#299 ‒ Optimizing muscle protein synthesis: the crucial impact of protein quality and quantity, and the key role of resistance training | Luc van Loon, Ph.D.

"It's the exercise that makes you respond way more to the same or less amount of protein that you ingest.” —Luc van Loon

Read Time 71 minutes

Luc van Loon is an internationally renowned expert in skeletal muscle metabolism. In this episode, Luc starts with an exploration of the roles of insulin and triglycerides in endurance exercise, highlighting their impact on skeletal muscle metabolism, and he offers profound insights into the significance of protein in this context. He elucidates how different protein types and forms influence muscle protein synthesis rates, exploring the nuances of protein absorption, digestibility, amino acid quality, and their implications for performance and recovery. Delving deeper, he differentiates between animal and plant protein sources, unraveling the distinctive properties of various protein types, from the differences between whey and casein to the emerging trends in collagen protein supplementation. Moreover, Luc dissects the intricate connections among physical activity, lean muscle mass, muscle protein synthesis induced by resistance training, and dietary protein.  


We discuss:

  • Luc’s background and insights about fuel selection during exercise [3:30];
  • Fuel utilization during endurance exercise [9:30];
  • Fat metabolism, intramuscular lipids, and the nutritional dynamics of endurance sports [17:15];
  • The optimal window for replenishing intramuscular fat stores and glycogen post-exercise [25:15];
  • Luc’s interest in protein metabolism and exploration of amino acids’ dual role as building blocks and signaling molecules in driving muscle protein synthesis [32:15];
  • How protein metabolism differs between sedentary individuals and those engaged in predominantly strength training or endurance training [38:45];
  • The basics of how proteins are digested and absorbed, and how muscle protein synthesis is measured [50:30];
  • How factors like food texture, cooking methods, and protein composition’s impact on muscle protein synthesis, and the importance of protein distribution throughout the day [59:45];
  • Differences in whey and casein proteins, and the ability of ingested protein to stimulate muscle protein synthesis [1:03:30];
  • Dietary protein distribution and quantity for the maximization of muscle protein synthesis [1:09:00];
  • Muscle loss with age and inactivity and the importance of resistance exercise to maintain type II muscle fibers [1:17:15];
  • Differences between whey and casein proteins, and the importance of both quantity and quality of protein sources [1:28:30];
  • Optimizing muscle protein synthesis: exercise, timing of protein intake, protein quality, and more [1:37:00];
  • How to preserve muscle while trying to lose weight [1:46:00];
  • Anabolic resistance and overcoming it with physical activity [1:55:45];
  • Importance of protein intake and physical activity in hospitalized patients [2:06:30];
  • Reviewing the efficacy of collagen supplements [2:13:30];
  • Plant-based diets: how to ensure a balance of amino acids, and other considerations [2:20:30];
  • Future research: understanding protein metabolism in the brain [2:23:45]; and
  • More.


Luc’s background and insights about fuel selection during exercise [3:30]

  • Luc didn’t didn’t know where to go to college
  • Most exercise physiologists are field athletes, so we want to know how our genetics can be compensated for by science
  • He wanted to do movement sciences, so he studied movement sciences at Maastricht in the Netherlands
  • After that, he went to Austin, Texas to work with Jack Wilmore at UT for his Master’s internship
  • After that, he finished his PhD in Maastricht again
  • Then, he went to Melbourne to work with Mark Hargreaves
  • After spending some time in Melbourne, he came back and has spent the rest of his career in the Netherlands
    • From assistant prof to associate and to full professor, over the past 15 years

The focus of this episode 

  • Today, we’re going to not talk so much about the movement stuff, although that would be very interesting to our audience
  • Instead we’re going to talk more on the nutrition side of things, specifically (and in great detail) about protein

Protein is not necessarily your first foray into nutrition, correct? 

  • No, that’s correct
  • Luc’s main interest in the beginning and also in his PhD was in fuel selection 
    • Substrate selection during exercise, and most of that stuff is done during endurance-type exercise 
  • And if you’re thinking about substrates, you’re not thinking about protein, which is from a quantitative point of view is not a very good substrate
    • Instead, it’s carbohydrate and fat metabolism
  • The most interesting thing for him at that time was that they had set up a stabilizer dope research facility where you could track metabolites
  • The first things that that lab did is actually measure carbohydrate oxidation rates
    • You would simply throw in some stable isotope labeled carbohydrates in your drink and simply by the oxidation of those carbohydrates, you would exhale 13CO2
      • If it’s labeled with 13C, you get 13CO2 after you oxidize it
    • And by simply acquiring your expired breath, you can calculate how much of your energy came from a sports drink
    • Luc explains, “That was so cool for me at that time.”

Just to be clear, you would also need to know the amount of oxygen consumption to be sure that that CO2 came from glucose and not from fat, correct? 

