Intermittent Fasting – Research Explained


Welcome to the next post in our Research Explained series, where we do a deep dive into a specific topic, spend hours scouring through the primary literature, and summarize the key findings so that you don’t have to. This is topic 8 — you can find the full list here.


How to Think About Nutritional Interventions

Nutrition is a touchy subject, on the same level of politics or religion. I’m interested in talking about nutrition from a purely health-focused perspective — if your dietary decisions are based on religion or ethics, I respect that, but we’ll be approaching the science with a focus on health optimization. One of my favorite sources for nutritional, health, and longevity based information is Dr. Peter Attia.

When discussing nutritional interventions with his patients, he describes three factors to his nutritional framework: dietary restriction, caloric restriction, and time restriction. Each factor can be manipulated independently of others to optimize for the desired outcomes.

Dietary restriction means limiting what you do or don’t eat. For example, maybe you avoid red meat or dairy. Caloric restriction means limiting how much you eat, which is the most common description of “dieting” that we think of when it comes to losing weight. Time restriction limits when you do and don’t eat, which brings us to intermittent fasting.


Intermittent Fasting Definitions

Speaking about intermittent fasting and similar interventions is confusing because most people, and often even researchers, aren’t careful about what they’re exactly talking about. Fasting is refraining from eating. When we refer to fasting, we normally are referring to water-only fasts, where consuming water is ok, or even teas and minerals, but not foods or drinks with any calories, sweeteners, or the like.

When you hear the term “Intermittent Fasting” being used by the public, they’re usually referring to time-restricted feeding (TRF) instead. Time-restricted feeding is where you limit the hours during which you eat each day to a feeding window. Most people without any effort normally stick to roughly a 14/10 window, meaning they’ll eat for 14 hours, and fast for 10 hours while they sleep and a little bit before and after. The window can be expanded to anything you want. When starting out, you may do 12/12, but eventually transition to the popular 16/8 or even 18/6.

Alternate day fasting (ADF) is somewhat of a misnomer, since you don’t normally go a full day without eating anything. Rather, every other day you switch to doing something other than eating ad libitum, meaning without restriction. Usually, these days are hypocaloric with 1,000 or 500 calories allowed.

Intermittent fasting (IF) in its most strict form is undergoing a fast of at least 24 hours at some frequency, or intermittently. For example, that could mean doing a 72 hour fast once every quarter, or a 5 day fast once per year. A true prolonged fast like this would only include water, tea, and minerals with zero calories.

As time-restricted feeding is what most people are referring to when they speak about intermittent fasting, that’s what we’ll be covering here.


What Do We Know About Time-Restricted Feeding and Intermittent Fasting?

Weight Loss

Weight loss boils down to a simple measurement of calories in and calories out. If you’re eating more calories than are burned, you’ll gain weight, and if you’re taking in fewer calories than you burn, you’ll lose weight. For this reason, dietary interventions for weight loss are primarily focused on continuous energy restriction (CER), or in other words, eating as you would normally, but just eating fewer calories. The issue with CER is that adherence is poor, typically declining within 1-4 months.

A recent review by Rynders and colleagues from 2019 concluded that, based on current literature, “intermittent fasting does not seem to produce greater weight loss than continuous energy restriction.” However, “adherence to weight loss interventions is the greatest predictor of weight loss success”, and some patients may respond better to caloric restriction, while others will respond more favorably to intermittent fasting or time-restricted feeding. Few studies were carried out long enough to properly assess adherence to the two different protocols.

Interestingly, time-restricted feeding seems better at preserving lean mass per a 2016 study by Moro and colleagues compared to continuous caloric restriction. Count that as a win for time-restricted feeding.

Metabolic Benefits

While IF is moderately successful for weight loss, there are a variety of interesting metabolic effects that occur. Kahleova et al compared time-restricted feeding to caloric restriction and found greater improvements in fasting glucose, increased oral glucose insulin sensitivity, decreased C-peptide levels, and decreased glucagon levels in the TRF group.

Sutton and colleagues in 2018 found that men with prediabetes who performed time-restricted feeding experienced improvements in multiple cardiometabolic health markers, beyond what would occur from simple weight loss.

