DONA™ FAQ

 

 

  • What is DONA™?

DONA™ is Crystalline Glucosamine Sulfate, i.e. the original glucosamine sulfate product. DONA™ is actually a prescription drug in Europe and elsewhere. However, in the United States of America, DONA™ is available as a dietary supplement (according to the Dietary Supplement Health and Education Act) proven to promote cartilage metabolism*, to protect joint structure* and to support joint mobility*.

Clinical studies and the world-wide clinical experience have shown that DONA™ helps maintain and stabilize the cartilage in the joints. Recent, state-of-the-art clinical trials have also demonstrated that DONA™ is the first compound that, when given for long-term treatment courses (i.e. at least 3 years), can decrease the need (by 57%) for a total knee replacement.

 

  • What is Glucosamine Sulfate?

Glucosamine sulfate is the salt of the natural amino-sugar glucosamine, which is normally synthesized in the healthy body and is the basic constituent of cartilage glycosaminoglycans and proteoglycans, i.e. the main substances that form the cartilage matrix and that are essential for cartilage health and function.

Glucosamine sulfate cannot be practically used as such for the preparation of medicinal products or dietary supplements because, for chemical reasons, it is a highly unstable compound. The Rotta Research Group has invented and patented a method to stabilize glucosamine sulfate, through a chemical process of co-precipitation with sodium chloride, thus obtaining Crystalline Glucosamine Sulfate. Crystalline Glucosamine Sulfate is the active ingredient in DONA™ and the original and only glucosamine sulfate that has been investigated in more than 150 pre-clinical and clinical studies, and to which over 90% of the scientific literature refers to.

Crystalline Glucosamine Sulfate is referred to in this document of Frequently Asked Questions as Glucosamine Sulfate, for simplicity.

 

  • Is the original Glucosamine Sulfate contained in DONA™ different from other glucosamine products?

As mentioned above, plain glucosamine sulfate cannot exist unless in stabilised form. Products claiming to contain glucosamine sulfate without declaring how it is stabilised, most likely do not contain this compound. Most of the products available as dietary supplements contain glucosamine hydrochloride, which is a simpler salt of glucosamine that may not share all the pharmacological properties of Glucosamine Sulfate (see below).

Furthermore, glucosamine-based dietary supplements available in the North American market have been recently criticized by studies from the University of Maryland showing major deviations from label claims in the amount of glucosamine actually contained. Conversely, DONA™ contains the original Glucosamine Sulfate, i.e. in stabilised form and manufactured according to Good Manufacturing Practices: this is certified by the status of prescription drug that DONA™ has in Europe and elsewhere. This means that the product has been approved by Health Authorities around the world according to a thorough, FDA-like, review process, that none of the glucosamine-derived dietary supplements underwent.

Of at least similar importance is that fact that over 90% of the scientific literature, including pharmacokinetics and clinical studies of efficacy and safety, have been performed with DONA™. Dietary supplements containing glucosamine-derived compounds make claims mostly based on the studies performed with DONA™, but they are definitely different products.

 

  • Is the original Glucosamine Sulfate contained in DONA™ different from other glucosamine products?

As mentioned above, plain glucosamine sulfate cannot exist unless in stabilized form. Products claiming to contain glucosamine sulfate without declaring how it is stabilized, most likely do not contain this compound. Most of the products available as dietary supplements contain glucosamine hydrochloride, which is a simpler salt of glucosamine that may not share all the pharmacological properties of Glucosamine Sulfate (see below).

Furthermore, glucosamine-based dietary supplements available in the North American market have been recently criticized by studies from the University of Maryland showing major deviations from label claims in the amount of glucosamine actually contained. Conversely, DONA™ contains the original Glucosamine Sulfate, i.e. in stabilized form and manufactured according to Good Manufacturing Practices: this is certified by the status of prescription drug that DONA™ has in Europe and elsewhere. This means that the product has been approved by Health Authorities around the world according to a thorough, FDA-like, review process, that none of the glucosamine-derived dietary supplements underwent.

Of at least similar importance is that fact that over 90% of the scientific literature, including pharmacokinetics and clinical studies of efficacy and safety, have been performed with DONA™. Dietary supplements containing glucosamine-derived compounds make claims mostly based on the studies performed with DONA™, but they are definitely different products.

 

  • What is the mode of action of DONA™?

After oral or parenteral administration of Glucosamine Sulfate, studies performed with the radiolabeled compound have shown that it accumulates in the articular cartilage of the joints. In this tissue, Glucosamine sulfate stimulates the synthesis of physiological-type proteoglycans by the chondrocytes, i.e. the only living cells of the articular cartilage, responsible for its formation and for its destruction. Proteoglycans are the essential constituents of the cartilage matrix and are responsible for the cartilage mechanical function within the joint, including the resistance to the mechanical load and the elasticity due to the proteoglycan water-binding capacity. The integrity of proteoglycans is progressively lost in degenerative diseases such as osteoarthritis.

