Chondroitin glucosamine complexes for joints are among the most popular supplements used by people with joint diseases or those at risk of joint damage, for the purpose of prevention and treatment.
According to statistics, among all those who take dietary supplements for joints, about 59% use glucosamine, and 54% use chondroitin 11.
Both supplements have been on the market for over 20 years, and their popularity remains strong, despite the increasing number of scientific studies questioning their effectiveness, both individually and in combination.
Chondroitin and glucosamine are important components of joint cartilage. The idea of using them for treatment and protection is based on this fact. The principle is as simple and ancient as the world: “what we want to improve in our body, we eat.”
In this article, we will examine how effective glucosamine chondroitin complexes are for treating joint diseases and their prevention (in sports), what possible side effects there are, how to take them correctly, and whether it is worth it.
Main thoughts:
What is glucosamine?
Glucosamine is an important substance for the synthesis of proteoglycan molecules – structural components of joint cartilage.
Cartilage consists of a matrix of collagen fibers, into which large proteoglycan molecules are “inserted.” One of the functions of these molecules is to attract fluid into the joint, which provides high mechanical strength to the cartilage.
In osteoarthritis/osteoarthrosis (the most common joint disease, characteristic of both the elderly and athletes), there is a disruption in the functioning of the collagen matrix, one of the reasons for which may be a decrease in the concentration of proteoglycans.
Glucosamine is a substrate for the creation of proteoglycans.
It is believed that its intake can slow the progression of osteoarthritis and reduce joint pain.
Glucosamine is mainly obtained from the protective coverings of mollusks or crabs. It can also be synthesized chemically.
Scientific studies do not unequivocally confirm the benefits of glucosamine for joints.
Patient reviews indicate the existence of analgesic effects of glucosamine, which doctors/scientists tend to explain by a strong placebo effect.
Glucosamine is a material for creating structural components of cartilage (including chondroitin), which provide their mechanical strength. Scientific studies do not unequivocally confirm the benefits of its intake for the treatment and prevention of joint diseases.
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What is chondroitin?
Chondroitin is one of the types of proteoglycans mentioned above, which provide mechanical strength to cartilage. It helps retain fluid in the cartilage, which ensures their physical properties: the ability to dampen load.
It is believed that the intake of chondroitin is beneficial for joint health due to the following mechanisms of action 5, 8:
- maintaining the necessary viscosity of synovial fluid in the joint cavities by stimulating the function of synovial cells that produce it;
- stimulating the function of chondrocytes – mini-factories for producing the composite components of joint tissues – which produce collagen and proteoglycans for creating new cartilage tissue;
- blocking the action of certain enzymes that have been found in the joint fluid of people with joint diseases (rheumatoid arthritis) and may be responsible for the destruction of joint tissues;
- promoting an increase in the number of chondrocytes.
The described properties may potentially contribute to the reduction of joint pain, improvement of mobility, and slowing down the degradation of cartilage.
As a component of chondroprotective drugs, chondroitin is extracted from the cartilage of animals: cows, pigs, birds, fish (sharks), or synthesized chemically in a laboratory.
Chondroitin, like glucosamine, is water-soluble.
Scientific studies, just like in the case of glucosamine, do not unequivocally confirm the effectiveness of chondroitin for the treatment and prevention of joint diseases.
Chondroitin is a structural component of cartilage that provides its mechanical strength. Its benefits for joint health are not unequivocally confirmed by scientists.
Assumption about the mechanism of action of the combination of glucosamine and chondroitin
It is believed that the combination of glucosamine and chondroitin carries the advantages of both substances and therefore may be effective in alleviating the symptoms of joint diseases (pain, mobility disorders) as well as restoring and protecting joint cartilage from degradation 5, 14.
In osteoarthritis, when the processes of cartilage tissue destruction begin to prevail over the processes of their creation, the intake of both substances may provide the supply of building material and thereby assist the chondrocytes, which are responsible for the internal synthesis of structural components of cartilage and may not cope with their function 14.
At different times, there have been suggestions that the greater effectiveness of glucosamine chondroitin complexes compared to each of the drugs individually may be explained by their synergistic action, resulting in improved absorption and delivery of nutrients to the joints 6.
The increased concentration of both substances may enhance the synthesis of structural components of cartilage – proteoglycans.
Everything makes sense, but nevertheless, some experts point out that such an interpretation is unlikely, as patients with joint diseases (osteoarthritis) do not show a decrease in proteoglycan concentration 5.
Moreover, it will be shown below that the intake of glucosamine in combination with chondroitin does not improve their absorption; on the contrary, according to some data, both drugs may “interfere” with each other’s absorption.
The most likely explanation is that glucosamine and chondroitin promote the synthesis of proteoglycans by chondrocytes, increasing their concentration, and inhibit the action of enzymes that destroy joint cartilage 5.
1 How effective are glucosamine chondroitin complexes in relieving joint pain? Scientific research
Among all studies on the effectiveness of the chondroitin and glucosamine complex, the GAIT (Glucosamine/chondroitin Arthritis Intervention Trial) experiment is the most widely cited, which actually consisted of several experimental branches, each with different objectives 4, 6, 7.
