rhonda patrick

Exercise as a Treatment for Depression – FoundMyFitness with Dr. Rhonda Patrick

Check out the Found My Fitness Episode Page & Show Notes

Key Takeaways

  • Exercise may help treat and prevent depression by:
    • Shifting the ratio of quinolinic acid to kynurenic acid in the brain
    • Reducing interleukin-6 (IL-6) levels
    • Increasing serum and brain levels of brain-derived neurotrophic factor (BDNF) levels
    • Increasing the circulation of natural cannabinoids and opioids


  • This is a short discussion from Dr. Rhonda Patrick (@foundmyfitness) about the relationship between depression and exercise and how exercise may improve depressive symptoms

The Evidence is Clear

  • “The scientific evidence continues to stack up that exercise may help prevent and treat depression.”
  • One study recently examined over 400,000 individuals and found that certain participants had genetic variants which increased the likelihood they’d be physically active and thus protected from getting depression
  • “There have been numerous randomized control trials that show exercise plays an important role in mitigating depressive symptoms, facilitating recovery from depressive disorders, and preventing relapse.”

Exercise Shifts the Quinolinic-to-kynurenic Acid Ratio

  • Exercise increases the availability of tryptophan in the brain, where it can form two things:
    • 1) Kynurenine, which can then go on to form two things:
      • 1) Quinolinic acid – this is a neurotoxic substance which can cause cells to die in the brain (it’s associated with depression and mental health disorders)
      • 2) Kynurenic acid
    • 2) Serotonin, a neurotransmitter essential for mood and cognition
  • Here’s what’s critical:
    • Stress hormones like cortisol can shunt tryptophan away from forming serotonin
    • Chronic inflammation activates an enzyme called indoleamine 2,3-dioxygenase – this enzyme takes tryptophan and shunts it away from serotonin, into kynurenine 
      • Looking at the ratio of kynurenine to tryptophan tells how active this enzyme is, and thus how inflamed you are
    • When you exercise, muscle cells take up kynurenine, preventing the formation of quinolinic acid, and thus reducing depression
      • Exercise also causes muscles tissue to increase the activity of a gene known as kynurenine aminotransferase which stops kynurenine from forming quinolinic acid (remember – this is neurotoxic) and instead makes it form kynurenic acid (which is neuroprotective)

Exercise Reduces Interleukin-6 (IL-6) Levels

  • When you get sick, two primary pro-inflammatory cytokines are activated – Interleukin one beta (IL-1B) and Tumor necrosis factor alpha (TNFa)
    • IL-1 activates another cytokine called interleukin 6, or IL-6
      • IL-6 is a “bad guy” – it’s consistently elevated in depressed people
        • High IL-6 levels are also associated with heart attacks, stroke, and cancer
      • IL-1 also activates IL-10, which is anti-inflammatory
    • Exercise activates IL-6 (also IL-10) like crazy, but doesn’t activate IL-1 or TNFa – this same thing happens in hyperthermia treatments (like using the sauna)
      • IL-6 plays a crucial role in exercise’s ability to induce insulin sensitivity
        • By exercising, and taking a nonsteroidal anti-inflammatory agent afterward, you block the effects of IL-6 (and thus prevent the beneficial metabolic effects of exercise)
        • There’s been studies showing taking high dose antioxidants (like vitamin C) suppressed the insulin sensitivity effects of exercise, possibly by suppressing IL-6
  • When you exercise, IL-6 rises briefly, but over time your base levels will drop

Exercise Increases Serum Brain-derive Neurotrophic Factor (BDNF)

  • BDNF encourages the growth, survival, and differentiation of new neurons/synapses
  • Exercise, particularly aerobic, increases BDNF levels in serum (it then crosses the blood-brain barrier to work its magic)
    • The longer you exercise, the more BDNF is produced
  • BDNF also plays a vital role in the neuroplasticity of the brain (the ability of the brain to remodel and reorganize itself based on experiences, behavior, and genes by forming new neural connections throughout life)
    • Neuroplasticity is disrupted in depression and other mental health disorders
      • The changes in neuroplasticity caused by stress have been shown to play a significant role in the development and onset of depression
  • Reductions of serum and plasma levels of BDNF have been found in people with depression
    • Decreases of BDNF in specific brain regions have also been found in people with major depressive disorder

Exercise Increases the Circulation of Natural Cannabinoids and Opioids

  • Both may be responsible for the positive feelings of well-being and the reduction in anxiety associated with exercise
  • Cannabinoids are a family of compounds that bind to receptors on cells
    • Some of the most well-known cannabinoids are THC and CBD, found in cannabis
  • The cannabinoids humans naturally produce are known as endocannabinoids
    • Some, like anandamide, are produced when exercising
  • beta-Endorphin activity is increased in the brain after long endurance runs (these are known as the “feel-good molecules”)

Strength Training

  • Resistance exercise has been associated with a 45% reduction in depressive symptoms according to a meta-analysis of 33 randomized control trials (study)
Found My Fitness - Rhonda Patrick : , , , , ,
Notes By MMiller

More Notes on these topics

Top Insights and Tactics From

31 Best Podcasts of All Time

FREE when you join over 35,000 subscribers to the
Podcast Notes newsletter

No Thanks