NEJM: Intermittent Fasting Effects Paper
IF is the new new thing. Actually, research on fasting started in 1934. Rats on a restricted calorie diet lived 80% longer than the ones who get to eat without limit. But there is a lot more to fasting than just rats living longer. People improve also – in some really surprising ways.
Effects of Intermittent Fasting on Health, Aging, and Disease 
First, the authors talk about the process:
When you stop eating for 8-12 hours – when you start fasting – your body switches from consuming glucose (which is gone, since you aren’t eating), to consuming keytones for energy. Once the keytones appear, this seems to be a general signal for your cells to start doing all sorts of different things – that tend to be surprisingly positive for your system overall.
“Ok boys we’re running on ketones now. You know what to do.”
How much of the benefit of intermittent fasting is due to metabolic switching and how much is due to weight loss? Many studies have indicated that several of the benefits of intermittent fasting are dissociated from its effects on weight loss. These benefits include improvements in glucose regulation, blood pressure, and heart rate; the efficacy of endurance training, and abdominal fat loss.
Studies in animals and humans have shown that many of the health benefits of intermittent fasting … elicits evolutionarily conserved, adaptive cellular responses that are integrated between and within organs in a manner that improves glucose regulation, increases stress resistance, and suppresses inflammation. During fasting, cells activate pathways that enhance intrinsic defenses against oxidative and metabolic stress and those that remove or repair damaged molecules. During the feeding period, cells engage in tissue-specific processes of growth and plasticity. However, most people consume three meals a day plus snacks, so intermittent fasting does not occur.
Preclinical studies consistently show the robust disease-modifying efficacy of intermittent fasting in animal models on a wide range of chronic disorders, including obesity, diabetes, cardiovascular disease, cancers, and neurodegenerative brain diseases. Periodic flipping of the metabolic switch not only provides the ketones that are necessary to fuel cells during the fasting period but also elicits highly orchestrated systemic and cellular responses that carry over into the fed state to bolster mental and physical performance, as well as disease resistance.
In humans, intermittent-fasting interventions ameliorate obesity, insulin resistance, dyslipidemia, hypertension, and inflammation.
Gee. Nothing important there. Only the stuff that kills most of us in the US.
So how do you do this fasting thing? They tell us in the paper:
1) a complicated 4 month program where you gradually reduce calories for 1-2 days per week down to 500 – but just for two days out of 7.
2) Make sure your “feeding period” each day is just 6 hours long. I.e. eat lunch at 1pm, dinner at 7pm, and that’s it. This is an 18-hour fast.
I do #2. Once my body got used to it – it takes about a month – it is no problem at all.
Pharma is excited about fasting – well kind of – they think they can develop a pill that pushes your body’s buttons in the same way that IF does.
You could wait for the Pharma product, hope it didn’t do anything bad a year down the line, or – you could just constrain your eating to a 6-hour period per day. Effectively: just skip a meal. I’ve tried a bunch of diets. Fasting is far easier than any of them.
There really is something that happens when my body flips from glucose to keytones. Something changes. And the longer I let it run, the less “starved” I feel – to the point where I suspect I could just do one meal per day without too much difficulty.
It appears that a large number of the risk factors for COVID are basically addressed with IF: obesity, insulin resistance (T2D), dyslipidemia, hypertension, and inflammation. Sure seems like IF might be something to add to the “terrain-building” arsenal.
You might consider handing this paper to your doctor. Ask them what they think. My doctor heard about this already – not sure if he’s pulled the trigger yet. He was definitely interested when I talked with him about it.
Its the new-new thing. And – best of all – its free! 🙂
As usual, good info Dave. My wife and I have done the 18 hour fast intermittently for many years. We find it easier to eat a light breakfast (can’t go without coffee) and eat a late lunch/early dinner around 2:00 or 3:00 pm. In doing this it also eliminates gerd issues if one has the problem. We also find our sleep is improved.
Great post, Dave. October 2019 I started IF with 16/8 and then eventually 18/6. I am 62 and I lost over 20 pounds in a year and hit my goal. It does feel great and you’re right it’s not hard at all. No calorie counting and I eat good food including moderate sweets. I recommend Gin Stephens’ book Delay Don’t Deny. And there are some great helpful support groups on Facebook including one that Gin runs.
I was doing IF for about a year. Once a week I would do a full 24 hr fast. I never felt better in my adult life. Cant remember why I ever stopped.
Say you have a bit of wine in the evening after beginning the daily IF at 6 pm, is that still IFing?
So this article here:
reviews the literature. Executive summary: yes, but.
Turns out, alcohol is yet another energy source for your body. Once you consume it, your body converts it into energy. Not glucose, not ketones, it is now using acetate. Fat burning slows – or stops – depending how much you drink.
Curiously, the body actually produces alcohol in the gut. Supposedly a third of a beer per day. Perhaps that’s why the body already knows how to make use of ethanol. That, and fruit ferments naturally, so on the plains of Africa it was probably an advantage to be able to use every energy source available. My guess.
The alcohol we consume gets converted into something called acetaldehyde and then into acetate. We can handle acetate, but if we drink too much too quickly, the enzymes responsible for this conversion can’t keep up and the acetaldehyde begins to spill over and can lead to damage and toxic effects. So it makes sense that as much as 77% of the alcohol you ingest becomes blood acetate and that we are well equipped to dispose of this acetate [Manzo-Avalos S, 2010].
The primary fate of circulating acetate is oxidation. In other words it gets burned as a fuel, eventually being metabolized to CO2 in heart, skeletal muscle, and even brain cells.
The rough translation of this is: if acetate it present in your blood it will get used in priority over fat or carbohydrate and protein.
In fact, blood acetate is such a priority that it’s mere presence can decrease lipolysis by ~50%, even when you are in the fasted state [Crouse JR, 1968]
And this is what happens when you drink during your fast. It’s not that you will gain more fat (unless you are drinking excessively), but you will stop releasing body fat, stop burning body fat, and burn acetate instead. This occurs without any change in insulin levels.
Right so – yes, but. As I understand it, alcohol doesn’t break your fast from the glucose standpoint, but there’s this new thing called acetate which gets burned instead of your fat (keytones).
The author also noted that large quantities of alcohol ends up interfering with sleep, which ends up reducing the HGH.
So I think the answer is – you can, but don’t drink too much. And nothing sweet, otherwise that’s glucose, and your fast ends, and it takes another 8-10 hours to get it back again. So dry wine, straight whiskey (and soda), etc. No port, no sauternes, no ice wine, no beer, etc.
Really interesting question. If you look up “alcohol and intermittent fasting” on a search engine, you will see this appears to be a very popular question. There are lots of hits.
There are lots of good people on you tube.
My two favorites for all things keto and fasting are Dr. Mindy Pelz and Dr. Sten Ekburg. Dr. Mindy is especially good to help women with fasting as women have hormone and cycle issues different from men.
Lots of good advice about what foods break your fast.