Glucosamine

There really are different forms, grades, and quality (purity) levels 

of what otherwise appears to be exactly the same ingredients… often with the same ‘first name.’

‘Calcium’ is probably one of the most common, and actually discussed examples found in nutritional supplements, but ‘glucosamine’ should be high on the list for anyone using joint supplements, because the differences are significant and important.

THERE IS NO SUCH THING AS JUST ‘GLUCOSAMINE!’

It’s akin to thinking all “Terry’s” are the same

all ‘trees,’ “bass,” or “cars” do the same thing, or that all petroleum products are the same.

There really are, scientifically different types of ‘glucosamine,’ with very different purposes, uses, absorption levels, and even different requirements for them to be actually used somewhere within a body. For example: the most commonly used type of glucosamine (HCl) used in supplements has been proven to scientifically NOT get to the joint tissues. It’s been proven to NOT have any significant impact on arthritis, joint injuries, or really any health of the joint areas. Yet, ‘glucosamine HCl’ continues to be the most commonly found form used in joint supplements on store shelves. That’s sad, really.

The reality is that the different types of glucosamine are very different, and how they function is absolutely different, what they do (and don’t do) in a body IS DIFFERENT!

Any company not clearly listing the TYPE of glucosamine their product contains, or those using the wrong type(s) in their ‘joint’ products, should be a sign that THAT COMPANY doesn’t really know much about nutrition!
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The easiest analogy I can come up with is petroleum.

Everyone understands that there are different types of petroleum products, from those ‘plastic’ fuel cans, to motor oil, to diesel, to kerosene, to regular or unleaded, with and without ethanol, and even super high octane gasoline, to actual jet fuel. All are petroleum based, but each has a particular use… certain benefits, when used for the right thing. Each can cause problems when used in the wrong way. Some might be impossible, damaging, or even dangerous when used wrongly. That plastic gas can isn’t going to get you very far if it’s empty when you’re out of gas, even though it’s made from petroleum. And putting jet fuel in the average car will make it sing for a time, until the heads burn up, block warps, or exhaust has major damage issues.
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Different types of ‘glucosamine’ have a different purpose, different requirements. Even when they have a similar purpose (like fuel), there are very different ‘heat’ (efficiency levels… as well as where and how it can really be actually used). The type is vital to purpose & goals.

The same is true for most all nutrients. The manner in which nutrients are created, combined, manufactured, delivered to the body, and used within the body are all different. 

    These are all things that help determine the ‘bio-availability’ (absorption), function, effectiveness, actual levels, and safety of each given ingredient.

    For instance, Glucosamine is available in
    1. Glucosamine HCL (though the ‘L’ is usually represented as a ‘lower case,’ which often has it confused with the letter ‘i’),
    2. N-ACETYL-Glucosamine,
    3. N-ACETYL-D-Glucosamine,
    4. Glucosamine Sulfate NACL form (same ‘i’ issue), and
    5. Glucosamine Sulfate 2KCL forms (same ‘i’ confusion).
    ~ the last of which is the higher absorption, function, and usability in a mammal’s joint tissues.

    In addition, the vast majority of the clinical research studies done over the last 50 years, saying ‘glucosamine actually works’ used Glucosamine SULFATE, and NOT the Glucosamine HCL counterpart that populates retail shelves (over 20 to 1).

    One of our very first products was liquid (the Complete Formula), and with a biochemist and bunch of professionals developing the formulas in the early and mid 90’s. If getting ‘glucosamine’ stabilized in liquid was possible we would have done it years ago! But, the doctor’s that formulated the products for MD’s Choice quickly learned that it wasn’t. Third party researchers around the world have known it’s not possible to stabilize glucosamine in liquid for over 40 years, yet there are companies out there – right now today – that sadly continue claiming their ‘liquid joint supplement’ works in hours or just a few days. One all over facebook proudly claims ‘just 3 drops a day… in less than 7 days.’ Sadly, if anything is ‘noticed’ with any of those ‘quick fix’ products, it’s not the glucosamine or any honest structural changes, that is reality. 

