Vitamin B12 is super-easy to supplement (ESP b/c it can be stored for weeks). In modern populations, most people have more than enough calcium - too much calcium is more common than too little, esp b/c calcium contributes to calcification of the arteries (and cellular apoptosis). There are zillions of plant sources of calcium…
I’m vegetarian and my blood levels of B12 and D are both high.
Climate change is not the only problem that stems from excess land allocated to agriculture (or methane emissions from agriculture) - there are MANY other issues - from habitat destruction [esp of CO2-sequestering forests] to [and especially] increased land/housing costs (b/c land for agriculture isn’t used to help people build). EO Wilson also said in one of his books that the world could support many more people if we all went vegetarian (and this would mean more people without causing conflicts with other people over land use, especially in a world where most of the available land has already been bought, causing housing costs to be more and more inflated).
In the NHS and HPFS cohorts, high animal-based protein consumption was associated with higher all-cause mortality (HR: 1.23; 95% CI: 1.11, 1.37), cardiovascular mortality (HR: 1.14; 95% CI: 1.01, 1.29), and cancer mortality (HR: 1.28; 95% CI: 1.02, 1.60). In contrast, vegetable-based protein intake was associated with lower all-cause mortality (HR: 0.80; 95% CI: 0.75, 0.85) and cardiovascular mortality (HR: 0.77; 95% CI: 0.68, 0.87) for both men and women ([54](javascript:;)). Analyses of the NHS cohort of 84,136 women aged 30–55 y, with no known cancer, diabetes mellitus, angina, myocardial infarction, stroke, or other cardiovascular disease, showed that higher intakes of red meat (RR: 1.16; 95% CI: 1.09, 1.23), red meat excluding processed meat (RR: 1.19; 95% CI: 1.07, 1.32), and high-fat dairy (RR: 1.03; 95% CI: 1.0, 1.06) were significantly associated with elevated risk of CAD. Vegetable protein was significantly associated with an 18% decreased risk when comparing the lowest and the highest intakes across quintiles (RR across quintiles: 1.00, 0.88, 0.85, 0.80, 0.72).
Reduction in protein intake of food also seems to increase longevity. Reduction in the protein content of food by 40%, led to a 15% increase in the lifespan of rats. The rats subjected to a protein-restricted diet early in life displayed a long-term suppression of appetite, reduced growth rate, and increased lifespan [58,59], and the increased lifespan in such animals was associated with significantly longer telomeres in kidney [58]. Consistently, the highest life expectancy of Japanese is associated with low protein and high-carbohydrate intake in diet. The source of protein also seems to be an important factor as replacing casein with the soy protein in rats, is associated with delayed incidence of chronic nephropathies and increased lifespan.
Vitamin B12 supplements are tricky for vegans. Psuedo vitamin B12 from ie chlorella which is not bioavailable can be sold. Synthetic forms have to be avoided in certain populations (ie kidney issues) despite what ex-vegan research institute Greger tells you. Then, you have to worry about mislabelling and quality issues for supplements. Again, the practicality keeps going down when there’s such a simple solution - add some lean meats/fish.
Low protein advocates downplay the muscle mass risks of low intake. Usually, it’s a “low met/met restriction” vegan ideology which doesn’t take into account all the other issues. In contrast, the NIH/NIA ITP finds glycine to be favorable with a similar effect on top of methionine-independent effects - what is a high glycine food?
Animal sources, especially animal cartilage, not plants.
I haven’t even gotten into creatine/taurine/etc etc that is only found in meat sources.
Ideology from veganism minimizes dietary protein is kind of like ideology from keto/Paleo minimizing the impact of LCHF diets on LDL particle number.
Read your own cited sources?
“In adults over 65, however, a high-protein diet was linked to lower mortality.” - NIH
“The new findings don’t prove that favoring plant-based proteins will add years to your life, but many other studies have associated high intakes of red and processed meats with shorter life span.” - Harvard
“However, malnutrition, including sarcopenia/frailty due to inadequate protein intake, is harmful to longevity/metabolic health.” - mechanism PubMed study
Processed meats are very different from animal protein causes death. It’s associated with smoking. Harvard Health’s recs are switching to fatty fish/lean meats + working out + nuts instead of processed red meats with high saturated fats. Not veganism. (Saturated fat is a more nuanced subject but basically stearic acid seems to be neutral)
Consumption of animal protein associated with a lower rate of mortality in older Italian adults, in a dose-response fashion. Plant protein showed no association with mortality.
Animal protein > plant protein longevity in older adults
Higher protein intake is associated with less functional impairment among older adults:
Animal protein is associated with more protection:
Meta-analysis of prospective cohort studies shows a positive relationship between protein intake and all-cause mortality:
vegans consume less than recommended daily protein:
In general, long-living humans overwhelmingly are omnivores>>>vegans with a bias close to what would be called “pescatarian”.
In general, get some muscle and bone mass for much more healthspan and the increase in lifespan will make sense when you don’t die from i.e. a fall. Reduces mortality in older age.
Beware dietary recommendations must always be put in the context of the individual - ie phytosterol intake is more atherogenic than regular cholesterol - which matters a lot in certain individuals who are “cholesterol hyperabsorbers”. Anything close to veganism should be very much avoided completely. High plant intake may also likely need to be avoided - mice don’t normally get heart attacks via atherosclerosis or dementia. Phytosterols are all the rage with vegans especially ex-vegan research institute Greger. If someone tells you to follow some ideological diet based on mice studies - you should be very, very wary.
Most humans are overwhelmingly omnivores, so it’s not surprising that most long-living humans are also omnivores.
