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People With The Lowest Overall Mortality Are Overweight

Discussion in 'Scientific Studies' started by haidut, May 12, 2016.

  1. haidut

    haidut Member

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    This Danish study further cements the status of the "overweight paradox" as something that will not soon go away or be explained away as a statistical anomaly. While previous studies looked at the survival of people with specific conditions and found the mildly obese to fare best, this study looked at overall mortality and found a BMI of 27 to be optimal. A BMI of 27 is well into the overweight category and close to the obesity line of 29.
    Another interesting finding was that obese people did NOT have higher mortality than normal weight people suggesting an inverted U-shape curve with the higher longevity around 27 and diminishing longevity on BOTH sides of the curve.

    Body Mass Index and Mortality Rates in Denmark
    BMI 27: The New Normal?
    Healthiest weight just might be ‘overweight’

    "...The body-mass index (BMI) value associated with the lowest risk for all-cause mortality is now 27, down from 24 in the 1970s, according to a large Danish cohort study. That means the lowest-risk BMI is now in the overweight category, said Børge Nordestgaard, MD, of Copenhagen University, Denmark, and colleagues in the Journal of the American Medical Association. In addition, compared to BMIs in the conventional normal range, the hazard ratio for all-cause mortality associated with a BMI of 30 or higher has dropped from 1.3 to about 1.0 over the same time period, the Danish scientists said. "To the extent these findings are replicable and generalizable, they raise both interesting hypotheses and reiterate points made in earlier work," said Tapan Mehta, PhD, an obesity researcher the University of Alabama at Birmingham, in an email to MedPage Today. Mehta is also on the advocacy committee of The Obesity Society."

    "...As a group, overweight people are living the longest nowadays, suggests an almost four-decade study in Denmark published May 10 in JAMA. And obese people seem to be at no higher risk of dying than those of normal weight. The new analysis fuels ongoing debate about what’s a healthy body mass index — especially in light of rising obesity rates (SN: 5/14/16, p. 5), improved heart health treatments and other factors influencing health and longevity. “This is a very carefully done study,” says Rexford Ahima, a physician who studies endocrine disorders at the University of Pennsylvania School of Medicine. The findings strengthen the notion that “BMI as a number alone may not be sufficient to predict health and risk of death. It has to be taken within context.” Ahima was not involved in the research but has analyzed previous studies urging a rethink of how BMI influences mortality."
     
  2. Westside PUFAs

    Westside PUFAs Member

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    This M.D. from the comment section of your 2nd link has a good response:

    "Studies like this will get big press because it perpetuates the myth that thinness is unhealthy and that it's beneficial to be overweight.

    It is true that we have better treatment for obesity-related illness, such as hypertension, dyslipidemia, and diabetes, so it's probably not as deadly to be overweight or obese now as it used to be. However, in addition to this, confounding variables may be at work here as well.

    There are a number of compounding variables that may give the appearance of increased mortality at lower BMIs in studies of this nature. Among these are smoking, which may result in pulmonary cachexia or an increased risk of cancer, occult malignancies, and other chronic, non-obesity-related illness. All of these conditions result simultaneously in an increased prevalence of lower BMI and increased risk of mortality.

    Recently, Aune, Sen, and colleagues conducted a meta-analysis of previous large cohort studies and specifically addressed the issue of these confounding variables. Overall, they examined the data from more than 30 million people!

    When they left out smokers, the optimal BMI for never-smokers appeared to be 23-24. When they looked at healthy never-smokers (to remove confounding by illness), the optimal BMI appeared to be 22-23. Lastly, when they looked at healthy, never-smokers with long-term follow-up (to remove confounding by occult illness), the optimal BMI was lower still, at 20-22 [Aune, Sen, et al. BMI and all cause mortality: systematic review and non-linear dose-response meta-analysis of 230 cohort studies with 3.74 million deaths among 30.3 million participants. BMJ 2016;353:i2156. doi: http://dx.doi.org/10.1136/bmj.i2156 (Published 04 May 2016)].

    This should be enough to dispell the myth that thinness is unhealthy and that a BMI of 27 should be some sort of goal.

    Moreover, much of the so-called obesity paradox can be explained by an interesting study published in the August, 2014 issue of Mayo Clinic Proceedings. This demonstrated that it is MUSCLE MASS that correlates with the risk of mortality, not FAT MASS, and that the apparent increased risk of death in thin people is not from not having enough fat, but from not having muscle, and that the mortality benefit seen in overweight folks was not from their fat, but because they tended to have a normal amount of muscle. [De Schutter, Lavie CJ, et al. Body composition and mortality in a large cohort with preserved ejection fraction: untangling the obesity paradox. Mayo Clin Proc. 2014 Aug;89(8):1072-9. doi: 10.1016/j.mayocp.2014.04.025. Epub 2014 Jul 16].

