A while back, I wrote an article titled Genetics and Strength Training: Just How Different Are We? Since that article was published, the question that’s come up the most often has been about non-responders. There can’t be people who simply don’t respond to exercise, right?
Back then, I made sure to point out that a “non-responder” in a scientific study simply didn’t respond to the training protocol used in the study, but that doesn’t necessarily mean they wouldn’t respond to any training program. Maybe the training protocol used in the study just wasn’t appropriate for them, or maybe they were participating in the study at a particularly bad point in their life for gaining muscle (high stress, poor sleep, not eating enough, etc.). I honestly hate the term “non-responder” – the only reason I use it is that it’s the terminology used in the literature.
However, since this question keeps coming up, I’ve been meaning to write an article to address the phenomenon of non-responders in a bit more detail.
This recently published study reminded me of the topic: Refuting the Myth of Non-Response to Exercise Training: ‘Non-Responders’ do Respond to Higher Dose of Training by Montero and Lundby (2017).
I’m not going to go into too much depth on this particular study because the details of it probably aren’t overly relevant to most of you, but briefly:
- A group of 78 people did endurance training for 6 weeks. They were split into 5 groups, training for an hour per session either 1, 2, 3, 4, or 5 days per week.
- After 6 weeks, if someone’s peak aerobic power didn’t increase, they were initially labeled a “non-responder.” 69% of the people training once per week were “non-responders,” 40% of the people training twice per week were “non-responders,” 29% of the people training three times per week were “non-responders,” and, tellingly, none of the people training four or five times per week were “non-responders.”
- The “non-responders” trained for another six weeks, doing two additional sessions per week. So the people initially training once per week started training three times per week, the people training twice per week started training four times per week, and the people training three times per week started training five times per week.
- After another six weeks of training, there were no non-responders. There was still a lot of variability in results – some people’s peak power increased a lot, and some people’s didn’t increase very much – but everyone’s fitness improved. To make sure they didn’t get any false positives, they ensured that everyone’s increase in peak power was at least 4% (i.e. the standard measurement error for peak aerobic power).
Now, I realize that most of you are primarily training to get strong and swole, so these results may not be that important to you, but they tie back into this article. If you’ll remember, it briefly touched on aerobic fitness. In a huge study with 481 participants, about 10 of them actually had small decreases in aerobic fitness, and quite a few more had essentially no change (within the range of standard measurement error).
But now we see that if the people who weren’t responding just trained harder, there’s a pretty good likelihood that all of them would have made some progress. There may still be one or two stragglers, but you’d expect the number of non-responders to drop near zero.
So, does the same concept apply to strength?
Maybe.
A 2015 study (with a slightly misleading title) helps shed some light on the issue: There Are No Nonresponders to Resistance-Type Training in Older Men and Women by Churchward-Venne et al.
This study measured changes in lean body mass, muscle fiber size, strength (leg press and knee extension), and physical function (chair rise time). They found that all 110 participants made gains in at least one of those measures.
The reason I say the title is a bit misleading is that most people are worried about non-response for a particular adaptation (i.e. strength or, especially, hypertrophy). Obviously, when you exercise, something is going to happen, but people are concerned that they won’t experience a particular type of adaptation. This study essentially showed that when you train, at least some positive adaptations always take place, but it didn’t show that all positive adaptations take place.
However, this study did show that there are no (or very, very few) people who don’t get either bigger or stronger in response to training. In fact, all but one person gained at least some strength. “Non-response” rate for strength is much lower than for hypertrophy in the first place, but this is impressive when you consider the population in the study. All participants were at least 65 years old; older people can absolutely respond well to strength training, but they generally don’t respond quite as well as young folks.
However, there were still quite a few people who didn’t gain any muscle, or, in fact, lost muscle. That may sound surprising, but it’s in line with a bunch of other research. So, what do we know about these people?
Not too much, unfortunately, but we have some hints.
One of these hints comes from data collected along with this study by Bamman et al. referenced in my last article on the subject.
A few of the differences between the non-responders and the high responders aren’t too surprising: the expression of genes that code from growth factors associated with hypertrophy increased more post-exercise in the high responders, and high responders had an easier time adding more myonuclei to their muscle fibers. However, another key difference is the overall “signature” of the cellular signaling response.
