Tissue and joint repair is an important topic among many people, especially athletes. Supplements such as glucosamine, chondroitin, MSM, and other products are often taken when there is joint pain or degeneration, in hopes that a cure can be found in a bottle. Sometimes these substances work and sometimes they don’t. Some research says they may help, other studies say otherwise. But whether you should take these supplements or not for your joint pain or injury is not the point of this article, but rather what brought you to even consider taking such a supplement is. You see, you’re supposed to make these compounds naturally in your body every day, and even consume some of them in the foods you should be eating. But first, a little bit of biochemistry to get you up to speed.
Making new connective tissue is all about something called GAGs. That stands for glycosaminoglycans which are primarily a bunch of sugar molecules linked together. They come from what is known as the glycolytic pathway – that’s the same pathway you use to make energy from sugar in your body.
Connective tissue is fibrous tissue found throughout your body in the form of tendons, and the framework of fibers in muscles, ligaments, bone, cartilage, and even blood and lymph tissue. Connective tissue not only connects body tissue together, but it protects organs and even stores energy.
Glucosamine’s Role in Tissue Repair
In order to make GAGs you need the main precursor, which is glucosamine. Glucosamine is high in the shells of shellfish as well as animal bones, which is why our grandparents who used to make soup with the animal bones in the pot received many of the necessary bone-building nutrients we lack today because most of us just buy the broth. But you also make glucosamine naturally through the glycolytic pathway (mentioned previously) with nutrients such as vitamins B1, B2, B3, and B5, as well as magnesium, lipoic acid, and potassium. Glutamine, which is an amino acid our bodies can synthesize, is also necessary and added into this step. Let’s learn more!
Glutamine is the most abundant naturally occurring, non-essential amino acid. It’s been shown to be useful in the treatment of serious illnesses, injury, trauma, and burns. Glutamine is also used by many athletes as a supplement because evidence indicates that glutamine may increase plasma human growth hormone levels by stimulating the pituitary gland, which in turn increases muscle growth. A healthy individual has plenty of glutamine.
Chondroitin’s Role in Joint Repair
Now when this glucosamine is linked to a protein it can form substances called proteoglycans, such as chondroitin and eventually into chondroitin sulfate, which is an important component of cartilage. Much of chondroitin is made up of more sugar molecules and glucuronic acid, another amino acid. This amino acid is primarily used in a process called glucuronidation which is how your body (primarily the liver) detoxifies certain drugs, pollutants, hormones (especially cortisol and estrogen), and other substances. Magnesium, manganese, vitamin B2, and vitamin C are all needed here in order to make this work. Artichokes are naturally high in glucuronic acid. Yum.
So we’re getting there. We have the amino acid glutamine and the glycolytic pathway working well so we’ve made glucosamine. Then we’ll will bring it down to make chondroitin as long as our liver hasn’t used up all our glucuronic acid dealing with a lot of detoxification. Next, we need some sulfur.
Sulfation and Tissue Health and Joint Repair
Sulfation is very important as sulfur is needed to make glucosamine sulfate and chondroitin sulfate which helps facilitate cartilage and joint repair. The amino acid L-cysteine is very high in sulfur and can sometimes be of great benefit as a supplement, and it’s also high in protein-rich foods like eggs and whey protein. Sulfates are high in foods such as broccoli, cauliflower, garlic, cabbage, onions, radishes, and mustard. Proper levels of magnesium, vitamin B12, vitamin B6, (in its active form of pyrodixal-5-phosphate), and folic acid, (also typically in its active form of 5-MTHF), are also needed for proper sulfation. Sulfation, like glucuronidation, is another major liver pathway and very necessary for the detoxification of hormones and drugs, especially NSAIDs. *Note, sulfa, which is a classification of drugs that many people are allergic to, is not the same thing as sulfur, the element.
Methylsulfonylmethane (MSM) is a biologically available source of sulfur, like the amino acid cysteine. MSM is a metabolite of dimethylsulfoxide (DMSO). DMSO is a solvent and is readily absorbed into the skin so it is often used as a drug delivery system. DMSO, a byproduct of paper manufacturing, was banned for some time by the FDA and allowed only in veterinary medicine, primarily equine vet care. It’s high in sulfur, which is why it can help with tissue repair and is known for its distinctive smell – some say it smells like garlic, others say rotten milk, and I’ve even heard old socks. You will stink! I can attest to the smell first-hand as I used DMSO a lot throughout my high school and college years as I was always injured. Skin burns are also very common using DMSO especially if it’s mixed with a NSAID and then applied directly to the injured area, as many athletes do.
So if you are having joint pain or a connective tissue problem, especially the common cartilage degeneration, what do you do? Do you take glucosamine sulfate for joint repair? Chondroitin sulfate? MSM? DMSO? Cysteine or glutamine? Taking all the nutrients I just mentioned won’t be practical, and multi-supplements won’t work. It’s more important to realize how you got to the point of even seeking out these supplements in the first place, and what you can do to possibly reverse and prevent further tissue and joint degeneration. Let’s look at the anatomy of an injury to understand this more.
