On an incidental note, I always find it perplexing that so many studies focus on acute effects rather than long-term adaptive response.
In the context of MPS or protein breakdown, this is especially problematic, as it’s the net effect on MPS that arbitrates on whether or not we get bigger and stronger, not the immediate effects seen in the post exercise-bout period.
Two relevant observations here:
1) The body is constantly ‘negotiating’ between protein synthesis and protein breakdown at the cellular level; it is not the transient state of the negotiation that matters, but the long-term balance that dictates training success; and
2) Given that the body is constantly seeking to re-establish homeostasis, it is almost certainly the case that any observed ‘spike’ in MPS in the acute phase will be followed by a compensatory depression of MPS (or more accurately, up-regulation of protein breakdown) in the chronic phase. If this were not the case, any number of well-documented protocols that demonstrate up-regulation of MPS (like PWO ingestion of amino acids and carbs) would result in massive gains when accumulated over a series of exercise bouts. The fact that these kinds of extraordinary gains do not eventuate ‘in real life’ demonstrates the faulty methodology of targeting insufficiently lengthy observation windows.
Cheers
Mavros
P.S. This is my first post, so g’day to all from down under!
Definitely a case of “lost in translation” Anatoly!
I believe the scientific method has a crucial role to play in exercise science.
My point was the following:
If you select an inappropriately small observation window (e.g. 8 hours post-workout), you only see the acute effects of a given stimulus - you don’t see the long-term effects.
And, since hypertrophy and strength gains are long-term adaptations, studies that focus solely on MPS up-regulation in the acute phase (immediately post-workout, or immediately post-feeding) are badly designed studies.
So, to summarise:
Appropriately designed scientific studies = hooray!
Badly designed scientific studies = boo!
Definitely a case of “lost in translation” Anatoly!
I believe the scientific method has a crucial role to play in exercise science.
I guess, still haven’t feed my brain with coffee, probably it’s a case.
mavros - 28 July 2010 06:10 AM
My point was the following:
If you select an inappropriately small observation window (e.g. 8 hours post-workout), you only see the acute effects of a given stimulus - you don’t see the long-term effects.
And, since hypertrophy and strength gains are long-term adaptations, studies that focus solely on MPS up-regulation in the acute phase (immediately post-workout, or immediately post-feeding) are badly designed studies.
So, to summarise:
Appropriately designed scientific studies = hooray!
Badly designed scientific studies = boo!
Cheers
Mavros
I understand
It’s like short-term hormone spikes after workout doesn’t do much for growth in long term, right?
I don’t think there are a lot of studies that covers checking both acute effects with long term adaptation.
I understand
It’s like short-term hormone spikes after workout doesn’t do much for growth in long term, right?
Precisely.
The key point is that the body always seeks homeostasis, so any short-term up-regulation of “x” will almost inevitably lead to a compensatory down-regulation of “x” later on.
Long-term adaptations (like hypertrophy and strength) are determined by the net effects of multiple factors, not by a transient increase in an isolated bio-marker (e.g. GH secretion).
The fact that so many studies in this area focus solely on the narrow view is part of the reason why exercise science struggles to compete with ‘bro-science’ in the lifting community…and as I said before, this is a lamentable fact.
Are you saying that, for example, during the night protein breakdown will go up to compensate for the increase seen during the day in response to exercise and/or amino acids? I agree that studies done over 8 hours might not be long enough, you should shoot for something like 24 to be able to see the entire time course of the raise in MPS caused by training (it could be even longer too)
Your hypothesis (that the body will compensate later by increased breakdown) has been tested for amino acids and exercise and the body does not increase breakdown to compensate. Here is one paper that talkes about this, the full text is free. “Regulation of muscle protein by amino acids.”
