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Treatment of Joint Pain


We are going to deviate from the mechanical discussions of joint pain treatment. Usual topics such as physiotherapy, stretching, manipulation, etc… and instead we’re going to discuss what looks to be a remarkably inexpensive yet potentially valuable tool in combating joint pain and inflammation.


Far removed from today’s ultra-popular yet often little tested “health foods” and “supplements” this tool has undergone testing and research typically avoided by “natural substances” and we’ll be discussing those studies in just a little bit.


The tool I’m referring to is the “Omega-3 Essential Fatty Acids”


Fatty acids are a chain (of variable length) of carbon atoms that have a starting carboxyl group (-COOH). The ending carbon of the chain is known as the omega carbon. The ending omega carbon is also a methyl group, meaning it is bonded with three hydrogen atoms (-CH3).


There are four broad categories of fatty acids***:


(see the appendix of this issue for a detailed chemistry primer of fatty acids and their components)


Saturated


Monounsaturated


Omega-3 polyunsaturated


Omega-6 polyunsaturated


Essential For Human Health


Importantly, both omega-6 and omega-3 fatty acids are essential for human health, and our patient’s bodies do not have the ability to create them from other fatty acids.


Consequently, both omega-6 and omega-3 fatty acids must be consumed in the diet. Dietary deficiencies in either omega-6 or omega-3 fatty acids are deleterious to our patients health.


Additionally, the ratio of omega-6 to omega-3 fatty acids is critically important. “Historical estimates place the ratio of omega-6 to omega-3 oils at nearly 1:1 for prehistoric humans.”


The ratio of omega-6 to omega-3 fatty acids has changed dramatically due to the widespread use of vegetable oils (mostly n-6 fats) in cooking and foods.


By 1900, the ratio of omega-6 to omega-3 fatty acids had increased to about 4:1.


The current American ratio is about 25:1.


This “sharp rise is due to increased vegetable oil consumption: from 2 lb. per year in 1909 to 25 lb. per year in 1985!” (Mark Boswell and B. Eliot Cole, editors;American Academy of Pain Management Weiner’s Pain Management, A Practical Guide for Clinicians; Seventh Edition, 2006, pp.584-585.)


*(For the biological enzymatic processing of omega-6 fatty acids schematic see the appendix at the end of this issue)


A critically important aspect of essential fatty acid biology is…


The 20-carbon long omega-6 and omega-3 fatty acids are the precursors to a group of powerful but short-lived hormone-like compounds called “eicosanoids.”


One category of eicosanoids is referred to as “prostaglandins.”


Another group is referred to as “leukotrienes.”


Clinical applications of this biochemistry includes:


Arachidonic Acid (AA), the 20-carbon long omega-6 fatty acid is enzymatically converted into the eicosanoids called “series 2 prostaglandins,” such as “Prostaglandin E2 (PGE2),” by enzymes referred to as “cyclo-oxygenase” or “COX.”


Prostaglandin E2 is pro-inflammatory, which alters the threshold of the pain afferent neurons in the region, and patients experience increased pain.


Arachidonic Acid (AA), is also enzymatically converted into the eicosanoids called “series 4 leukotrienes,” such as “Leukotriene B4 (LTB4),” by enzymes referred to as “lipo-oxygenase” or “LOX.”


Leukotriene B4 is also pro-inflammatory, and patients experience increased pain.


Eicosapentaenoic acid (EPA), the 20-carbon long omega-3 fatty acid is enzymatically converted into the eicosanoids called “series 3 prostaglandins,” such as “Prostaglandin E3 (PGE3),” by the same cyclo-oxygenase (COX) enzymes that convert arachidonic acid into pro-inflammatory prostaglandin E2.




Historically, the conversion of arachidonic acid into pro-inflammatory prostaglandin E2 has been inhibited by utilization of nonsteroidal anti-inflammatory drugs (NSAIDs) that block the cyclo-oxygenase (COX) enzymes.


However, as noted in the article reviews below, long-term use of these drugs can cause problems in some patients.


Additionally, the article reviews below indicate that nonsteroidal anti-inflammatory drugs (NSAIDs) do not inhibit the lipo-oxygenase (LOX) pathway and therefore do not inhibit the formation of pro-inflammatory series 4 leukotrienes.


In contrast the omega-3 fatty acid Eicosapentaenoic acid (EPA) inhibits both cyclo-oxygenase (COX) and lipo-oxygenase (LOX) enzymes, reducing the production of both pro-inflammatory prostaglandin E2 and series 4 leukotrienes.




Pain:


“Omega-3 Fatty acids (fish oil) as an anti-inflammatory: an alternative to nonsteroidal anti-inflammatory drugs for discogenic pain”

Surgical Neurology 65 (April 2006) 326– 331 This paper won first prize in the poster competition at the American Association of Neurological Surgeons Annual Meeting, New Orleans, LA, April 2005


Joseph Charles Maroon, MD, Jeffrey W. Bost, PAC


These authors are from the


Department of Neurological Surgery, University of Pittsburgh Medical Center


FROM ABSTRACT:


Background:


The use of NSAID medications is a well-established effective therapy for both acute and chronic nonspecific neck and back pain.


