MS Nutrition | Researcher 10+ Years | Scientific Communicator
Arizona, USA
Joined December 2018
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The cure for most cases of type 2 diabetes (T2DM) requires fat loss. This thread will discuss research showing restoration of carbohydrate tolerance in those with T2DM through addressing the underlying pathology (ectopic fat) rather than just focusing on symptom management.
This study is literally direct support for CICO, or energy balance more specifically.
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Alex Leaf retweeted
This reflects an extraordinary level of insecurity and I don’t understand how anyone would want a relationship like this. I can understand the rationale for a couple of these, but I’d never want to be in a relationship with someone who was this paranoid over what-ifs, or whose desire to be with me I felt compelled to police.
Monitoring someone doesn’t create commitment anyway. It may temporarily constrain their opportunities, but it doesn’t change their intentions. If someone wants to cheat, they can find a way. And if your loyalty depends on multiple externally imposed “guardrails,” you should reconsider whether you actually want the commitment you’ve agreed to.
Underrated Marriage hacks:
•No hot nannies.
•Keep location sharing on.
•Know each other's passwords.
•No opposite-sex jujitsu coaches.
•No opposite-sex personal trainers.
•Ignore your kids once a week & do date nights.
• No private DMs or solo lunches with the opposite sex.
•Spouse gets veto power on close friends and plans.
Keep God in the center, pray together, laugh together & choose each other daily.
Reversal is a perfectly reasonable word to use when discussing type 2 diabetes pathophysiology, and Roy Taylor made the case for it back in 2019 (PMID: 31097391). It simply means that the underlying causes of type 2 diabetes have returned to normal.
Remission is clinically defined as an HbA1c below 6.5% for at least three months without glucose-lowering medications (PMID: 34462270).
Someone can be in remission without necessarily having reversed the underlying pathology if they, for example, are eating a low-carbohydrate diet. But under mixed-diet conditions, the two generally go hand-in-hand.
Reversal is incorrect - and not the word used in diabetes - remission yes. Type 2 Diabetes has a strong genetic component. Diet, activity, and weight loss can improve it and sometimes produce remission. Those facts coexist. Improving a genetically influenced disease doesn't prove genetics were never involved.
"Not genetic" is wrong. "100% genetic" is wrong. "Completely reversible, full stop" promises an outcome nobody can guarantee. Remission is real, and so is relapse. And patients who still need medication haven't failed a character test, they have diabetes
The diabetes genetics shenanigans that is going on right now serves as a good example of where many people misunderstand what heritability means.
Fundamentally, when we say something is XX percent genetic or whatever, which is usually from a heritability estimate, we are describing how much of the variation in that trait or disease within a specific population can be attributed to genetic differences.
Nothing about this tells us whether a disease is caused by genetics.
Imagine scurvy, as a simple example. Let's say that scurvy is XX percent heritable because there are genetic differences that influence how susceptible someone is in developing scurvy. That stuff might matter in a population with a low intake of vitamin C, but the disease itself is still caused by low vitamin C, not genes.
Type 2 diabetes is more complex, but the same principle applies. Genetics impact how susceptible someone is to developing it, but they don't cause it. The cause is excessive fat accumulation within the liver and pancreas that drive dysfunction of these organs.
And focusing on genetics isn't helpful anyway because what are you supposed to do about it? It's a purely external locus of control. Even if genetics influence susceptibility, the question always comes back to agency: what can you do to mitigate that risk?
Many of these ultra-processed foods are engineered in the way that they are because they are palatable and convenient, which makes choosing to eat them easy, particularly when focused on perceived short-term rewards.
Eating behavior is influenced by many things, like taste, convenience, cost, habit, and associations people have made with things like emotional state and stress.
Since food companies want to make money, obviously they try to influence people's choices for picking their food, but ultimately those are choices being made. There is no way for them to create foods that compel eating.
So, yeah, the modern food environment is obesogenic, but not because these foods hold magical powers over our brains that compel us to eat them. It's because these foods are easy for people to incorporate into their eating behaviors, often in amounts that promote overeating.
