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Side effects glucosamine and chondroitin: Uses, Benefits, Side Effects, and Dosage

by alexxlab

Uses, Benefits, Side Effects, and Dosage

Glucosamine and chondroitin are two popular supplements said to help manage joint pain.

Despite their widespread use, though, research on glucosamine and chondroitin has showed mixed results. In fact, some studies have shown they’re not effective.

This may leave you wondering whether you should take glucosamine and chondroitin or if you’re better off without them.

This article discusses the uses, potential benefits, side effects, and recommended dosage of glucosamine and chondroitin.

Glucosamine and chondroitin are two naturally occurring compounds within your cartilage.

Cartilage is a main type of connective tissue in your body. One of many important purposes of cartilage is to protect and cushion the ends of your bones, which is why it’s found within your joints (1, 2).

In people with osteoarthritis, this cartilage is wearing down, which can cause the bones to rub together. Over time, this can lead to pain and decreased joint mobility, commonly in the knees, hips, hands, and spine (1, 2).

Glucosamine and chondroitin, typically taken combined in a single supplement, are said to relieve arthritis pain by acting as natural anti-inflammatories and slowing down the deterioration of cartilage.

With upward of 3.6% of the global population living with this debilitating condition, many people use or have tried using combined glucosamine and chondroitin supplements to alleviate osteoarthritis pain (2).

Summary

Glucosamine and chondroitin are two compounds that occur naturally in your cartilage. Available in supplement form, they’re commonly taken together to lessen osteoarthritis pain and manage symptoms.

Glucosamine and chondroitin supplements are controversial, since many experts don’t agree on their effectiveness.

Both the American College of Rheumatology (ACR), the Arthritis Foundation, and the Osteoarthritis Research Society International (OARSI) all strongly discourage these supplements due to a lack of evidence and a high risk of bias in available studies (3, 4).

Contrarily, the European Society for Clinical and Economic Aspects of Osteoporosis (ESCEO) suggests that pharmaceutical grade — or crystalline — glucosamine and chondroitin can be used as a first-line treatment for knee osteoarthritis (4).

These mixed recommendations may partially stem from the fact that the manufacturer and type of the supplements can result in different study results. For example, pharmaceutical-grade varieties appear more effective compared with over-the-counter options (4, 5).

Summary

Despite their widespread use, glucosamine and chondroitin are controversial when used to treat osteoarthritis pain, due to conflicting research and recommendations.

There are many studies available on the use of glucosamine and chondroitin for osteoarthritis pain, though they have conflicting conclusions on the effectiveness of the supplements.

Glucosamine

Glucosamine has been extensively studied for its role in osteoarthritis pain management.

In a 2017 analysis in 1,625 people with hip or knee osteoarthritis, glucosamine supplements did not significantly improve osteoarthritis pain or function compared with a placebo (6).

On the other hand, a 2018 analysis showed small improvements in knee osteoarthritis pain with regular use of glucosamine sulfate, though the authors suggested that higher-quality data is needed (7).

Also, a 2-year cohort study found a 36% reduction in nonsteroidal anti-inflammatory drug (NSAID) use when taking 1,500 mg of crystalline glucosamine daily (8).

In the same study, 1250 mg/day of glucosamine hydrochloride, 1,200 mg/day of chondroitin sulfate, 100 mg/day of diacerein, 300 mg/day of avocado-soybean unsaponifiable (ASU), and a placebo didn’t change NSAID use (8).

Finally, a 2 1/2-year study in 407 women with overweight ages 50–60 found 1,500 mg/day of glucosamine sulfate to significantly decrease the risk of knee osteoarthritis compared with a placebo, suggesting that it may work as a preventive therapy (9).

Chondroitin

Chondroitin has also been well studied as a remedy for osteoarthritis symptom management.

A 2017 double-blind, randomized study in 604 participants with knee osteoarthritis compared the effects of taking 800 mg/day of chondroitin sulfate, 200 mg/day of a popular NSAID known as celecoxib, and a placebo on osteoarthritis pain management (10).

After 6 months, chondroitin sulfate led to similar pain scores as celecoxib and significantly lower scores than the placebo. Thus, the authors concluded that chondroitin sulfate may be an effective pain remedy for those with knee osteoarthritis pain (10).

