Dr. Rhonda Patrick here. Today I wanna talk about exercise and addiction, and why vigorous exercise might be the perfect thing to start doing when taking a break from something addictive like alcohol, for example. It's long been known that exercise causes many measurable metabolic changes in the body. For example, our muscles produce lactic acid during intense anaerobic activity, and this fuels the brain as lactate. Another substance that is released both by muscle and the liver during exercise is a hormone called FGF21. A recent study found that giving FGF21 as a drug reduced alcohol consumption up to 50% in mice and vervet monkeys that were addicted to alcohol.

FGF21 produced as a result of exercise, particularly vigorous aerobic exercise, can cross the blood-brain barrier and bind to receptors in the hypothalamus. It also alters dopamine signaling. Dopamine is used in reward pathways in the brain, which play a role in alcohol-seeking behavior. FGF21 is normally produced in the liver and fat tissue and controls many aspects of our metabolism: glucose uptake, insulin sensitivity, blood lipid cholesterol levels, and our body weight. While FGF21 might have an effect on our behavior, that relationship seems to go both ways. Increased blood levels of FGF21 have been observed after acute exercise, long-term fasting, very low-calorie diets, excessive carb intake, and drinking alcohol.

So with that basic understanding of FGF21, let's dive into 2 recent studies that hint at FGF21's role in regulating addictive behaviors. and how exercise could help treat these behaviors. In the first study, a small randomized crossover trial, 10 healthy active young men were randomly assigned to either bike or resistance train for 1 hour. Then 6 to 10 days later, they switched programs and did the opposite workout. They biked at 70% of their VO2 max, an exercise intensity roughly equivalent to a steady run and then engaged in resistance training involving a specific sequence of weighted exercises. Scientists found that FGF21 levels were elevated 15 minutes after exercise, peaked around 60 minutes later, and then returned to baseline 2 hours after exercise.

This study found there was a rise in FGF21 after biking but not resistance training. However, a separate study published in 2019 found an increase from both aerobic exercise and resistance training. In the second study I want to focus on today, researchers used several different animal model experiments to try and tease out FGF21's role in addictive behaviors. They found 3 main things in mice. First, they found that FGF21 is released from the liver after alcohol consumption. This has also been shown in humans. Second, they found that mice lacking the ability to release FGF21 consumed more alcohol than those that could release it. And finally, they found giving mice an FGF21 analog as a drug decreased alcohol consumption by as much as 50% compared to those not given the FGF21 drug.

In addition to the mice, researchers also conducted an experiment with vervet monkeys. Some vervet monkeys will voluntarily drink alcohol, sometimes in excess, when they're given the option. The researchers gave half of these monkeys the FGF21 drug. Those given FGF21 reduced their alcohol consumption in comparison to those given— not given the FGF21 drug. This implies that FGF21 is involved in telling our brains whether we should drink more alcohol or not. It also implies giving FGF21 as a drug may decrease alcohol consumption. Additionally, the researchers identified what they called a homeostatic liver-to-brain circuit involved in regulating alcohol consumption. This prompted the study's authors to make 2 interesting comments. One is that the FGF21 pathway isn't working properly.

It could contribute to alcohol dependency. The second is that they believe that there's potential to target FGF21 therapeutically to help treat alcohol dependency. However, there is more to this story. These 2 studies taken together suggest that some types of exercise, particularly aerobic exercise, could play a role in helping treat alcohol abuse disorders and potentially other substance abuse disorders. And there is data to support that link. In a meta-analysis of 7 randomized controlled trials using exercise interventions for the treatment of alcohol abuse disorders, exercise reduced alcohol consumption in individuals with alcohol abuse disorder.

The exercise interventions included all forms of exercise such as aerobic exercise, resistance training, and compared them to standard treatments. Other studies have also shown exercise is a useful adjunctive tool to combat alcohol abuse disorders, possibly by acting on hormones and other neurotransmitters involved in the mechanisms of addiction. Exercise physiology is incredibly complex, and substance abuse disorders are hugely multifaceted, so much more research is needed to understand the connection between the two. Ultimately, FGF21 might play a small part in a much larger story. The biggest story of all, however, is and will continue to be exercise frequently and vigorously if possible. The benefits for the brain and even behavior are enormous. I'm Dr. Rhonda Patrick, and I'll catch you next time.