Tissue and joint repair is an important topic for 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. 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.
GAGS: Glycosaminoglycans
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—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 also protects organs and even stores energy.
Glucosamine’s Role in Tissue Repair
To make GAGs, you need the main precursor, which is glucosamine. Glucosamine is high in the shells of shellfish and animal bones, which is why our grandparents who made 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 with nutrients such as vitamins B1, B2, B3, and B5, as well as magnesium, lipoic acid, and potassium. Glutamine, an amino acid our bodies can synthesize, is also necessary and added to this step. Let’s learn more!
Glutamine
Glutamine is the most abundant naturally occurring, nonessential amino acid. It’s been shown to be useful in the treatment of serious illnesses, injuries, 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 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 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 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 help 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 pyridoxal-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 is 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 firsthand, as I used DMSO a lot throughout my high school and college years because I was always injured. Skin burns are also very common when using DMSO, especially if it’s mixed with an 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 multisupplements won’t work. It’s more important to realize how you got to the point of seeking out these supplements, 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 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 the day, and usually right after a workout or a low-carbohydrate meal. You may be irritable and moody from the roller coaster of blood sugar levels hitting more highs and lows than internet stocks of the early 2000s. 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 dysregulation. Insomnia and waking up frequently are very common too.
In order to properly make the glycolytic pathway work so you have glucose available to make glucosamine, you 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 low-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 by estrogen and certain drugs such as anticoagulants, immune-suppressive agents, and antibiotics. Ladies, that means you’re more susceptible to joint issues than 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. 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 fewer 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 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. An interesting fact is that NSAIDs restrict sulfate availability, so cartilage cannot be repaired. This is shocking for many people trying to help their injury with these drugs (aspirin and ibuprofen), yet they are actually doing more harm than good by depleting their sulfate levels. Research shows that NSAIDs are only beneficial for two to three days after the injury. Taking them longer (many people 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 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 gets 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 affects 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 the health problem. The GAGs lesson is over.