Besides promoting the synthesis of proteoglycans, studies have shown that Glucosamine Sulfate is also able to depress cartilage degradation activities by inhibiting the action of catabolic enzymes. In addition, Glucosamine Sulfate has been shown to possess distinct, mild fast acting properties through a mechanism which is independent of the synthesis of prostaglandins (and is therefore not burdened with the side effects of conventional non-steroidal -drugs). All studies describing the mechanism of action of Glucosamine Sulfate are described in the Product Monograph of DONA™.

 

  • What is the role of sulfate ions and why is it preferable to administer Glucosamine Sulfate rather than other glucosamine salts, such as glucosamine hydrochloride?

Proteoglycans in the articular cartilage matrix consist of a protein filament with side chains consisting of glycosaminoglycans, which are complex polysaccharides and are sulfated in their main constituents (which are glucosamine derivatives). Therefore the rate of proteoglycan production depends on the quantity of sulfate available to the chondrocytes. Furthermore, the sulfate esters of the glycosaminoglycan side chains of proteoglycans are essential for the elasticity and water-binding capacity in the cartilage matrix. Finally, sulfate ions also contribute to the inhibition of cartilage degrading enzymes.

Therefore, Glucosamine Sulfate offers these distinct pharmacological advantages compared to simpler glucosamine salts such as glucosamine hydrochloride. In any case, since practically all available clinical trials have been performed with Glucosamine Sulfate, it is impossible to know if glucosamine hydrochloride has the same efficacy and safety in the absence of comparative studies.

 

  • What was the clinical development of DONA™?

DONA™ has been evaluated in clinical trials in more than 6000 patients to date. The most recent clinical development of DONA™ has been conducted according to the strict guidelines published by scientific organizations, such as the “Osteoarthritis Research Society International” (OARSI), and Health Regulatory Agencies such as the Food and Drug Administration (FDA) and the European Agency for the Evaluation of Medicinal Products (EMEA). Indeed, this product has been approved as a prescription drug in more than 60 countries around the world, according to an FDA-like review process.

The comprehensive clinical trial program performed with DONA™, includes short-term studies (up to 6 months) on the signs and symptoms of joint discomfort and long-term studies (up to 3 years) on the modification of joint stuctures. These studies are published and they are summarized in details in the Product Monograph of DONA™.

 

  • What is the effect of DONA™ on the signs and symptoms of joint discomfort?

Short-term (up to 6 months), randomized, controlled clinical studies have shown that, already within the first 2 weeks of treatment, DONA™ induces improvement in function which is of the same magnitude of that obtained with non-steroidal drugs (NSAIDs) up to 4 weeks.

Thereafter, the improvement with DONA™ continues in a linear fashion and tends to be greater than that of NSAIDs, till the completion of a 12-week treatment course, which can be considered the optimal short-term treatment duration with DONA™. Indeed, the clinical improvement is strong and long-lasting, i.e. for at least 2 months after the end of such a 12-week treatment course. Long-term (up to 3 years), randomized, placebo-controlled studies have shown that the significant improvement on overall joint function can be similarly obtained over chronic treatment courses, using either cyclic or continuous administration regimens.

 

  • Does DONA™ have any effect on the progression of osteoarthritis?

Two very recent, randomized, placebo-controlled clinical studies performed by Reginster et al. and by Pavelka et al., have shown that the continuous administration of DONA™ for 3 years in patients with joint issues in the knee, besides assuring symptom relief, can prevent the progression in joint changes, assessed by radiological joint space narrowing.

These findings have been recently presented at the most important scientific congresses including the American College of Rheumatology meeting, where they attracted a huge attention and were welcome as the first evidence that a pharmacological intervention can prevent the progression of joint issues.

 

  • Is DONA™ a safe product?

In all clinical studies, the safety of DONA™ was always similar to placebo (even in the long-term 3-year studies) and, of course, significantly better than unspecific symptomatic agents such as conventional non-steroidal drugs (NSAIDs).

Furthermore, as a prescription grade product, the safety of DONA™ in the normal clinical practice is constantly monitored and periodically reported to Health Authorities worldwide, assuring a rigorous control that cannot be achieved by standard dietary supplements: millions of people have been treated with the compounds with very few and mild adverse reactions, assessed by Health Authorities, and that confirmed the excellent safety profile described in clinical trials.

 

  • What may be the few and mild adverse reactions of DONA™?

Transient and mild adverse events, may include gastric discomfort and pain, constipation, diarrhea, meteorism and nausea. Since the proportion of these events is low and similar to the one observed with placebo in comparative clinical studies, these events may be related to the mild discomfort that may be evident with any oral drug intake in some patients. Indeed, the incidence of these adverse events is much, significantly, lower than with conventional NSAIDs and without any of the gastrointestinal complications of the latter. Hypersensitivity reactions were reported in some patients and included cutaneous rashes with pruritus and erythema. Very rarely and most likely without any relationship with DONA™ administration, headache, visual disorders and hair loss have been reported.

