# Research timeline and gaps: Protein Intake and Muscle Function in Older Adults

Selected publication milestones, not an exhaustive history or discovery priority claim.

**2006 — 2006 acute EAA/leucine tracer experiments demonstrate composition-sensitive synthesis.** [Original PMID16507602](https://pubmed.ncbi.nlm.nih.gov/16507602/).

**2012 — 2012 bed rest shows reduced anabolic response, linking inactivity to a physiological boundary.** [Original PMID22338078](https://pubmed.ncbi.nlm.nih.gov/22338078/).

**2012 — 2012 nutrition-only frailty trial improves SPPB without mass gain.** [Original PMID22889730](https://pubmed.ncbi.nlm.nih.gov/22889730/).

**2012 — 2012 separate training trial increases lean mass without added strength or SPPB benefit.** [Original PMID22770932](https://pubmed.ncbi.nlm.nih.gov/22770932/).

**2015 — 2015 PROVIDE retains secondary chair-rise and lean-mass positives with primary functional nulls.** [Original PMID26170041](https://pubmed.ncbi.nlm.nih.gov/26170041/).

**2015 — 2015 weight-loss formulation preserves lean mass without additional function.** [Original PMID25646324](https://pubmed.ncbi.nlm.nih.gov/25646324/).

**2017 — 2017 factorial weight-loss study reports modest achieved dose separation and endpoint-specific interactions.** [Original PMID28166780](https://pubmed.ncbi.nlm.nih.gov/28166780/).

**2018 — 2018 controlled feeding tests above-RDA intake with no functional advantage in its enrolled group.** [Original PMID29532075](https://pubmed.ncbi.nlm.nih.gov/29532075/).

**2018 — 2018 malnourished frailty dose trial identifies highest-dose mass and gait benefit.** [Original PMID30475969](https://pubmed.ncbi.nlm.nih.gov/30475969/).

**2020 — 2020 year-long whey trial in sarcopenia reports functional nulls.** [Original PMID31734121](https://pubmed.ncbi.nlm.nih.gov/31734121/).

**2021 — 2021 CALM separates ineffective protein alone from effective heavy loading.** [Original PMID33564844](https://pubmed.ncbi.nlm.nih.gov/33564844/).

**2021 — 2021 PRO-Elderly finds no nutrition add-on to training.** [Original PMID34358827](https://pubmed.ncbi.nlm.nih.gov/34358827/).

**2026 — 2026 small fermented-whey trial supplies a positive multinutrient replication lead.** [Original PMID41805014](https://pubmed.ncbi.nlm.nih.gov/41805014/).

**2026 — 2026 adequate-intake older-women trial finds training benefits without added leucine.** [Original PMID40926079](https://pubmed.ncbi.nlm.nih.gov/40926079/).

## Research gaps

A universalabove-RDA targetcannotbe readfromanacuteMPS plateau or observational dietassociation.

The relativecontributionofproteinquantity,quality,energy correction,vitaminD andexercise needsmatchedcomponent controls.

Longterm musclefunction isnotidenticaltoDXA/BIA leanmass orbiochemicalanabolism.

Achievedintake andbaselinefrailty/nutrition interactionsneed independentprospective replication;frailtyalone isnot aresponderdefinition.

Medication-assistedweightloss protein/training evidence isstilldirectlyneeded;protocols do notvalidateallGLP-1muscle-loss mitigation claims.

Renalstate,exposure duration andproduct ingredientsdefine safetyinference;short unchangedcreatinine isnotall-populationsafetyproof.

## Boundary experiment

A preregistered multicenter isocaloricproteinquantitytrial with0.8g/kg/day comparator and clearlyachieved higherintake, stratifiedbeforeoutcomes bynutrition/frailty andincluding a factorial resistance-training component; GLP-1treated adults needtheirown controlled stratum withmeasuredfunction.