View Full Version : Re: Spaceflight muscle wasting - AA metabolites essential for musclemaintenance?

Marshall Price
May 16th 08, 07:51 PM
Taka wrote:
> One implication of this is that in physically active people who are
> moving in the Earth gravity field or even put weights on their moving
> bodies the arachidonic acid (AA) is constantly being "depleted" by
> conversion into the "good" prostaglandins (another way of depletion
> may be sex, because the PROSTAte gland also produces
> PROSTAglandins ...).

Aren't you jumping to conclusions here? Are you aware of any studies
showing connections between sexual activities and prostaglandins? It
occurs to me that male orgasm, by lowering libido, might have the
opposite effect.

> But once one gets sedentary, the AA has chance
> to accumulate to higher amounts in tissues. If the tissues are
> overloaded with AA it gets released spontaneously or in a response to
> minor stressors and in the absence of the prostaglandin-making
> machinery it gets converted by oxidation to the dangerous leukotrienes
> such as LTB4 which stimulate destructive inflammation/allergic
> responses. Ever noticed you catch cold easier when inactive?
> Fortunately, one can reduce AA not only by exercise but also by
> appropriate diet :-) BTW I am wondering which fats they are putting
> into the astronaut's food ?
> Taka
>> NASA Discovers the Anabolic Properties of Prostaglandins
>> In the January 1999 issue of the American Journal of Physiology, a new
>> study performed on astronauts during spaceflight demonstrates the key
>> role played by prostaglandins in maintaining the strength of muscles.
>> A major problem during spaceflight is the rapid loss of lean muscle
>> mass in both animals and humans. This prevents the space agencies from
>> sending men into space for extended periods without threatening their
>> health. It is, of course, the lack of resistance and weight due to the
>> weightlessness that is the cause of muscle atrophy. The million dollar
>> question is: how does this lack of resistance alter the intracellular
>> environment so that muscle wasting is free to take place?
>> Why are these experiments relevant to bodybuilders? Simply because the
>> pathways triggering the muscle wasting in space flight are the same
>> that make our muscle grow when we train. They just work in opposite
>> directions in each case.
>> --------------------------------------------------------------------------------
>> Hormone fluctuations during spaceflight
>> Hormones are obvious candidates as possible mediators of this wasting
>> process. The favored hypothesis is that spaceflight induces some major
>> alterations in our hormone levels. Two main pathways could be
>> involved. First, the levels of catabolic hormones could rise and so be
>> the cause of this wasting. Second, the level of the anabolic hormones
>> could drop so that the constant basal renewal of muscle protein could
>> not take place at a sufficient rate, resulting in a net negative
>> balance.
>> The study by Dr. Peter Stein [1] of the University of Medicine and
>> Dentistry of New Jersey consisted of measuring the key hormones in
>> astronauts during a space shuttle mission. Cortisol, a known wasting
>> hormone, was one of the favorite candidates. Unfortunately, a
>> consistent pattern of fluctuations in cortisol level was not apparent.
>> Cortisol increased in some but not all subjects. As all of them
>> experienced significant muscle loss, cortisol excess does not explain
>> the consistent wasting. Another paradox is that, once back on the
>> ground, the astronauts regained lean body mass while cortisol level
>> was at its peak.
>> This means that you can waste away while having a normal cortisol
>> level, and you can put on lean mass despite a high cortisol level. It
>> should be a major eye-opener for bodybuilders.
>> Next on the list of candidates were the catecholamines (epinephrine
>> and norepinephrine). Depending on whom you listen to, catecholamines
>> are either anti-catabolic or catabolic. Whatever their effect, every
>> scientist would agree that it is at best mild. The expected drops and
>> rebounds of catecholamines were detected during the flight and the
>> post flight periods, respectively. To explain the lean mass
>> fluctuations, it would mean that catecholamines are very potent
>> anabolic or anti-catabolic substances -- information that no research
>> has ever demonstrated even at high doses in humans. So they are not
>> the mediator the scientists were looking for.
>> The next substances to be measured were the anabolic hormones and
>> growth factors such as GH, IGF-1 or insulin. Stein did not find any
>> significant alteration of their levels taking place during the phase
>> of wasting or regrowth. He did notice that T3 (an active thyroid
>> hormone) level dropped during the flight, to rebound after landing. T3
>> fluctuations concur with the mass loss and regain, so Stein suggests
>> that T3 could be one of the mediators of the lean mass fluctuation. As
>> T3 drops during the flight, so would the rate of muscle protein
>> synthesis. After landing, the increased T3 would boost anabolism and
>> therefore muscle growth.
>> I disagree with Stein on this point. I consider the space-induced drop
>> in T3 as a protective mechanism against excessive muscle wasting
>> rather than a mediator of the growth inhibition. T3 is both an
>> anabolic and catabolic hormone. A minimal amount of T3 is required for
>> muscle to grow at an optimal rate, but as the T3 level increases, its
>> catabolic actions start to predominate and overwhelm its anabolic
>> properties.
>> This is why you'll never meet a bodybuilder claiming to have gained
>> muscles by taking only T3. In fact, bodybuilders using T3 start to
>> lose both lean and adipose mass. Studies performed in bed-rested
>> people which attempt to duplicate weightlessness showed that in this
>> situation, exogenous T3 promoted protein degradation and not
>> anabolism. Therefore, T3 is unlikely to be the mass modulator we are
>> looking for.
>> Stein's genuine breakthrough came from the fact that he measured the
>> levels of prostaglandins in both the blood and urine and compared them
>> with the degree of muscle wasting.
>> Both measures were used for better accuracy as the levels of
>> prostaglandins are very hard to evaluate, prostaglandins being mainly
>> a local and not systemic growth modulator. Skeletal muscles and bones
>> are both net producers of prostaglandins with muscles being the major
>> site of manufacture. Those locally produced prostaglandins will
>> eventually pass into the blood before being quickly destroyed. So the
>> blood level of prostaglandins roughly reflects the rate of production
>> of prostaglandins inside the muscles. With urine prostaglandins,
>> results tend to be harder to interpret as prostaglandins produced in
>> the kidney tend to bias the figures. Nevertheless, Dr. Stein found out
>> that both measures agreed anyway.
>> To the surprise of the scientific community (but not to bodybuilders),
