~Arthritis, part 4 - Blocking PLA2

~Arthritis, part 4 - Blocking PLA2
Blocking PLA2

  • Copper Deficiency
  • Curcumin


Dietary factors can influence how much arachidonic acid is produced in the body. An enzyme that is needed to convert dietary factors into arachidonic acid is phospholipase A2 (PLA2). Arthritic pain and inflammation are the end result of a pathway known as the arachidonic acid cascade.

Researchers have been seeking agents that block the PLA2 enzyme in order to reduce the amount of arachidonic acid produced in the body. By suppressing PLA2 enzyme activity, arachidonic levels are reduced along with the proinflammatory compounds it generates, such as leukotrienes, thromboxanes, and PE2. Suppressing PLA2 enzyme activity interferes with the arachidonic acid cascade that is responsible for the chronic pain and tissue destruction seen in so many age-related diseases. High levels of PLA2 enzyme activity have been found in synovial tissue in the joint, and scientists have linked elevated levels of serum PLA2 to activity associated with RA (Vades et al. 1985). In fact, PLA2 has been found in a variety of human tissues, including platelets, cartilage cells known as chondrocytes, placenta, cartilage, peritoneal cells and peritoneal fluid, and the spleen (Vades et al. 1990).

Scientific studies have shown that inflammation that accompanies arthritis is directly linked to enzymatic actions. As can be seen from this chart, the PLA2 enzyme increases arachidonic acid, which is then converted by enzymatic actions (COX-2, lipo-oxygenase, COX-1) into PE2, leukotrienes, and thromboxanes. In fact, the evidence has demonstrated that excessive concentrations of extracellular PLA2 may initiate and spread inflammation and cause cellular damage. High activities of PLA2 have been identified in several inflammatory diseases, including RA and OA (Vades et al. 1985).

In their quest to find PLA2-inhibiting agents, scientists have discovered a group of compounds trademarked under the name Inflacin. When tested, these topically applied compounds alleviated pain associated with arthritis and increased joint mobility.

In a double-blind, patient-randomized, placebo-controlled, crossover clinical trial enrolling 30 participants, Inflacin was tested to evaluate its analgesic benefit when applying the topical cream to areas of the body affected by stiffness, soreness, and pain. These included hands, feet, knees, and shoulders and muscles of the neck, arms, legs, and back. Assessment tools used to measure changes in pain and handgrip strength included a visual analog scale (VAS) that recorded pain levels and a hydraulic hand dynamo meter that evaluated changes in handgrip strength. The VAS is a common assessment tool that accurately evaluates pain and stiffness based on a ranking recorded on a 0-10 scale, with zero being no pain and 10 being very severe pain. Each assessment in the study was conducted 3 times using this method, and an average of three rankings was recorded as the value for that time point.

Assessments using the hydraulic hand dynamometer were recorded 3 times with each hand by holding the device at arm's length vertically. After initial assessments, the blinded investigator applied measured amounts of either Inflacin or placebo to affected areas. Subsequent assessments were then recorded at intervals of 5 minutes, 60 minutes, and 120 minutes.

Results of the study showed that Inflacin significantly reduced pain and stiffness after just one application of 2 grams. On average, Inflacin reduced pain by 45% (as compared to 15% in the placebo group) after one dose in the first 60 minutes of application. In several test subjects, researchers recorded a dramatic reduction of pain. In some subjects, a complete eradication of pain and almost total loss of stiffness occurred. Over the next 60 minutes, pain and stiffness returned among those in the placebo group, while subjects in the Inflacin group continued to experience a decrease in pain and stiffness. Moreover, subjects in the Inflacin group experienced an average increase in grip strength of 10% in both hands; grip strength did not improve in subjects using the placebo.

In the clinical test, Inflacin showed an immediate effect (within 5 minutes) of statistically reducing pain and stiffness (by as much as 72%, compared to 15% for the placebo in one subject). Inflacin was also shown to improve handgrip strength within 5 minutes, whereas the same improvements were not demonstrated among those using the placebo.