In a 2014 review of 43 studies on the use of chondroitin for osteoarthritis, chondroitin taken alone or with glucosamine showed significantly lower pain scores — with a 10% mean difference — compared with a placebo. However, the overall quality of studies was low (11).

In the same review, the supplement was not found to improve joint mobility or function compared with a placebo (11).

Glucosamine and chondroitin together

Though the two can be taken separately, glucosamine and chondroitin are commonly taken as a single supplement. This combination has been more extensively studied.

A 2015 2-year double-blind, randomized study showed no differences in pain or joint space narrowing — a sign of cartilage deterioration — after taking either 1,500 mg/day of glucosamine sulfate, 800 mg/day of chondroitin sulfate, a combination of both, or a placebo (12).

Similar results were observed in a 2018 analysis, where combined glucosamine and chondroitin didn’t significantly improve pain or stiffness. Meanwhile, chondroitin alone led to minor improvements in pain (13).

On the other hand, another 2018 analysis observed a significant improvement in pain scores when glucosamine and chondroitin were taken together, while no improvements were found when the supplements were taken separately (14).

Similarly, a 2015 sponsored study showed that combining 1,500 mg of glucosamine hydrochloride with 1,200 mg of chondroitin sulfate effectively reduced knee osteoarthritis pain, stiffness, and swelling compared with 200 mg of the osteoarthritis NSAID celecoxib (15).

Another 2015 study also found that combined glucosamine and chondroitin supplements were comparably effective as celecoxib (16).

Ultimately, no firm conclusions can be made on the effectiveness of glucosamine, chondroitin, or the two combined as a treatment for osteoarthritic pain or stiffness. Due to the large inconsistency in results and quality of available research, continued research is needed.

Summary

Taken together or individually, both glucosamine and chondroitin may provide minor relief from osteoarthritis pain. However, not all studies have shown them to be beneficial, and more research is needed.

Most studies have shown that both glucosamine and chondroitin are safe to use for most people and no serious side effects have been reported. Only mild side effects like stomach upset, nausea, and headache have been observed (13, 17).

However, keep in mind that glucosamine is commonly derived from chitin — a compound found in shellfish. Therefore, those with a shellfish allergy should read the label carefully and opt for varieties made from cows or pigs (17).

Glucosamine may also be made from a fungus or fermented corn. And due to the animal origin of some ingredients, the supplements may not be suitable for those following a vegan or vegetarian dietary pattern.

Finally, it’s postulated that glucosamine and chondroitin supplements may affect blood sugar levels, reduce insulin sensitivity, and interact with anticoagulant medications likes Warfarin. That’s why you should consult a healthcare professional before trying them (17).

Summary

Generally, glucosamine and chondroitin are considered safe, though they may not be suitable for those with shellfish allergies, diabetes, or taking anticoagulant medication. Talk with a healthcare professional first.

Due to the conflicting data on the effectiveness of glucosamine and chondroitin, no standard recommendations are available.

That said, studies that have observed improvements in osteoarthritis symptoms routinely used dosages of 1,500 mg glucosamine sulfate and 1,200 mg chondroitin sulfate, which can be obtained over the counter (14, 15, 16).

However, it’s best to first consult a healthcare professional, who can provide recommendations tailored to you and your health.

Summary

Some studies have found 1,500 mg of glucosamine sulfate and 1,200 mg chondroitin sulfate to be the most effective. However, due to conflicting research, general recommendations cannot be made.

Glucosamine and chondroitin are popular supplements used to alleviate osteoarthritis pain.

Their use remains controversial, however, due to conflicting research. While some studies have shown that taking glucosamine and chondroitin supplements may reduce pain and stiffness, others have found that they provide no benefits.

The supplements are considered safe for most people, except for those with shellfish allergies, with diabetes or metabolic disorders, or taking anticoagulant medications.

If you’re interested in trying glucosamine and chondroitin, speak with a healthcare professional first to determine whether it’s right for you.

Overview, Uses, Side Effects, Precautions, Interactions, Dosing and Reviews

Overview

Glucosamine is a chemical found in the body. Glucosamine supplements are sold as glucosamine sulfate, glucosamine hydrochloride, and N-acetyl glucosamine.

