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Abstract
Glucosamine supplementation has mainly been focused by many researchers to establish its benefits and effects on people experiencing joint pains especially in the knee due to cartilage damage or osteoarthritis. Some tests have been carried out involving patients with knee pain of unknown origin. They performed the tests for 3 months while assessing their improvements throughout the period. They compared the efficacy of glucosamine, methlysulfonylmethane (MSM), and placebo.
They divided patients into two or more groups and later used the findings to report on the efficacy of the supplements. Most studies reported glucosamine as superior and most effective among the supplements and also indicated fewer side effects as compared to the other supplements. Most studies proposed glucosamine supplementation to be used as pain relievers.
This paper discusses the effects of glucosamine supplementation on people. Some experiments have been highlighted in the study to compare different findings. Side effects of glucosamine have been discussed as well. Effects of glucosamine on glucose metabolism have been explained.
Introduction
When glucosamine is converted to glucosamine sulfate or hydrochloride, it helps in regenerating or restoring cartilage and displays any anti-inflammatory effects (Braham, Dawson, & Goodman, 2003, p.13). This can result in deterioration of cartilage and advancement of osteoarthritis.
It is significant to point out that there is range of compounds and chemicals inside cartilage and intake of glucosamine alone should not be seen as the only solution. After a while, daily tear and wear, imbalance diets, normal injuries, and aging may lead to uneven and damaged cartilage, tissues, and tendons.
Maintaining healthy and steady joints is an essential part of keeping ourselves active and staying pain free. Glucosamine have been indicated to fulfill above issues through maintaining healthy and flexible joints by restoring and lubricating connective tissues.
Most studies have shown that glucosamine supplements may offer great assistance in reducing or eliminating pain in the body, particularly knee pain and improvement of physical function. This paper is a critical assessment of the accessible research information on the effects of glucosamine supplementation to individuals having knee pain.
Discussion
The occurrence of knee and ankle injuries is possibly higher in sports than any other event and often prevents participants in training and competitions. Glucosamine and chondroitin are two well-known substances which are used for joint health maintenance. It is considered that glucosamine can assist to improve the structural integrity and flexibility of bone cartilage.
Glucosamine may retard the development of osteoarthritis, at least in adults. From some literatures, it showed that glucosamine assists adults with knee injury since it produces a palliative effect and acts as an option or adjuvant cure to non-steroid anti-inflammatory medicine (Maughan, 2006, p.90).
The safety assessment of glucosamine supplements in line with the latest indications and dosage treatments showed that glucosamine is possibly safe. Diarrhea and bloating can be experienced and people with shellfish allergies should abstain from taking glucosamine (Maughan, 2006, p.90). Footballers always like to use glucosamine supplements as a way of reducing knee pain or osteoarthritis.
Moreover, this practice in sports may be premature since there is lately no evidence to show that glucosamine could act as prevention to knee pain and/or osteoarthritis in healthy athletes. It is as well very important to point out that all the researches of the effects of glucosamine have been performed in older persons, and therefore it is uncertain if such results may be assumed to be same to young footballers experiencing joint pain and/or osteoarthritis.
Since 1960s in Germany, glucosamine has been considered to be curative substance for OA. The form of glucosamine sulfate can originate from chitin. Chitin is a well-known highly abundant polymer in the world and accessible form, for instance, it may as well be made from synthetic methods. In most parts of Europe, glucosamine is accessible as a prescription drug. In North America, the substance is available as a nutritional supplement which has approved pharmaceutical efficacy and properties.
Glucosamine is located in almost all body tissues but cartilage kidney and liver have higher quantity of glucosamine. It is the most essential element needed for biosynthesis of different chemicals comprising of glycoproteins, proteoglycans, and hyaluronate, which are chemical compounds closely entailed with joints structure and function.
Glucosamine can be provided in three ways; intra articular, intramuscular, intravenous, and oral means. The following three methods are practiced in Europe, except in UK. About 75% of the oral glucosamine sulfate is taken through intestine and removed through renal means. Most medical tests on oral glucosamine have utilized normal prescription of glucosamine, 500mg taken thrice every day, even if the patients do not need the pain relievers.
