Intermittent fasting for fat loss or anti-aging?



Lots of people, even including those wanting to build muscle, are doing intermittent fasting (IF) these days. The goal for these people is to lose body fat and, hopefully, retain muscle or build muscle at the same time.

Others practice IF as an anti-aging method. This has solid science behind it, and it may even be more beneficial for anti-aging purposes than calorie restriction, heretofore the most effective strategy for inhibiting or reversing aging.

Branched-Chain Amino Acids

Many of those in the first camp (lose body fat, retain muscle) use branched-chain amino acids (BCAAs), or leucine (one of the BCAAs) or perhaps whey (which is rich in BCAAs) during their fast. BCAAs are powerful signals that tell cells to ramp up muscle protein anabolism and to decrease muscle protein catabolism. So the use of BCAAs while fasting is the practice that will give one the best shot at retaining or even building muscle, even while doing regular, periodic IF.

However, one thing that BCAAs, whey, or leucine do is to stop autophagy, the cellular self-cleaning process. This process is radically enhanced by fasting, and it is responsible for the beneficial effects of calorie restriction and fasting. No autophagy, no anti-aging benefit from fasting. One of the ways (not the only one) that BCAAs increase muscle protein synthesis is through increased insulin levels. Insulin suppresses autophagy.

So, if you practice IF for the purpose of anti-aging, you must not take any BCAAs, nor, if you are in the habit of taking small amounts of food during a fast, must you ingest any protein or carbohydrates, which raise insulin and stop autophagy, which is the central component of the anti-aging effect of IF.

Avoiding Intermittent Fasting Sabotage

However, fat, or in any case small amounts of it, do not raise insulin and do not signal the metabolic machinery to stop autophagy. Therefore you won’t sabotage an anti-aging fast with small amounts of fat. The best thing to do here, if needed, is to drink coffee or tea with cream; the fat in the cream will help satisfy the appetite, and the caffeine in coffee or tea will also decrease hunger.

That’s why you should be clear on what your intermittent fasting purpose is. If it is for fat loss, by all means use BCAAs to decrease muscle breakdown. If your purpose is anti-aging, you should avoid BCAAs.


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  1. Anonymous says:

    Interesting. My primary goal is muscle gain (I consider myself an amateur powerlifter) and I’ve been IFing for a few years now but I hold a strict fast, no calorie intake of any kind. I don’t feel like I’m losing muscle and I am gaining strength, although it would be interesting to see a study of IF+BCAA vs. strict IF.

  2. Mangan says:

    Yes, it would be interesting to see a study on that. Unfortunately for a lot of things we can only speculate intelligently. Was discussing with someone how we know that autophagy increased after 16 hours of fasting, but I believe there are no human studies.

  3. Richard says:

    Breakfast is the most important meal of the day. Surely IF would be more optimal to skip dinner instead of breakfast? A feeding window between 8am – 4pm, with a 24 hr fast (breakfast sunday to breakfast monday) once per week. Would this be more beneficial than the traditional IF program of skipping breakfast every day? I believe so, if only because of my TCM training (unscientific as it may be) which theorizes that “qi” is in the stomach and spleen “meridians” most prevalently in the morning (7am – 9 am stomach, 9am – 11am spleen/pancreas). Thus there is more energy available for healthy digestion during those times, and conversely less energy available for digestion after 7pm at night.

    • P. D. Mangan says:

      Richard, it’s undoubtedly perfectly OK to do the fast with the timing you indicate. Whether breakfast is the most important meal of the day I’m very skeptical. Research on whether eating breakfast helps weight loss has been decidedly mixed. Many people, including myself, feel the least hungry in the morning, which I think a good indication of… something.

  4. Haven M. says:

    Cool info…I wondered if I was doing something wrong by taking fish oil and Vitamin d with my coffee in the morning. What about the protein in a theanine dose with coffee? Should I take the amino acids later or just not do it on IF days.

    • P. D. Mangan says:

      No, not at all. Go ahead take your fish oil and vitamin D, you’re still fasting. Theanine is an amino acid, but I doubt it has much effect on fasting or autophagy since it’s not an amino acid found in proteins, plus the dose at ~200 mg is small enough that it shouldn’t matter.

  5. Rob H says:

    Hi P.D,

    Here’s a controversial question for you: from what I have seen to date, I don’t believe it is necessary to fast or calorie restrict at all. Indeed, from all the research I have read, the only thing you need to do to bring all the health/ longevity benefits are to a.) restrict protein and b.) restrict carbs for at least 16 hours for just a couple of times a week. Pure fat intake (on its own that is) does not affect either autophagy, ketosis or even IGF-1 levels. So go ahead and eat a scoop of coconut oil, MCT oil, spoon of extra virgin olive oil, grass-fed butter, cream in your coffee etc – no problems – get all the health benefits without ever feeling hungry.. You could also add in some low protein/carb but high fibre veg to fill you even further such as spinach, mushrooms and sauerkraut (fermented cabbage), etc. Actually you will feel quite full after eating this!

    Of course, this is only for those who are not trying to lose body fat, as of course the body will be using the exogenous fat supplied for energy generation (via ketones) in place of endogenous body fat.. But would this not be an excellent long-term health strategy for those who have already reached their weight loss goals or are indeed trying to gain lean muscle? (If you’re trying to lose body fat, just go easy on the fat and ramp up the fibrous/ low-carb vegetables instead). Would be great to hear if you have seen any science that goes against what I am proposing here..