Glucosamine is used by the body to make other chemicals that build tendons, ligaments, cartilage, and the fluid that surrounds joints. Joints are cushioned by the fluid and cartilage around them. Taking glucosamine might increase the cartilage and fluid around joints and/or help prevent their breakdown.

People commonly use glucosamine sulfate and glucosamine hydrochloride for osteoarthritis. Glucosamine is also used for joint pain, rheumatoid arthritis, multiple sclerosis, and many other conditions, but there is no good scientific evidence to support these other uses.

Uses & Effectiveness ?

Likely Effective for

  • Osteoarthritis. Taking glucosamine sulfate by mouth for at least 4 weeks can provide some pain relief and improve function for people with knee osteoarthritis. Products that contain glucosamine hydrochloride do not seem to work as well unless they are taken in combination with other ingredients. Taking glucosamine sulfate doesn’t seem to reduce the risk of getting osteoarthritis.

There is interest in using glucosamine for a number of other purposes, but there isn’t enough reliable information to say whether it might be helpful.

Side Effects

When taken by mouth: Glucosamine sulfate is likely safe in most adults when used for up to 3 years. Glucosamine hydrochloride is possibly safe for most adults when used for up to 2 years. N-acetyl glucosamine is also possibly safe when used for up to 6 months. Glucosamine can cause some mild side effects including bloating, nausea, diarrhea, and constipation.

When applied to the skin: N-acetyl glucosamine is possibly safe when used for up to 10 weeks.

When given as an enema (rectally): N-acetyl glucosamine is possibly safe when used in doses of 3-4 grams daily.

Special Precautions and Warnings

Pregnancy and breast-feeding: There isn’t enough reliable information to know if glucosamine sulfate, glucosamine hydrochloride, or N-acetyl glucosamine is safe to use when pregnant or breast-feeding. Stay on the safe side and avoid use.

Asthma: Glucosamine might make asthma worse. Until more is known, people with asthma should be cautious about taking products that contain glucosamine.

Diabetes: There used to be some concern that glucosamine might increase blood sugar levels. But most research shows that glucosamine doesn’t increase blood sugar levels in people with diabetes.

Glaucoma: Glucosamine might increase the pressure inside the eye and could worsen glaucoma. If you have glaucoma, talk to your healthcare provider before taking glucosamine.

High cholesterol: There used to be some concern that glucosamine might increase cholesterol levels. But most research shows that glucosamine doesn’t seem to increase cholesterol levels.

High blood pressure: There used to be some concern that glucosamine might increase blood pressure. But most research shows that glucosamine does not seem to increase blood pressure.

Shellfish allergy: Glucosamine is produced from the shells of shrimp, lobster, and crabs. If you have a shellfish allergy, talk to your healthcare provider before using glucosamine.

Interactions ?

    Major Interaction

    Do not take this combination

  • Warfarin is used to slow blood clotting. Taking glucosamine with or without chondroitin increases the effects of warfarin. This can increase the risk for serious bruising and bleeding. Don’t take glucosamine if you are taking warfarin.

    Moderate Interaction

    Be cautious with this combination

  • Some medications for cancer work by decreasing how fast cancer cells can copy themselves. Glucosamine might block these medications from working. Taking glucosamine along with some medications for cancer might decrease the effectiveness of these medications.

    Minor Interaction

    Be watchful with this combination

  • Taking glucosamine SULFATE and acetaminophen together might affect how well each works. But more information is needed to know if this interaction is a big concern.

  • Glucosamine might increase blood sugar levels. Taking glucosamine along with diabetes medications might reduce the effects of these medications. Monitor your blood sugar closely.

Dosing

Glucosamine sulfate and glucosamine hydrochloride have most often been used by adults in doses of 1500 mg by mouth daily for up to 3 years. Speak with a healthcare provider to find out what dose might be best for a specific condition.

Keep in mind that glucosamine used in supplements often comes from the shells of shellfish. Talk to your healthcare provider before taking these supplements if you have a shellfish allergy. Also, some glucosamine products aren’t labeled correctly. In some cases, the amount of glucosamine actually in the product has varied from none to over 100% of the amount stated on the product’s label. Some products have contained glucosamine hydrochloride when glucosamine sulfate was listed on the label.