    There is no danger in being thin per-se. If you're thin because you have sarcopenia (not enough muscle), that's a problem. If you're thin because you have emphysema, cancer, poorly controlled type-1 diabetes, chronic kidney disease, and so on, that's a problem. The studies I've noted should be a reality check for those who have read "BMI 27: The New Normal?" and conclude (or believe) that thinness itself is unhealthy."
     
  3. OP
    haidut

    haidut Member

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    His argument is not valid. The exact same conditions he listed as reasons for lower BMI are actually much more prevalent in people with higher BMI, all other things being equal. People with cancer or kidney disease do not become very thin until the later stages of their disease, and on average it is much more likely to find a person with higher BMI having one of these conditions than a person with lower BMI. That being said, the study was on mortality, not health, so I agree that the conclusion should not be "it is healthier to be overweight". However, his arguments do not hold much...weight (pun intended). And btw, this specific study controlled for some of these variables (i.e. cachexia, diabetes, kidney disease were some of the conditions they actually looked at and excluded).
    I think the problem is that instead of using BMI as a sign/symptoms of something being potentially wrong, most doctors look at it as a goal to be achieved with dieting and exercise and drugs, and that is certainly contributing to the issue of underweight people having poorer health. If the question was framed as "what is causing people to have high BMI" it would probably result in a much more productive research than saying "low BMI is good, so let's get to it no matter how".
     
  4. Westside PUFAs

    Westside PUFAs Member

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    You named this thread with the term "overweight" in the title but then your first sentence says "This Danish study further cements the status of the "obesity paradox"

    If we look back to this thread: Scientists now think that being fat can protect your health

    I said: "From one of the studies they cite:

    "Conclusions and Relevance Relative to normal weight, both obesity (all grades) and grades 2 and 3 obesity were associated with significantly higher all-cause mortality. Grade 1 obesity overall was not associated with higher mortality, and overweight was associated with significantly lower all-cause mortality. The use of predefined standard BMI groupings can facilitate between-study comparisons."

    Association of All-Cause Mortality With Overweight and Obesity Using Standard Body Mass Index Categories: A Systematic Review and Meta-analysis

    And that is why the term "obesity" in the paradox should not be used and anyone who supports this view should simply use the term "overweight paradox."
     
  5. robknob

    robknob Member

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    When I see this I think people who are genetically prone to storing fat are also storing away the toxic pufas and heavy metals they ingest, keeping them locked away in a sense, and that protects their vital organs and they end up living longer. The thin fast metabolisms can do well when they are young, but after enough time in a toxic environment, liver and kidney damage accumulate and they start to age quickly. If the environment is non toxic then I think the thin fast metabolisms will outlive the storers. RP himself has been careful to eat healthy for a large part of his life, so I think he will live a lot longer than a fat man his age.
     
  6. OP
    haidut

    haidut Member

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    Fair enough, I changed it to "overweight paradox".
     
  7. tara

    tara Member

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    Nice finds.
    I have not seen this myth you speak of propagated, not have I seen any significant number of people taking BMI 27 as some sort of goal. Have you?
    I take these findings Haidut has posted as confirmation that BMI 25-30 is consistent with better health for many people than is BMI 18-25, and therefore it is meaningless to give it a general label of 'overweight'.

    This is not in the above studies, but from more general principles: The stats only tell something about averages, not about individuals. People can be healthy at a wide range of BMIs. Some people may be overweight and some people underweight at BMI 22 or 27 or 32, depending on their own body, and quite possibly changing over adult lifetime. Probably not so many would be overweight at BMI 22 or underweight at 32. But if one happened to be in the relevant minority, one could be harmfully mislead by treating the average as a prescriptive ideal rather than just descriptive. Trying to force it (in either direction) by under- or over-eating can cause harm. As can the currently common disrespect aimed at people mis/labelled 'overweight', counteracting which is one potential benefit of having these studies known.
     
  8. tca300

    tca300 Member

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    The thing I worry about with being overweight specifically from extra fat mass, not lean mass is that adipose tissue is a major source of estrogen. It's also nice to be able to move my body with ease. I've been pretty heavy before, and it makes walking, climbing, swimming, getting up off the floor, walking up stairs, playing with your kids, sleeping on a hard surface etc.. really difficult. Also makes you more injury prone, from my experience. Not to mention, extra chub isn't very attractive in my vain opinion.
     