Vitamin B12 supplements are tricky for vegans. Psuedo vitamin B12 from ie chlorella which is not bioavailable can be sold. Synthetic forms have to be avoided in certain populations (ie kidney issues) despite what ex-vegan research institute Greger tells you. Then, you have to worry about mislabelling and quality issues for supplements. Again, the practicality keeps going down when there’s such a simple solution - add some lean meats/fish.
You’re just cherry-picking this one single issue and blowing it way out of proportion to its relevance (plus you did not even add citations to the “B12 supplements are tricky” claim - this makes you sound like another Dr. Mercola). FWIW I’m near vegan and my blood levels of B12 have always been above-average, and I don’t take B12 supplements each day. B12 supplements are small/very-tasty and much more palatable than most other supplements.
All the sources I cited say “low protein early in life, high protein later-in-life” is ideal. Most people who read what I write (and the vast majority of the population) are well under age 65. See this Morgan Levine paper
My biggest concern with veganism has always been carnosine/creatine/taurine - these can be easily supplemented, and it’s still unclear if these have effects on lifespan. These can be supplemented, as Bryan Johnson (who is basically vegan) does.
High plant intake may also likely need to be avoided - mice don’t normally get heart attacks via atherosclerosis or dementia
um, this isn’t relevant. Mice die of cancer so they don’t die of the other causes. Also, the strongest evidence in favor of vegetarianism/high plant foods is on heart attacks.
The evidence in favor of vegetarianism is based on ALL the studies - both human and mice. Vegetarians have lower mortality than meat-eaters.
As Michael Pollan says in his nutritional aphorism, “eat mostly plants”.
On glycine… it’s not 100% clear if supplemental glycine can scavenge moderate-high methionine (it can reduce methionine toxicity at the highest levels of methionine, but what about moderately high levels?)
Methionine toxicity can be blocked by dietary glycine (Luka et al., 2009), consistent with the notion that GNMT is the principal effector of methionine clearance, at least at toxic levels. These data suggest that excess dietary glycine might depress methionine levels and thus mimic some of the benefits of a low methionine diet
The strategy was based on the understanding that glycine is the only acceptor for methyl groups by the action of glycine-N-methyl transferase (GNMT), and that in turn GNMT represents the only pathway for the clearance of excess methionine in mammals (Luka et al., 2009). Supplemental glycine, however, was found (Brind, 2011) not to reduce plasma methionine levels, in contrast to the 60% reduction in plasma methionine levels seen in rats on a low methionine diet. This result suggested that elevated glycine levels, in plasma or tissues, might in themselves produce health benefits and increased longevity
More from Karl Pfleger (posted to grg.org mailing list):
Nutrition is complex and there are many controversies with many researches
publishing on both sides of any controversy, so for any given side of any
controversy, it’s easy to find a paper that supports that side of the
issue. In order to decide who is right, one needs to triangulate many
different types of scientific evidence.
I disagree with this paper based on the totality of evidence. My read is
that saturated fat is bad. Here is a write-up I did recently on the many
diverse lines of scientific work that, to me, suggest that low-fat,
low-protein WFPB (whole-foods plant-based) diet is most likely best for
human nutrition. Such a diet is (as much as possible) fee of (added)
sugars, oils, & salt (SOS-free) and is inherently (mostly as a consequence
of the above) high fiber, high carb, low-protein, & low-fat (HF HC LP LF).
Note that the following is long relative to normal emails on this list (but
not relative to the length of a paper such as the one you attached).
And BTW, my sense from years of reading nutrition literature and currently
working in the aging/longevity field is that consensus amongst the most
knowledgeable researchers is shifting in the past 5 years or so slowly but
steadily towards the view I’m laying out here.
To me, the convincing thing is the many converging lines of
quite disparate types of evidence from different scientific sub-fields &
communities that when viewed as a whole mostly all point in the same
direction.
Note that this list mostly emits specific paper citations because there are
just too many to bother with for most of the points & most of those
statements are relatively uncontroversial. Most of the bullets below each
represent many (often dozens or hundreds) of primary research papers that
are easy to find representative examples of. Here’s my list of disparate
important (and mostly well-replicated) scientific findings:
CR (limiting total calories) extends healthy lifespan (without
diabetes and without significant frailty) in most/all animal species tried.
The only way for humans to do this with optimal nutrition (getting enough
micronutrients) is through consumption of mostly plants, especially veggies
& fruits, and such diets are necessarily low fat (& low saturated fat).
CR in humans has been shown to have all kinds of beneficial effects in
terms of moving biomarkers of risk for most top-killer diseases in the
less-risky directions (including diabetes markers).
CR in humans has been shown to regenerate the thymus, one of the most
important organs for the immune system, which itself is super important for
long-term health. (CALERIE study data.)
Very mild CR in humans has been shown to slow rate-of-aging as
measured by the best rate-of-aging methylation clock (DunedinPACE). (Again
CALERIE study data. Paper: https://www.nature.com/articles/s43587-022-00357-y)
Protein restriction extends healthy lifespan in most/all animal
species tried even without restricting total calories.
A series of studies in a subfield dubbed “nutritional geometry”
showed (in invertebrates & mice) that systematically varying macronutrient
distribution to try to map the whole multi-dimensional space leads to the
optimum distribution being more than 10x as much carb as protein with the
optimal ratio being very consistent across species. See Dietary protein, aging and nutritional geometry - PubMed esp fig 3. These diets are
also inherently low-fat (necessary for carbs to get to that high a multiple
of protein).
Both mice & humans fed high fat diets generally have terrible
long-term health, obesity, & accelerated aging.
