Combining Three Supplements at Low Doses Shown to Delay Age-Related Bone and Muscle Decline

Highlights

• The combination of supplements significantly enhanced muscle size and exercise performance in aged mice.
• The combination also attenuated age-related bone loss.
• The combination’s improvements to muscle and bone matched or surpassed the benefits of any of the supplements on its own, suggesting comprehensive effects against age-related muscle and bone loss.

Age-related deterioration of the body’s network of bone, muscle, and joints (collectively referred to as the musculoskeletal system) poses a major challenge for many older adults. For example, osteoporosis, an age-related condition where bones weaken and become brittle, affects an estimated 19.7% of people globally. Moreover, sarcopenia, another age-related condition characterized by the progressive loss of muscle mass and strength, has a reported global prevalence between 10% and 27%. Finally, osteoarthritis, a progressive and degenerative age-related joint disease, has a global prevalence estimated at 7.6%. Dishearteningly, these age-related musculoskeletal conditions often occur together in some patients.

To intervene against and possibly prevent these age-related conditions, researchers have identified a small protein called colostrum basic protein (CBP) that promotes bone growth and strength in animal models. Also, researchers have established the potential of another supplement, β-hydroxy-β-methylbutyrate (HMB), to positively influence muscle mass and function in animal studies and human trials. Furthermore, a molecule called hyaluronic acid (HA) is under investigation for its potential to reduce pain, stiffness, and inflammation for the management of osteoarthritis.

Even though osteoporosis, sarcopenia, and osteoarthritis often occur together as a collective dysfunction of the musculoskeletal system, supplemental interventions typically target only one of them in isolation. In other words, no known supplemental formula contains ingredients that target all three conditions simultaneously.

Now, as published in Food & Function, scientists from Sun Yat-sen University in China show that combining a low dosage of CBP, HMB, and HA significantly enhances exercise performance in aged male mice. The combination also attenuated age-related bone loss, and the combination’s effects matched or surpassed the benefits of any of the supplements on its own. The researchers went on to show a correlation between these benefits and increased levels of molecules with key roles in the muscle-bone axis—the two-way chemical communication between muscles and bones.

“Our findings highlight the potential effects of [HMB], CBP, and HA supplementation on delaying age-related progression of muscle and bone loss, and their combined application appears to provide comprehensive and multiple benefits,” say Zhu and colleagues, who published the study.

The Combination of Supplements Prevents Muscle Loss, Enhances Physical Performance, and Attenuates Bone Loss

To evaluate the effect of the combination of supplements on bone and muscle function, the scientists started with 12-month-old male mice (roughly equivalent to 44-year-old humans). They treated the mice with the combination of supplements or each supplement individually for six months, until 18 months of age (equivalent to about 56 years old for humans).

Following the six-month intervention, the researchers sought to gauge any effect on muscle size. To do so, they analysed the size of a thigh muscle and found that all of the interventions prevented a decline in muscle volume in the aged mice, as measured by the area of a cross-section of muscle. More specifically, the combination treatment conferred a muscle area about 1.35-fold greater than that of old, non-treated mice, while the HMB treatment conferred about 1.29-fold greater area, the CBP treatment conferred about 1.15-fold greater area, and the HA treatment conferred about 1.14-fold greater area. These results suggest that, while all treatments had a preservative effect, both the combination and HMB treatments conferred the most significant preservation of muscle size in aged mice.

Given the findings showing that the supplements preserve muscle size, the researchers sought to determine whether the muscle preservation affects physical performance. Indeed, they found that the combination of supplements improved the distance the aged mice could run until exhaustion, significantly more than any of the other treatments. This finding supports that, while all treatments improve physical performance to some degree, the combination of supplements works better than any of the supplements on its own.

To then assess how the supplements affect the bones, the scientists measured bone mineral density, the amount of calcium and other minerals packed into a bone segment, which serves as an indicator of bone strength and thickness. They found that the combination of supplements and CBP supplementation conferred comparable preservation of bone mineral density and that these two treatments were superior to treatment with either HMB or HA. These data suggest that CBP works effectively to preserve bone strength and thickness and that this effect also exists with the combination of treatments.

To investigate the potential molecular mechanism by which the supplements improve parameters of muscle function and bone strength, the researchers measured the circulating levels of hormone-like proteins called myokines. Myokines work as signaling molecules in the muscle-bone axis. Notably, the China-based researchers measured how the supplements affected circulating levels of the myokine, irisin, which supports bone formation and helps regulate metabolism.

Interestingly, the scientists found that irisin levels drop dramatically in old, non-treated mice, but that HMB and the combination supplements significantly increased irisin levels. Importantly, the combination treatment increased circulating irisin levels more significantly than any of the treatments on its own. This finding suggests that HMB supplementation can increase irisin levels and that the combination treatment trends toward having an even greater effect than HMB. The increased circulating irisin may, in part, help explain how the combination of supplements enhanced bone strength and thickness to help improve exercise capacity in the aged mice.

Combining the Three Supplements at Lower Doses

The study did not assess the supplement interventions’ effects on joint degeneration, a key limitation. HA is meant to affect cartilage and joint function, and, interestingly, none of the data showed that HA worked comparably to the combination of supplements. If the scientists had assessed the supplement interventions’ effects on joint degeneration and function, they may have found that HA worked comparably to the combination of supplements, since HA may have its most significant effects on joint function. Future studies should analyze how each of the treatments affects joint health for confirmation.

The findings related to how the interventions affect physical performance serve as, perhaps, the most important indicator of the supplements’ capacity to preserve the musculoskeletal system during aging, since physical performance is one of the most crucial functions of the musculoskeletal system. Interestingly, the combination of supplements worked significantly better than any of the treatments on its own in improving the running distance to exhaustion, a key measure of physical performance. This finding suggests that the combination of supplements has an additive effect to better preserve the musculoskeletal system than any of the supplements on its own.

Another interesting aspect of the study comes from the low dose of each supplement used in the combination treatment. In that regard, the combination of treatment contained 37.5% of the typical dose of HMB, 20% of the typical dose of CBP, and 14% of the typical dose of HA compared to the dose given with each supplement on its own. The reason why these lower doses conferred significant benefits at such low doses when combined needs further research. However, the authors of the study speculated that this effect may have stemmed from the combined modulation of molecules, like myokines of the muscle-bone axis, when the three supplements were put together.

Anyone wanting to try these supplements for potential preservation of the musculoskeletal system can find them for purchase online. If the animal model data from this study translates to humans, it remains possible that combining the supplements at lower doses than recommended by the supplement manufacturers could work better than any of the supplements on its own.