Glucosamine Hydrochloride
Glucosamine has relieved the symptoms of osteoarthritis more than any other one nutrient. Glucosamine is manufactured by the body and is primarily to help form the cushioning components of joint fluids and surrounding tissues. It thickens synovial fluid, making it more elastic; repairs the cartilage in damaged arthritic joints; and creates more support for joints, including the vertebrae. Besides helping to form the cartilage, tendons, ligaments, and synovial fluid in the joint, it also plays a role in the formation of nails, skin, eyes, bones, and heart valves. And, finally, it's involved in the mucous secretions of the digestive, respiratory, and urinary tracts.
As we age, we lose the ability to manufacture glucosamine, which results in degeneration of the structures within the joints. Since we don't get a significant amount in our diets, we need to supplement with some form of glucosamine. Available sources of glucosamine are derived from chitin, the exoskeleton of shrimp, lobsters, and crabs. Presently, it's commercially sold in three forms:
- glucosamine sulphate (GS)
- N-acetyl-glucosamine (NAG)
- glucosamine hydrochloride (GHCL)
The N-acetyl-glucosamine has been found to be not as effective in treating joint conditions, and actually very little, if any, ends up in the joints. After reading the research comparing glucosamine sulphate to the glucosamine hydrochloride, Dr. Cochran started recommending the hydrochloride form because it's found to be just as effective, and it's less expensive.
There will be many health care providers who claim that the sulphate form of glucosamine is more effective than the hydrochloride form, but the information found by Dr. Cochran is convincing. First of all, most of the studies done from 1980 to 1994 were with the sulphate form because it was made available by the Italian pharmaceutical company, which had a proprietary position or patent on the sulphate. So, it was to their advantage to make the sulphate form available for clinical studies. However, in studies performed as early as 1971, comparing the effects of glucosamine sulphate, glucosamine iodide, and glucosamine hydrochloride, it was found that glucosamine hydrochloride had the strongest effect.
The reason for its stronger effect is that it's much more pure. Actually, glucosamine sulphate is made from glucosamine hydrochloride by adding either sodium or potassium sulphate. Adding these additional compounds increases the cost by another 50%. All of the glucosamine sulphate imported into the United States is only 80% pure, with the remaining 20% being sodium or potassium chloride. This is done because the glucosamine sulphate is very unstable and tends to decompose, turn brown and lose its effectiveness. Glucosamine hydrochloride, on the other hand, is very stable and is 99 % pure. In this unmixed form, it delivers 83 % of the glucosamine to the joints. Glucosamine sulphate mixed with other salts distributes only 62 percent of the glucosamine to the joints. Put another way, you would have to take 1995 milligrams of glucosamine sulphate to equal the effects of 1500 milligrams of glucosamine hydrochloride! This decreases your cost even further.
You may also hear that the sulphur in the glucosamine sulphate is necessary for the construction of the cartilage matrix. The original researchers of glucosamine sulphate found, however, that the results obtained in treating osteoarthritis were due to the glucosamine and not to the sulphate. They discovered that the sulphate, chloride, and iodide salts are passed from the body as waste. And the sulphur used to construct these joint structures actually comes from existing proteins present in the cartilage. Sulphur is, however, critical in reconstructing connective and joint tissue and can be increased by consuming more sulphur-containing foods including garlic, onions, eggs, and asparagus, or by taking a supplement like MSM.
Another interesting point to consider is what really happens during the digestion of glucosamine sulphate. Your stomach contains hydrochloric acid, which is necessary for the digestion of food. When the glucosamine sulphate enters the stomach, the sulphate portion is split off and the hydrochloride is attached to the glucosamine, creating glucosamine hydrochloride! The sulphate molecule is essentially lost due to its very low concentrations, compared to the large amount of hydrochloric acid present in your stomach. If your body is going to turn it into glucosamine hydrochloride, why not take it in that form in the first place and eliminate all the unnecessary salt that you probably don't need anyway.
Glucosamine sulphate use and delay of progression of knee osteoarthritis: a 3-year, randomised, placebo-controlled, double blind study.
Pavelka K, Gatterova J, Olejarova M, Machacek S, Giacovelli G, Rovati LC.
Department of Medicine and Rheumatology, Charles University, Prague, Czech Republic.