Human clinical trials of people with existing heart disease (plaque in
arteries) put on an Ornish or Esselstyn diet of <10% of calories from fat
and no more than 10-15% protein (most people use 80-10-10 as the targets)
show that the heart diseases reverses: the plaque is less on scans and the
recurrence rate of cardiac events is almost zero—better than any current
medical intervention for CVD that science/medicine has at the moment. The
only reason cardiologists don’t use this regularly is that they don’t think
most people can stick to the diet (read this in an actual scientific
journal). The evidence was good enough that Medicare blessed the program as
reimbursable. Now the study cohorts in Ornish & Esselstyn’s clinical
studies weren’t huge, but some of the initial studies were published
decades ago and there have been more recent papers with some longer-term
follow-up, mostly focused on heart/CVD outcomes but I’ve noted no mentions
of higher diabetes or frailty/sarcopenia incidence with the longer-term
followup.
Okinawa is one of the blue zones with good long-term
healthspan/lifespan and the Okinawan diet in the 20th century according to
1 paper I saw was 85/9/6% carbs, protein, fat. These people had lower
incidence of most major chronic diseases (including diabetes AFAIK)
compared to global prevalence rates or genetically similar Japanese (who
ate less carbs and more protein & fat). They ate a huge proportion of
calories from sweet potatoes. 3 paper citations can be found at the
end of this
blog post https://fanaticcook.com/2015/03/14/the-diet-of-okinawa-1949-low-fat-high-carb-very-little-meat/,
which contains an extracted table from one of the papers detailing the
exact components of the Okinawan diet and showing the macro breakdown.
One of the biggest effects of CR & PR is to down-regulate the mTOR
pathway, which seems primarily to be a pathway sensitive to protein intake.
A drug that very selectively exhibits the mTOR pathway was also found
previously: rapamycin. Rapamycin is one of if not THE most reliably
pharmacological agent for extending healthy lifespan of mice and other
species tried. mTOR is up-regulated by dietary protein intake.
Vegetarian diets broadly seem on average to be healthier than
non-vegetarian diets. Vegan diets seem broadly on average to be healthier
than vegetarian diets. Many studies support this (many of which can be
found in the works of the experts noted in the next bullet point).
Vegetarian diets are lower in fat & protein than non-vegetarian diets and
vegan diets are lower still in both.
A huge number of physicians & nutrition researchers advocate vegan or
mostly vegan diets that emphasize whole or unrefined foods for long-term
health (not just cardiovascular disease as noted above), and many of these
experts have huge followings of people who have followed these diets for
years seemingly with good anecdotal results. Huge numbers of books with
extensive scientific references have been published broadly all consistent
with one another and advocating low-protein, low-fat (and especially very
low to no animal protein & fat) by the following people: Walter Willett
(one of the top nutrition researchers/profs in the world, at Harvard, one
of the top cited academic authors in all of clinical medicine), Michael
Greger (MD), Joel Fuhrman (MD), John McDougall (MD), T. Colin Campbell
(prof), Neal Barnard (MD), Luigi Fontana (prof), and the aforementioned
Drs. Ornish & Esselstyn. The advice from prominent GI & immune system
researchers who have written well-referenced books on the subject (Stanford
prof Justin Sonnenburg & Will Bulsiewicz) is also broadly consistent.
The biggest argument for low-carb comes from worries about diabetes
but lots of data shows that diabetes risk is minimized eating the high carb
WFPB type diets advocated by the above authors & others. Lots of
well-referenced material pushing this view (with lots of scientific refs).
Here’s a short partial list. [Note that a good friend of mine whose hba1c
was in the pre-diabetic range for a long time had great success with this
approach after reviewing the below material after having tried low-carb for
a while unsuccessfully.] Here’s some of the material I know about:
The book “Dr. Neal Barnard’s Program for Reversing Diabetes: The
Scientifically Proven System for Reversing Diabetes Without Drugs”
The chapter “How Not to Die of Diabetes” in the book “How Not to
Die” by Greger, and a compendium of related links from Greger’s website: diabetes | Health Topics | NutritionFacts.org
The book “Mastering Diabetes” by Khambatta & Barbaro appears to
also be well referenced. [And it’s n=1 but the personal anecdote
related in
the first review on Amazon from a mom (Anna Soman) who met the
author at a
wedding was a great personal story.]
Human long-term epidemiological data & some clinical studies on named
diets discussed in the scientific literature shows that the diets that seem
to work the best in terms of creating the healthiest long-lived humans are
broadly consistent with the above (Mediterranean diets, blue zone diets).
To the extent that certain human diets other than full CR have been
named & studied clinically for things like the ability to reverse
biomarkers that indicate risk of various diseases (such as reducing blood
pressure or cholesterol) even without the diets being full CR diets (eg
DASH diet, MIND diet) these diets tend to broadly be consistent with the
above guidelines. There’s even data showing a “Daniel fast” for only 3
weeks remarkably lowers various risk biomarkers.
So overall, that’s a lot of disparate lines of research, with a mix of
human data and animal data, and many variations on the exact details, all
generally pointing to the same basic conclusions.
Now back to the meta-analysis paper you shared. Meta-analyses often suffer
from many problems, such as squishing together a very diverse set of papers
that all use different doses. But the most likely problem I’m guessing is
that, without checking, my guess is that most of the studies that they
include that show no benefit from switching away from (sat) fat in a human
diet have 2 problems: (1) that we’re talking about deviations from a pretty
average/typical starting diet (which is terrible), and (2) I’ll bet that in
many cases the calories that replace the fat cals are often refined carbs
rather than WFPB veggies, fruits, whole grains, & legumes.
Plenty of evidence shows that lowering cholesterol (total and/or LDL) via
either diet or drugs lowers CVD events, in a dose dependent manner. Some
people claim that the benefits from statins (lowered cardiac events on them
is not in question) come from other effects they have rather than the
cholesterol lowering, but consensus in the field is that the cholesterol
lowering is important and the similar event lowering from lowering
cholesterol by only dietary means strongly suggests that the other side
effects of statins (which are in general different from the other side
effects of the low-fat dietary interventions) are not to be solely credited
with statins benefits."