  9. Tarmander

    Tarmander Member

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    Nice post. I was going to actually come here to say this.

    I will add this. These studies are interesting, but I think of BMI a bit like height. Yes you can say that small people tend to live a bit longer then tall people, or that tall people have certain other advantages. But as soon as you act on these by breaking your leg bones and separating the edges so that new bone will grown in between and you will be taller after you heal...well are you really helping yourself ? (This is popular in certain Asian countries) As soon as you have to use force on your body to get it to do something, you invite in disease.
     
  10. tyw

    tyw Member

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    That could be a possible mechanic ;) -- relatively inert fat stores as isolators of stressful compounds.

    Also, this is in Denmark, which does have very big seasonal swings in daylight hours (Peat would link low daylight hours to higher stress)

    On the other side of the spectrum, we've got the Okinawans in a sub-tropical region, staying mildly calorie restricted (10-15%), and having an average BMI at 30 years old of about 22.0 for females and 22.4 for males. (this climbs to about 24 when they are above 65 years old, which the researchers of the first paper below attribute to height loss)

    - http://www.okicent.org/docs/anyas_cr_diet_2007_1114_434s.pdf
    - Caloric restriction, caloric restriction mimetics, and healthy aging in Okinawa: controversies and clinical implications. - PubMed - NCBI
    - Caloric Restriction, the Traditional Okinawan Diet, and Healthy Aging - WILLCOX - 2007 - Annals of the New York Academy of Sciences - Wiley Online Library

    This is not a fair comparison though, since the Okinawan diet at the time of the study was definitely low PUFA.

    Also, in my mind, "chronic calorie-restriction" means "PUFA depletion" -- you are constantly mobilising and getting rid of PUFAs when chronically calorie restricted. This PUFA depletion also pans out in animal experiments.

    Correspondingly, the "youth hormones" like DHEA remain higher in the Okinawans. IMO, this has everything to do with PUFA depletion and higher metabolic rate (calorie restriction reduces body mass, but increases metabolic rate per unit mass).

    Where your body mass settles after chronically adopting metabolism enhancing interventions will definitely depend on a multitude of factors.
     
  11. tara

    tara Member

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    Yeah.
    Funnily enough, I haven't heard so much about the 'height epidemic' threat to the public health and health system where I am yet.
     
  12. Peater Piper

    Peater Piper Member

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    Are there any near obese Centenarians?
     
  13. Westside PUFAs

    Westside PUFAs Member

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    No, which is another reason to not have excess adipose tissue. And your chance of becoming a centenarian is extremely low. There have only been 5 well documented cases of centenarians who lived to 117 and older. In a world of 7 billion, you are extremely unlikely to be one of them.

    c.jpg
     
  14. m_arch

    m_arch Member

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    That's an interesting take TYW. All I've heard before about calorie restriction on raypeatforum is that its inherently bad since it lowers metabolism.

    What you're saying makes sense though, like usual. Context is king...

    When I was travelling around Aus, I was on an epi-paleo diet (keto with focus on seafood for those that are curious) and I was lean like a rake. I've probably gained 10kg since then since Peating, and a lot of it is on my abdomen which is now obviously thicker. And I hear this is common when people switch to a more peat-inspired diet.

    My thoughts are that the extra fat is possibly estrogenic... However I guess we're looking at context here again, and the extra fat has almost definitely come from sugar (and so its a saturated fat). My CO2 readings are high so I doubt I have anything to worry about.

    Like Paleo Osteo I also need more fat to feel good
     
  15. lollipop

    lollipop Guest

    Interesting statistics. My first guess would have been much higher than 5 living 117+yrs. IMO, emphasizes the importance of the quality of life lived rather than stress over quantity. Hence diet plays a major role in quality.
     
  16. Ahanu

    Ahanu Member

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    The 2 oldest humans were both smoking. I dont know how much sense it makes to compare the majority with the few centenarians..
     
  17. tyw

    tyw Member

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    Well, context be king, but the king lives by the laws of the Universe ;).

    What we try to do is to bring plausible mechanical explanations to empirical observations, in hopes of making better decisions for the future.

    Observation always wins, but we also always try to assign mechanics to observation.