Extreme complications, including gastric ulcers, bleeding, myocardial infarction, and even deaths, are associated with their use.


An alternative treatment with fewer side effects that also reduces the inflammatory response and thereby reduces pain is believed to be omega-3 EFAs found in fish oil.


We report our experience in a neurosurgical practice using fish oil supplements for pain relief.


Methods:


From March to June 2004, 250 patients who had been seen by a neurosurgeon and were found to have nonsurgical neck or back pain were asked to take a total of 1200 mg per day of omega-3 EFAs (eicosapentaenoic acid and decosahexaenoic acid) found in fish oil supplements.


Results:


78% were taking 1200 mg and 22% were taking 2400 mg of EFAs.


After an average of 75 days on fish oil:


59% discontinued to take their prescription NSAID medications for pain.


88% stated they were satisfied with their improvement and stated they would continue to take the fish oil.


There were no significant side effects reported.


Conclusions:


Our results mirror other controlled studies that compared ibuprofen and omega-3 EFAs demonstrating equivalent effects in reducing arthritic pain.


Omega-3 EFA fish oil supplements appear to be a safer alternative to NSAIDs for treatment of nonsurgical neck or back pain.


KEY POINTS FROM AUTHORS


Maroon & Bost from


Department of Neurological Surgery,


University of Pittsburgh Medical Center


1) The use of NSAIDs is associated with occasional extreme complications, including gastric ulcers, bleeding, myocardial infarction, stroke, and even death.


2) In this study, after 75 days on fish oil, 59% of patients who were taking NSAIDs for chronic spinal pain and who had degenerative spine disease, were able to discontinue their prescription NSAIDs, and 88% stated they were satisfied with their improvement and that they would continue to take the fish oil.


3) In this study, fish oil supplementation was not associated with any significant side effects.


4) “Omega-3 EFA fish oil supplements appear to be a safer alternative to NSAIDs for treatment of nonsurgical neck or back pain.”


5) “More than 70 million NSAID prescriptions are written each year, and 30 billion over-the-counter NSAID tablets are sold annually.”


6) “5% to 10% of the adult US population and approximately 14% of the elderly routinely use NSAIDs for pain control.”


7) Selling NSAIDs is a 9 billion dollar per year US industry.


8) Prescription NSAIDs for rheumatoid and osteoarthritis alone conservatively cause 16,500 deaths per year.


9) “NSAIDs are the most common cause of drug-related morbidity and mortality reported to the FDA and other regulatory agencies around the world.”


10) “The agent best documented by hundreds of references in the literature for its anti-inflammatory effects is omega-3 EFAs found in fish and in pharmaceutical-grade fish oil supplements.”


11) The beneficial anti-inflammatory affects of high-dose fish oil include the reduction of joint pain from rheumatoid and osteoarthritis, improvement in dry eyes and macular degeneration, reduced plaque formation, reduced arrhythmias, and reduced infarction from coronary arthrosclerosis.


12) COX-2 inhibitors significantly increase gastric and cardiovascular side effects.


13) Omega-3 EPA is used to make the anti-inflammatory eicosanoids (PGE3), whereas excess omega-6 EFAs form inflammatory arachidonic acid based eicosanoids (PGE2).


14) “Animal proteins, especially red meat, also contain an abundant amount of arachidonic acid.”


15) A deficiency in omega-3 fatty acids, especially EPA, will result in a deficiency of anti-inflammatory prostaglandins.


16) “To encourage the production of anti-inflammatory PGs and to discourage the production of inflammatory PGs, saturated fats, trans-fatty acids, and arachidonic acid should be reduced in the diet; blood glucose should be controlled; and appropriate amounts of omega-3 fatty acids found in fish oils should be consumed.”


17) Omega-3 supplementation is safe and effective for many inflammation-related conditions and has a low incidence of side effects.


18) “The US Department of Agriculture has limited fish consumption to 1 fish serving per week in adults and even less in children and pregnant women because of the concern of toxic contaminants such as mercury, polychlorinated biphenyls, and dioxin in our fish population.”


19) These authors did not recommend the fish oil for those on anticoagulants or fish-related allergies, but noted “aspirin use was not a contraindication.”

Fish oil:


what the prescriber needs to know Arthritis Research & Therapy Volume 8, Issue 1, 2006, pp. 402


Leslie G Cleland, Michael J James and Susanna M Proudman


FROM ABSTRACT:


There is a general belief among doctors, that patients with arthritis need nonsteroidal anti-inflammatory drugs (NSAIDs).


Implicit in this view is that these patients require the symptomatic relief provided by inhibiting synthesis of nociceptive prostaglandin E2, a downstream product of the enzyme cyclo-oxygenase (COX), which is inhibited by NSAIDs.


However, the concept of ‘safe’ NSAIDs has collapsed following a multiplicity of observations establishing increased risk for cardiovascular events associated with NSAID use, especially but not uniquely with the new COX-2-selective NSAIDs. This mandates greater parsimony in the use of these agents.