One example of many where veganism becomes impractical. Impracticality is a big issue - you need to control for many more factors - for example, we cannot assume having to take multiple supplements is a harmless thing - there is anything from mislabeling to contaminants to undeclared additives.
When a lot of things become impractical - you also risk several issues, such as social isolation, psychological problems, and poor adherence. Psychosocial problems do affect health negatively.
There are also potential side effects for CR which are poor thermotolerance, loss of libido, sexual dysfunction, chronic fatigue, poor sleep, muscle weakness, infection risks, impaired wound healing, etc.
There is also a very real probability that CR or low protein diet may shorten the lifespan in some people.
These are completely unproven - show me the evidence that will be easier to do? How do you know that we can regenerate bone and muscle mass in say 40 years? There is literally no evidence that we can do that even in animals right now.
Eating “mostly plants” does not mean veganism at all. That’s literally not vegan by definition. Not only that, Michael Pollan claims we evolved to be omnivores. Mostly is intentionally imprecise - it means above 50%, but less than “almost all”. It does not mean veganism or even lacto-ovo-vegetarian.
The Scientific Consensus of the AHA literally recommends at least 2 servings of fish per week, but makes no similar recommendation for fish oil supplements (not to mention, there commonly are issues with supplement quality). By definition, that is a recommendation against veganism or vegetarianism. The ACC recommendations point to the Mediterranean diet while minimizing processed meats and sugar intake - specifically with an emphasis on increased fish intake. That is literally against a vegan or vegetarian recommendation.
I’ll also mention Levine herself says she eats fish. She also does not know if IF is even beneficial and emphasizes calorie restriction can be harmful in some.
Veganism is definitely practical. The fact that many people (esp effective altruists) are vegan shows it. B12 supplementation is easy af (I have high blood levels). Taurine+carnosine+creatine is harder, but these are not necessary nutrients (whether or not they prolong already-longer-vegan-lifespan is unknown, but vegans do live longer at least than non-pescetarian omnivores).
These are completely unproven - show me the evidence that will be easier to do? How do you know that we can regenerate bone and muscle mass in say 40 years? There is literally no evidence that we can do that even in animals right now.
They slow decline in muscle mass - we’re not sure about regeneration yet (though in a few decades, fast AGI timelines may make the latter feasible). Slowing decline is strictly easier than regeneration, and these are a possible alternative to eating high-protein later in life (which carries its own associated risks, even if those risks are currently lower than the risks of sarcopenia)
Eating “mostly plants” does not mean veganism at all. That’s literally not vegan by definition. Not only that, Michael Pollan claims we evolved to be omnivores. Mostly is intentionally imprecise - it means above 50%, but less than “almost all”. It does not mean veganism or even lacto-ovo-vegetarian.
No it does not mean veganism, but we didn’t have to get into a huge debate over veganism here. I can change all my posts to “mostly plant-based” and that’s that. Walter Willett, the Harvard nutritionist says “less meat” but there probably isn’t a huge difference between a little meat and no meat.
The Scientific Consensus of the AHA literally recommends at least 2 servings of fish per week, but makes no similar recommendation for fish oil supplements (not to mention, there commonly are issues with supplement quality). By definition, that is a recommendation against veganism or vegetarianism. The ACC recommendations point to the Mediterranean diet while minimizing processed meats and sugar intake - specifically with an emphasis on increased fish intake.
That is literally against a vegan or vegetarian recommendation.
This does not mean it’s the best recommendation - AHA recommendations are not truth. If we look at the mortality hazard ratios, vegetarianism has the strongest evidence against ischemic heart disease. Effects are weaker on other causes of death (but still exist)
==
There are very very wide ranges on calorie restriction, but 10% is not a severe amount of CR, and already does a lot to reduce epigenetic age. As CR becomes more severe, the variance in outcomes becomes much wider, but prolonged CR is extremely difficult for most people.
The fact is that veganism is strongly associated with a high incidence of multiple deficiencies - it’s plenty impractical in many people. It’s also associated with negative mental health indicators (depression/anxiety/mood disorders/self-harm), lower lean mass, and osteopenia - that’s more than enough pause. Unsupplemented vegan diets are much more likely to have worse brain health and we do not understand all the possible reasons. It could end up being say the central action of IGF-1 being better for the brain for example. If that’s true - it could be say 95% pescatarian/Mediterranean diet + IGF-1R antagonists that do not cross the BBB is one way to go about it. But we don’t know. Now let’s say one is concerned about say long-term CVD risk with literally no risk factors and a “perfect” lifestyle (according to current guidelines) - how much purported absolute risk reduction in CVD risk would there be if we simply added/substituted fatty fish intake with all other lean meats (to maximize EPA/DHA intake) and added say 15g/day psyllium husk (as food) as opposed to switching to veganism with “perfect” supplementation?
Now try running a minimum daily calcium intake of 1000 mg/day (IOM) without calcium supplementation. Show me how you get enough calcium with a vegan diet with total grams of each diet. Then tell me how many pounds of vegetables you need to actually get enough? It quickly becomes clear a spreadsheet of a unicorn vegan diet is impractical for most people. Not to mention, calcium supplementation, but not dietary calcium, has a significant association with CVD.
There is a much faster decline at age 50 for lean mass. How many years do you have before age 50? It’s a pretty big bet to assume you won’t already have significant sarcopenia or osteopenia by the time we actually have advances in new drugs if it even happens. It’s unclear what the impact of low protein intakes among the young is on the prevalence of sarcopenia among the elderly either.