    Sidenote: I will always doubt that "extra fat" comes from sugar. Rates of De novo lipogenesis are horribly low unless in massive caloric excess, which these researchers (using a metabolic ward study), claimed "Glycogen storage capacity in man is approximately 15 g/kg body weight and can accommodate a gain of approximately 500 g before net lipid synthesis contributes to increasing body fat mass." -- Glycogen storage capacity and de novo lipogenesis during massive carbohydrate overfeeding in man.

    What is happening is more likely that sugar oxidation partially inhibits fatty acid oxidation, and allows for more incoming dietary fat to be stored. Therefore what is stored is most likely the fat that was consumed in a mixed meal.

    If we want to get pedantic, the Randle Effect is not uniform across tissues :blackeye:. ie: in some tissues, fatty acids inhibit carbohydrate oxidation more so (eg: cardiac muscle), in some tissues carbohydrate oxidation inhibits fatty acid oxidation more so (eg: the liver), and in some tissues like the muscles, glycogen synthesis may even bypass the question of carbohydrate oxidation completely :banghead: (carbohydrate gets quickly stored, and therefore do not participate in Randle-inhibitory effects, which have everything to do with metabolic by-products and metabolic enzymes).​


    But yes, Peat Principles are just "principles". Exact implementations will vary. Personally I had the experience of weight maintenance (around 76-78kg) on my 1.5 years of keto, and then the experience of rapid fat loss (to 71kg) on a Peat-inspired PUFA depletion protocol ;)

    .....

    Also, to clarify my claim that "Chronic PUFA depletion is akin to PUFA depletion".

    We need to distinguish Dietary PUFA restriction from metabolic PUFA clearance.

    Not eating PUFA is restricting PUFA input from the dietary side. This is the preferred choice.

    Caloric restriction usually also means a reduction in PUFA (since you reduce total food quantity), and increases metabolic turnover of PUFAs (likely mechanics explained below).

    First, the observations:

    - You will find the same trend toward PUFA-depletion-esque metabolic improvements (as measured by O2 consumption and proton leak) in 30% calorie-restricted rats (they are eating 70% of "what they should"). The Calorie Restricted diet is still what I would call a high PUFA diet (30% fat, all Corn Oil) -- http://biomedgerontology.oxfordjournals.org/content/56/3/B116.full

    - Same thing, but much more detailed study showing decrease in Tissue Unsaturation and just overall better mitochondrial mechanics (less ROS and more O2 consumption) with Calorie Restriction despite having PUFA in the diet -- https://biomedgerontology.oxfordjournals.org/content/61/8/781.full

    I like how you can see which tissues is PUFA is depleted the most, which are usually the peripheral tissues and the liver, and where it is conserved.

    Also note that this study showed a marked difference in Unsaturation Index -- number of double bonds, which is probably the better indicator for "PUFA depletion", rather than total moles of PUFA. eg: 10 moles of 22:6 (DHA, 22 carbons, 6 double bonds) is much more peroxidisable than 10 moles of 18:2 (Linoleic acid, 18 carbons, 2 double bonds).

    Sidenote: some supporting evidence that brain PUFAs are preserved in rats under caloric restriction -- Long-term calorie restriction has minimal impact on brain metabolite and fatty acid profiles in aged rats on a Western-style diet. - PubMed - NCBI . I would personally expect humans to behave in a similar fashion, where endogenous auto-regulation of brain PUFA content occurs when PUFAs are restricted. IMO, this is the preferred route


    Of course, the Okinawan People of the 1950s were eating only 2.3g of PUFA a day (4.8% of 1785kcal is around 2g of PUFA) -- http://www.okicent.org/docs/anyas_cr_diet_2007_1114_434s.pdf

    This is close to best context for PUFA depletion to take place.

    But NOTE! As Denise Minger pointed out, Roy Swank actually helped many Multiple Sclerosis patients on a diet that was high carb and 10-40g PUFA a day :android: -- https://rawfoodsos.com/2015/10/06/in-defense-of-low-fat-a-call-for-some-evolution-of-thought-part-1/

    My personal pet theory for this observation is that PUFA oxidation, while bad on many levels, does not actually stop Complex 1 activity as much as Saturated fat does. This is again found in Peter@Hyperlipid's FADH2:NADH ratio posts, but the short answer is that oxidising PUFAs still allow insulin to signal properly, and therefore any NADH from carbohydrate oxidisation is allowed to be processed, while insulin still allows further carbohydrate intake into the cell.

    Is this ideal? In my opinion, no. I'd rather see PUFAs being kept low, and overall fat intake not be very high either.