    That company, in particular, but most with ‘quick results’ hype is contrary to science, and ignores reality. Glucosamine HCl has a 24hr life expectancy in liquid, Glucosamine Sulphate (NACl or 2KCl) has 6 months, at best… which starts the moment it hits the liquid, and often before it touches any store shelf (much less actually used).
    N-acetyl-glucosamine (as well as N-acetyl-D-glucosamine) have zero active uptake by joint tissue, although you’ll see it in some of our competitors product (apparently because it contains the word ‘glucosamine’ – as there sure isn’t any real scientific reason). But, there are people that blindly believe all that ‘liquid joint supplement’ and ‘quick fix’ marketing hype. Real science proves it’s false, regardless of those claims. Anything ‘felt’ by those products is because of herbal pain killers or symptom blockers, not any actual healing, structural changes, or real health benefits.

    Furthermore, there are some major differences within the same compound. Yes, it can get very complicated. Which is why the professionals at MD’s Choice designed formulas that actively use the best forms, with specific ratios, with the optimum combinations of ‘contributing nutrients’ to create the most bio-available products. This ensures the maximum amount of key nutrients were safely made available to the body, to actively help the body either solve specific problems, or maintain optimum health.

No magic… just real science!

There are thousands of studies regarding all types of ‘glucosamine’ – these are just a few, spanning nearly 40 years, hundreds done by unbiased independent third parties from around the world, involving thousands of bodies, and often double blind placebo studies.

The science is real, and there were reasons the NIH, and those involved with the GAIT study completely avoided the Glucosamine Sulphate’s… particularly the 2KCl form which has decades of major positives, proven results, and real tests.
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Glucosamine Sulphate Study Results:
Curr Med Res Opin. 1980;7(2):110-14.
Double-blind clinical evaluation of oral glucosamine sulphate in the basic treatment of osteoarthrosis.
Pujalte JM, Llavore EP, Ylescupidez FR.
“The use of glucosamine sulphate also resulted in a significantly larger proportion of patients who experienced lessening or disappearance of symptoms within the trial period. No adverse reactions were reported by the patients treated with glucosamine, and no variation in laboratory tests was recorded.”
PMID: 7002479 DOI: 10.1185/03007998009112036
[Indexed for MEDLINE]
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Pharmatherapeutica. 1982;3(3):157-68.
Oral glucosamine sulphate in the management of arthrosis: report on a multi-centre open investigation in Portugal.
Tapadinhas MJ, Rivera IC, Bignamini AA.
“The improvement obtained lasted for a period of 6 to 12 weeks after the end of treatment. Objective therapeutic efficacy was rated by the doctors as ‘good’ in 59% of patients, and ‘sufficient’ in a further 36%. These results were significantly better than those obtained with previous treatments … Oral glucosamine was fully tolerated by 86% of patients, a significantly larger proportion than that reported with other previous treatments”
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Arzneimittelforschung. 1991 Feb;41(2):157-61.
Antireactive properties of glucosamine sulfate.
Setnikar I1, Cereda R, Pacini MA, Revel L.
The pharmacological therapeutic index of glucosamine with regard to the antiinflammatory activities seems therefore comparable or superior to that of the known non-steroidal anti-inflammatories.
PMID: 1645969
[Indexed for MEDLINE]
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Arzneimittelforschung. 1991 May;41(5):542-5.
Antiarthritic effects of glucosamine sulfate studied in animal models.
Setnikar I1, Pacini MA, Revel L.
the therapeutic margin with regard to prolonged treatments of inflammatory disorders results 10-30 times more favourable for GS than for indometacin. GS can therefore be considered as a drug of choice for prolonged oral treatment of rheumatic disorders.
PMID: 1898426
[Indexed for MEDLINE]
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Osteoarthritis Cartilage. 1994 Mar;2(1):51-9.
Glucosamine sulfate in osteoarthritis of the knee.
Noack W1, Fischer M, Förster KK, Rovati LC, Setnikar I.
The aim of this study was to define the activity and safety of glucosamine sulfate on the symptoms of patients with OA, using a multicenter, randomized, placebo-controlled, double-blind, parallel-group study design. It is concluded that glucosamine sulfate may be a safe and effective symptomatic Slow Acting Drug for OA.
PMID: 11548224
[Indexed for MEDLINE]
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Arthritis Rheum. 2007 Feb;56(2):555-67.
Glucosamine sulfate in the treatment of knee osteoarthritis symptoms: a randomized, double-blind, placebo-controlled study using acetaminophen as a side comparator.
Herrero-Beaumont G1, Ivorra JA, Del Carmen Trabado M, Blanco FJ, Benito P, Martín-Mola E, Paulino J, Marenco JL, Porto A, Laffon A, Araújo D, Figueroa M, Branco J.
OBJECTIVE: To assess the effects of the prescription formulation of glucosamine sulfate (1,500 mg administered once daily) on the symptoms of knee osteoarthritis (OA) during a 6-month treatment course.
CONCLUSION: -The findings of this study indicate that glucosamine sulfate at the oral once-daily dosage of 1,500 mg is more effective than placebo in treating knee OA symptoms. Although acetaminophen also had a higher responder rate compared with placebo, it failed to show significant effects on the algofunctional indexes.
TRIAL REGISTRATION: ClinicalTrials.gov NCT00110474.
PMID: 17265490 DOI: 10.1002/art.22371
[Indexed for MEDLINE]
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Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2008 Jan;33(1):47-52.
[Effect of various intervention factors on MMP-3 and TIMP-1 level in synovial fluid in knee joints with osteroarthritis].

