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Recent research is shedding light on how the human milk oligosaccharide (HMO), 3’-sialyllactose (3’-SL) could have an important role in preventing bone loss and promoting bone health, making it a potential treatment for osteoporosis in the future.
Osteoporosis is a bone disease that causes bone to become brittle and weak, increasing the risk of fractures. It’s sometimes known as a silent disease because many people do not realise they have it until a bone breaks.
Anyone can develop osteoporosis, but it’s much more common in older people and usually develops in women in the few years after menopause. However, men and younger people can also develop the condition[i].
Osteoporosis is the most common bone disease affecting one in three women and one in five men over 50 globally[ii]. Because there is no cure for osteoporosis, there is a need to find effective ways to manage the condition which currently means medicine and exercise.
However, current therapies focus on symptom management rather than prevention or cure, or even preventing further damage. Yet, emerging and nuanced research suggests that a specific human milk oligosaccharide, 3’-SL, could have several important effects on bone health that could slow down the progression of the disease.
3’-sialyllactose is a sialylated human milk oligosaccharide which means it has a sialic acid added to the end of its carbohydrate chain.
Figure 1. The chemical structure of 3’-sialyllactose.Source: Pub Chem (2024).[iii]
3’-SL has numerous health benefits for humans and is involved in the development of the early human gut microbiome because it is the most dominant sialylated HMO in human breast milk[iv].
Some of the potential benefits of 3’-SL on human health include:
HMOs have been identified for their importance in the growth and development of infants, and are a critical nutritional source, particularly for the early residents of the human gut.
In adult and animal models, 3’-SL has been shown to be important for bone health. For example, in mice, 3’-SL reduces the severity of collagen-induced arthritis by blocking a particular network involved in regulating the cellular responses to pathogens and danger signals called the NF-kB signalling pathway[x].
3’-SL can also repress oxidative stress and inflammation. Oral supplementation with the HMO can prevent cartilage destruction in osteoarthritis[xi]. Furthermore, pig models demonstrate that injecting 3’-SL directly into a rheumatoid arthritic knee joint had a therapeutic effect at a cellular level[xii].
Together, these studies suggest that 3’-SL can improve osteoarthritis outcomes and slow the condition's progression by preventing cartilage degradation and promoting regeneration.
Building on these findings, Baek and Colleagues (2024) investigated the underlying effects of 3’-SL on osteogenic and adipogenic differentiation of bone marrow cells to see how 3’-SL could be used as a therapy for osteoporosis.
Bone formation begins with osteogenesis, where stem cells differentiate into bone-producing cells called osteoblasts. In the study by Baek et al (2024), 3’-SL was shown to promote osteogenesis in human bone marrow stromal cells (hBMSCs), the cells responsible for the formation of new bone tissue in humans.
Through the activation of the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signalling pathway, via the enhanced expression of laminin subunit gamma-2, 3’-SL increased the differentiation of hBMSCs into osteoblasts, promoting stronger bone formation.
Both bone-forming and fat-forming cells can be found in bone marrow. Fatty tissue or bone marrow adipose tissue (BMAT) is thought to be an important element in the bone marrow microenvironment, with roles in:
However, it can also be a contributor to several chronic diseases with high levels of BMAT correlating with low bone mineral density and increasing the risk of fractures[xiii]. The current study found that hBMSCs treated with 3’-SL showed reduced numbers of fat cells (adipocytes) (Figure. 2). Therefore, 3’-SL can inhibit the differentiation of hBMSCs into adipocytes.
Figure 2.hBMSCs treated with 3’-SL (+) showed less adipocytes than those that were not treated with 3’-SL (-).
Bone formation is critical for health but so is bone breakdown, to make way for new, healthier bones. Osteoclasts are cells that are responsible for breaking down old or damaged bones, also known as bone resorption[xiv]. However, if osteoclasts become too active, it can lead to increased bone breakdown, a classic sign of osteoporosis.