BACKGROUND: Conventional symptomatic treatments for osteoarthritis do not favorably affect disease progression. The aim of this randomised, placebo-controlled trial was to determine whether long-term (3-year) treatment with glucosamine sulphate could modify the progression of joint structure and symptom changes in knee osteoarthritis, as previously suggested. METHODS: Two hundred two patients with knee osteoarthritis (using American College of Rheumatology criteria) were randomised to receive oral glucosamine sulphate, 1500 mg once a day, or placebo. Changes in radiographic minimum joint space width were measured in the medial compartment of the tibiofemoral joint, and symptoms were assessed using the algo-functional indexes of Lequesne and WOMAC (Western Ontario and McMaster Universities). RESULTS: Osteoarthritis was of mild to moderate severity at enrolment, with average joint space widths of slightly less than 4 mm and a Lequesne index score of less than 9 points. Progressive joint space narrowing with placebo use was -0.19 mm (95% confidence interval, -0.29 to -0.09 mm) after 3 years. Conversely, there was no average change with glucosamine sulphate use (0.04 mm; 95% confidence interval, -0.06 to 0.14 mm), with a significant difference between groups (P =.001). Fewer patients treated with glucosamine sulphate experienced predefined severe narrowings (>0.5 mm): 5% vs 14% (P =.05). Symptoms improved modestly with placebo use but as much as 20% to 25% with glucosamine sulphate use, with significant final differences on the Lequesne index and the WOMAC total index and pain, function, and stiffness sub scales. Safety was good and without differences between groups. CONCLUSION: Long-term treatment with glucosamine sulphate retarded the progression of knee osteoarthritis, possibly determining disease modification.
Glucosamine and chondroitin sulphate's in the treatment of osteoarthritis: a survey
de los Reyes GC, Koda RT, Lien EJ.
Department of Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90089, USA.
For more than 30 years, non-steroidal anti-inflammatory drugs (NSAIDs) have been used as standards in the treatment of osteoarthritis (OA). Serious and often life-threatening adverse effects due to these agents are common. Clinical findings have revealed that glucosamine sulphate and chondroitin sulphate are effective and safer alternatives to alleviate symptoms of OA. Experimental evidence indicates that these compounds and their low molecular weight derivatives have a particular tropism for cartilage where they serve as substrates in the bio synthesis of component building blocks. This paper is a literature review of the chemistry, mechanism of action, pharmacokinetics, clinical efficacy and safety of these two nutraceuticals.
A randomised, double blind, placebo controlled trial of a topical cream containing glucosamine sulphate, chondroitin sulphate, and camphor for osteoarthritis of the knee.
Cohen M, Wolfe R, Mai T, Lewis D.
Department of Complementary Medicine, Faculty of Life Sciences, RMIT University, Bundoora, Australia.
OBJECTIVE: To assess the ability of a topical preparation of glucosamine sulphate and chondroitin sulphate to reduce pain related to osteoarthritis (OA) of the knee. METHODS: Sixty-three patients were randomised to receive either a topical glucosamine and chondroitin preparation or placebo to be used as required over an 8-week period. Efficacy was assessed using a visual analogue scale (VAS) for pain as well as the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the SF-36 questionnaire. RESULTS: VAS scores indicated a greater mean reduction in pain for the glucosamine/chondroitin preparation group (mean change -3.4 cm, SD 2.6 cm) compared to the placebo group (mean change -1.6 cm, SD 2.7 cm) after 8 weeks. After 4 weeks the difference between active and placebo groups in their mean reduction from baseline was 1.2 (95% CI 0.1 to 2.4, p = 0.03) and after 8 weeks was 1.8 (95% CI for difference between groups, 0.6 to 2.9 cm; p = 0.002). CONCLUSION: Topical application of glucosamine and chondroitin sulphate is effective in relieving the pain from OA of the knee and improvement is evident within 4 weeks.
Intermittent treatment of knee osteoarthritis with oral chondroitin sulphate: a one-year, randomised, double blind, multi center study versus placebo.
Uebelhart D, Malaise M, Marcolongo R, DeVathaire F, Piperno M, Mailleux E, Fioravanti A, Matoso L, Vignon E.
Department of Rheumatology, Institute of Physical Medicine, University Hospital Zurich, Switzerland.