  • Yeah, it’s a combination of indirect telemetry, so that’s total oxygen uptake and total carbon dioxide production, combined gives you total energy expenditure and also total oxidation of carbohydrates and fats
  • Then, because you know what percentage of the carbohydrates derived CO2 was expired by 13CO2, you could calculate back how much of the carbohydrate is coming from your drink
    • That is cool, because then you’ll see how much of the drink are you actually using
  • Peter mentions a method that uses deuterated water in C-13 (doubly labeled water) to measure energy expenditure in a free living environment over a long period of time

Is the method you are referring to only using labeled carbon and therefore only suitable for a short period of time to evaluate glucose oxidation, or do you also label oxygen and potentially get energy expenditure over a long period of time? 

  • If you use doubly labeled water, you need several days to do that
    • You’re getting carbohydrates in, you start oxidizing them, that CO2 is also mixed in your blood
  • It takes a while before the expiration of labeled carboy is a good proxy for the amount of carbohydrates that you’re oxidizing
  • In 2 hours, they’re in a nice steady state
    • That’s why he’s measuring oxidation rate at 1-2 hours for endurance athletes
    • That’s only for exercise trials

Peter asks, “Did this tend to be more accurate than the estimate you would get of carbohydrate oxidation rate just using the indirect calorimetry and the Weir equation? Or was the point here to determine not total carbohydrate metabolism, but specifically how much is coming from the drink?

  • Exactly, you can see how much of that carbohydrate is coming from your drink (versus glycogen)
  • You have your glycogen coming from your liver, you have your glycogen coming from your muscle, you can actually detect that with an intravenous glucose tracer with a different label, and then you have your 13C label in your drink, so you can actually see all 3 substrates
    • You can see what is coming from the drink, what is coming from your muscle glycogen, and what is total coming from your plasma glucose
      • Plasma glucose includes the drink, but you can subtract that from the total
  • That was not enough for Luc, he also wanted to know what fatty acids are being used from your intramuscular triglycerides (the fat inside your muscle fibers) and what is come actually from the fat tissue that is releasing fatty acids and then transported to the circulation and taken up in the muscle
    • Because that is also an important topic for athletes, and also diabetes patients


Fuel utilization during endurance exercise [9:30]

Peter is preparing for a long endurance event 

  • An event that’s going to take about 20 hours
  • It’s been so long since he’s thought about how to prepare energetically for something like this
  • Peter believes that nutrition can make or break you in these 20-hour marathon events

What did you learn about the rate of carbohydrate metabolism, muscle glycogen, liver glycogen in the steady state? 

  • One of the most important things is that all the glucose that is coming into circulation will be used for oxidation during exercise

It’s a good idea to have a continuous supply of glucose coming from your gut 

  • To keep your liver glycogen intact, or at least not to deplete too fast
  • You want to maximize your liver glycogen
  • We know that glucose polymers are oxidized at a rate of 1.0-1.1 grams per minute
    • About 60-70 grams per hour
    • However it can be a little bit higher if you add some fructose
      • Because fructose requires a different transporter
      • So if you combine glucose with fructose, you can get a little bit higher, but that’s only for the high-end athletes that can actually gain that high energy expenditure
      • Then you go up to maybe 1.3-1.4 grams per minute

{end of show notes preview}

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Luc van Loon, Ph.D.

Luc van Loon studied movement sciences at Maastricht University in the Netherlands, after which he completed an internship at the University of Texas at Austin in the Department of Kinesiology and Health Education. He then earned his Ph.D. in the Department of Human Biology at Maastricht University, where he studied the effects of exercise and nutrition on muscle fuel selection. Next, he completed post-doctoral research at both Maastricht University and Deakin University in Melbourne, Australia. Currently, Dr. van Loon is a Professor of Physiology of Exercise and Nutrition in the Department of Human Biology and head of the M3-research group at Maastricht University Medical Centre. The objective of his research is to gain insight in the benefits of more physical activity and exercise training on health and performance, and the impact of nutrition on the skeletal muscle adaptive response to exercise training.

Dr. van Loon has expertise in the area of skeletal muscle metabolism and has published over 500 peer-reviewed articles. Current research in his laboratory focuses on the skeletal muscle adaptive response to physical (in)activity, and the impact of nutritional and pharmacological interventions to modulate metabolism in both health and disease. The latter are investigated on a whole-body, tissue, and cellular level, with skeletal muscle as the main tissue of interest. To support the use of stable isotopes in biomedical research, Luc is also scientific coordinator of the Stable Isotope Research Centre (SIRC) at Maastricht University Medical Centre+. [Maastricht University]

Disclaimer: This blog is for general informational purposes only and does not constitute the practice of medicine, nursing or other professional health care services, including the giving of medical advice, and no doctor/patient relationship is formed. The use of information on this blog or materials linked from this blog is at the user's own risk. The content of this blog is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Users should not disregard, or delay in obtaining, medical advice for any medical condition they may have, and should seek the assistance of their health care professionals for any such conditions.


