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Mechanism

Remember the precautionary principal

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The other day I was at a research conference conversing with a good number of intelligent, motivated, health optimizers who were going to great lengths to improve their health through sometimes quite elaborate self-experimentation with novel experimental therapies.   these conversations and hearing their stories motivated me to offer one perspective.here taking a specific example, for consideration.

In a forum of optimizers it is easy to forget the enemy of a good plan is the dream of a perfect plan.   Incremental or lower probability gain is often reached for with disproportionate risk.

Take for example transfusion of “young blood” modeled after parabiosis.  This podcast is priceless but a few nuggets to emphasize here: https://www.ihmc.us/stemtalk/episode-91/

  summary is mine

1) parabiosis in contrast with transfusion therapy has not only blood factors but also the organ reserve and function of the younger organism and psychosocial and physical stimulation of close proximity to a companion ( via suturing the skin together)

2) current data suggest more benefit from diluting old blood harmful factors than enhancing protective factors ( though probably involves both)

3 Risk of infection,

4) risk of anaphylaxis

5) risk of rare but serious  GVHD

6) any method to filter the blood to reduce the risk of infection may also remove any potential benefits

7) perhaps most insidious the unknown - even with thousands using similar technology for other purposes, inadequate data to exclude subtle and delayed hypothetical predisposition to potentially life changing autoimmune conditions such as multiple sclerosis.

Though they obviously stand to gain financially from it I like the Conboy’s proposed solution better ( I will leave you in suspense to listen , otherwise you will miss a lot of other great content such as  increasing evidence for   oxytocin’s connection with protection from sarcopenia,  osteoporosis, etc.

We should certainly be proactive and be willing to take on appropriate risk for our tolerance and values and all be granted the autonomy and respect to make our own choices.

 It is good in making such assessments to consider that a strong motivation to mitigate risk can sometime bring on substantially more risk, cost, or possibility of serious harm than what is likely to be gained by stretch for “perfect”  If after considering all the risks as well as benefits the choice is made to go forward, should something happen regret is minimized knowing the decision was made with open eyes.

 

Edited by Mechanism

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I fully agree, Mechanism.

Another aspect I believe is risk appetite, and specifically risk appetite dependent on the specific individual situation or propensities.

For example, the idea of young blood transfusion simply does not attract me. Injecting the blood of another individual, even if younger and maybe in better health, conceptually seems a violation of my biological privacy and individuality. With the actual potential consequences you outlined.

Whereas I'm pretty much willing to accept the potential risks of cold exposure, which, besides its purported health benefits, fits into my appreciation of self discipline, stoicism, and mental strenght. 

Conversely, some other people may be attracted to parabiosis even though with a knowledge of the potential risks. 

Gambling is part of human nature and, the riskier the gamble, the greater the potential benefit or loss.

At the end though, maybe it's good that the precautionary principle govern, however not excluding small foreys into riskier territories !

Edited by mccoy

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Great comments McCoy.   Besides the risk/reward ( and anticipated probability) considerations I also find like you that philosophy influences my health and lifestyle choices.  

These can change over time too.  I aspire to maintain scientific objectivity being open to new data, and this, in turn, encourages new insights and paradigms in health.

For example, the ancestral paradigm with a whole foods / minimally processed emphasis is a conceptually sound heuristic towards mitigating risk and other benefits.  My initial feeling growing up in the 80s was vegetable oils  are by their nature processed and eschewed them.   This seemed to be supported by the limited lower quality evidence at the time.  

However as the data evolved, so has my position and hence philosophy to be congruent with it.  So although most of my fat intake comes from nuts and avocados ( olives making up only a small % due to the sodium), I do partake in EVOO.  Particularly if enables a particular dietary goal - for example for diversification or if I desire to keep my net carbohydrates modest while gaining substantial weight on a given day and do not wish to exceed my personal upper limit on nut consumption.  

I have had a similar evolution in “unnatural” supplementation staring initially with vitamin B12, then D3, etc.

My own evolution of philosophy makes me sympathetic to individual differences in our preferences, values, risk aversion, subjective assessment of the likelihood and magnitude of benefit as well as personal circumstances in governing health choices.  I feel that the governing principal for a wise choice is one that is based on awareness of the best current “state of the science”  evidence with self-awareness.

Mindful choices also should be congruent with our long term values projecting forward into implications of our choice on our future self and the broader stakeholders including our loved ones.

I like your example of CE.  There is increasing support for the position that fat remodeling and related cell biology ( for example in the peroxisomes and mitochondria) mediates a significant portion of the influence of CR in model organisms, for example through PGC1alpha.  

Indeed, Rosalyn Anderson speculates that part of the mechanism by which 40% CR failed in some mouse strains may be due to inadequate remodeled fat  to mediate the metabolic and signaling switch seen in CR.  Recall follow-up work demonstrated less aggressive CR worked for most of these such that now ~95% of models have demonstrated CR benefit.  So is this the CE effect on that minimal residual fat needed to mediate CR or another mechanism?

Adipose tissue remodeling and metabolic pathways indeed seem to be playing an important role - but whether CE per se is is not yet well-established.  There are a multitude of questions such as “is browning necessary and if so how much?” and even if it is necessary whether CR by itself can mediate this effect adequately and if so under what conditions and limitations  ( WAT goes up and BAT goes down with obesity and the reverse with lower weight), etc.  

Despite the greater uncertainty of the contingent dependence of, extent of benefit, etc, lest of all the balance of potential good for a given individual, I have for several years now hedged bets with “convenience CE.”  

I do this not because I am convinced it is a material benefit for my fairly optimized lifestyle, but because at these modest levels I perceive this natural approach to be low risk even while the upside is not well defined for someone following my relatively evidence-based lifestyle.  This represents low hanging fruit that are unlikely to materially harm, yet have the potential for upside.  

The harder question and greater risk is the temptation to “go all out” and reach for something that may indeed confer significant benefit but with far less certainty than focusing  energy on optimizing better established and safer practices.  Particularly so when - in contrast with my modest CE example - the extent and magnitude of the risk are correspondingly less defined.

Edited by Mechanism

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Thanks for the link. I listened to the parabiosis interview (I m glad to know they don't sew mice in pairs any longer) and found that it filled significant gaps I had in my knowledge on the subject.

I listed to one other podcast from the series and also found it illuminating.

Thanks for turning me on to it.

Edited by Ron Put

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I’m happy to hear that Ron.  i also enjoy STEM talks very much.  The host has a bit of pro high protein, pro-keto orientation, but generally they try to remain as objective as possible, and moreover consistently have good questions for their guest in this well-curated podcast.

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On 8/8/2019 at 12:39 AM, Mechanism said:

i also enjoy STEM talks very much.  The host has a bit of pro high protein, pro-keto orientation, but generally they try to remain as objective as possible

The fact that they invited Valter Longo in one of their episodes belies a degree of objectivity. Also, the host did not insist too much questioning Longo on an issue of meat consumtion.

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