by Mansal Denton , January 14, 2019

Is Fasting Good for You? Q&A on Fasting

Fasting can be an integral component of a healthful lifestyle, but it is not a magic bullet any more than nootropics or smart drugs are. Extending the number of years we are healthy and functional (i.e., healthspan) and optimizing our performance requires many different practices of which calorie restriction or fasting-related behaviors is one.

We’re wrapping up our complete guide to fasting diets with this piece. In How to Intermittent Fast, we provided a brief introduction to fasting (“what is fasting”), in What to Expect While Intermittent Fasting we outlined applicable fasting practices and fasting diets (“how to do fasting”) and in Anti-Aging Benefits we clarified the mechanisms that provide fasting benefits.

In this article, Is Fasting Good for You? Q&A on Fasting, we will focus on answering common questions from the Neurohacker Collective community. Some of the questions we hear (does fasting work for everyone? Is fasting healthy?) show that there are concerns about fasting. We generally have a positive view of fasting, but understand that every physiological intervention has a trade-off. Understanding possible risks and benefits are important when making a decision to start a new habit.

Before I get to questions, I want to remind you of an important point I covered in more detail in How to Fast and What to Expect While Intermittent Fasting. Fasting (as applied by biohackers and researchers) isn’t one thing; it’s several different eating patterns. These include time-restricted eating (TRE), fasting-mimicking diet (FMD), and several forms of intermittent (alternate-day and 5:2) and periodic fasting.

A general rule of thumb for people who are new to this would be to start fasting with something easier and shorter. In terms of ease and safety concerns, I’d rank them (from easiest/least concern to hardest/higher concern) as:

TRE > FMD (3 days or less) > FMD (4-5 days) > Periodic Fast (2-3 days) > Longer Fasts

I also choose to participate on both ends of the ranking spectrum. I do TRE daily and longer fasts (3 days or more) quarterly.

Is Fasting Healthy?

In general, both prolonged calorie restriction and periodic fasting for short periods of time seem to be “good” on a population level (in terms of healthspan and lifespan in organisms like worms, fruit flies, mice and primates), but not for every individual within the population.

While most of the organisms within a large group benefit, CR and periodic fasting have not been as helpful (and in some instances might have been harmful) for some individual organisms. Factors like age and genetics have influenced outcomes in animals.

Fasting behaviors provide health benefits for most people, but there are downsides and risks primarily for elderly. Risks would be lowest (to non-existent) for TRE but increase when you don’t eat anything for at least 24 hours, especially if a person fasts for longer periods of time.

Many of the downsides or risks are age-specific (people older than 70 have increased risk).

These risks include:

Bone thinning and development of osteoporosis
Weakened immune system (especially after exposure to infection, injury, or surgery)^{1 and 2}
Reduced lean body mass
Compliance and cognitive distraction associated with a lower calorie intake

For elderly people who already struggle with frailty (maintaining lean muscle mass) or injury, we do not suggest fasting regimes. Most young, healthy adults can partake in fasting without seeing downsides. It’s generally not a good idea for children and teens to fast.

Caloric restriction is a catabolic activity (breaking down) so healthy adults who require peak physical performance and anabolic environments (i.e., professional athletes, bodybuilders etc) may consider limiting the length of their fasts. In theory, fasting can hurt physical strength and performance, but the results are mixed.

In one anecdotal account of the fast mimicking-diet (FMD), Quantified Bob managed to have muscle gains and fat loss during his FMD. He also experienced a further muscle rebound after his FMD was finished and he was eating normally again.³

Whether fasting negatively impacts physical strength and lean mass may depend upon the “interindividual variability”⁴ of each person. For persons concerned about losing muscle, following a TRE or FMD protocol might be a better choice than doing a water fast.

Who should NOT fast?

