Criteria included types of joint involvement studied,study designs, numbers of patients enrolled, and pain index variables analyzed.27 Itwas concluded that chondroitin sulfate may be use
Description of Products
Glucosamine
Glucosamine is an amino monosaccharide (amine sugar) that can be found in chitin,glycoproteins, and the glycosaminoglycans (mucopolysaccharides), such as heparin
Glucosamine and chondroitin sulfate, along with hyaluronic acid, are commonly used for joint health, with chemical names such as 2-amino-2-deoxy-beta-D-glucopyranose and chitosamine These compounds are available over the counter as nutritional supplements, including forms like glucosamine hydrochloride (glucosamine HCl), glucosamine sulfate, and N-acetyl-glucosamine Research predominantly focuses on the chlo-ride and sulfate salts, which are the most widely purchased forms for therapeutic use.
Glucosamine has a positive charge at physiological pH, with its salt forms—such as glucosamine sulfate (containing sulfate anions) and glucosamine HCl (containing chloride anions)—neutralizing this charge, while N-acetylglucosamine features an acetylated amino group resulting in a neutral charge; all forms are water-soluble Nutritional supplements typically derive from marine exoskeletons, extracting chitin from seashells, although synthetic versions also exist Since glucosamine is classified as a medicinal product under the 1994 Dietary Supplement Health and Education Act (DSHEA), its manufacturing is unregulated, leading to a lack of standardization in active ingredients, concentrations, and labeling Consequently, consumers cannot be certain of the product contents, especially since glucosamine is inherently unstable and often combined with other ingredients for stability Analyses frequently reveal discrepancies, indicating that many formulations do not contain the ingredients listed on the label.
Chondroitin Sulfate
Chondroitin sulfate is a glycosaminoglycan (GAG) that makes up the ground substance in connective tissue’s extracellular matrix It consists of repeating units of D-galactosamine and D-glucuronic acid and is present in human cartilage, cornea, bones, arterial walls, and skin The most common form, chondroitin sulfate A (chondroitin 4-sulfate), differs from chondroitin sulfate C (chondroitin 6-sulfate), which is found in the cartilage of humans, fish, and sharks A B form, dermatan sulfate, is found in heart valves, tendons, skin, and arterial walls Molecular weights of chondroitin sulfate range from 5,000 to 50,000 daltons, and it is widely available as an over-the-counter supplement, often in a mixture of the A and C forms These supplements are typically sourced from animal by-products such as pork, bovine, whale, and shark cartilage.
Mechanisms
Glucosamine
Glucosamine is a small, easily absorbed molecule produced naturally in the body through reactions involving glucose and glutamic acid, primarily found in cartilage As humans age, the body's production of glucosamine may decrease, making supplementation necessary since it is not present in common foods It plays a vital role as a key component of the cartilage's substrate matrix, with smaller amounts also found in tendons and ligaments, supporting joint health and integrity.
190 Sports Nutrition: Fats and Proteins
The exact actions of glucosamine as a nutritional supplement remain unclear, though it is purported to promote and maintain cartilage structure and function in joints, with reported anti-inflammatory effects Biochemically, glucosamine—a sugar and sulfated amino monosaccharide—is involved in glycoprotein metabolism and is a key component of proteoglycans, specifically glycosaminoglycans (GAGs), which make up 95% of the ground substance in connective tissue Hyaluronic acid, a vital GAG, plays an essential role in articular cartilage by providing shock absorption and deformability While in vitro studies suggest that glucosamine can alter chondrocyte metabolism, it is uncertain whether oral intake effectively reaches chondrocytes in vivo Most pharmacokinetic studies on glucosamine have been conducted in animals, indicating that approximately 90% of the administered salt is absorbed in the small intestine, transported to the liver, and extensively metabolized during first-pass, with little to no free glucosamine detectable in human plasma after oral ingestion The extent to which glucosamine reaches human joints remains unknown, though some uptake has been observed in animal articular cartilage.