Baek and Co found that 3’-SL can stop the differentiation of osteoclasts from bone marrow-derived macrophages. In other words, this HMO can suppress osteoclast activity and reduce bone resorption, helping to promote a balance between bone formation and breakdown.
To understand the real-world importance of the benefits of 3’SL on bone health, the researchers used an animal model of osteoporosis - ovariectomized mice – to simulate postmenopausal bone loss. Some research shows that osteoporotic fractures are common in postmenopausal women (82.2%)[xv]. Therefore, understanding how 3’-SL could improve osteoporosis outcomes is important, particularly when the disease is so prevalent in this demographic.
The results from this study were promising. Overall, mice who were treated with 3’-SL demonstrated improved bone density and positive bone remodelling, which suggests that 3’-SL could be a powerful option for managing osteoporosis in the future.
The results from the study by Baek et al (2024) help to further confirm the potential for 3’-SL to offer therapeutic benefits for bone health. Promisingly, 3’-SL has been found to promote bone formation and prevent bone resorption, a major osteoporosis characteristic. The study was also the first to demonstrate that 3’-SL inhibited the adipogenic differentiation of hBMSCs in vitro and that it could be critical in the balance between osteoblast and adipocyte differentiation of human bone marrow cells.
Further research is needed to fully understand the effects of 3’-SL in humans, but current animal research is encouraging.
Current treatments for osteoporosis are limited to medications which can also have undesirable effects. However, the discovery that naturally produced human breast milk components, like 3’-SL, could offer an alternative solution in preventing and treating bone conditions is exciting.
Just by encouraging the formation of new, healthy bone and preventing bone resorption, makes 3’-SL a powerful candidate for maintaining and improving bone health.
Further research is needed but 3’-SL could provide an important solution for osteoporosis treatment in the future.
Do you want to get ahead of the trend? Our SuperHMO® Prebiotic Mix delivers 200mg of 3’-SL to your gut each day or why not capitalize on the combined effects of the SuperHMO® Synbiotic?
Written by: Leanne Edermaniger, M.Sc. Leanne is a professional science writer who specializes in human health and enjoys writing about all things related to the gut microbiome.
[i] Osteoporosis [Internet]. U.S. Department of Health and Human Services; 2023 [cited 2024 Oct 9]. Available from: https://www.niams.nih.gov/health-topics/osteoporosis
[ii] Epidemiology: International osteoporosis foundation [Internet]. [cited 2024 Oct 9]. Available from: https://www.osteoporosis.foundation/health-professionals/about-osteoporosis/epidemiology#:~:text=Osteoporosis%20is%20a%20major%20non,age%20of%2050%20worldwide%20%5B1%5D
[iii] 3’-Sialyllactose [Internet]. U.S. National Library of Medicine; [cited 2024 Oct 12]. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/3_-Sialyllactose
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[x] Kang L, Kwon E, Lee KM, Cho C, Lee J, Ryu YB, et al. 3′‐Sialyllactose as an inhibitor of P65 phosphorylation ameliorates the progression of experimental rheumatoid arthritis. British Journal of Pharmacology. 2018 Oct 17;175(23):4295–309. doi:10.1111/bph.14486
[xi] Jeon J, Kang LJ, Lee KM, Cho C, Song EK, Kim W, Park TJ, Yang S. 3'-Sialyllactose protects against osteoarthritic development by facilitating cartilage homeostasis. J Cell Mol Med. 2018 Jan;22(1):57-66. doi: 10.1111/jcmm.13292. Epub 2017 Aug 7. PMID: 28782172; PMCID: PMC5742729.
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[xv] Imran M, Singh A, Bhardwaj A, Agrawal D. Prevalence of Osteoporosis and Associated Risk Factors among Postmenopausal Women: A Cross-Sectional Study from Northern India. J Midlife Health. 2022 Jul-Sep;13(3):206-212. doi: 10.4103/jmh.jmh_114_22. Epub 2023 Jan 14. PMID: 36950199; PMCID: PMC10025819.