In the high responders, the subsequent cellular responses “looked” like a growth response. In the non-responders, on the other hand, it looked much more like a magnified inflammatory response. Pro-inflammatory signaling increases post-training in everyone, of course, but not nearly to the degree seen in the non-responders in this study.
We get another hint from a study looking at the molecular networks activated in high and low responders. Interestingly, the high responders actually had blunted mTOR activation signature compared to the lower responders, which is surprising because the mTOR pathway is strongly implicated in initiating muscle protein synthesis. However, mTOR is also implicated in activation and regulation of the immune system – the people who responded worse may have had elevated activity in the mTOR pathway due to the excessive post-exercise inflammation alluded to earlier (post-workout inflammation and a localized immune response go hand-in-hand).
We also know that the initial (excessive) muscle damage people experience when they first start training likely inhibits hypertrophy – it’s all the muscles can do to just repair themselves, much less start growing. It takes a few weeks for a collection of adaptations to ramp up and partially protect the muscles from damage (this is known as the repeated bout effect), after which point the muscles start growing pretty rapidly.
Taken together, it looked like hypertrophic non-responders – people whose muscles either don’t grow or grow very little in response to resistance training – may be experiencing a hiccup in that protective system, so they wind up with excessive muscle damage and inflammation that prevent their muscles from growing.
This tentative explanation would make sense in light of the training protocol used in the Bamman paper: it involved 3 sets a piece of squats, leg press, and knee extensions, three times per week, with all sets taken to failure. That’s 27 hard sets, which is probably overboard for a fair amount of new lifters. It’s even more volume than the recent German Volume Training study where guys with some degree of training experience failed to grow on the notoriously high-volume program, likely because training volume was too high even for them.
As opposed to the cardio study I presented in the outset of this article in which people failed to improve because they weren’t training enough, it’s more plausible that a lot of the hypertrophic non-responders in resistance training studies fail to make gains because they’re training too much, and their muscles take longer to start adapting and protecting themselves from the assault of resistance training.
Now, it is possible, of course, that a lot of non-responders really are just screwed, and that nothing will help them build muscle. After all, markers of metabolic health actually worsen in a non-negligible amount of people when they take up exercise (which, strangely, not many people talk about), so it’s clear that some people’s bodies just respond to training in very unexpected ways. However, I think it’s unlikely that the “true” hypertrophic non-response rate is nearly as high as most studies report. With that in mind, here are 4 simple strategies to try to get more out of your training if you’ve been disappointed by how much muscle you’ve been able to build:
- Take care of business outside the gym. Sleep more. Manage stress as well as you can (if there’s nothing you can do to decrease the stressors in your day-to-day life, I’d strongly recommend taking up meditation). Eat more calories and especially protein (up to around 1g/lb, or 2g/kg).
- Assuming you’ve already tried increasing training volume (which should be your first thought, since higher training volumes generally mean more muscle growth) instead try decreasing your training volume for a while to maybe ~4-5 sets per muscle per week. Since non-responders have a magnified inflammatory response to training (which may be one of the major factors inhibiting hypertrophy), decreasing the intensity of the stressor may put it back into a beneficial, hormetic range.
- Give it time. Post-training inflammation tends to decrease with continued training, and the muscles’ protective adaptations continue accruing over time. It may be that muscles of people who respond well to training go through the initial “shock” phase in 1-3 weeks, and then start growing, but that “non-responders’” muscles take a few months to get through that phase, but will eventually toughen up and start growing.
- Try something new. As mentioned in the last article, a couple of papers (one, two) show that certain styles of training produce great results for some people but not others. If your muscles haven’t grown from heavy sets of 5 with long rest periods, they may instead grow from lighter sets of 20 with short rest periods, or from explosive training with low reps and no grinders. An approach to training that produces great results for the majority of people may not be what your body responds to.
At the end of the day, it’s crystal clear that some people simply respond way better to training than others. It’s also clear that damn near everyone gets stronger when they start training. However, muscle growth is a bit trickier, and almost every study (especially large studies) has some non-responders. Unlike aerobic training, we don’t know yet if simple programming modifications can ensure that everyone improves, though my hunch is that “true” non-response rate (i.e. people who simply cannot gain muscle in response to any sort of training) is considerably lower than the ~10-20% often seen in research.
