is this a temporary fad that will pass, or the paradigm shifting dietary intervention

we're led to believe? Let's find out.

Dr. Jubbal, MedSchoolInsiders.com.

Welcome to the next episode 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 episode 8 — you can find the

full list on our Research Explained playlist. Link in the description.

Nutrition is a touchy subject, on the same level of politics or religion. Just look at

the comments on my video where I spoke about stopping a plant based diet after 5 years.

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.

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.

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.” please do a highlight effect on the relevant line on page 18 of

the PDF, like how Jeff Nippard does so in his videos that reference scientific papers

However, “adherence to weight loss interventions is the greatest predictor of weight loss success”

bottom of page 14, 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 of 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.

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 cardio metabolic 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. top of page 9 Cabo in 2020 also highlighted the benefits in blood

pressure, heart rate, endurance training effects, and abdominal fat loss.

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 enhances 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, and 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.

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 lead to increased expression of antioxidant

defenses, DNA repair, protein quality control, mitochondrial biogenesis, autophagy, and down-regulation

of inflammation.” bottom left page 2544 from Cabo 2020

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 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.

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 increased expression of LC3A, an autophagy gene, suggesting that more autophagy

occurred with early time restricted feeding.

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

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 channel going over my

experience, including the benefits and drawbacks I've experienced over the last year. Link

in the description.

Thank you all so much for watching. If you've tried intermittent fasting or time restricted

feeding, what was your experience like? Let us know with a comment down below. Much love,

and I will see you guys in that next one.