Chondroitin Sulfate
The precise actions of chondroitin sulfate as a dietary supplement remain unclear, although it is commonly believed to support cartilage structure and function in joints, with reported anti-inflammatory and pain-relieving benefits As a glycosaminoglycan (GAG) vital for maintaining healthy articular cartilage, chondroitin sulfate shares similar properties with hyaluronic acid While intra-articular hyaluronic acid injections have proven to alleviate joint pain and enhance mobility, similar effects have not been established for oral chondroitin sulfate It is hypothesized that consuming chondroitin sulfate orally may boost hyaluronic acid levels, potentially inhibiting cartilage breakdown.
Absorption of substances occurs primarily in the stomach and small intestine Low molecular weight forms are significantly absorbed after oral intake, whereas high molecular weight forms are not The exact amount of these substances that reach human joints remains unknown, although it is confirmed that some do enter the joint space.
Review of Research Studies and Clinical Trials
Glucosamine
Glucosamine has been studied for its potential to reduce osteoarthritis symptoms since 1969 Early research involving 20 patients demonstrated that glucosamine sulfate could significantly lessen or eliminate symptoms within 6 to 8 weeks, without causing adverse reactions Additionally, Barclay and colleagues reviewed the pharmacology and pharmacokinetics of glucosamine, highlighting its role in joint health and its therapeutic potential for osteoarthritis management.
A review of literature from 1965 to 1997 by Glucosamine and Chondroitin Sulfate 191 found three key studies indicating a reduction in osteoarthritis symptoms; however, research flaws prevent definitive recommendations for oral glucosamine efficacy Conversely, intramuscular glucosamine has demonstrated effectiveness in managing osteoarthritis symptoms Despite some studies suggesting benefits, one research group concluded that glucosamine sulfate offers no significant advantage over a placebo in pain relief, as no statistically significant differences were observed.
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Chondroitin Sulfate
Chondroitin sulfate has been recognized for its potential chondroprotective benefits based on in vitro studies conducted several years ago A comprehensive multicenter, randomized, double-blind, controlled trial involving 143 osteoarthritis patients further investigated its effectiveness, highlighting its role in managing joint health.
Research on 192 sports nutrition studies indicates that different formulations of chondroitin sulfate can significantly improve subjective symptoms within three months of treatment Notably, a single daily dose of 1200 mg is as effective as taking three doses of 400 mg each, highlighting the convenience and efficacy of higher-dose, once-daily supplementation.
A meta-analysis of chondroitin sulfate supplementation analyzed 16 selected studies examining various joint involvements, study designs, patient populations, and pain assessment methods The findings suggest that chondroitin sulfate may be beneficial in osteoarthritis management; however, the coexistence of analgesic or NSAID use in many studies complicates the ability to draw definitive conclusions Additionally, some researchers propose that chondroitin sulfate can serve as an effective anti-inflammatory agent without posing significant risks to gastrointestinal health, platelet function, or kidney safety.
Research by Conte and co-workers demonstrated that single daily doses of 0.8 g and split doses of 0.4 g led to increased plasma concentrations of chondroitin sulfate over a 24-hour period, indicating its bioavailability In a study with 20 male volunteers, plasma levels of chondroitin sulfate increased in all subjects, peaking after 2 hours However, it remains uncertain what degree of chondroprotection can be achieved through oral administration of chondroitin sulfate Baici and colleagues found no significant changes in serum glycosaminoglycan concentrations before and after ingestion of chondroitin sulfate in patients with rheumatoid arthritis and osteoarthritis, casting doubt on the claimed benefits and suggesting they may lack biological and pharmacological basis.
Uebelhart and colleagues evaluated the efficacy and safety of chondroitin 4- and 6-sulfate in treating knee osteoarthritis over one year in 42 patients They found that this combined preparation is an effective and safe symptomatic slow-acting drug for knee osteoarthritis management Importantly, their study was the first to suggest that the natural progression of osteoarthritis could be modified with symptomatic slow-acting drugs (SYSADOAs), a claim supported by other research in the field.
Combined Glucosamine and Chondroitin Sulfate
Research indicates that combined preparations of low molecular weight chondroitin sulfate and glucosamine may be more effective in alleviating mild to moderate osteoarthritis symptoms, with some studies suggesting a synergistic effect A randomized, placebo-controlled study involving 93 patients demonstrated the efficacy of this combination therapy in relieving knee osteoarthritis symptoms Additionally, safety has been shown in trials with 34 young males experiencing chronic pain and radiographic evidence of degenerative joint disease, though this group does not represent the typical older osteoarthritis population.
