Many thanks to Dr. Rhonda Donahue for this great research!
Eicosatetraenoic Acid & Stearidonic Acid
Omega-3 fatty acids are now well-known inflammation fighters. Controlled clinical trials clearly show that they fight inflammation, reducing and in some cases eliminating the need for anti-inflammatory drugs with their disturbing short- and long-term side effects. Both omega-3 fatty acids, and nearly all anti- inflammatory drugs, work through their effects on a group of local, cellular “hormones” called eicosanoids.
Eicosanoids are messengers that cells use to communicate with one another, coordinating their activities. Some (“bad”) eicosanoids promote inflammation, while other (“good”) eicosanoids have potent anti-inflammatory functions. Thus, the body’s inflammatory response rests in large part on the balance of “good” and “bad” eicosanoids produced by your cells when they hear the immune system’s inflammatory call.
“Bad” eicosanoids are made from an omega-6 fatty acid called arachidonic acid. Most drug approaches to inflammation, from aspirin and the older NSAIDs (Non-Steroidal Anti-Inflammatory Drugs, like ibuprofen) to the new “COX-2 inhibitor” drugs, like celecoxib [Celebrex®] and rofecoxib [Vioxx®]), work by inhibiting the formation of the series-2 prostanoid group of “bad” eicosanoids. Prostanoids are formed from arachidonic acid by an enzyme called cyclooxygenase, or COX. (AA).
But while these drugs certainly provide symptomatic relief in the short term, COX-2 inhibitors can actually accelerate the underlying inflammatory disease in the long term, by diverting arachidonic acid into another, slower-acting, and ultimately more destructive pathway: the lipoxygenase (LOX) enzyme pathway, which produces the ravaging series-4 leukotrienes. Leukotrienes are the eicosanoids released by immune cells involved in the body’s inflammatory responses, and are more responsible for the long-term consequences of inflammation, which can result when a deranged immune system attacks the very body that it was designed to defend.
Therefore, blocking the COX pathway alone results in an imbalance – an imbalance that ultimately trades short-term gain for long-term pain. What people suffering with autoimmune disorders most need is a “dual pathway inhibitor:” a molecule which will shut down COX-2 and LOX alike, preventing the formation of all “bad” eicosanoids.
Transnational pharmaceutical giants are racing to create such drugs. But Nature is already waiting for them at the finish line, with two rare omega-3 fatty acids.
Introducing ETA and SDA
Eicosatetraenoic acid (ETA) and its precursor stearidonic acid (SDA), are omega-3 fatty acids you probably haven’t heard much about. Because ETA and SDA are so rare in food sources, there’s been little study of their role in the effects of diet on chronic disease (unlike eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are commonly found in fatty fish and in regular fish-oil supplements).
While ETA is very rare in the normal Western diet, it is found in significant amounts in the fatty acids of the green-lipped mussel (Perna canaliculus). Many early studies in humans and animals found that crude extracts of Perna were effective in reducing inflammation, and in relieving the symptoms of rheumatoid and osteoarthritis – but other studies found no effect.
The reason, as later studies confirmed, was that the anti-inflammatory properties of the green-lipped mussel were due to their content of SDA and ETA. Most green-lipped mussel supplements are not stable fatty acid extracts, but are crude concentrates or are based on mucopolysaccharides. When seven commercially-available green mussel products were put to the test by comparing them with a stable fatty extract rich in ETA and SDA, the fatty acid extract revealed strong anti-inflammatory powers, while the other extracts were found to vary wildly in strength. Great variations were even revealed in different batches of the same product.
More tellingly, when the inflammation-fighting powers of a stable ETA- and SDA-rich extract were compared with crude P. canaliculus extracts whose fatty acid content had been deliberately removed, the fatty acid extract of the mussel exhibited potent anti-inflammatory effects, while the ETA-depleted preparation was found to be completely ineffective.
ETA and SDA Top the Omega- 3’s
Two direct comparison studies have been performed in animals to compare the anti-inflammatory effects of the ETA- and SDA-rich oil of P. canaliculus against those of salmon, cod liver, flaxseed, and two mixed fish oils. These studies clearly show that the ETA- and SDA-rich fatty acid extract of P. canaliculus is far superior to other omega-3 sources at quenching the fires of inflammation, giving more potent anti- inflammatory benefits at significantly lower doses.
Using the series of tests discussed above, ETA/SDA supplementation lowered arthritis scores by 4213% to 7515%, versus 0 to 31% using conventional omega-3 sources. Likewise, rear paw swelling was reduced by 96-98% by the ETA/SDA-rich oil, while swelling was only lowered by 7 to 38% with common omega-3s! These results are all the more remarkable because the dose of ETA/SDA-rich P. canaliculus oil was only about 1% of that used for the standard omega-3 oils.