P.S. This started as a research update email to the Stronger By Science subscribers, but eventually grew into an article as I kept writing. Sign up here if you’d like to get research updates straight to your inbox.
P.P.S. I’ll be speaking at Powerlifting University’s Online Powerlifting Summit tomorrow at 5pm EST about squat biomechanics. Check out this page if you’re interested. The live talk is free, but I’m pretty sure the replays aren’t.
Read Next
- Genetics and Strength Training: Just How Different Are We?
- Your Drug-Free Muscle and Strength Potential, Part 1
- Your Drug-Free Muscle and Strength Potential, Part 2
Grant says
I believe most of the “non-responders” out there are just living out their own self fulfilling prophecy. If you believe that you are a non-responder or a hardgainer you are going to have a significantly harder time making progress when sub consciously you have convinced yourself that you can’t. You are much better off believing you are that one in a million with the best genetics and you are just one tweak away from taking off.
Great article!
Greg Nuckols says
For strength, I tend to agree. With hypertrophy, though, since it’s purely a physiological response, I really don’t think belief makes quite as much of a difference. I think causality would work in the opposite direction (people with good genes who respond well gain confidence based on their results, and vice versa for people who try but don’t respond well).
Brent says
How likely is it that a non-responder who has a magnified inflammatory response to training would benefit from a low dose of anti-inflammatory medicine until their post-training inflammation has decreased enough to not be a limiting factor?
Greg Nuckols says
That’s a great question. I didn’t want to recommend NSAIDs in the article because that may technically be illegal (not totally sure about the legality of it, but NSAIDs are drugs, I’m not a doctor, and there’s a difference between describing what a drug does and recommending people take a drug), but I think you’re on the right track. In studies on older people (higher baseline levels of inflammation), NSAIDs tend to actually increase rates of hypertrophy, whereas they blunt hypertrophy in younger people, on average; maybe nonresponders will benefit too?
Brent says
I figured you probably didn’t mention it due to the whole “medical advice” thing. You could always be like the drug commercials:
“Ask your doctor if ibuprofen is right for you.”
Niall says
Isn’t inflammation a good thing when it comes to hypertrophy, though? Like if you took an NSAID after training wouldn’t that blunt the bodies response for hypertrophy?
Greg Nuckols says
Like anything else, the dose makes the poison. None is probably suboptimal, some is good, too much is bad.
Lawrence Lin says
How exactly would someone go about using an NSAID to decrease excessive post workout inflammation? Would they take it immediately after their workout or when the DOMS is at its peak? What would the dosage be?
Greg Nuckols says
Before the workout. As for dosage, consult a doctor (I’m not legally allowed to say anything other than “read the bottle,” basically).
Lawrence Lin says
Thanks greg!
Paul Kopalek says
I swear that there was an article of yours (maybe years ago?) where you suggested that it’s POSSIBLE that ibuprofen may inhibit your gains via affecting satellite cell activity. Something like they talk about here:
https://www.bodybuilding.com/fun/can-pain-pills-kill-your-bodybuilding-gains.html
I’m not sure if what you’re talking about might be completely unrelated or completely related — but just thought I’d bring up the satellite cell thing, since I was looking for it here in this conversation and didn’t see it.
Note: IANAD and I’m bad at science and I’m weak
Greg Nuckols says
In general, yes. But it’s a context-dependent thing. They decrease rate of progress in younger people, but actually tend to increase rate of progress in older people (i.e. 60+). I’m just proposing here that low responders may be a bit more like older people in that regard.
Louis D says
Great stuff as usual Greg,
One question. If someone was to start adding more sessions per week to their strength/hypertrophy training (similar to the 2nd 6 week block of the study discussed) would you think volume per session should remain the same or is there a ball- park %-ge to reduce each session by to temper increase in weekly volume?
Greg Nuckols says
I think your best bet is to start by leaving weekly volume the same (so reducing per-session volume) and then increasing volume after frequency if needed.
