Glycogen and leptin: a neglected interaction in fat loss? Part 2 of 2

(You can find the first post in this two-part series here).


Glycogen is the storage form of carbohydrate in humans. From what evidence I could gather (which is not as much as I’d like), it appears that humans can store up to 600 g (454 g/lb = 1.32 lbs) of glycogen (see PMID 3165600). I suppose that this will vary depending on training status and body size. There’s an excellent literature review of glycogen synthesis and biochemistry by Roy Jentjens and Asker Jeukendrup (see PMID 12617691).

So why am I talking about glycogen? My hypothesis from Part 1 (but in full-form) is the following:

Leptin regulates metabolic rate. Leptin has been observed to decrease during fasting or severe calorie restriction. So prolonged calorie restriction will subdue metabolic rate, and thus, the rate of body fat loss. Carbohydrate intake has been shown to enhance leptin secretion, but it also enhances insulin secretion, which impairs fat oxidation (needed for body fat loss). Glycogen is used as a storage form of carbohydrate during times of fasting, exercise, and low food intake. Glycogen, by being a source of carbohydrate during fasting, assists in keeping leptin secretion elevated. When glycogen is depleted, this source of carbohydrate is depleted, and leptin secretion drops accordingly. This explains why leptin decreases during short term fasting, much more than body fat drops during the same period (leptin secretion is thought to correlate with body fat, except during fasting). If there is a way to maximize glycogen stores, while minimizing insulin secretion, one could maintain relatively high leptin secretion via use of glycogen stores (and thus keep metabolic rate elevated) and have energy while fasting and exercising, while minimizing insulin secretion (maximizing fat oxidation). 

The question is: “is there a way to do this?” If there were (and I’m correct in my analysis here), it should be great as a fat loss strategy.

It turns out that there appears to be a few ways to do this!

Recall the literature review paper by Roy Jentjens and Asker Jeukendrup (PMID 12617691). In this paper, they assert the following:

Initially, there is a rapid phase of glycogen synthesis, which generally lasts between 30–60 minutes. This phase can proceed without the presence of insulin[38,39] and is therefore also called
the insulin-independent phase.

Wonderful! So perhaps there’s a way to (1) consume carbohydrates to (2) increase leptin secretion, while (3) keeping insulin low. There is one caveat here: the quote above states that there is an “insulin-independent phase” of glycogen synthesis. This does not necessarily mean that if you eat carbs during this window, you won’t secrete insulin. It could be that you still secrete just as much insulin (which will inhibit fat oxidation) after a high-carb meal, it’s just that muscle cells don’t need it to synthesize glycogen. But I think there’s some evidence that suggests that insulin is at least reduced if carbs are consumed during this window.

So how does one go about taking advantage of this “30-60 minutes” where glycogen is synthesized without the presence of insulin? Here’s the quote from Roy Jentjens and Asker Jeukendrup you’re paying me for:

Several studies have demonstrated that the pattern of muscle glycogen synthesis following exercise-induced glycogen depletion occurs in a biphasic manner…..It has been suggested hat the rapid phase only occurs when post-exercise muscle glycogen concentrations are lower than 128–150 mmol/kg dw[38,41] and CHO is provided immediately after exercise.[43] Following this rapid phase of glycogen synthesis, muscle glycogen synhesis occurs at a much slower rate (slow phase or insulin-dependent phase) and, in the presence of  CHO availability and high insulin levels, this phase can last for several hours.[7]

Now, knowing the range of muscle glycogen concentrations won’t do most people much good, because measuring them isn’t exactly convenient. However, there are some ways to ensure glycogen is low, namely fasting and exercise, and it’s probably optimal to do both, simultaneously.

“So I’m supposed to go exercise when I haven’t eaten in 12-16 hours?” Well, yes. “How do I know this works?” Well, it turns out that there’s some evidence for it, both scientific and anecdotal. This brings me to the topics of fasted cardio, intermittent fasting, and the interesting (and apparently successful) experiments of Martin Berkhan at I hypothesize that all of these strategies (1) deplete glycogen by combining fasting and exercise, and Martin Berkhan astutely makes a point to (2) consume the majority of one’s daily carbs immediately after the fasting exercise whenever possible. Excellent idea Martin!

