If the treatment is relatively mild, the dropouts are comparable between groups then I am not sure that per protocol will introduce much bias. What do you think? In that case it can be a decent tool for enhancing power, although the results will always be considered "post hoc" and "hypothesis-generating".
From experience I would say that intention-to-treat analysis is the standard in large studies of drugs and supplements, while per protocol is often performed as a secondary analysis. Especially when ITT is marginal and you have to go fishing for some results to report and to justify follow-up research.
The supplement industry and similarly the cosmetics industry is a jarring example of what can happen with no oversight or the wrong kind of oversight. Although, to be charitable to the libertarian position, one can argue that many supplement and cosmetics companies are forced to provide inferior products since efficacious products, even when rather safe, cannot be sold on the free market for various reasons (e.g. higher doses of potassium or retinoids for photoaging).
Thank you for the write-up! Just as a minor quibble, veganism has not been considered the "healthiest choice" ever, or at least not for a long time, if I were to make a guess about "consensus" in the field. While it has been clear for a while that a diet biased towards plants is healthy, the data for the addition of certain food groups (fatty fish, fermented and low-fat dairy, etc) is pretty strong as is the data for the health benefits of individual carninutrients (creatine or even taurine).
As you correctly point out, the issue of residual confounding is unsolvable. All we can take from these studies are hints and ideas. The recent failure of Vitamin D to live up to the hype, initially generated by observational studies, is a case in point.
I am particularly weary of studies of dietary patterns, whether they are vegetarian or Mediterranean or others, since I would expect to see the strongest biases here (because these patterns are associated with lifestyles, class, belief etc). Nevertheless, studies on surrogate endpoints like cholesterol and studies on single food groups do support the whole idea of reducing meat consumption.
I think the consensus among nutritionists is that a well-planned vegan diet is among the healthiest possible diets. Almost everyone in the US would benefit from "going a bit more vegan". Nevertheless, it is probably not optimal on certain axes.
It would seem that the best diet to improve long-term health is a flexible pescolacto-vegetarian diet supplementing certain carninutrients, e.g. creatine. So not vegan.
Tradeoffs are real and you have to optimize for one thing over another. For example, a standard (unsupplemented) vegan diet may not be optimal for mental and physical performance due to the higher risk of iron deficiency, low protein intake and lack of dietary creatine intake, among other things. A lot of those issues can be alleviated through careful planning. However, it may very well be that low-moderate intakes of protein and iron are one of the reasons why a vegan diet is healthy and you will have to weigh this against the potential performance aspect.
We have two types of evidence in favour of veganism:
We can extrapolate that veganism is healthy from first principles by studying individual foods and nutrients. For example, we know that saturated fat often found in animal foods increases LDL which is a validated marker of cardiovascular disease. Saturated fat intake will be low on a vegan diet. Another example is iron, we know that even unprocessed red meat is problematic because it is a rich source of iron and we know that many men consume too much iron (whereas some women consume too little). We know that iron intake and availability will be lower on a vegan diet and we have relatively strong evidence that elevated iron levels are harmful to health.
Or we can be lazy and just take a bird's eye view and look at mortality data in observational studies. These studies clearly show that both vegetarian and vegan diets are associated with reduced mortality and superior health outcomes. Unfortunately this kind of study design is subject to different biases like residual confounding, e.g. it may be that vegans are healthier than average even after we controlled for obvious variables associated with health like income, cholesterol, body weight, etc. While this does not prove that veganism is healthy, it definitely shows that veganism is consistent with above-average health outcomes.
2We have to be careful not to offset the health benefits of a vegan diet. There is a surprising amount of evidence suggesting that low-normal iron stores are beneficial and may reduce cancer incidence, mortality and perhaps increase longevity. Specifically, as strongest, I would point out the FeAst study and numerous recent Mendelian randomization studies on iron and longevity (e.g. Daghlas and Gill 2021). It is prudent to test ferritin to know whether you are too low or too high.
