A new kind of fasting provides significant immune system benefits

I've written about fasting and its effects on health before. Six years ago, a study showed that a 3-day fast can essentially reset the immune system, providing many potential benefits. These benefits include better cardiovascular health, better endurance, lower blood pressure, and reduced inflammation.

Newer data, which I'll get to in a minute, shows that you might not have to fast nearly that long to get these benefits.

In the 2014 study, Valter Longo and colleagues at USC found that fasting lowered white blood cell counts, which in turn triggered the immune system to start producing new white blood cells. White blood cells (or lymphocytes) are a key component of your body’s immune system. Once you start eating again, according to Longo, your stem cells kick back into high gear to replenish the cells that were recycled.

The idea behind this strategy is that you have to fast for several days to get the benefits: basically, you have to fully deplete your energy reserves (in the form of glycogen), and it takes your body at least 24 hours, and probably 48 hours or more, to do this. That's the not-so-good news. The good news is that you probably only need to fast once or twice a year to gain the benefits that Longo described.

Last week, in a paper just published in the New England Journal of Medicine, Rafael de Cabo and Mark Mattson reviewed multiple strategies for fasting that have been tested in the years since Longo's study. The news continues to be very encouraging: intermittent fasting is good for you. I don't have time or space here to discuss all the results, but I want to focus on one fasting strategy that has surprisingly good benefits.

It turns out that you can get many of the benefits of fasting without doing a 3-day fast, which for most people is really, really difficult to accomplish. Instead, you can try a much easier type of fasting, called "time-restricted" fasting. With this strategy, you fast every day, by eating all of your food in a 6-hour or 8-hour window. Or you can go with the more difficult strategy (but still easier than a 3-day fast) where you fast for 2 entire days per week. Here, then, are two intermittent fasting strategies that have similar health benefits:

• Time-restricted: eat lunch starting at 12 noon, and finish dinner by 8:00pm. Fast until the next day at noon (16 hour fast). Do this every day.
• 5:2 fasting: fast for 2 different days each week, which means eating just 500-700 calories worth of food and drink on those days. Eat normally on the other 5 days.

The first strategy–a daily 16-hour fast–is the easiest, but its benefits might be equal to those of 5:2 fasting and the 3-day fast. (No study has directly compared these 3 fasting regimens.)

The benefits of intermittent fasting are numerous. As de Cabo and Mattson explain, they include

"[improvements in] blood pressure; resting heart rate; levels of HDL and LDL cholesterol, triglycerides, glucose, and insulin resistance.... In addition, intermittent fasting reduces markers of systemic inflammation and oxidative stress that are associated with atherosclerosis."

Fasting also helps with weight loss, for obvious reasons. Cutting out all snacks in the evening, which is the biggest change imposed by time-restricted fasting, means not only a reduction in calories consumed, but also a reduction in the amount of highly processed ("junk") foods in one's diet as well.

Furthermore, because intermittent fasting reduces inflammation, it may also improve symptoms of arthritis and even rheumatoid arthritis.

Why does fasting work? It's all about getting your body to switch over from glucose metabolism to ketone metabolism. Our usual 3-meal-a-day diet provides our body with a constant source of fuel in the form of glucose. Once that glucose is used up, though, our body switches to using fatty acids and ketone bodies. Ketone bodies provide more than fuel: as de Cabo and Mattson explain,

"Ketone bodies regulate the expression and activity of many proteins and molecules that are known to influence health and aging."

Ketone metabolism seems to bring a host of health benefits. The trick is getting our bodies to switch over to it, now and then. If we eat constantly, then our bodies happily subsist on glucose and never make the switch.

Does fasting truly reset your immune system? Six years ago, I concluded that a 3-day fast does the trick, at least partially. The science suggests that, if you can do it, a prolonged fast for 2-3 days will induce your body to clean out some old immune cells and switch on production of new ones. Now we're learning that intermittent fasting, which is easier to do, may work in much the same way, with multiple health benefits.

[Note: one of the authors of the NEJM study, Mark Mattson, is a Professor at Johns Hopkins School of Medicine, making him a colleague of mine. However, we are in different departments and we have never met.]

Can fasting help you burn off those vacation pounds?

Vacation's over, and with it comes the end of the french fries, ice cream, and other delicious but fattening foods that are hard to resist. "I'm on vacation," we tell ourselves, "I can diet later."

Well, it's later now. How about fasting? Is that an effective way to take off the weight?

Fasting has been growing in popularity in recent years. One of the latest fads is intermittent fasting, in which you fast at regular intervals and then eat all you want in between. There's the 5-2 fast, where you eat for 5 days and fast for 2, every week. Or there's alternate-day fasting, where you eat one day and fast the next, for as long as you can. Or you can fast every day for 16 hours and get all your eating done in the other 8.

Here's the thing: eating is easy, and fasting is hard. If you're going to fast to lose weight, you probably will lose a bit, but the evidence is that most people gain the weight back fairly soon once the fasting diet is over. So fasting might provide a quick reward in terms of weight loss, but the loss will be fleeting.

Suprisingly, though, fasting may be a good idea. A recent review by Stephen Anton and colleagues, in the journal Obesity, found that intermittent fasting may come with a variety of health benefits, including reducing inflammation, improving the ratio of lean tissue to fat, improving cognitive function, preventing type 2 diabetes, and possibly even prolonging life span.

