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What is anabolic resistance?
Anabolic resistance is the phenomenon in which muscle does not respond to stimulus with normal muscle protein synthesis, but rather a reduced response. The stimuli that would elicit such a response are resistance training, as the academics call it, and ingestion of protein. In young, healthy people, these stimuli cause increased muscle synthesis, and over the longer term this means bigger muscles, as they adapt to continued stimulus.
Sarcopenia and the “hard gainer”
In sarcopenia, that is muscle wasting, which is most often seen in older people, basal muscle anabolism and catabolism can be normal, but the muscle fails to respond properly to stimulus, namely resistance training and protein consumption.
In younger men, we find the phenomenon of the so-called “hard gainer”, the guy who lifts and lifts and eats and eats, but can’t seem to put on much muscle, or at least finds it much more difficult than others to do so.
The cause of anabolic resistance
Anabolic resistance has actually been studied a fair amount because it’s a common condition in older people that leads to sarcopenia. Since sarcopenia often leads to disability, the inability to care for oneself (nursing homes) and ultimately death (from falls leading to hip fractures and the like), anabolic resistance is actually a major public health problem.
Researchers often focus on ways to fix it, but as to the cause, they are often reduced to saying that it’s just “age”. Sure, we know detailed cellular mechanisms of resistance, but why age causes these is another story.
However, I’ve come to the rescue, since I know what causes anabolic resistance. In a nutshell, inflammation, which increases greatly with age. Inflammation is also a cause of insulin resistance, also more common with age, and the two are related. It follows that with less inflammation and greater insulin sensitivity, anabolic resistance will diminish.
A large clue to how all this works is the fact that omega-3 fatty acids from fish oil are anabolic. For example, Omega-3 polyunsaturated fatty acids augment the muscle protein anabolic response to hyperinsulinaemia–hyperaminoacidaemia in healthy young and middle-aged men and women. In this study, fish oil caused a ~30% increase in muscle protein synthesis, and a ~50% increase in mTOR phosphorylation.
Even better results were seen in the elderly: Dietary omega-3 fatty acid supplementation increases the rate of muscle protein synthesis in older adults: a randomized controlled trial.
Fish oil can also help treat a condition that’s similar to sarcopenia, cachexia: Eicosapentaenoic acid (EPA, an omega-3 fatty acid from fish oils) for the treatment of cancer cachexia.
How does fish oil decrease anabolic resistance?
Fish oil decreases anabolic resistance probably by two different means: it decreases inflammation, and restores normal fluidity in cell membranes, allowing receptors to work properly. Fish oil has clinically important anti-inflammatory effects.
How to overcome anabolic resistance
There are several ways that anabolic resistance may be overcome.
1. Fish oil: by decreasing inflammation and increasing insulin and other receptor sensitivity.
2. Increased protein consumption. In younger people, 20 grams of protein in one meal may be enough to promote maximum protein synthesis. Older people may need more. In one study, older men undergoing resistance training had better muscle protein synthesis when they ingested 40 grams of whey protein as opposed to 20.
3. Exercise itself reduces anabolic resistance.
4. “Faster” protein: the protein in meat, eggs, and the like digests slowly, and amino acids in the bloodstream therefore do not rise to as high a level as they do with a protein that digests faster, such as whey. The level of amino acids in the blood is a crucial determinant of anabolism. Therefore, taking a fast protein such as whey, whether with a workout or without it, will cause greater anabolism, other things being equal, such as quantity.
5. BCAAs and leucine: BCAAs, particularly leucine, crucially determine the amount of muscle protein synthesis. So ingesting protein high in BCAAs / leucine will cause greater anabolism. Whey has the highest fraction of BCAAs of any protein.
6. In older people, resistance training. It appears that sarcopenia may arise from a combination of inflammation (“inflammaging”) or just disuse. Older people typically have good responses to resistance training, even into their 90s.
Don’t let age be an excuse
There you have it. It is not “age” that causes anabolic resistance, but various metabolic derangements that accompany it. If you’re older, or you’re a hard gainer, you can use some of these methods I outlined to overcome anabolic resistance.
P.S.: I was asked what type of whey I like, and the answer is NutraBio, which is cold-processed and undenatured. Best one available, IMO.
19 Comments
Wow!
Very informative post, Mr.Mangan.
I’m in the”hardgainer” boat at the moment. Even force-feeding myself, my gains have been slow going.
I knew fish oil was good for you, but now I know why. I will be investing in a BCAA powder in the near fututre as well.
Thanks, glad you got something out of it.
Thanks, Dennis. I am 62, so this post has relevance to my situation.