View References

CONDITIONS OF USE AND IMPORTANT INFORMATION: This information is meant to supplement, not replace advice from your doctor or healthcare provider and is not meant to cover all possible uses, precautions, interactions or adverse effects. This information may not fit your specific health circumstances. Never delay or disregard seeking professional medical advice from your doctor or other qualified health care provider because of something you have read on WebMD. You should always speak with your doctor or health care professional before you start, stop, or change any prescribed part of your health care plan or treatment and to determine what course of therapy is right for you.

This copyrighted material is provided by Natural Medicines Comprehensive Database Consumer Version. Information from this source is evidence-based and objective, and without commercial influence. For professional medical information on natural medicines, see Natural Medicines Comprehensive Database Professional Version. © Therapeutic Research Faculty 2018.

instructions for use, price, analogues, composition, indications

Coated tablets, white or white with a yellowish tint, interspersed, oval, with a biconvex surface.

One tablet contains active ingredients: glucosamine hydrochloride – 500 mg, chondroitin sulfate (as sodium chondroitin sulfate) – 500 mg; excipients : calcium hydrogen phosphate dihydrate, microcrystalline cellulose, sodium croscarmellose, stearic acid, magnesium stearate, opadry (including polyvinyl alcohol, partially hydrolyzed; titanium dioxide E 171; macrogol 3350; talc).

Other non-steroidal anti-inflammatory and antirheumatic drugs.
ATX code : M01AX.

Pharmacodynamics
Glucosamine
Mechanism of action
Glucosamine hydrochloride is a salt of the amino monosaccharide glucosamine, which is an endogenous component and a preferred substrate for the synthesis of glycosaminoglycans and proteoglycans in articular cartilage and synovial fluid. Glucosamine hydrochloride inhibits the activity of interleukin-1 beta and other inflammatory mediators.
Clinical efficacy and tolerability
The safety and efficacy of glucosamine hydrochloride has been confirmed in clinical trials with treatment durations up to three years. Short- and medium-term clinical studies have shown that the effectiveness of glucosamine hydrochloride in relation to the symptoms of osteoarthritis is observed after 2-3 weeks of its use. However, unlike non-steroidal anti-inflammatory drugs (NSAIDs), glucosamine hydrochloride has a long-lasting effect that lasts from six months to three years.
Clinical studies with daily administration of glucosamine hydrochloride over a period of up to three years have shown a gradual improvement in symptoms of the disease and a slowdown in structural changes in the joint, as demonstrated by plain radiography.
Glucosamine hydrochloride has been shown to be well tolerated during both short and long term treatments.
Evidence of the effectiveness of the drug was demonstrated when it was used for three months, with a residual effect for two months after its withdrawal. The safety and efficacy of the drug have also been confirmed in clinical trials for up to three years of use. Continuous treatment for more than three years cannot be recommended, as there are no safety data for taking glucosamine for more than three years.
Chondrotin sulfate
Chondroitin sulfate is a high molecular weight mucopolysaccharide. It is the main component of proteaglycans, which, together with collagen fibers, make up the cartilage matrix.
Pharmacokinetics
Glucosamine
Absorption
After oral administration of 14C-labeled glucosamine, it is rapidly and almost completely absorbed, and about 90% of the radioactive label is recorded in the systemic circulation. The absolute bioavailability of glucosamine in humans after oral administration was 44%, taking into account the first pass. Following daily oral administration of 1500 mg glucosamine hydrochloride to healthy volunteers under fasting conditions, peak plasma concentrations at steady state (C max , SS ) averaged 3 hours (T max ) about 1602±426 ng/ml. At steady state, AUC was 14564±4138 ng h/mL. It is not known whether food intake has a significant effect on oral bioavailability. The pharmacokinetics of glucosamine is linear over the 750-1500 mg dose range, deviating from linearity at the 3000 mg dose due to lower bioavailability. There are no gender differences in absorption and bioavailability of glucosamine. The pharmacokinetics of glucosamine was similar in healthy volunteers and patients with osteoarthritis of the knee.
Distribution
After oral absorption, glucosamine is distributed into various vascular compartments, including synovial fluid, with an apparent volume of distribution 37 times greater than the total fluid volume in humans. Glucosamine does not bind to plasma proteins. Therefore, it is highly unlikely that glucosamine is capable of drug interactions when co-administered with other drugs that are highly bound to plasma proteins.
Metabolism
The metabolic profile of glucosamine has not been studied, since, being an endogenous substance, it is used as a “building material” for the biosynthesis of articular components of cartilage. Glucosamine is primarily metabolized to hexosamine, independent of the cytochrome system. It does not act as an inhibitor or inducer of human CYP450 isoenzymes, including CYP 3A4, 1A2, 2E1, 2C9 and 2D6.00. There is no clinically significant interaction of glucosamine with other drugs that could be mediated through inhibition and/or induction of human CYP450 isoforms.
Excretion
In humans, the plasma half-life of glucosamine is 15 hours. After oral administration of 14C-labeled glucosamine, urinary excretion was 10 ± 9%, and fecal excretion was 11.3 ± 0.1% of the administered dose. The average excretion of unchanged glucosamine after oral administration in humans is about 1% of the administered dose, suggesting that the kidneys and liver do not play a significant role in the elimination of glucosamine, its metabolites and/or its degradation products.
Pharmacokinetics in various categories of patients
In patients with renal and hepatic insufficiency renal or hepatic insufficiency have not been performed. These studies were deemed inappropriate due to the insignificant contribution of the liver and kidneys to the metabolism, degradation and excretion of glucosamine. Therefore, given the favorable safety profile and good tolerability of glucosamine, patients with renal or hepatic insufficiency do not require dose adjustment.
Children and adolescents
Pharmacokinetic studies of glucosamine in children and adolescents have not been conducted.
Elderly patients
Pharmacokinetic studies in elderly patients have not been conducted, however, clinical trials of the efficacy and safety of glucosamine have mainly included elderly patients. It has been shown that in this category of patients there is no need for dose adjustment.
Chondrotin sulfate
Pharmacokinetics has not been studied.

