The sad truth about metabolism: why nothing works

I saw this going viral:

The above tweet illustrates how proponents of CICO tend to focus on the calories-in “CI” side of the equation and ignore the calories-out “CO” half, such as metabolism. However, aside from the occasional anecdotal evidence, there is scant to no evidence to suggest it’s possible to meaningfully raise “CO” without also getting fatter in the process. Based on my research, which I will expound on in this post, there is no reproducible diet or other method that is safe and appreciably raises “CO” in a general population or even replicates at an anecdotal level.

The guy who posted the tweet, @fire_bottle, despite being held up as an expert and selling product on his website that he claims helps at improving metabolic dysfunction, is still fat. So if such a way exists to increase “CO” safely and easily, he hasn’t found it. He’s not wrong in so far that metabolic dysfunction plays a role in obesity, but the sad reality is there may be no way to fix it. GLP-1 drugs such as Ozempic work on that “CI” part, but drugs that target “CO” tend to be of limited efficacy and possibly unsafe.

The reality is, “CO” is largely innate. That is, for a given bodyweight, how many calories an individual burns is determined almost entirely by genes. Controlling for key factors such as weight, height, and gender, this varies considerably at an individual level, similar to IQ. Two people can be near 100-percent identical in terms every important variable such as weight, height, and physical activity level, be yet vary by 50-100% in terms of daily energy expenditure level (e.g. 2000 kcal/day vs 3000kcal/day) to maintain homeostasis for a given weight, and no one knows why this is. And also like IQ, there is nothing that can be done to raise it meaningfully, except for perhaps tons of stimulants and drugs such as DNP or clenbuterol, which are unsafe when used for weight loss purposes.

I would love to eat 3kcal+/day and not get fat like some people on social media claim to do (or maybe they are lying or on drugs, which which would not surprise me either). Genetics provides a hard limit as to what is feasible. ‘Shit genetics’ are a thing, just as ‘god tier’ genetics also exist. Compare pro athletes to those who cannot even make a high school tryout. We can debate hyper-palatable foods vs seed oils as the cause of obesity, but there seems to be compelling evidence that some people have an innate propensity to store fat compared to others. For example, “@Ed_Realist” was unable to lose weight on a 1,200 kcal/day diet, and finally found success with Mounjaro, which is a powerful GLP-1 drug:

Interestingly, @Ed_Realist lost weight despite eating the same quantity of calories, so it’s possible GLP-1 drugs can raise “CO”–more research is needed. It’s also possible to blame miscounting. People tend to be notoriously bad at self-reporting calorie intake. But Metabolism is one of many variables that can explain obesity and weight gain, and I posit among the most important ones. Calories are either burned or stored as fat–with very few exceptions (such as malabsorption, which is rare)–so metabolism must play a key role.

No one knows why humans vary so much in metabolism, such as which genes are to blame, similar to how humans vary so much in intelligence, also due to genes. Humans vary so much in terms of BMI despite the environment more so less being held constant (it’s not like thin people live in areas where there are food shortages; in fact, wealthier areas tend to be thinner). A quarter of Americans are neither obese or overweight, and on the opposite side of the distribution, quarter are severely or morbidly obese. It makes sense from an evolutionary perspective why there is so much variability: during famine, those with the sluggish metabolisms will outlive those who quickly waste away to skeletons, but a propensity to gain weight may come at the cost of speed or endurance or some other drawback.

Trying to raise “CO” with cardio is not uncommonly offset entirely or to a large extent by adaptive thermogenesis, meaning your body burns fewer calories at rest in such a way that your “CO” is unchanged despite expending more effort. This is corroborated by many studies, such as famously by the recent work of Herman Pontzer. What he found is that humans exhibit a sort of constrained energy expenditure, meaning that burning more calories through exercise is offset by burning fewer calories at rest, such as reduced NEAT, within the constraint of one’s energy curve. And also, increased hunger afterwards. Eating a cup of oats or yogurt after a long walk or run will easily negate those extra burned calories from cardio.

Building muscle also does not work that well. Not only does this lead to increased hunger, but muscle burns little calories, at just 6kcals/day per pound of muscle. Not to mention, the vast majority of drug-free individuals will add only small quantifies of muscle with training. Sure, strength training has benefits, such as reduced risk of falls by improving leg strength and balance, but weight loss is typically not among them. Also, weight lifting as a form of exercise burns a tiny amount of calories compared to running or other moderate to high intensity cardio.

To get an idea of how inconsequential this is, consider a bodybuilder with 50 extra pounds of muscle compared to a control group, which is an outlier even by bodybuilding standards and would be a very impressive physique. The extra 300 calories he burns is still within a single standard deviation even at his original weight. So maybe going from 2,500kcal/day to 2,800kcal/day, which is within normal for a man at 180 lbs instead of 230 lbs. So 3/4 of a McDonald’s cheeseburger of extra calories for a hulking 50 extra pounds of muscle. So what does burn calories? The organs, especially the brain, which despite weighing little consumes a fifth of RMR (resting metabolic rate) for the day.

T3/T4? Nope. Therapy to treat hypothyroidism is no substitute for the real thing. If it worked so well for weight loss, why all the talk and demand for GLP-1 drugs instead of the far cheaper thyroid drugs? Same for exogenous testosterone/TRT despite being popular among the likes of Rogan, Huberman and other fitness or health influencer-types. TRT is actually cheaper than GLP-1 drugs. A good benchmark for effective weight loss treatment is, “Is it a substitute for the wildly-popular, non-Medicare-covered $1000/month drug?” If people have no choice but to choose the $1,000/month drug which insurance will not cover, then you can be sure there are few better drug alternatives. [0]

There is also no evidence to suggest it’s possible to raise metabolism by changing macros (e.g. high fat vs. low fat) [1] or that ketogenic diets raise metabolism much if at all. My research shows, optimistically, ketosis adds maybe 50 kcal/day of additional calorie burn. Same for caffeine. Based on my research, it’s inconclusive if caffeine raises metabolism at all, and any boost is tiny even with very high quantities of caffeine.

Finally, overeating to kickstart a sluggish metabolism into overdrive in the hope of inducing an afterburner effect when calories are restricted again. Any increase of metabolism by overeating is offset by weight gain. This is sometimes called a ‘refeed’, and as to if it works, likely not. As soon as you stop eating at a surplus, your metabolism drops at a commensurate rate, so no afterburn effect and added weight loss. All you’ve done is set back your progress.

Same for adherents of the ‘Ray Peat’ diet, who subscribe to the belief that a diet high in fructose or sucrose will boost the metabolism and lead to weight loss. Again, the evidence is lacking, and many gain weight on this type of diet. Of course, some may lose weight, but based on my research there is little to no evidence to suggest it’s more effective than other diets or that it confers the sought metabolism boost without also gaining weight. Like all dieting advice, it’s highly individualistic: if you can make it work, then by all means go for it.

Overall, to wrap this up, either you’re on a diet or not. Diets have a high failure rate for a reason: feeling hungry is unpleasant and it does not go away without eating more, which axiomatically means you’re no longer dieting. There are no hacks or tricks to chasing that elusive metabolism boost that will allow one to consume more food without also gaining weight. This is why Ozempic works consistently, by restricting “CI”, when these other strategies fail or success is limited to irreproducible anecdotal evidence.

[0] There are older, related drugs which are cheaper such as Rybelsus, which is an oral form of semaglutide, but they do not work as well for weight loss compared to injectable semaglutide.

[1] There is a high thermic effect of protein, at 25-30% vs 5-10% for carbs and 2% for fat, but the evidence is lacking that high protein diets outperform others.