This is the first in a series of posts with the most useful replies I made in the íntermittent fasting thread on Answers have been edited/updated when needed.

Calorie Restriction (CR) vs Intermittent Fasting

Q: I think CR in general is probably more healthy for some people than “fasting”.

A: Depends on how you define “healthy”. The whole premise of CR for life extension may sound great on paper, but it’s not much fun to chronically restrict calories for rest of your life in order to live a few years more. Especially if the price you pay is hunger and weakness.

Studies hint that IF may have life extension benefits on it’s own, some of them are unique to IF and not seen with CR: disease prevention, protection against brain disorders (i.e Alzheimers), immune system support and improved pulmonary function, even on higher calorie intakes.

IF at energy balance > CR.

So perhaps we can get all the benefits of CR, and then some, without having to restrict intake as harshly. Here’s an example of some of the exclusive benefits of IF vs CR;

…Nevertheless, intermittent fasting resulted in beneficial effects that met or exceeded those of caloric restriction including reduced serum glucose and insulin levels and increased resistance of neurons in the brain to excitotoxic stress. Intermittent fasting therefore has beneficial effects on glucose regulation and neuronal resistance to injury in these mice that are independent of caloric intake.

From “Intermittent fasting dissociates beneficial effects of dietary restriction on glucose metabolism and neuronal resistance to injury from calorie intake” by Anson et al.

Then again, it may be wishful thinking. Main support for the hypothesis comes from animal research, human research is still sparse. However, there are some recent studies that lends support for the hypothesis to be valid for humans as well, for example:

…These findings demonstrate rapid and sustained beneficial effects of ADCR on the underlying disease process in subjects with asthma, suggesting a novel approach for therapeutic intervention in this disorder. ” (the authors conclude that alternate day fasting > CR)

From “Alternate Day Calorie Restriction Improves Clinical Findings and Reduces Markers of Oxidative Stress and Inflammation in Overweight Adults with Moderate Asthma” by Johnson et al.

The mechanism by which fasting protects the heart is not known, but may involve an enhanced ability of cells to cope with oxidative and metabolic stress. Wan et al speculated that…

A recent study showed that alternate-day caloric restriction can reduce systemic markers of inflammation and oxidative stress and can reduce symptoms in subjects with asthma” (Here they are referring to the human trial by Johnson et al)


Intermittent Fasting imposes a mild beneficial stress on cells.

And affects adiponectin:

Adiponectin concentration was twofold greater in the plasma of rats that had been maintained for 3 months on the IF diet

Conluding that Adiponectin may possibly explain some of the beneficial effects:

Adiponectin has previously been shown to have cardioprotective and anti-inflammatory actions.

Yet finishing with some reservations, as the research is still scarce on this topic:

IF results in changes in levels of several circulating factors including decreased levels of insulin, leptin and cholesterol, and increased levels of testosterone [27]*. It will therefore be important to elucidate the roles for, and interactions, of these different factors in cardiovascular responses to IF.

* The effects on testosterone seems unique to rodents so far (personal conslusion based on my review of the topic).

The above is from “Cardioprotective effect of intermittent fasting is associated with an elevation of adiponectin levels in rats” by Wan et al. A recent paper discussed the cardioprotective benefits with regards to humans:

Short-term modified alternate-day fasting: a novel dietary strategy for weight loss and cardioprotection in obese adults” by Varady et al.

I wrote the above almost two years ago (added some recent studies for the sake of context). Since then, there’s been some additional findings, though nothing groundbreaking. There’s a lot on this topic, but I’m gonna cut it short here. Have written plenty on this in the book. To summarize my response to the question: intermittent fasting may or may not have exclusive benefits which cannot be obtained with a traditional, calorie restricted diet. However, due to the scarcity of research on humans, and due to many confounders present in the available research (i.e some of the studies on IF/ADF does not use a CR control group), it’s hard to say anything for certain yet.

Intermittent Fasting and PPOS

Q: The Life Extension Foundation is big on the idea that big meals = elevated post prandial oxidative stress (PPOS) which is obviously a negative. Any opinion on this seemingly negative effect of IF/Big Meals?

A: Studies* show oxidative stress is less on intermittent fasting compared to regular calorie restriction. Yes, even when comparing the same calorie intake with varying meal splits (i.e 3 big meals vs 6-9 small meals). The neuroprotective effects of the fast yields the net effect of PPOS being lesser on IF – despite larger meals.

* in ref to Anson et al.

Catabolism during the fast

Q: So, how long does it take for significant muscular catabolism to start? Over 24 hrs?

A: That’s context dependent, but consider that blood glucose is maintained within range mostly by gluconeogenesis beyond the 16 hr mark*. That answer might not make a lot of sense, but eat sufficient amounts of slow releasing protein before going to bed and it shouldn’t be an issue even if you go for longer than 16 hrs.**

They key factor in whether you’ll lose muscle or not is the severity of calorie deficit, not meal time intervals within a non-retarded range.

  • * note that the studies looking at this contained nutrional regimens very different from what we are doing (i.e Cahill et all fed test subjects 100 g cho before bed time, no protein, and then had them fast for several days to gauge the rate by which liver glycogen vs gluconeogenesis contributes to maintain blood glucose).
  • ** hell there’s even a study out there suggesting proteolytic gene expression does not become turned on until the 40 hr mark or so.

A more recent question on the same topic –

Q: Hey guys, got a question about fasting length. I’m currently IF’ing by doing two 24 hour fasts per week (two days with complete fasting) My question is, could I do both fasts consecutively and do one large 48 hour fast? What is the longest amount of time that it is safe to fast before LBM loss/metabolic downregulation?

A: Safest? Well, consider that de novo gluconeogenesis escalates beyond 16 hrs. 16 hrs is the tipping point – your glucose demands after this point is met primarily (more than 50%) by conversion of stored amino acids into blood glucose. Liver will support the brunt of glucose needs before that point. Theoretically, proteolysis will occur to the greatest extent 24-48 hrs into the fast. Of course, there are numerous confounders here to take into account (i.e a casein heavy meal before the fast will delay proteolysis further).

Metabolic downregulation? Up to 72 hrs according to most studies.

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