Glucosamine: not just for better joint health, but also a proven longevity drug!

From all of the supplements which support joint health, glucosamine is probably the best known among them.
Yet, while it works wonders for a majority of people, a minority won't experience relief from joint pain .

Unfortunately yours truly is among that small group of people who didn't benefit from its use, most likely because chronic shoulder pain has been bothering me for well over 25 years.

About two weeks ago, I I gave up and switched to ASU Forte as per the advice of 'Mister Glucosamine' , the nickname of Kris Kuiper. He got that nickname since he read just about every single study in existance about this miracle supplement.

When I told Kris about the switch, he advised me to keep using glucosamine. Not so much for joint support, as it obviously didn't work wonders for me, but because glucosamine is also a powerful anti-aging supplement.
That really made perk up my ears as I'd totally forgotten about this aspect of glucosamine when writing about its usefulness in an earlier blog article "Glucosamine for healthy joints and gut"

Glucosamine and mortality 

Glucosamine was originally discovered during the 1960s in Italy. Glucosamine is one of the most commonly used dietary supplements and is typically taken to help with the joint pain and inflammation associated with aging.

Glucosamine is a polysaccharide that is found naturally in cartilaginous joint tissues, bones, skin, ligaments, and nails, and it is involved in protein and lipid synthesis. In the context of joints, synovial fluid contains glucosamine and occupies the space between joints, helping to reduce the friction of joint surfaces.

Glucosamine supplementation also seems to correlate with lower all-cause mortality and other mortality risks, such as cardiovascular disease (CVD), cancer, respiratory and digestive diseases. A recent analysis published in the journal BMJ showed that glucosamine supplementation conveys around a 15% reduction of all-cause mortality.

Associations of regular glucosamine use with all-cause and cause-specific mortality: a large prospective cohort study

This is a considerable amount when compared to other lifestyle interventions as well as other supplements. The data gathered is from a large number of people, and the trend of reduced mortality is unmistakable.

This population-based prospective cohort study in the UK included half a million adults with a mean age of 56 1/2 years. Participants were recruited from 2006 to 2010 and were followed up through 2018.
When all-cause mortality and mortality due to cardiovascular disease (CVD), cancer, respiratory and digestive disease was evaluated, regular glucosamine supplementation was associated with lower mortality due to all causes, cancer, CVD, respiratory and digestive diseases.

Given the large patient group in this and in other analyses along with the popularity of this supplement, glucosamine appears to have by far the most significant influence on all-cause mortality.
Given that glucosamine is cheap and freely available with an excellent safety profile, it may be worth adding this to your daily supplement regime.

On extracellular matrix, connective tissue and glucosamine

Connective tissue is one of the 4 types of tissues that form the human body. The others are the nervous, muscle and covering or “epithelial” tissue.
The connective tissue supports all the other tissues by binding them together. The connective tissue also nourishes, oxygenates, electrifies and detoxifies all the cells of the body. The connective tissue includes bones and the internal material within which the various organs of the body are embedded. The skin gets its resilience from supportive connective tissue, that is located in the dermis. The heart sits on a framework of connective tissue. The strength and elasticity of the arteries, veins, capillaries and lymphatic vessels depends on connective tissue, while even the blood itself is a type of liquid connective tissue.

Interestingly, the cells that compose the connective tissue are NOT connected to each other. They come close but they don’t touch. Rather, the spaces between connective tissue cells are filled in with “grout”, which is really a type of jelly or biological gel substance, that is secreted from connective tissue producing cells (fibroblasts). This gel plays a major determining factor in the health of the connective tissue.

This jelly-like material is a type of matrix and, because it is secreted outside of cells, it is called an extra-cellular matrix (ECM). This extracellular matrix is the prime determinant of the health of connective tissue and the body as whole. That’s because, the way the system works, the extracellular matrix is responsible for feeding, breathing and detoxifying cells. Once the extracellular matrix becomes defective or clogged up, with cell breakdown, death and disease begins. When we talk about connective tissue disease, when we talk about aging, when we talk about cancer, when we talk about ALL health challenges, what we are really talking about is some defect in the extracellular matrix. So, while all disease is cell disease, cell disease begins with a defective extracellular matrix.

Cartilage is a classic example of extracellular matrix. Collagen is a component of the extracellular matrix. Hyaluronic acid is a component of the extracellular matrix, as is chondroitin, bone, tendons, ligaments, muscle, and even blood (aside from the red and white cells). That means that pretty much all health issues that involve the structure of the body are at least partially issues with the extra-cellular matrix.

That makes working on producing a healthy extracellular matrix a critical element of health, wellness and anti-aging. Once the extracellular matrix is formed, there’s not much that can be done, but what we can do is work on tomorrows extracellular matrix. That means working with fibroblasts by ingesting nutrients that support the health of the fibroblasts and giving the body raw materials that the fibroblasts can use to make a healthy extracellular matrix.