Data indicated that at every time point in the trial (at 5, 30, 60, and 120 minutes) Inflacin improved the pain score and performed better than the placebo in decreasing pain.

The overall conclusions drawn from the study indicate that in subjects with mild-to-moderate pain, Inflacin is an effective compound for reducing pain and stiffness and improving grip strength when applied topically. Despite some relief of pain and stiffness noted within the first 60 minutes among those in the placebo group, symptoms ultimately began to return. Additionally, subjects who used the placebo cream reported no improvement in handgrip strength (Keller 2002).

Inflacin's combination of active ingredients and unique delivery system makes it an effective anti-inflammatory topical analgesic. The patent-pending ingredient used to make Inflacin specifically inhibits certain enzyme systems that mediate a variety of physiological responses, including a cascade of biochemical reactions that help facilitate pain, fever, inflammation, and other functions. The resulting anti-inflammatory action is much more effective than that used in other marketed topical products that have a counterirritant mode of action but are only marginally effective at disguising the pain.

Copper Deficiency

Research suggests that people with RA tend toward copper deficiency. A study in the Journal of Rheumatology showed that patients with RA had low levels of several micronutrients, including copper, compared to the typical American diet (Kremer et al. 1996). Consequently, the authors suggested that "routine dietary supplementation with multivitamins and trace elements is appropriate in this population." A deficiency may also explain why copper, which is an anti-inflammatory agent, is useful in the treatment of RA and other inflammatory conditions. An early study in the Journal of the American Medical Association reported that copper supplementation surpassed aspirin in terms of anti-inflammatory action, boasting 130% of the activity of cortisone (JAMA 1974; 229: 1268-1269).

Unlike other micronutrients that can be taken in large doses before reaching a toxicity threshold, a small amount of copper is all that it takes to perform its meticulous tasks that are so essential to human health. An excess of copper may encourage free-radical activity and subsequent oxidative damage at the cellular, tissue, and organ level (Dameron et al. 1998). Good dietary sources of copper include crabmeat, oysters, beans (such as kidney, pinto, and black beans), brown rice, potatoes, and spinach. Vitamin and mineral supplements containing trace amounts of copper will also ensure that proper levels are achieved.

Curcumin

Curcumin comes from a plant similar to ginger and is an anti-inflammatory that inhibits both COX-2 and LOX enzyme activity. In addition, curcumin interferes with NF-KB to stop autoimmune activation and lessen tissue destruction (Joe et al. 1997; Plummer et al. 1999).

Some studies revealed that users of curcumin supplements were not getting optimal benefits from the extract. The reason is that for curcumin to be effectively assimilated into the bloodstream, it must be combined with small amounts of piperine (a component of black pepper). Piperine has been shown to enhance the serum concentration, the extent of absorption, and the bioavailability of curcumin in both rats and humans with no adverse effects (Shoba et al. 1998).

An Innovative Alternative to Joint Replacement

When a joint threatens to deteriorate completely, orthopaedic surgeons can repair or replace it. However, replacement parts wear away or loosen over time and often need an additional operation (sometimes more). A novel method of treating degenerative cartilage diseases has been developed by an orthopaedic surgeon in Miami, FL, as a possible alternative to invasive procedures such as joint replacement.

The innovative procedure developed and patented by Dr. Allan Dunn involves the injection of human growth hormone directly into the affected joint spaces of the arthritic patient that, in turn, stimulates the growth of cartilage. The cartilage regrowth causes increased space between the ends of the bones, often up to 4 mL in volume, enough to ease pain and stiffness in the affected joint. Growth hormone also increases the production of collagen, the strong fibrous connective tissue that attaches cartilage to bone and provides a framework for the gelatinous matrix, the resilient part of cartilage.

IntraArticular Growth Hormone (IAGH) gives the body the cues it needs to set the cartilage growth process in motion. Stimulation of cartilage regeneration with growth hormone reproduces the same environment in which joint tissues grow during childhood. The IAGH procedure has been successfully used on hips, knees, ankles, shoulders, and elbows. (Dr. Allan Dunn may be reached at (888) 848-6534.)

Continued . . .


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