How does fasting produce these benefits? Professor Valter Longo of USC, one of the leading researchers on fasting and longevity, hypothesizes that fasting forces your body to recycle many of its immune cells, particularly white blood cells. Then your body works hard to replenish its white blood cells, essentially re-setting parts of your immune system. Longo is also the inventor of the fast-mimicking diet, where you eat a special diet for 5 days every month, one that makes your body think you're fasting even though you're getting adequate calories and nutrients. (See Alice Walton's story in Forbes for more about that.)

Another effect of fasting is a change in metabolism. As Anton's article explained:

"the key mechanism responsible for many of these beneficial effects appears to be flipping the metabolic switch." 

This happens when the body runs out of its normal fuel, glucose, and begins to burn fat, which means it's converting fat to fatty acids, which in turn produce ketones. The body then uses ketones instead of glucose.

So how much fasting do you need to flip the switch from glucose to ketones? Anton et al. write that

"The metabolic switch usually occurs between 12 and 36 hours after cessation of food consumption, depending on the liver glycogen content and on the amount of exercise during the fast."

This doesn't tell the whole story, because once the switch occurs, you need to burn ketones for some time to gain any benefits. Back in 2014, I wrote about new evidence (from Valter Longo's research) that a longer fast, such as 3 days or more provide significant long-term health benefits. Three days is a long time to fast, but Longo has said that you don't need to do it more than a few times per year.

If you do decide to try a fast, don't expect it to be easy: you're going to get really hungry, and fasting can also interfere with social obligations in an inconvenient way.

I should emphasize that the evidence isn't yet clear for any of these strategies, and there are multiple studies going on now that may provide a clearer picture. Nonetheless, despite the current fad of fasting strategies and diets, fasting really does seem to have some potential health benefits.

(A final caveat: fasting can be harmful, especially for people who have other health problems. If you’re seriously thinking of trying this, you should consult your doctor first.)

Does a 3-day fast reset your immune system?

I’ve been hearing new reports lately that sound an awful lot like pseudoscience: that fasting for an extended time, two days or longer, can reset your immune system and provide other health benefits. I first heard about this when a friend and colleague at Stanford University announced he was going on a 3-day fast. To explain, he pointed to a recent study, which I’ve now read.

Diet advice, including fasting-based diets, can be found all over the Internet, and much of it is nonsense, so I was very skeptical about these latest claims.

This time, though, there might be something to it. The scientific study that my colleague told me about was published back in June by USC’s Valter Longo, who studies aging and longevity. In this paper, Longo and colleagues described remarkable metabolic changes that occurred as a result of prolonged fasting. They found that fasting for 3 days or longer–drinking only water and eating less than 200 calories per day–can truly “reset” some components of your immune system. 

The research looked at both mice and humans. (It’s far easier to run the experiments in mice, of course, but we can’t always trust that the same effects will occur in humans.) In both species, fasting lowered white blood cell counts, which in turn triggered the immune system to start producing new white blood cells. White blood cells (or lymphocytes) are a key component of your body’s immune system.

Longo’s hypothesis is that fasting (or starvation) forces your body to “recycle a lot of the immune cells that are not needed” which explains the drop in the white blood cell count. Two of the key mechanisms are an enzyme called PKA and a hormone called IGF-1, both of which are reduced by fasting. Once you start eating again, your stem cells kick back into high gear to replenish the cells that were recycled.

The human part of the study was much more limited: a group of cancer patients fasted for 1, 2, or 3 days prior to chemotherapy. The idea is that fasting might reduce the harmful side effects of chemotherapy, particularly the immunosuppression caused by some chemotherapeutic drugs. These results are very preliminary: the patients are participating in a phase I clinical trial, which is designed to assess safety, not effectiveness. Nonetheless, the results indicate that a 3-day fast (but not a 1-day fast) was beneficial for these patients.

A key finding in this research is that you have to fast for several days to get any benefit: basically, you have to fully deplete your energy reserves (in the form of glycogen), and it takes your body at least 24 hours, and probably 48 hours or more, to do this. This is much harder than a 1-day fast, which many people do routinely. 

On the other hand, Valter Longo has compared the effects of periodic fasting to long-term caloric restriction, which has been shown to prolong lifespan in mouse and other animals. In a separate review article, Longo wrote: 

“Fasting has the potential to delay aging and help prevent and treat diseases while minimizing the side effects caused by chronic dietary interventions.”

Caloric restriction is extremely difficult to achieve for humans: you have to nearly starve yourself for years. Compared to this, an occasional 3-day fast should be a snap.

Caveats: fasting can be harmful, especially for people who have other health problems. If you’re seriously thinking of trying this, you should consult your doctor first. And this preliminary evidence, though encouraging, is primarily based on mice, not people. We might eventually learn that the benefits of fasting are outweighed by other problems. Fasting for more than two days isn’t easy, either: you’re going to get really hungry. 

Does a 3-day fast truly reset your immune system? Well, maybe not a total reset, but at least a mild refresh. The science suggests that, if you can do it, a prolonged fast for 2-3 days or longer may induce your body to clean out some old immune cells and switch on production of new ones. Stay tuned.

[An interesting aside: this study was lengthy and complex, and the authors apparently went to great lengths to satisfy the peer reviewers: the paper was submitted in October 2012, re-submitted after revision in December 2013, and finally accepted in April 2014. 18 months is a very long time.]