Endurance vs. Strength Training: Which Is Best for Managing Depression?

By Adin Smith, MS | Posted June 10, 2023

Endurance exercise (aerobic or cardio) is more effective than strength training at reducing feelings of anxiety and depression.^[1]da Costa TS, Seffrin A, et al. Effects of aerobic and strength training on depression. Eur Rev Med Pharmacol Sci. 2022 Aug;26(15):5601-5610. This cardio training advantage exists because sustained exercise increases neurotrophin production in the brain, enhancing neuronal growth and survival.^[2]Miranda M, Morici JF, et al. Brain-Derived Neurotrophic Factor. Front Cell Neurosci. 2019 Aug 7;13:363. Healthier neurons have better connectivity, which positively affects mood and cognition.

Emerging research suggests that the mood-boosting properties of endurance training are related to a unique cascade of reactions in the body called kynurenines.^[3]Valente-Silva P, Ruas JL. Tryptophan-Kynurenine Metabolites in Exercise and Mental Health. 2018 Mar 8.

Kynurenines and mental health

Kynurenines are bioactive substances produced from the amino acid tryptophan in a group of reactions that comprise the kynurenine pathway (KP). This pathway is primarily active in the liver but also exists in many other cell types that help perform immune and energy-related reactions.^[4]Badawy AA. Kynurenine Pathway of Tryptophan Metabolism. Int J Tryptophan Res. 2017 Mar 15;10:1178646917691938. For instance, kynurenines promote immune tolerance—a protective process that limits or prevents tissue damage. Immune tolerance is essential to the brain and eyes because it helps ensure these structures are protected from excessive immune activation and inflammation. The KP also helps generate cellular energy by producing nicotinamide adenine dinucleotide (NAD+), which is especially important during physical exercise.

However, when certain medical conditions cause heightened concentrations of kynurenines, some of these molecules accumulate in the central nervous system and brain where they may cause harm.^[5]Sanacora G, Treccani G, Popoli M. Towards a glutamate hypothesis of depression. Neuropharmacology. 2012 Jan;62(1):63-77. Furthermore, when the KP gets activated during times of stress or inflammation, it may impact psychological well-being and behavior. For instance, during a viral infection, the body’s production of cortisol and inflammatory molecules can rapidly induce depression symptoms.^[6]Raison CL, Capuron L, Miller AH. Cytokines sing the blues. Trends Immunol. 2006 Jan;27(1):24-31. Chronic autoimmune diseases such as rheumatoid arthritis can also activate the KP and are strongly associated with an increased risk of depression.^[7]Ren H, Lin F, et al. The prevalence and the effect of interferon -γ in the comorbidity of rheumatoid arthritis and depression. Behav Brain Res. 2023 Feb 15;439:114237. Additionally, human and animal research shows that having a higher-than-average Body Mass Index (BMI) induces KP activation.^[8] Favennec M, Hennart B, et al. The kynurenine pathway is activated in human obesity. Obesity. 2015 Oct;23(10):2066-74. ^[9]Huang T, Song J, et al. Adipocyte-derived kynurenine promotes obesity and insulin resistance. Nat Commun. 2022 Jun 17;13(1):3489. And having an elevated BMI is a well-known risk factor for depression.^[10]Hajek A, König HH. Are changes in body-mass-index associated with changes in depressive symptoms? BMC Psychiatry. 2018 Jun 8;18(1):182.

Endurance exercise promotes brain health by altering kynurenine

Kynurenine (KYN) is essential to neurological function, but excess accumulation of KYN in the brain can be neurotoxic.^[11]Agudelo LZ, Femenía T, et al. Skeletal muscle PGC-1α1 modulates kynurenine metabolism. Cell. 2014 Sep 25;159(1):33-45. Recently, scientists discovered that forty-five minutes of cycling at a moderate intensity promoted the clearance of kynurenine (KYN) in the bloodstream in healthy adults.^[12]Joisten N, Kummerhoff F, et al. Exercise and the Kynurenine pathway. Exerc Immunol Rev. 2020;26:24-42. This clearance mechanism occurs when exercising muscles convert KYN into other related compounds that cannot enter the brain. Based on these preliminary findings, endurance exercise may prevent excess KYN from building up and damaging neurons.

