KempyKolibri

I’m not aware of any compelling evidence that the n3:n6 ratio actually matters as long as you’re meeting the absolute required levels of each.

There was a big push for this hypothesis in the 2010s, but on closer inspection the only research that seemed to support it was where the “low n3:n6 ratio” cohort were there by virtue of low n3, not high n6.

Where studies compare groups of people where ratios were manipulated but both were at adequate levels, I don’t believe we see any evidence of a deleterious effect.

There’s a good pod on this exact subject with nutrition scientists: https://sigmanutrition.com/episode538/

The TL;DR (IIRC) is that we tend to only see this in trials where atrial fib is a tertiary endpoint so there’s not really compelling data to suggest AF is a risk.

But give it a listen and see what you think, it was a while ago I listened to it and I’m not qualified to give actual advice!

There’s essentially no evidence that the degree of ultraprocessing affects a food’s healthfulness. There are tenuous and broad associations between UPF content of a diet and health outcomes, but these are based on invalidated FFQs for the exposure we’re interested in, and all the subgroup analyses where available suggest this is driven by SSBs and processed meat.

I’m not sure why we’d consider oils, emulsifiers or fortification and indicator of poor health outcomes.

Whole grain cereals are associated with positive health outcomes so I’m not sure why something being a liquid cereal would be a negative.

FWIW I would agree that oat milk is probably an inferior milk to dairy in most aspects except fibre content, but that’s not because of the reasons you gave. And soy milk seems either equal or superior to dairy milk in all outcomes that I’ve seen.

Yeah, IMO there’s a continuum between lean meats that I’d classify as relatively middle-of-the-road healthwise (like chicken), and processed red meat (pretty adverse health outcomes even from small amounts), and the fact that there’s a “butter and bacon are health foods” movement seems insane to me.

Unfortunately trends towards plant-based food seem to have taken a step backwards in recent years and I suspect the current moral panic around UPFs hasn’t helped. But the evidence on UPFs as harmful is pretty tenuous at the moment, while the evidence on meat and adverse health effects is considerably more comprehensive.

UPF meat substitutes do tend to be healthier than their meat-based equivalent (see the SWAP-MEAT trial, for example).

Eating mostly plants does not mean one has to have protein deficiency.

Seitan, tofu, tempeh, TVP, etc etc. All plant based, all high protein.

Fair point! I’m not that woke on the relative health impacts of vaping but agree that the positive impact of vaping is not akin to that of actual food, no matter how processed.

By heuristic, I just mean “a rule used in decision making”.

Under that usage, the fact that the rule doesn’t provide fine-grained advice doesn’t disqualify it from being a heuristic. Eating mostly plants is a rule used in decision making when considering what to eat.

> The extreme is that it is advising people to seek treatment if they suffer from pica or bulimia.

How is that entailed?

It's just a dietary heuristic, why would it have to explain everything? If you want that, just go and look at the literature on overweight and obesity or, say, substitution of animal protein for plant protein. It's all there.

This area is very interesting and lots of this is on the money. That said, I think there are some places where it overreaches and possibly verges on fear mongering based on pretty weak evidence.

I'm not sure NSS are necessarily "healthwashing" - they are genuinely a healthier alternative, at least in SSBs. Pointing to some very speculative research about "gut microbiome disruption" as if that somehow means NSS are something we should be concerned about in our diet doesn't seem to reflect the body of evidence on the subject. On balance they seem to be either a neutral or beneficial product, depending on what they replace in the diet.

I think one important distinction between UPF and cigarettes is that we have lots of examples of healthy UPFs. Are there any such examples for cigarettes? Even those researchers who voice concerns about the health impacts of UPFs (Kevin Hall, Samuel Dicken) seem to be largely interested in identifying _which_ UPFs might drive poor health outcomes and why, so we can regulate industry to make their products more health promoting.