    • P. D. Mangan says:

      Hi Rob, yes I think you’re right. If you’re familiar with fasting with Bulletproof coffee, this is essentially what its inventor Asprey advocates: coffee with butter and MCT oil instead of a complete fast. That should give you all the benefits without going hungry. Indeed, you could probably eat as much fat as you want and get the benefits, as shown in that study with infused lipids: no differences in insulin, glucose, ketones, with lipids as opposed to completely fasting.

  6. Rob H says:

    Many thanks for clarifying on that one P.D. The thing that bugs me is that you quite often read on sites such as Mark’s Daily Apple the recommendation to eat ‘good’ fat: but always caveated with ‘in moderation’. I never understood what science he is basing the ‘in moderation’ bit on. From everything I have read it does seem that eating pure dietary fat will of course impact body fat loss HOWEVER, I have not seen any evidence that eating pure dietary fat will cause a lean individual to gain body fat (or indeed any other negative affects – so long as the ‘good’ fat is not eaten together with high carbs).. So why the ‘in moderation’ caveat do you think?

    • P. D. Mangan says:

      Possibly due to both weight loss considerations and residual anti-fat bias. As for weight loss, I’ve found that in this racket, the majority of people want to know just one thing, how to lose weight, and if you don’t cater to them, your readership has greatly shrunk. And as for bias, we’ve had it drummed into our heads for the past 4 decades that fat is bad, and if Mark Sisson were to tell people to eat as much fat as they ant, they might think he was crazy or dangerous, and go elsewhere. Those are my guesses.

      I’ve noticed though that Bulletproof coffee has gone mainstream to some extent, so now you have ordinary people putting butter in their coffee. I mean, I actually know people in real life (besides myself) who do that. Times are changing.

  7. Rob H says:

    Hi Dennis,

    I have been reading that Leucine taken on its own is broken down solely into ketones (as opposed to the other 2 branched chain aminos that can be broken down into glucose – see this link:

    I’m hypothesising that leucine taken on its own during a fast may not hinder autophagy.. Have you seen any studies which back-up or contradict this hypothesis? If correct, that would be very useful as we already know that leucine taken on its own will help prevent muscle catabolism during a 16 hour fast..

    • P. D. Mangan says:

      Rob, the effects of leucine are so engraved in my mind that I had to go back and see where I got them. As usual, Wulf Droge, from whom I learned so much, explains well, Autophagy and aging—importance of amino acid levels:

      Melendez et al. [Science 301 (2003) 1387] have recently shown that the increased longevity of Caenorhabditis elegans mutants with defective Daf-2 protein, i.e. an insulin receptor analog, involves increased autophagy. Autophagy increases the free amino acid pool and is in certain cells essential for survival at times of limited amino acid availability. In addition, autophagy plays an important role in the turnover of proteins and organelles including mitochondria. The autophagic activity is sensitive to changes in physiological conditions, i.e. it is strongly inhibited by an increase in amino acid concentrations or in insulin receptor signaling. In line with this fact, clinical studies indicate that autophagy mainly occurs at times of low plasma amino acid and insulin concentrations in the post-absorptive (fasted) state, and that the post-absorptive amino acid-sensitive protein catabolism may be taken as a bona fide indicator of autophagic activity. The increased longevity of insulin receptor mutants or of organisms subjected to calorie restriction may, therefore, be attributed to an increase in autophagic activity. Importantly, the autophagic activity decreases with age. Recent studies suggest that this decrease may result from an age-related increase in post-absorptive amino acid levels and/or from an increase in baseline insulin receptor signaling. If so, it is potentially reversible.

      Leucine metabolism in regulation of insulin secretion from pancreatic beta cells

      Leucine, a the branched-chain amino acids that must be supplied in daily diet, plays an important role in controlling protein synthesis and regulating cell metabolism in various cell types. In pancreatic β cells, leucine acutely stimulates insulin secretion by serving as both metabolic fuel and allosteric activator of glutamate dehydrogenase to enhance glutaminolysis. Leucine has also been shown to regulate gene transcription and protein synthesis in pancreatic islet β cells via both mTOR-dependent and -independent pathways at physiological concentrations.

      Leucine Limitation Induces Autophagy and Activation of Lysosome-dependent Proteolysis in C2C12 Myotubes through a Mammalian Target of Rapamycin-independent Signaling Pathway

      Bottom line: leucine activates insulin signaling and mTOR, strongly promotes muscle synthesis – the only amino acid that does so – and its absence initiates autophagy and muscle protein degradation.

      Unfortunately, we can’t have our cake and eat it too. Leucine abolishes autophagy and thus shouldn’t be taken during a fast if that fast is for anti-aging purposes, though it would be perfectly acceptable for fat loss.

      • Rob H says:

        Thank you for your extremely comprehensive reply on that one Dennis: I guess that answers that question then! But I would also be very interested to hear your thoughts regarding the Jaminet article stating that leucine reduces iron accumulation in the brain..

  8. Rob H says:

    Just found another very enlightening article on this subject which I am sure will capture your interest: leucine supplementation on its own reduces iron accumulation in the brain, as well as being purely ketogenic (and not glucogenic, so I’m guessing has no impact on raising insulin levels or negatively impacting autophagy..)

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