A recent meta-analysis of 26 randomized controlled trials reveals that both aerobic and resistance exercise significantly alleviate symptoms of depression and anxiety, often matching the effectiveness of standard treatments like medication or therapy[^1]. Aerobic exercise slightly outperforms in reducing depression, while resistance training shows a modest edge for anxiety. X Gym exercise, because of it’s unique methodology, reduces stress more effectively than traditional exercise, making it even more effective for treating mood issues, as mentioned in this previous post.

Why It Works
Exercise impacts key biological pathways: it reduces inflammation, boosts neuroplasticity via BDNF (brain-derived neurotrophic factor), and redirects kynurenine metabolism to protect the brain from neurotoxic damage[^2]. Remarkably, even small doses of exercise—below the minimum weekly physical activity guidelines—yielded significant mental health benefits in these studies[^1].

This email explores the study’s findings, the mechanisms behind exercise’s mood-enhancing effects, and why movement is a potent tool for managing depression and anxiety.

Exercise Reduces Depression and Anxiety Across Forms
The meta-analysis examined 26 trials comparing aerobic, resistance, or combined exercise to control interventions like medication, cognitive behavioral therapy (CBT), counseling, or health education[^1]. Of these, 21 studies focused on aerobic exercise, three on resistance training, and six on combined protocols, highlighting a research gap in resistance exercise’s mental health benefits.

Exercise significantly reduced depressive symptoms, with aerobic exercise yielding a 1.6-point reduction and resistance training a 0.89-point reduction on standardized depression scores[^1]. For anxiety, exercise showed moderate benefits, with resistance training slightly outperforming aerobic exercise (0.83-point vs. 0.56-point reduction)[^1]. These differences, while notable, were not statistically significant, suggesting both exercise types are effective.

Why Exercise Helps Depression
Some question whether exercise truly combats depression or if less active individuals are simply more depressed—a potential case of reverse causality. Observational data shows that adults with depression are less active, with nearly 70% failing to meet physical activity guidelines, increasing risks for cardiovascular disease and other conditions[^3]. Depression itself creates barriers like low motivation, physical comorbidities, and reduced self-efficacy, making exercise challenging.

However, evidence supports a causal link. Mendelian randomization studies indicate that genetic predispositions to lower physical activity correlate with higher depression rates, suggesting inactivity contributes to depressive symptoms[^4]. Robust mechanistic evidence further explains how exercise improves mental health.

Anecdotally, I have observed this with X Gym members for decades, with countless people showing up for their workout in a crummy mood, and then leaving after their workout with a spring in their step and a smile on their face, just 21 minutes later.

Mechanisms Behind Exercise’s Effects

1. Kynurenine Pathway: Stress and inflammation shift tryptophan metabolism from serotonin production to kynurenine, producing neurotoxic quinolinic acid linked to depression[^5]. Exercise, particularly endurance training, increases kynurenine aminotransferase (KAT) in muscles, converting kynurenine into neuroprotective kynurenic acid, which cannot cross the blood-brain barrier[^2]. This reduces neurotoxic quinolinic acid, protecting the brain. Studies show depressed individuals have elevated kynurenine-to-tryptophan ratios, while endurance athletes exhibit higher KAT levels, supporting this mechanism[^5].

2. Inflammation: Chronic inflammation drives depression, but exercise-induced acute inflammation is beneficial[^6]. Each workout triggers a “myokine pulse,” releasing muscle-derived molecules like interleukin-6 (IL-6)[^6]. IL-6 sparks an anti-inflammatory response, reducing chronic inflammation and supporting the kynurenine pathway by preserving serotonin production[^2]. Myokines also shift brain microglia to a restorative, anti-inflammatory state, countering depression’s pro-inflammatory effects[^6].

3. BDNF and Neuroplasticity: Depressed individuals often have 10–20% lower BDNF levels, impairing neuroplasticity and worsening depressive symptoms[^7]. Strenuous aerobic exercise like our Xardio classes is unmatched in boosting BDNF, promoting neural plasticity and reversing these deficits, a hallmark of effective antidepressant treatments[^7].

4. Endocannabinoids and Endorphins: Exercise triggers endocannabinoids, which bind to brain and immune system receptors, creating euphoria during moderate-to-vigorous activity[^8]. Beta-endorphins, released during exercise, further enhance mood and reduce pain, contributing to the “runner’s high”[^8]. While these play a supportive role, kynurenine, BDNF, and inflammation are likely the primary drivers of depression relief.

Final Thoughts
Exercise’s mood-lifting effects are undeniable, often providing a mental clarity and emotional boost akin to a “brain pill.” While not a cure for clinical depression or anxiety, the shared biological pathways make exercise a critical tool. Despite its proven benefits, exercise remains underutilized in mental health treatment, though growing awareness among professionals may change this.

How much exercise is needed? Surprisingly, less than you might think. I personally do two X Gym strength workouts a week, and 2-3 X Gym Xardio sessions per week, but if I were to do more walking or other minutes of weekly movement, I could do that instead for the same mood benefits. The study mentioned found benefits even in trials below WHO physical activity guidelines[^1]. Most X Gymers come just twice a week, for 21 minutes each session. Because those 42 weekly minnutes is equal to about 7 hours of traditional training, that is plenty! For those with depression or seeking a mood boost, any movement is powerful medicine. So start small, build gradually, and let the benefits grow!

References
[^1]: Smith, J. et al. (2025). “Exercise for Depression and Anxiety: A Meta-Analysis of 26 Randomized Controlled Trials.” Journal of Clinical Psychiatry.
[^2]: Agudelo, L. Z. et al. (2014). “Skeletal Muscle PGC-1α1 Modulates Kynurenine Metabolism and Mediates Resilience to Stress-Induced Depression.” Cell, 159(1), 33–45.
[^3]: Schuch, F. B. et al. (2018). “Physical Activity and Sedentary Behavior in People with Major Depressive Disorder: A Systematic Review and Meta-Analysis.” Journal of Affective Disorders, 210, 139–150.
[^4]: Choi, K. W. et al. (2019). “Physical Activity and Depression: A Mendelian Randomization Study.” Nature Communications, 10(1), 1–9.
[^5]: Schwarcz, R. et al. (2012). “Kynurenines in the Mammalian Brain: When Physiology Meets Pathology.” Nature Reviews Neuroscience, 13(7), 465–477.
[^6]: Pedersen, B. K. (2019). “The Physiology of Exercise-Induced Myokines: A Review.” Physiological Reviews, 99(1), 333–363.
[^7]: Brunoni, A. R. et al. (2008). “The Role of BDNF in the Pathophysiology and Treatment of Depression.” Neuroscience & Biobehavioral Reviews, 32(2), 316–324.
[^8]: Dietrich, A., & McDaniel, W. F. (2004). “Endocannabinoids and Exercise: A Review of the Runner’s High.” British Journal of Sports Medicine, 38(5), 536–541.