Animal studies indicate that chondroitin sulfate and glucosamine sulfate promote chondrocyte growth in laboratory and animal models However, there is no direct evidence to confirm that these supplements lead to cartilage regeneration in osteoarthritis patients.
In knee osteoarthritis, glucosamine sulfate can be shown to prevent knee joint space
Glucosamine sulfate, chondroitin sulfate, and chondroitin polysulfate have been shown to prevent cartilage narrowing and osteoarthritis progression in the fingers, as demonstrated on radiographs However, these effects do not indicate true cartilage regeneration Additionally, topical creams containing glucosamine sulfate, chondroitin sulfate, and camphor have been evaluated and shown to effectively relieve pain within four weeks.
Research indicates that glucosamine and chondroitin sulfates are safe and effective alternatives to NSAIDs, which can cause serious adverse effects A meta-analysis of 15 rigorously selected studies revealed moderate to large therapeutic effects, although many studies had methodological flaws Chondroitin sulfate, being a larger molecule, is poorly absorbed, and some studies suggest no additional benefit when combined with glucosamine, though both have minimal side effects To improve absorption, manufacturers now utilize low molecular weight chondroitin sulfate.
Deal and Moskowitz (2019) reviewed the use of glucosamine, chondroitin sulfate, and collagen hydrolysate in treating osteoarthritis symptoms, concluding that current evidence makes it difficult to provide definitive recommendations, especially for long-term use of non-FDA-evaluated supplements They noted that these treatments, costing $30 to $45 per month, may be financially challenging for older adults on limited incomes While some believe current therapies offer limited benefits and pose risks due to insufficient human data, glucosamine and chondroitin sulfate show modest effectiveness when combined, though long-term safety remains unproven Meta-analyses suggest some positive results, indicating these supplements can be effective and safe for osteoarthritis management.
The preliminary results of the multicenter, double-blind, placebo- and celecoxib-controlled GAIT (Glucosamine/Chondroitin Arthritis Intervention Trial) have been published, involving 1,583 patients with knee osteoarthritis Participants were randomly assigned to one of five treatment groups and followed over a 24-week period to evaluate the effectiveness of orally administered therapies, including glucosamine, chondroitin, and celecoxib This study aims to assess the potential benefits of these treatments in alleviating osteoarthritis symptoms and improving joint function.
A study evaluating the effectiveness of various treatments for knee pain involved administering 500 mg of glucosamine hydrochloride three times daily, 400 mg of sodium chondroitin sulfate three times daily, a combination of both supplements, 200 mg of celecoxib daily, or a placebo Participants were categorized based on WOMAC™ pain severity as either mild or moderate to severe The findings indicated that glucosamine and chondroitin sulfate, whether alone or combined, did not significantly reduce pain across the overall patient population However, in individuals with moderate to severe knee pain, the combination therapy showed some efficacy Notably, 60% of patients in the placebo group experienced positive effects, raising controversy regarding the study’s design and statistical analysis methods.
194 Sports Nutrition: Fats and Proteins
Side Effects
Glucosamine
There are no known contraindications to glucosamine supplementation, but concerns exist regarding its potential to increase insulin resistance when administered intravenously, as observed in both normal and diabetic animals However, this effect has not been seen with oral preparations Some researchers advise caution or avoiding glucosamine in individuals with diabetes due to potential impacts on insulin secretion Diabetic or overweight individuals should monitor blood sugar levels carefully when taking supplements Additionally, due to a lack of sufficient data, children, pregnant women, and nursing mothers are advised to avoid glucosamine supplementation.
Glucosamine generally has few and mild side effects, primarily digestive issues such as upset stomach, nausea, heartburn, and diarrhea, suggesting it is best taken with food Short-term adverse effects may include headache, drowsiness, and skin reactions, but no allergic reactions have been reported It has no known interactions with other supplements, drugs, herbs, or foods, and there are no reports of overdose, with biochemical and hematological tests confirming its safety The recommended daily dose for benefits is 1500 mg.
Chondroitin Sulfate
Chondroitin sulfate supplementation has no known contraindications, but caution is advised due to its potential antithrombotic and immunosuppressive effects Individuals with hemophilia or those taking anticoagulants like warfarin should avoid it Additionally, since most supplements are salt-based, those on salt-restricted diets should opt for salt-free versions Due to lack of data, children, pregnant women, and nursing mothers are advised to avoid consumption.