[Article in Chinese] Xu HT1, Chen Y, Chen LK, Li JY, Zhang W, Wu B.
OBJECTIVE: – To examine the expression of MMP-3 and TIMP-1 in the synovial fluid in knee joints with osteoarthritis before and after being treated with hyaluronic acid(HA), glucosamine sulfate(GS) and arthroscopic de bridment(AD), and to explore the therapeutic mechanism.
CONCLUSION: – (1) HA, GS and AD all can decrease the level of of MMP-3 and the ratio of MMP-3/TIMP-1 in the synovial fluid in knee joints with OA. (2) The level of TIMP-1 in the synovial fluid has no difference before and after being treated with HA. The AD group and GS group can increase the level of TIMP-1, which indicates that the AD group or GS group might produce better therapeutic effect. (3) The level of TIMP-1 increased in the AD group is more than that in the HA’ group and the GS+HA’ group after being treated for 4 weeks, which indicates that the AD group might get better therapeutic effect than the other 2 groups. (4) One of the most important mechanisms of HA, GS and AD in treating OA might be attributed to the expression of MMPs and TIMPs in knee joints with OA.
PMID: 18245904
[Indexed for MEDLINE]
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Osteoarthritis Cartilage. 2008 Feb;16(2):254-60. Epub 2007 Jul 27.
Total joint replacement after glucosamine sulphate treatment in knee osteoarthritis: results of a mean 8-year observation of patients from two previous 3-year, randomized, placebo-controlled trials.
Bruyere O1, Pavelka K, Rovati LC, Gatterová J, Giacovelli G, Olejarová M, Deroisy R, Reginster JY.
OBJECTIVE: – To assess the incidence of Total Joint Replacement (TJR) during the long-term follow-up of patients with knee osteoarthritis (OA) formerly receiving treatment with glucosamine sulphate or placebo.
METHODS: Knee OA patients participating in two previous randomized, placebo-controlled, double-blind, 3-year trials of glucosamine sulphate and receiving treatment for at least 12 months, were systematically contacted to participate in a long-term follow-up retrospective assessment of the incidence of total knee replacement.
CONCLUSIONS: Treatment of knee OA with glucosamine sulphate for at least 12 months and up to 3 years may prevent TJR in an average follow-up of 5 years after drug discontinuation.
PMID: 17681803 DOI: 10.1016/j.joca.2007.06.011
[Indexed for MEDLINE]
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Osteoarthritis Cartilage. 2008 Sep;16(9):973-9. doi: 10.1016/j.joca.2008.01.006. Epub 2008 Mar 4.
Comparison of pharmacokinetics of glucosamine and synovial fluid levels following administration of glucosamine sulphate or glucosamine hydrochloride.
Meulyzer M1, Vachon P, Beaudry F, Vinardell T, Richard H, Beauchamp G, Laverty S.
OBJECTIVE: – To compare the pharmacokinetics of glucosamine and the synovial fluid levels attained following treatment with glucosamine sulphate or glucosamine hydrochloride in a large animal model at clinically relevant doses.
CONCLUSION: – Following oral administration of a clinically recommended dose of glucosamine sulphate (Dona), significantly higher synovial fluid concentrations of glucosamine are attained, when compared to an equivalent dose of glucosamine hydrochloride.
PMID: 18295513 DOI: 10.1016/j.joca.2008.01.006
[Indexed for MEDLINE]
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Phytother Res. 2008 Oct;22(10):1342-8. doi: 10.1002/ptr.2498.
The relationship between chondroprotective and antiinflammatory effects of Withania somnifera root and glucosamine sulphate on human osteoarthritic cartilage in vitro.
Sumantran VN1, Chandwaskar R, Joshi AK, Boddul S, Patwardhan B, Chopra A, Wagh UV.
It also confirmed that glucosamine sulphate exhibited statistically significant, anti-inflammatory and chondroprotective activities in human OA cartilage.
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Curr Ther Res Clin Exp. 2009 Jun;70(3):185-96. doi: 10.1016/j.curtheres.2009.05.004.