I’m not claiming AHA recs are “truth” but it does reflect the general expert consensus. The strongest evidence is not “truth”, but the strongest evidence out there is very different than what you were claiming as the strongest evidence. You better have a very, very strong case to take a contrarian opinion with strong causal evidence base with a strong effect - if there are significant risks. Contrarians are usually wrong. And if you size your position incorrectly - you risk significant losses. I don’t see the point in a potential small benefit in absolute terms to trade for a potentially significant loss. If I am betting contrarian - there better be a big enough potential benefit in all-cause mortality with relatively low potential risk if I’m wrong.
Show me mortality hazard ratios with real statistical significance where isocaloric adjusted and controls? AFAIK, there aren’t any such long-term studies. There are a lot of potential confounders in using mortality hazard ratios in observational studies when we look at diets. The main limitation is healthy person bias - which is huge - “meat eaters” generally translate to being more likely to smoke, eating more highly processed foods, and doing other potentially harmful things.
Let’s try looking at a similar subpopulation cross sectional with a wider range of meat intakes. There were wide ranges of meat intake in the Adventist Health Study 2 with no detectable health difference - but pescatarians had the best all-cause mortality reduction.
There is literally no moderate or strong evidence that switching to a vegan diet with supplements will result in a strong absolute risk reduction in all-cause mortality and/or a significant increase in quality-adjusted life years. An extrapolated potential absolute risk reduction is insignificant for low-protein diets if we use rat studies (which also point to high protein in older rats). Hardly worth the bet even if we assume genetically diverse cross-animal studies replicate these findings.
Meanwhile, we have some evidence against veganism - mental health/depression, bone health, and lean mass are real issues even if we completely address all known deficiencies with “perfect” quality supplements and a unicorn vegan diet on a spreadsheet.
I am not “searching” for health reasons to avoid being a vegan or 99% vegan + low protein diet btw, I’m pointing to real-world issues that are clearly unresolved for what appears to low potential benefit when we run potential absolute risk reduction vs the potential harms. If it was clear to me that veganism or vegetarianism had a strong potential benefit in absolute risk reduction with a strong evidence base with relatively lower risks - I’d jump on it.
I suggest you read this piece from Kaeberlein about anti-aging diet hype (which Levine agrees with btw):
Vegetarian diets are worth trying for many people (if only b/c they are better for the planet + allow the planet to support more people w/o land/fisheries use conflicts), and it’s not too hard to test if one “feels worse” on a diet (I acknowledge that Irene Pepperberg feels worse on the diet and she cares about the moral case way more than most). Many people do not feel worse on such diets, some do. For the ones who don’t feel worse, vegetarianism is continually worth trying both for ethical+land use + health reasons. Both Al Gore and Arnold report feeling better after going veg*n
Conflicting evidence was found on the association between vegetarian or vegan diets and depression. Eleven (44%) of the outcomes indicated that vegetarian and vegan diets were associated with higher rates of depression, while seven (28%) outcomes revealed beneficial effects of the diets on depression. Seven (28%) outcomes found no association between vegetarian and vegan diets and depression, although two of these studies found a higher risk of depression in some groups. The quality of evidence was rated as good for four of the studies with the remaining 19 studies rated as fair. The evidence on the effect of vegetarian and vegan diets on depression is contradictory, possibly due to the heterogeneity of the studies analysed
Unsupplemented vegan diets are much more likely to have worse brain health and we do not understand all the possible reasons. It could end up being say the central action of IGF-1 being better for the brain for example. If that’s true - it could be say 95% pescatarian/Mediterranean diet + IGF-1R antagonists that do not cross the BBB is one way to go about it
This is a strong claim and we do not know. In any case, I supplement with supplemental plasmalogens from OpenCures (these also attach the plasmalogens to omega-3’s). Reducing central aging rate >>> everything else (b/c regeneration+response to follistatin/slowing down further decline is always easier in a body that is less aged) and lower mTOR is lower aging
Now try running a minimum daily calcium intake of 1000 mg/day (IOM) without calcium supplementation. Show me how you get enough calcium with a vegan diet with total grams of each diet. Then tell me how many pounds of vegetables you need to actually get enough? It quickly becomes clear a spreadsheet of a unicorn vegan diet is impractical for most people. Not to mention, calcium supplementation, but not dietary calcium, has a significant association with CVD.
Calcium is easily found in tofu/soymilk/nut milks + certain vegetables, and too much calcium is associated with adverse cardiovascular outcomes + muscle cramping. I have to specifically get nut milks with low calcium b/c I am concerned enough. There are many many other nutrients that one should be way more concerned for.
Supplementation in the form of fortified milk can increase CVD risk - but this may be only in those who already have plenty of dietary calcium. If tofu/nut milks is your only real bioavailable source of calcium, it’s easy enough to control calcium intake to the desireable level and no more… Meat-eaters often tend to eat fortified milk on top of the calcium they get from other sources.
Reducing core aging rate is the most important thing for increasing the potential maximum lean muscle mass you have at any age (in a less aged body where osteoblasts/stem cells are less damaged, you can weight-train at later ages for higher gain at the same age). Stem cell depletion (esp of the satellite cells) is a feature of aging and anything that reduces oxidative stress/aging rate should factor into that, and it is the factor which drives whether or not you can gain muscle at later ages. In any case, a book based on the Harvard Grant Study says that it is later-life exercise that matters way more for longevity than early-life exercise.
Muscular response to follistatin will be overall higher in a less aged individual, and may more than make up for earlier deficits in protein synthesis due to vegetarianism/calorie restriction.
