A new randomized controlled trial compared a regimen of cutting calories on just 3 nonconsecutive days a week—a modified form of intermittent fasting—with standard daily calorie restriction over a full year.

The results?

While body weight and cardiometabolic risk factors improved in both groups, intermittent fasting was more effective for improving body weight, BMI, insulin sensitivity, and fat mass than daily calorie restriction.

There was one caveat: The modified fasting group reduced their daily energy intake more—cutting their calories by around 160 per day compared to 90 in the daily calorie restriction group.

These findings suggest that modified forms of intermittent fasting can be more effective than daily calorie restriction, especially for weight management and metabolic health—challenging the notion that intermittent fasting strategies are merely trendy or unsustainable.

Structured fasting protocols appear not only effective but potentially optimal for meaningful long-term health improvements, likely due to their high adherence rate.

But fasting is just one approach to weight loss and health, and while beneficial, it's not for everyone. In today’s email, we’ll explore the science of fasting and what this new study means for how we think about approaching weight loss and metabolic health.

The Benefits—and Risks—of Intermittent Fasting

My thoughts on fasting—and those of the health space in general—have evolved over the years. I've chatted extensively about the benefits of fasting with previous podcast guests like Valter Longo (who appeared most recently on episode #42) and Mark Mattson (who appeared on episode #66). They advocate periodic fasting for cellular rejuvenation and longevity and their research has highlighted numerous benefits of fasting, which include:
 

• Extended lifespan and healthspan: Animal research demonstrates up to a 40% increase in lifespan with calorie restriction.
• Reduced age-related diseases: Fasting reduces the risk of diabetes, cardiovascular disease, and neurodegenerative diseases; improves insulin sensitivity and overall metabolic health; and lowers cancer incidence.
• Metabolic health: Fasting promotes a shift from glucose metabolism to fat burning, improving so-called metabolic flexibility. It also enhances glucose regulation, improves insulin sensitivity, and promotes ketone body production by the liver.
• Neuroprotection and cognitive function: Fasting increases the production of BDNF, a neuroprotective molecule that aids in neuroplasticity, memory, and learning. The benefits of fasting also extend to protection against neuronal dysfunction and neurodegenerative diseases like Alzheimer's and Parkinson's disease.
• Cancer prevention and treatment: Fasting makes cancer cells more vulnerable to chemotherapy while protecting healthy cells—enhancing cancer treatment efficacy and reducing side effects. It does this by exploiting cancer cells' reduced flexibility that results from mutations in growth signaling pathways like IGF-1.
• Hormesis and cellular adaptation: Fasting activates ancient survival pathways that thrive during intermittent, mild stressors like fasting. This enhances our body's resilience to oxidative damage, metabolic stress, and toxic environmental exposure.
• Renewal and repair: Prolonged fasting triggers autophagy (cellular recycling) and apoptosis, clearing damaged cellular components. There's also an uptick in stem cell activity and a regeneration of immune cells after fasting cycles.
   

There’s another benefit of fasting that doesn't get enough attention: its practicality and sustainability. Research consistently shows that fasting (and time-restricted eating) have higher adherence compared to chronic calorie restriction. This means the lifestyle (and its benefits) can persist for several years or more.
 

However, fasting (when it's prolonged) also carries some risks—elevating the potential for muscle mass loss, particularly in older adults and people who aren't performing resistance training. Severe caloric restriction, whether in the context of intermittent fasting or not, can cause some women to lose their menstrual cycle or stop ovulating—but this appears to happen when calories are slashed dramatically for a long period of time. Unless women (or men) are severely limiting their calorie intake and performing extreme endurance exercise simultaneously, some form of daily time-restricted eating or even the occasional 24-hour or prolonged fast is probably safe.
 

According to experts like Dr. Stuart Phillips, the main "downside" of fasting may be related to muscle loss—without adequate muscle reserve built when young and preserved when old, we more quickly reach a "disability threshold." Check out this clip where he shares his thoughts on the limits of extrapolating animal research on fasting to humans and why he's cautious about fasting for long-term health.
 

In my opinion, time-restricted eating is a good daily practice for everyone. Full-on fasting—skipping one or more meals during the day—is likely not necessary for normal weight people to do on a daily basis.
 

But for some people, meal skipping or simply limiting calories on just a few days per week can be an effective way to lose weight without compromising muscle mass. A new study tested this form of modified fasting and its effects on weight loss and other metabolic health outcomes. The results were promising.

4:3 Fasting Outperforms "Dieting"

The problem with most diets is that they're not sustainable—chronically reducing calories every day eventually gets hard, people stop doing it, and weight returns to normal. Fasting and certain forms of time-restricted eating aim to solve this problem by providing a sustainable, effective, and tolerable form of calorie restriction.