Louis says
Thanks man, I’ll look in to that.
Charlie says
Great article. I have a story relating to the to excessive muscle damage and GVT (German volume training). I tried GVT ages ago and it did not work at all for me, it just left me very sore. Recently I tried it again but with a modification rather than starting out with 60% of 1rm for 10×10 from the outset and trying to decrease rest time (this is how I understand original GVT). I started with 67% of 1rm for 3×10 and added a set each week until eventually after 8 weeks doing 10×10 with 67%. I have to say the last couple of weeks were tough but nothing like as tough when I tried 60% for 10×10 from the ouset. I did this for bench press and chin ups (although with chin ups I started with 3×5 working up to 10×5 just with BW). I got very noticeable gains in my lats, triceps and pecs from this. My strength however did not increase as I expected given the size gains. But I have now ran a cycle of linear periodization in the manner you (Greg) outlined in a t-nation article and I hit a 10kg pr on the bench press.
This might sound crap to a lot of people (basically 4 months for a 10kg PR) but I am not naturally a strong person and regard myself as a “hardgainer”. What I have released is I need a lot of volume to grow but I can’t just jump in at the deep end and do 10×10 I need to start with low volume and slowly work up to give my body a chance to adapt and grow and then I need a slow and steady strength phase to transfer those gains into a new PR.
In a nutshell I think my experience anecedotely confirms what you are alluding to in your second point, that some people need to do way “more” than they imagine to get a response but crucially in order to do more you have to work up a lot slower than you would imagine.
Iason P. says
Interesting “case study”. Could you answer some of these?
-How many years had you been lifting?
-What did your training look like(frequency,split)?
-What weights did you use?
-Were you in maintenance, surplus or deficit?
-Which peaking program did you use?
Charlie says
This will be embarrassing but I will answer your question honestly otherwise it isn´t much use to you. I´ll give you some background on me first so you have context but if that is not interesting to you can skip to 17 months onward.
Background on me: 29 years old, lifting for about 20 months, my current lifts are 160kg deadlift, 140kg squat, 100kg bench, 65kg OHP. I was seriously weak when I started, 40kg squat, 40kg bench and 20kg ohp all for about 5 reps (didn´t deadlift for first year).
My training history:
First 6 months – any old crap. I knew nothing. I just knew that “free weights were good”. Got to about 40kgx5 on OHP, 70kgx5 on Squat and 60kgx5 on Bench all performed badly!
7-9 months – Did variations on 5×5 and 3×5 and got to about 100kgx3 on squat, 70kgx5 on bench and 50kg x 5 on OHP. Most of these gains were purely technique very little muscle size (although of course some). My fat percentage went up alot though because I tried GOMAD. This period of training was very fustrating. I was constantly deloading.
10-16 months
Did texas method and 5/3/1. I hated this more than 3×5. My bench at this point was 90kg x 1, squat about 130kg x 1 and OHP 60kg x 1. My deadlift did OK with this style of training. It was maybe around 150ish kg. Again constantly deloading everything except my deadlift. Bench was the worst though, it was being deloaded all the time and I was fat.
17-18 months
I decided to just increase the volume. Increasing weight which was the idea behind the programs I tried thus far was clearly not working for me. I had horrible tendonitis from constantly lifting heavy (I am thinking here more about the texas method). I looked shit and was generally miserable. So I worked out full body 3 days a week.
Monday – Bench 60kg (67% of 1rm) for 10 reps and 3 plus sets (i.e week 1 only 3 sets, week 2 bumps up to 4 sets until week 8 is 10×10). This is supersetted with chin ups for BWx5 reps for the same number of sets as bench and as much rest as needed is taken in between each superset (so not really a true superset). I also did leg extensions and hamstring curls for my lower body (this was the first time I had used machines really) and it helped ease my tendonitis.
Wednesday – Bench press with 60kg for 3 sets of 10 (this stayed the same every week) I also did 3 sets of 5 chinups (this stayed the same every week). I also did some OHP and a little leg press. Again first time I had used leg press and the variation helped freshen things up.
Friday – Basically the same as wednesday except for some squats rather than leg press. I didn,t deadlift during this cycle because my back was fucked from all the low bar squatting and deadlifting I had done up until now.
