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!

Making Drinking Less Harmful

We often talk of the many ways alcohol harms our health, and we advocate for reducing (or eliminating) its consumption. However, it’s not necessarily as easy as all that, and it might not even be a goal that everyone has. So, if you’re going to imbibe, what can you do to mitigate the harmful effects of alcohol?

There is no magical solution

Sadly. If you drink alcohol, there will be some harmful effects, and nothing will completely undo that. But there are some things that can at least help—read on to learn more!

Coffee

It’s not the magical sober-upperer that some would like it to be, but it is good against the symptoms of alcohol intoxication, and slightly reduces the harm to your body, because it is:

• Hydrating (whereas alcohol is dehydrating)
• A source of antioxidants (whereas alcohol causes oxidative stress, which has nothing to do with psychological stress, and is a kind of cellular damage)
• A stimulant, assuming it is not decaffeinated (it’s worth noting that its stimulant effects work partly by triggering vasoconstriction, which is the opposite of the vasodilation caused by alcohol)

To this end, the best coffee for anti-alcohol effects should be:

• Caffeinated, and strong
• Long (we love espresso, but we need hydration here and that comes from volume!)
• Without sugar (you don’t want to create an adverse osmotic gradient to draw water back out from your body)

As for milk/cream/whatever, have it or don’t, per your usual preference. It won’t make any difference to the alcohol in your system.

Antioxidants, polyphenols, flavonoids, and things with similar mechanisms

We mentioned that coffee contains antioxidants, but if you want to really bring out the heavy guns, taking more powerful antioxidants can help a lot. If you don’t have the luxury of enjoying berries and cacao nibs by the handful, supplements that have some similar benefits are a perfectly respectable choice.

For example, you might want to consider green tea extract:

L-theanine 200mg (available on Amazon)

Specialist anti-alcohol drugs

These are somewhat new and the research is still ongoing, but for example:

Dihydromyricetin (DHM) as a novel anti-alcohol intoxication medication

In short, DHM is a flavonoid (protects against the oxidative stress caused by alcohol, and has been found to reduce liver damage—see the above link) and also works on GABA-receptors (reduces alcohol withdrawal symptoms after cessation of drinking, and thus also reduces hangovers).

Once again: the marketing claims of such drugs may be bold, but there’s a lot that’s not known and they’re not a magic pill. They do NOT mean you can take them alongside drinking and drink what you like with impunity. However, they may help mitigate some of the harmful effects of alcohol. If you wish to try them, these can be purchased at pharmacies or online, for example:

Alcohol Defense Capsules (available on Amazon)

Bottom line

Alcohol is bad for your health and none of the above will eliminate the health risks. But, if you’re going to have alcohol, then having the above things as well may at least somewhat reduce the harm done.