While many studies on intermittent fasting use a 5:2 approach (participants fast or limit calories on 2 nonconsecutive days each week), a recent study used a modified fasting method (referred to as IMF) in which the participants cut their calories by 80% on three nonconsecutive days each week. On the other days, they ate as they desired, within limits of course. This means they never completely went without eating, though they had days where food intake was very limited.

Another group of participants performed daily calorie restriction (DCR), cutting their calories by 35% every day of the week. Both groups were prescribed the same dietary restriction of 35%, they just achieved it using two different approaches. Each participant was also told to perform 300 minutes of moderate to vigorous intensity exercise each week—the standard recommendation for weight loss.

Over the 12-month intervention, both IMF and DCR groups achieved significant improvements in several metabolic outcomes, but IMF generally demonstrated greater effectiveness. 

Specifically, the IMF group experienced significantly greater weight loss, losing 7.7 kg (~17 lb) compared to 4.8 kg (~10.5 lb) for the DCR group.

IMF also had a slight advantage for:

• BMI: a drop of 2.67 vs. 1.67 with DCR
• Lean mass: a 1.8 kg loss vs. a 0.6 kg loss with DCR
• Fat mass: a 6.0 kg loss vs. a 3.9 kg loss with DCR

Regarding metabolic health, the IMF group demonstrated significantly greater improvements in insulin resistance measured by HOMA-IR (almost a three-fold improvement). Triglycerides improved significantly (by 24 mg/dL) only within the IMF group.

Surprisingly, neither dietary strategy led to significant improvements in blood pressure, LDL cholesterol, total cholesterol, or fasting glucose when comparing between groups.

There was, however, one confounding factor to consider—calories. 

The average calorie reductions over the 12-month study were ~160 per day and ~90 per day in the IMF and DCR groups, respectively—a difference of nearly 70 calories per day. This means that, unintentionally or not, the participants who fasted ate less than those who practiced daily calorie restriction. In fact, a difference of 70 calories per day between groups amounts to a roughly 7 lb difference in weight loss when considered over an entire year—almost exactly the gap in weight loss that was observed at the end of the study.

Final thoughts

Depending on how you look at it, the calorie issue could be a positive or a negative finding. On one hand, it prevents us from concluding that fasting is better than daily calorie restriction if total calories are equated (because they weren't). On the other hand, it means that fasting might allow one to eat less with less effort and stick to it! In fact, neither group achieved their goal of reducing calories by 35% for 12 months, but the IMF group got closer.

This study is a great reminder that there are many ways to accomplish a goal—whether that be a training goal or a weight loss goal. Some people thrive by precisely tracking every calorie they eat and meticulously logging their meals. Others would prefer to watch the clock or the calendar. If you’re in the latter camp, then modified forms of fasting and time-restricted eating can be incredibly powerful dietary tools, whether you want to shed a few pounds or simply improve your metabolic health to live longer and healthier.

While I'm more skeptical of chronic, long-term dietary restriction for meaningful life extension, as one of a number of tools for ameliorating metabolic disorders, it may still have its place.

Craving more content on fasting and time-restricted eating? Check out these timestamps from a few previous FoundMyFitness member Q&As:

Q&A 19 (1/9/2021)

• 32:48 - Can athletes reduce inflammation with time-restricted eating?
• 33:54 - How does Ramadan fasting affect inflammatory biomarkers?
• 35:27 - Is alternate-day fasting effective against inflammation in metabolic syndrome?
• 35:50 - How are fasting blood sugar levels linked to C-reactive protein?
• 37:00 - Which type of time-restricted eating does Rhonda practice?
• 37:50 - Weekly 24-hour fasting vs. quarterly 3-day fasting—which is better?
• 46:30 - Should you enter ketosis before starting a fast?

Q&A 43 (1/7/2023)

• 21:04 - What is Rhonda’s current take on time-restricted eating?
• 22:10 - Can you fast without losing muscle?
• 22:57 - How does fasting enhance cellular repair?
• 23:45 - Can you meet protein goals while practicing time-restricted eating?
• 24:08 - Does prolonged fasting lead to muscle loss if you're overweight?
• 24:55 - Are there unique benefits of prolonged fasting for healthy individuals?
• 25:37 - How soon does autophagy start during a prolonged fast?
• 26:28 - How prolonged fasting benefits immune and stem cells
• 26:42 - How much prolonged fasting is too much for healthy individuals?

With appreciation,

Rhonda and the FMF Team