Shorter Intervals Between Meals Linked to Higher Mortality

Becky McCall

December 01, 2022

A shorter time interval of 4.5 hours or fewer between meals is associated with increased risk of all-cause mortality compared with longer intervals, according to a large, new prospective study that looked at both frequency of and intervals between meals in US adults 40 years of age and older.

The study also indicates that eating one meal per day — compared with three — is associated with higher mortality, both cardiovascular disease (CVD)-related as well as all-cause mortality, although when participants with diagnosed CVD and cancer at baseline were excluded from the analysis the statistical significance disappeared. 

As such, the findings may raise questions about the health benefits of limiting both the number of and interval between meals across the day, said lead author Yangbo Sun, MBBS, PhD, Department of Preventive Medicine, The University of Tennessee Health Science Center, Memphis.

"At a time when intermittent fasting is widely touted as a solution for weight loss, metabolic health, and disease prevention, our study is important for the large segment of American adults who eat fewer than three meals each day," she said in a press release. "Our research revealed that individuals eating only one meal a day are more likely to die than those who had more daily meals." 

"Among them, participants who skip breakfast are more likely to develop fatal cardiovascular diseases, while those who skip lunch or dinner increase their risk of death from all causes," compared with those who eat three meals a day, noted Sun.

"Based on these findings, we recommend eating at least two to three meals spread throughout the day," she said.

The findings were published in the Journal of the Academy of Nutrition and Dietetics, and the authors believe it is the first study to show that among people eating three meals per day, an average interval between two meals of 4.5 hours or less was associated with a higher risk of all-cause mortality.

Not When We Eat but What We Eat?

However, Courtney Peterson, PhD, Department of Nutrition Sciences, at the University of Alabama at Birmingham, has reservations about the study, which she explained to Medscape Medical News.

She pointed out that the devil is in the details, noting the researchers should have accurately accounted for, and discussed, the number of calories consumed, and most importantly, the diagnosed medical conditions and diseases at the study start.

"They had these great results that basically indicate that skipping a meal is bad for you no matter how you parse it, right?" she said, but added that "unfortunately, when they removed everyone who had cancer or heart disease to start with, almost nothing is statistically significant anymore."

Also commenting for Medscape Medical News was David Unwin, MBBS, a GP with a special interest in diabetes control using the low carbohydrate diet. In an email, he noted that as an epidemiological study, this research suggests associations not causation.

"A far better study seems to be contradictory," he notes. Published in BMJ in 2019, a meta-analysis of randomized controlled studies found that in trials relating eating breakfast to weight change and energy intake, "there was a difference in weight loss favoring participants who skipped breakfast," he said.

"For me, the quality of what we eat rather than its timing is far more important, especially the avoidance of hyper-processed 'junk foods'," added Unwin, referring to other published data showing that ultra-processed food consumption is associated with increased risk of all-cause and cardiovascular mortality.

In particular, he noted, "sugar content was likely to account for the largest proportion of the relation between junk foods and mortality. My motto is 'Just eat real foods' like lots of green veg, meat, nuts, eggs, dairy, and berries."

How Does Meal Frequency, Interval Between Eating Impact Health Outcomes?

According to the US National Health and Nutrition Examination Survey (NHANES) in 2009-2010, 40% of Americans skip meals and at least one in five skip breakfast or lunch, underlining the importance of understanding the risks and benefits of meal patterns and their relationship with premature mortality.

"We already know that skipping your breakfast is not a good idea for cardiovascular health, but we wondered about other meals of the day, like lunch and dinner. Also, we wanted to know whether the intervals between meals were associated with mortality," said Sun in an interview with Medscape Medical News.

The researchers also felt the need to address health outcomes associated with meal frequency, skipping, and intervals because recommendations around these aspects were omitted from the 2020-2025 Dietary Guidelines for Americans due to a lack of evidence.  

A total of 24,011 adults from NHANES (1999-2014) aged 40 years or older participated. "We based our study on a nationally representative sample of US adults, the findings of which can be directly translated to the general population," Sun pointed out.

Eating behaviors, including surveys of 24-hour recall of foods and beverages and times of eating, were collected between 1999-2014, and using mortality data (up to December 31, 2015), any potential associations between eating behaviors and mortality including those specific to cardiovascular death and all-cause mortality were calculated. 