My concern with this analogy between cigarettes and UPFs is that we end up with a movement to completely ban UPFs when they have lots of useful properties (can be stored at ambient temperature, long shelf life, reliable quality) that make them very important for people with limited means. The dream scenario, IMO, is that we regulate out the worst of the harmful properties, rather than trying to get rid of them entirely (which I think is the dream scenario with cigarettes).

No, because we have a huge body of evidence pointing to both the safety and efficacy of lipid lowering medications. We know that as far as LDL-c goes, the lower the better, so since we have safe drugs that lower more effectively than lifestyle interventions, these are the first line option in most cases.

What’s the evidence that lifestyle intervention is more effective than combination medication therapy?

Because medication is more effective. Side effects from statins are relatively uncommon and generally mild, so it wouldn’t be ethical to use lifestyle as a first-line treatment in place of, say, a combination of low dose statin and pcsk9 inhibitors.

However many clinicians do take a “let’s sort out the problem as quickly as possible with medication, and if you want to try lifestyle and back off (or even stop entirely) the meds and see how your cholesterol is afterwards, we can do that.”

This seems like a good balance to me.

Feels a bit like this though, no?

https://xkcd.com/2557/

The reason we want people to get vaccinated is to stop people getting the diseases…

Triggered mine too, especially “Modern JavaScript applications aren't just a few scripts anymore — they're sprawling codebases”

I wasn’t aware of that critique, thanks for sharing. Before I read the response my first thought was “why such consistency across different SNPs, then?”, so I would certainly agree with that aspect of the defence.

In general, Ference’s explanation just seems more parsimonious than Schooling’s. It’s possible that they’re right, but I think they would need to show that the specific genes in Ference’s study are affected by age in this way.

I wouldn’t claim to be a great expert in MR, though. I can just about keep up with surface level understanding of them but once you get into the nitty gritty stats, pleitropy testing etc it’s a bit over my head tbh.

> I thought that was basic enough that I didn't need to explain it. But here goes...

This is quite the tone to take when the actual point being made has demonstrably sailed over your head, considering the reference provided to you explains it very clearly.

Which is more likely - nigh on every lipidologist, cardiologist and nutrition researcher is wrong, or you might have made a mistake yourself?

> Mendelian is characterized by effects having strong influence from a single gene. Heart disease is clearly more complex than gene -> heart disease

This seems like a misunderstanding. A single SNP clearly can affect CVD risk, that’s precisely what the paper shows. The assumptions required for an MR study to be valid do not include “the outcome must only be affected by a single gene and no other gene”. It’s required that there’s no pleiotropy present in the exposure (I.e. the SNPs). The exposure here isn’t heart disease, it’s SNPs that affect LDL-c levels, and the outcome being measured is CVD. So your point doesn’t pose an issue for the study and the inferences it makes.

But honestly - just read the paper. I think both that paper and the EAS consensus paper are very approachable.

Graboy has provided the citation I would have given, as well as an excellent explanation. I’m not sure what you mean by “heart disease is clearly not Mendelian”.

Yep - the SAMSON trial suggests that nearly all side effects attributed to statins are actually just nocebo: https://www.jacc.org/doi/10.1016/j.jacc.2021.07.022

The band aid analogy doesn’t make sense when we consider the MR studies showing the lower your genetically determined LDL-c, the lower your risk of CVD. If everything was randomised except the number of band aids, why would having fewer band aids result in lower CVD risk?

> This is one of the reasons statins reduce the number of heart attacks, but don't always seem to reduce all-cause mortality.

That’s one potential explanation, but I don’t think it’s the most likely one. We tend to see non significant ACM in smaller, less powered trials, or those with lower LDL-c lowering. ACM is simply a less sensitive endpoint - if you have a treatment that reduces CVD incidence, then the “CVD incidence” endpoint will give you significant results with fewer CVD event differences between study arms compared to ACM since your power to detect differences is diluted by other fatal events that aren’t affected by statins (cancer, motor accidents etc).

Why do we see consistent dose response between LDL lowering SNPs and cardiovascular disease in Mendelian randomisation studies, then?