    ----

    Why I say "Chronic Calorie Restriction is akin to PUFA depletion" is due to the likelihood of stored PUFAs being mobilised more easily. This PUFA-preferred mobilisation of stored fatty acids is most likely true everywhere except the nervous system.

    So you have a case of energy deficiency (any PUFAs that are eaten have pressure to be oxidised), constant fat mobilisation (because of calorie restriction), plus the fact that PUFAs are likely to be mobilised in this context and disposed of. Do this long enough, and you're PUFA depleted, despite eating more than what Peat (and everyone here) would consider healthy.

    For many reasons discussed on this forum already, this is not an ideal route to take (side effects of PUFA oxidation during the depletion process, plus PUFA breakdown products). This is probably made even worse when you start from a place of being overweight and with a life time of PUFA consumption.

    Calorie restriction in this fashion is not recommended o_O, but it likely does explain how calorie restricted organisms get PUFA depleted at some point. PUFA restriction is the more sensible methodology to use.


    ....
     
  18. m_arch

    m_arch Member

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    Damn that's good info.
    Does protein interact in any potentially destructive ways with Carbs?
    I tried your rice diet and after two meals in I was bored of it... However I blamed a lack of fat, after the past few basic meals I've had (chicken or lamb with rice) I'm thinking perhaps it was the lack of protein that wasn't satisfying.

    You say that dietary pufa depletion is the ideal - what about supplements like niacinamide and aspirin? From memory @haidut and others have posted about gaining weight using these. They inhibit the fat from being oxidised, and so it instead just goes into storag, I take it? Basically not a good strategy for long teerm
     
  19. tara

    tara Member

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    That's a bit circular - excess = more than optimal.
     
  20. tyw

    tyw Member

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    Well, Walter Kempner (creator of the rice diet) said himself that his diet was "a monotonous and tasteless diet which would never become popular...." ;)

    I didn't eat exactly according to his prescription of course (eg: definitely some eggs and lean protein, definitely added salt), but it's definitely a boring diet. Good thing I'm a boring person :oldman:

    ----

    Protein + Carbs is a bit too broad a topic to give a coherent answer to. We're talking about whole food sources here, and whole food sources have at least protein and carbs (and meats will likely have fat as well). We will have to delve into specifics of particular amino acids to distinguish their effects, but I honestly don't see that as a useful place to discuss the Protein + Carb combination.

    Specific amino acids should be discussed on the basis of their own individual effects.

    If anything, Protein + Carb is more ANABOLIK :wtf::wtf::wtf: to ensure ur gains stayz loyal :wtf::wtf::wtf:. (Just means that building and holding on to lean tissue is probably better with protein + carbs). I won't discuss mechanics here, search all the physique-obsessed sites for info.

    ----

    As much as I support Niacinamide, caution needs to be applied to its use.

    I claim that Niacinamide should only be used during daylight hours, and should always be used together with adequate energetic intake. Using it at night will likely lead to disruption of healthy bodily cycles.

    If you really want to geek out on Niacinamide and NAD+ mechanics as a whole:
    AND NOW I RANT ABOUT DIS :banghead::banghead::banghead:

    The problem is, this is all details ... no guiding model is presented. No model as a guide means no basis for falsification

    (ノಥ益ಥ)ノ ┻━┻ :blackeye:

    NOTE: This is not to say that discussion of this level of granular detail is worthless. But without a guide post to say, "What does this really specific pendantic fact about BLEHFOO signal mean in terms of our model of cellular energetics?", you will lose your way in talking about endless signalling details.

    It is also a way to twist the narrative in a way that may seem logically sound by signalling mechanics, but not compatible with other more fundamental observations (high mitochondrial respiration). I personally think the authors of those 2 articles get the details spot on, and their conclusions wrong (like how they couple NAD+ and SIRT1)

    Sorry, but I insist that information be presented alongside a practical guiding model (which may be falsified), which allows us to actually converge on useful solutions (as opposed to more and more discussion ....)​

    I've said this many times -- Nature is horrible architect ....

    The cell is exactly akin to the bloated mess of software you get when some centrally-controlled Government agency decides to hire 300 contractors to piece together something workable, only to realise 3 months later that the implementation is useless ...

    And then they proceed to hire another 300 contractors to clean up the mess of the previous 300 ....

    And on and on .... until you've got some hulk of a steaming garbage piece of software that only understands you if you stand in front of it and wave your hands in a figure 8 formation :grumpy: and chant the magic password :ghost: and issue some sacred command in COBOL :speechballoon:

    All I see with all these enzymes is the cell going, "Oh, I need another way to sense this new signal ... time to make another massively-complex Enzyme :playful:"

    No wonder we have no many redundant sensing systems ..... and no wonder the cell seems to responds to different hormones in the same way (based on Energetic State).