This is one of the largest experiments and therefore the most indicative. It was initiated by the National Institutes of Health of the USA to clarify the understanding of the benefits/ineffectiveness of chondroitin, glucosamine, and their combination for the treatment and prevention of joint diseases.
The researchers set several goals:
- to determine how effective the glucosamine-chondroitin complex is in reducing joint pain;
- whether the combination of drugs has a synergistic effect that improves the absorption of each of them;
- Does glucosamine together with chondroitin protect joint cartilage from destruction more effectively than each of the drugs separately?
Before the experiment to determine the effectiveness of glucosamine-chondroitin complexes in combating joint pain, which involved more than 1583 people, all participants were classified by the severity of pain: mild – 1229 participants, moderate/severe – 354 participants 4.
The subjects took glucosamine at a dose of 1500 mg or chondroitin at a dose of 1200 mg, their combination in the same doses, or a placebo.
“The combination of chondroitin and glucosamine is no more effective than placebo in reducing joint pain in the mild pain group,” the researchers concluded.
This is a case where the ineffectiveness of the drugs was not demonstrated, but the placebo effect turned out to be very strong: 60% of participants taking placebo reported a reduction in joint pain. The values in the group taking only glucosamine, only chondroitin, and their combination were only 4-7% higher.
The analgesic effect from taking glucosamine and chondroitin was more pronounced in the group with severe joint pain: 79% of participants noted significant pain reduction, while in the placebo subgroup – 54%. In this subgroup, the combination of the drugs was much more effective than chondroitin and glucosamine separately.
This result is supported by some meta-analyses (analyses of available studies).
In the meta-analysis of the effectiveness of chondroitin, glucosamine, and their combination for the treatment of joint diseases led by Wandel S 8, which reviewed 10 studies with a total of more than 3800 patients with joint diseases, the authors provide the following assessment of the analgesic effect of glucosamine-chondroitin complexes:
“If we illustrate the effect of pain reduction on a 10 cm ruler, then with glucosamine it will differ by 0.4 cm from placebo, with chondroitin – by 0.3 cm, and with the chondroitin-glucosamine complex – by 0.5 cm.”
This review also notes an interesting fact: studies funded by manufacturers of joint drugs generally show more significant results than independent ones.
The conclusion of the scientists: compared to placebo, glucosamine, chondroitin, and their combination are not effective in reducing joint pain and do not protect joint cartilage from destruction (see below).
Scientists’ review of the effectiveness of glucosamine and chondroitin in reducing joint pain: “The combination of chondroitin and glucosamine is no more effective than placebo in reducing joint pain in patients with mild pain and shows some effect in patients with moderate/severe pain”
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2 Does the absorption of glucosamine and chondroitin improve when taken together?
Another direction of the GAIT experiment, initiated by the National Institutes of Health in the USA, was to study the effectiveness of the combination of glucosamine with chondroitin in increasing the concentration of each in the blood, i.e., improving absorption 6.
Researchers studied the effect of taking glucosamine (dose 1500 mg) and chondroitin (dose 1200 mg) separately and together in healthy individuals, as well as patients with knee joint pain who had taken these chondroprotectors in the same dosages for a long time (at least three months).
The conclusions reached by the scientists are impressive:
1 Chondroitin is not absorbed into the bloodstream when taken in any doses
“We did not find any change in the concentration of chondroitin in the blood when taken in any doses, both in people with joint pain who had taken it for a long time (3 months) and in healthy individuals (including athletes) who took it for the first time either alone or in combination with glucosamine.”
2 The maximum concentration of glucosamine in the blood is significantly higher when taken alone than when taken in combination with chondroitin
Taking chondroitin together with glucosamine hinders the absorption of the latter.
The reason may be the influence of chondroitin on the function of intestinal cells responsible for the absorption of glucosamine.
“Our data suggest that the effect of chondroitin and glucosamine in reducing joint pain, which is noted in some studies, is not related to their synergistic action that improves their absorption.
This follows from the fact that the concentration of chondroitin in the blood does not change whether taken alone or in combination with glucosamine.
Moreover, it seems that chondroitin affects the absorption of glucosamine, the concentration of which in the blood decreases when taken together. The reason may be their indirect action on intestinal and liver cells.”
Scientists’ review on the absorption of glucosamine-chondroitin complexes: “The concentration of chondroitin in the blood does not change whether taken alone or in combination with glucosamine… chondroitin affects the absorption of glucosamine, the concentration of which in the blood decreases when taken together”
3 Do glucosamine and chondroitin help protect joint cartilage from destruction?
As part of the GAIT experiment, scientists also studied the effect of glucosamine-chondroitin complexes, as well as their individual components, on the dynamics of the joint gap (a measure of cartilage degradation) over 24 months in 572 patients with joint diseases 7.