OBJECTIVE: To investigate the efficacy and tolerability of a 3-month duration, twice a-year, intermittent treatment with oral chondroitin sulphate (CS) in knee osteoarthritis (OA) patients. DESIGN: A total of 120 patients with symptomatic knee OA were randomised into two groups receiving either 800 mg CS or placebo (PBO) per day for two periods of 3 months during 1 year. Primary efficacy outcome was Lequesne's algo-functional index (AFI); secondary outcome parameters included VAS, walking time, global judgment, and paracetamol consumption. Radiological progression was assessed by automatic measurement of medial femoro-tibial joint space width on weight-bearing X-rays of both knees. Clinical and biological tolerability was assessed. RESULTS: One hundred and ten of 120 patients were included in the ITT analysis. AFI decreased significantly by 36% in the CS group after 1 year as compared to 23% in the PBO group. Similar results were found for the secondary outcomes parameters. Radiological progression at month 12 showed significantly decreased joint space width in the PBO group with no change in the CS group. Tolerability was good with only minor adverse events identically observed in both groups. CONCLUSION: This study provides evidences that oral CS decreased pain and improved knee function. The 3-month intermittent administration of 800 mg/day of oral CS twice a year does support the prolonged effect known with symptom-modifying agents for OA. The inhibitory effect of CS on the radiological progression of the medial femoro-tibial joint space narrowing could suggest further evidence of its structure-modifying properties in knee OA.
San Diego Clinic Immunological Center Clinical Study On Cetyl Myristoleate (CMO) vs Arthritis
A Study on Dose Effectiveness and Patient Response conducted by the San Diego Immunological Center
The Purpose:Having previously established the effectiveness and non toxicity of CMO tm (cerasomal-cis-9-cetylmyristoleate) for arthritis symptoms of pain, inflammation, and impaired mobility, the purpose of the study was:
- To determine optimum dosage levels for various types of arthritis,
- To determine if different dosage levels would be required relative to the severity of each type of arthritis,
- To observe response time required for initial and partial relief of symptoms,
- To observe response time required for complete relief of symptoms, and
- To determine factors influencing subjects who may not respond to the protocol.
The Subjects Subjects were volunteers treated as outpatients. They presented with osteoarthritis, rheumatoid arthritis and other forms of reactive arthritis.
The Study The study involved 48 subjects. Female subjects (28) ranged from 33 to 83 years of age. Male subjects (20) ranged from 29 to 74 years of age. All races and many ethnic backgrounds were represented. Age, gender, race, and ethnological background appeared to be irrelevant to patient response in this study.
The Protocol CMO(tm) was administered orally in the form of 75 mg capsules each morning and evening. The number of capsules and duration of treatment varied for each group of subjects. Subjects were advised to take capsules on an empty stomach with water only; and to avoid tea, chocolate, alcohol, coffee, cola, and other caffeinated drinks for five hours after taking the capsules. Subjects were advised to completely avoid chocolate and alcohol during the entire trial period of two to three weeks duration. With a few exceptions for subjects who could not function without them, steroids were also prohibited. Otherwise diet was not controlled in any way. Subjects were permitted to continue taking their customary pain and non-steroidal anti-inflammatory medications until they were no longer needed. Subjects were asked to visit or call in to report progress at least twice weekly.
The Results Only two subjects failed to show marked or complete relief of all symptoms of pain and limited mobility normally associated with arthritis. Both of these non-responding subjects had suffered prior hepatic problems: one from alcohol abuse resulting in cirrhoses of the liver; the other, a former professional athlete, presented with considerable liver damage from steroid abuse. Further studies are necessary to determine the role of liver function capacity with respect to this protocol. Liver damage resulting from steroids previously prescribed for arthritis may also prove to be a factor affecting patient response.
Group #1 Mild to moderately severe osteoarthritis and reactive psoriatic arthritis. In Group #1, eleven (11) subjects presented with mild to moderately severe osteoarthritis and one with reactive psoriatic arthritis were supplied with 16 capsules, two 75mg capsules to be taken each morning and evening for four days. Nine reported about 20% to 30% improvement in articulation and inflammation and about 40% to 50% relief of arthritic pain within 36 hours. In these nine subjects, improvement continued rapidly for the next 60 hours, reaching a 70% to 80% improvement by the end of the four days. Two of the subjects continued to improve over the following week despite the fact they were no longer taking any capsules. However about half of this group experienced the return of some mild arthritic symptoms after about three to five weeks. (Although not included as part of this study, all the subjects in this group were treated again and their symptoms have not returned.) The patient with reactive psoriatic arthritis also experienced an almost complete reversal of his associated very severe psoriatic skin condition affecting about 20% of his total skin area.
