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BOSTON -- When it comes to the development of non-alcoholic fatty liver disease (NAFLD) it may not only be what you eat, but when you eat it.

In an analysis of National Health and Nutrition Examination Survey (NHANES) data, researchers found that the more meals people ate during the day, the lower their risk of developing NAFLD -- 10% lower for each additional meal consumed (95% CI 5%-14%). By the same token, skipping breakfast and lunch was associated with significantly increased likelihood of NAFLD.

"Meal timing and how calories are distributed during the day may be associated with the presence of fatty liver," said , of the Medical College of Wisconsin in Milwaukee.

"In our modern society we see things like more shift and long distance air travel," Esteban told reporters at the . "And people are staying up later than usual because of electric light, the internet, or TV."

Additionally, has shown that the liver "has its own sort of circadian clock," Esteban said, which plays an important role in regulating metabolism and energy homeostasis, and that for this circadian rhythm.

With that in mind, Esteban and his colleagues wanted to see whether mealtime patterns and the distribution of calories during the day are associated with NAFLD.

They turned to the third NHANES, which included a 24-hour dietary recall, as well as a gall bladder ultrasound. After excluding subjects with incomplete data, hepatitis B or C, significant alcohol intake, and hepatoxic medication use, the researchers were able to include 9,015 people in their analysis.

For the analysis Esteban and his colleagues divided a 24-hour day into four intervals: 10 p.m. to 4 a.m., 4 to 10 a.m., 10 a.m. to 4 p.m., and 4 to 10 p.m.

Using the 24-hour dietary recall data, the researchers were able to see how many meals these subjects ate, when they ate those meals, if they skipped meals during certain segments of the day, and how calories were distributed during the course of those 24 hours.

In a regression analysis, the researchers adjusted for age, sex, ethnicity, smoking, alcohol use, and total daily caloric intake.

"It was important that we adjusted for total calories," Esteban said. "Our goal was to show that even when you adjust for everything they ate during the day, the timing of when they ate food has an association with fatty liver."

Esteban and his colleagues found that:

• Skipping the morning and midday meals was associated with 20% (95% CI 5%-36%) and 73% (95% CI 26%-138%) increases, respectively, in the odds of developing fatty liver
• Consuming a greater percentage of the day's calories in the morning decreased the likelihood of developing fatty liver by 14% to 21%
• Eating meals late at night -- from 10 p.m. to 4 a.m. -- increased the probability of developing significant fibrosis by 61% (95% CI 10%-136%)

The researchers concluded that the odds of developing NAFLD could be reduced by distributing caloric intake over more meals, not skipping morning and midday meals, consuming more daily calories during the morning and daytime periods, and avoiding having meals anytime between midnight and 4 a.m.

Keeping in mind that this was a survey -- though a particularly big one that was designed to be representative -- Esteban said the findings suggest there is an association between NAFLD and meal timing and how caloric intake is distributed during the day

"These findings are intriguing," said Esteban, especially considering how societal changes seem to be affecting eating patterns. "They could warrant a prospective study to actually quantify the risk and incidence of fatty liver with these particular meal time patterns."

He added that since there is the possibility that mealtime patterns are a risk factor for NAFLD, physicians should be questioning their patients about those patterns.

"It's a very reasonable recommendation to try and balance meals to minimize the risk of obesity and all that encompasses, including fatty liver," commented , of the Massachusetts General Hospital here, who moderated a press conference in which this study was presented. "I think these are sound recommendations for any patient in a primary care practice."

"A corollary to this is whether the deck is stacked against people who do night shift work," Chung added, "It's no surprise that these workers are at risk for higher BMI and other health issues. So for certain strata that are at risk for missing these meals, we should try to come down harder on these kinds of recommendations."

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