> However, the study authors emphasize that more research is needed to confirm these mechanisms and determine whether the survival benefit observed in this real-world analysis represents a direct anti-cancer effect or an indirect result of improved metabolic health
Given it’s an observational study, I would bet on the latter. It’s really hard to know you’ve controlled for all confounding factors, and there’s a strong null hypothesis because we know that losing weight can have huge and wide-ranging health benefits.
I'm a big fan of intermittent and water fasting. Have seen things in my blood work that doctors would require me on meds to reverse. Outside of that, I can't speak to the positive impacts on my mood, and general ability to focus.
The simplest solution to a lot of problems is consuming less with the assumption that, most of us (maybe not you), have a lot of spare energy sitting around.
A lie that we don't unlearn as we grow up is we "require" three meals a day. This is true for children who need obscene amounts of energy to grow, but, not for us desk-bound adults.
In the end, giving the body a break to heal by fasting or just consuming significantly less is going to leave more resources for the body energy to deal with other things.
An interesting FYI is a comment made by Peter Attia on his podcast.
He had a patient with metabolic markers that were not improving and they had exhausted all the typical avenues. Presumably they were things like weight loss.
They put the patient on GLP-1 but injected into the thighs (or butt, I don't recall) for the metabolic benefits without the hunger blunting effects.
It seems like GLP1, even in skinny patients (implied by Attia in this particular case), has metabolic benefits.
The longevity community seems to be hinting that there may be geroprotective aspects of GLp1 as well, so we may be looking at the benefits beyond weight loss for metabolism.
It shouldn't make any difference where you pin it, it's systemic it just has to be administered subcutaneously because it's a peptide and it isn't orally active.
Don't listen to these YouTubers about health and fitness, most of them are clueless
It shouldn't, and yet for me it seems to make a difference! I don't think it's placebo, because I am really losing weight. My anecdata: When I start with a particular dose of GLP-1, I inject in thigh. I get strong appetite suppression, heart rate increase, digestion slow down etc. After some time, the effect decreases as my body adjusts. I then move injection to abdomen, and I get a huge bump in suppression, systemic effects, etc. No idea why this happens, but I've seen it with Zepbound and 5, 7.5, and 10mg. It's allowed me to stay on each dose for far longer than my doctor expected.
Usually this type of anecdata becomes the basis of legitimate, controlled studies and over time can inform and/or adjust.
It would be premature to simply write off all influencers or limiting to only accept the medical profession as the immutable truth.
The reality tends to exist somewhere in the middle, outside of a formal proof.
I've listened to many health influencers and among the legitimate and balanced tend to be Rhonda Patrick and Peter Attia.
Attia provides guidelines for how to think about items, but usually it's the fan base that tends to sully the messaging as the base tends to be far more polarized and dogmatic over bits.
It is interesting to see that there is another poster confirming a slightly different effect though. Regardless of things being "systemic", just understanding that fluids dynamics are complex, I imagine diffusion of a systemic molecule like GLp1 could possibly be variable? Or perhaps there is a localized tissue fatigue?
Many potential options do exist to propose as hypothesis.
Peter Attia is a graduate of Stanford medical school and spent 5 years in surgical residency at Johns Hopkins, and his podcast is largely using his expertise to give context to recently published research. His opinions are always pretty directly linked to peer reviewed research and he updates his stances as new research becomes available and explains why (eg, his shift away from fasting).
He really shouldn't be lumped in with the general "health and fitness Youtubers".
While the area under the curve for glp1 administration may be the same, good chance that the story is informing us of a mechanism such as the absorption rate between two different sites.
Slower absorption in the thigh may blunt the immediate peak dosing and the acute hunger effects.
As always, the small details matter. I'd guess that pharmacology also has their own thundering herd problem with the dosing of certain drugs.
One of the interesting bits about pharmacology seems to not be the active molecule as much as the innovations in delivery mechanism.
Awesome insight. It's not the disability I have, it's that I have never tried healing by fasting. Of course. Because my body was always busy trying to eat food instead of fixing and regrowing all the malformed tissue. Because that's how it works. When a person without legs starts to fast, the legs will suddenly develop.
It would be sensible for you to examine and interrogate why reading a general and fairly anodyne opinion about what might be a solution to a problem some people have led you to interpret it as a prescriptive and judgemental suggestion about the specific problem you specifically have.
In my mind it is a slippery slope that leads to a sickly Steve Jobs eating kilograms of raw carrots.
Obviously a healthy lifestyle is good. And this includes not eating over your requirements. But sometimes there is actually something wrong. And in these cases, first trying out to just eat healthy can worsen the situation by delaying proper treatment. And proper treatment does equal a bunch of pharmaceutical drugs.
I disagree, I think it’s fairly easy to read this passage in particular
> The simplest solution to a lot of problems is consuming less with the assumption that, most of us (maybe not you), have a lot of spare energy sitting around.
as energy-woo / thanks-I’m-cured material.
You can weasel your way around criticism by calling it “a general and fairly anodyne opinion about what might be a solution to a problem some people have,” but consider -
It does make sense that someone who’s struggled with a chronic condition would be tired and embittered by the endless snake oil evangelizing they’ve had to endure, on top of already struggling with their health.