I felt great doing this because I was consistently hitting the targets I wanted to and all the tendonitis that had accumulated in my elbows and knees was finally starting to dissipate. On top of this my weight was staying the same but I was clearly gaining muscle. So I felt great. I was making progress without having to drink 4 litres of milk.
At the end of this 8 weeks I could do 60kg for 17 reps on bench press. A lot more reps than I could at the start but this didn´t translate into a new 1rm because I wasn´t efficient anymore with heavier weights.
So I ran this https://www.t-nation.com/training/how-to-use-linear-periodization for 2 months while cutting and hit 100kg bench (10 plus PR), 140kg (10 plus PR), 65kg (OHP 5kg plus PR) and 160KG deadlift (10ish plus PR). I would say that the squat and deadlift PR are attributatable to the linear periodization and not being in pain anymore but the OHP and Bench press are because of the volume training.
I wrote all of this out in the hope that it helps someone else out avoid the pain and fustration of persisting with starting strength and the texas method when it is clearly not working for them. Yes I did make progress on those programs but it came at a very high cost.
Height – 181cm
Weight –
67KG on day one of training
83Kg and fat at the height of TM
80KG during my volume training block (with waaaay lower body fat compared to TM)
77KG at the end of Linear periodization (40cm neck circum, 85/84 waist circum at navel so somewhere in the 13-15% body fat range).
I hope this helps
Basti says
That is actually pretty much exactly what Dr. Mike Isratael recommends. But he says to progress from your minimum effective dose to your maximum recoverable volume in 4-6 weeks. So maybe you can make some faster progress if you add 2 sets each week, deload and repeat.
Nik says
One small thing I’m confused about (and I may be interpreting this wrong) is that here you state in a study that at first the non-responders gained nothing after 6 weeks of exercise and only started to prosper after the second 6 weeks. But on the genetics article the study showed that non-responders were quite the opposite, responding in the first 8 weeks (80% of total development) and then making very little progress thereafter. Am I misinterpreting the data or are the two studies looking at different things?
Greg Nuckols says
They’re looking at two different things. The study at the start of this article was looking at aerobic fitness with an increase in training volume, and the study you’re referring to in the old article was looking at strength gains with no changes to the training program.
Clark says
Is it not obvious why some lost muscle mass in the Bamman study? Take an untrained senior citizen and put them on a regimen of 27 sets to failure every week? Holy crap. That’s not training muscle, that’s obliterating muscle. In many cases quite literally obliterating it.
As you suggest, training (like poison) is in the dosage. We wouldn’t be surprised if people died from massive doses of vaccine. Why should be surprised if a massive volume of exercise (to failure!) produces negative results?
Greg Nuckols says
It’s worth noting that the exercise dose in the Hubal study (from the last article) was considerably smaller, and it still had some nonresponders as well. And it wasn’t just the senior citizens. If memory serves, they reported that something like 3 of the nonresponders were young men and 4 were young women (I’d need to look back to verify the exact numbers; I remember for sure that there were people from all four age/sex groups in all of the responder clusters, though)
Pat Bloomfield says
Great article Greg.
I think I must be a hardgainer as my strength and LBM have been negligible over the last year or two despite training four days a week and trying a few strength training program, including a couple of yours for over a year. I was feeling completely beat up between workouts and really had to force myself to do physical work outside of the gym. Maybe I suffer more inflammation as suggested here, and added to that I hit the big 50 last year. After running your 16 program the first time I added 10-15lbs to me bench but since then it’s deteriorated back down again.
I struggle with auto-regulation like RPE as once I’m under the bar I’ll just grind out the reps. So a couple of months ago I decided to give Velocity Based Training a go. It’s taken a while to get used to using it with programs based on 1RM and RPE and it has forced me to drop weights quite a bit. However, I have noticed by learning to perform the reps as hard as possible I’m able to produce more power at lighter loads. It has also reduced DOMS significantly and I’m starting to stop being hung-up about the weight on the bar. Unfortunately, I don’t know whether this will help with strength and hypertrophy yet as I’m in a fat loss phase but hopefully it’ll set me up for good gains in a few months when I get back into calorie surplus.