>> the levels of the prostaglandins measured dropped during the flight --
>> especially the PGE2.
>> After landing, there was a significant rebound of the prostaglandin
>> levels, especially of the PGF2. Those fluctuations closely reflected
>> the observed changes in lean muscle mass.
>> The major cause of this drop is the lack of resistance placed on both
>> the muscles and bones. As we flex our muscles, a local formation and
>> release of prostaglandins is taking place. The harder we flex, the
>> more the local level of prostaglandins is elevated. Weightlessness
>> prevents the astronauts from flexing their muscles against a
>> resistance. Therefore, a significant drop in muscle prostaglandins can
>> be expected. As less prostaglandins are produced in our muscles, the
>> drop will quickly be reflected by the blood measurements.
>> This may explain the well known development of insulin resistance
>> occuring during space flight as prostaglandins mediate many of the
>> actions of insulin on muscles. This resistance also contributes to the
>> muscle protein loss and again we find prostaglandins as key mediators
>> of this phenomenon.
>> Stein's interpretations of these new findings are somewhat less
>> convincing. Scientists are expected to accurately measure the results
>> they obtained during an experiment, but also they are also expected to
>> interpret their results. Sometimes, their discussion is well
>> researched and documented which provides a worthwhile reading.
>> Unfortunately, many times it is not so well researched and the
>> discussion is a big step backward. This is the case in the above
>> mentioned study. The basic ideas are bright and the results original
>> but the comments made by the team of scientists is at the very least
>> poor. Paradoxally, they reached a good conclusion with a biased
>> reasoning.
>> The discussion part of this study is based on a very selective reading
>> of the scientific literature while the bottom line conclusion is very
>> good. It concludes that "the inflight data support a major role for
>> decreased prostaglandin production in the protein loss by muscles."
>> This is very refreshing as the average scientist considers
>> prostaglandins as mediators of wasting and certainly not of muscle
>> growth. Stein's conclusion fits very well with his findings. The fall
>> in muscle prostaglandins induced by the lack of resistance during the
>> spaceflight results in a sharp fall in protein synthesis.
>> For a quick recap:
>> Our muscles are subjected to a constant protein turnover. This means
>> that the old proteins composing the contractile tissue of each cell
>> are constantly destroyed (catabolism) and replaced by new proteins
>> (anabolism).
>> If you are a sedentary person between 20 to 40 year old, this constant
>> basal turnover is neutral. The rate of catabolism is roughly equal to
>> the rate of anabolism.
>> Young growing adolescents acquire their muscle mass as anabolic rate
>> exceeds catabolism.
>> Elderly people slowly waste away as anabolism is slower than
>> degradation.
>> During spaceflight, anabolism is reduced, causing the rebuilding
>> mechanisms to be overwhelmed by the catabolic pathways. A loss of lean
>> mass ensues.
>> The big issue is to understand which hormones or factors are involved
>> in the drop of anabolism.
>> Stein based his reasoning on the common belief concerning
>> prostaglandins, i.e., that PGF2 is anabolic and PGE2 is catabolic.
>> From there, he tries to explain how PGE2, a catabolic factor according
>> to him, could make our muscle grow. Good luck! Also, if PGE2 is a key
>> mediator of muscle wasting as many believe, how to explain its drop
>> while catabolism is intense? This belief concerning the so-called
>> wasting effect of PGE2 is due to some old, badly conducted, and flawed
>> studies which other laboratories have been unable to reproduce. Other
>> newer and more comprehensive studies have shown that PGE2 has an
>> overall positive influence on the protein turnover [2]. In other
>> words, PGE2 is an anabolic mediator rather than a catabolic one.
>> This fits better into the NASA findings. During the flight, muscle
>> prostaglandins fall, which depresses anabolism. After the flight,
>> muscle prostaglandin production bounces back as astronaut muscles are
>> once against submitted to the resistance of gravity. The extra
>> prostaglandins strongly stimulate anabolism which explains the fast
>> muscle rebuilding.
>> --------------------------------------------------------------------------------
>> Let's speculate a little!
>> With this major role of prostaglandins in mind, let's try to go a bit
>> further. Scientists specializing in Aeronautics have spent years
>> trying to combat space-induced wasting. In fact, the main research on
>> bodybuilding hormones has mostly been conducted by those scientists.
>> They have tried to administer hormones such as GH or IGF-1 during
>> spaceflights in order to combat the muscle loss. They have had little
>> success -- hardly surprising in light of recent findings. As the
>> levels of these peptide hormones hardly fluctuate, administering some
>> more does not appear to be the optimal solution. Usage of anabolic
>> steroids during weightlessness has achieved some but not exceptional
>> results. The next step is now to administer prostaglandins during a
>> flight and see what will happen.
>> The lack of effects of the tested anabolic hormones on muscles
>> suggests that their receptors failed to function normally. In other
>> words, the lack of muscle contractions rapidly produce a receptor
>> insensitivity. What if it was the level of muscle prostaglandins that
>> was one of the major controllers of the sensitivity of the main
>> anabolic hormones? I've mentioned that the potency of steroids was
>> enhanced by exogenous PGF2. By the same token, PGF2 sensitivity is
>> enhanced by androgens.
>> So:
>> Prostaglandins control androgen and IGF-1 receptor activities.
>> Androgens control prostaglandin receptor expression.
>> IGF-1 and anabolics are major controllers of the level of muscle
>> prostaglandins.
>> This looks like a righteous anabolic cycle. Therefore, the major issue
>> for the scientists of the third millennium is to figure out how, at
>> which part of the cycle and where to enter this anabolic cycle for
>> maximal effectiveness of our muscle building tools.
>> --------------------------------------------------------------------------------
>> References:
>> Stein TP. 1999 Jan. Endocrine relationships during human spaceflight.
>> Am J Physiol. 276:E155-62.
>> Fagan JM, Goldberg AL. 1986 Apr. Inhibitors of protein and RNA
>> synthesis cause a rapid block in prostaglandin production at the
>> prostaglandin synthase step. Proc Natl Acad Sci U S A. 83(8):2771-5.
>> http://www.mesomorphosis.com/articles/dharkam/anabolic-properties-of-prostaglandins.htm
>> AND SOME RELATED READING (just to see how prostaglandins are also mis/
>> used):
>> http://www.mesomorphosis.com/articles/dharkam/prostaglandins.htm
>> http://www.mesomorphosis.com/articles/dharkam/how-dharkam-uses-pgf2.htm