The efficacy and tolerability of glucosamine sulfate in the treatment of knee osteoarthritis: A randomized, double-blind, placebo-controlled trial.
Giordano N1, Fioravanti A2, Papakostas P1, Montella A1, Giorgi G3, Nuti R1.
OBJECTIVE: – The aim of the study was to assess the efficacy and tolerability of glucosamine sulfate (GS) in the treatment of knee OA.
CONCLUSIONS: – GS 1500 mg QD PO for 12 weeks was associated with statistically significant reductions in pain and improvements in functioning, with decreased analgesic consumption, compared with baseline and placebo in these patients with knee OA. A carryover effect was detected after treatment ended.
PMID: 24683229 PMCID: PMC3967292
DOI: 10.1016/j.curtheres.2009.05.004
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Bioconjug Chem. 2009 Aug 19;20(8):1547-52. doi: 10.1021/bc9000883. Epub 2009 Jul 17.
Optimal 99mTc radiolabeling and uptake of glucosamine sulfate by cartilage. A potential tracer for scintigraphic detection of osteoarthritis.
Sobal G1, Menzel J, Sinzinger H.
Although the uptake at pH 7 (0.1 mg tin) is comparable with that at pH 2 (2.5 mg tin), the washout of the tracer amounted only to 4.10 ± 1.25% and 2.05 ± 0.65% after 3 h and 24 h, respectively. During degeneration of cartilage, incorporation of (99m)TcGS is high and could therefore be a promising tracer not only to target osteoarthritis but also to monitor the effects of therapy.
PMID: 19610614 DOI: 10.1021/bc9000883
[Indexed for MEDLINE]
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J Med Assoc Thai. 2010 Jul;93(7):805-11.
Comparable clinical outcomes between glucosamine sulfate-potassium chloride and glucosamine sulfate sodium chloride in patients with mild and moderate knee osteoarthritis: a randomized, double-blind study.
Wangroongsub Y1, Tanavalee A, Wilairatana V, Ngarmukos S.
BACKGROUND: Glucosamine sulfate has been recommended for treatment of knee osteoarthritis in several published guidelines. However, there are various preparations of glucosamine that may result in different pharmacokinetic and clinical outcomes.
OBJECTIVES: Comparison of clinical outcomes of two different preparations of glucosamine sulfate (Sodium chloride salt and Potassium chloride salt) in patients with mild and moderate degree knee osteoarthritis. Laboratory tests to monitor drug safety were also studied. Serum potassium level increased more significantly in the GS-K group but did not exceed normal value.
CONCLUSION: In this short-term randomized comparison, glucosamine sulfate with potassium salt (GS-K) is as effective in pain relief and as safe as glucosamine sulfate with sodium salt (GS-Na) for treatment of mild and moderate degree knee osteoarthritis.
PMID:20649060
[Indexed for MEDLINE]
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BMC Musculoskelet Disord. 2010 Jul 15;11:162. doi: 10.1186/1471-2474-11-162.
Comparison of glucose derivatives effects on cartilage degradation.
Phitak T1, Pothacharoen P, Kongtawelert P.
BACKGROUND: Glucosamine (GlcN) is a well-recognized candidate for treatment of osteoarthritis. However, it is currently used in derivative forms, such as glucosamine-hydrochloride (GlcN-HCl) or glucosamine sulfate (GlcN-S). In this study, we compared the effects of Glucose (Glc), Glucuronic acid (GlcA), Glucosamine hydrochloride (GlcN-HCl) and Glucosamine sulfate (GlcN-S) on cartilage degradation.
CONCLUSION: This study shows that glucosamine derivatives can alter anabolic and catabolic processes in HACs induced by IL-1beta. The chondroprotective study using porcine cartilage explant showed that GlcN-S had the strongest effect.
PMID: 20630114 PMCID: PMC3161396
DOI: 10.1186/1471-2474-11-162
[Indexed for MEDLINE]
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Arthritis Res Ther. 2010;12(4):R138. doi: 10.1186/ar3077. Epub 2010 Jul 13.