But what if you’re healthy without any chronic medical conditions? A meta-analysis and systematic review by Cho et al. in 2019 concluded that “intermittent fasting improves glycemic control and insulin resistance with a reduction in BMI, a decrease in leptin level, and an increase in adiponectin concentration,” which are generally considered favorable changes for most individuals. Cabo in 2020 also highlighted the benefits of blood pressure, heart rate, endurance training effects, and abdominal fat loss.

Cognitive Benefits

Cognitive effects have been primarily studied with regards to caloric restriction, not time-restricted feeding, although it’s not unreasonable to assume similar findings. After all, time-restricted feeding and other intermittent fasting protocols often lead to decreased caloric intake compared to feeding ad libitum.

Studies in animals show enhancement in multiple domains of cognition, including spatial memory, associative memory, and working memory. Caloric restriction has been associated with improved verbal memory in older adults. In a separate study involving overweight adults with mild cognitive impairment, 12 months of caloric restriction led to improvements in verbal memory, executive function, and global cognition. More recently, Leclerc et al in 2020 performed a large multi-center randomized trial demonstrating that 2 years of daily caloric restriction led to significant improvements in working memory.

Other Effects

Stress isn’t always a bad thing. With intermittent fasting and time-restricted feeding, cells are forced to cope with the lack of a relatively continuous glucose source and engage in a “coordinated adaptive stress response that leads to increased expression of antioxidant defenses, DNA repair, protein quality control, mitochondrial biogenesis, autophagy, and down-regulation of inflammation.”

The effects on aging are likely present but not yet well established. While several studies have demonstrated benefits to the aging process in animals, the evidence is less clear cut when it comes to human longevity and a healthy lifespan. After all, we haven’t been able to research IF or TRF for decades among clinical subjects.

In terms of cardiovascular disease, intermittent fasting has been associated with improvements in multiple cardiovascular markers, including blood pressure, resting heart rate, HDL and LDL cholesterol, triglycerides, and insulin resistance. Additionally, IF has been associated with reductions in markers of systemic inflammation and oxidative stress that are associated with atherosclerosis, which is the clogging of your arteries.

Early versus Late Feeding Windows

Next, does the time of day during which your feeding window is scheduled matter? Jamshed and colleagues in 2019 studied early time-restricted feeding (eTRF) by shifting the entire feeding window earlier in the day. While far from a perfect study, it demonstrated several interesting findings: first, early time-restricted feeding resulted in lower average glucose and insulin levels. Second, avoiding food for a prolonged period before bed was also associated with lower nighttime cortisol and overnight glucose. And third, there was an increased expression of LC3A, an autophagy gene, suggesting that more autophagy occurred with early time-restricted feeding.


Should You Try Time-Restricted Feeding or Intermittent Fasting?

Evidence-based medicine focuses on making treatment decisions based on the best evidence available in the scientific literature. It’s fantastic at addressing things like infectious diseases because infections are acute and binary in outcome and interventions are generally straightforward, like an antibiotic or antiviral, thus making measuring inputs and outputs relatively straightforward.

The problem, however, is that most things related to health are much more complicated. Those opposed to intermittent fasting are quick to say “there isn’t sufficient evidence to support a fasting protocol for disease X or Y, therefore you should not do it.” But to most accurately assess the situation, you need to compare the risk of the intervention, which is what we normally think of, with the risk of not doing the intervention, which people are less likely to consider.

I am not saying that you should begin time-restricted feeding or intermittent fasting, particularly if you have another pre-existing medical condition, and you should speak with your physician. I am saying, however, that if there is a favorable asymmetric risk profile for you personally, meaning the potential upside is relatively large and the potential downside is relatively small for any lifestyle intervention, experimentation may not be a bad idea.

After consulting the literature and considering the potential upsides and downsides in my own personal life, I decided to give it a shot. I first started in 2017 when I was in a plastic surgery residency, but I quickly realized that I was losing too much weight since I couldn’t eat while in the operating room. I then started again about a year ago, back in 2019.

I’ve been doing time-restricted feeding for close to a year now, and I’m enjoying it enough to stick with it. It’s also been a gateway intervention of sorts, paving the way for me to perform 36 and 48-hour fasts a few times, and has even been a practice in building discipline. I just released a video on my personal YouTube channel going over my experience, including the benefits and drawbacks I’ve experienced over the last year.

Thank you all so much for reading. If you’ve tried intermittent fasting or time-restricted feeding, what was your experience like? Let us know with a comment down below!


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