Tier 2 — strong

Supplements with purported effects on muscle mass and strength

Valenzuela PL, Morales JS, Emanuele E, Pareja-Galeano H, Lucia A
European Journal of Nutrition 2019 58(8):2983-3008

Bibliography

PubMed
PMID 30604177
DOI
10.1007/s00394-018-1882-z
Funding
Pedro L. Valenzuela was supported by University of Alcalá (FPI2016); Javier S. Morales by the Spanish Ministry of Education, Culture and Sport (FPU14/03435); Helios Pareja-Galeano by Universidad Europea de Madrid (2017/UEM05) and Cátedra Real Madrid–Universidad Europea (2017/RM03); Alejandro Lucia by the Spanish Ministry of Economy and Competitiveness and FEDER (PI15/00558).
Competing interests
The authors declared no conflict of interest.

Study snapshot

DesignNarrative review with structured evidence-grading (levels A to D) across multiple supplement categories
ModelNot applicable — literature review, human sports-nutrition evidence base
SampleNot applicable — literature review
InterventionNot applicable — reviews the published human evidence for creatine, protein, nitrate, caffeine, branched-chain amino acids, arginine, ornithine, alpha-ketoglutarate, and other supplements marketed for muscle mass or strength
DurationNot applicable
EndpointsStructured evidence grading (A = consistent benefit, D = no evidence) for each supplement's effect on muscle mass or strength

What the study showed, in plain terms

This 2019 review in the European Journal of Nutrition graded the human evidence behind popular muscle-mass and strength supplements — and it is an important honest counterweight in this Data Center, not a supporting citation.

The authors placed creatine, protein, and polyunsaturated fatty acids at their strongest evidence grade (A) for long-term muscle mass and strength benefits. Alpha-ketoglutarate, alongside ornithine, was placed at the lowest grade (D): no evidence found for an effect on muscle mass or strength, as of the review's 2019 literature base.

This does not contradict the newer 2025 mouse sarcopenia data in this hub — that paper is preclinical animal evidence published six years after this review, using a specific aging model and specific AKG dose, and the two papers ask different questions. But it does mean that, as of 2019, the human sports-nutrition literature specifically had not shown a muscle-mass or strength benefit for AKG — and readers deserve to see that stated plainly rather than only seeing the more favourable animal data.

Key findings

  • Strongest evidence grade (A) went to creatine, protein, and polyunsaturated fatty acids: the review found consistent, long-term muscle mass and strength benefits for these three supplement categories.
  • Alpha-ketoglutarate was graded D — no evidence found: the review states explicitly that no evidence was found for ornithine or alpha-ketoglutarate having an effect on muscle mass or strength, based on the human literature available at the time of the review.
  • Safety caveat noted for high intakes: the review flagged that some adverse events had been reported for several supplements — including alpha-ketoglutarate — after large intakes, though most supplements were considered safe at typical doses.

What this study can and cannot tell us

Literature base is now dated for AKG specifically. This review's AKG evidence grade reflects the human sports-nutrition literature available up to 2018. It predates the 2025 mouse sarcopenia mechanistic data now in this Data Center and does not incorporate it.

Narrative, not systematic, methodology. The review does not describe a pre-registered systematic search and screening protocol for each supplement category.

Human sports-performance framing. The review's grading targets muscle mass and strength specifically in the context of exercise and hypertrophy, not the broader ageing, frailty, or metabolic-health questions this Data Center otherwise tracks for AKG.

Citation network

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Biohack Blueprint analyses that reference this study in their evidence base.

Editorial review

Reviewed by the Biohack Blueprint research team

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Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology