Top 5 protein metabolism publications by Kevin Tipton

On January 9, 2022, Dr Kevin Tipton passed away. I have written a tribute (click here) to describe my stories and memories of many years of friendship and several years of working together at the University of Birmingham. Kevin was regarded as one of the world’s leading experts in protein metabolism. He was particularly interested in what happened after exercise and what we could do to improve recovery and adaptation in the muscle.

In this blog I want to highlight 5 of his most important scientific papers. There may be other papers that have been even more impactful. But these are my personal top 5. These papers hugely helped our understanding of protein metabolism and influenced the recommendations we give to athletes.



Paper 1: Muscle protein turnover after exercise

  • Increased rates of muscle protein turnover and amino acid transport after resistance exercise in humans. Gianni Biolo, Sergio P Maggi, Bradley D Williams, Kevin D Tipton and Robert R Wolfe . Am J Physiol 268: E514-E520, 1995

Exercise increases protein breakdown and synthesis

This was one of Kevin’s very first scientific publications. Gianni Biolo is the first author and Bob Wolfe was the senior author on this paper from a study performed in Galveston Texas. The main finding of this paper was that after exercise both protein synthesis and degradation are increased. This was an invasive study that used a new method of stable isotopic tracers, arteriovenous catherization of the femoral vessels (essentially drawing blood from an artery and a vein in the leg) in combination with biopsies of the vastus lateralis (quadriceps muscle). The paper debunked the simplistic view that is often communicated: during exercise muscle protein breakdown is increased and after exercise you make new proteins. This is an oversimplification. Both breakdown and synthesis are increased after exercise, and there is an increased turnover. This is likely because damaged proteins need to be broken down first and then replaced with new ones. The study also suggests that blood flow to the leg plays a very important role in delivering amino acids, which may facilitate the transport of those amino acids into the muscle. This paper may not have changed the recommendations to athletes immediately, but it helped our understanding of how the recovery/adaptation process works.



Paper 2: Protein metabolism over 24 h

  • Acute response of net protein balance reflects 24h balance after exercise and amino acid ingestion. Kevin D Tipton, Elisabeth Borsheim, Steven E Wolf, Arthur P Sanford and Robert R Wolfe. Am J Physiol 284: E76-E89, 2003


Muscle protein synthesis over 24h after protein intake

This is the first study (at least that I am aware of) that looked at 24 hour protein metabolism in exercising individuals with and without amino acid ingestion. Most studies had performed measurements for 3 or 4 hours after exercise. But it always was a big question whether what you measure in 3 hours can also be extrapolated to 24 hours or longer. In other words if I measure that I can increase muscle protein synthesis over 3 hours after resistance exercise by a particular nutrition intervention, does this mean that it will also do this over 24 hours ? and will this ultimately result in more muscle mass?


These studies are very hard to conduct because stable isotope tracers have to be infused intravenously for 24 hours, diets need to be standardized, exercise needs to be supervised and so on. Kevin had some great stories about this study. Not only was this study quite invasive (with arteriovenous differences across the leg, infusion of stable isotopes and muscle biopsies), they were also difficult because of the sampling that needed to occur around the clock.

When the subjects in this study were sleeping, the researchers were still monitoring everything, and taking blood samples. And so far, no one had attempted these measurements over 24 hours.

It turned out that the results 3 hours after exercise were comparable to the 24 hour results. In this study an intervention of essential amino acids increased protein synthesis after exercise. And the elevation measured with essential amino acid feeding after 3 hours was still noticeable after 24 hours. So in a way this validated the use of the shorter studies as others later also confirmed by increases in muscle mass and strength over an even longer period of time.



Paper 3: Whey protein intake and protein synthesis: dose response

  • Myofibrillar muscle protein synthesis rates subsequent to a meal in response to increasing doses of whey protein at rest and after resistance exercise. Oliver C Witard, Sarah R Jackman, Kenneth Smith, Anna Selby and Kevin D Tipton. Am J Clin Nutr 99: 86-95, 2014.


