Why Intermittent Fasting (& GLP-1 Drugs!) Might Not Work For You

GLP-1 receptor agonists such as Ozempic, Wegovy, Mounjaro, and all the others are ubiquitous these days, in wealthy industrialized nations at least.

And while they have their downsides (see: Most People Who Start GLP-1 RAs Quit Them Within A Year (Here’s Why)), it’s generally considered uncontentious that they do, at least, work strongly for weight loss.

In a similar vein, intermittent fasting has a very good reputation too: Intermittent Fasting: What’s The Truth?

But for some people, neither will deliver as expected:

Intermittent fasting is great for weight loss, unless…

…your body is in a state of obesity, in which case, it no longer works the same way.

Researchers (Dr. Helena Neudorf et al.) discovered that fasting (and ketogenic-style diets) affect metabolism and immune response differently according to obesity levels.

A quick note on that: because of the cellular processes at hand, the reason for this is almost certainly about adiposity, not mass, but the study used BMI as the metric, which wasn’t helpful. Indeed, they even referred the the lower-BMI study participants as “lean”, which again, is about adiposity not size. A bodybuilder will generally have a high BMI, and yet will be very lean. Meanwhile, someone who just happens to be unusually tall may have a very low BMI despite higher body fat percentage. So, that’s a limitation here.

Despite the failings of BMI (which are many), chances are good that in their study population, BMI correlated to adiposity, so one figure may grudgingly be used as a stand-in for the other.

See also: When BMI Doesn’t Measure Up

Ketogenic-style diets are mentioned here because they are very low-carb, which tends to prompt some physiological responses similar to fasting.

As a result, the ketogenic diet is generally good for fat loss in the short term: Ketogenic Diet: Burning Fat Or Burning Out?

Anyway, how Dr. Neudorf and her team discovered this was by with blood samples taken before, during and after fasting to measure hormones, metabolites, metabolic rate, inflammation and T-cell activity.

What they found:

• Low BMI group (called “lean”): immune cells adapted by burning more fat, and fasting shifted their immune system towards a more balanced, anti-inflammatory state
• High BMI group (called: “with obesity”): participants had more pro-inflammatory T cells, continued producing inflammatory signals after fasting, showed smaller increases in ketones, and had weaker chemical reactions linked to immune regulation

You can read the paper in full, here: Altered immunometabolic response to fasting in humans living with obesity

As an aside: “humans living with obesity” seems to this writer like a really odd way of saying it, it’d be like describing me as “a human living with long hair” or something. In all likelihood, it was an effort at “person first” language, something that’s generally only brought out when talking about an attribute that society considers negative, while not having that attribute. Same vibe as “people with autism” (autistic people, in contrast, will tend to say “autistic people”). Note also that in the study paper, there’s a double-standard that makes this motivation clear: they had no problem saying “lean participants”, and did not feel the need to euphemize this as “humans living with leanness”. Fat justice activist Aubrey Gordon has written about this kind of thing a lot, and you can read about some of it here: Fat’s Real Barriers To Health ← including the stigmatization that occurs precisely because of people overcompensating for a fear of offence by dancing around “the f-word” (fat) like many research papers do. “Fat”, she says, is a morally neutral word.

What about GLP-1 drugs?

This one’s simpler: for almost any drug, some people are simply “non-responders”, meaning that for some reason (often a genetic factor, often not known for sure why), the drug will simply not work as it does for most people.

For GLP-1 receptor agonists, there is a portion of the general population for whom they simply will not work, and so far there is no known way of predicting it (probably at someone point it’ll be figured out, and this writer’s money would be on it being either a SNP mutation or a microbiome thing). So, you roll the dice, you take the GLP-1 drug, you wait and see, and there’s a 15% chance (that doesn’t sound like a lot, but it’s about 1 in 6, in other words, the same probability as rolling a “1” on a fair, six-sided die).

You can read about how that can go, here: Ozempic didn’t work for me. I was furious—and ashamed

Ok, so, what to do instead?

Check out:

How To Lose Weight (Healthily!) ← for a gentle, sustainable, way that has about the highest probability of success

Take care!