Chitosan is generally well-tolerated, with few mild side effects such as nausea, heartburn, and diarrhea, and no reported allergic reactions It does not interact with other supplements, medications, herbs, or foods, although it may reduce nutrient absorption when taken Safety assessments, including biochemical and hematological tests, confirm that chitosan is safe with no reports of overdose The recommended effective dose is 1200 mg to achieve health benefits.
Use in Sport and Exercise
Glucosamine and chondroitin sulfate are widely used in sports and exercise for their potential chondroprotective effects, aiming to reduce inflammation and pain following injuries Many athletes and active individuals use these supplements proactively to prevent injuries and promote joint health, rather than solely for post-injury recovery It is believed that these supplements may help prevent joint damage, accelerate healing processes, and serve as beneficial adjuncts after surgical procedures.
Exercisers, especially runners and athletes involved in contact and cutting sports, place stress on chondral surfaces, which can lead to wear and injury Supplementation is particularly popular among these groups to support joint health and prevent ligament injuries, helping to maintain optimal performance and reduce the risk of damage.
Many athletes experience meniscal injuries or tears, highlighting the need for effective chondroprotection However, current research provides no conclusive evidence of benefits for healthy athletes, as existing studies primarily involve individuals with osteoarthritis where supplements are used alongside other treatments It remains uncertain whether these supplements would have the same positive effects in athletes without joint damage.
Supplement use is widespread among athletes, despite limited evidence of their efficacy A survey of Olympic athletes revealed that common substances include NSAIDs, used by all surveyed gymnasts, and supplements like glucosamine and chondroitin sulfate, often initially taken to reduce injury-related pain and swelling Many athletes become chronic users of these supplements, raising concerns about potential adverse effects on the gastrointestinal, hepatic, and renal systems Anecdotal reports also suggest that athletes often consume glucosamine and chondroitin sulfate even in the absence of injury.
While current evidence suggests that supplement consumption appears safe, long-term studies are still needed to confirm their safety profile Athletes should make informed decisions based on available information, as there are no specific warnings against use It's important to recognize the placebo effect, as taking a product believed to reduce pain may itself produce a beneficial psychological response, enhancing perceived relief.
Summary and Recommendations
Glucosamine and chondroitin sulfate have been used as nutriceuticals since 1969 11
Homeopathic remedies are believed to improve osteoarthritis symptoms by reducing inflammation and promoting cartilage regeneration; however, while animal studies show promise, human research remains inconclusive, and no definitive conclusions have been reached Nonpharmacological treatments, such as regular exercise—including aerobic and strength training—and a healthy diet, are recommended for managing symptomatic osteoarthritis of the hip and knee Notably, exercise has been found to be as effective as NSAIDs in alleviating pain and enhancing function, suggesting that, particularly for certain groups, supplement and drug therapies could potentially be minimized or avoided.
Human research is urgently needed to understand the long-term effects of supplements like glucosamine sulfate and chondroitin sulfate, especially in athletes consuming these substances in large quantities While anecdotal evidence suggests these supplements may help alleviate osteoarthritis symptoms and could be effective for some individuals, the American College of Rheumatology Subcommittee on Osteoarthritis is still evaluating clinical guidelines for their use The National Institute of Arthritis and Musculoskeletal and Skin Diseases emphasizes the importance of ongoing research to determine safety and efficacy.
In 1999, NIAMS partnered with the National Center for Complementary and Alternative Medicine (NCCAM) to launch a comprehensive multicenter study evaluating the effectiveness of glucosamine and chondroitin sulfate This collaborative effort aimed to gather large-scale data to better understand the potential benefits of these supplements for joint health.
Initial studies on 196 sports nutrition subjects focusing on fats and proteins did not demonstrate overall efficacy However, there is evidence suggesting that these supplements may be beneficial for individuals experiencing moderate to severe pain, highlighting their potential role in pain management among athletes.