Also following a previous comment, I may consider taking an anti-inflammatory when DOMS is at it’s peak to see whether that helps too.
Khetag Krapotkin says
It seems it’s kinda in line with the recent recommendations in strength and hypertrophy training from Russia (Kasatov, Grachev, Seluyanov etc.). That training above certain intensity (failure or relative load) causes damage that takes anywhere from 10-18 days to rebuild and nothing can hasten that process. Training which causes damage again done during that time will blunt hypertrophic repsonse by destroying accumulated metabolites and so forth. Now steroids and other individual differences can make that less severe allowing some to progress, but some will stagnate or lose.
http://power35.ru/informatsiya/biblioteka/bazovyj-trening-v-pauerliftinge-agrachev
http://power35.ru/informatsiya/biblioteka/otdyh-vsemu-golova-dkasatov
http://power35.ru/informatsiya/biblioteka/teorija-praktika-metodicheskie-osnovy-silovogo-treninga-dkasatov-agrachev
Wonder what your opinion is on the subject, Greg?
Greg Nuckols says
Any sources for this in English? When I run the articles through google translate, the translation is pretty rough.
Khetag says
Most of the work published on that is written by Seluyanov and from what I can gather it’s all in Russian. There are articles in English with his training recommendations somewhere, but unfortunately I haven’t been able to find any articles that would explain the reasoning behind them. I think some of the work done by Grachev was mentioned briefly in Pavel Tsatsouline’s book PTP Professional and in a few articles on his blog StrongFirst, but what he includes in there is mostly oversimplified and/or outdated and/or misinterpreted.
Yea, the translate is rough but it’s mostly decipherable, I think.
As for the gist of Grachev’s work, he’s mainly criticizing various authorities like Verkhoshansky, Sheiko, Zatsiorsky etc. for their poor / non-existent understanding of muscle biochemistry
Jeffo says
I would LOVE to learn about what types of programs he recommends his athletes use. I had always been a low volume/high intensity of effort type of guy, but I’ve been starting (at age 52!) to experiment with more volume at less intensity of effort.
Chris baiata says
Great article Greg! As someone who finds it pretty difficult to grow, even doing everything I can to maximize hypertrophy but eating right, sleeping enough, and the right programming…I still know there is hope lol! It’s just a slower process for people like me, and know that some people can just look at a weight and get bigger!
Really enjoy how you make the research so much more understandable and applicable for people.
Keep up the fantastic work man, i really enjoy it!
Thom says
Greg, I just got done watching your seminar over at Powerlifting University. My problem on bench is the “feels heavy coming down” – especially a few inches from the chest, as you described. As such, I’m thinking about incorporating some Spoto press. Would this be programmed similar to “regular” bench hypertrophy, where I’d want to do most work at 60-80%? Or just start a bit lower (such as 135 lb) and work up as possible? Thanks – for all the good work.
Greg Nuckols says
Get a decent idea of what your 1rm Spoto press would be (you don’t need to work up to a true 1rm, but work up heavy enough that you have a good idea), and then yeah, work mostly between 65-80% or so
Thom says
Makes sense. Thanks.
Alex says
What sort of program would you recommend to try if I am not responding well to 5×5 at 85% (stronglifts)? I am trying to troubleshoot why I have not been getting stronger and I am not sure if the intensity is too high, or maybe the volume is too low?
Greg Nuckols says
You may just be at the point where you need something other than a basic beginner program like SL. Check out this article. I think it’ll point you in the right direction.
Christian says
Thanks for the trainingsguide!
KR from Hamburg, Germany
Nic says
I was wondering how would you design or what would be a good template for a beginner who’s primarily looking for hypertrophy right off the bat.
Most beginner programs out there are more oriented towards strength. I understand the merit of it in terms of strength and motor learning and wouldn’t mind doing something like that for compounds.
But I’d be interested to hear from Greg himself, I read some of the programs you’ve put out on the Internet and I like your way of doing this. Cheers.
Greg Nuckols says
It would primarily just consist of adding accessory work to strength programs, targeted at the muscles you want to grow.
Spanias Charalampos says
Great article, keep the good information coming!