Another recent study tested the effects of these novel fatty acids in a rat model of arthritis. After 15 days of administering omega-3 fatty acid extracts from P. canaliculus, rear paw swelling was significantly reduced by 34% and fore paw inflammation by 60%. Deterioration in total body condition was reduced by 52% compared to controls. The extract also decreased inflammatory response in the spleen, and it had a 35-70% inhibition of leukotriene metabolites. Serum levels of the inflammatory biomarker ceruloplasmin were reduced compared to control mice, indicating a less severe disease state. Interestingly, the fatty acids had comparable potency to the known anti-inflammatory agent piroxicam. The fatty acid extract had no adverse side effects. These results suggest a potential benefit not only in rheumatoid arthritis, but also in other inflammatory diseases such as psoriasis, asthma and cardiovascular disease.
A New Human Trial
In a new randomized, double-blind, controlled trial involving rheumatoid and osteoarthritis sufferers, significant improvements were reported in morning stiffness and measures of joint functionality during the double-blinded phase among rheumatoid arthritis sufferers taking the SDA/ETA- rich oil; further, night pain was “much improved” in 40% of subjects, and vanished in an additional 26.7%. Improvements were also seen in some patients’ grip strength and overall visual-scale pain scores, but these results were not found statistically meaningful. Assessment by doctors and patients concluded that 73% of the persons with rheumatoid arthritis had experienced a good response – including 20% who became completely symptom-free by the end of the double-blind phase. The results were similar in the osteoarthritis victims.
Similar results have been reported in an unpublished pilot trial and in case reports. A double-blind, placebo-controlled trial vouches for the benefits of an SDA- and ETA-rich fatty acid supplement in bronchial asthma, and testimonial accounts and animal studies suggest benefits in premenstrual syndrome as well.
How Does It Work?
Why does the SDA- and ETA-rich oil of Perna canaliculus so remarkably outperform other omega-3s? The anti-inflammatory powers of all omega-3 fatty acids are grounded in biochemistry: the omega-3s’ ability to bind up key enzymes involved in making “bad” eicosanoids. And as studies show, ETA, and SDA working through it, more potently prevent the formation of both types of “bad” eicosanoids: series-2 prostanoids and series-4 leukotrienes. Mechanisms are believed to include:
- A stronger ability to tie up delta-5 desaturase, the enzyme that forms arachidonic acid.
- Indirectly increasing the production of the “good” eicosanoids from DGLA. ETA’s close chemical resemblance to arachidonic acid, leading to stronger tying up of the LOX enzyme.
In addition to these advantages, SDA and ETA share anti-inflammatory mechanisms that are common to all omega-3 fatty acids. Thus, ETA and SDA are natural COX-2 inhibitors. Remarkably, omega-3s accomplish this feat not only because their natural metabolites bind up COX-2, but also by actually working at the gene level to reduce the production of COX-2 from the DNA code. And SDA/ETA block the formation of inflammatory cytokines (immune system messenger chemicals) such as tumor necrosis factor alpha (TNF-alpha) and interleukin-1 (IL-1).
Revolutionary new painkillers – such as etanercept (Enbrel®) are so effective because they target TNF-alpha. ETA/SDA-based omega-3 supplements are an orthomolecular revolution, providing powerful support against inflammation in ways that other natural supplements can’t match. The biochemistry explains the results seen in animal studies and clinical trials. But only you can experience them … for yourself.
Sing M, Hodges LD, Wright PFA, Cheah DMY, Wynne PM, Kalafatis N and Macrides TA. The CO2-SFE crude lipid extract and the free fatty acid extract from Perna canaliculs have anti-inflammatory effects on adjuvant-induced arthritis in rats. Comparative Biochemistry and Physiology. 2008;Part B 149:251-258.
Gibson SL, Gibson RG. The treatment of arthritis with a lipid extract of Perna canaliculus: a randomized trial. Compl Ther Med. 1998; 6: 122-6.
Macrides TA, Treschow AP, Kalafatis N, Wright PF, Wynne PM. The anti-inflammatory effects of n-3 tetraenoic fatty acids isolated from a lipid extract from the mussel, Perna canaliculus. Prostaglandins Leukot Essent Fatty Acids. 1997 Aug; 57(2): 250(Abs W20).
Whitehouse MW, Macrides TA, Kalafatis N, Betts W, Haynes DR, Broadbent J. Anti-inflammatory activity of a lipid fraction (Lyprinin) from the NZ green-lipped mussel. Inflammopharmacol. 1997; 5(3): 237-46.
Brien S, Prescott P, Coghlan B, Bashir N, Lewith G. Systematic review of the nutritional supplement Perna Canaliculus (green-lipped mussel) in the treatment of osteoarthritis. QJM. 2008 Mar;101(3):167-79. Epub 2008 Jan 25. Review.
Darlington LG, Stone TW. Antioxidants and fatty acids in the amelioration of rheumatoid arthritis and related disorders. Br J Nutr. 2001 Mar; 85(3): 251-69.
Moxxor Contains All 18 Omega-3’s The names of the Omega-3’s found in MOXXOR are as follows:
- Alpha -Linolenic Acid
- Stearidonic Acid
- Eicosatrienoic Acid
- Eicosatetraenoic Acid (2 forms)
- Eicopentaenoic Acid (4 forms)
- Docosapentaenoic Acid (2 forms)
- Docosahexaenoic Acid (3 forms)
- Tetrocosapentaenoic Acid (2 forms)
- Tetracosaheexaenoic Acid (2 forms)