 

  • What is the optimal treatment duration with DONA™?

Clinical studies have shown that the optimal short-term treatment duration with DONA™ for the relief of joint issues should be 12 weeks (i.e. 3 months). Since, the benefit achieved is long-lasting, i.e. for at least 2 months after the end of such a treatment course, the product can be taken in cycles predetermined as such, or anyway at the recurrence of symptoms.

However, very recent, long-term trials have shown that if taken continuously for at least 3 years, DONA™ can support joint health.

 

  • Does Glucosamine Sulfate impair glucose metabolism and/or is it contraindicated in diabetic patients?

Recent reports using, in animals, unphysiological experimental settings and suprapharmacological doses of glucosamine, claimed that the compound may increase insulin resistance. However these are only speculations and have never been proven in men. On the contrary, very recent human studies using intravenous or intra-arterial glucosamine at doses much higher than used in the normal clinical practice, found that this supposed mechanism is not active in humans. Furthermore, both short-term and long-term (up to 3 years) clinical studies with DONA™ have shown that glucose plasma levels are not modified by the administration of the product in normal patients, or in those with relatively high baseline glucose levels, or even in diabetics.

It seems therefore that in humans, oral Glucosamine Sulfate at therapeutic doses does not affect glucose metabolism. No Health Authority has ever contraindicated DONA™ in diabetics.

 

  • DONA™ contains sodium: is it contraindicated in hypertension? 

As stated above, Crystalline Glucosamine Sulfate is glucosamine sulfate stabilized by co-precipitation with sodium chloride (NaCl). The NaCl content in each DONA™ packet/sachet that is used once daily, is 384 mg (equivalent to about 150 mg of sodium ion).

This quantity is very low, compared with the standard daily intake of 6-10 g of NaCl (equivalent to 2.36-3.93 g of sodium ion). In hypertensive patients a mild dietary sodium restriction is advised, i.e. up to 5 g NaCl per day (equivalent to 1.97 g of sodium ion). This restriction will not be modified therefore by the small quantity of sodium contained in the daily dose of DONA™. No Health Authority has ever contraindicated DONA™ in hypertension.

 

  • Can DONA™ cause allergic reactions and/or is it contraindicated in subjects allergic to seafood? 

Glucosamine Sulfate can rarely cause allergic reactions that may manifest themselves as cutaneous rashes with pruritus and erythema: this may happen with any medicinal product or dietary supplement of any nature.


Contrary to some dietary supplements (or drugs, in some countries) used to protect joints and that are tissue macromolecular extracts with potential proteic and other impurities that may frequently give rise to allergic reactions, the original Glucosamine Sulfate is obtained by a chemical synthesis process (that assures a high degree of purity), starting from a substance called chitin and which is of sea origin.

Chitin is a highly purified polysaccharide and does not contain proteic impurities that are responsible for allergic reactions in some subjects eating sea-food. Any other potential impurity would be in any case eliminated by the chemical process from which Glucosamine Sulfate is obtained. DONA™ is therefore not contraindicated in subjects allergic to sea food, but only in those subjects who already suffered an hypersensitivity reaction to Glucosamine Sulfate.

 

  • Are there any interactions with other drugs when using DONA™?

Due to its physico-chemical and pharmacokinetic properties, Glucosamine Sulfate is a compound with no potential for pharmacokinetic or other interactions with any other drugs, as detailed in Product Monograph of DONA™. The only exception is represented by the suggestion that the oral administration of Glucosamine Sulfate may enhance the gastrointestinal absorption of tetracyclines and decrease that of penicillin or chloramphenicol. In clinical trials, DONA™ has been associated with several drugs for concomitant diseases, without any clinically significant interaction even being reported. The concomitant medications used include the most commonly prescribed drugs such as antihypertensive agents, nitrates, antiarrhyics, anxiolitics, antidepressants, hypoglycemic agents, hormones, gastric antisecretives, etc.

 

  • Can DONA™ be combined with non-steroidal anti-inflammatory drugs (NSAIDs)?

State-of-the-art clinical trials have shown that the degree of the clinical improvement on joint health with DONA™ is so strong after a standard 12-week treatment course, that it can not even be differentiated from that obtained combining the compound with NSAIDs. Both DONA™ and the combination of DONA™ with an NSAID may be actually more effective than the NSAID alone. However, the combined treatment has an onset of action over the first 2 weeks of administration that is even greater and faster than that of either drug alone. Therefore, the combination of DONA™ with NSAIDs may be advisable when an immediate therapeutic response is required. Alternatively, this association may be appropriate when the possible superimposed component of the disease is clinically relevant. It should be borne in mind that DONA™ has a safety which is similar to that of placebo and it is significantly better tolerated than NSAIDs. However, combining DONA™ with NSAIDs does not protect from the adverse reactions to the NSAID, although it may improve patient's compliance.

 

*These Statements Have Not Been Evaluated By The Food & Drug Administration. This Product Is Not Intended To Diagnose, Treat, Cure or Prevent Any Disease.