6′-Sialyllactose supports cholesterol, cellular hydration, and aerobic exercise capacity, new study shows

A recent human study conducted by researchers at Texas A&M University has highlighted the potential of 6′-Sialyllactose (6′-SL) to support aerobic exercise capacity while producing noteworthy changes in cholesterol ratios, body water distribution and metabolic substrate utilization.¹

At week six, participants supplemented with 6′-SL demonstrated reductions from baseline in both the low-density lipoprotein (LDL) and high-density lipoprotein (HDL) ratio and Total Cholesterol/HDL ratio.

The study was conducted using Siallac6®, the 6′-SL manufactured by GeneChem Inc., at a daily dose of 900 mg. GeneChem is an AI-based enzyme engineering company that develops and produces sialyllactose through enzymatic synthesis.

The findings are particularly notable because the study involved healthy men between the ages of 18 and 42 who had normal lipid profiles and continued their normal diets without dietary restrictions. Previous research into sialyllactose and cardiovascular health has largely focused on animals consuming high-fat diets, where supplementation has been linked with improvements in insulin resistance and reductions in LDL cholesterol.²

The Texas A&M findings extend this research into healthy adults living under normal dietary conditions and suggest that 6′-SL may support lipid balance even when cholesterol levels are already within normal ranges.

Study details

The twelve-week, randomized, double-blind, placebo-controlled human study evaluated the effects of 6′-SL supplementation in healthy men between the ages of 18 and 42, who maintained their normal diets and daily lifestyles throughout the intervention.

Researchers assessed changes in LDL/HDL and Total Cholesterol/HDL ratios, Total Body Water, Intracellular Water, submaximal glucose and fat oxidation, Relative Maximal Oxygen Uptake and oxygen utilization at the ventilatory threshold, or VANT. The findings indicated statistically significant changes across several markers related to lipid metabolism, cellular hydration, metabolic flexibility, and aerobic exercise capacity.

Optimizing cholesterol ratios in healthy adults

The LDL/HDL and Total Cholesterol/HDL ratios are widely used to evaluate the balance between atherogenic and protective cholesterol fractions. The week-six findings suggest that 6′-SL may help optimize these ratios rather than acting only as a means of lowering elevated cholesterol. This distinction matters because the participants entered the study with normal lipid markers and continued consuming their normal diets.

The following discussion integrates the clinical observations from the Texas A&M study with supporting evidence from previous mechanistic and preclinical research to provide plausible biological explanations for the observed findings.

The proposed mechanism centers on hepatic LDL handling – specifically, the clearance of circulating LDL and the regulation of hepatic LDL production. 6′-SL may support the activity of hepatic LDL receptors, which are responsible for removing circulating LDL cholesterol from the bloodstream.

Supplementation may also increase the sialylation of circulating LDL; when LDL particles remain appropriately sialylated, the liver may recognize that sufficient normal LDL is already present in circulation and reduce additional LDL production.

Together, increased clearance of circulating LDL and reduced hepatic LDL synthesis may explain how 6′-SL could contribute to lower LDL cholesterol, higher HDL cholesterol, and improved cholesterol ratios.

Intracellular hydration emerges as a new finding

Another key finding of the Texas A&M study was the first reported human evidence connecting 6′-SL supplementation with improved hydration. At week six, Total Body Water and Intracellular Water were significantly higher in the 6′-SL group than in the placebo group.

The increase in Intracellular Water may be connected to improved glucose handling and greater storage of glucose inside cells. When glucose is stored as glycogen, water is stored alongside it, so a rise in Intracellular Water may indicate that more glucose is being efficiently transported into cells and retained as glycogen.

Improved cellular hydration has been associated with several physiological advantages, including nutrient transport, cellular activity, and protection against age-related cellular decline. It also supports the broader interpretation that 6′-SL supplementation improves metabolic flexibility.

Supporting metabolic flexibility

Metabolic flexibility refers to the body’s ability to shift efficiently between carbohydrates and fats as energy sources depending on availability and physical demand. At week six, the researchers observed statistically significant changes in Submaximal Glucose Oxidation and Submaximal Fat Oxidation compared with both baseline and placebo, indicating that participants supplemented with 6′-SL became more efficient at utilizing different metabolic fuels during submaximal exercise.

Taken together with the body water findings, this describes a more flexible metabolic profile: glucose moving more efficiently into cells and being retained there as glycogen, alongside more effective fat oxidation during exercise.

Metabolic health and sarcopenia

The potential effects of 6′-SL on lipid ratios, cellular hydration, and fuel utilization all sit within the same domain: metabolic health. Most often discussed in relation to type 2 diabetes, early metabolic decline has also been identified in recent research as a contributing factor in age-related sarcopenia.

An analysis of 22,482 records from the US National Health and Nutrition Examination Survey examined this relationship and found that prediabetes was associated with reductions in appendicular skeletal muscle and a higher prevalence of sarcopenia.³

Sarcopenia prevalence was reported at 5.41% among individuals in the normal glycemic group, increasing to 11.8% among individuals with prediabetes and 22.37% among individuals with type 2 diabetes.

Muscle quality, evaluated using the relationship between Appendicular Skeletal Muscle and Body Mass Index, also showed a statistically significant association with glycemic status. The research further indicated that sarcopenia-related changes may already begin when glycohemoglobin (HbA1c) levels rise above approximately 5.2%, emphasizing the importance of addressing metabolic health before the development of type 2 diabetes.