Marshall Price of Miami
Known to Yahoo as d021317c

Marshall Price
May 18th 08, 08:40 AM
Taka wrote:
> On May 17, 3:51 am, Marshall Price > wrote:
>> Taka wrote:
>>> One implication of this is that in physically active people who are
>>> moving in the Earth gravity field or even put weights on their moving
>>> bodies the arachidonic acid (AA) is constantly being "depleted" by
>>> conversion into the "good" prostaglandins (another way of depletion
>>> may be sex, because the PROSTAte gland also produces
>>> PROSTAglandins ...).
>> Aren't you jumping to conclusions here? Are you aware of any studies
>> showing connections between sexual activities and prostaglandins? It
>> occurs to me that male orgasm, by lowering libido, might have the
>> opposite effect.
> Perhaps, but the prostate produces prostaglandins and the ejaculate is
> rich in them so it's a way of getting them out of the body.

That remains to be seen.

> However,
> the amount may be too small compared to the daily manufacture of AA
> from the vegetable oil precursors ingested ...

And so does that.

Besides, it's not as though the endogenous production of arachidonic
acid is out of control. As the chapter I quoted from /Metabolism at a
Glance/ points out, it's a pathway involving about eight steps
(including chain elongation), four of which are mediated by enzymes
embedded in the membrane of the smooth endoplasmic reticulum, and it
requires energy.

Marshall Price of Miami
Known to Yahoo as d021317c