If “highest number of n=1 studies wins” is your yardstick for causal inference then you’re part of the reason the keto crowd isn’t taken seriously. Wish I could sugar coat it more but that’s the reality, and I think some people on that side of the fence could do with some home truths.

> They don't wave around CVD risks: they show you that all the pro "SFA is bad because of CVD" crowd is also full of biases and very bad science and pharma sponsored studies that shill statins etc...

That is hand waving. The implicit claim being made by your statement is that because researchers have biases (true of all researchers) or they’re sponsored by interested parties (also true of keto studies, and not necessarily an indication of an issue with any given study) or also push medications or supplements (again, also true of keto studies) then we should treat all hypotheses tested in ways that contain these “flaws” as identical in validity.

However, that’s absurd. The evidence in favour of the claim that substituting PUFA in place of SFA reduces CVD incidence is absolutely mountainous in comparison to the evidence base supporting the claim that ketogenic diets cure mental health disorders.

In both cases, there exist sponsored studies, biased researchers and medication peddlers that support the hypothesis. Yet it sounds like you are willing to believe one but not the other. So what explains the difference in your attitude towards the two? Why do you believe it’s likely that keto cures these mental health issues but not that SFA consumption increases CVD incidence?

We have some case studies and pilot studies without any kind of control. Perhaps keto/low carb could be helpful (it certainly is with epilepsy!), but I certainly haven’t seen any evidence that it’s superior to other diets that achieve the same things (I.e. weight loss, or higher clinician contact time - a lot of these pilot studies end up losing a bunch of weight and getting several extra hours per week of contact with their clinician - who knows if much/all of the benefit comes from this?).

Having had quite a lot of experience with the keto/low carb crowd, I think we’d see a lot more adoption/interest in their ideas if they approached things in a less ideological/dogmatic way. It’s hard for responsible clinicians to get involved with, say, Metabolic Mind when people like Bret Scher hand wave around the CVD risks from high SFA intakes, or big up low quality work like the godawful Keto-CTA paper.

There _are_ responsible keto advocates out there like Ethan Weiss, and I suspect that if the keto/low carb community were to promote _their_ work rather than that of people like Nick Norwitz and Dave Feldman then their diet of choice would be taken more seriously.

Unfortunately much of the low carb movement is quack town at the moment. I hope they get their act together, there are benefits in there for people in need, but they need to get serious first.

> A "very high evidence bar" that isn't described anywhere is one that doesn't actually exist

If your claim is: “if a standard isn’t explicitly written down somewhere such that one can utilise it to ascertain whether something meets it without ambiguity then it doesn’t exist” then the entailments are absurd. The world is full of standards that do not meet such a bar (“reasonable doubt”, for example) yet obviously this is a real standard.

> COVID was full of this stuff

Yet when I asked you for to give examples of “this stuff” you failed to do so. How come?

> when the universities get disestablished

Lmao. Not going to happen, I see we’re off in cloud cuckoo land now.

> A lot of the COVID pseudo-science was specifically designed to manipulate people's emotions (e.g. journals rejecting correct papers because fewer people might take vaccines as a result [1]).

1. What Covid pseudo science are you referring to?

2. How does the x thread you referenced show “journals rejecting correct papers because fewer people might take vaccines as a result”? As I read it, the rejection was because the journal had a higher bar for evidence on claims around herd immunity than the researchers were able to meet. That is, they’d happily publish papers suggesting lower levels of herd immunity, but the papers would require more rigour than that which was provided.

It’s not clear to me that this bar existed just to increase vaccine uptake, but to generally avoid moves towards relaxing interventions based on insufficiently strong evidence (social distancing, mask wearing, etc).

It’s not clear to me what objection one would have to having a high threshold for evidence when publishing research with such high potential to impact public health. That seems like a good thing to me.

jjui is amazing, sometimes I feel like I shouldn't rely on it so much so I learn the CLI, but it's just so useful!

The evidence base on eggs is a funny one because of: 1. Genetic traits influencing response to dietary cholesterol. 2. The effect of baseline dietary cholesterol on the impact of additional dietary cholesterol (if you're already consuming ~300mg/d cholesterol, adding more on top is unlikely to increase risk by much). 3. The effect of baseline CVD risk on the impact of egg consumption.