One of the most important of these supportive nutrients is a glucose derivative called glucosamine, an abundant sugar molecule that is produced in the human body. It's found in cartilaginous foods like pig snouts and chicken feet, as well as the shells of shrimp, crabs and lobsters. Mushrooms are also a decent source of this important biological raw material. Of course, the most important source of glucosamine, for most folks, is in dietary supplements, where it is derived primarily from the chitin, that forms the exoskeleton of crustaceans (crabs, prawns, and lobsters), as well as the cells of fungi.

Once ingested, glucosamine enters into the blood stream and is delivered to the fibroblasts (the cells that form the connective tissue). There it plays a key role in the production of hyaluronic acid, chondroitin sulfate, as well as keratan sulfate, which, along with collagen, are the most important components of the extracellular matrix. In fact, glucosamine production is the rate-limiting step in glycosaminoglycan-synthesis. Without it, the extracellular matrix could not be produced. By eating glucosamine rich foods and by using glucosamine as a nutritional supplement, the production of a healthy extracellular matrix can be supported.

On the role of hyaluronic acid in aging

Hyaluronic acid is is best known for its ability to reduce wrinkles, which is why it is often added to creams and applied onto the skin. However most of the hyaluronic acid that is applied on the skin does not penetrate the skin.

Hyaluronic acid is an important building block of our skin. Hyaluronic acid is a very long molecule consisting of mainly disaccharides, composed of D-glucuronic acid and N-acetyl-D-glucosamine. Other skin components can bind onto it, among which glycosaminoglycans (GAGs), collagen, and elastin.
All these complex substances build up the extracellular matrix, which is the glue that holds together our cells. Hyaluronic acid is an important component of that intercellular glue.

Hyaluronic acid levels deplete when we get older, contributing to thinner, less elastic, less smooth skin as well as more vulnerable intestingal lining.

Acetyl-glucosamine is a very interesting molecule, given it can extend lifespan in various lab organisms. Acetyl-glucosamine should not be confused with glucosamine, which has lifespan effects on its own.

Scientists believe that acetyl-glucosamine can extend lifespan by inducing the unfolded-protein response Our cells normally mount this response when they detect too many proteins that are accumulating. Accumulation of proteins is one of the reasons why we age. So Acetyl-glucosamine can reduce this protein accumulation by inducing this repair response.

When hyaluronic acid is consumed parts of it are digested into individual acetyl-glucose molecules, which are taken up by the gut and enter blood circulation.

By using hyaluronic acid you can both reduce aging-related wrinkle formation as well as diminish cellular aging.

On the role of glucosamine in aging and longevity

Few people know a much more interesting role of glucosamine in health: its ability to slow down aging and lengthen lifespan.

Studies show that glucosamine can extend lifespan in various organisms.
Scientists believe that glucosamine can extend lifespan by mimicking a calorie-restricted diet. More specifically, glucosamine slightly inhibits the ability of the mitochondria to process sugars, so that the cells believe they do not have enough energy. In response, cells create more mitochondria (also known as mitochondrial biogenesis) to improve their energy levels.
The more mitochondria you have, the more energy they can produce to help the cells to maintain themselves well. Exercise also induces new mitochondria.

But glucosamine’s effect on mitochondria is not the only reason why this substance can impact aging.
The older we get, the more our bodies get inflamed (it’s called “inflammaging”). This smoldering inflammation accelerates the aging process. Glucosamine can reduce inflammaging.

Glucosamine can also protect DNA against damage. Glucosamine is able to prevent specific forms of cross-linking, relieve oxidative stress, and induce autophagy (clearing up proteins that accumulate during aging).

Glucosamine is not just a joint supplement, but can also improve skin health and slow skin aging.
This happens because glucosamine inhibits matrix metalloproteinases, enzymes that break down collagen and elastin fibers in our skin, a process that contributes to skin wrinkles.
Glucosamine can also inhibit inflammation processes in the skin, which increases with the aging process.
Furthermore glucosamine increases the expression of collagen, hyaluronan synthase and other important proteins that build up our skin.

These and many other health benefits explains why glucosamine was one of the very few supplements that have been shown in large human studies to be correlated with increased lifespan.

Given the many health benefits of glucosamine, this very interesting ingredient deserves much more attention besides just being a “healthy joint supplement”.

Summary of the ways glucosamine can slow down the aging process and keep you healthy

• strengthens circulatory vessels
• liquifies blood improving delivery of nutrients to extremities
• improves production of bone mass
• prevents fine lines and wrinkles
• supports skin moisturization and reduces dry skin
• facilitates electrical conduction in the heart
• supports intestines, improving symptoms of Leaky Gut Syndrome and bowel disease
• enhances the production of joint cartilage and reduces arthritis inflammation
• helps reduce receding gums and helps prevent gum disease
• increases the production of mitochondria
• reduces whole-body inflammation
• increases the expression of collagen and other skin-building proteins
• protects DNA against damage

Not just for humans

Cats and dogs will also benefit from glucosamine supplements. In a meta-review of 16 animal studies researchers found that preparations containing glucosamine could provide a “moderate level” of comfort and were on a par with some prescription drugs. While often available as special veterinary supplement, there’s also nothing wrong with sharing your own human glucosamine supplement with your pet.

A good dose is around 25mg of glucosamine per kilogram of body weight.