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6′-Sialyllactose research shows potential in countering age-related muscle loss

As populations around the world grow older, healthy aging has become a critical public health priority.

In the US, the proportion of adults over 65 is projected to nearly double from 52 million in 2018 to 95 million by 2060, presenting significant challenges for the healthcare system, economy, and families.¹

Among these concerns, age-related sarcopenia – a progressive loss of muscle mass, quality and strength – has emerged as a key risk factor impacting mobility, independence, and quality of life in older adults.

In light of these challenges, research into nutritional interventions to support muscle health is gaining momentum. One promising compound is 6′-sialyllactose (6′-SL), a naturally occurring sialylated oligosaccharide present in human breast milk. 6′-SL is primarily known for its benefits in supporting infant health by aiding the gut microbiome and immune development. However, it is also a source of sialic acid, and there is known to be a strong correlation between sialic acid deficiency and sarcopenia.

Research has shown that different types of sialic acid are present in varying amounts according to age, and could be linked to the appearance of sarcopenia.²⁻³ This compound’s potential to counteract sarcopenia and muscle atrophy has sparked investigations into whether it could help mitigate some of the physical issues associated with aging.

6′-SL: Pursuing the research

GeneChem is one company investigating this potential by carrying out various studies examining the efficacy of 6′-SL at enhancing muscle mass, strength, and exercise performance, as well as its potential to help prevent muscle atrophy.

Furthermore, the company is also conducting research into its exact effect on muscle function to fully understand the potential impact of this compound when used as a supplement for individuals living with sarcopenia. One of the benefits of pursuing research in this area is that prior studies have already found 6′-SL to be safe not only for consumption in functional foods for the general population, but even for use in infant formula.⁴

GeneChem conducted a pilot clinical trial to analyse the pharmacokinetic properties of 6′-SL, and to evaluate the safety and efficacy in patients with GNE myopathy.⁵ This condition is a rare progressive genetic muscle disease that is characterized by progressive muscle weakness which typically worsens over time. The disease is caused by mutations in the GNE gene, leading to reduced enzymatic activities and a decline in sialic acid levels.

The results of the study showed that free sialic acid levels significantly increased with 6’SL treatment at both high-dose (6g per day) and low-dose (3g per day) after 12 weeks, compared to baseline values. In terms of motor function, after 96 weeks of treatment, motor powers of the high-dose group tended to increase on a variety of measures, such as hand grip and hip flexion.

In the low-dose group, motor powers were mostly retained, with knee extension metrics showing improvement. Overall, the study found a dose-dependent protective effect of 6′-SL against muscle degeneration.

Advantages in muscle building and exercise

GeneChem has also been involved in research investigating whether 6′-SL could enhance exercise performance via increased muscle mass and strength.⁶ The compound was tested on mice, and the results showed that it was able to increase muscle weight, muscle fibre size, and myosin heavy chain (MHC) protein expression. Interpreting these results allowed the authors to suggest that 6′-SL supplementation could enhance endurance exercise performance, including exhaustion time, total distance, and work output, by increasing muscle mass and strength.

In a further study, GeneChem conducted trials on the effects of 6′-SL on preventing muscle fatigue during treadmill exercise.⁷ The data showed that administration of 6’-SL significantly reduced blood lactate levels and improved blood glucose levels. Additionally, it was found to increase markers related to slow-twitch muscle fibre, the muscle type known to be involved in reduction of fatigue and increased performance in endurance activities.

Promising solution for sarcopenia

With such broad potential benefits of 6′-SL to prevent muscle degradation and to improve performance during exercise, GeneChem next sought to understand whether it would be able to help in the prevention and treatment of sarcopenia. The company tested this by investigating the impact of 6′-SL on a dexamethasone-induced muscle atrophy model of sarcopenia to determine whether it has preventative or therapeutic effects.⁸

The trial included test of in vitro conditions and mice, with the latter receiving the 6’-SL treatment for 10 weeks in oral doses, followed by dexamethasone injection during the 9th and 10th week. The mice were then tested on various measures of grip strength, endurance and muscle weight.

In their analysis, the study authors found that 6′-SL inhibited the dexamethasone-induced decrease in size and mean minimal Feret’s diameter of the gastrocnemius (leg) muscle. In addition, the treatment was also observed to inhibit the decrease in the weight of the gastrocnemius, quadriceps, and tibialis anterior caused by dexamethasone injection.

In terms of exercise performance, when dexamethasone was administered alone, rotarod, grip strength, and treadmill endurance all decreased. However, mice that received 6′-SL showed significant improvement in rotarod and grip strength, though the improvement in treadmill exercise was not significant.

The authors concluded that treatment with 6′-SL is able to prevent dexamethasone-induced muscle atrophy both in vitro and in vivo. These results open up the potential to investigate the effects of 6′-SL in muscle atrophy and sarcopenia in the elderly in future research. It also suggests that there is high potential for the compound to be used as a dietary supplement for the prevention and improvement of these conditions.

Based on its research, GeneChem has demonstrated that 6′-SL supplementation offers a potential solution to enable healthier living in aging populations. To harness this potential, the company is preparing to launch products containing 6′-SL to support those with age-related health issues, such as sarcopenia. Backed by its research expertise, GeneChem is a leading player in the glycosylation industry and is the partner for any company looking to harness the benefits of 6′-SL.

More details about sialyllactose are available upon request by emailing info_siallac@genechem.co.kr.

References

1. Fermini, B.; et al. On the perspective of an aging population and its potential impact on drug attrition and pre-clinical cardiovascular safety assessment. Journal of Pharmacological and Toxicological Methods. 2022. Volume 117, 107184.
2. Marini, M.; et al. Expression of sialic acids in human adult skeletal muscle tissue. Acta Histochem. 2014 Jun;116(5):926-35.
3. Harada, H.; et al. New diagnostic index for sarcopenia in patients with cardiovascular diseases. PLoS ONE. 2017. 12(5): e0178123.
4. Gurung, R.B.; et al. Toxicological evaluation of 6′-sialyllactose (6′-SL) sodium salt. Regul Toxicol Pharmacol. 2018 Jun;95:182-189.
5. Park, V-E.; et al. Pharmacokinetics and clinical efficacy of 6′-sialyllactose in patients with GNE myopathy: Randomized pilot trial. Biomedicine & Pharmacotherapy. 2023. Volume 168, 115689.
6. Park, E.J.; et al. 6′-Sialyllactose Enhances Exercise Performance via Increased Muscle Mass and Strength. Nutrients. 2024 Aug 7;16(16):2600.
7. Park, E.J.; et al. 6′-Sialyllactose Alleviates Muscle Fatigue through Reduced Blood Lactate Level after Treadmill Exercise in Mice. Nutrients. 2024 Sep 3;16(17):2957.
8. Go, H.; et al. 6′-sialyllactose prevents dexamethasone-induced muscle atrophy by controlling the muscle protein degradation pathway. Biochemical and Biophysical Research Communications. 2024. Volume 736, 150892.