Relief of symptoms (mild to moderate pain), with a gradual development of effect, in adequately diagnosed osteoarthritis of the knee, hip joints and osteochondrosis of the spine.

Adults, including elderly patients
The recommended dose is 1 tablet 2-3 times a day (1000-1200 mg of chondroitin sulfate and 1500 mg of glucosamine per day). The recommended duration of treatment is at least 3-6 months.
Children and adolescents
The drug is not recommended for use in children and adolescents under the age of 18 due to lack of data on safety and efficacy.
Patients with renal and/or hepatic insufficiency
No data on the need for dose adjustment.
How to use
The tablets may be taken before, during or after a meal. It is recommended that patients who do not tolerate fasting medicines take this medicine after a meal. Tablets should be swallowed whole with sufficient liquid. If desired, the tablet can be broken or crushed to facilitate swallowing.

The following frequency of adverse reactions was determined using the following note: very often (≥ 1/10), often (≥ 1/100 to < 1/10), infrequently (≥ 1/1000 to < 1/100), rare ( ≥ 1/10000 to < 1/1000), very rare (< 1/10000), unknown (cannot be determined from the available data).
General adverse event profile
The most common adverse reactions associated with oral glucosamine and chondroitin sulfate are nausea, abdominal pain, dyspepsia, flatulence, constipation, and diarrhea. These adverse reactions, as a rule, were moderately severe and transient. In the following table, adverse reactions have been grouped based on the MedDRA classification.

Class of systems or organs Very common
≥ 1/100		 Often
≥ 1/100 to < 1/10		 Uncommon
≥ 1/1000 to < 1/100		 Rare
≥ 1/10000
up to < 1/1000		 Very rare
< 1/10000		 Unknown*
From the side of the immune system Allergic reactions**
From the side of metabolism and nutrition Inadequate glycemic control in diabetes
Mental disorders Insomnia
From the side of the nervous system Headache
Drowsiness		 Dizziness
From the organ of vision visual impairment
From the side of the heart Arrhythmias, including tachycardia
From the vascular system tides
Respiratory, thoracic and mediastinal Asthma/worsening of asthma
From the gastrointestinal tract Diarrhea
Constipation
Nausea
Flatulence
Abdominal pain
Dyspepsia		 Vomit
From the skin, subcutaneous tissue Erythema
Itching
Rash		 Angioedema
Hives
From the side of the liver and biliary tract Increased levels of “liver” enzymes in the blood and jaundice ***
General violations Fatigue Edema / peripheral edema
From the side of laboratory and physiological parameters Increased “liver” enzymes, blood glucose levels, increased blood pressure, INR fluctuations

