What Are the Negative Health Effects of Jet Lag?

Constant traveling and jet lag may have a greater effect on your body than you think.

In fact, researchers found that chronic jet-lag can increase the risk of obesity-related liver disease and liver cancer, during a recent study using a mouse model.

When exposed to light, the body’s central circadian clock in the brain resets. When people are constantly traveling through different time zones, the central clock becomes chronically disrupted.

The researchers modeled the effects of chronic jet lag in normal mice fed a healthy diet by changing the times the lights went on and off during the night each week. The results of the study, published in Cancer Cell, found that the mice gained weight and fat, and developed liver disease, which progressed into chronic inflammation. In some cases, it eventually progressed into liver cancer.

“Liver cancer is on the rise worldwide, and in human studies we’ve now seen that patients can progress from fatty liver disease to liver cancer without any middle steps such as cirrhosis,” said co-lead researcher David Moore. “We knew we needed an animal model to examine this connection, and studies in the FU Lab [co-lead researcher Loning Fu] found that chronically jet-lagged mice developed liver cancer in a very similar way as that described for obese humans.”

In the study, the jet-lagged mice lost normal control of liver metabolism, which included the buildup of fat, as well as the increased production of bile acids that the liver produces to help digest food.

Earlier studies have linked high-bile acid levels to liver cancer in mice and humans.

The current study showed that when the circadian clock is disrupted, it activates 2 nuclear receptors that help regulate liver bile acid metabolism. The receptor FXR keeps bile acid level in the liver within a normal psychological range. Jet-lagged mice that lacked this receptor had higher levels of bile acid and a greater amount of liver cancer.

The CAR receptor regulates bile acid breakdown and is known to promote liver cancer. Mice that lacked CAR did not grow any liver tumors.

For the study, the researchers hypothesized lifestyle changes that generate chronic jet lag can also disrupt the body’s internal homeostasis, and increase the risk of liver cancer in humans.

“Recent studies have shown that more than 80% of the population in the United States adopt a lifestyle that leads to chronic disruption in their sleep schedules,” Fu said. “This has also reached an epidemic level in other developed countries, which is coupled with the increase in obesity and liver cancer risk.”

Future research will focus on whether drugs that interact with the nuclear receptors could help prevent jet lag from affecting bile acid levels in the liver. The ultimate goal would be to potentially use them as pharmaceutical strategies to prevent liver cancer, the authors concluded.

“This experiment allowed us to take several threads that were already there and put them together to come to this conclusion,” Moore said. “We think most people would be surprised to hear that chronic jet lag was sufficient to induce liver cancer.”

Researcher Fu added, “To us, our results are consistent with what we already knew about these receptors, but they definitely show that chronic circadian disruption alone leads to malfunction of these receptors. And thus, maintaining internal physiological homeostasis is really important for liver tumor suppression.”