Teriparatide can be used to increase low bone density. I have friends at Minicircle who are also currently running trials (like follistatin plasmid therapy and gene therapy) for increasing muscle and even bone mass [they offered to put me on the trial - I am waiting for results first before I consider it]. I have several decades before I have to worry about the detrimental effects of low muscle/bone mass - by then it will be MUCH easier to find therapeutics to treat them, and they are much more likely to work in a less aged body. Right now it is not an issue - I just need to get not-too-frequent DEXA scans in the future to make sure the mass is not decreasing [and if it is, I can get a teriparatide Rx]. In fact, follistatin may make a low-protein diet ideal for a longer fraction of life than was previously the case.
Aging is not classified as a disease, but sarcopenia/osteopenia are diseases, and it is way easier to create drugs/therapeutics for sarcopenia/osteopenia than for aging. Expect to see many more come soon. Aging is WAY WAY WAY more complex than sarcopenia/osteopenia so it follows that sarcopenia/osteopenia are more “reversible” than aging.
Vegan bodybuilders exist too - veganism does not doom one to lower lean mass if one chooses to eat the needed plant proteins.
I’m not claiming AHA recs are “truth” but it does reflect the general expert consensus. The strongest evidence is not “truth”, but the strongest evidence out there is very different than what you were claiming as the strongest evidence. You better have a very, very strong case to take a contrarian opinion with strong causal evidence base with a strong effect - if there are significant risks. Contrarians are usually wrong. And if you size your position incorrectly - you risk significant losses. I don’t see the point in a potential small benefit in absolute terms to trade for a potentially significant loss. If I am betting contrarian - there better be a big enough potential benefit in all-cause mortality with relatively low potential risk if I’m wrong.
Experts are also disease-focused, and experts still do not treat aging as a disease. AHA is based on CVD, not longevity.
AHA also got its sodium intake recommendations wrong - Addressing The Salt Controversy (Unbiased Review) - YouTube (it’s Na to K ratio that matters, and slightly higher concentrations than the RDA have lower death rates [yes there are many confounders but adding more K is more important than avoiding Na])
And that Seventh-Day Adventurist Study you mentioned that controlled for healthy habits? Vegetarian Dietary Patterns and Mortality in Adventist Health Study 2 - PMC It mentioned that vegans, lacto-ovo, and pescovegetarians ALL have lower death rates than non-vegetarians (for men, vegans are tied with pesco-vegetarians as having the lowest death rates - vegans have lower death rates than lacto-ovo-vegetarians). It’s clear that a vegan diet (EVEN WITHOUT supplementation for “strange deficiencies” like creatine/taurine/carnosine) is associated with greater longevity ON AVERAGE (maybe with higher variance).
The oceans are also now polluted af and fish, unsurprisingly, have microplastics in them [also 2]. The smaller kinds (which are lower in heavy metals and the only kinds that Mike Lustgarten will eat) often cannot even tell the difference between microplastics and their natural diet (eg zooplankton). It’s true that microplastics are now so pervasive that they are present in fruit/vegetables too… [it is not fully clear if microplastics are more present in fish than vegetables, but after writing+researching this, I am prepared to accept the counterintuitive possibility that they are MORE present in vegetables]
There is also a strong extreme moral case for vegetarianism, especially if you care about sustainability. There are also variants of vegetarianism like vegetarianism + bivalves (b/c bivalves do not have nervous systems or suffer) that I am slowly tapering onto (I do not like bivalves that much but am not refusing them on rare occasions)
For many years, there has been interest in understanding if protein source plays a role in health, with the greatest focus on understanding if there is a difference between the effect of plant protein and animal protein. Several studies have suggested that plant-based protein is healthier. One study found that consumption of a plant-based vegan diet decreased all-cause mortality, coronary heart disease and a decrease in risk of developing obesity in humans (98); a more recent study showed that a plant based diet significantly lowered the incidence of cardiovascular disease (CVD), CVD mortality, and all-cause mortality in a cohort of middle-aged adults (99). Vegan diets have also been implicated in reducing the risk of developing metabolic syndrome, lowering triglycerides, blood pressure, glucose, waist circumference and body mass index (100), and decreasing fat mass and insulin resistance (101).
One possibility that has been advanced to explain the beneficial effects of plant protein is that there is a difference in protein quality – the specific amino acid composition of the protein. Plant-based diets have a reduced level of methionine as compared to animal sources, and humans consuming a vegan diet have reduced plasma levels of methionine compared to humans who eat animal proteins (102, 103). As discussed below, significant data now suggests that the level of methionine – as well as of several other dietary amino acids – has a profound effect on health and longevity, not only in rodents, but also in humans. An overview of recent studies is provided in Table 1 and Table 2).
You can do that with rapamycin and/or calorie restriction. All macronutrients activate mTOR, but you can’t starve and decide to never eat. In mice, calorie restriction is the bulk of the effect (caveat in humans, some may live shorter lives with calorie restriction)
The potential longevity benefit from protein restriction on top of calorie restriction in rats extrapolated is not significant when you translate it to humans. You might live an extra <1 year if it pans out and if we looked at it in isolation - but there is no prospective human trial proving long-term protein restriction will yield any extension. It’s quite possible you could live a much shorter life with protein restriction, and perhaps severe calorie restriction as well.
Humans are not mice in a cage. Protein is good for body composition, muscle, and bone. Muscle isn’t going to build as much later in life. Frailty is a real issue for human and body composition. Higher bone density is shown to reduce death from falls and fractures. This won’t be reflected in your mice data. When you count potential quality-adjusted life years, it’s likely you will lose out. Seems like you’re making a bad gamble - trying to gain a little while giving up a lot
You mean fortified foods? The dominant explanation against supplemental calcium is supplementary calcium might be too rapidly absorbed and likely the same goes with fortification based on the examples you gave
The question is whether a diet is likely to be reasonably practical for most people at the present moment. It’s a no.