The categorization of glucosamine as a nutritional supplement rather than a drug means that the producers are not required to abide by Good Practice in Manufacturing as provided to pharmaceutical manufacturers. Tests have indicated that there are differences in both content and purity of glucosamine from several producers and varying consignments from the same producer.
The study done by US National Institute of Health on the quality of glucosamine for cure of OA did not established an appropriate source which has stable quantities from batch to batch and they decided to make their own substance.
Ronca (1999) found out that there is significant sum of data from medical tests relating to patients experiencing osteoarthritis which indicate that taking glucosamine chondroitin sulfate daily for 8 to 24 weeks can decrease the severe pain and progress physical functions of joints.
Ronca showed the impacts of 12 weeks of glucosamine supplements on people with knee pain, indicating the same progress in clinical and functional trials in the cure of placebo subjects. However 88% of the subjects indicated some progress in knee pain than individuals in placebo group which was simply 17%. Most studies which have been published supported partially these study but they were concerned about the extent of efficacy and accuracy for these analyses and also the quality of the accessible statistics.
Latest researchers (Mindell & Colman, 1998) have failed also to offer better and dependable conclusion, possibly due to differences in study methods, number and extent of pain in subjects tested. The facts concerning the efficacy of glucosamine sulfate can be superior to other supplements. Studies have yet to study the benefits for athletes experiencing knee pain; however there have been no appropriately managed tests in athletes.
A study by US military on people with knee and back pain indicated intense progress after administering glucosamine but there is no effect on trials of running performance. Nevertheless, subjective relief by itself has particular worth and this potential benefit should not be disregarded. There have been no much reports about the side effects of glucosamine, but the extensive use of the substance indicates a positive effect and the problems should become evident.
How it works
The joints of the body consist of two-third of water and yet unluckily they are not capable to keep it. More studies have indicated that glucosamine is essential in maintaining the cartilage flexible and healthy by attracting and keeping water and nutrients in its surroundings.
Studies have gone on to support the view that glucosamine assists in renewing cartilage when they become damaged, therefore maintaining function and mobility of the joints. It has been considered to play an important part in reducing knee pain. Due to its capacity to assist maintain and lubricate joints, it is greatly used by athletes, footballers, and in gyms.
Physically active people like footballers and athletes a times experience damaged cartilage because of many years of recurring movements and exhaustion of their joints. Always such cartilage damage leads to painful knees, shoulders, and elbows. Glucosamine has enormous reputation due to its evident capacity to lubricate and assist renew tendons, ligaments, and cartilage.
Reinforcing connective tissue assists maintain joints healthy and resilient enough to act as effective shock absorbers and prevent injuries resulting from intensive exercise and recurring motion or by the ordinary effects of aging.
Some people who start to experience in premature stages of osteoarthritis have extreme cartilage damage where bone rubs on bone at the body joints, creating a hard or impractical move. Research has indicated that glucosamine may assists fight this situation by renewing cartilage, facilitating the making of connective tissue, and as well serving as an anti-inflammatory.
Glucosamine Ease Knee Pain
Glucosamine supplements are sulfur which contains amino sugar which takes place naturally in connective cartilage and tissue. The cells are motivated by glucosamine sulfates; these are cells which engage in fresh bone and cartilage creation and hence contributing in sustaining the mobility, flexibility, and strength of joints tissues and cartilage. The experiment carried out randomly supplementing 45 subjects with either placebo or glucosamine for 3 months.
Joint line palpation, was one of the analyses done in the research for a distance of three meters, stair climb and answering two types of questionnaires, i.e. the Knee Pain Scale (KPS) and the Knee Osteoarthritis Outcome Score (KOOS). Braham, Dawson, & Goodman (2003) did a study to analyze the effects of glucosamine supplements on those facing knee pain and other studies which will be highlighted below supported the above findings.
The outcomes of the functional and clinical examination indicated progress in 3 months but lacking any major difference between both groups. The findings from the questionnaires as well indicated progress within that period, however the glucosamine collection was established to possess considerably better KOOS life quality after 2 months and the last examination, at the third month, and lesser scores at second month when matched up to the group of placebo.
