How exercise treats depression

How exercise treats depression by Dr. Joseph Mercola for Mercola

In this short video, Rhonda Patrick, Ph.D., a biomedical scientist and researcher with the Salk Institute for Biological Sciences in La Jolla, California, discusses the science behind the mood-lifting effects of exercise.¹ Indeed, many experts agree that exercise is one of the most powerful tools available for the prevention and management of depression.

For example, a meta-analysis² published in 2016, which looked at 23 randomized controlled trials in which exercise was used as treatment for unipolar depression, found that, compared to no intervention, exercise “yielded a large and significant effect size,” which led them to conclude, “Physical exercise is an effective intervention for depression.”

How exercise ameliorates depression

One of the ways exercise promotes mental health is by normalizing insulin resistance. Mechanistic studies, several of which are highlighted in Patrick’s video, have also linked the antidepressant effects of exercise to molecular mechanisms involving:

• Kynurenine, a neurotoxic stress chemical produced from the amino acid tryptophan
• Myokines
• Brain-derived neurotrophic factor (BDNF), a growth factor that regulates neuroplasticity and new growth of neurons
• The endocannabinoid system
• Beta endorphin, an endogenous opioid neuropeptide and peptide hormone

Exercise boosts metabolism of kynurenine

As explained by Patrick, tryptophan is an essential amino acid required for the synthesis of serotonin, melatonin, vitamin B3 and kynurenine. While kynurenine is associated with stress and depression at higher levels, higher levels of serotonin are associated with improved mood.

To a degree, exercise will allow you to control what the tryptophan will be synthesized into. By allowing for more tryptophan to be transported into your brain, exercise raises your serotonin and inhibits conversion into kynurenine, thereby boosting mood and preventing depression.

Conversely, chronic stress and low-grade inflammation makes more tryptophan available for conversion into kynurenine and less into serotonin, which has a depressive effect.

Kynurenine, in turn, is a precursor to a neurotoxic compound called quinolinic acid, as well as a neuroprotective compound called kynurenic acid. Here too, exercise — and especially endurance exercise — activates a gene that prevents kynurenine from forming quinolinic acid, and makes it form kynurenic acid instead.

Animal research³ has also shown that well-trained muscles have higher levels of an enzyme that helps metabolize kynurenine, thereby ridding the body of it. As noted by the authors:⁴

 “Our initial research hypothesis was that trained muscle would produce a substance with beneficial effects on the brain. We actually found the opposite: well-trained muscle produces an enzyme that purges the body of harmful substances. So in this context the muscle’s function is reminiscent of that of the kidney or the liver.”

Endurance training promotes anti-inflammatory myokines

Myokines are a type of a chemical messenger in a class called cytokines. Many of the cytokines we already know about are the kind liberated from adipose tissue, your body fat, particularly the truncal fat mass that gives you that apple-shape.

Many of these are inflammatory cytokines, such as tumor necrosis factor alpha (TNF-alpha) and interleukin-1 family (IL-1), which are involved in a variety of disease states, including cancer. Interestingly, the cytokines produced by muscle tissue, which are known as myokines (“myo” being the Latin root for muscles), have anti-inflammatory effects.

Myokines also increase your insulin sensitivity by improving glucose utilization inside your muscles and, acting as chemical messengers, myokines help inhibit the release of inflammatory cytokines produced by body fat.

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