Early-age exercise has a protective effect on health and brainpower. These have effects on quality-adjusted life years.
That is a third-line treatment because of significant side effects - not a great pick. The first line is to fix your lifestyle because safety is best and can be done long-term. The second line is bisphosphonates in general.
Here are possible serious side effects worth mentioning - hypercalcemia, gout, calciphylaxis (can lead to death by sepsis), and a theoretical risk of osteosarcoma (a few cases that may have been teriparatide described in humans but difficult to say for sure). Not only that, there is a lack of evidence for long-term efficacy - that’s why it’s not generally recommended after 2 years to avoid long-term side effects. You are basically buying yourself time and going back for a limited short run of bisphosphonate which also has its own risks - i.e. atypical femur fractures (Asian is a risk factor for this), erosive esophagitis (perforation can be deadly), osteonecrosis (jaw). All of these are textbook pertinent side effects that shouldn’t be ignored.
Even if you happen to get no side effects and luck out, these drugs are just a short-term bandaid. Not for long-term use. Keep in mind the patients on these aren’t continuing severe protein restriction and/or calorie restriction. So there’s no guarantee you’d get the same exact effects either. I’d suspect such a short-term boost with pretty poor trade-offs won’t hold up as long as you’d think. Have you actually read through the literature on these drugs?
I never said vegans cannot be bodybuilders. Pro bodybuilders are almost always on steroids if they want to win. You need even more plant protein to get protein requirements. I guarantee you these guys aren’t doing protein restriction so not sure why you’re mentioning it - bodybuilding is a completely different game full of negative health effects associated with steroid use and quite a long list of potentially harmful substances.
Optimal quality-adjusted life years which includes functional strength, bone density, and lean mass as measures of frailty are going to be a completely different story.
Sarcopenia and osteopenia are often age-related.
Actually, if you read carefully, the difference in mortality with vegan men was mainly due to ischemic heart disease which is explained by averages of lower LDL and atherosclerosis incidence. However, mice don’t get heart attacks like humans. Not your biased vegan/low protein mice longevity theories that you’re trying to fit in without carefully checking the data.
Risk can be cut in half or more over 30 years with PCSK9 inhibitors, or if one can’t afford it, maybe intermittent low-dose rosuvastatin and ezetimibe if you are very careful with pharmacogenetics and all regarding statins.
You said yourself that CVD is NOT longevity.
But the fact is atherosclerosis which is the underlying cause of ischemic heart disease is a huge impact on all-cause mortality and disability - probably top 1 or 2 depending on your risk factors. Atherosclerosis includes dementia, heart attacks, stroke, peripheral vascular disease, and not to mention - erectile dysfunction etc. Clearly a lot of death and disability in humans not wild-type mice (or most animals actually) that you’re ignoring - doesn’t seem you’re familiar with lipidology or how vascular pathology works in humans.
Ignore quality-adjusted life years just like you are with clear frailty measures ie bone and muscle health at your own peril. You’ve already gotten a T score on DEXA suggesting early osteoporosis it seems. If technology doesn’t catch up you won’t be able to wait as long as you’d think without taking massive risks.
Your kitchen sink to potential longevity doesn’t matter if you’re dead from say frality or atherosclerosis (vegans still die aplenty of atherosclerosis-related causes even with lower LDL on average, especially male. Not to mention, phytosterols in some people are actually more atherogenic! Not something you’d find in mouse studies). Not to mention, your chances could go down a spiral with certain disabilities
Too much uncertainty with microplastics but I just gut the fish, don’t eat the organs, and pee out a good amount of nanoplastics by drinking more water anyways. I don’t eat shellfish. Cuts the bulk of a theoretical risk. And that’s assuming fish inherently has more (I am very picky with sourcing and for a good amount of time I eat hydroponically grown fish that doesn’t have microplastics).
The evidence shows medium to larger size fish accumulate far less microplastic and are able to clear enough out to keep it low on the filet. Maybe about 1 microplastic particle in more than half of select filets in real world instead of resorting to hydroponic fish. My intake of microplastics is probably low enough to eliminate a good amount faster than taking it in - although I’m waiting for a test available to prove it.
Even with trying to avoid it from fruits - with all the supplements you’re taking trying to avoid fish/meats - you probably have a good amount of microplastic intake that you’re not counting - maybe even more than meat. No supplement is certified microplastic-free and even then there’s not much you can do to enforce it. I guarantee you many of the supplements you’re taking has more microplastics than you think.
At this point, lab-grown fish is possible. The first lab-grown chicken meat has just been FDA-approved (but I am averse to it because chicken itself is not a natural organism [chickens themselves have been bred to become overweight]). It will take time for lab-grown fish to reach the market, but the timelines for this are within 5-10 years (‘Fishless fish’: the next big trend in the seafood industry | Environment | The Guardian), which are well before the point before I have to really worry about sarcopenia. I cannot ethically advise people to consume vertebrates, especially at the current world population size.
Plant proteins are different from animal proteins, as I have shown in studies before (because of the low methionine content) - methionine restriction alone can yield many of the benefits of CR without the downsides of feeling hungry all the time. I am also not fully calorie restricted - my basal metabolic rate is 1150 kcal/day, and my calorie consumption is well over that.
You mean fortified foods? The dominant explanation against supplemental calcium is supplementary calcium might be too rapidly absorbed and likely the same goes with fortification based on the examples you gave
The question is whether a diet is likely to be reasonably practical for most people at the present moment. It’s a no.
The fact that numerous vegetarians exist and already live longer than meat-eaters proves your argument moot. Vegetarianism is already reasonably practical for most people, and lab-grown meat will become economical within the next 10-15 years.