To be clear, we agree that the food environment sucks and contributes to obesity and associated health problems, for a variety of reasons.
Where I push back strongly, in general, is on the conventional views of addiction, including food addiction. I think they lean to heavily on a largely discredited brain disease model.
Think Alex has some fair pushback on me here, and I went too far with words like “addictive” or “hijacked.” But… I disagree on some of the sentiment.
He says “food companies try to engineer foods that taste good and provide pleasure to those eating them. That’s it, and that pleasure contributes to motivation for many to continue eating them,” but I think that really understates what is happening.
What engineering for “pleasure” and the “motivation… to continue eating them” looks like in reality: these companies employ armies of food scientists to optimize products for precisely the combination of sweetness, saltiness, texture, crunch, etc, that maximize appeal.
What’s more, these companies are in an arms race with each other. They want to create a product that people crave more than the others. To create a product people come back to more often than the others. To market it better than the others. They don’t invest in that because it doesn’t work.
Maybe that’s not creating “addiction” (ehhh) or “hijacking” our brains like I originally wrote, but it certainly is doing something.
Food today is cheap, hyperavailable, hyperpalatable, and often hypercaloric. It’s engineered that way because it makes people want to come back for more. This is very different from the food environment our brains evolved in.
Look at the obesity rates in the last few decades. You can’t convince me that our food environment isn’t playing a significant role, or that companies aren’t deliberately designing food this way because it creates repeat customers and that creates profits.
Also, I don’t think there is anything wrong with acknowledging the food environment we live in today is problematic nor that doing so takes away anyone’s agency. My original phrasing wasn’t great, and perhaps done in such a way as to lean towards taking away agency. Again, I don’t want to dismiss criticism even if I disagree with some of the underlying sentiment, and I'll take it on "hijacking" in particular.
Instead, I think acknowledging the problematic food environment can be empowering. It helps explain why maintaining a healthy diet can be difficult, can reduce some of the guilt people experience around food, and it can help people be more deliberate in how they structure their personal food environments.
"Has it backwards"... What? No, absolutely not.
Fasting absolutely eats muscle. Your body requires EAAs to function and they come mostly from skeletal muscle when dietary intake is inadequate.
Oliver Owen did the classic fasting research on this and found that 21 days of fasting in obese men led to half of their weight loss coming from lean mass, of which 60% was structural protein (PMID: 9665093).
And yes, his research showed it takes about 5 days for protein sparing mechanisms to kick in (see first image), but even at max capacity your skeletal muscle is never "protected" or "spared" in the sense that you can prevent muscle loss.
And muscle loss is substantially worse the leaner you get. Abdul Dulloo did a lot of work on this with data from the Minnesota Starvation Experiment and others, finding that the ratio of protein losses to non-protein losses increase exponentially with lower levels of body fat (PMID: 10673906; see second image).
Another study observed the same thing and found that protein contributed 2-3 times more energy in normal weight vs obese adults during prolonged fasting (PMID: 10574520). In fact, they didn't even really observe an adaptation in normal weight people like they saw with obese people, with oxidation being consistent for up to a month of fasting.
The worry that fasting eats muscle has it backwards, because the body raises growth hormone during a fast to spare protein. By day five of a fast in one study, 24-hour growth hormone was about three times higher than on a fed day, and between day one and day five free fatty acids rose almost fourfold and the ketone acetoacetate rose about fourteenfold. That's a body moving to its own fat for fuel while it protects muscle, and in my view it can do that because insulin has fallen low enough to allow it.
I think we need to stop calling foods, substances, and behaviors "addictive" because it carries some really erroneous conotations.
Like, what does addiction even mean in these situations?
1) It's rewarding and people want to keep using. Okay, that's a meaningless definition that accompanies all pleasurable activities.
2) People want to use despite negative consequences. Okay, this can again apply to virtually anything and is also completely subjective in terms of what constitutes a consequence.
3) It changes the brain in ways that compel people to continue regardless of conscious intent. This is basically the brain disease model of addiction, which has been largely discredited in addiction research.