Athletes are always seeking natural methods to improve their performance and gain a competitive edge Although current research lacks sufficient human data to classify glucosamine and chondroitin sulfate as proven ergogenic aids, their safety profile allows athletes to consider using these supplements without significant risk Since there is minimal potential for harm, athletes can safely incorporate glucosamine and chondroitin sulfate into their routines if they believe these supplements may provide benefits.
They can be found in pills, powders, and beverages (“joint juice,” “motion potion”).
Recent research suggests that the most potential benefit from joint supplements may come from preparations combining glucosamine with low molecular weight chondroitin sulfate Athletes can safely use these supplements, but they should consider the cost of $30 to $45 per month against the mixed evidence regarding their effectiveness, which can take several months to manifest Proper regulation of these supplements is essential due to possible long-term side effects and uncertain treatment durations Since athletes are generally healthy, their response to supplements may differ from individuals with osteoarthritis An authoritative book offers effective regimens for pain reduction, which some users report as successful; however, for osteoarthritis sufferers, exercise itself might serve as the most beneficial "drug" for managing joint health.
1 Morelli, V., Naquin, C., and Weaver, V., Alternative therapies for traditional disease states: osteoarthritis Am Fam Physician,67, 339, 2003.
2 Brief, A.A., Maurer, S.G., and Di Cesare, P.E., Use of glucosamine and chondroitin sulfate in the management of osteoarthritis J Am Acad Orthop Surg.,9, 352, 2001.
3 Chard, J and Dieppe, P., Glucosamine for osteoarthritis: magic, hype, or confusion?
4 Sutton, L., Rapport, L., and Lockwood, B., Gucosamine: con or cure? Part II Nutri- tion,18, 693, 2002.
5 Skillman, J.M., Ahmed, O.A., and Rowsell, A.R., Incidental improvement of breast capsular contracture following treatment of arthritis with glucosamine and chon- droitin Br J Plast Surg., 55, 454, 2002.
6 Hendler, S.S and Rorvik, D., Eds., PDR for Nutritional Supplements, Thomson
7 Abimbola, O., Cox, D.S., Liang, Z., and Eddington, N.D., Analysis of glucosamine and chondroitin sulfate content in marketed products and the Caco-2 permeability of chondroitin sulfate raw materials J Am Nutraceut Assoc., 3, 37, 2000.
8 Towheed, T.E and Anastassiades, T.P., Glucosamine and chondroitin for treating symptoms of osteoarthritis Evidence is widely touted but incomplete JAMA, 283,
9 Setnikar, I., Palumbo, R., Canali, S., and Zanolo, G., Pharmacokinetics of glu- cosamine in man Arzneimittelforschung, 43, 1109, 1993.
10 Setnikar, I and Rovati, L.C., Absorption, distribution, metabolism and excretion of glucosamine sulfate A review Arzneimittelforschung, 51, 699, 2001.
11 Sutton, L., Rapport, L., and Lockwood, B., Gucosamine: con or cure? Nutrition, 18,
12 Pujalte, J.M., Llavore, E.P., and Ylescupidez, F.R., Double-blind evaluation of oral glucosamine sulfate in the basic treatment of osteoarthritis Curr Med Res Opin.,
13 Barclay, T.S., Tsourounis, C., and McCart, G.M., Glucosamine Ann Pharmacother.,
14 Reichelt, A., Forster, K.K., Fisher, M., Rovati, L.C., and Setnikar, I., Efficacy and safety of intramuscular glucosamine sulfate in osteoarthritis of the knee A ran- domised, placebo-controlled, double-blind study Arzneimittelforschung, 44(1), 75–80, 1994
15 Hughes, R and Carr, A., A randomized, double-blind, placebo-controlled trial of glucosamine sulphate as an analgesic in osteoarthritis of the knee Rheumatology, 41,
16 Braham, R., Dawson, B., and Goodman, C., The effect of glucosamine supplemen- tation on people experiencing regular knee pain Br J Sports Med 37, 45, 2003.
This 3-year placebo-controlled study conducted by Bruyere et al investigates the correlation between radiographic severity of knee osteoarthritis and future disease progression The research evaluates the impact of glucosamine sulfate on slowing the progression of osteoarthritis, providing valuable insights into disease management and potential treatment strategies.