During this period, some participants took glucosamine (500 mg three times a day), others took chondroitin sulfate (400 mg three times a day), a third group took glucosamine and chondroitin (in the same doses), a fourth group took Celecoxib (200 mg a day), and a fifth group received a placebo.
Result:
“There were no significant changes in the joint gap size (degree of cartilage degradation) across all groups.
The best results were seen in those who took glucosamine, followed by chondroitin sulfate. In the group taking the glucosamine-chondroitin complex, the joint gap changed the most (the condition worsened even more than in the placebo group).”
A meta-analysis led by Wandel 8 confirms this conclusion: “The effect of glucosamine, chondroitin, or their combination on the dynamics of joint gap changes for all medications is very insignificant.”
The authors of the study titled “Does glucosamine or chondroitin prevent the destruction of joint cartilage in osteoarthritis?” answer this question – “no.”
Explaining the reason for some “positive” trials supporting the ability of these drugs to affect cartilage structure by restoring it, the authors point to the low accuracy of the methods used to assess the joint gap size (X-rays), as well as the fact that glucosamine has anti-inflammatory effects, which also manifest in changes in the geometric sizes of joint elements 9.
“Neither chondroitin sulfate nor polysulfate prevent the development of osteoarthritis in healthy joints,” the scientists conclude.
“In diseased joints, only chondroitin injections show some effectiveness in preventing the destruction of joint cartilage; the oral form does not” 9.
Commenting on the recommendations of glucosamine and chondroitin for the prevention and treatment of joint diseases provided by some authoritative organizations, the authors of the study note that they “are premature, as the methods used to assess effectiveness in positive studies are imperfect” 9. This fact is also confirmed in the GAIT study 4.
Review of scientists on the effectiveness of glucosamine and chondroitin for protecting joint cartilage from destruction: “The effect of taking glucosamine, chondroitin, or their combination on the dynamics of joint space change (a measure of cartilage degradation) for all drugs is very minimal”
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Harm and Possible Side Effects
The safety of chondroitin and glucosamine for health with long-term use is confirmed in numerous studies and meta-analyses 2, 3.
Glucosamine is recognized by scientists as safe in doses up to 2000 mg per day, and chondroitin sulfate – 1200 mg per day 13.
During the aforementioned 6-month GAIT study, serious side effects were recorded in 61 participants out of 1583 during the experiment; however, only three were deemed related to the study subject: chronic heart failure (in the group taking chondroitin and glucosamine), stroke (in the celecoxib group), and chest pain (in the glucosamine group) 4.
The majority of side effects were mild and evenly distributed among the groups, indicating their independence from the type of drugs taken.
Among the relevant side effects – primarily mild digestive disorders.
No effect on blood glucose levels was noted – one of the potential side effects characteristic of glucosamine.
Due to the fact that in most cases glucosamine is made from shellfish, it can be a cause of allergic reactions in people with this type of food allergy.
Glucosamine, chondroitin, and their combination are considered safe health products. Among the possible side effects are mild digestive disorders.
How to take glucosamine-chondroitin complexes and is it worth it? Recommendations
Experts (doctors, scientists) almost never prohibit the use of chondroprotectors, including the glucosamine and chondroitin complex, despite the ambiguity of scientific research.
Given the lack of serious side effects from both drugs and the obvious fact of positive reviews from people with joint pain, there is no sense in a ban.
The summary of expert recommendations is contained in the following comment by Fred Tudiver, a scientist from East Tennessee State University 9:
“I tell my patients with osteoarthritis that glucosamine sulfate (but not chondroitin sulfate) may help address joint pain and improve mobility, but there is no safe and reliable means to treat and stop the destruction of joint cartilage.”
Expert recommendations on taking glucosamine and chondroitin: “Glucosamine sulfate (but not chondroitin sulfate) may help address joint pain and improve mobility… there is no safe and reliable means to treat and stop the destruction of joint cartilage.”
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Conclusion
The American College of Rheumatology in its 2012 recommendations does not recommend either chondroitin or glucosamine, nor their combination for the treatment of joint diseases (osteoarthritis) (while in 2000 it recommended 10), while in the recommendations of the European League Against Rheumatism both drugs have the highest effectiveness rating as “slow-acting drugs for alleviating the symptoms of joint diseases, which may also restore the structure of joint cartilage” 1.
Scientific studies do not unequivocally confirm the effectiveness of either glucosamine or chondroitin in treating the symptoms of osteoarthritis (joint pain, mobility issues), nor their ability to restore cartilage.
However, patient reviews on glucosamine and chondroitin indicate that a significant percentage of them experience relief when taking these substances.
At the same time, it is worth noting that it does not matter much whether this result is due to the placebo effect or the actual action of the drugs: a person will never pay for something that does not work.
For this reason, experts almost never prohibit the intake of either glucosamine or chondroitin, or their combination. However, they do note that if there is no effect, there is no point in continuing the intake.
Serious side effects are absent for both substances.
The significant difference in the results of experiments may be explained by the varying dosages of chondroitin and glucosamine, as well as their quality. The content of active substances in products from different manufacturers varies significantly 9.