Vitamin D testing certainly could be useful, even though recent clinical trials testing vitamin D supplements are between somewhat to highly disappointing, but deficiency is presumably not strongly linked to veganism.
I do not think this is entirely accurate. Lung cancer in smokers hits unusually young people because, well, they are smokers. Heart disease is a disease of old age and accelerating it somewhat through an unhealthy diet would have complex effects. However, making matters even more complicated, ultraprocessed foods also promote cancers and obesity -- the latter is definitely a huge healthcare burden which does not kill people immediately.
This is hard to model since there can be a shift from a disease that kills slowly to one that kills quickly and early (dementia to lung cancer), but you can have also the opposite shift (e.g. from a non-disease state to chronic COPD and frailty preceding death).
All we can say for sure is that the harmful effects of smoking and junk food diets may be offset to some extent. More so for smoking than junk food.
Either way, it would appear the consensus is that "in high-income countries, lifetime health care costs are greater for smokers than for non-smokers, even after accounting for the shorter lives of smokers"
https://www.tobaccoinaustralia.org.au/chapter-17-economics/17-2-the-costs-of-smoking
While the term "healthspan" can be useful for public messaging it is not necessary to use it instead of "lifespan" as study after study shows. When the word "lifespan" is used in the correct context people are very willing to embrace even radical lifespan extension. It seems prudent to combine both concepts.
Asked “If doctors developed a pill that enabled you to live forever at your current age, would you take it?” a surprising number of people turned out to be hardcore life extensionists: "There were no differences by age...Among young adults, 40.0% indicated they would not take the pill, 34.2% indicated they would take the pill, and 25.8% indicated they were unsure."
Barnett, Michael D., and Jessica H. Helphrey. "Who wants to live forever? Age cohort differences in attitudes toward life extension." Journal of Aging Studies 57 (2021): 100931.
Knowing your risk does not change behavior, at least that seems to be the case with genetic risks. That means dietary and lifestyle approaches towards cardiovascular disease are out. As a good approximation, everyone who wants to have a healthy lifestyle already has one*.
On the other hand, it is possible that more people would benefit from wide-spread use of statins and that they could be convinced to actually take them.
Cardiovascular disease is definitely not a neglected cause area. It is a multi-billion dollar industry and a very popular research field. Neither is targeting cardiovascular disease an effective approach towards improving population health due to Taeuber's paradox:
"..[the complete] elimination of neoplasms as an underlying cause would result in 3.83 life years to be gained among men, and 3.38 life years to be gained among women. Elimination of cardiovascular diseases results in a larger gain in life expectancy: 4.93 years among men and 4.52 years among women. "
https://jech.bmj.com/content/53/1/32.short
As you can imagine the benefit to human healthspan and lifespan due to a marginal reduction in cardiovascular disease achievable through refinements of diet and drugs would be minuscule.
The only way to significantly (and efficiently) improve human healthspan in developed countries is through slowing aging which is a risk factor for all major diseases.
*A potential cause area would be to work on legislative change that will compel people to change their lifestyle, this could be feasible, e.g. via taxation.
I enjoyed a lot of the other content and hence am now much more inclined to read the EA forums rather than lesswrong. These changes could mean that people like me, who are primarily interested in progress studies and applying science and reasoning to better humanity and themselves, may miss out on relevant AI content when they move to another site. Then again perhaps the EA forums are more relevant to me anyway and I should spend more time reading these.
While I agree with the logic of avoiding subjecting highly unsaturated oils to heat we do have to be cautious here with speculation.
When you say things like that: "Nonetheless, if these things are poisonous at high concentrations, they're probably not great at low concentrations."
It does not clearly follow that such a dose-response exists. The word "hormesis" gets thrown around a lot in the lay press, and there is actually some truth there. Plenty of moderate (even genotoxic) stressors have health benefits at lower doses. Of course, I would not gorge on lipid hydroperoxide based on this, because we have better evidence-based "hormetic" stressors, but it also does not follow that lipid oxidation products at low doses are harmful.