If you follow this link: http://jn.nutrition.org/cgi/content/full/132/10/3219S and read under “Diurnal changes in muscle protein balance”
So, if the body doesn’t compensate, why do “long term” studies often show mixed or no results? It’s because they aren’t really long term at all. Muscle growth takes time, and to see a statistically significant difference between, say, a PWO shake and no PWO shake takes time and a lot of subjects. And measuring increases in muscle size can be hard and the accuracy will depend a lot on the methods used. How small a difference can you detect with your equipment?
In addition, a lot of studies are done on untrained subjects and may not translate into trained. Or, that it simply takes even longer for the trained to see an effect since gains are slower. This is why you should always look for p values in long term studies (well, any studies, really) on muscle growth. The authors might say no difference, but there is a mean difference and the P value is 0.20.. that’s not enough for most authors to call it a trend, and it’s not enough to conclude anything about a hypothesis from a scientific standpoint, but from a practical standpoint I’d say it’s pretty good. If someone tells me that if I take this supplement there is an 80% chance (ok that’s very simplified, but still) I’ll grow more, I’ll do it!
I’m not saying we should infer everything from short term studies, but they are important and should be used along side long term studies.
If you select an inappropriately small observation window (e.g. 8 hours post-workout), you only see the acute effects of a given stimulus - you don’t see the long-term effects.
And, since hypertrophy and strength gains are long-term adaptations, studies that focus solely on MPS up-regulation in the acute phase (immediately post-workout, or immediately post-feeding) are badly designed studies.
Welcome, Mavro to exercise biology. Good first post and well written. Do write something about yourself in Miscellaneous about what you do and stuff..
I would never call it badly designed studies. I would just simply call them acute studies.
I don’t think we can make a across the board statement that acute results will never be consistent with long term results. It really depends on what we are talking about and we would only know that by doing a long term study.
Milk and soy is a case in point. They showed in acute studies that how milk has greater protein synthesis after resistance training and net positive amino acid balance. On the basis of the short term study, they did along term study which measured lean body mass and showed milk to significantly increase LBM compared to controls and soy group. This is a classic example of how research is done.
If you want to get funded, you do a pilot study, or an acute study and show how your results are favorable to your hypothesis and hence should be funded for along term study.
So both acute studies and chronic studies have its place. Of course, chronic studies will be the gold standard. But they both help bolster your case.
Thanks for your post; you make a number of interesting observations. I will adress them in turn, if I may:
“Your hypothesis (that the body will compensate later by increased breakdown) has been tested for amino acids and exercise and the body does not increase breakdown to compensate. Here is one paper that talkes about this, the full text is free. “Regulation of muscle protein by amino acids.”
If you follow this link: http://jn.nutrition.org/cgi/content/full/132/10/3219S and read under “Diurnal changes in muscle protein balance””
This depends on the time-frame. As I point out (and as you also point out) hypertrophy and strength gains are long-terms adaptations, and as such, the 24hr time-frame of the study above is insufficient. So, yes, the study shows that ‘for 24hrs’ the MPS is not followed by a compensatory up-regulation of breakdown, but this just begs the question!
This study (which was actually referenced by the study you quoted): http://www.ncbi.nlm.nih.gov/pubmed/8306544?dopt=Abstract
was taken over a 12 day period and found that “Mean daily rates of synthesis and degradation did not change with protein intake”.
“So, if the body doesn’t compensate, why do “long term” studies often show mixed or no results? It’s because they aren’t really long term at all. Muscle growth takes time, and to see a statistically significant difference between, say, a PWO shake and no PWO shake takes time and a lot of subjects”
It’s true, that’s one explanation. Another is that there are so many confounding variables that may contribute miniscule effects that isolating the influence of just one variable is impossible. Another is that the magnitude of the effect/s are statistically insignificant due to their being causally insignificant.
