Natural Anti-inflammatory Agents for Pain Relief
Written by Editor   
Monday, January 11, 2016 12:00 AM

This primer from the NIH of natural anti-inflammatory agents is well documented.

The inflammatory pathway is a complex biochemical pathway which, once stimulated by injury, leads to the production of inflammatory mediators whose initial effect is pain and tissue destruction, followed by healing and recovery.

Various studies have also shown that NSAIDs can delay muscle regeneration and may reduce ligament, tendon, and cartilage healing. Specifically, NSAIDs are believed to wipe out the entire inflammatory mediated proliferative phase of healing associated with WBC actions (days 0–4). A study of the effects of NSAIDs on acute hamstring injuries was done in humans by Reynolds et al., and these investigators concluded that patients who used NSAIDs did not experience a greater reduction of pain and soft-tissue swelling when compared with the placebo group. Interestingly enough, the authors noted that the NSAIDs’ group had worse pain associated with severe injuries compared with the placebo group.

The NSAIDs are also known to have adverse effects on kidney function. Dehydration or preexisting chronic renal failure or disease may predispose certain populations to acute renal failure through inhibition of prostaglandin synthesis, which can occur when taking NSAIDs. The National Kidney Foundation asserts that approximately 10% of kidney failures per year are directly correlated to substantial overuse of NSAIDs.

An estimated 15–20 million people in the US were using selective COX-2–inhibiting NSAIDs on a long-term basis. These drugs became the most commonly used pharmaceutical agent with more than 70 million NSAID prescriptions written each year and 30 billion over-the-counter NSAID tablets sold annually. It was estimated that 5–10% of the adult population used NSAIDs, and among the elderly the use of these drugs was as high as 15%. The general acceptance of these drugs was due to the perceived lack of serious gastrointestinal side effects that had been associated with the nonselective class of NSAIDs.

On September 30, 2004, Merck Research Laboratories announced the global withdrawal of its primary selective COX-2–inhibiting NSAID. A Vioxx study (known as the APPROVe study) showed that there was double the risk of serious thromboembolic events, including myocardial infarction, which became apparent after 18 months of Vioxx treatment.

Because of the significant side effect profiles of steroidal and NSAID medications, there is a greater interest in natural compounds, such as dietary supplement and herbal remedies, which have been used for centuries to reduce pain and inflammation. Many of these natural compounds also work by inhibiting the inflammatory pathways in a similar manner as NSAIDs.

Plant- and animal-derived nutraceutical preparations have been used for hundreds and even thousands of years to obtain effective pain relief. Herbal medications are becoming increasingly popular because of their relatively few side effects. Nevertheless, there are problems associated with these dietary supplements, and their use requires knowledge of their biological action, clinical studies (both affirmative and negative), and potential interactions with other nutraceutical products and prescription medications.

The evaluation of nutraceutical preparations with appropriately designed controlled studies has exploded in recent years. There is now a greater degree of confidence based on controlled study design and improved quality of the investigators that has strengthened positive findings found using natural compounds to treat diseases. It is important for healthcare practitioners to learn about these scientific studies to counsel patients who are taking various dietary supplements, herbs minerals and vitamins for both disease treatment and prevention.

The use of fish oil (in the form of cod liver oil), an omega-3 EFA, for the treatment of muscular, skeletal, and discogenic diseases, can be traced back to the late 18th century.  Unfortunately, because of the rapid onset of rancidity of this polyunsaturated oil when exposed to air, and hence its disconcerting odor, cod liver oil fell out of favor. With improved extraction techniques, such as using a protective nitrogen blanket and enhanced oxygen-free encapsulation methods, there is less chance of oxidation during the manufacturing process. The therapeutic benefits of fish oil can now be realized without the regurgitation and odor of previous products caused by peroxides and rancid tasting fish oil. 

Research has shown that the omega-3 polyunsaturated fatty acids are some of the most effective natural anti-inflammatory agents available. With the discovery that vascular inflammation is the underlying cause of coronary artery disease, fish and fish oil supplements are now recommended by the American Heart Association for the prevention of this disease. Countries that have the highest fish consumption also have a lower incidence of neurodegenerative disease and depression.  The biological basis for the effectiveness of fish oil in treating arthritis has been well documented with many positive clinical studies, when compared to traditional pharmaceutical anti-inflammatory agents.

Bark from the white willow tree is one of the oldest herbal remedies for pain and inflammation, dating back to ancient Egyptian, Roman, Greek, and Indian civilizations, as an analgesic and antipyretic agent. Because of the gastric side effects of aspirin, there has been a resurgence in the use of white willow bark for the treatment of inflammatory syndromes. The mechanism of action of white willow bark is similar to that of aspirin which is a nonselective inhibitor of COX-1 and COX-2, used to block inflammatory prostaglandins.

Various randomized, placebo-controlled studies comparing white willow bark with nonsteroidal agents have shown an efficacy comparable to these agents and aspirin. Salicin from white willow bark is converted to salicylic acid by the liver and is considered to have fewer side effects than aspirin. However, it is costlier than aspirin, and should not be used in children (to avoid the risk of Reye’s syndrome), or in patients with peptic ulcer disease, poorly controlled diabetes, hepatic or renal disorders, or other conditions in which aspirin would be contraindicated. The usual dose of white willow bark is 240 mg/day.

Curcumin is a naturally occurring yellow pigment derived from turmeric (Curcuma longa), a flowering plant of the ginger family. It has traditionally been used as a coloring and flavoring spice in food products. Curcumin has long been used in both Ayurvedic and Chinese medicines as an anti-inflammatory agent, a treatment for digestive disorders, and to enhance wound healing. Several clinical trials have demonstrated cur cumin’s antioxidant, anti-inflammatory, and antineoplastic effects.  It may be considered a viable natural alternative to nonsteroidal agents for the treatment of inflammation.