Fish oils contain a natural inhibitor of COX, reduce reliance on NSAIDs, and reduce cardiovascular risk through multiple mechanisms.


Fish oil thus warrants consideration as a component of therapy for arthritis, especially rheumatoid arthritis, in which its symptomatic benefits are well established.


A major barrier to the therapeutic use of fish oil in inflammatory diseases is ignorance of its mechanism, range of beneficial effects, safety profile, availability of suitable products, effective dose, latency of effects and instructions for administration. This review provides an evidence-based resource for doctors and patients who may choose to prescribe or take fish oil.


KEY POINTS FROM AUTHORS


Cleland, James & Proudman as Published in


Arthritis Research & Therapy


1) There is a general belief among doctors that patients with arthritis need nonsteroidal anti-inflammatory drugs (NSAIDs). This is because the pain of arthritis is primarily caused by PGE2, which is derived from the omega-6 fatty acid arachidonic acid through the activity of the enzyme COX. NSAIDs inhibit the COX enzyme.


2) However, NSAIDs increase the risk for cardiovascular events.


3) Fish oils contain a natural inhibitor of COX, reduce reliance on NSAIDs, and reduce cardiovascular risk.


4) Omega-6s (n6) and omega-3s (n3) are dietary essential fatty acids which cannot be synthesized endogenously.


5) Diets in industrialized Western countries are generally abundant in n6 PUFAs and poor in n3 PUFAs.


6) “Because Western diets are typically low in LC n3 PUFAs, substantial increases in tissue LC n3 can be achieved by taking a fish oil supplement.”


7) It is unlikely that one can consume the amount of fish required to achieve anti-inflammatory doses (minimum of 2.7 g/day) of LC n3 PUFAs.


8) “The conversion of C18 n3 PUFAs [such as flax oil] to C20 and C22 n3 PUFAs [fish oil] occurs relatively inefficiently in humans, and so vegetable sources of dietary n3 PUFAs alone fail to achieve the tissue levels seen with fish oil.”


9) “EPA [fish oil omega-3] is both an inhibitor of arachidonic acid metabolism and an alternate substrate for COX.”


10) “EPA [fish oil omega-3] also inhibits the metabolism of arachidonic acid into leukotriene B4 by LOX enzymes, which NSAIDs do not do. Consequently, EPA fish oil is superior to NSAIDs in creating an anti-inflammatory effect.”


11) “The anti-inflammatory dose of fish oil requires delivery of 2.7 g or more of long chain n3 PUFAs daily.” [Important]


12) A daily intake of less than 2.7 g eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) is “insufficient for an anti-inflammatory effect.”


13) Symptomatic improvement from fish oil supplementation can take 2–3 months, and “it is important that potential users understand that this delay exists.”


14) Patients should also reduce ingestion of n6 PUFA by substituting olive oil for vegetable oils.


15) “At anti-inflammatory doses, cod liver oils, which are rich in the fat-soluble vitamins A and D, contain more vitamin A than recommended intakes.” Vitamin A has been associated with reduced bone density and increased risk for hip fracture.


16) Vitamin A toxicity is not a problem with anti-inflammatory doses of fish body oils because they contain very little vitamin A.


17) “Fish oil (obtained from the body of the fish) is preferable to cod liver oil, which can deliver undesirable amounts of vitamin A at anti-inflammatory doses.”


18) “Within the Western context, fish oil supplements have not been associated with an increased bleeding tendency, even in patients taking aspirin or warfarin for antithrombotic effect.”


19) “Methylmercury is an industrial contaminant that accumulates in long-lived fish (e.g. swordfish, marlin, sea perch, shark).”


20) “Methylmercury is a neurotoxin that impairs neural development, especially in the foetus and infants.”


21) Fish consumption is associated with increased blood and urine mercury.


22) “Properly processed fish oils contain very little mercury.”


23) “Chlorinated biphenyls (PCBs) are byproducts of industrial synthesis of organic chemicals. They are structurally related to dioxins and are potentially toxic.”


24) PCBs are poorly biodegradable and they accumulate in the land and marine food chains.


25) Polybrominated biphenyl (PBB) fire retardants are similar to PCBs.


26) “Halogenated biphenyls can be removed from fish oils by molecular distillation and should be present at low levels in good quality products.”


27) “In a medical environment in which messages molded by pharmaceutical interests stress the ‘need’ for NSAIDs, prescribers should consider the NSAID-sparing effects, the lack of serious side effects and the positive health benefits of fish oil.”


“A meta-analysis of the analgesic effects of omega-3 polyunsaturated fatty acid supplementation for inflammatory joint pain” Pain… May 2007, 129(1-2), pp. 210-223


Robert J. Goldberg and Joel Katz


Abbreviations:


ALA Alpha-linolenic acid


18 carbon long omega-3 plant fatty acid


EPA Eicosapentaenoic acid


20 carbon long omega-3 fish fatty acid


DHA Docosahexaenoic acid


22 carbon long omega-3 fish fatty acid


LA Linoleic acid