The prescription for a case of the blues might be a pair of running shoes and advice to get moving. A new study from the U.K. adds to the growing evidence that exercise really can fight depression—and make you less likely to develop it in the first place.

In the study, active people reported fewer symptoms of depression than their sedentary peers, a reduction that became more pronounced the more often they exercised. In fact, the researchers estimated that an inactive adult who begins to exercise three times a week can cut his or her risk of depression by 19 percent.

While it’s not exactly a groundbreaking finding—exercise has been linked to a reduction in depression for years—the scope of the study adds heft to the claims, according to Madhukar Trivedi, M.D., a professor of psychiatry at UT Southwestern Medical Center.

That’s because it looked at more than 11,000 people over three decades, so the researchers were able to study the effect of exercise on depression on the same people over a substantial amount of time.

Even though it seems clear that exercise can improve depression symptoms, the way in which it does so is foggier. In this U.K. study, the researchers hypothesize that it could be an indirect link—like by providing distraction from stressful situations or influencing things like diet or sunlight exposure.

But they also think it’s possible that exercise can actually be working directly on your brain.

How Exercise Can Affect Your Brain

We don’t know how exactly exercise helps, but that’s not so strange in the world of depression. In fact, we don’t really understand the exact mechanism involved in a lot of antidepressants, says Dr. Trivedi.

And a lot of what we do know about exercise is gleaned from animal studies. But one potential cause that seems especially promising is related to neurogenesis, or the growth of new neurons in the brain, says Dr. Trivedi.

According to this theory, new neurons are normally produced in a part of the brain called the hippocampus. This is necessary to maintain proper mood control. But studies have shown that depressed people tend to have smaller-sized hippocampi. Researchers think it might be because they’re not producing enough new neurons.

Exercise, on the other hand, is thought to spark the production of new neurons, possibly by increasing the levels of certain endorphins, a 2006 review in Journal of Psychiatry and Neuroscience concluded. This can help alleviate depressive symptoms.

That said, a Swedish study just published in the journal Cell introduces an interesting new theory: Exercise causes changes in your muscles, which helps purge the blood of a substance produced by stress that can harm the brain.

The researchers bred mice to have high levels in their muscles of a specific protein called PGC-1a1. The levels of this protein have previously been shown to spike with exercise. When they exposed these mice and regular mice to the same stressful situations, they found very different results.

“Although all the animals perceived stress, the mice with more PGC-1a1 in their muscles did not develop depressive-like behavior,” says study author Jorge Ruas, Ph.D.

That’s because those mice also had higher levels of an enzyme called KAT. The researchers think that KAT is important because it breaks down a certain substance formed during stress that’s linked to depression. This prevents it from passing from the blood to the brain.

Sure, it’s interesting in mice, but people are another, well, animal. So in order to see if the link holds up in humans, the researchers tested people’s muscles after three weeks of endurance training. They found their levels of both the protein and the enzyme increased. More research is needed, but this shows that the same mechanism may play a role in how exercise protects against depression in people, too.

So How Much Exercise Do You Need?

Prior research has found that treating depression with exercise can be as effective as popping Zoloft. So if you’re diagnosed with depression, you don’t have to necessarily go right to the meds.

Instead, you can ask your doctor about starting with an exercise plan first, says Dr. Trivedi. And if you’re already on an antidepressant that doesn’t seem to be cutting it, adding exercise to the mix can help you recover.

Using exercise to treat clinical depression should be thought of like any other prescription. That means you need to talk to your doctor first before you start anything on your own, says Dr. Trivedi.

But the “dosage” of the prescription seems a little clearer than how it’s actually working in the first place. According to a 2013 study by Dr. Trivedi, you can shoot for the following schedule.

Set aside three to five times a week for aerobic exercise, and make sure you’re sweating for about 45 to 60 minutes a session. You want to maintain your heart rate at about 50 to 85 percent of its max.

Like to pump iron instead? The research on resistance training is more limited, so a recommendation for that isn’t as clear-cut, says Dr. Trivedi. Make sure you’re adding it to your aerobic training and you’re hitting both upper and lower-body muscles. Dr. Trivedi recommends doing three sets of eight reps, at a weight that’s 80 percent of your 1-rep max.

Depressive symptoms can be temporarily reduced immediately after exercise, but it takes weeks or months to see a sustained effect. In Dr. Trivedi’s trials, they noticed results after about three months.

There’s less research out there on how these regimens work in guys who are just feeling a little down, but don’t have full-fledged clinical depression. In this case, if you find that exercise makes you feel better, you should continue with it, says Dr. Trivedi.

And also be on the lookout for symptoms that your blues may actually be depression. Call your doctor if you notice any of the following: a sad mood for a sustained period of time—usually at least two weeks—lack of interest or pleasure in things you used to enjoy, feelings of helplessness, hopelessness or worthlessness, and changes in sleep, appetite, or concentration.

Christa Sgobba For nearly 10 years, Christa has created health, fitness, nutrition, and wellness content that’s steeped in science but engaging enough that people actually want to read it.

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