What is glucosamine?

Glucosamine is an amino sugar that your body makes from glucose and certain amino acids. Glucosamine is then used in the hexosamine biochemical pathway to make various proteins and lipids that need to have glucose attached to them (“glycosylation”) to do their job. Glucosamine occurs naturally in all human tissues, but it's best known as a precursor for glycosamines, which are concentrated in cartilage, where glucosamine is key to joint strength and mobility.

Effects of glucosamine on lifespan and healthspan 

While it’s not feasible to do lifespan experiments on people, there’s tentative evidence that glucosamine use might extend the lifespan and healthspan of people. In surveys of big groups of people, glucosamine supplementation has repeatedly been associated with reduced risk of dying from all causes combined as well as of dying from cardiovascular disease, cancer, and respiratory diseases, respectively. This apparent risk reduction holds even after statistically adjusting for variables that could make the associations spurious. 

This signal of life extension is backed up by the little research on the effects of glucosamine products on the lifespans of other animals too. Most notably, when added to the chow of C57BL/6NRj mice starting just past the halfway point in their lives, glucosamine extended maximum lifespan of both females and males. 

How glucosamine can extend lifespan is an ongoing debate. Several mechanisms have been proposed, most of which converge on the idea that glucosamine use mimics Calorie and/or carbohydrate restriction, and Calorie restriction remains the intervention that has most consistently extended the lives of other animals. 

A key way by which glucosamine mimics Calorie restriction is by inhibiting the first step in glycolysis, the pathway through which glucose is burned to generate energy (ATP). Glucosamine does this by first entering cells via the glucose transporter. Then, when it’s been tagged with phosphate (becoming glucosamine-6-phosphate), it blocks the enzyme (hexokinase) that speeds the first step of glycolysis. Glucosamine targets the form of this enzyme (hexokinase-1) that is involved in glycolysis in the liver, specifically. This blockade ultimately reduces ATP. In turn, glucosamine intake increases a protein in cells that is a key player in nutrient sensing. In humans, the equivalent protein is AMP kinase, or AMP kinase, which helps animals thrive in times of scarcity by triggering a host of pro-longevity adaptive responses, including autophagy, the process that recycles dysfunctional cellular components. AMP kinase is best known for its roles in regulating energy metabolism when energy availability is low by modifying fuel use, including by increasing the burning of fatty acids. It also inhibits mTOR, a growth-promoting pathway that is nullified by some longevity drugs, most famously rapamycin.  

The lifespan experiments mentioned above found that glucosamine also transiently increased oxidative stress in mitochondria. In response, the animals’ mitochondria remodelled themselves to cope with this additional stress, increasing antioxidant defences and the number of mitochondria in cells. This type of beneficial response to a transient, manageable stressor is called hormesis, and when it’s specific to mitochondria it’s known as mitohormesis. When the researchers blocked the increase in mitochondrial oxidative stress, glucosamine no longer extended the lives of the animals. Interestingly, the scientists found that there’s a particular protein (in humans, the equivalent is NRF2) that responds to the oxidative stress and in turn influences the expression of other genes that are involved in glucosamine’s lifespan-extending actions. 

Based on the above, glucosamine seems to target several hallmarks of aging, including deregulated nutrient sensing, disabled macroautophagy (and therefore most likely loss of proteostasis), mitochondrial dysfunction, and chronic inflammation. There is also evidence that glucosamine targets other hallmarks, such as dysbiosis, but the support for other hallmarks is less strong.

Positive effects of glucosamine on human health

As it’s used to synthesise glycosamines, the vast majority of studies on the effects of glucosamine intake have focused on whether it improves the health and function of connective tissues. By far the best-studied use of glucosamine is its effects on osteoarthritis, which produces pain and impedes joint function. Much of this research has focused on osteoarthritis of the knee, specifically. 

Glucosamine sulfate improves joint health 

Glucosamine sulfate can improve joint health. While research on the effects of glucosamine on arthritis hasn’t always reported benefits, much of it has, and the most recent systematic review of the literature shows that glucosamine sulfate, the form used in Coastline, reduces joint space narrowing. Like other interventions, glucosamine won’t reverse the disease, but it does seem to help slow its progression. Given its good safety profile, glucosamine is often recommended by medical professionals to help manage osteoarthritis as an alternative to drugs (in particular, non-steroidal anti-inflammatory drugs) when they aren’t well tolerated.

