A study published last week showed that 4 days of a fasting mimicking diet(FMD) partially reversed inflammatory bowel disease-related pathology in mice.  Repeated cycles of the fasting mimicking diet decreased intestinal inflammatory and immune markers while increasing markers of tissue regeneration.  Of course this may pique the interest of people suffering from IBD, but it’s important to understand what we’re dealing with before jumping to any conclusions.

Let’s dig in to this study to determine whether this is something we can apply to humans.

A fasting mimicking diet to treat inflammatory bowel disease?

This study used the chronic dextran sodium sulfate-induced colitis mouse(DSS) as a model for human IBD, a very commonly used model.  The mice were exposed to DSS for 5 days with 9 days of no treatment for 4 cycles(8 total weeks).  Prior to and immediately after the 4th cycle, mice were given a fasting mimicking diet for 4 days, normal chow, or a 2 day water fast.  The fasting mimicking diet outperformed both the normal chow and the 2 day water fast, but you may be wondering why the water fast was 2 days instead of 4 like the fasting mimicking diet?

The thing is, fasting works much better in mice than it does in humans, particularly for weight loss.  In order to prevent weight loss from exceeding 20% of starting bodyweight, the water fast had to be kept to 2 days while the fasting mimicking diet was 4.  This essentially matched the mice by weight loss.

This is a pretty big problem when comparing mice to humans as a 150lbs human would need to lose 30lbs to match the mice in terms of weight loss.  Instead, most humans would lose closer to 5% of their bodyweight, or less than 10lbs.

Another pretty significant problem in applying this study to humans is the way that mice respond to DSS-induced colitis and calorie restriction.  When colitis is induced in mice, they reduce their physical activity, which may mirror some aspects of human IBD.  The problem is that when mice are put under calorie restricted conditions, their behavior is completely different.

First, they eat all of their food in a 2-3 hour period.  So in addition to a 4 day period of calorie restriction, they are also observing a 22 hour fast each day for 4 days.  Second, when provided food at the same time every day as they were in this study, calorie restricted mice begin something called food anticipatory activity.  Basically, starting approximately 2 hours before their scheduled feeding time, the mice hop on a wheel and run until presented with food.

Thus, there are a few confounders that make some of the mouse groups not comparable to one another AND some of the mouse data not applicable to humans.  First, in mice exposed to DSS and given standard chow physical activity levels would be lower, there was no calorie restriction, and the feeding window could be as long as 24 hours as the mice were presented with food 24 hours a day.

With regard to the fasting mice and the FMD mice, physical activity wasn’t monitored.  Additionally, the FMD contains fiber in the form of inulin as well as polyphenols that would help the gut.  Honestly, I think it’s a mistake to look at the fasting-mimicking diet as fasting at all.  I look at it more as calorie restriction with optimal nutrition.

As for using this data in humans, I think it’s important to look at the feeding window and physical activity as factors that people need to take in to consideration.  A shortened feeding window gives the gut longer to heal, and the myokine irisin, released from exercising muscle, has successfully improved lymphatic infiltration and gut inflammatory markers in a different mouse model of colitis.

Finally, fasting and calorie restriction in mice and humans is on a totally different timescale.  A 4 day fast in mice is equivalent to around a 7 day fast in humans, so a 5 day fasting mimicking diet in humans may under-perform comparatively to a 4 day fasting mimicking diet in mice.

Conclusion-Will the fasting mimicking diet work?

I think there’s a ton of usefulness in using the fasting-mimicking diet for all areas of health, especially the gut.  In fact, I regularly recommend people observe days of caloric restriction as a tool to help heal the gut.  I’d say the fasting mimicking diet simply optimizes the nutritional aspect while concentrating monthly calorie restriction to 5 consecutive days in a month.

However, there are a couple of caveats.  I think some people may take the structure of the fasting mimicking diet as being 5 days of perfect followed by 25 days of hedonism.  If your goal is to heal a major gut problem like IBD, I don’t think that will work.  I’d make sure that the other 25 days were on lockdown, particularly if you have adrenal, thyroid, or blood glucose regulation problems.

As part of the study, they followed people performing 3 rounds of the fasting mimicking diet to see how it affected systemic inflammatory markers.  While the fasting mimicking diet decreased these markers, they measured either immediately following the first cycle of the fasting mimicking diet or 5-7 days after the 3rd round.  While inflammatory markers were still lower 7 days after the 3rd round, I’d really like to see what they were 25 days after it.

Another caveat is that calorie restriction works by optimizing circadian rhythms.  So I’d at least optimize light exposure and perform time restricted eating as a general rule moving forward.  Ideally you’d layer everything together including physical activity and tinker with food quality or macronutrient ratio.  As you may have guessed, I believe optimizing circadian rhythms is one of the best ways to improve gut function.

Finally, make sure you’re getting enough physical activity.  Contracting muscles secrete signaling molecules called myokines that are eiteherdirectly anti-inflammatory, block the release of inflammatory cytokines, or a combination of the 2.  The anti-inflammatory effects of these myokines likely have synergy with the anti-inflammatory effects of 2 other circadian hormones, cortisol and ghrelin.

“Stacking” the anti-inflammatory effects of these molecules through healthy lifestyle behaviors can only make the results of the fasting mimicking diet better.  There’s a lot of buzz around the fasting mimicking diet, but I don’t think it’s realistic to expect to reverse years of damage to your gut by just doing 5 days of calorie restriction per month followed by 25 days of poor eating habits.

Coupled with other good habits, I believe the fasting mimicking diet could be very beneficial for people looking to heal gut problems.  I also think it will be useful for addressing a number of chronic health issues that come as we grow older.