Reduced Intervals Between Two Meals Show Worse Outcomes

Results related to the associations between mortality and meal frequency, intervals between two meals, and skipping meals.

When the frequencies (1 to ≥ 4 meals) of meals across the day were linked to CVD mortality and all-cause mortality, results showed that the less meals, the greater the mortality (Table 1).

Table 1. Meal Frequency and Mortality Rates

Outcome 1 meal/day 2 meals/day 3 meals/day ≥ 4 meals/day
All-cause mortality,
no. of cases/participants
224/1116 1137/6315 2424/13,626 390/2954
All-cause mortality, HR[a] 1.30 1.07 Ref 0.91
CVD mortality,
no. of cases/participants
54/1116 242/6315 504/13,626 78/2954
CVD mortality, HR[a] 1.83 1.10 Ref 0.92
HR = hazard ratio
a. Significant using fully adjusted analysis (education, income, smoking status, alcohol intake, physical activity levels, total energy intake, overall diet quality, food insecurity status, snacks frequency, baseline diabetes, baseline hypertension, baseline hypercholesterolemia, baseline cardiovascular disease, baseline cancer, and body mass index).
 

However, when participants with baseline diagnosed CVD and cancer were excluded from the analysis, the results related to meal frequency were no longer significant.  

Regarding the relative effect of skipping any meals, compared with skipping none, researchers found that according to the analysis adjusting for the factors listed earlier, missing breakfast had a nonsignificant hazard ratio (HR) of 1.11 for all-cause mortality but a significant HR of 1.40 for CVD-related mortality.

Skipping lunch was associated with a significant HR of 1.12 for all-cause mortality, but a nonsignificant HR of 1.15 for CVD-related mortality. Similarly, skipping dinner was significant for all-cause but not CVD-related mortality at an HR of 1.16 and 1.19 respectively. 

And when researchers looked at the intervals between meals, they found mixed results. Eating at intervals of 4.5 hours or less or more than 5.5 hours – compared with 4.6-5.5 hours -- was significantly associated with all-cause mortality but nonsignificantly associated with CVD mortality (Table 2).

Table 2. Meal Intervals and Mortality Rates

Outcome Meal interval
≤ 4.5 hours
Meal interval
4.6-5.5 hours
Meal interval
> 5.5 hours
All-cause mortality,
no. of cases/participants
666/3270 1111/5770 647/4586
All-cause mortality, HR[a] 1.17 Ref 0.98
CVD mortality,
no. of cases/participants
136/3270 230/5770 138/4586
CVD mortality, HR[b] 1.22 Ref 0.98
HR = hazard ratio
a. Significant using the fully adjusted analysis (education, income, smoking status, alcohol intake, physical activity levels, total energy intake, overall diet quality, food insecurity status, snacks frequency, baseline diabetes, baseline hypertension, baseline hypercholesterolemia, baseline cardiovascular disease, baseline cancer, and body mass index).
b. Nonsignificant using same adjustments.
 

Reduced Interval Between Meals Overloads Metabolism

Sun and co-authors point out several possible reasons why skipping meals is a probable risk factor for disease and mortality. Firstly, they note food insecurity, which has been shown to be associated with higher CVD risk, adding that skipping breakfast, in particular, might be a behavioral marker for unhealthy dietary and lifestyle habits.

"However, the results remained significant after adjustment for food insecurity status, and a variety of dietary and lifestyle factors including smoking, alcohol use, physical activity levels, total energy intake, and overall diet quality, making them less likely explanations for the observed association between skipping meals and mortality," they write.

They also highlight that skipping meals usually means eating meals with a larger energy load, which could aggravate the burden of glucose metabolism regulation, leading to subsequent metabolic deterioration.

"This could also explain the association between a shorter meal interval; for example,4.5 hours, and mortality, as a shorter waiting time in between meals also means a larger energy load in a given period of time."

Senior investigator, Wei Bao, MD, PhD, epidemiologist from the University of Iowa, pointed out that, "Our findings are based on observations drawn from public data and do not imply causality. Nonetheless, what we observed makes metabolic sense."

Nevertheless, they conclude: "These findings need replication and assessment in other populations."

Sun, Bao, and Peterson have reported no relevant financial relationships. Unwin runs a not-for-profit diet program for people with type 2 diabetes.

J Acad Nutr Diet. Published online August 10, 2022. Full text 

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