Pharmacoproteomic study of the effects of chondroitin and glucosamine sulfate on human articular chondrocytes.
Calamia V1, Ruiz-Romero C, Rocha B, Fernández-Puente P, Mateos J, Montell E, Vergés J, Blanco FJ.
INTRODUCTION: Chondroitin sulfate (CS) and glucosamine sulfate (GS) are symptomatic slow-acting drugs for osteoarthritis (OA) widely used in clinic.
RESULTS: A total of 31 different proteins were altered by GS or/and CS treatment when compared to control. Regarding their predicted biological function, 35% of the proteins modulated by GS are involved in signal transduction pathways, 15% in redox and stress response, and 25% in protein synthesis and folding processes. Interestingly, CS affects mainly energy production (31%) and metabolic pathways (13%), decreasing the expression levels of ten proteins. The chaperone GRP78 was found to be remarkably increased by GS alone and in combination with CS, a fact that unveils a putative mechanism for the reported anti-inflammatory effect of GS in OA. On the other hand, the antioxidant enzyme superoxide dismutase 2 (SOD2) was significantly decreased by both drugs and synergistically by their combination, thus suggesting a drug-induced decrease of the oxidative stress caused by IL-1β in chondrocytes.
CONCLUSIONS: CS and GS differentially modulate the proteomic profile of human chondrocytes. This pharmacoproteomic approach unravels the complex intracellular mechanisms that are modulated by these drugs on IL1β-stimulated human articular chondrocytes.
PMID: 20626852 PMCID: PMC2945029 DOI: 10.1186/ar3077
[Indexed for MEDLINE]
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Rheumatology (Oxford). 2013 Aug;52(8):1408-17. doi: 10.1093/rheumatology/kes414. Epub 2013 Jan 30.
Ayurvedic medicine offers a good alternative to glucosamine and celecoxib in the treatment of symptomatic knee osteoarthritis: a randomized, double-blind, controlled equivalence drug trial.
Chopra A1, Saluja M, Tillu G, Sarmukkaddam S, Venugopalan A, Narsimulu G, Handa R, Sumantran V, Raut A, Bichile L, Joshi K, Patwardhan B.
CONCLUSION: – In this 6-month controlled study of knee OA, Ayurvedic formulations (especially SGCG) significantly reduced knee pain and improved knee function and were equivalent to glucosamine and celecoxib.
PMID: 23365148 DOI: 10.1093/rheumatology/kes414
[Indexed for MEDLINE]
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Ulus Travma Acil Cerrahi Derg. 2013 Jan;19(1):8-12. doi: 10.5505/tjtes.2013.03256.
Glucosamine-sulfate on fracture healing.
Uğraş A1, Güzel E, Korkusuz P, Kaya I, Dikici F, Demirbaş E, Çetinus E.
The aim of this study is to determine whether glucosamine-sulfate has any effects on bone-healing.
METHODS:
A unilateral fracture was created in the tibia of sixty-one female rats. Rats were given no drug or 230 mg/kg glucosamine-sulfate daily. Fractures were analyzed during the first, second and fourth weeks after creation of fracture. Quantitative measurement for new bone formation and osteoblast lining were determined histologically. Semiquantitative score for fracture healing was used for histomorphometric analyses. Bridging bone formation was assessed radiographically.
RESULTS:
New bone formation and osteoblast lining were significantly higher in glucosamine-treated group at week 1. Surrounding connective tissue was more cellular and vascular, and the newly formed bone trabecules were present in greater amounts in glucosamine-treated group, compared to control group at week 1 and 4. But radiologically, the control group had better scores than that of the glucosamine-treated group at week 4.
CONCLUSION:
These data demonstrate that daily glucosamine-sulfate administration accelerates early phase of fracture repair in the rat tibia, with increased new bone formation and osteoblast lining histologically, but radiologic bone union is not favored on radiographs.
PMID: 23588972
[Indexed for MEDLINE] 

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