Why Muscle Doesn’t Respond: Protein Efficiency, Obesity & Resistance Training | Dr. Nick Burd

Burd mapped out the unique metabolic situation of the endurance athlete. During a run, leucine oxidation provides carbon skeletons for the TCA cycle. Post-exercise, amino acid kinetics show a persistent negative net leucine balance that even standard feeding couldn't reverse in his studies because the exogenous amino acids were partitioned to oxidation replacement rather than anabolic incorporation. He therefore recommends targeting the immediate post-exercise period with a fast protein (whey isolate) plus carbohydrate to spike amino acids and insulin, shutting down oxidation and channeling leucine into MPS. Once that acute phase is covered, the athlete can return to whole food meals for the remaining recovery. He contrasted this with weightlifters, who have a prolonged anabolic window and don't need to rush protein intake.

Burd described collaborating with Luke van Loon's group and testing various strategies to overcome digestive anabolic resistance in aging. While older adults are often told to simply eat more protein, that advice fails with satiety issues. His group experimented with an enzyme blend (containing proteases) during a mixed meal and found it boosted plasma amino acid concentrations. Another acute study using a plant protein (P protein) also showed increased net postprandial plasma amino acid concentrations with protease supplementation. Though he personally doesn't use it, he would recommend it to his grandparents. The work is still in early stages but suggests a viable approach for those who can't eat large protein portions.

Burd's group conducted a series of food matrix experiments. The whole egg vs. egg white study demonstrated that an isonitrogenous amount of egg white produced less MPS than whole eggs, even though the leucine peak didn't differ, meaning factors beyond leucine were at play. Similarly, a whole salmon filet outperformed a beverage containing the identical macronutrients. Excited by these results, they tested whether a lipid-rich ground meat (80% lean pork, a common purchase) would similarly boost MPS. Surprisingly, it suppressed the anabolic response compared to lean ground pork. Burd connects this to the heavy processing: grinding and re-adding fat trimmings likely alters the food matrix such that the normal synergistic effects of lipids are lost, and the meal may even provoke a pro-inflammatory or slow-digesting pattern that blunts acute MPS. For consumers, he suggests that whole, less manipulated animal proteins are preferable, but the key is to test specific foods rather than assume all 'whole foods' are equal. He is extending this work to obese muscle to see if certain food matrices can help overcome intrinsic anabolic resistance.

Burd explained that obese individuals have abundant protein intake and normal digestion, yet their MPS response to a 36g protein bolus was severely blunted. The problem is intrinsic to the muscle tissue: limited capillary density restricts nutrient delivery, mTOR — the master kinase for anabolism — remains trapped in the sarcoplasm away from the membrane where it should be activated, and intramuscular fat droplets physically impede signaling. This constellation means simply eating more protein won't rescue the response; instead, the focus must be on remodeling the muscle's internal environment through consistent resistance exercise. He emphasized that his acute lab tests showed no rescue from a single protein dose, but repeated training over time can restore efficiency. 'The quantity is there, but the quality is poor,' he said, underscoring that obese muscle needs turnover improvement, not more substrate.

Burd defined protein efficiency as: 'When we consume the same absolute amount, so if we eat 20 grams of food protein... if you're efficient... you're going to get a large incorporation to the myofibrillar [protein].' He sees this as a trainable quality. Resistance exercise makes muscle more anabolic per unit of amino acid, meaning a well-trained individual may achieve similar remodeling with less protein than someone sedentary and inefficient. He hinted that many recommendations blindly apply the upper confidence interval (e.g., 1.6 g/kg) without asking whether the lower end (1.2 g/kg) might suffice if the person trains consistently. This reframes protein needs as dynamic, not static.

Burd explained that when an endurance athlete runs for an hour, they oxidize leucine and other amino acids as fuel, entering a negative leucine balance. Unlike weightlifters whose muscle is sensitized and ready to incorporate amino acids anytime after training, endurance athletes face a double burden: the ingested protein must first replace the oxidized leucine losses before any can be used for remodeling. His work showed that feeding after a run failed to fully recover the leucine net balance because the food was 'fighting two battles.' Therefore, the post-exercise meal must deliver amino acids rapidly and in sufficient quantity. He advocates a fast protein (whey isolate) + carbohydrate blend immediately (within 1-2 hours), then returning to whole foods later. Overall daily protein intake for these athletes is usually adequate, but timing is the missing piece.

Burd detailed his lab's series of food matrix studies. In the egg study, whole eggs generated a greater myofibrillar protein synthetic response than an equal amount of protein from egg whites, despite similar leucine spikes. A salmon study replicated this: a whole salmon filet outperformed a beverage containing the same macronutrients. However, when they tested an 80% lean ground pork (heavily processed, fat added back), the lipid-dense meat suppressed MPS after weightlifting compared to lean ground pork. This inverted the pattern. Burd hypothesizes that the difference lies in the physical processing: minced, re-formed meat creates an abnormal matrix that alters digestion kinetics, and in that scenario the leucine trigger hypothesis became predictive (higher leucine correlated with higher MPS), whereas in intact foods it didn't. He cautioned against extrapolating from one food matrix to another; each must be tested individually.

Burd recounted that prior to the results, he was convinced animal protein would be superior, but the outcomes showed equivalence when comparing whole-food vegan meals to animal-based meals under his experimental conditions. He attributes the delay in publication to shifting nutritional narratives. This finding adds nuance: with careful meal composition (likely including factors like food matrix and total protein dose), vegan diets can support remodeling. He didn't go into specific meal compositions, but the takeaway is that dogmatic 'animal is necessary' positions are unproven.