    Reading the manual for each botched implementation (all these individual enzymes) does not tell you how the core of the system works

    All these enzymes are just Signal Flares that decide to make a ruckus with varying degrees of eagerness.

    Some are quick to jump to "LOOK AT ME!!! LOOK AT ME NOW!! DON'T YOU TRIGGER ME SOME MORE :arghh::arghh::arghh:" (SIRT1 can kinda be like this)

    Others only notify you of their presence when you are shocked by the sound of their dead bodies crashing your on floor and ruining your carpet :fire: (FoxO3a is like this)

    Doesn't matter, ALL of them are just signalling tools ( :loudspeaker::loudspeaker::peeking::peeking::peeking: MEEP MEEP! )

    How about fixing the original machinery (Mitochondrial Respiration) that actually generates these signals naturally.

    Back to NAD+, having High NAD+ for the sake of high NAD+ is missing the entire point of having high NAD+ (which should ideally be metabolically generated).

    The point of NAD+ is to use that NAD+ to actually drive further metabolism (feedback to recycling and cleanup and shutdown facilities). This assumes that not enough NAD+ is the reason that your metabolism is bad in the first place, which is definitely NOT ALWAYS THE CASE (see all the possible enzymatic failures, or Nitric Oxide overload, or heavy metal overload, or lack of co-factors, or perhaps the enzymes used to transport NAD+ metabolites into the mitochondria are not working well to begin with, etc ....)

    "Niacinamide causes insulin resistance" (and therefore potentially fat gain) is potentially true .... especially if you take it at the wrong time.

    Watson correctly stated that SIRT1 shows some amazingly stubborn Circadian Rhythmicity. Dark => high SIRT1, Light => low SIRT1

    What happens when you artificially mess with the body's SIRT1 signalling by shutting down SIRT1 during darkness? CHAOS :wtf::wtf::wtf: See some of the papers cited in those linked articles, which show how failure of SIRT1 to rise at night leads to insulin resistance the next morning. Biased observers (against interventions like Niacinamide) will look at this and start pouring hate onto Niacinamide and other SIRT1 inhibits, and then start chanting for the chugging of copious amounts of Resveratrol :hilarious:

    We should not think that we should inhibit SIRT1 all the time -- these things work in cycles, and those cycles need to be respected. However, when the time is right, we push HARD on the metabolic support. Again, take metabolic supportive agents like Niacinamide when there is a need to meet higher energy demands (or added stress), and then when it is time to rest, it is probably time to rest.

    Note: there are many supplements advocated here that are not "directly metabolically oriented" but are highly beneficial. (Mitolipin!)

    Sidenote: will taking Niacinamide at night be alright if you also eat at night? Dunno. Possibly. Experiment! (remember that I am ranting here ;))​

    Again, everything works in cycles. Estrogen needs to be high at times for cell growth. Nitric Oxide needs to be high at times to deposit cholesterol and heal arteries. Mitochondria cycle between Complex 1 and Complex 2 activity all the time, etc ....

    All we can hope to do with supplements like Niacinamide is to bias these cycles just in time, in just the right amount, to support the required energetic demands placed on the body.

    Systemic changes to things like PUFA depletion leading to long-lasting increases in metabolism requires systemic interventions. (Except Mitolipin :phantom:, that one actually helps you with PUFA depletion).

    In any case, we treat each potential supplement based on its individual merits, and make the intervention choices which we deem appropriate for experimentation.

    -----

    We should also recognise that we cannot force the body's circadian signalling to OBEY just by providing both an energy source and a SIRT1 inhibitor like Niacinamide. You cannot change the course of a Hunking piece of software/hardware by pulling on a couple of levers :penguin:. The only real way to possibly change those rhythms is by actually simulating a 24 hour day (including all the sunlight, the magnetic changes, the air pressure changes, etc ....). Circadian entrainment is powerful.


    TL;DR -- When daylight, METABOLISM TO THE MAX :wtf:. When darkness, Go to sleep.


    ----- END RANT -----
    (as with any rant, mistakes have likely been made ;) faulty logic should be called out)


    Regarding Aspirin, this is a bit of a wild card. It's mechanical effects are basically unknown -- you have Aspirin on cell membrane => some side effects happens (like metabolic uncoupling).

    All we can do is observe those side effects and then test it on ourselves.

    .....
     
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