Suggest to read this article:

https://www.nejm.org/doi/pdf/10.1056/NEJMra1905136?articleTools=true

De Cabo, Mattson. NEJM 2019

Thomas W Buford Fantasic recent article. Thanks. It was easy to sign up for free for full article viewing. I plan to read after I meet my daily blabber quota below.

I don't think there is any "Best"

Personally on this topic I suspect much low grade structural harm will result from endorsement of there being any "best" method. (By analogy, the fiction of a "best diet" for humans will, sadly, I predict, continue to conjure calamitous perpetual distraction from life-saving focus on desired end points reachable via any number of means). Perhaps within 10 years a viable set of direct autophagy markers will become consumer-available, whereupon N=1 "try 10 things and learn what works best for you" could be applicable. Until then, I'd hope people could at least lean in to the spirit of expecting that kind of future. Also, I would also caution against measures of "best" including practicality as I have seen, as in "this might not be the most healthy, but because it is easier and more likely engender good compliance it is the best."

Having said that, I'd offer a few things for consideration:

(1) Measure what you can

Use blood ketone measurement or breath ketone measurement, in the absence of exogenous ketones, as a proxy for autophagy, particularly if dietary calories are not predominantly fat (i.e., ketones more likely to indicate fat reserve break down). Good intermittent fasting behaviors are those that result, at the very least, in any measurable ketone level for more if not most of the hours of the day on more days per week versus never.

(2) Hepatic Glycogen

Consider hepatic glycogen stores as an intermediate point of integration. Try to pulse stores downward. The less time spent exercising under conditions of glyconeogensis, the greater the need for going longer without eating, and vice versa. The higher the amount of processed carbohydrates in the diet, the greater the need for extended non-feeding hours. Intuitively, this should be part of any real-world applied regimen.

(3) Resistance Training

Similar to the above, consider the role of resistance training in triggering increased sarcoblastic amino acid requirements. For any given feeding interval, like 18/6, the stronger the sarcoblastic impetus, the deeper into autophagy the body will need to dip in order to meet protein needs via recycling poorly functioning proteins and organelles. Conversely, regardless of caloric expenditure from exercise (ex: 20 minute run vs 60 minute run) a bout of resistance training to fatigue (say 5 minutes of completely exhausting squats) could take the place of some duration of non-feeding for similar benefit.

(4) Hit and Run

A number of interventions seem to have disproportionate benefit in a "hit and run" fashion. Doing a 18 hour fast one day per week is more than 1/7th as effective as doing so seven days a week. Doing one 36 hour fast once a week could accrue overall benefit corresponding to some number of days of 18/6. Doing one 36 hour fast once a month could likely swap out some equivalent number of sub-day fasts over the same month. (By this token, the people at Prolong are, perhaps astoundingly, highly opposed to skipping breakfast or intermittent fasting.)

(5) Switch it up

Chances are that unpredictable stochastic pulsing increases intervention impact. For some analogies, Star Trek fans might relate to "phase modulation" during Borg skirmishes. Or, cross training in fitness has emphasized switching amongst exercises in order to keep the body "off guard" and less able to adapt toward being able to be more "lazy". When one studies the mechanisms of diminishing return in hormesis (adaptive response) some intuition might arise that it is easier to adapt away from some benefit when the intervention is a static one time permanent shift. This intuition would argue that intermittent fasting might be most effective to the degree that it does not follow the same pattern every day or every week.

(6) Overlap with sleep

Fasting periods should overlap with sleep. Kind of a no-brainer, but the value of allowing all localized chronological clocks to synchronize during repair mode is sometimes undervalued. Starting an 18 hour fast at 6am misses this boat (for non-night shift people).

(7) 4-5 day threshold

When "intermittent" becomes "long term". (Most will agree much terminology imprecision at work here!) ... it seems that very distinct immune system regeneration benefits emerge upon re-feeding after a fasting duration of at least 4 or 5 days. The emerging Prolong protocol to consistently drop A1C is three months in a row of 5 day fast mimicking protocol (where they are actually at about 1000/cal day of stuff least likely to spike any insulin at all and least likely to activate any mTOR at all). Fasting methods could probably be lumped, in terms of qualitative character, into two piles of less than 4 or so days and greater than 3 or so days.

(8) Literature heads up - adaptation

Some current literature on the topic still fails to control for adaptation periods. A longer term response to new IF is likely to be different from the initial response over the first 2-3 weeks. For IF fans, this is something to look for in IF studies showing "adverse" results.

Also, I noticed some epigenetic literature.

Ex:

Article Fasting unmasks differential fat and muscle transcriptional ...

Article 36 h fasting of young men influences adipose tissue DNA meth...

Food scarcity when you and your progenitors were in the womb impacts your expressed phenotype.

So, better fasting methods per person likely depend on factors including

a) the person's gene polymorphism makeup, as well as

b) the pre-natal environment of that person, and

c) the pre-natal environment of that person's ancestors.

I followed weekly fasting for many years. Now I am 74 year-old and therefore, I usually avoid my dinner to keep me in good health.I am very energetic and doing all my work.

If one eats more boiled vegetables, fresh seasonal fruits, nuts than deeply fried and fatty foods, health will be good.Further, I advise that dinner must be completed by 7 PM before going to bed at 10 PM.

Agree with Prof Mahendra Pal that stop eating few hours before going to bed is very good for health. And I suggest this time span should be at least 5 hours to ensure that one's stomach is empty before going to bed.

Though I can't fully understand due to the language barrier, I appreciate the effort made by Menassel Kawther

Intermittent fasting strategy may not be generalized as i myself felt a hypoglycemia on skipping my morning breakfast as a part of it following and also happened to receive same feed back from a few of my patients..

Thanks Hima Bindu Ponnam for sharing your personal experience.

6pm-10 am

There is, for example, a short fast of 2-5 days. Trained people can survive 30 days.

Regards, Sergey Viktorovich Pushkin

Dear Foad Alzoughool thanks for your valued response. Do you personally follow the fasting schedule that you mentioned? I appreciate it.

Dear Sergey Viktorovich Pushkin thanks for your contribution. You have mentioned a short fast of 2-5 days. How frequently should one follow it? Is it monthly?

No meal after 6pm

Dear Harasit Kumar Paul

Fasting can be done once a month. The main thing at this time is to drink enough water. These recommendations are known / based on kilograms of weight. Otherwise, slags and toxins will have the opposite effect.

Regards, Sergey Viktorovich Pushkin

I worry of stomach ulcers. Are health benefits of fasting. It is more of religion commit.

No fat

follow

Fasting three days within full moon days.