Not So Fast: Study Finds Benefits of Intermittent Fasting to Vary Widely Based on Age and Sex, With Males Reaping More Rewards

In our modern society, with constant access to refrigerators full of snacks, late-night drive-throughs, and services like Postmates delivering takeout to our doors at all hours, we have never had as much food readily available as we do today. Rather than eating three square meals per day, people are now consuming food and drinks in a non-stop manner — some studies even estimate people eat upwards of ten separate times on any given day.

We know that eating too much food contributes to poor health outcomes and unhealthy body weight. But is when we eat just as important as how much? To answer this question, researchers are now looking at time-restricted eating (TRE) — intermittent fasting that limits the number of hours that you eat to an 8–10-hour window. However, most studies have only looked at how TRE affects young male mice. Now, researchers out of the Salk Institute in San Diego look at whether these benefits apply to other populations, like female or older mice. Published in the journal Cell Reports, Chaix and colleagues show that while many benefits of TRE, like body weight and muscle mass, differ largely by age and sex, this shorter eating window improves several other health and metabolic outcomes across males, females, young, and old. 

Men Are From Mars, Women Are From Venus?

Across species, males and females have dozens, if not hundreds, of differences — and health outcomes are no exception. The global prevalence of unhealthy body weights and body fat percentages are higher in women, though females appear to have slightly better heart and metabolic health than males. In mice fed a high-fat diet, young females are less likely to become obese than older females or males of any age. Despite these vast differences, most health and metabolic research is still done with young male mice.

Chaix and colleagues, led by senior author Dr. Satchidananda (Satchin) Panda — renowned researcher of circadian rhythms and intermittent fasting — aim to put an end to this sex- and age-specific type of study. The Salk Institute-based team looks at how restricting feeding windows to 9 hours per day affects various health outcomes in both young and middle-aged male and female mice — even when that shorter feeding window consists of unhealthy, high-fat, and high-sugar Western foods. This 12-week study compared TRE-fed mice to mice fed ad libitum with an unrestricted diet, with all groups consuming an equivalent number of calories per day.

Males Experience Extended Benefits from Time-Restricted Eating

One of the main purported claims of intermittent fasting is that it can boost weight or fat loss. However, the results from this study show that losing weight is, unfortunately, only likely to occur in males. After 12 weeks of being fed a Western diet, either TRE or ad libitum, both the 3-month-old male mice (about 20 in human years) and the 12-month-old male mice (about 42 in human equivalence) experienced significant preventions of body weight and fat gain, with even greater effects in the older mice.

Whereas normally-fed mice on a lower-fat diet might experience a weight gain of 8% during this 12-week period, the 12-month-old TRE-fed mice only gained 5%. Conversely, the younger TRE-fed mice gained about 19% (due to the Western diet), and the ad libitum mice gained 28% of their body weights. However, the female mice of any age did not experience this prevention of weight gain, gaining 28-36% for young and middle-aged mice on the TRE diet, respectively.

Similarly, only the male mice exhibited significant increases in lean muscle mass, which was an unexpected finding. After 12 weeks of TRE, young and middle-aged male mice had lean mass percentages of 72% and 70%, respectively. As the older ad libitum-fed mice had much lower lean muscle mass than the younger ad libitum mice, but the TRE-fed mice showed such close percentages, the researchers suggest that TRE may be an effective strategy for fighting the commonly seen age-related muscle loss. Similarly, the 12-month-old TRE-fed mice performed significantly better on a challenging task that requires muscular function and sensory-motor coordination than the same-aged ad libitum mice and the older female mice.

Intermittent Fasting Fights Fatty Liver in Females

However, the results were not all one-sided in favor of males — both ages of female mice experienced benefits to their liver and metabolic health. Time-restricted eating for 12 weeks significantly reduced abnormal buildups of fat in the liver (fatty liver), which is a leading risk factor for dysfunctional metabolic health.

Similarly, both male and female mice on the TRE diet showed improvements in blood glucose (sugar) control. During the fasting and feeding periods, the mice with restricted eating windows had significantly lower blood glucose and much faster returns to normal blood sugar levels after a large meal. These results suggest that eating in a TRE-style way may help to support healthier blood sugar control, which protects against metabolic dysfunction.

Lastly, although TRE protected against fatty liver and supported healthy glucose control in both sexes, only the males also exhibited lower levels of blood cholesterol and adipose (fat) tissue inflammation.

Should We All Shrink Our Eating Windows?

So, should we all be restricting our food intake to a 9-hour window? Well, it depends — if you’re looking to lose weight or body fat, this research suggests that only males may experience these benefits to body composition. However, as both sexes significantly improved their liver health and blood sugar control, keeping your eating periods to just 8 to 9 hours per day may be beneficial for males or females with liver or metabolic concerns —no matter how unhealthy the food you are eating is. (Keep in mind, however, that this isn’t a free pass to spend 8 hours per day binging cookies, chips, and cheeseburgers!)

As first author, Amandine Chaix — a former staff scientist in the Panda lab and now an assistant professor at the University of Utah — states, "This was our first time studying female mice, and we weren't sure what to expect. We were surprised to find that, although the females on TRE were not protected from weight gain, they still showed metabolic benefits, including less-fatty livers and better-controlled blood sugar."

Although more research is needed to tell for certain if these benefits translate to humans — and to study the mechanisms behind the surprising benefits of TRE on muscle mass in males — the team is hopeful about the future in this field. As Dr. Panda concludes, "These are very exciting questions for us, and we look forward to studying them in more detail.” 

References:

Amandine Chaix, Shaunak Deota, Raghav Bhardwaj, Terry Lin, Satchidananda Panda. Sex- and age-dependent outcomes of 9-hour time-restricted feeding of a Western high-fat high-sucrose diet in C57BL/6J mice. Cell Reports, 2021; 36 (7): 109543 DOI: 10.1016/j.celrep.2021.109543