Start with a short primer on IMF.
Catenacci: There are two main types of intermittent fasting that have been studied for weight loss. Time-restricted eating (TRE) is where you limit your energy intake, or your eating, to a specific window every day. For instance, with what is called the 16:8 plan, you fast 16 hours and eat all your meals within an eight-hour window daily.
The other type is more of a true “intermittent” fasting, where you restrict your calorie intake significantly, usually by over 75%, on selected days of the week. You can do that every other day, two days a week (5:2), or, as in our study, three days a week (4:3). So, three days a week, our participants restricted to about 400 to 700 calories, according to body size. The other four days, they ate their normal diet, with no restrictions or calorie counting, but with a focus on healthy foods and portion sizes.
Why did you choose the 4:3 plan?
Ostendorf: We think that the 4:3 IMF paradigm ended up being really important because it was like a sweet spot in the IMF strategies that have been studied to date. In the studies that have evaluated the 5:2 paradigm, their weight loss wasn’t as high, and I think that two fast days a week just did not produce enough of a calorie deficit to impact weight more than DCR. Whereas in the alternate-day fasting approach, it might have been too rigid and difficult to adhere to long term.
So, with this 4:3 approach, where they’re fasting three days a week (which are flexible and can be worked around a personal schedule), it might be a middle ground where they feel like they can adhere to it, and it’s feasible to implement in their daily lives. And it also produces a significant calorie deficit across the week.
What else made the study stand out?
Catenacci: The two interventions were designed so that the weekly calorie deficit would be the same. The intermittent fasting group restricted calories by 80% on the three fast days per week. That averages out to about a 34% deficit over the course of a week. And then the DCR group restricted calories by 34% every day.
There have been only five other published studies that have approached it the same way, where they matched the energy deficit between the IMF and DCR groups. And those other studies either evaluated the alternate day fasting paradigm or the 5:2 fasting paradigm. And all of the studies to date have found that those paradigms produce similar weight loss as daily calorie restriction. So our findings with this 4:3 paradigm producing more weight loss are unique.
What else did you learn about differences between the groups?
Ostendorf: We looked at how many of these participants actually achieved 5% weight loss, a weight-loss benchmark that is usually associated with clinically meaningful changes in outcomes like blood pressure, glucose and hemoglobin A1C. That’s a really important benchmark in most lifestyle weight-loss programs for people to achieve.
We found that 58% in the 4:3 IMF group met that 5% weight loss mark, whereas 47% in the DCR group met the mark.
Did that then translate to greater cardiometabolic changes?
Ostendorf: Yes. We ended up seeing more favorable changes in systolic blood pressure; total cholesterol; fasting glucose; and hemoglobin A1C in the 4:3 IMF group compared to the DCR group. Those were secondary outcomes, so we need a larger study where we’re actually powered to look at those changes to make conclusive declarations on what changes are happening.
Do you think having those fasting days provides other metabolic or health benefits compared to the daily calorie restriction paradigms?
Ostendorf: We do. We’ve collected stool samples to look at the microbiome and blood samples for looking at things like changes in hunger-related hormones, so we do want to explore whether there are other metabolic and health benefits of these fasting periods and this particular approach. But we’re still running all these additional analyses to try to understand where that benefit lies and what specifically is going on physiologically. But our data suggests the primary reason for the greater weight loss in 4:3 IMF was greater adherence to 4:3 IMF compared to DCR.
What did you learn about adherence?
Catenacci: We were able to objectively measure calorie intake in the two groups using the doubly labeled water (DLW) intake balance method. It’s a technique that uses isotopes of hydrogen and oxygen to measure free living energy metabolism, providing a very accurate estimation of the degree of calorie restriction that these two groups achieved over the course of the study. The Colorado Nutrition Obesity Research Center (NORC) Energy Balance Assessment core lab on our campus analyzes those isotopes in our participants’ urine samples. It is one of the few labs in the country that does this, and we are fortunate to have this here.
What we found was that even though the weekly calorie deficit was designed to be the same, the 4:3 IMF group restricted their calories more, which means that they were more adherent to the intervention. Also, participant drop-out rates were lower for the 4:3 IMF group at 19% at the 12-month mark compared with 30% for the DCR group.
How were calorie restrictions determined?
Catenacci: We measured participants’ resting energy expenditure at baseline. We calculated what their baseline energy requirements for weight stability were, and they got an individualized calorie goal to produce the target 34% weekly energy restriction. Most people in the DCR group ended up with a calorie target between 1,300 and 1,800/day for women and between 1,500 and 2,000/day for men. In the 4:3 IMF group, fast day calorie targets were between 400 and 600/day for women and 500 and 700/day for men. And both groups were taught how to track their calories.
What was the study’s behavioral component like?
Ostendorf: It was a really important component, because it provided a source of accountability and social support. It was pretty intensive, which is aligned with our current guidelines for treating obesity. They met weekly for the first 12 weeks with a registered dietician as a group. And then they met every other week for the remainder of the year. And they had access to the fitness center at the AHWC.
What are your next steps?
Catenacci: There are several specific populations that still need to be studied to see if this is a safe and effective weight loss intervention for them, including older adults and people with diabetes, cancer or cardiovascular disease. We just finished piloting this 4:3 IMF intervention in 15 women, all stage 1 to 3 breast cancer survivors, who’ve completed their primary treatment. We’re actually starting another group for this pilot study in about two months.
Also, we have one year of data comparing 4:3 IMF to DCR in 165 subjects, which is good, but we would love to have longer-term data around the effectiveness of these two interventions compared head-to-head. We have recently submitted a grant to NIH that would include this long-term follow-up.
Ostendorf: We’ve gotten questions about how people can actually access a program like this in real-world settings. And right now, a specific comprehensive program focusing on 4:3 IMF doesn’t exist to our knowledge. So, I want to work on how to design this for implementation in clinics and community programs that are accessible to people and make this something that they can afford.
This interview was edited for length and clarity.