(Not that fasting doesn’t work for some people, as you say! it’s more the grandiose claim that it’s “The simplest solution to a lot of problems” coupled with some vague anecdote about blood work and knowing better than doctors that waves a red flag)
I for one don't "require" three meals a day, but I'm hungry in the morning, ergo, I like breakfast.
It's not so much about how often you eat but what and how much. Generally speaking, of course, I can't speak for any benefits of intermittent fasting (assuming equal daily calorie / macronutrient intake) because I'm uneducated in that regard. But TL;DR, I will agree that desk jockeys will need less calories than people with a more active job or lifestyle, and people need to adjust their lifestyle accordingly else they'll gain weight.
Maybe this goes away after a while, but when I tried this in the past I get so hungry I can't think or work. So clearly it's a non-starter for me on work days.
One approach is to first reduce carbs (and particularly highly-processed carbs), then begin intermittent fasting. An initial lower-carb diet for 2--4 weeks may help with compliance on the IF diet.
ALmost everyone who shares their positive, any length fasting experience here gets downvoted. I will always upvote them. Ive done two 48 hour fasts and they were so relaxing and felt so natural. It just feels great to occasionally go about your day and not eat anything. Your gut tries to heal itself in between meals. The fact that almost all of HN just cant stand anyone mention they fast with positive benefits (and mounting evidence) is kidna sad. I guess every community has to be exceptionally closed minded about something.
Of course. That's why the nobel prize in medicine in 2016 was awarded to a cell biolgoist studying cellular autophagy for over a decade. It must be why glucose is not an essential dietary macronutrient and our liver can synthesizie it endogenously from fats and proteins (it just felt like doing that one day and stored all those chemical pathways in our genes I guess). That must also be why ketones produced from our fat stores burn so cleanly with less reactive inflammatory byproducts. In fact the cells in our brain actually prefer ketones to glucose. There's no such as water fasting. It's just random chance that when the body is in a state of ketosis it suppresses ghrelen and other hunger hormones or that countless other chemical pathways (de)activate or change. That's right the body has absolutely no design or adaptation for scarcity of food. Water fasting is totally foreign to the human body, that's why whenever we study ancient cultures...we find they practiced purposeful fasting. There's just no such thing as water fasting, it must be a modern eating disorder.
There's no chance it has anything to do with the last few million years of our evolution. It has no benefit or relevance now.
Interesting that GLP-1s might have different effects on cancer _incidence_ vs. cancer _survival_.
A different study "GLP-1 Receptor Agonists and the Risk of Thyroid Cancer" was published in the Diabates Care journal in February 2023*
The conclusion of the 2023 study: "we found increased risk of all thyroid cancer and medullary thyroid cancer with use of GLP-1 RA, in particular after 1–3 years of treatment."
I wonder what the mechanistic hypothesis could be for GLP-1s increasing thyroid cancer _incidence_ (the probability of thyroid cancer occurring in patients taking GLP-1s) but increasing colon cancer _survival_ (the probability of surviving in patients taking GLP-1s who have colon cancer).
Of course there are numerous important differences across the studies (cancer type, France vs. USA data, etc.), I'm just curious about a why this might be the case.
I'd be cautious for the same reason: thyroid cancers are also positively associated with obesity, and people who take GLP-1s are often obese.
Below a table, it says "adjusted for social deprivation index, hypo- and hyperthyroidism, and use of other antidiabetic drugs..." -- but nothing about obesity.
What if the GLP-1-prescribed patients tended to be more obese?
Yeah, most GLP-1 benefits (or even adverse effects, like muscle loss) seem to be caused by the weight loss. We already knew obesity massively increases risk from a host of diseases, but GLP-1s are still treated with scepticism of the "oh but what about the side-effects we don't know about?!" variety?
> The cardioprotective effects of semaglutide were independent of baseline adiposity and weight loss and had only a small association with waist circumference, suggesting some mechanisms for benefit beyond adiposity reduction.
They won't, GLP-1 has almost no direct effect on skinny people. Many women with BMI around 22-23 are trying them to lose weight to match beauty standards and usually end up disappointed, not able to drop more than 1-2 kilos.
The article also says that the effects persist after adjusting for BMI:
> After adjusting for age, body mass index (BMI), disease severity and other health factors, GLP-1 users still showed significantly lower odds of death, suggesting a strong and independent protective effect.
The observed reduction in mortality is also quite large:
> Health sites, researchers found that those taking glucagon-like peptide-1 (GLP-1) medications were less than half as likely to die within five years compared to those who weren’t on the drugs (15.5% vs. 37.1%).
More research is needed, but if I were diagnosed with colon cancer I would definitely be asking my doctor about the risks vs. potential benefits of getting on GLP-1 meds based on this study alone.
Given it’s an observational study, I would bet on the latter. It’s really hard to know you’ve controlled for all confounding factors, and there’s a strong null hypothesis because we know that losing weight can have huge and wide-ranging health benefits.