The usual dosage of standardized turmeric powder is 400–600 mg taken three times per day. Side effects are few, but with extended use, this agent can cause stomach upset, and in extreme cases gastric ulcers may occur at very high doses. Caution should be used if the patient is taking anticoagulant medications or high doses of nonsteroidal drugs. Studies have shown that curcumin may be used in combination with lower doses of nonsteroidal medications.

Green tea has long been recognized to have cardiovascular and cancer preventative characteristics due to its antioxidant properties. Its use in the treatment of arthritic disease as an anti-inflammatory agent has been recognized more recently. Green tea research now demonstrates both anti-inflammatory and chondroprotective effects. The usual recommendation is 3–4 cups of tea a day. Green tea extract has a typical dosage of 300–400 mg. Green tea can cause stomach irritation in some, and because of its caffeine content, a decaffeinated variety is also available; but the polyphenol content is currently unknown.

Pycnogenol, like white willow bark, is a nutraceutical material that has been used since ancient times. Pycnogenol is derived from the bark of the maritime pine tree (Pinus maritima) and has been used for more than 2000 years. It has been considered helpful for wound healing, treating scurvy, healing of ulcers, and reducing vascular inflammation. It is one of the most potent antioxidant compounds currently known.  Studies have shown that pycnogenol is 50–100 times more potent than vitamin E in neutralizing free radicals and that it helps to recycle and prolong the activity of vitamins C and E. Studies have shown pycnogenol to be effective in reducing blood pressure and reducing the risk of venous thrombosis by its effect on vascular endothelium. The usual dosage is 100–200 mg daily. Few side effects from the use of pine bark extracts have been reported, the most frequent being mild gastrointestinal effects such as diarrhea and upset stomach. Pycnogenol should not be taken by patients who are being treated with immunosuppressants or by those receiving corticosteroid drugs because it can enhance immune system function and interact with drugs that suppress the immune system.

The Boswellia species are trees located in India, Ethiopia, Somalia, and the Arabian Peninsula, and they produce a gum resin called olibanum, better known in the western world as frankincense. This resin possesses anti-inflammatory, anti-arthritic, and analgesic properties. Clinically, the substance is used in the treatment of degenerative and inflammatory joint disorders. It reduces the total white blood cell count in joint fluid, and it also inhibits leukocyte elastase, which is released in rheumatoid arthritis. In one recent study, a statistically significant improvement in arthritis of the knee was shown after 8 weeks of treatment with 333 mg B. serrata extract taken three times a day. The treatment improved function, but radiographically there was no change in the affected joints.

Boswellia typically is given as an extract standardized to contain 30-40% boswellic acids (300-500 mg two or three times/day). Boswellia has been well tolerated in most studies, although some people may experience stomach discomfort, including nausea, acid reflux, or diarrhea.

Resveratrol is a plant-based polyphenol molecule that is found in various concentrations of many different plant sources. The plant is called Japanese Knot weed or Polygonum cuspidatum, and the skins of red wine grapes are believe to have the most concentrated amounts of resveratrol. In plants, resveratrol is generally found in the plant skin and acts as a phytoalexin to protect the plant from infection, excessive UV radiation and aide in general plant defense. Resveratrol has also been found to have significant anti-mutation, anti-inflammatory, antoxidant and DNA protective actions, when consumed by animals and humans.

Resveratrol is available commercially as a dietary supplement capsule, generally from the P. cuspidatum source. The trans-resveratrol is the active form, and although there is not an established dosing range, the typical dose is from 50 to 500 mg daily. Any significant side effect or safety issues with resveratrol have not been established, but due to an experimentally shown anti-platelet effect, caution should be exercised when taking other prescription or herbal anti-platelet or coagulation altering products.

Uncaria tomentosa and Uncaria guianensis are Peruvian herbs derived from woody vines with small claw-like thorns (hence the vernacular name, cat’s claw) at the base of the leaf, which allow the plant to climb to heights of up to 100 ft. Traditionally, the bark of cat’s claw is used to treat arthritis, bursitis, and intestinal disorders. The active ingredients appear to be polyphenols (flavonoids, proanthocyanidins, and tannins), alkaloids, and sterols. Various studies indicate that this Peruvian herb induces a generalized reduction in proinflammatory mediators.

Side effects may include nausea, although it has shown an impressive protective effect on indomethacin-induced enteritis in laboratory studies.  In general, toxicity and side effects are considered minimal. Two case reports of acute renal failure in a patient with lupus erythematosus have been recorded. Cat’s claw can be consumed as a tea (1000 mg root bark to 8 oz water), or as a dry, standardized extract in a capsule (20-60 mg daily).

Capsicum annum is a small spreading shrub which was originally cultivated in the tropical regions of the Americas but is now grown throughout the world, including the US. The small red fruit commonly used to accentuate chili owes its stinging pungency to the chemical, capsaicin. This was isolated by chemists more than a century ago and constitutes approximately 12% of the chili pepper. This fruit has been used for various medicinal purposes by the native peoples of the American tropics for hundreds of years.

Capsaicin can cause a burning sensation when it comes in contact with human flesh, and also in the digestive tract. This herb is rarely used alone but is generally mixed into other natural anti-arthritic preparations. There are topical capsaicin formulations now available to treat post-herpetic neuralgia. Other uses have been studied for peripheral neuropathies and chronic musculoskeletal pain.