Is kynurenine metabolism different in people with depression?

Measuring compounds in the human brain is complex. And more advanced technology is needed to assess whether excess levels of kynurenine captured from the bloodstream have neurotoxic effects that lead to depressive symptoms. Most meta-analysis studies report that people with clinical depression have reduced blood levels of kynurenine and tryptophan as compared to those without depression.^[13]Almulla AF, Thipakorn Y, et al. The tryptophan catabolite or kynurenine pathway in major depressive and bipolar disorder. Brain Behav Immun Health. 2022 Oct 21;26:100537.

The reasons such reduced levels might occur are complicated. Researchers commonly report low albumin status in those with major depressive disorders.^[14]Maes M, Wauters A, et al. Total serum protein and serum protein fractions in depression. J Affect Disord. 1995 Apr 16;34(1):61-9. Albumin is the main protein in human plasma responsible for carrying and releasing many important substances to several body tissues. Because 80-95% of tryptophan is bound to albumin, a reduction in this blood protein may limit the amount of tryptophan available for its release into the brain. And considering that tryptophan brain entry is critical for the production of serotonin (the neurotransmitter that helps regulate mood and sleep), low albumin is thought to represent a cause in the development or exacerbation of depression.

Conclusion

Cardio endurance training at moderate intensities lasting at least forty-five minutes may improve mood and neuronal health by metabolizing kynurenine in the skeletal muscles. Such activities may include bicycling, elliptical training, hiking, jogging, or walking.

Regular aerobic training also reduces the body’s stress hormones such as adrenaline and cortisol, further promoting normal kynurenine metabolism, healthy brain function, and positive mood. Although strength training also induces similar effects on the kynurenine pathway, endurance exercise appears more effective.

Article Sources

References[+]

References
↑1	da Costa TS, Seffrin A, et al. Effects of aerobic and strength training on depression. Eur Rev Med Pharmacol Sci. 2022 Aug;26(15):5601-5610.
↑2	Miranda M, Morici JF, et al. Brain-Derived Neurotrophic Factor. Front Cell Neurosci. 2019 Aug 7;13:363.
↑3	Valente-Silva P, Ruas JL. Tryptophan-Kynurenine Metabolites in Exercise and Mental Health. 2018 Mar 8.
↑4	Badawy AA. Kynurenine Pathway of Tryptophan Metabolism. Int J Tryptophan Res. 2017 Mar 15;10:1178646917691938.
↑5	Sanacora G, Treccani G, Popoli M. Towards a glutamate hypothesis of depression. Neuropharmacology. 2012 Jan;62(1):63-77.
↑6	Raison CL, Capuron L, Miller AH. Cytokines sing the blues. Trends Immunol. 2006 Jan;27(1):24-31.
↑7	Ren H, Lin F, et al. The prevalence and the effect of interferon -γ in the comorbidity of rheumatoid arthritis and depression. Behav Brain Res. 2023 Feb 15;439:114237.
↑8	Favennec M, Hennart B, et al. The kynurenine pathway is activated in human obesity. Obesity. 2015 Oct;23(10):2066-74.
↑9	Huang T, Song J, et al. Adipocyte-derived kynurenine promotes obesity and insulin resistance. Nat Commun. 2022 Jun 17;13(1):3489.
↑10	Hajek A, König HH. Are changes in body-mass-index associated with changes in depressive symptoms? BMC Psychiatry. 2018 Jun 8;18(1):182.
↑11	Agudelo LZ, Femenía T, et al. Skeletal muscle PGC-1α1 modulates kynurenine metabolism. Cell. 2014 Sep 25;159(1):33-45.
↑12	Joisten N, Kummerhoff F, et al. Exercise and the Kynurenine pathway. Exerc Immunol Rev. 2020;26:24-42.
↑13	Almulla AF, Thipakorn Y, et al. The tryptophan catabolite or kynurenine pathway in major depressive and bipolar disorder. Brain Behav Immun Health. 2022 Oct 21;26:100537.
↑14	Maes M, Wauters A, et al. Total serum protein and serum protein fractions in depression. J Affect Disord. 1995 Apr 16;34(1):61-9.