The publication of a round-up of studies on the safety and efficacy of Metagenics' NG440 formulation of rho iso-alpha acids (RIAAs) from hops, rosemary and oleanolic acid adds weight to its use in medical foods for inflammation.
Traditionally, non-steroidal anti-inflammatory drugs (NSAIDS) like aspirin, ibuprofen, naproxen and COX-2 inhibitors have been used to counter inflammatory conditions. However these have been associated with gastrointestinal complications.
Moreover, serious safety and public health concerns were raised about COX-2 inhibitors in 2004, when studies found a connection between the use of some such drugs on the market and an increased risk of cardiovascular events like heart attack and stroke. The drugs in question, including Vioxx, were subsequently withdrawn.
Dr Robert H Lerman, MD, PhD, Metagenics director of medicine and bariatric surgery told NutraIngredients.com:
"Doctors and their patients are seeking safe alternatives to NSAIDs including COX2 inhibitors… Thus, there is a growing acceptance by physicians of efficacious alternatives.
"With a patient's health at stake, more and more practitioners are counselling their patients to make the natural choice."
He added, though, that this acceptance would be more widespread if insurers covered natural products such as NG440 in the US, in the same way prescription medicines are covered.
Metagenics' NG440 formula - known commercially as Luduxin - was developed after company researchers tested more than 200 natural compounds. Dr Lerman said: "We believe it may be a new class of therapeutic agent".
The formula is presently used in several medical food products available in the United States, Canada and Mexico: UltraMeal Plus 360 for metabolic syndrome support; UltraGlycemX Plus 360 for support of type 2 diabetes; and UltraInflamX Plus 360 for support of inflammatory bowel disease.
Luduxin is also understood to be available in other world markets, including Europe.
The published report is a round-up of studies conducted to investigate factors such as pain relief in patients suffering from osteoarthritis and joint discomfort, safety and toxicity studies, and potential cardiovascular or gastrointestinal side effects.
The researchers used two versions of the NG440 formula for added flexibility: NG440-1, which had 440mg of active ingredients per tablet (200mg RIAAs, 200mg rosemary extract and 40mg of oleanolic acid); and NG440-2, with 225mg of RIAAs, 112,5mg rosemary extract and 1mg oleanolic acid per tablet.
The conclusion of the published paper was that "NG440 may serve as a safe and efficacious alternative in some areas where specific COX-2 inhibitors have traditionally been used".
Animal toxicology study
A group of mice were given either a control or one of three doses of NG440-1 for 21 days (25, 75, or 250 mg/kg).
No adverse effects were found.
Cardiovascular health parametres
Four separate clinical trials looked at the safety of NG440 constituents RIAAs, rosemary and oleanolic acid as determined by prostacyclin production, blood pressure and clinical chemistries.
RIAAs were seen to have no effect on secretion of either PGIM or TxB2 prrostanoid secretion.
No significant changes were seen in systolic or diastolic blood pressure.
No significant changed were seen in general chemistries.
Gastrointestinal health parametres
A randomised, 14-day crossover study with healthy men aged 18 to 45 compared the effects of naproxen and NG440-1 on gastrointestinal health, and specifically on the production of fecal calprotectin (a measure of gastrointestinal injury).
While naproxen was seen to raise faecal calprotectin to 154 per cent above baseline, no difference was seen in the levels of those taking the NG440-1, either 14-days after treatment or during three-year follow up.
A clinical multicentre trial using NG440-2 was conducted to determine relief of pain symptoms. This involved 56 adults aged between 28 and 85 years, of unspecified sex.
Twenty-six of the 56 subjects responded to NG440 therapy.
A three-arm, open-label clinical study with six subjects in a Latin square design assessed the effects of two different doses of NG440-1 versus a standard dose of 200mg of COX-2 inhibitor on the inhibition of PGE2 synthesis.
Inhibition of PGE2 synthesis was seen in all subjects, regardless of whether they were taking the NG440-1 or the COX-2.
Canadian Journal of Physiology and Pharmacology (National Research Council Canada)
Title: Clinical safety and efficacy of NG440: a novel combination of rho iso-alpha acids from hops, rosemary, and oleanolic acid for inflammatory conditions.
Authors: Deanna Minich, Jeffrey Bland, Jeffrey Katke, Gary Darland, Amy Hall, Robert Lerman, Joseph Lamb, Brian Carroll, and Matthew Tripp.