Dr. Valter Longo (author of The Longevity Diet) recommends the following people NOT engage in fasting:

Pregnant women
People who are underweight, have very low BMI, or suffer from anorexia
People over age 70 (unless in superior health and with doctor’s approval)
Anyone with liver or kidney disease
People affected by pathologies (unless prior approval is given from specialized doctor)
People who take medications should seek approval first
People who have low blood pressure
People with rare genetic mutations that block capacity to produce glucose from glycerol and amino acids (gluconeogenesis)
Athletes during training or competition

It is worth noting that Dr. Valter Longo created this list specifically for the fasting mimicking-diet (FMD), which was formulated to be the least physiologically demanding while still gaining the health benefits associated with fasting. Long-term or multi-day water fasts may be even more challenging so proceed with caution even if you do not fall within the categories above. If there is any question, start with small fasts and work your way to extended calorie restriction, or find a doctor or coach who has experience helping people with fasting

Dr. Longo’s list for FMD did not mention children and teenagers (basically anyone who is growing). I’d add them to the list.

Is it OK to skip breakfast?

Issues of breakfast will mostly apply to the subtype of intermittent fasting called time-restricted eating (TRE) where daily food is eaten within a specific time window.

Breaking the fast is important, but not in the way that most people have been told. Abigail Carroll (author of Three Squares: The Invention of the American Meal) shares that the invention of the phrase “breakfast is the most important meal of the day” was actually coined and popularized by John Harvey Kellogg, the founder of Kellogg, who might not have wanted you to skip breakfast cereal. This conflict of interest went unnoticed until fairly recently, but the myth has permeated health wisdom as fact.

Bias aside, calorie restriction data suggests that timing matters. One 2014 study in Diabetologia found that eating larger meals in the first half of the day could support healthy metabolic markers⁵ while restricting food intake to the evening showed negative metabolic results.⁶ Finally, individuals consuming more food in the morning had more weight loss than those who has the same calorie intake in the evening.⁷

There is compelling evidence that eating more of our daily food in the morning can be more effective for at least some benefits of fasting, but compliance becomes a challenge. Humans are social animals and many social events (especially food-related ones) occur in the evening. It may vary by culture, but in the western world, dinner is more social. The best fast is the one that you maintain. My mother has tried TRE (by not eating in the evening or finishing her last meal by 5:30 PM) and failed many times because of the social challenges to compliance. Shifting the TRE eating window later in the day might not be as theoretically beneficial but there’s no benefit to something you won’t do.

Are there compounds that mimic calorie restriction?

Yes, there are compounds that mimic the healthspan and lifespan benefits of calorie restriction and exercise. These are called calorie restriction and exercise “mimetics.” Understandings in this area are still a work in progress, but there’s a large (and growing) amount of research in these areas.

One of these is resveratrol, which is a naturally occurring polyphenol found in plants. If you remember some of the mechanisms we explained in Benefits of Intermittent Fasting, resveratrol activates AMPK and sirtuins.

Resveratrol is considered by many to be “...the strongest natural [sirtuin-activating compound]...,”⁸ because it supports mitochondrial biogenesis (generation of new mitochondria), enhances sensitivity to insulin, and supports autophagy (cellular cleanup). For a more in-depth understanding listen to this podcast with Dr. Peter Attia and Dr. David Sinclair.

Another biohacker favorite is metformin, a prescription drug used for type-2 diabetes therapy. In animal models, metformin can extend lifespan⁹ though no human trials exist. These studies show that metformin supports increased antioxidant protection, reduced chronic inflammation, and induction of autophagy.

While our understanding of individual interventions (like metformin or exercise) has been growing, we still know little about the anti-aging mechanisms at play when two or more interventions are combined, however. On December 2018 Aging Cell published a study suggesting that metformin inhibits (prevents) the positive mitochondrial adaptations of exercise. In simplified terms, metformin prevented some benefits of exercise.

Exercise is one of the most powerful healthy aging strategies and metformin has extended lifespan and healthspan in animals. Interestingly, the two together were not additive. Instead, metformin subtracted from some of the benefits of exercise. As with all CR and exercise mimetics, the authors suggested that “...prior to prescribing metformin to slow aging, additional studies are needed…”¹⁰

Rapamycin (known as sirolimus or rapamune) is another CR mimetic, which inhibits mTOR (mammalian target of rapamycin). This prescription drug is an immunosuppressive with limited medical applications, but can also downregulate mTOR, increase Fox-O and autophagy (considered beneficial mechanisms for life extension). Unfortunately, there are side effects including hyperglycemia and insulin resistance. Intermittent use of rapamycin might be one way to experience the positives while minimizing these unwanted effects.