“This is why you should always look for p values in long term studies (well, any studies, really) on muscle growth. The authors might say no difference, but there is a mean difference and the P value is 0.20.. that’s not enough for most authors to call it a trend, and it’s not enough to conclude anything about a hypothesis from a scientific standpoint, but from a practical standpoint I’d say it’s pretty good”
I wouldn’t. The whole reason why we use concepts of statistical significance is to avoid leaping to causal conclusions where there are none. If you tried to act on any number of univariant correlations that have generated weak correlation values, you’d be well and truly stuffed.
“If someone tells me that if I take this supplement there is an 80% chance (ok that’s very simplified, but still) I’ll grow more, I’ll do it!”
Well, that’s certainly good news for the supplement companies!
“I’m not saying we should infer everything from short term studies, but they are important and should be used along side long term studies.”
Again, in the context of our discussion, this merely begs the question. If I’m right, then short term studies applied to a long-term adaptive response are often irrelevant.
But if you’re right, then we should be seeing significant long-term differences between trainers on different feeding protocols, based on their acute MPS responses. After all, if you extrapolate on the nitrogen balance increases that are found by acute studies, you should be seeing steroid-like gains…but we don’t.
The only conclusion I can draw is that the transient up-regulation of MPS brought about by protein feeds is compensated for by protein breakdown as part of the body’s return to homeostasis (as opposed to the ongoing effects of, say, exogenous testosterone, which clearly has the capacity to disrupt homeostasis in a significant way).
I appreciate your insights into the logistics and funding contexts that surround study design. I think you’re quite right about this.
I also agree that a short-terms study looking at acute effects is not synonymous with a badly designed study. I think the error comes from the interpretations and extrapolations that some people derive from acute studies, not from the design of the studies themselves…thanks for clarifying this point for me.
As you say, if the short term studies are seen as ‘bolstering’, rather than proving the causal case, then this is entirely appropriate.
Thank you also for the welcome. I think this is an excellent forum, and the articles on your site are top notch. Kudos.
If you want to put anything in quotes, you just select the text and press the quote button on top. Just make sure they are wrapped around the text. Like this [quot]quote example [/quot]. Hope that helps, Mavro.
And staying with the subject, the same goes for animal studies. You can never say you will expect the same result in humans. But they always bolster the case and is need to support your hypothesis. For ex, drug testing always starts with in vitro studies/cell culture studies to show a biological mechanism which MAY help. After this, it is tested on animals. If it is favorable, it goes to the phase 1 trials in humans. Every researcher knows that in vitro studies and rat studies can never measure up with human studies, but that’s how you do it. Interestingly, aspirin causes congenital disorders in rats.
My point is multiple lines of evidences are usually desired to show where the evidence leans. You will never find an RCT which you cannot pick holes in or conclusively proves the case. So all evidences help.
And thanks for all the comments. I hope we get more scientific minded people like you on board.
Mavros, thanks for your reply. P values are there for us to be sure enough to conclude something scientifically. Researchers often themselves admit that bigger and longer studies must be done. There is a reason why researchers often do power tests to figure out how many subjects they will need to get significant results. What if the p value is 0.06, or 0.07? Where do you draw the line? 0.05 as statistical significanse is just set there because someone thought it was a good number. If you do studies in very well trained individuals (say elite marathon runners) you’re gonna have a very hard time finding significant results, but a decrease in marathon time of 1-2% could mean a new world record.
Also, I’d rather you refrain from trying to make cheap points through comments like
Well, that’s certainly good news for the supplement companies!
I can’t find the full text to the article you linked to, so it’s hard for me to critique it, but that study didn’t look at whether the body increased protein degredation to compensate for earlier increases in protein synthesis, it looked at whether the body adapts to a high protein intake through increased rates of protein oxidation, which it does (though it’s hard for me to talk with a lot of confidence about the study since I can’t find the full text). The enzymes that oxidate amino acids are known to fluctuate with protein intake.