Results also suggest that support of metabolic health may be relevant not only to glucose metabolism and cardiovascular health but also to the long-term preservation of skeletal muscle.

Aerobic work capacity and cardiovascular health

Aerobic exercise is actively recommended as one of the most effective lifestyle interventions for supporting cardiovascular health, and the Texas A&M findings suggest that 6′-SL may improve the body’s ability to perform aerobic exercise efficiently.

At week six, Relative Maximal Oxygen Uptake increased significantly in the 6′-SL group compared with placebo, and participants supplemented with 6′-SL required less oxygen at the VANT assessment while performing the same workload.

Using less oxygen to sustain an equivalent workload indicates improved aerobic efficiency and suggests that the cardiovascular and respiratory systems were able to perform the exercise with reduced physiological demand.

6′-SL supplementation and regular aerobic exercise may therefore provide complementary benefits: exercise directly supports cardiovascular fitness, while the potential effects of 6′-SL on cholesterol balance and metabolic flexibility may help support the metabolic environment underlying cardiovascular health.

Muscle protein balance and sarcopenia

Previous studies have reported that 6′-SL may support muscle mass, muscle strength, and exercise performance, and the Texas A&M study adds improved aerobic exercise capacity to this existing body of evidence.^1,5

Beyond exercise performance, 6′-SL has also attracted attention for its potential role in maintaining the balance between muscle protein synthesis and muscle protein breakdown. The mechanisms described below come from separate preclinical studies.^6-8

Muscle protein synthesis is primarily regulated through the mTOR signaling pathway. Myostatin, a negative regulator of muscle growth, can interfere with mTOR activity and suppress muscle protein synthesis.^6,7 Previous findings indicate that 6′-SL suppresses Myostatin expression, helping to protect normal mTOR activity and thereby supporting the process of muscle protein synthesis.⁶

Myostatin is also involved in muscle protein breakdown, promoting the expression of MuRF-1 and Atrogin-1, two key markers involved in the degradation of muscle proteins.⁸ By suppressing Myostatin and the downstream expression of both markers, 6′-SL may help reduce protein breakdown, while simultaneously supporting protein synthesis – a dual mechanism that provides a biological explanation for the previously reported improvements in muscle mass and muscle strength associated with 6′-SL.^5,6,8

Ultimately, these mechanisms suggest that 6′-SL may help build and maintain muscle mass by supporting protein synthesis while keeping breakdown at bay. Rather than acting alone, it holds strong potential as a complementary ingredient to protein, amino acids, or HMB, helping to maximize the overall efficacy of these traditional muscle-health staples.

A combined approach to cardiovascular and muscle health

The Texas A&M findings indicate that 6′-SL may have effects across several physiologically connected systems rather than acting on one isolated health marker. Within the six-week data, the proposed sequence runs from enhanced metabolic flexibility through more efficient glucose and fat utilization, to increased intracellular glycogen and water storage, optimized cholesterol ratios, and improved aerobic work capacity.

Separate preclinical evidence on the suppression of Myostatin and its downstream muscle degradation pathways suggests 6′-SL may also help preserve muscle protein balance.^6-8

These mechanisms may be particularly relevant to healthy aging because cardiovascular health and skeletal muscle health are physically and functionally interdependent: healthy circulation is necessary to deliver oxygen and nutrients to muscle tissue, while maintaining skeletal muscle supports glucose disposal and metabolic health.

The combination of muscle-preserving activity and improved metabolic flexibility positions 6′-SL as a promising functional ingredient for formulations targeting cardiovascular wellness, active nutrition, healthy aging, and sarcopenia-related muscle decline.

Find out more information on Siallac6® and GeneChem Inc.’s sialyllactose here, or contact info_siallac@genechem.co.kr.

References

1. Estes, L.; et al. Efficacy of human milk oligosaccharide 6′-sialyllactose supplementation on exercise performance and training adaptations. Nutrients. 2026;18(11):1743.
2. Zhu, M.; et al. Potential effects of sialic acid and 3′-sialyllactose on intestinal health and anti-cardiovascular disease in mice fed with a high-fat diet. Journal of Functional Foods. 2024;116:106215.
3. Zhang, W.; et al. 3′-Sialyllactose regulates glucose and lipid metabolic disorders via the gut–liver axis in mice fed a high-fat diet. Food Science and Human Wellness. 2025;14(8):9250185.
4. Li, S.; et al. Prediabetes is associated with loss of appendicular skeletal muscle mass and sarcopenia. Frontiers in Nutrition. 2023;10:1109824.
5. Park, EJ.; et al. 6′-Sialyllactose enhances exercise performance via increased muscle mass and strength. Nutrients. 2024;16(16):2600.
6. Go, H.; et al. 6′-Sialyllactose prevents dexamethasone-induced muscle atrophy by controlling the muscle protein degradation pathway. Biochemical and Biophysical Research Communications. 2024;736:150892.
7. Amirouche, A.; et al. Down-regulation of Akt/mammalian target of rapamycin signaling pathway in response to myostatin overexpression in skeletal muscle. Endocrinology. 2009;150(1):286–294.
8. Lokireddy, S.; et al. Myostatin promotes the wasting of human myoblast cultures through promoting ubiquitin-proteasome pathway-mediated loss of sarcomeric proteins. American Journal of Physiology-Cell Physiology. 2011;301(6)–C1324.
9. Dickinson, JM.; et al. Mammalian target of rapamycin complex 1 activation is required for the stimulation of human skeletal muscle protein synthesis by essential amino acids. Journal of Nutrition. 2011;141(5):856–862.