Food companies try to engineer foods that taste good and provide pleasure to those eating them. That's it, and that pleasure contributes to motivation for many to continue eating them.
There is no circumstance where one's brain becomes "hijacked," and I actually find such wording to be quite defeating for those struggling to change their behaviors. It essentially tells people that they have no control and are victims to their food, drug, or behavior or choice.
@doctortro is right, the food environment we live in today is literally engineered to be as addictive as possible.
Turns out there's big money in hijacking our neurology.
All that said, can anyone explain how Berry's response is relevant... at all?
I'm highly skeptical of this finding. Need to see the full-text when published, but a few issues pop out to me based on the conference abstract (screenshots included for convenience).
First, how is reverse causality accounted for? One of the primary indications for TRT in women is sexual dysfunction, and a 2024 meta-analysis of nearly 150,000 participants found that cardiovascular diseases are themselves associated with sexual dysfunction in women (PMID: 38297501).
Second, what was the testosterone exposure? There's no info about formulations, doses, duration of treatment, serum levels, etc.
Third, composite cardiovascular events increases statistical power to detect differences between groups, but they aren't interchangeable. This isn't necessarily a bad thing, but I'd want to see the individual outcome rates and whether any association was driven by less severe diagnoses.
Fourth, how is surveillance bias accounted for? Women on hormone therapy are more likely to be part of the medical system than those not receiving it, so the likelihood of documenting something is higher by this alone.
Fifth, what is going on with their data table? There were supposedly 3164 women in each group (testosterone vs control), but in the second row, 305 events at 3.2% would be over 9,000 participants in the group. Maybe they meant to put 105. Could just be a simple error.
Anyway, these are just some things off the top of my head. Might be more. Sucks that such findings can make the rounds and strike unnecessary fear before any meaningful review of their study is even possible.
I think back to that time Bryan Johnson canceled his workout because he had regular coffee before bed and "wrecked" his sleep. Hilarious.
I stayed up until 2:30 am last night to finish some edits on a book chapter for a project I've been working on, rolled out of bed after just 3.5 hours of sleep, and just had an incredible leg workout in the gym. All my lifts felt amazing.
Part of resilience is doing the hard things when you don't want to do them. Don't build a body or mindset that is so fragile that you skip a workout just because you didn't max out your sleep score.
I couldn't imagine using an entire playbook to try and manipulate women into sleeping with me. Such degenerate behavior.
Here’s how I ran my dating app operations when I was single from 2013 to 2021. I ended up sleeping with roughly half my matches, 75% of women I went on a first date with, and 99% of women I went on a second date with.
First: get fit, get paid, and get smart. You need to actually be valuable enough for women to swipe right on you in the first place.
When you match, DON’T JESTER-MAX. As I said, attractive women know they’ll match with virtually any guy they swipe right on. If she swiped right on you, she’s already interested. Wasting time only increases the likelihood that she’ll get bored, get distracted, or move on to another guy.
Opening line: “Thought you looked cute, had to swipe right.”
You’re being direct and establishing romantic intent. She’ll respond with some variation of “thank you” and will usually compliment you back. This further establishes mutual romantic interest in her mind.
Second line: ASK HER OUT.
“Let’s get drinks at X.”
Your invitation should include a firm location, date, and time. The date/time should be no more than 48 hours from your message and no further than five minutes from your place.
Remember, YOU are asking HER out. Women are stupid and indecisive, so you should already have the plan locked and loaded. Every second you waste on chit chat increases the odds that she gets distracted, loses interest, or finds something better to do. Generate mystery for her now. You can do “talking stages” on the date.
In the overwhelming majority of cases, she’ll either agree or propose an alternative date or time that better fits her schedule. Either way, you’re in.
On the date: Arrive 10-15 minutes early, get a seat facing the door, and make sure you know what she looks like. When she walks in, greet her with a one-armed hug and a kiss on the cheek. Again, we’re being direct about our intentions and reinforcing the romantic nature of the encounter.
Study the menu beforehand and have two or three recommendations ready.