Whey protein intake and protein synthesis: dose response relationship

In this study (Olly Witard being the first author and Kevin Tipton the senior author), the relationship between protein dose and muscle protein synthesis was investigated. A group of 48 volunteers conducted a strength training session followed by the ingestion of different doses of whey protein isolate (for the differences between whey protein and isolate or hydrolysate read this blog). The volunteers ingested no protein, 10, 20 or 40 grams of whey protein isolate. There was a dose response relationship from 0-20 grams of protein but with 40 grams even though the dose obviously doubled from 20 grams there was no significant improvement. It was therefore concluded that 20 grams of whey protein is probably enough in a meal and increasing this to 40 grams will increase urea production and oxidation of the amino acids. This study of course has very important practical implications.

This project was based on volunteers of 80 kg and it was acknowledged by the authors that heavier athletes (>100kg), could have slightly increased needs but this study can neither confirm nor deny this.



Paper 4: A review of the protein metabolism literature

  • Protein and amino acid metabolism during and after exercise and the effects of nutrition Michael J Rennie and Kevin D Tipton. Annu Rev Nutr 20:457-83, 2000.


Key points about protein metabolism and exercise by Rennie and Tipton

One of the publications that Kevin was most proud of was a paper he co-authored with Mike Rennie. Mike was someone who Kevin respected very much for his scientific opinions and work. So to summarise all the work on protein metabolism up to that point together with one of the greatest physiologists was an honour for Kevin. The result was a very comprehensive review of the literature with some clear conclusions:


  • Endurance exercise stimulates the breakdown and oxidation of amino acids (especially branched chain amino acids). This will also result in ammonia production. The higher the exercise intensity the more ammonia will be produced.

  • The contribution of protein to energy expenditure is small.

  • If the exercise is intense enough, there is a net loss of muscle protein (as a result of decreased protein synthesis, increased breakdown, or both).

  • Protein balance is restored after exercise, but no muscle hypertrophy occurs with endurance exercise.

  • Resistance exercise causes little change in amino acid oxidation but may depress protein synthesis and elevate breakdown acutely.

  • After exercise, protein synthesis rebounds for </=48 h,

  • Breakdown will remain elevated after exercise, and net positive balance is achieved only if amino acid availability is increased.

  • There is no evidence that habitual exercise increases protein requirements. In fact, the opposite may be true. Protein metabolism may become more efficient as a result of training and therefore protein needs will decrease.



Paper 5: No effect of protein on Tim trial performance and recovery


  • No effect of carbohydrate-protein on cycling performance and indices of recovery. Leigh Breen, Kevin D Tipton, Asker E Jeukendrup. Med Sci Sports Exerc 42(6):1140-8, 2010.


Protein has no effect on performance or recovery when ingested during endurance exercise

As one of the papers I had to pick a joint publication. In this study by Leigh Breen, then a PhD student and now a lecturer at the University of Birmingham, we wanted to know whether there was a benefit of adding protein to carbohydrate drinks during exercise. We wanted to see if protein had the potential to affect performance or perhaps improved recovery post exercise.


Therefore, in a double-blind, crossover design, 12 trained male cyclists performed 2 hours of cycling exercise at a moderate intensity, followed by a time trial lasting approximately 1 h. At 15-min intervals during exercise, subjects ingested either carbohydrate drinks with or without protein. Several measures of recovery were monitored for the 24 hours after the exercise. The results showed that there were no differences in performance (not positive, not negative). The added protein also did not have any effect on plasma creatine kinase, a marker of muscle damage, measures of muscle soreness or muscle function in the 24 hours after exercise.


So from a practical point of view one might conclude from this study that there was no benefit of adding protein to a carbohydrate drink during endurance exercise.

References


Increased rates of muscle protein turnover and amino acid transport after resistance exercise in humans. Gianni Biolo, Sergio P Maggi, Bradley D Williams, Kevin D Tipton and Robert R Wolfe . Am J Physiol 268: E514-E520, 1995


Acute response of net protein balance reflects 24h balance after exercise and amino acid ingestion. Kevin D Tipton, Elisabeth Borsheim, Steven E Wolf, Arthur P Sanford and Robert R Wolfe. Am J Physiol 284: E76-E89, 2003


Myofibrillar muscle protein synthesis rates subsequent to a meal in response to increasing doses of whey protein at rest and after resistance exercise. Oliver C