Notably, interventions that improve joint function or reduce joint pain could make strenuous exercise more tolerable, and exercise is of course key to good health. For example, a study of people with knee osteoarthritis who completed a 12-week strength training program compared 1,500 mg glucosamine each day (the same dose as in Coastline) to 1,200 mg of ibuprofen and found that glucosamine reduced pain related to exercise and modestly enhanced knee extension exercise performance. 

Precisely how glucosamine affects joints continues to be studied. Changes in cartilage mass depend on the balance between the formation of new cartilage and breakdown of existing cartilage. Osteoarthritis occurs when excessive collagen degradation makes this balance negative. As a precursor for glycoproteins and glycosaminoglycans in cartilage, much of the glucosamine consumed is rapidly incorporated into cartilage, so glucosamine might slow the breakdown of cartilage. This is supported by studies finding glucosamine reduces markers of collagen breakdown, such as CTX-II, as found in soccer players and cyclists. Furthermore, glucosamine might have anti-inflammatory effects in joints, protecting them against damage from excessive immune system activity. Consistent with this, glucosamine intake can reduce levels of inflammatory cytokines while boosting levels of an anti-inflammatory cytokine. Finally, glucosamine can activate autophagy in cartilage, which might help clear dysfunctional cells from the tissue.

Glucosamine sulfate might be good for skin health 

Glucosamine is likely to positively affect the functions of other connective tissues too. For example, the effects of glucosamine on skin health have barely been studied, yet connective tissue makes up much of the skin. There are various reasons glucosamine is likely good for skin health. At the time of writing, there's been a single study of the effects of glucosamine sulfate on skin though, and it was “open-label”, meaning the people knew what they were getting. In it, 8 women aged over 50 consumed just 250 mg glucosamine daily for 8 weeks. The researchers then took a skin biopsy and found increased expression of genes that encode several proteins important to connective tissue structure, the proteins including including vimentin, fibromodulin, biglycan, xylosyl transferase, hyaluronan synthase, collagen types I and III, bone morphogenic protein-1, and decorin. 

Our use of glucosamine

Regarding dose, Coastline contains 1,500 mg glucosamine sulfate per day, the dose most commonly used in studies showing positive effects of glucosamine on osteoarthritis.

Regarding timing, the 1,500 mg daily dose is split evenly into two doses, for there’s evidence that a split dose more effectively alleviates joint pain than a single dose.

Regarding form, there are many types of glucosamine, including hydrochloride, N-acetyl-glucosamine, chlorohydrate, D-glucosamine, and glucosamine sulfate, which is what is in Coastline. While D-glucosamine was used in the lifespan experiments on roundworms and mice mentioned above, glucosamine sulfate is by far the best-researched and most used form in people, so it’s reasonable to assume that most of the people in the studies linking glucosamine use to longer lives and reduced disease risk used glucosamine sulfate. Glucosamine sulfate has also proven more effective as a joint health aid than glucosamine hydrochloride, the next-most studied form. This is probably in part because the sulfate group is involved in glycosaminoglycan synthesis and is incorporated into cartilage. Glucosamine sulfate is particularly good at raising sulfate in the blood, which relates to sulfate elsewhere, including in the synovial fluid that lubricates joints. 

Regarding source, many glucosamine products are still extracted from chitosan in the exoskeletons of shellfish (crabs, shrimp, etc). However, we use a vegan source of glucosamine sulfate. We wanted to use a vegan form for ethical reasons and to make the product accessible to as many people as possible.

Glucosamine typical dietary intakes and safety

Most omnivores consume a very small amount of glucosamine from foods rich in cartilage (think chicken leg with the skin on and eating the cartilage in the knee joint) and from the chitin in the exoskeletons of shellfish such as shrimp and crab. Vegans and vegetarians don’t consume any, however.

Since glucosamine inhibits glycolysis in some cells, some have questioned whether glucosamine use might worsen blood sugar levels, which could pose problems for people with diseases such as diabetes. Fortunately, this doesn’t seem to be the case, and long-term clinical trials of oral glucosamine intake haven’t found that glucosamine impairs blood sugar control or sensitivity to the glucose-disposing hormone insulin. Overall, glucosamine supplementation is clearly very safe, and a systematic review reported no differences in adverse events in people taking glucosamine versus others taking placebo.