Nicotinamide riboside (NR) has become a poster-child for the anti-aging movement, but almost all niacin equivalents may produce positive effects on NAD+ and the ratio with NADH. As we age, cellular levels of NAD+ decrease while NADH levels increase. A higher ratio of NAD+ to NADH can promote more healthy aging. While NR is one (expensive) supplement choice, others include nicotinic acid (inexpensive), niacinamide (inexpensive), or nicotinamide mononucleotide (NMN) (also very expensive).

What breaks a fast?

The pathways and mechanisms that provide fasting benefits are still being researched. We do know that certain food choices can partially break fasts while others may not. While there are no definitive answers based on the existing data, we are getting closer to understanding how these might affect the fasting response.

A common question is whether coffee or caffeine breaks a fast. The conventional wisdom is that something with no calories, like black coffee, does not break the fast. This might be true; however, there’s no direct evidence either for or against it (it hasn’t been studied). We’ll share what two experts think and what limited animal experiments suggest.

According to Dr. Satchin Panda (Salk Institute for Biological Studies) and Dr. Rhonda Patrick, coffee DOES break some elements of the fast.¹¹ Patrick later confirmed:

“Anything that affects the brain, gut, liver, etc. sets the clock. Caffeine does this”¹²

By “clock” Dr. Patrick is referring to the body’s circadian system. This system affects many aspects of cellular function including blood sugar regulation and autophagy. In essence she believes that if things we consume affect clock function (which caffeine does) they might also affect some of the underlying mechanism responsible for the benefits of fasting and this might occur even if the substance affecting body clock function has no calories.

Dr. Satchin Panda estimates that drinking coffee is not the same as a water fast. If a true water fast is 100% fasted, drinking coffee is the equivalent of being 40 - 50% fasted.¹³

Based upon the limited evidence we don’t think drinking a cup of coffee a few hours before ending a period of fasting is likely to derail a period of time-restricted eating. If anything, the animal research suggests that the coffee might amplify the autophagic response for few hours following according to a 2014 study in Cell Cycle.¹⁴

The key would be to consume actual coffee rather than simply using caffeine. Coffee has polyphenols that may improve the desired response to a period of fasting while caffeine alone may not.

Another common question is whether fat breaks a fast. The trend of adding MCT oil or butter to coffee has been popularized over the past decade. The marketing that goes with these fat-based drinks suggest they do not break the fast, but this may or may not be factual.

Dietary fat is considered calories. This means that certain longevity mechanisms that are sensitive to calorie intake are likely to be impacted once fat is consumed. Some of the longevity mechanisms (such as mTOR) are protein sensitive, which may suggest theoretical evidence that fat alone may not impede certain fasting mechanisms. This hypothesis is discussed briefly by Dr. Jason Fung in this video, but there are no studies on the subject.

We do know that the body utilizing solely fat for energy is different from a cognitive and metabolic perspective than utilizing dietary glucose. There may still be cognitive and physical benefits of using butter coffee while fasting, even if some of the longevity and anti-aging effects of fasting are diminished.

Are the Health Benefits of Fasting Variable?

(And we have a fasting challenge for you!)

The question of what breaks a fast and our analysis of existing data brings up a good teaching opportunity. We do not fully understand all of the mechanisms involved with fasting and what does and does not turn everything on and off. These mechanisms should be looked at as more of a spectrum than an “on / off” switch. If this is true, we are likely to get many of the benefits whether or not we have a cup of coffee.

Fasting isn’t a single thing. It’s a range of behaviors, all of which, even the least extreme, like time-restricted eating, can have health benefits.

If in doubt, do less for a shorter amount of time. There is no need to start with a 3 or 5-day water fast. Instead, you can start by eating as much as you usually do, but within a smaller window of time. This creates a bigger daily fasting period as a side effect.

Whether you have experience with fasting or not, the challenge is to pick one of the fasting behaviors I’ve mentioned in this complete guide to fasting (specifically What to Expect While Intermittent Fasting) and start fasting. Pick a start date (ideally in the next 30 days), put a reminder on your calendar, and start your self experiment.

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