She’ll almost always pick one. Order for both of you. Engage her in conversation, be attentive and passionate, and always agree with whatever nonsense she brings up, unless you can turn it into an unserious, teasing flirt. Repeat for two drinks.
When the waiter asks whether you want a third, casually mention that you live nearby (which is why LOCATION MATTERS) and ask whether she’d like to open a bottle of wine back at your place.
If you haven’t been a complete sperg during the conversation and the attraction is mutual, she will say yes.
YOU PAY FOR EVERYTHING. Then leave together.
Once she’s at your place (WHICH YOU HAVE THOROUGHLY CLEANED BEFOREHAND), give her a short tour. When you get to your bedroom, kiss her passionately and let things progress naturally from there.
There is never a third drink back at your place.
Good luck! And remember, after a few years of this, you’ll become a shallow husk of a man, utterly jaded and nihilistic about the world.
But do not despair! When this happened to me, it forced me to fundamentally change who I was. I found Christ, became sanctified, and discovered that all those years of experience had turned me into an apex predator compared to the sheltered church boys competing with me for trad, virgin church girls in their early 20s.
I’m now happily married with multiple kids.
Important to remember that the Minnesota Starvation Experiment involved men with an average starting BMI of 21.7, who lost 25% body weight and ended with an average BMI of 16.4. These results can't be extrapolate to people with excess fat mass dieting for weight loss.
Alex Leaf retweeted
Vegas for my 41st → 6ish months later.
What happened in Vegas didn’t stay in Vegas this year😭😂
Alex Leaf retweeted
Me and my little sidekick over the last 4 Halloweens. Year 2, he was not having any of letting me take a picture with him lol. That was right after he learned to walk, and he basically started running everywhere from that moment on.
But I realized something going through these pictures. I’ve been pregnant every single October since 2023, with each of those previous pregnancies ending in first trimester losses. And this October, I’ll be hitting viability with our second little boy🥹 So grateful🙏🏼
No, you absolutely cannot "almost always tell" who underwent IVF by looking at these things post-birth.
Best case scenario is pure confirmation bias because, as a midwife, you will know how conception happened beforehand.
We have data suggesting that IVF itself is associated with greater relative risks of some placental and cord issues, but those issues affect a small minority of all pregnancies. There is definitely not some "IVF phenotype" that you can just look at post-birth.
I'm disappointed to see Speth publish a piece on rabbit starvation with so little empirical evidence investigating the issue (DOI: 10.1016/j.qeh.2026.100120).
I've written about the upper limit to protein metabolism, which I'll ink to in a follow-up comment, and the available evidence indicates that no such upper limit has yet been found.
In fact, no limit is observed even at doses of amino acid infusions that cause participants to vomit.
Speth, to my surprise, relies on the old Bilsborough and Mann 2006 review which itself relies exclusively on an old 1973 publication by Rudman, who himself later acknowledged his study was properly designed to test the concept.
As such, Speth makes bogus claims like the upper limit being about 300 grams per day, and then further puts the limit "typically between about 5.0–6.0 g/kg/d or even slightly higher," without any references.
He basically just took the 300 grams and divided it by the average hunter-gatherer / forager body weight of 50 to 60 kg.
Everything after that is historical accounts of "rabbit starvation", but none of these indicate that protein intake per se was the issue.
Rather, as I state in my article, rabbit starvation is just a term used to describe the predictable consequences of sustaining on exceptionally lean and nutritionally limited foods, particularly when super active with a high energy expenditure.
- High thermic cost of metabolizing protein, meaning that people needed more total food to obtain the same net energy.
- Difficulty consuming enough lean meat to meet high energy demands.
- Inefficient use of protein when nonprotein energy was scarce
- Nutrient deficiencies (essential fatty acids, fat soluble vitamins, and minerals)
My article for anyone interested in the research directly investigating our intrinsic capacity to metabolize protein.
alexleaf.com/does-an-upper-l…
My opinion on collagen for skin health outcomes leaned heavily on a prior 2025 meta-analysis my Myung (PMID: 40324552), so that is going to be my comparison point when looking at this recent publication by Grimes.