18 Pavelka, K., Gatternova, J., Olejarova, M., Machacek, S., Giacovelli, G., and Rovati, L.C., Glucosamine sulfate use and delay of progression of knee osteoarthritis: a 3- year, randomized, placebo-controlled, double-blind study Arch Intern Med., 162,
19 Houpt, J.B., McMillan, R., Wein, C., and Paget-Dellio, S.D., Effect of glucosamine hydrochloride in the treatment of pain of osteoarthritis of the knee J Rheumatol.,
20 Reginster, J.Y., Bruyere, O., Lecart, M.P., and Henrotin, Y., Naturocetic (glucosamine and chondroitin sulfate) compounds as structure-modifying drugs in the treatment of osteoarthritis Curr Opin Rheumatol., 15, 651, 2003.
21 Drovanti, A., Bignamini, A.A., and Rovati, A.L., Therapeutic activity of oral glu- cosamine sulfate in osteoarthritis: a placebo-controlled double-blind investigation.
22 Phoon, S and Manolios, N., Glucosamine A neutraceutical in osteoarthritis Aust.
23 Noack, W., Fischer, M., Forster, K.K., Rovati, L.C., and Setnikar, I., Glucosamine sulfate in osteoarthritis of the knee Osteoarthritis Cartilage, 2, 51, 1994.
24 da Camara, C.C and Dowless, G.V., Glucosamine sulfate for osteoarthritis Ann.
25 Pipitone, V.R., Chondroprotection with chondroitin sulfate Drugs Exp Clin Res.,
26 Bourgeois, P., Chales, G., Dehais, J., Delcambre, B., Kuntz, J.L., and Rozenberg, S., Efficacy and tolerability of chondroitin sulfate 1,200 mg/day vs chondrotin sulfate
3 × 400 mg/day vs placebo Osteoarthritis Cartilage, 6 (Suppl A), 25, 1998.
27 Leeb, B.F., Schweitzer, H., Montag, K., and Smolen, J.S., A meta-analysis of chon- droitin sulfate in the treatment of osteoarthritis J Rheumatol., 27, 205, 2000.
28 Ronca, F., Palmieri, L., Panicucci, P., and Ronca, G., Anti-inflammatory activity of chondroitin sulfate Osteoarthritis Cartilage, 6 (Suppl A), 14, 1998.
29 Conte, A., Volpi, N., Palmieri, L., Bahous, I., and Ronca, G., Biochemical and pharmacokinetic aspects of oral treatment with chondroitin sulfate Arzneimittelfor- schung, 45, 918, 1995.
30 Volpi, N., Oral bioavailability of chondroitin sulfate (Chondrosulf) and its constituents in healthy male volunteers Osteoarthritis Cartilage, 10, 768, 2000.
31 Baici, A., Horler, D., Moser, B., Hofer, H.O., Fehr, K., and Wagenhauser, F.J., Analysis of glycosaminoglycans in human serum after oral administration of chondroitin sulfate Rheumatol Int., 12, 81, 1992.
32 Uebelhart, D., Thonar, E.J., Delmas, P.D., Chantraine, A., and Vignon, E., Effects of oral chondroitin sulfate on the progression of knee osteoarthritis: a pilot study.
33 Das, A and Hammad, T.A., Efficacy of a combination of FCHG49 glucosamine hydrochloride, TRH122 low molecular weight sodium chondroitin sulfate and man- ganese ascorbate in the management of knee osteoarthritis Osteoarthritis Cartilage, 8(5), 343, 2000
In a randomized double-blind, placebo-controlled pilot study, Leffler et al (Year) investigated the effectiveness of glucosamine, chondroitin, and manganese ascorbate in managing degenerative joint disease of the knee and low back pain The study highlights the potential benefits of these supplements for joint health, emphasizing their role in alleviating symptoms associated with osteoarthritis This research supports their use as a non-invasive treatment option for individuals suffering from degenerative joint conditions.
35 Priebe, D., McDiarmid, T., Mackler, L., and Tudiver, F., Do glucosamine or chon- droitin cause regeneration of cartilage in osteoarthritis? J Fam Pract., 52, 237, 2003.
36 Cohen, M., Wolfe, R., Mai, T., and Lewis, D., A randomized, double blind, placebo controlled trial of a topical cream containing glucosamine sulfate, chondroitin sulfate, and camphor for osteoarthritis of the knee J Rheumatol., 30, 523, 2003.