Group #2 Severe to crippling rheumatoid arthritis, in Group #2, nine (9) subjects presenting with severe to crippling rheumatoid arthritis were supplied with 50 capsules to be taken in two series, two 75mg capsules each morning and evening for seven days, with a seven day interval before repeating the same dosage for 5 1/2 more days. Four of these subjects were unable to walk and were accustomed to being transported by wheelchairs. One, her femur being fused at the hip, was unable to achieve a sitting position for wheelchair transport. She could, however, move about slowly on crutches as long as she was accompanied by someone to aid her in maintaining her balance. Otherwise she could only stand or lie down. The remaining four could move about with canes or walkers. All nine subjects presented with pain, inflammation, and marked deformation of nearly all proximal interphalangeal and large joints. Five presented with limited lumbar flexion and pain in the vertebral column. All had difficulty grasping and manipulating common objects.
On the fourteenth day, at the end of the one week interval without treatment, six(6) subjects reported minor continuing improvement; two reported maintaining their improved status and one continued to show no improvement. Treatment was resume on the fifteenth day for 5 1/2 more days. By the end of the treatment period, all but two subjects reported to be 90% free of pain with a return of 70% to 100% mobility. The fused hip joint remained fused, of course, but with a return of over 70% mobility in other joints, the subject felt hip surgery now to be worth consideration. The non-responsive subject proved to have cirrhoses of the liver, which may have been the reason for her inability to respond to treatment. Further investigation is necessary to determine the role of liver function in this protocol.
Group #3 Mild to moderately severe rheumatoid arthritis In Group #3, fourteen (14) subjects presenting with mild to moderately severe rheumatoid arthritis were supplied with 24 capsules, two 75 mg capsules to be taken each morning and evening for 6 days. After three days of treatment, eleven reported about 20% to 30% improvement in articulation and inflammation, and about 40% to 50% relief of arthritic pain. In these eleven subjects, improvement continued rapidly over the next four days, approaching the 80% to 100% level. The remaining three subjects reported similar improvement by the end of the fourth day, with an overall improvement of 70% to 80% after seven days.
Most of the subjects continued to report minor additional improvement for one week or more, even though they were no longer under treatment. However, six in this group began to experience the return of some mild arthritic symptoms after about three to four weeks. (Although not included as part of this study, all subjects in this group were treated again and their level of improvement has subsequently stabilized.)
Group #4 Severe to crippling osteoarthritis In Group #4, fourteen (14) subjects presenting with severe to crippling osteoarthritis were supplied with 50 capsules to be taken in two series, two 75 mg capsules each morning and evening for seven days, with a seven day interval before repeating the same dosage for 5 1/2 more days. Three of these subjects were unable to walk and were accustomed to being transported by wheelchairs. The other eleven could move with crutches, walkers and canes. All presented with pain, inflammation and marked deformation of nearly all interphalangeal and large joints. Four presented with limited lumbar flexion and pain in the vertebral column. Ten had difficulty grasping and manipulating common objects.
After four days of treatment, ten in this group reported 30% to 50% improvement in articulation and inflammation and about 40% to 60% relief of arthritic pain. In these ten subjects, improvement continued rapidly over the next three days, reaching 80% to 100% by the end of seven days. One reported no perceptible change.
On the fourteenth day, at the end of the one week interval with out treatment, nine subjects reported continuing minor improvement, four reported maintaining their improved status and one continued to show no improvement. Treatment was resumed on the fifteenth day for 5 1/2 more days.
By the end of the treatment period, eleven subjects reported 80% to 100% relief of pain with a return of 80% to 100% mobility. Two subjects reported a 70% to 80% of articular mobility with a 70% to 90% reduction of arthritic pain. The one non-responsive subject proven to have previous liver damage as a result of sports related steroid abuse. Further studies are necessary to determine the role of liver function in this protocol.
Summary The results of this study lead to several conclusions regarding its five principal objectives:
- Optimum dosage levels appear to be equal for all three types of arthritis investigated: osteoarthritis, rheumatoid arthritis and reactive psoriatic arthritis. This is evidenced by the gradual return of minor arthritis symptoms in several of those treated with only 16 to 24 capsules, and no regression in those treated with 50 capsules in two series separated by one week without treatment.
- Dosage level requirements appear to be equal irrespective of the severity of the subject's condition.
- Initial response time for minor improvement appears to vary from two to seven days, irrespective of the severity of the subject's condition.
- The time for maximum attainable response appears to vary from seven to twenty one days, resulting in 70% to 100% overall improvement. (Apart from this study, three of the most severely afflicted subjects were treated again after a five week interval, resulting in an additional 10% to 20% overall improvement).
- The two non-responding subjects both proved to have suffered previous damage to the liver from steroid or alcohol abuse, indicating that impaired liver function may preclude success with this protocol.
In addition, it was evident that for many subjects, the relief of inflammation resulted in marked improvement in joint deformation.