The outcomes of the participant subjective assessments proposed a major variation between both groups with positive outcomes for glucosamine supplementation. 23 of the 25 subjects (92%) in the subjects indicated progress in their knee pain matched up to merely 4 of 20 (20%) tests in those administered with placebo (maughan, 2006).
The study proposed that using a glucosamine supplement can relieve pain and advance function in those with frequent knee pain, probably resulted from earlier cartilage injury. Glucosamine is a substance which occurs biologically and that is cartilage constituent.
Its core role is to assist in prevention of the cartilage breakdown between bones and joints. Since the knee is a main location for this breakdown, making sure that the body has enough quantity of glucosamine on a frequent basis is essential in preventing knee injury and maintaining healthy knee joints and cartilage.
Oral administration is the most broadly standard way in which doctors uses to give glucosamine to their patients; the efficiency of glucosamine provided by the means of injection is still under investigation. For instance, there presently exists an FDA permitted treatment, SYNVISC, for the general cure of pain related with joint disorder. The treatment comprises of injection of a glucosamine with glycosaminoglycan at the patients knee.
The use of oral glucosamine prescription has been seen not to be effective in treatment of knee pain since it may not reach the targeted location. Merely small quantity of the measured glucosamine is considered to be available to the targeted tissue through the use of oral treatment. Though, SYNVISC is presently permitted just for treatment of the injured knee. Both United States and United Kingdom do not recognize glucosamine supplements as a medication and only provide them in from of dietetic substance.
Concerning healthy athletes without evident symptoms of body tissues injuries, there is lately no evidence reported regarding what occur if glucosamine and chondroitin sulfates is used and later stopped. Some studies done showed that using glucosamine and chondroitin sulfates supplements may assist to create a stronger body tissues matrix and also prevent or eliminate the incidence of future injuries and/or growth of arthritis in the future.
Hence the advantage of using glucosamine and chondroitin sulfates for young people of any age, particularly if they have any joint pain or firmness, comprises enhancement of joint lubrication, better shock abortion, decrease in injuries occurrence or stiffness, assist in softening and stronger skin, hair, and nails, and improve tissues hydration. It helps in reducing the future injuries mostly in athletes.
Glucosamine and OA: biological plausibility studies
The decrease in the cartilage proteogylycans hinders the cartilage medium affinity for water and the capacity of water to simply flow in and out of the body joint system.
Studies have shown that such variation in the composition of these molecules have destructive effect on the biomechanical functions of healthy person articulate cartilage and synovial fluid (Lockwood, 2007). The variations in the composition of the molecules create articular cartilage sustainable to the impacts of tensile and other effects to the body which happens while the body is in motion.
In literature, exogenous provision of glucosamine or chondroitin sulfate to chondrocytes will improve the inequality between cartilage degradation and synthesis happening in the people with OA and assist in preventing more harm to the articular cartilage of the body joints.
Experimental tests have proposed that glucosamine substance can be taken up through the gastrointestinal structure. Radioisotope researches on glucosamine have indicated fast supply all over the human body where the cartilages take more quantity. While the vitro analyses have shown that the substance may facilitate synthesis of proteoglycan and glycosaminoglycan inside the joint structure. In animal analysis, large amount of the dose of the same substance indicated to have had a mild anti-inflammatory impact.
The anti-inflammatory impact mechanism of glucosamine substance is evidently not carried out through the cyclooxygenase and adjustment of prostaglandin path, like in anti-inflammatory medicines which are not steroidal, but it is perhaps derived from its capacity to make proteoglycans that is required to raise the intracellular ground element and alleviate cell membranes. Glucosamine does not possess the capacity to openly serve as a palliative substance.
Rather, glucosamine seems to openly decrease the progression of joint medium degradation and possibly facilitate restoration of glucosamine through promoting the creation of osteoglycans. Regardless of discussions given in these tests, the physiological description on the way glucosamine have effects on cartilage degradation still requires more research.
Assessment of efficacy
Glucosamine sulfate supplementation in people experiencing knee pain has been showed to assist in easing joint pains and enhance their functions. For instance, Maughan, King, & Lea (2004) examined the results of three years of glucosamine sulfate supplementation on continuous joint deterioration and its symptoms related to knee OA.