Stress and Joint Problems
Chronic stress is the cause of most injuries. You do not just wake up one day with a sore knee or neck; and you do not “catch” ITB syndrome or pull a hamstring one day while running because you just overdid it on that particular day. You sure don’t all of a sudden develop “bone-on-bone” joint problems or joint degeneration. Chronic stress, whether from overtraining, lack of sleep, ingestion of too much caffeine or refined sugar, or an emotionally unstable job or relationship, leads to hormonal imbalances. The hormone cortisol increases as a result. This decreases tissue insulin sensitivity – a phenomenon termed “insulin resistance.” It is very important because it leads to the decreased absorption of glucose into the body’s cells. When glucose doesn’t enter the cells, not only is energy production impaired, but joints ultimately cannot be repaired due to the inability to make GAGs, as discussed previously.
In insulin resistance, the cells are starving for sugar that is sitting right outside the doorway in the bloodstream waiting to be let in, and often you will crave sweets. You may crave something sugary throughout most of day, and usually right after a workout or a low carbohydrate meal. You may be irritable and moody from the roller coaster blood sugar levels hitting more highs and lows than most Internet stocks of early 2000. Over time, your muscles may start to spasm or cramp up. You may also experience what some physicians describe as “restless leg syndrome” and other sleep problems related to blood sugar dis-regulation. Insomnia and waking up frequently are very common too.
So in order to properly make the glycolytic pathway work so you have glucose available to make glucosamine you obviously have to monitor and deal with your stress levels. High stress = high cortisol = decreased glucose absorption = inability to make glucosamine = an injured athlete. This may mean training more aerobically rather than anaerobically, cutting down caffeine, getting more sleep, adjusting your life or work schedule; you get the idea. Diet plays a huge role here too. More protein, healthy fats (fish, grass fed beef, flax, eggs, avocado, nuts, seeds, coconut, butter, olive oil), and a low grain and sugar diet will help you use fat primarily as a fuel allowing the body to focus on making glucosamine and GAGs. That means the less stress you’re under and the healthier you eat, the healthier your joints will be! I think a Paleo-Type Diet is great to implement here. This GAGs process is not just inhibited by cortisol, but also estrogen as well as certain drugs such as anticoagulants, immune-suppressive agents, and antibiotics. Ladies, that means you’re more susceptible to joint issues than us guys, due to your estrogen levels, and you’ll be even more at risk if you take birth control pills or other hormonal replacement drugs.
When it comes to repairing an injury, or making sure an injury doesn’t surprise you tomorrow, you’ve also got to have sulfation and glucuronidation working well for you as I’ve talked about. So remember that glucuronidation has to do with liver detoxification of hormones, drugs, and other pollutants. So the less environmental stress you’re under (think air pollution, for example), the less medications you take, and the less cortisol you make (because you’ve dealt with stress levels), the more you have glucuronidation working for you. Now for the sulfation part.
Sulfates as a reminder, are present in foods such as broccoli, cauliflower, garlic, cabbage, onions, radishes, and mustard. But more importantly, sulfates are also depleted during high stress levels too because they are needed to detoxify cortisol in the liver. Do you see a pattern here? I sure hope so. If you are under a lot of stress then cortisol really makes a mess of every part of this GAGs pathway! The key is to not deplete more sulfur than you take in. Interesting is the fact that NSAIDs restrict sulfate availability, so cartilage cannot be repaired. This is a shocking fact for many people who are trying to help their injury with these drugs, (aspirin and ibuprofen) yet are actually doing more harm than good by depleting their sulfate levels. Research shows that NSAIDs are only beneficial 2-3 days after injury. Taking them longer, or for the many that take them every day, is inviting greater problems later in life. Deficiency of the trace mineral molybdenum also inhibits sulfate availability.
Once glucose is available, because it was allowed inside the cells since you’ve managed your stress, (normal cortisol levels), your body can make glucosamine and then ultimately make chondroitin, which will happen because you’ve got good glucuronidation going on. This all looks for the sulfur, (which is present when there are also low stress levels and no signs of NSAID abuse), to make chondroitin sulfate – the ultimate prize in injury repair. And of course we needed some glutamine along the way but we have plenty of that because a healthy individual naturally makes more than enough and is getting some in their diet – beef, chicken, fish, eggs, dairy products, cabbage, beets, beans, spinach, and parsley.
The big idea here is actually very simple in such a complex way. You have to embrace a healthy lifestyle because it all is going to affect the health of your tissues and joints. Make sure your diet contains some of the foods mentioned so you have the resources available to make GAGs happen. Consider looking at individual nutrients you may be deficient in to help you repair your tissue. Deal with your excess stress whether that’s adjusting your training, diet, or lifestyle. If you take one of the joint/cartilage supplements and it benefits you that’s fine as it may be very necessary to get you going in the right direction; it’s better than taking some drug to deal with your problem, but you should still investigate why you aren’t making the substance on your own to truly fix your health problem. The GAGs lesson is over.