The study, funded by Abbott Nutrition, USA, aimed to determine whether adding HMB to whey protein would augment the anabolic response in muscle, particularly the postprandial rate of muscle protein synthesis (MPS), in older men and women who are susceptible to anabolic resistance and sarcopenia.
HMB is a metabolite of leucine, an essential amino acid that triggers MPS by activating the mTOR signaling pathway. HMB, while being anabolically less potent than leucine, plays an equally key role in muscle preservation by preventing catabolism (muscle breakdown)
Observing differences in response between the sexes, researchers in the UK and USA wrote in Nutrients: “Surprisingly, 40 g whey did not maximize the anabolic response in older women, and HMB further increased the MPS feeding response to protein”.
Prof. Shawn Baier, an HMB research scientist & senior director of global ingredient science at TSI Group, which manufactures myHMB, told NutraIngredients that the study provides a deeper understanding of the benefits of HMB.
“What stood out was that myHMB further increased muscle protein synthesis feeding response to protein and helped maintain suppression of muscle protein breakdown for a longer period of time than whey protein alone,” he said.
“That is particularly relevant in aging because the challenge is not simply stimulating muscle growth due to anabolic resistance, it is also limiting the ongoing loss of muscle tissue that occurs over time.”
Muscle protein synthesis in older age
Consuming dietary protein rich in essential amino acids stimulates increases in muscle protein synthesis (MPS) by 2-3 fold, but this effect declines 2-3 hours after eating.
In older age, anabolic resistance can blunt the anabolic response to dietary protein intake. Anabolic resistance may occur due to compromised digestion and absorption, increased retention of amino acids by abdominal organs (splanchnic uptake), and microvascular dysfunction in the muscles.
Therefore, prior evidence suggests that a relatively large protein meal is needed to stimulate muscle protein synthesis (MPS) in older adults. Additionally, some evidence suggests sex differences in responses to protein intake, which may be due to differences in basal MPS rates and factors such as menopause.
However, Prof. Baier commented that he would be cautious about drawing broad conclusions from the current study: “The study was not specifically designed or powered to fully investigate sex differences. What it does provide is a strong rationale for future research examining whether women may derive particular anabolic benefits from combining HMB with protein.”
He added: “From a practical standpoint, the most important takeaway is that myHMB continued to suppress muscle protein breakdown regardless of sex. The female-specific muscle protein synthesis findings are intriguing and could have important implications for healthy aging nutrition, but they should be viewed as an area for further investigation rather than a definitive conclusion.”
Study details
The researchers randomly assigned 24 healthy older adults aged 65-75 to ingest a supplement containing either 40 g whey protein alone (control) or 40 g whey protein combined with 3 g calcium HMB (HMB), supplied by TSI, China.
After a 4-week washout period, the participants crossed over to the alternate intervention.
The researchers used a constant infusion of phenylalanine to assess muscle protein synthesis (MPS) and muscle protein breakdown (MPB) at the start and end of the study. They also measured other markers, including plasma HMB, MPS rates, and muscle blood flow, using blood samples and muscle biopsies.
The results showed that both interventions displayed significant increases in MPS in response to feeding. The addition of HMB further enhanced MPS in older women.
“In brief, we report that HMB adjuvant to a 40 g whey protein bolus increased MPS beyond 40 g of protein alone in older women but not older men,” the researchers wrote.
While both interventions decreased MPB relative to the fasted value, HMB reduced MPB more in the late-fed period than whey protein alone, and females only showed decreases with HMB in this period - not with whey protein alone.
The researchers called for further studies “to understand the apparent sexual dimorphic MPS response to high protein.”
Looking beyond protein alone
Prof. Baier emphasized the importance of looking at growing evidence around HMB and creatine for healthy aging. He noted that while protein remains foundational because it provides the amino acids needed for muscle synthesis, HMB and creatine are receiving attention for their complementary roles in muscle preservation, energy production, strength and performance.
“As the healthy aging category continues to mature, I think we’ll see growing interest in a multitude of evidence-based ingredient combinations rather than single-ingredient solutions,” he said.
However, he also emphasized the need for convenient delivery systems for older adults who experience pill fatigue or difficulty swallowing.
“From my perspective, it’s no longer enough for a formulation to be clinically supported or have the right ingredients,” he commented.
“The future of muscle health products requires pairing clinically validated ingredients with delivery formats that consumers are willing and able to take consistently. Ultimately, adherence is what allows the science to translate into real-world results.”
Source: Nutrients 2026, 18(9), 1449; https://doi.org/10.3390/nu18091449
“The Effect of β-Hydroxy-β-Methyl Butyrate (HMB) upon Acute Fed-State Muscle Protein Turnover in Older Men and Women: A Randomized Double-Blind Controlled Crossover Clinical Trial.”
Authors: K. Smith et al.