The outcomes showed that causes of knee pain, joints firmness, and physical functions were enhanced. Likewise, Lozada (2007) examined the safety and effectiveness of supplementation mixtures of glucosamine and methlysulfonylmethane (MSM) in group facing knee OA.
They established that supplementation with MSM and glucosamine decreases swelling and knee pain, whereas enhancing the physical role of the joints. The results of many tests demonstrated that glucosamine supplementation can have curative advantages for those with OA.
As a result, chondroitin, MSM, and/or glucosamine dietary supplementations have been proposed especially for active persons. In theory, glucosamine supplementation can offer additive advantages to people experiencing knee OA when beginning a training and weight loss course.
Maughan (2006) stated that 3-years of glucosamine sulfate supplementation assists in prevention and advancement of joint-space narrowing and enhanced WOMAC scores in people having knee OA.
He further established that glucosamine supplementation (2,000 mg/d of 12-weeks) enhance quality of life markers and individually indicated views of knee pain in people experiencing frequent knee pain. He concluded that dietary glucosamine and/or supplementation (1,500 mg/d of 12-weeks) generated an a palliative and anti-inflammatory result, decreased pain, and enhanced physical functioning capacity of joints in people with mild to fair knee OA.
In addition, Lockwood (2007) examined the effects of 12-weeks of consuming a dietary supplement which have 1,300 mg/d of glucosamine hydrochloride, 400mg/d of shark cartilage powder, 75-110 mg/d of chondroitin, and 50 mg/d of quercetin on synovial fluid characteristics of people with OA.
The studies further stated that the people with OA facing major improvement in pain, capability to exercise normal activities (moving up and down the stairs and walking), and changes in characteristics of synovial fluid properties. Lastly, Russell & McCarty (2009) stated that dietary glucosamine sulfate supplementation (1400 mg/d for 8-weeks) decreased OA symptoms in people walking at least 40 minutes daily.
All these results supported the literature that glucosamine supplements can offer several curative advantages to people experiencing knee OA.
In 2003, researchers examined the reported findings of 16 studies in glucosamine on knee OA and came up with the view that glucosamine supplementation assisted in joints mobility of 1 out of 4 patients and suggested that it can make the narrowing of the joints gaps slow. However, though the researchers who analyzed such studies came up with conclusion that there seem to be some level of efficiency of glucosamine supplements and also stated some concerns with some faults in all the researches comprising poor quality of the studies, bias because of company financial support, biased reports of knee pain and few people being examined in the researches.
Further analysis by Lockwood (2007, p.90) provided people with regular knee pain 3 months of a glucosamine supplement showed that it may reduce pain to a certain extent and enhance mobility of people with regular knee pain because of cartilage problem and/or likely osteoarthritis. 90% of the people provided with glucosamine did not report minimal knee pain.
Additionally, there were no aimed improvement in both groups in the physical function examinations and hence should be pointed out that the decrease in knee pain was self reported.
Qualitatively, the study of Braham, Dawson, & Goodman (2003) was suported by the results of all above studies which have proposed that glucosamine supplementents offer certain levels of pain relieve and enhanced mobility to individuals with regular knee pain that can be because of cartilage damage and probably OA. In the study done by Braham, Dawson, & Goodman (2003), 88% of glucosamine group and merely 17% of placebo group personaly experienced pain ease and mobility improvements in the study time.
Such individual information showed that most of the benefits happened between fourth week and eighth week, as recognised in other analysis. Usually, some forms of anti-inflammatory and analgesics serve in managing the OA. Latest researches have shown that glucosamine, which is a amino sugar formed in the body, may offer assistance in reducing pain in the body (Russell & McCarty, 2009).
Adams (2009) did a systematic research on RCT on the efficiency in treating people with OA and glucosamine toxicity. This seems to be the first presented methodical study on glucosamine effects on OA which have been carried out through the use of precise method needed during these studies.
Most of the main reviews indicated results measures on motions, functional state and pain. 15 RCTs (11 on knee OA, 1 on multiple locations, 2 on spine OA and one did not indicate location) were used for the tests. 12 subjects were in the group of placebo-controlled and four of them were in the group of active-NSAIDs-controlled (Adams, 2009).
