolism — Metabolism, a popular buzzword in the wellness world, is how our body converts food or drinks for energy and eliminates waste. This process produces byproducts called metabolites, which can signal how metabolic health is changing in response to exercise, O'Sullivan says.

To drill down on how soldiers' metabolisms adapted to exercise, the researchers identified 201 metabolites in the soldier's blood, tracked those metabolites, and observed how they were affected by exercise.

After completing the exercise regimen, participants showed changes to numerous metabolites thought to positively influence immune function, increase blood flow, and fight inflammation, including the metabolites ARG, ORN, and I3P.

Participants experienced positive changes in other metabolites involved in blood clotting, the opening of blood vessels, the breakdown of protein, and stress reduction. The group showed "highly-significant" changes across other metabolic compounds like lipids, ketone bodies, endocannabinoids, and nucleotides.

Participants' trained, energy-efficient muscle also shifted: Post-exercise, participants used far more fuel like fat and ketone bodies, as shown by a reduction of plasma fatty acid and ketone body intermediates in the blood.

"Global metabolism was dramatically changed in response to chronic exercise," O'Sullivan says.

These changes can lead to positive health gains like less stress, inflammation, or fat accumulation in the body.

Interestingly, not all participants showed these changes: Those who had high levels of the metabolite DMGV didn't experience these metabolic benefits. DMGV levels are typically influenced by genetics, the researchers explain, as well as diets. For example, sugary drinks cause DMGV levels to rise while vegetables cause DMGV levels to fall.

Low levels of DMGV could signal metabolic dysfunction, in otherwise young, healthy males, the researchers say. It could so mean those same people need strategies other than exercise to reduce their cardiovascular risk.

The study was conducted on a homogenous, male group, so how these results play out in a larger, more diverse population remains to be seen.

Ultimately, the new research cements the role of exercise in preventing cardiovascular disease, O'Sullivan says.

Maybe the myriad of physiological benefits will get you off the couch and into the gym. Or you may work out just because you feel good. Either way, your metabolism will thank you.

Longevity Hacks is a regular series from Inverse on the science-backed strategies to live better, healthier, and longer without medicine.

HOW THIS AFFECTS LONGEVITY — This study shows that exercise sets off a cascade of metabolic changes and reprograms the way our bodies burn fuel. Exercise is a critical health choice, the researchers say, and essential to preventing cardiovascular disease.

WHY IT’S A HACK — It’s well established that exercise is good for us, but this study shows that it more profoundly affects health than previously realized. The “magnitude of changes seen were far greater than any previously reported,” senior author John F. O’Sullivan says.

SCIENCE IN ACTION — In this study, positive changes — like a strengthened immune system, increased blood flow, and going into ketosis — were seen after the participants engaged in chronic exercise. This means 1.3 hours of physical activity per day, either through aerobic exercise or strength training — exercise that you can do as well.

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Abstract:

Aims: To examine the metabolic adaptation to an 80-day exercise intervention in healthy young male adults where lifestyle factors such as diet, sleep, and physical activities are controlled.

Methods and results: This study involved cross-sectional analysis before and after an 80-day aerobic and strength exercise intervention in 52 young, adult, male, newly enlisted soldiers in 2015. Plasma metabolomic analyses were performed using liquid chromatography, tandem mass spectrometry. Data analyses were performed between March and August 2019. We analysed changes in metabolomic profiles at the end of an 80-day exercise intervention compared to baseline, and the association of metabolite changes with changes in clinical parameters. Global metabolism was dramatically shifted after the exercise training programme. Fatty acids and ketone body substrates, key fuels used by exercising muscle, were dramatically decreased in plasma in response to increased aerobic fitness. There were highly significant changes across many classes of metabolic substrates including lipids, ketone bodies, arginine metabolites, endocannabinoids, nucleotides, markers of proteolysis, products of fatty acid oxidation, microbiome-derived metabolites, markers of redox stress, and substrates of coagulation. For statistical analyses, a paired t-test was used and Bonferroni-adjusted P-value of <0.0004 was considered to be statistically significant. The metabolite dimethylguanidino valeric acid (DMGV) (recently shown to predict lack of metabolic response to exercise) tracked maladaptive metabolic changes to exercise; those with increases in DMGV levels had increases in several cardiovascular risk factors; changes in DMGV levels were significantly positively correlated with increases in body fat (P = 0.049), total and LDL cholesterol (P = 0.003 and P = 0.007), and systolic blood pressure (P = 0.006). This study was approved by the Departments of Defence and Veterans’ Affairs Human Research Ethics Committee and written informed consent was obtained from each subject.

Conclusion: For the first time, the true magnitude and extent of metabolic adaptation to chronic exercise training are revealed in this carefully designed study, which can be leveraged for novel therapeutic strategies in cardiometabolic disease. Extending the recent report of DMGV’s predictive utility in sedentary, overweight individuals, we found that it is also a useful marker of poor metabolic response to exercise in young, healthy, fit males.