37 de los Reyes, G.C., Koda, R.T., and Lien, E.J., Glucosamine and chondroitin sulfates in the treatment of osteoarthritis: a survey Prog Drug Res., 55, 81, 2000.
38 McAlindon, T.E., LaValley, M.P., Gulin, J.P., and Felson, D.T., Glucosamine and chondroitin for treatment of osteoarthritis: a systematic quality assessment and meta- analysis JAMA, 283, 1469, 2000.
39 Deal, C.L and Moskowitz, R.W., Nutraceuticals as therapeutic agents in osteoarthri- tis The role of glucosamine, chondroitin sulfate and collagen hydrolysate Rheum.
40 Walker-Bone, K., ‘Natural remedies’ in the treatment of osteoarthritis Drugs Aging,
41 McAlindon, T., Glucosamine and chondroitin for osteoarthritis? Bull Rheum Dis.,
42 Towheed, T.E., Published meta-analyses of pharmacological therapies for osteo- arthritis Osteoarthritis Cartilage, 10, 836, 2002.
43 McClain, D.A., Hexaosamines as mediators of nutrient sensing and regulation in diabetes J Diabetes Complications, 16, 72, 2002.
44 Clegg, D.O., Reda, D.J., Harris, C.L., Klein, M.A., O’Dell, J.R., Hooper, M.M., et. al., Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis N Engl J Med., 354, 795, 2006.
45 Hochberg, M.C., Nutritional supplements for knee osteoarthritis: still no resolution.
46 Ernst, E., Vassiliou, V.S., and Pelletier, J.P., Glucosamine and chondroitin sulfate for knee osteoarthritis: correspondence N Engl J Med., 354, 2184, 2006.
47 McClain, D.A and Crook, E.D., Hexosamines and insulin resistance Diabetes, 45,
48 Adebeowale, A., Cox, D.S., Liang, Z., and Eddington, N.D., Analysis of glucosamine and chondroitin sulfate content in marketed products and the Caco-2 permeability of chondroitin sulfate raw materials J Am Nutraceut Assoc., 3, 37, 2000.
49 Volpi, N., Inhibition of human leukocyte elastase activity by chondroitin sulfates.
50 Hungerford, D., Navarro, R., and Hammad, T., Use of nutraceuticals in the manage- ment of osteoarthritis J Am Nutraceut Assoc., 3, 23, 2000.
51 Huang, S.H., Johnson, K., and Pipe, A.L The use of dietary supplements and med- ications by Canadian athletes at the Atlanta and Sydney Olympic Games Clin J.
52 Garsline, R.T and Kaeding, C.C The use of NSAIDs and nutritional supplements in athletes with osteoarthritis: prevalence, benefits and consequences Clin Sports Med.,
53 Morelli, V., Naquin, C., and Weaver, V., Alternative therapies for traditional disease states: osteoarthritis Am Fam Physician, 67, 339, 2003.
54 Deal, C.L., Osteoporosis: prevention, diagnosis, and management Am J Med., 102, 35S, 1997.
55 Long, L and Ernst, E., Homeopathic remedies for the treatment of osteoarthritis: a systematic review Br Homeopath J., 90, 37, 2001.
56 Bischoff, H.A and Roos, E.M Effectiveness and safety of strengthening, aerobic, and coordination exercises for patients with osteoarthritis Curr Opin Rheumatol.,
57 Bucci, L., Pain Free: The Definitive Guide to Healing Arthritis, Low-Back Pain and
Sports Injuries through Nutrition and Supplements Summit Group, Fort Worth, TX,
58 O’Rourke, M., Determining the efficacy of glucosamine and chondroitin for osteo- arthritis Nurse Pract., 26, 44, 2001.