Green leafy vegetables (esp collard greens) are also one of the best sources of calcium. Yes the bioavailability is lower due to oxalates but you can cook vegetables to destroy the oxalates.
That is a third-line treatment because of significant side effects - not a great pick. The first line is to fix your lifestyle because safety is best and can be done long-term. The second line is bisphosphonates in general.
I have not seen any real negative side effects from teriparatide. They do not seem as pronounced as those of all the other potential ways to boost bone formation.
Sarcopenia and osteopenia are often age-related.
They are not the drivers of core aging rate.
Not to mention, phytosterols in some people are actually more atherogenic
This needs a strong citation. Vegetarian diets work better on atherosclerosis (and cancer) than other causes of death.
Even with trying to avoid it from fruits - with all the supplements you’re taking trying to avoid fish/meats - you probably have a good amount of microplastic intake that you’re not counting - maybe even more than meat. No supplement is certified microplastic-free and even then there’s not much you can do to enforce it. I guarantee you many of the supplements you’re taking has more microplastics than you think.
Supplements are way purer (and way easier to purify + confirm purification) than whole foods.
Not surprised you are not familiar with the possible issues when you are overly focused on “core aging rates” rather than healthspan by gambling on what will happen in the future by a certain timeline. It’s more likely commercially viable nuclear fusion is coming in 20 years (“will come in next 20 years” has been perpetually the case for the last several decades) to save the planet from climate change rather than some of the biotech advances you are expecting as a reasonable high safety option from an independent patient safety professional.
To be extra clear, phytosterol intake is certainly fine for the “average person” and is one of the reasons (besides soluble fiber intake, etc) why there is lower ischemic heart disease for a diet with a high intake of plants (with a tradeoff of higher stroke relative to fish eaters, if you are vegan), but one cannot assume that all plants always equal good and meat always equals bad. There are specific instances ie low FODMAP for IBS or low omega 6 diets for AERD where it clearly matters to avoid plant-based fats and a range of plants in the diet. You have to account for individual variation always for “precision health”. The problem is when ideological groups claim that there is only one diet and cherry-pick evidence. This has been extensively documented by highly reputable anti-health fraud groups that certain thinly veiled animal rights groups promoting health benefits from ideological veganism as clear quackery and health fraud.
Phytosterols are generally minimally absorbed in a reasonable amount of vegetable intake for the average person, but when it does get in as a xenosterol it can be dangerous. Partly why ezetimibe may be a better option in those cases. Some people won’t realize phytosterol issues until it becomes pathologically apparent because it can show up as a low to normal blood cholesterol level for a long time and the numbers are definitely underestimated.
Here’s a review:
“Accumulation of xenosterols in any significant amount is clearly associated with increased toxicity, and data suggest that at even low levels there may be effects.”
“Increased absolute plaque levels of free CH, precursors and plant sterols predict an ischemic event in patients with advanced carotid artery stenosis.”
Unless they are USP-grade supplements (the list of these are incredibly small where I’m pretty darn sure you aren’t getting only USP grade), you must be kidding. Supplements are as close to the wild west as one can get. The standards are less than highly regulated food, which as you already know still has some issues.
The problem is I guarantee you very few supplements have frequent rigorous independent third-party testing and very few have high actual standards ie AlzChem Creapure creatine monohydrate, assuming you get it directly wholesale without intentional or unintentional accidental batch mixing when it gets closer to the retail side.
Unless supplements have incredibly compelling human data with high safety profiles or aren’t far out of what well-studied human subpopulations can consume from a diet - it should be considered an untested drug that you are gambling on. We’ve seen that with multivitamins/beta carotene/Vitamin E increasing mortality, despite being widely recommended and promoted due to presumed solely benign effects. Tell me what test you could have done to predict higher mortality with that type of vitamin supplementation? There aren’t any predictive ones AFAIK.
Many APIs/compounds used in supplements are literally from China - which is a crapshoot for quality vendors, made worse recently with COVID supply-chain issues. I’ve been to the trade fair personally, I can read/write/speak the language, and have seen what happens there on-site for APIs. Unless you 100% trust all Chinese manufacturers to have high-quality standards for say heavy metals, you should probably actually test your supplements to see if you’ve been taking in tons of heavy metals and other proven toxins at the very least unknowingly. Not only that, a good friend of mine literally owns a supplement and skincare product manufacturing facility in the US. He doesn’t personally take his own supply.
Medical textbooks on supplements point out that as many as one-third or more supplements can be adulterated with variations between batches of the same product from the same manufacturer and when someone comes in for supplement-induced hepatotoxicity - it is difficult to know what exactly caused it when it happens. It’s not uncommon for heavy metals to be higher than the limits.
Risking your liver, kidney or brain isn’t longevity. Your “core aging rate” matters very little if you have a higher risk of neurodegenerative disorders by known toxins like heavy metals above the limits or your liver or kidney isn’t functioning well to remove toxins because say an untested drug or contaminant decided to knock out your kidneys. I’ve seen it happen when a patient of mine (a “kitchen sink” type of supplement taker) took red yeast rice labeled “citrinin free”. It was not citrinin free.
You seem to have a huge bias towards intervention without actually getting all the safety details meticulously down - that is possibly harmful even when assuming you have a large budget and are not particularly concerned about cost-effectiveness.
Any intervention should look at the possible harms. Any potential gain (it seems some of the potential gains you are aiming for are pretty small even if your theory pans out - which statistically for the top experts has piss poor results and does not pan out on average) is not worth large potential losses.
What’s your view on low doses, every other day dosing of: any long half life statin, ezetimibe, ace inhibitor or angiotensin blocker? (Kidney brain health), pde5 inhibitors, Trimetazidine, meldomium? Gabapentin, baclofen, tiagabine for Slow wave sleep enchantment?
