Recent developments in joint health and tissue regeneration – scientific and clinical support for genonutrients

Arthritis and joint inflammation remains a therapeutic challenge, primarily because NSAIDs (non-steroidal anti-inflammatory drugs), the mainstay of pharmaceutical approaches (prescription or over-the-counter), alleviate the symptoms but not the disease process. In other words while pain and perhaps stiffness are managed, the inflammatory processes continue to destroy the joint. Over time this can cause severe anatomical disturbances like “bone on bone” conditions where the cushioning cartilage is completely eroded. Further, the side-effects of this class of drugs can be staggering.

Given the aging population, this problem is having a serious impact on the quality of life for an enormous number of people. Ideally, what is needed is a therapeutic approach that not only stops the damage but also promotes repair and restitution of joint structure and function, to recreate healthy, properly functioning joints.

Natural products have been approaching this problem, but recently published breakthroughs suggest that the solution we dreamed of may now be here. Historically, the primary approach in natural products has centered on replacement therapy with glucosamine or chondroitin or the combination. Why is this replacement therapy? Well, these natural chemicals are the building blocks of the cartilage cushion, and they are released when cartilage cells or inflammatory cells release enzymes (MMPs) that chop the cartilage into pieces like molecular scissors. The theory is that if you ingest enough of what is lost through this destructive process then the tide of damage can be halted and maybe reversed.

Clinical experience has been mixed with both positive [1,2] and negative [3,4] outcomes. The central problem has been that glucosamine or its more complex form chondroitin, need active growth or repair factors in order for them to be reinserted back into cartilage or collagen. These critical repair factors are suppressed with aging and inflammation, so our natural restorative powers do not work as they did when we are young. While this can be readily demonstrated on a genetic level, it is also intuitive.

So how do we re-energize this critical repair process and stop the damage? Recently, a combination of two medicinal plants from South America, called Reparagen®, has been shown to protect human cartilage from the destructive effects of inflammation, while at the same time energizing the critical repair gene, IGF-1 within cartilage cells [5]. This was a conceptual breakthrough, because for the first time it was shown that normal repair function could be maintained in human cartilage despite the suppressive effects of inflammation.

The critical next step, a randomized controlled clinical trial on Reparagen was completed and recently published [6]. In this study Reparagen was compared to glucosamine sulfate over 8 weeks in subjects with moderate osteoarthritis of the knee. A key finding was that response rate to Reparagen was an impressive 94% using the same criteria as the recent GAIT study [3]. Furthermore, at all assessment periods, the response rate to Reparagen was greater than glucosamine, with reductions in pain, stiffness and improved function - all significant within the first week of therapy. Additionally, subjects taking Reparagen consumed significantly less pain medication than those taking glucosamine at every assessment period starting in week one.

This is a remarkable result and suggests that there is indeed hope that an entirely new approach to joint health is now here and available. Extending these concepts, another breakthrough was reported in human cartilage by the same authors in collaboration with Case Western Reserve University. They noted that another Amazonian extract, Progrado®, was able to protect cartilage, activate the repair factor and block the molecular scissors (MMPs) that slice and dice cartilage and collagen [7]. Introduced for gastrointestinal (IBS) and topical applications, this breakthrough extends the concept that these genonutrients have potent anti-aging activities. Using the Reparagen example, the ability of genonutrients to turn our own genetic clock back to a youthful setting is likely to be source of some remarkable therapeutics in the coming years.


  1. Pavelka K, Gatterova J, Olejarova M, Machacek S, Giacovelli C, Rovarti LC. Glucosamine sulphate use and delay of progression of knee osteoarthritis: a 3-year, randomized, placebo-controlled, double-blind study. Arch Intern Med 2002, 162: 2113-2123.
  2. Herrero-Beaumont G, Ivorra JAR, Trabado MC, Blanco FJ, Benito P, Martin-Mola E, Paulino J, Marenco JL, Porto A, Laffon A, Araujo D, Figueroa M, Branco J: Glucosamine sulfate in the treatment of knee osteoarthritis symptoms. A randomized double-blind, placebo-controlled study using acetominophen as a side comparator. Arthritis Rheum 2007, 56: 555-567.
  3. Herrero-Beaumont G, Ivorra JAR, Trabado MC, Blanco FJ, Benito P, Martin-Mola E, Paulino J, Marenco JL, Porto A, Laffon A, Araujo D, Figueroa M, Branco J: Glucosamine sulfate in the treatment of knee osteoarthritis symptoms. A randomized double-blind, placebo-controlled study using acetominophen as a side comparator. Arthritis Rheum 2007, 56: 555-567.
  4. Vlad SC, LaValley MP, McAlindon TE, Felson DT. Glucosamine for pain in osteoarthritis: why do trial results differ? Arthritis Rheum 2007, 56: 2267-2277.
  5. Miller MJS, Ahmed S, Bobrowski PJ, Haqqi TM: The chondroprotective actions of a natural product are associated with the activation of IGF-1 production by human chondrocytes despite the presence of IL-1b. BMC Complement Altern Med 2006, 6: 13.
  6. Mehta K, Gala J, Bhasale S, Naik S, Modak M, Thakur H, Deo, Miller MJS. Comparison of glucosamine sulfate and a polyherbal for the relief of osteoarthritis of the knee: a randomized controlled trial [ISRCTN25438351]. BMC Complement Altern Med 2007, 7: 34.
  7. Miller MJS, Bobrowski P, Shukla M, Gupta K, Haqqi TM. Chondroprotective effects of a proanthocyanidin rich Amazonian genonutrient reflects direct inhibition of matrix metalloproteinases and upregulation of IGF-1 production by human chondrocytes. J Inflammation (Lond.) 2007, B: 16.

Biography: Mark JS Miller, PhD

Dr. Miller has had a distinguished career as an academic, pharmaceutical industry researcher, consultant and entrepreneur. His research has made major contributions to numerous fields of medical research including gastroenterology, perinatology, cancer, rheumatology, inflammation and therapeutics. His recent interests centre on the development of therapeutic agents from South American ethnomedicines. Dr. Miller reviews grants for numerous international agencies, peer reviews for 40 journals and consults with the World Bank on industry development.


Dr. Miller is the Head of the Scientific Advisory Board for Rainforest Nutritionals, Inc and Park Labs, LLC. For these consulting services he has received an equity interest.

Contact information: [email protected]

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