The process of glucosamine administration changed through the tests. In the 12 subjects under placebo-controlled, glucosamine was established to be greater in 11 subjects. In the other 4 subjects under active-NSAIDs, glucosamine was established to be equal to two tests and greater in the remaining two tests.
The researchers pointed out that glucosamine are superior and very effective in the 15 subjects in both cases. Those who withdrew because of the side effects of glucosamine were approximated as 1.5%. Of the 990 subjects on glucosamine, merely 62 indicated poor responses. With reference to the excellence of the main reviews, the researchers gave a conclusion that average design score was 3/8, average analysis score was 6/8 and sum average median quality score was 10/16 (Adams, 2009).
They further noted what they believed to be severe flaws in the main reviews, comprising insufficient standardization in the diagnostic measures of OA, minimal period of follow-up, blinding and randomization mechanisms, short of sample size evaluation, and intent to treat examination in addition to short of pre-randomization exclusion and inclusion measures.
Additionally, the authors, identified that 12 out of 15 main studies were rather linked to Rotha Pharmaceutical, producers of glucosamine which is located in Italy (Lozada, 2007). They concluded by saying that there was better evidence on glucosamine that was efficient and secure in administering OA.
They did not provided long-term efficiency and side effects of the substance therapy in people with OA. They further concluded that at that moment, it was unclear if the substance produced by manufacturers, excluding Rotha Pharmaceutical, would be safe and efficient in administering to people with OA. In this methodical assessment, the authors did not evaluate the likelihood and the effect of publication partiality, for instance, through the use of a simple funnel plot study.
Effects of Glucosamine on Glucose Metabolism
Adams (2009) did two sensitive metabolic ward tests where large quantity of free-based glucosamine (7 g or 9.6 g) were infused more than 5 hours without changing the standards of blood glucose. 16 chronic tests had assessed to the standards of fasting plasma glucose. Fasting blood glucose standards non-considerably from 92.8 to 89.8 mg/dl for values indicated from six tests. Adams (2009) analysis involved 105 subjects and made a follow-up for 3 years; he indicated that plasma glucose values were rather under standard values.
He evaluated the blood glucose values in 23 diabetic and 13 controlled tests over 3 months and pointed out that there were no major changes. He showed that every day prescription of glucosamine supplements, 1500 mg for 3 months, was linked with no major changes in insulin and in fasting blood glucose values or oral glucose tolerance trial. They further showed that patients taking 1500 mg glucosamine for 7 weeks had no impact on glucose tolerance or even insulin for 11 tests for those under diabetic conditions.
Altogether, indications from sixteen tests comprising 855 subjects which were analyzed for 9 months showed that there were no major variations in blood glucose values. For all the 32 chronic tests of mainly older subjects, glucosamine caused diabetes in four subjects while placebo treatment caused diabetes in two subjects.
Side Effects
The common glucosamine side effects may comprise of, insomnia, sleepiness, headache, mild, and a few digestive problems like vomiting, diarrhea, heartburn, lack of appetite, tiredness, and constipation. Some have stated that glucosamine, in prescription use to cure osteoarthritis; can deteriorate insulin, blood sugar, and/or hemoglobin A1C degrees in persons with insulin resistance or diabetes.
In theory, glucosamine can raise the likelihood of bleeding. People using anti-platelet or anti-clotting, those with bleeding disorders, or those who use supplements which may raise the likelihood of bleeding like red cover, ginkgo, garlic, or vitamin E, should not use glucosamine except if they are under the care of a healthcare professional (Adams, 2009). The study of the effects and safety of glucosamine in admitted and expectant women is yet to be done.
Glucosamine contributes largely in glucose metabolism through raising insulin resistance. Through animal tests, it was reported that glucosamine raised insulin resistance regularly and in tested diabetic animals. People with OA appears to be old and overweight, due to that they seem to be likely to type-2 diabetes.