I’m a hardgainer who’s been enjoying reading your blog for a long time. I feel like I’m doing almost everything right, but I cannot ever put on muscle mass. I would greatly appreciate it if you were to use your encyclopedic knowledge to think of my case and offer me some advice:
Five years ago, I was a 28 year old who didn’t exercise much and was getting fat (38″ waist). I then got my act together and have been Paleo for about five years, I eat very little processed foods, sugars, starches and carbs, and eat loads of protein, fat, fruits, and vegetables. I exercise heavily at least twice a week (mainly heavy lifting, crossfit, soccer, swimming) and my waist has been around 32″ for years. My T-levels are pretty high (700+), and my medical tests are all ok. I’ve tried protein supplements, creatine, and amino acid pills but to no avail. I’m not lanky or very skinny, I have a nice figure to my body, but it just refuses to get very muscular. My shoulders are narrow, my wrists are very thin, and my arms and legs refuse to bulk up no matter what I do. Further info that might be relevant: even at 33, I have still not grown a full beard, I was pretty late to hit puberty, and my skin is still pretty soft like a child’s.
Do you have any idea what my problem might be? I may not do everything perfectly, but I have been reading about this for years and following all the smartest advice I get, but continue to not see positive results.
Thank you for this; very helpful. Just yesterday, my dad turned 70 but he still looks 50, and his dad was a very unhealthy chain-smoker who grew up in a place with low life-expectancy but still lived to his 60s. I think you hit the nail on the head. Do you think anything can be done about that? Obviously I’d like to keep the aging and logevity side, but would like more muscles!
I’ve tried the path of extra weight training, but it makes me stronger and skinnier. I can lift more than my very buff friends, and have much better core strength. If I bump into a weightlifter who’s much bigger than me on the soccer field, it’s astonishing to see him bounce off of me like he’s the lightweight, while I shrug him off like nothing hit me.
Would you think taking Human Growth Hormone might help? Could it possibly be down to me having estrogen levels that are too high? (I haven’t gotten that tested, but am planning on it.)
Thank you again!
BTW, I discovered I was heterozygous for the Klotho gene, which is associated with longer life. The way it does that apparently is by lowering levels of IGF-1, through which GH works. So you see the hormonal association there. Despite that, I was able to start from skinny and put on 35 pounds of muscle, so it can be done even if you are less than genetically inclined to it.
Thanks again. Do you have any reading recommendations on HGHs’ positives and negatives?
I recently took Clomid and it boosted my T levels to 1300, but it still didnt help me gain.
Veryhardgainer: That’s a tough one. One clue might be your relatively youthful looks and lack of beard. If you’ve read some of my other stuff, you know there’s a strong relation between growth and aging. It seems possible that you have a genetic makeup that predisposes against growth and aging and for longevity. That of course won’t help your hardgaining.
Another thing, swimming and soccer won’t help you get bigger. They would if you were otherwise untrained, but in your case you’re not. Maybe instead of a swimming session or soccer game just use that time and energy for weights instead. I assume that you’re training properly and don’t need advice there (always to failure, compound exercises, etc.)
In some studies I’ve read, a lot of extra protein helped, like 3 or 4 whey shakes a day. Also, while being ex-overweight you’re probably very concerned about calories, but you’ll need at least a little calorie excess to build muscle.
Hope that helps, if you have any particular questions, I’ll try to answer them. I’m more well-versed in the nutrition and biochem areas than in the actual training, though of course I train myself.
You’re welcome. I rather doubt that estrogen levels would be an issue, since your T is well within normal range, and I’m not aware that estrogen is anti-anabolic itself. HGH probably would help, but then you’re facing the growth-longevity tradeoff. More GH, more aging. One of the ways that the growth-longevity tradeoff works is through GH, so I’m afraid there’s no way out of that dilemma.
If you took an aromatase inhibitor, that would boost your T maybe 50%, and that might help your gains.
What about the effects of whey protein on acne? I’m a young healthy male who’s trying to build muscle, but I also have acne. Recently I cut out all dairy, including whey, and my acne has greatly improved. Are there any non-dairy alternatives to whey? Or, should I try to add whey back to my diet?
As for the pros and cons of taking HGH, you might try the site of Jeffry Life. https://drlife.com/ or Cenegenics.
alex, alternatives are really few. I mean there’s soy which you don’t want to touch, and casein, which is a slower protein but it’s also dairy so that might affect your acne. I think I would concentrate on enough protein from food: meat, eggs, in fact it just occurred to me that you could try egg whites, which are sold in the grocery store.
BTW, I might write a post about this, but I had adult acne for most of my adult life, and two things rid me of it: going low-carb paleo, and I quit washing my face with soap. I take whey and it doesn’t seem to bother my skin.
Thanks again, Mangan.
I’m going to start seriously and consistently lifting and taking SeroVital hgh next week. Will let you know how it goes.
Dear P.D.,
Thanks for this very useful article. As you are aware I have just started lifting weights at age 62. I have always been lean (Martial Arts and Yoga when younger) and would very much like to build some muscle. I have started taking Whey protein shakes on the days on which I lift.
Excellent! Add to that this study which showed that adding Glycine to Leucin will overcome the
anabolic resistance while being in a state of inflammation:
https://ajpendo.physiology.org/content/310/11/E970