* Frequency cannot be estimated from the available data.
** Predisposed patients may develop severe allergic reactions to glucosamine.
*** Increasing liver enzymes and developing jaundice have been reported, but a causal relationship with glucosamine use has not been established.
Cases of hypercholesterolemia have been reported, but a causal relationship with glucosamine use has not been established.
Reporting suspected adverse reactions
Medical workers are encouraged to send information about any suspected adverse reactions and inefficacy of the medicinal product to the address: Republican Unitary Enterprise “Center for Expertise of Tests in Health Care”, Tovarishchesky per., 2a, 220037, Republic of Belarus, e-mail: [email protected].

Hypersensitivity to the main and auxiliary components of the drug.
The drug should not be prescribed to patients suffering from shellfish allergy, because. the active substance (glucosamine) is obtained from mollusks and crustaceans.
Childhood.
Pregnancy and lactation.

Glucosamine
Before using the drug, you should consult your doctor to exclude the presence of joint diseases for which other methods of treatment are provided.
Cases of exacerbation of symptoms of bronchial asthma after the start of the use of glucosamine are described. Patients suffering from bronchial asthma should be informed about the possible worsening of the symptoms of the disease.
This medicinal product contains 56 mg to 111 mg sodium per daily dose, which should be taken into account by patients on a sodium restricted diet.
Patients with impaired glucose tolerance should be careful when taking glucosamine. Patients with diabetes mellitus are advised to monitor glycemic levels and determine insulin requirements before starting and periodically during treatment. No special studies have been conducted in patients with renal or hepatic insufficiency. The toxicological and pharmacokinetic profiles of glucosamine suggest no limitations for these patients. However, the use of glucosamine in patients with severe renal insufficiency should be under medical supervision.
Chondroitin sulfate
Very rarely (<1/10000) in patients with heart and / or renal insufficiency treated with chondroitin sulfate, there have been cases of edema or fluid retention. This phenomenon may be due to the osmotic effect of chondroitin sulfate.

Glucosamine
Special studies on the interaction of glucosamine with other drugs have not been conducted.
There are reports of an increased effect of coumarin anticoagulants, therefore, in patients who are simultaneously taking coumarin anticoagulants (for example, warfarin or acenocoumarol), more careful monitoring of coagulation parameters is necessary.
Oral administration of glucosamine sulfate may increase the absorption of tetracyclines from the gastrointestinal tract, but the clinical significance of this interaction is low.
It is acceptable to take steroidal or non-steroidal anti-inflammatory drugs at the same time as glucosamine.
Chondroitin sulfate
Interactions with other drugs are not described.

Due to the lack of sufficient clinical data on the use of glucosamine in pregnant women or excretion in breast milk, the use of the drug during pregnancy and breastfeeding is not recommended.

Special studies on the effect of the drug on the ability to drive a car and work with mechanisms have not been conducted. However, if headache, drowsiness, fatigue, dizziness, or visual disturbances occur while taking glucosamine, driving or operating machinery is not recommended.

So far, no cases of intentional or accidental overdose are known. In case of an overdose, the drug should be discontinued, symptomatic treatment aimed at restoring the water and electrolyte balance.

5 or 10 tablets in a blister pack made of PVC film and aluminum foil.
12 blister packs of 5 tablets (No. 5×12) or 6 blister packs of 10 tablets (No. 10×6) together with the leaflet are placed in a cardboard box.

In a place protected from moisture, at a temperature not exceeding 30 °C.
Keep out of the reach of children.

2 years. Do not use after the expiration date.

Over the counter.


Manufacturer information
Open Joint Stock Company “Borisov Plant of Medical Preparations”, Republic of Belarus, Minsk region, Borisov, st. Chapaeva, 64, tel/fax +375 177 735612, 731156.

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2020-10-01 19:55:23