Generally when we take this into consideration, we see a linear increase in risk from increased egg consumption. For example this paper suggests that the higher your genetic risk for CVD, the higher the increase in risk from egg consumption, but even those with lower CVD risk see a ~6% increase in CVD events per 3 eggs/week increase: https://www.sciencedirect.com/science/article/pii/S000291652....

Additionally replacing the 1tbsp butter with plant oils would likely reduce ACM risk by ~17% (http://doi.org/10.1001/jamainternmed.2025.0205), but I'll be the first to admit that there's nothing that really replaces butter on a taste basis :D. Got to find the happy balance between health and hedonism IMO!

> In the same way that increased salt intake causes increased water retention, and thus increased weight, but this increased level of water weight goes away after a few days if you start consuming less salt, and there's no evidence of this causing long term harm.

We've already gone over data showing that when we summate data from RCTs and salt consumption we see reduced salt consumption leads to reduced cardiovascular disease events, so it's demonstrably not the case that there's no evidence of this causing long term harm.

Additionally we have strong evidence of a dose-response curve regarding blood pressure and atherosclerosis, so that additional 5mmHg is contributing to additional plaque burden. Even after you reduce your salt intake, that plaque is still going to be there, increasing your risk of a CVD event.

Additionally when we look at the results of INTERSALT, age-related increases in blood pressure only seemed to occur in populations consuming more than 2-3g salt per day, which suggests that in addition to acute rises in BP, higher salt consumption than this may also be responsible for much larger rises in the long term that are not reversed when salt consumption is dropped.

Taking that whole body of evidence in totality, I think it's hard to argue that the effects of salt on the risk of adverse health outcomes is akin to water weight.

> I could see where if one already had severe CVD, maybe eating more salt could be the straw that breaks the camel's back, and thus until they heal the CVD it could be wise to limit salt. But this would be no indication that the salt is the cause of the CVD or causes any long term chronic problem. And it is the long term chronic CVD that is by far the most important to address IMHO. If salt is not causing that, this whole discussion is largely misdirected energy.

Again, even small increases in BP over normal range (and even slightly below - we tend to see increases in risk once systolic BP rises about 110) is associated with increases in CVD, so the raised blood pressure is one of the forces driving that long term chronic CVD.

> We disagree here but that's a separate issue from salt so I'll leave it. :)

Well if you're open-minded about the topic but think refined oils are a health risk, you're the same as I was a few years ago. I ended up changing my view on the topic. If you think there's a health concern not addressed by https://uprootnutrition.com/blog/seedoils I'd be genuinely interested to know.

> And this is where I think salt has been scapegoated in a way that probably just distracts from the root problem as I describe above.

I think the evidence very strongly suggests that sodium consumption is one of the root problems driving chronic health issues in the West.

Monkey nut paste and big hairy ball juice, obviously.

Sorry, I summarised what I thought was your goalpost earlier in the exact same words and you didn’t correct me, so I made the assumption in subsequent replies. I’m not interested in straw manning your argument, just trying to understand.

I’m going to pass on the crash test dummies bit. You’ve misunderstood the point I was making, but it could be poor communication by me and I think the point is becoming increasingly tangential.

> When it comes to pharmaceutics and food additives, our mechanistic understanding is insufficient so we often have to resort to empirical studies on humans, including RCTs

> It does, because again, mechanism is provided. You could say that the study has weak evidence for the mechanism and it works like that perhaps only for sugar. Because that some mechanism is found in mice does not mean it is also found in humans, and it would be a fair point. This is why many species are tested and so far the results held up (testing humans takes too long for obvious reasons).

So you don’t feel you’re being straw manned again, can I get a clear answer to this: is your argument that if we stack together sufficient numbers of mechanistic animal studies we can be sufficiently confident enough in the translation rate of such studies to humans that we can roll out public health interventions without any evidence of efficacy in human populations?