Fasted Cardio

Here’s one scientific paper studying the effects of fasted cardio: PMID 21051570. And a quote of the relevant bits:

Here we investigated the effect of consistent training in the fasted state, vs. training in the fed state, on muscle metabolism and substrate selection during fasted exercise. Twenty young male volunteers participated in a 6-wk endurance training program (1-1.5 h cycling at ∼70% Vo(₂max), 4 days/wk) while receiving isocaloric carbohydrate-rich diets. Half of the subjects trained in the fasted state (F; n = 10), while the others ingested ample carbohydrates before (∼160 g) and during (1 g·kg body wt⁻¹·h⁻¹) the training sessions (CHO; n = 10)…..In F, exercise-induced intramyocellular lipid (IMCL) breakdown was enhanced in type I fibers (P < 0.05) and tended to be increased in type IIa fibers (P = 0.07)…..In addition, F (+21%) increased the exercise intensity corresponding to the maximal rate of fat oxidation more than did CHO (+6%) (P < 0.05). Furthermore, maximal citrate synthase (+47%) and β-hydroxyacyl coenzyme A dehydrogenase (+34%) activity was significantly upregulated in F (P < 0.05) but not in CHO. Also, only F prevented the development exercise-induced drop in blood glucose concentration (P < 0.05). In conclusion, F is more effective than CHO to increase muscular oxidative capacity…..

Now, before we get too excited, I want to point out that they exercised for 1-1.5 HOURS in the fasted state – that’s a lot! (at least in my personal experience). I personally go for a light jog for 20-30 mins, and I have 5 g of BCAA in coffee before doing so, and I’m beat afterwords.

Essentially, my recommendations (which I’m now implementing) to optimize diet and exercise for fat loss are the following:

  1. Fast between 12-16 hours (helps deplete glycogen)
  2. Towards the end of the fast, perform exercise (also depletes glycogen), either weightlifting  or cardio (a few, very-low-calorie supplements beforehand, like BCAA, is suggested)
  3. Immediately (ASAP) after finishing exercising, consume your first meal. This meal should be the highest-carb meal of the day. Ideally (and this is an off-the-cuff, no-research recommendation), I suggest consuming 50-75% of one’s carb intake (and perhaps even 50% of your calories for the day) at this one meal. Doing this will (presumably) minimize insulin secretion, while maximizing glycogen synthesis.
  4. Taper-off carbs for the rest of the day, with the last meal of the day ideally being only protein and fat (no carb).
  5. Repeat often.
  6. In the case you don’t exercise on a given day, I recommend still getting 30-60% of your carbs for “break-fast” (i.e breaking your fast), and taper carbs for the rest of the day (see (4) above).
  7. Finally: note I’ve said nothing about the dose of carbs (this is something I’m still trying to figure out, at least for myself, i.e. my body type, body fat, metabolism, insulin sensitivity, etc.)

If you’re interested in other protocols, I recommend looking into Martin Berkhan’s It’s apparent to me from my recent research on this topic (and from reading parts of Martin’s site and seeing his results), Martin knows what he’s talking about, and is giving good recommendations there. Here is a place to start:

I could probably optimize on Martin’s recommended protocols applying what I’ve discussed here. But given that Martin appears to have achieved excellent results, and my hypothesis is still in testing (on myself), I’ll refrain from making suggestions until I’m convinced my ideas are effective.

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Maximus Peto is a longevity scientist focused on the biology of aging, health, nutrition, exercise, lifestyle, and longevity. In his scientific research, he has scanned 160,000+ scientific articles, read 8,000+ scientific abstracts, and studied 1,500+ full-text scientific publications. Maximus has worked with several leading organizations in aging and longevity, including the SENS Research Foundation, the Methuselah Foundation, and the Life Extension Foundation. He shares his knowledge of keeping people alive and healthy at Long Life Labs.