Jim is a 32-year-old single man referred to me by his mother. By coincidence, I have seen his two younger siblings previously. He is a thin, wiry-looking young man who is balding prematurely. Wearing casual workout clothes, he followed me into my office and seated himself on my couch.

“I used to take Zoloft starting in the sixth grade," he said. "I stayed on it until I finished college and then weaned myself off. I did pretty well until recently.”

“When do you think things started to change, and what changes were occurring in your life around the same time?” I asked.

Jim responded, “I ran competitively in college, but after graduating, I didn’t have the time to keep up. About a year ago, I decided I wanted to run races again, so I knew I would have to get in shape. I lost 20 pounds and began increasing the distance I ran. I started slowly, but currently, I run up to 70 miles per week.”

I think my jaw dropped. The distance he covered in a week was the equivalent of running from New York City to New Haven, Connecticut. And he did this every week during race season!

Jim did not lose weight in an unhealthy way. He increased his consumption of fruits and vegetables and eliminated processed foods. He drank enough water. He couldn’t keep the weight on because of his extreme exercise, which he loved. He told me he slept well. Obviously, his daytime energy was more than adequate—in addition to training, he worked a full-time but undemanding job. Surprisingly, his mood was excellent. His two concerns were intense gastrointestinal issues and worsening anxiety over the past year.

Jim is already under the care of a gastroenterologist. His initial physical exam and laboratory studies were normal. The day after I saw him, he was scheduled for a colonoscopy—a procedure during which the doctor inserts a narrow tube into the patient’s colon under anesthesia to get a clear view of the anatomy of the lower part of the digestive tract.

Jim is not under any undue stress. He lives with his parents, with whom he is close. He has a stable job but is in the process of interviewing for one in a field more in line with his graduate degree. He does not have financial issues. At the suggestion of his mother, he started taking one of his sibling’s prescriptions for Prozac. Although he was still anxious, he felt as though it might be helping.

The eldest of three children, he was physically small and teased in school. In sixth grade, he began seeing a child psychiatrist who prescribed an antidepressant. He did very well on the medication without side effects. Jim started running in middle school to prepare for playing soccer, which he realized he did not like. At his mother’s suggestion, he joined the track team and fell in love with the sport. In college, he was a walk-on varsity athlete.

Isn't exercise good for the GI tract and mood?

Aerobic exercise and resistance training increase muscle production and improve muscle functioning. Regular exercise can help decrease your blood pressure, fasting glucose level, and unhealthy lipid composition in your blood. In this way, regular exercise offers protection against many types of chronic illness as well as mood and anxiety disorders. In November, I published an article on this blog entitled “How Exercise Can Benefit Our Mental Health.” I cited numerous ways exercise can treat depression and anxiety, including improvement in self-confidence, sleep quality, and life satisfaction, as well as a reduction in loneliness. Exercise also increases the body’s production of anti-inflammatory factors and decreases the body’s level of stress hormones.

However, the type of strenuous exercise that Jim regularly endures can lead to a phenomenon known as overtraining. This occurs when continuously high training levels coupled with inadequate recovery results in fatigue.

According to a 2022 article in Biology,¹ prolonged training of this kind can lead to overtraining syndrome, which causes reduced performance and fatigue even after adequate rest. Overtraining syndrome involves alterations in your autonomic nervous system, causing fatigue, depression, low motivation, low heart rate, insomnia, irritability, agitation, and anorexia. In a survey involving athletes,² approximately 30 percent of nonelite endurance athletes and 60 percent of elite athletes reported overtraining. The researchers hypothesize that overtraining causes trauma to the athlete’s’ musculoskeletal system and results in inflammation.

Long-distance running at a challenging pace (Jim runs a 4-minute mile) can lead to damage to the athlete’s small intestine and cause an increase in permeability to the gut’s protective layer. This can be problematic because alterations in the intestinal barrier allows unhealthy bacteria to leach into the bloodstream, potentially affecting other organs, including the brain.

How does “leaky gut” cause anxiety?

The human body has two brains: one that resides in our head, and another that lives in the walls of our digestive tract. Early in the development of an embryo, in a process called embryogenesis, a temporary structure called the neural crest grows and provides the cells that eventually become your brain and spinal cord. The same primitive structure provides the cells that develop into the enteric nervous system, also called “the second brain.”

There is a direct connection between your brain and your gut through a structure called the vagus nerve. Think of this as a major highway that has traffic flowing in two directions: from the brain to the gut, and from the gut back to the brain. The “traffic cops” that mediate the flow of information on this highway include the autonomic nervous system as well as sensory nerves and hormones. Your brain and your gut are besties—they talk all the time. If your brain is feeling sad or anxious, it sends a signal to your gut which responds with messages to say, “We feel the same way.” The reverse is true as well. If your gut is feeling off, your brain hears about it and responds, “Guess we must feel off, too!”

The brain also has a protective barrier known as the blood-brain barrier. When inflammation occurs in the body, this barrier may be disrupted. This mechanism has been implicated in several neurodegenerative diseases. Research shows stress (of any kind) can lead to the development of depression and/or anxiety. In Jim’s case, my assessment is that his overexercise directly causes his gastrointestinal symptoms and indirectly caused his anxiety.

What do we do about this?

Fortunately, Jim’s colonoscopy was completely normal as I had predicted. His question to me was reasonable, “What do we do now?” I treat my patients in a comprehensive way. My mnemonic for this is MENDS.

• M = medication. I don’t think Jim will need long-term medication. He is tolerating his sister’s Prozac prescription. I suggested providing him with his own prescription for a short time while he eases into his new job. I did, however, suggest he start a probiotic which will support the growth of healthy bacteria in his gut.
• E = exercise. Most of the time, I am prescribing an increase in exercise for my patients. However, in this case, I have recommended that Jim decrease his total running mileage to one that is more reasonable. We agreed to 40 miles per week (still seems extreme to me!). He also agreed to longer recovery periods.
• N = nutrition. Jim already eats a healthy diet. He mainly consumes fruits, vegetables, lean meats, and fish. I suggested he look at the Mediterranean diet endorsed by the American Heart Association. It includes many of the foods he already eats but also provides a list of anti-inflammatory foods to add to his already healthy diet.
• D = dhyana, derived from Hindu, meaning "a refined meditative practice." To help manage his anxiety, I recommended a meditation app for Joe to load on his phone.
• S = sleep. Surprisingly, when Joe trains at the most intense level, he sleeps best. As he backs off on the intensity, he may have more difficulty maintaining the deepest level of sleep. Currently, I am not making any additional recommendations but plan on monitoring his progress.