I’m not saying there are no weaknesses of short term studies, of course there are, as you can’t see if the body adapts to your stimulus over time. But adapting to it and purpusley trying to ruin it are two different things, I’m fairly confident that an acute increase in protein balance from exercise will stay there and not be compensated for later, but if that increase will be the same after you’ve exercised for a month is another question. If you look at one study done in untrained that shows x increase in muscle protein balance, then you probably can’t say that increase will be the same after they have trained for a while. This is why it’s important to do these acute studies not only in the untrained, but also the trained. And if exercising + a supplement (not necessarily a protein supplement) results in a higher raise in protein balance over, for example 24 hours, than exercising only, why should that change over time? Maybe the body adaps and the responses to both become smaller over time (as I would presume happens, given that it’s harder for someone who’s well trained to gain mass than someone who is untrained), but why wouldn’t there still be a difference between the two?
I just got into this discussion to say that protein breakdown doesn’t increase later in order to compensate for an earlier raise in synthesis (I realize the study is only over 24 hours, but why would the compensation happen at a later period of fasting? and the study you linked to does not test this specific hypothesis. All the evidence I’ve seen is in favor of an acute raise not being compensated for later). However, I should have added the adaptation argument as one of the reasons why long term studies don’t always agree with short term studies in my previous post.
Also, why would the gains have to be steroid like? Have you calculated how much protein would be gained over, for example a month, based on data from protein synthesis studies? I don’t think it would amount to steroid like. Also, keep in mind that you can’t look only at MPS, you must look at MPS minus muscle protein breakdown.
Of course I think you’re right about the arbitrary nature of the statistical significance threshold…and I wouldn’t advocate that we discount a causal relation purely on the basis of a P value that falls below the threshold.
But, in the context of the very well-documented and very strong chronic effects on hypertrophy elicited by (a) total protein intake (please don’t ask for studies!), (b) resistance training, and of course, (c) anabolic androgenics, I think that the comparatively minuscule and acute effects of say, protein timing, or amino acid supplementation, are afforded way too much attention by the exercise science/exercise nutrition community. You know, the proverbial forest being missed for the trees.
You may of course be right that acute increases in MPS are not always followed by increases in protein breakdown (in fact, you must be right, otherwise hypertrophy would be well nigh on impossible!), but the real world prevalence of static muscle mass in highly trained subjects (and more readily increasing muscle mass in novices) suggests that some sort of homeostatic drive is effectively ‘keeping a lid’ on net protein synthesis - even when subjects are getting acute rises in MPS from protein timing, macronutrient manipulation etc.
Now, if that’s not via up-regulation of protein breakdown, then maybe it’s through down-regulation of protein synthesis in the hours/days following the acute phase…who knows?
But the point is, one way or another, the homeostatic drive (in the absence of AAS) conspires to severely mitigate against the acute MPS up-regulation we see in many studies, thus vitiating the utility of the studies’ findings.
Cheers
Mav
P.S. Sorry if I offended you re the supplement companies comment…was not my intention; just trying to be humorous. But seriously, it is certainly the case that supp companies prey on the mentality that “oh well, I’ll give it a try, even if the science doesn’t prove a positive effect”. After all, the history of the supp industry reads like a play-by-play account of ‘how to sell ice to eskimos’.
I get what you’re saying, and I’m not arguing for protein timing, etc, being super important. IMO, if you want to be big you need to eat enough food to grow, train hard and rest well. Once you got that down all the other stuff (well, except AAS and such things) won’t make THAT much of a difference. I think the reason why such small things are afforded so much attention is that we know the basics and everyone wants to know what supplement or what special technique can get them that extra 1-2% that makes them just a little bit stronger, bigger or faster.
And it’s interesting to speculate on what happens when trainees’ gains become less and less as time goes by and eventually reach the point where more growth is almost impossible. Something interesting is definitely going on there. I don’t know how big of a spike well trained individuals get from one bout of resistance exercise. It would be interesting to see and I suspect that it’s much lower than less trained individuals. If it’s not much smaller, then something different must be going on in the recovery between sessions of highly trained vs less trained people.