Sara Chelland Campbell and Robert J Moffatt
11.2 The Role of Carnitine in Fat Metabolism 204
11.2.2 Carnitine Pools: Distribution and Excretion 204
11.4.1 Does Carnitine Supplementation Make Sense? 207
11.4.2 When Would Carnitine Supplementation Be Effective? 207
11.5.1 Dietary Supplementation and Body Carnitine Levels 207
11.5.2 Carnitine Levels and Acute Exercise 208
11.5.3 Carnitine and High-Intensity Exercise 209
11.5.4 Influence of Chronic Exercise Training on Carnitine Status 211
11.5.5 Summary of Carnitine and Training Effects 212
Carnitine, derived from the Latin words "carno" or "carnis" meaning flesh or meat, was first discovered in muscle extracts in 1905 by Gulewitsch and Krimberg, as well as Kutscher, who initially believed it played a role in muscle function They identified its chemical structure as 3-hydroxy-4-N-trimethyl-aminobutyric acid (C7H15NO3), a finding later confirmed in 1927 by Tomita and Sendju This discovery marked the beginning of understanding carnitine's biological significance and structural configuration.
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The concept of 202 Sports Nutrition: Fats and Proteins was introduced in 1962 and was definitively characterized in 1997 as L- or R-3-hydroxy-4-N,N,N-trimethylaminobutyrate Initially, carnitine was known as vitamin BT due to its essential role in the growth of the yellow mealworm, Tenebrio molitor Over time, the widespread presence of carnitine in the organs of mammals, lower animals, plants, and microorganisms was thoroughly established.
Carnitine plays a crucial role in the transport of long-chain fatty acids into mitochondria, enabling their β-oxidation and ATP production in skeletal muscle It functions as a cofactor for enzymes such as carnitine translocase and acylcarnitine transferases I and II, which facilitate the movement of activated fatty acids across mitochondrial membranes This process involves the esterification of fatty acids to acylcarnitines by carnitine acyltransferase I (CAT I), their translocation into mitochondria via carnitine translocase, and reconversion to acyl-CoA by CAT II for energy generation through β-oxidation, Krebs cycle, and electron transport chain Additionally, carnitine is involved in maintaining membrane integrity, regulating mitochondrial coenzyme A:acetyl-CoA ratios, and reducing lactate production, highlighting its essential roles beyond fatty acid transport.
Carnitine plays a crucial role in mitochondrial function by regulating the acyl-CoA:free CoA ratio through its unique interaction with acyl-CoA When acyl-CoAs are produced at a faster rate than they are used, the intramitochondrial acyl-CoA levels increase, disrupting the balance, but carnitine can bind to excess acyl-CoAs to restore normal ratios This regulation helps optimize energy production, especially during high-intensity exercise, by inhibiting the downregulation of pyruvate dehydrogenase (PDH) caused by elevated acetyl-CoA levels, thereby reducing lactic acid buildup.
L-carnitine is the biologically active form naturally produced in the human body, while D-carnitine is a synthetic form that is not physiologically active Research indicates that supplementing with D-carnitine can deplete the body's endogenous L-carnitine stores, potentially leading to a deficiency, particularly during intense exercise Therefore, D-carnitine supplementation is not recommended, as it may negatively impact both health and athletic performance.
Carnitine plays a crucial role in substrate metabolism in healthy individuals, with the typical American diet providing about 100 to 300 mg daily, primarily from red meat and dairy, while vegetables contain minimal L-carnitine Despite adequate intake for most, some individuals experience carnitine deficiencies due to metabolic abnormalities like defective synthesis, increased degradation, impaired transport, or abnormal renal handling These disturbances can lead to primary carnitine deficiency, which manifests as muscle fatigue, cramps, hypotonia, and muscle atrophy in its myopathic form, and more severe symptoms such as nausea, vomiting, and coma resulting from excessive fat storage due to reduced hepatic function in its systemic form.
FIGURE 11.2 Roles of carnitine in the movement of long chain fatty acids into the mito- chondrial matrix.
ATP + CoA Fatty acyl-CoA Acyl-CoA synthase
Fatty acyl-CoA Mitochondrial matrix
204 Sports Nutrition: Fats and Proteins
Carnitine supplementation has proven effective in various health states, particularly in cardiac diseases where the myocardium relies on fatty acids as its primary fuel source A deficiency in carnitine can significantly impair heart rate, stroke volume, and overall cardiac output Research consistently supports the use of carnitine supplements in cardiac patients, demonstrating normalization of abnormal fatty acid metabolism This chapter focuses on the effects and efficacy of carnitine supplementation in healthy populations, specifically as a potential ergogenic aid to enhance athletic performance.
11.2 THE ROLE OF CARNITINE IN FAT METABOLISM