  1. Muscle protein synthesis is in sustainable beyond a certain point. At that point the myonuclei domain becomes too expansive and incorporation of new myonuclei is necessary. This is accomplished via satellite cell activation into myoblasts and subsequent fusion with existing myofibers, donating fresh myonuclei. This is influenced by igf-1 and other growth factors and the whole process can be initiated by resistance exercise. Certain drugs and natural substances can potentiate this response

  2. This conversation very insightful and useful.
    Thank you Luck van Loon Ph.D. and Peter Attia M.D.

  3. Okay. After listening to this podcast and reading the articles mentioned, I think I’ve got it figured out. I weigh 200lbs and want to consume 200g of protein in an 8 hour window. Am I correct in now thinking I can do this in three 60g meals with one 20g protein snack (or maybe even three 70g meals)? I used to consume 40g every two hours (0, 2, 4, 6, 8 hrs). Do all these feeding routines produce the same general metabolic response?

  4. This is really interesting thanks for publishing. As a consumer of primarily plant-based protein (including protein powders), what total amount of leucine, lysine and methionine should I be shooting for daily? My current protein powder blend has 1900, 1800 and 500g respectively per serving and I generally have 2 servings of this powder per day on top of a normal vegan-ish diet. Is that enough for a 195 lb man?

  5. This is a great point:
    “What we now often with patients going home earlier (especially with COVID) is when a lot of older people go home, their bed is put downstairs, and those people will never walk stairs anymore”

    This is the biggest issue I have with 55 and Older Senior Housing (since when is 55 a “senior”?) where homes are built without stairs and marketed to emphasize everything is on one level. Able bodied people should climb stairs and/or walk hills as much as possible.

  6. Those of us with hip or knee implants are warned about high-impact stresses or activities causing implant friction (jumping, running, weight lifting, etc.) because of the particles created from the HMWPE acetabular or tibial components that create osteolysis and bone loss that necessitate revision. If resistance exercises are needed at my age (75), how do I reconcile osteolysis potential with the need to stimulate type II muscle fibers? In addition, I have a fracture plate with 12 screws in my femur from a post-op fracture that limits femur flexibility such that something like weighted squats could jeopardize screw integrity. I guess I was just dealt a poor deck of cards. I’m open to suggestions.

    • The use of resistance bands could be beneficial there ,hard on the muscle soft on the joints. I think there’s a form of Yoga-Asana Yoga or so wich is also quite strenuous (I’m not an expert in yoga…)And for zone 2 training cycling and swimming.

  7. I’m on ADT. My personal experience is that Dr Luc is correct that resistance exercise and sufficient protein are extremely helpful. That said, the Zero Testosterone life style provides many metabolic and other challenges.

    I was shocked that my oncologist had no recommendations for living with the therapy but did send me to a nutritionist that specializes in T2D. A naturopath ran tests and quickly told me to eat dramatically more protein and recommended a number of supplements to help fix impaired carbohydrate metabolism.

  8. My goodness! I absolutely love all the podcasts, but boy this one really stands out! It was just utterly captivating. I found myself gasping, laughing and saying “Wow!” out loud. Peter and guests, thank you so much for this content!! It just means the world to get access to this cutting edge research in a digestible (pun intended) manner!
    The point about the speed of digestion of protein based on it’s intake form and preparation is fascinating and I would actually be very curious hear more about this phenomenon with respect to FIBER. By all counts, there is little doubt that fiber is critical to overall health for several reasons, but it can be challenging to get the recommended amounts. I would be very curious to know how the preparation and ingestion of fiber alters its health promoting effects on the body. For example, eating an avocado vs putting one in a smoothie. If one benefit of fiber is slowing the absorption of carbohydrates to blunt the the glycemic effect, then does macerating it in a blender reduce or even eliminate that benefit. However another benefit of fiber is as a prebiotic…so if we’re talking about feeding the gut microbiome, then maybe it doesn’t matter if the fiber is macerated? Let’s get a fiber expert to comment!

  9. Thanks for this fantastic podcast with Luc. This is exactly what I ‘m looking for,definitely need to go through a second time.And yes concerning the elderly patient – particularly post surgical procedures – one cannot emphasise enough muscular training plus protein intake for recover.

  10. Not really related to protein but related, I think to protein synthesis and muscle growth, since older pee, in general, loss muscle mass at an increasing rate, should we be taking Creatine to aid muscle growth? Thank you for any insight.

  11. Muscle protein synthesis? Rapid turnover? This comment is “going to the birds”. Why? Because some birds go through (by human standards) truly INSANE cycles of atrophy/hypertrophy of muscle tissue and other tissues. e.g. flight muscles atrophy and they become flightless for months and then, in 2-3 weeks, hypertrophy and regain flight for migration. Fat stores and other body systems completely reorganize. Cycle is repeated over and over.
    Jehl, Jr., J. R. (1997). Cyclical changes in body composition in the annual cycle and migration of the Eared Grebe Podiceps nigricollis. Journal of Avian Biology 28:132-142.
    The biological potential is there waiting to be unlocked.

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