I want to also note upfront that none of this is dealing with biological plausibility or mechanisms. The question here is whether such things manifest into benefits in humans.
First and foremost, Grimes isn't a new meta-analysis, but instead a reanalysis of two prior publications from 2021 and 2023. The latter searched through December 2022, so it is missing more recent studies (e.g., Myung includes four published after that).
There are also inclusion criteria differences. Grimes effectively excluded studies that used combination treatments (due to relying heavily on the 2023 analysis that excluded them) while Myung included them and then sub-group analyzed the collagen alone vs placebo.
Second, Grimes was genuinely valuable in that they found data handling errors in prior studies, which can materially affect the outcomes. The heterogeneity problem is also very real and remains something showing up in Myung.
Third, I don't actually think Grimes analysis itself is very strong. They reported everything as meta-regression coefficients per unit of collagen dose. In other words, their table 2 is asking if the effect of collagen changes with the dose of collagen.
This is a huge issue because Grimes erroneously concludes that the lack of significant dose-response means the treatment benefit probably doesn't exist.
It could very well be the case that collagen works but the effects plateau with higher doses because of saturation (e.g., imagine this was done with creatine because changes to strength didn't increase as dose increased from 3 to 5 to 20 grams over several months). Other reasons could be non-linear dose-response or non-equivalency in grams of collagen between formulations.
On that note, the hydration analysis is actually compatible with a dose-response effect, with a confidence interval that barely crosses zero (-0.01 to 0.14). So even with their own data, it is more accurate to say that higher doses of collagen likely increases the effect on hydration parameters than saying it doesn't.
When you look Myung, benefit compatibility argument gets further support.
Non-industry funded:
- Hydration: 0.33 (-0.06 to 0.73)
- Elasticity: 0.29 (-0.04 to 0.62)
High-quality (RoB 2 and Jadad):
- Hydration: 0.86 (-0.28 to 2.01)
- Elasticity: 0.52 (-0.09 to 1.14)
Also note that significance is achieved when looking at high-quality studies with RoB 2 alone (hydration and elasticity) and Jaded alone (elasticity and wrinkling). It's only when combined that estimates don't cross p=0.05.
None of this, from Grimes or Myung, establishes that "collagen has no effect or doesn't work".
The appropriate conclusion is, "aggregate high-quality and independent research doesn't establish a statistically significant benefit, but their confidence intervals remain compatible with small to moderate beneficial effects."
Certainly, the evidence base is messy. But my position remains that collagen likely improves some aspects of skin health, particularly hydration and elasticity.
A new meta-analysis finds no good evidence for benefit of supplementing with collagen for skin aging. It audits previous widely cited meta-analyses claiming benefit which contained numerous errors. Once the errors were corrected, the findings no longer suggested a statistically significant difference.
Such errors included:
- Misrepresentation of methodology
- Incorrect usage of percentage difference
- Failure to convert standard error to standard deviation (standard errors treated as standard deviations, which can give a result too much weight)
- Missing/Omitted studies, or even omitted data from found studies
- Inclusion of studies with no placebo control
- Inappropriate inclusion of studies (one papers hydration data was based on a survey question without any objective analysis which should not have been included)
- Inconsistencies in effect size reporting/used
- Listing incorrect numbers of subjects
Furthermore the general quality of the trials themselves were poor. The underlying trials were often small and short, typically 8-12 weeks. Many did not adequately track other skincare, procedures or usual protein intake. Some gave little detail about the placebo, making it hard to judge how well participants were blinded. Few trials defined how large a change would matter to patients, which is important given a short-term change in a skin measurement mechanistic proxy does not establish a visible, let alone a lasting effect on aging skin.
I continue to take the view that the recommendation of collagen supplements for general skin health / prevention of skin aging is not epistemically justified on the quality of the available evidence.
It might be justified in a burn unit or wound healing context for very large wounds (where a massive amount of collagen synthesis is required), but that's a completely different discussion.