A slight degeneration of insulin resistance in such group of people can therefore lead to subsequent longer-term sequelae. Though, at present, contraindication does not exist to overseeing glucosamine in people with diabetic. However, proper thorough follow-up of people who are in diabetic condition would be necessary. Some scholars have proposed that glucosamine cannot be given to expectant women and people experiencing rheumatoid arthritis or underage children.
Implications
Majority of the people believe that, probably, the forthcoming tests will portray clinically appropriate benefits of some of the glucosamine supplementation. Some will contend that a number of patients involved in the tests in all studies were either too sick in radiological conditions to benefit and that the state in which they were could not be influenced further by the trial preparations.
While others will state that many patients were not sick enough in clinical expressions and that their minimal quantity of experienced pain indicated that they might not have any advantage from the analgesic effects of the trials. To solve the above issues, some researchers would prefer the need for the fourth industry independent tests, which can entirely comprise people experiencing pain concentration at baseline of as a minimum 4 cm on a 10 cm scale and mild osteoarthritis.
The test should employ coded drug sets with arrangements and placebos of equal form and taste to cover treatment provision and make sure that the patients and the care providers should not notice. Completely abide by the guideline of intent to treat through the inclusion of every patient in the study in the groups to which they had been assigned to. The assessed arrangements should have gone through quality control to guarantee proper supplements concentrations.
Conclusion
Whether a person experience knee pain linked with mere wear and tear or long-term sports injury or possibly a premature beginning of osteoarthritis, glucosamine is an effective selection for keeping the joints healthy.
Since glucosamine is the same as chondroitin in its structure, characteristics in addition to action methods, some scholars have proposed that they can function more effectively if used jointly to assist marinating healthy joints, ease connective-tissue damage, and prevent inflammation. From the above experiments, comparing glucosamine with other sublimates, it can be noted that glucosamine is superior for the treatment of OA. Furthermore, the studies noted that different producers of glucosamine may not be uniformly effective.
They have also shown that it seems to be fairly and highly effective to use glucosamine in reducing symptoms related to osteoarthritis. The longest studied clinical examination on glucosamine and OA is a period of three years. Provided the state of OA as a chronic illness course, the data on the lasting side effects of glucosamine supplements is still not there.
Glucosamine might negatively have an effect on glucose metabolism; detailed tests reported no unpleasant effects on glucose homeostasis. Most studies showed that there were fewer occurrences of side effects through the use of glucosamine than using placebo. Glucosamine seems to be moderately to highly efficient in reducing cases caused by osteoarthritis. Future research may help in discovering some other benefits of glucosamine.
A lot of researches on the benefits and effects of glucosamine should be carried out. Some studies have reported that glucosamine may have the benefits of making the skin to look younger due to its capacity to fasten the making of collagen. In elderly people, there is slow production of collagen and this is the reason why their skin sags and wrinkles.
Since glucosamine supplements are natural and are made normally by human body, it is considered that it does not have many side effects. This study has shown the relationship between the tests done by Braham, Dawson, and Goodman (2003) and other studies given above, they proposed the use of glucosamine suppliments in the treatment of knee pain.
References
Adams, M. E. (2009). Hype about glucosamine. Lancet , 355: 354-355.
Braham, R., Dawson, B., & Goodman, C. (2003). The effect of glucosamine supplementation on people experiencing regular knee pain. British Journal of Sports Medicine , 37(1): 45-49.
Lockwood, B. (2007). Nutraceuticals: a guide for healthcare professionals. Chicago: Pharmaceutical Press.
Lozada, C. J. (2007). Glucosamine in osteoarthritis. Cleveland Clinic Journal of Medicine , 75: 66 70.
Maughan, J., King, M. R., & Lea, T. M. (2004). Dietary supplements. Journal of Sports Sciences , 21: 96 112.
Maughan, R. (2006). Nutrition and football: the FIFA/FMARC consensus on sports nutrition. New York: Taylor & Francis.
Mindell, E., & Colman, C. (1998). Earl Mindells Supplement Bible. New York: Simon and Schuster.
Ronca, F. (1999). Anti-inflammatory activity of chondroitin. Osteoarthr Cartil , 6: 15-22.
Russell, A. L., & McCarty, M. F. (2009). Glucosamine in osteoarthritis. Lancet , 356-359.
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