Krill Oil Optimizes Multimodal Arthritis Control
By Jason Ramirez
If you or someone you know suffers arthritic pain and swelling, you’re aware that conventional medicine has largely failed to offer long-term relief.
The reason for this failure is simple.
To date, the preferred interventions—drugs, exercise, heat cold therapy, joint protection, and physiotherapy treatment—do not effectively and safely target the pro-inflammatory factors behind arthritis.
Chief among these factors are destructive molecules synthesized by the aging body that attack joint tissue. This activity must be suppressed in order to eliminate arthritis symptoms.
Emerging data suggest that fatty acids from small shrimp-like organisms called krill act in synergy with other natural anti-inflammatory compounds such as omega-3 fish oils.
New data indicate krill may help treat arthritic joint tissue by neutralizing pro-inflammatory activity.
In a group of aging individuals inflicted with arthritic pain, 300 mg per day of krill oil alone slashed pro-inflammatory C-reactive protein activity in half after just one month.1
In a separate study of krill oil combined with hyaluronic acid and astaxanthin—both of which target pro-inflammatory agents in the body—arthritis patients reported a 55% pain reduction in under three months, with 63% entirely pain-free!2
Krill are among the most populous animal species on the planet.3 Tiny, shrimp-like crustaceans, krill flourish in the frigid waters of the Antarctic Ocean.3,4 Because the temperature in that salty environment hovers near the freezing point of fresh water, krill evolved a way to keep their cell membranes fluid.
Unlike long-chain polyunsaturated fatty acids from other animal sources, a high proportion of krill oil fats are found in a form known as phospholipids, which may help explain their unique function in the joints.4
Rapid Relief from Joint Pain
Osteoarthritis (OA) is the leading cause of joint pain and disability in middle-aged and elderly people.5,6 Osteoarthritis is characterized by progressive loss of joint cartilage that eventually leads to degradation of many important components of the joint.5 Unchecked, osteoarthritis progresses to greater degrees of inflammation and the release of destructive enzymes that literally tear the joint apart.5,7
To date, no drug therapy has proved effective at slowing or reversing joint damage in osteoarthritis.6,8 Natural compounds like glucosamine and chondroitin have shown some benefit at relieving symptoms, especially in patients with moderate to severe disease.8,9
Glucosamine and chondroitin help protect cartilage from further damage.10 Used over the long term, they can restore joint cartilage to a more youthful state, increasing its pressure resistance and naturally high elasticity.10 Laboratory and clinical studies show glucosamine and chondroitin can modify, stabilize, retard, or even help reverse the joint damage in osteoarthritis.10,11
But arthritic joints need more than structural repair. They need something to slow or even stop the inflammatory processes that steadily destroy their cartilage. Marine oils such as those from fish and krill, rich in omega-3 fatty acids, offer exceptional anti-inflammatory protection. One study showed that adding the omega-3s EPA and DHA from marine oils to a glucosamine supplement produced superior pain relief compared with the glucosamine supplement alone.12
So why not simply supplement with fish oil along with your regular joint health supplements? Fish oils, after all, lower levels of inflammatory cytokines throughout the body. They also provide major cardiovascular benefits, as is well known.13,14
It turns out that there are subtle but important differences. Both fish oil and krill oil increase blood levels of omega-3s at about the same rate, which is good.15 But krill oil is superior at protecting joint cartilage from inflammatory damage, while fish oils are better at suppressing the circulating inflammatory cytokines that cause cardiovascular disease.14,16
So those with arthritic concerns should continue using fish oil to support heart health and add a lower dose of krill oil to manage joint pain, as we’ll now see.
Exciting Findings in Animal Studies
Animal models of experimentally induced arthritis have provided the first supportive data on the value of krill oil as a powerful and safe joint-targeted anti-inflammatory agent.
Arthritis-prone mice were fed diets supplemented with fish oil (known to have anti-inflammatory effects), krill oil, or placebo.22 The placebo group of the control-fed mice all developed arthritis by day 60.22 Fifty-seven percent of the control animals suffered such severe inflammation that they died.
By contrast, the mice fed fish oil or krill oil demonstrated much milder disease, which progressed much more slowly. By day 54, only 15% of the krill oil group had detectable arthritis, compared with 43% of controls.22 Clinical arthritis scores were significantly lower in the krill oil group throughout, while fish oil-supplemented mice had lower scores only on about half of the days when scores were measured.
Those mice that were fed the special fish oil diet significantly reduced their arthritis scores and paw swelling early in the study, but the krill oil group saw significant relief during the later phase. In addition, the krill oil–supplemented group had lower amounts of infiltration of inflammatory white blood cells into the joint and its lining, an important measure of arthritis severity.
Interestingly, the krill oil-supplemented animals had no changes in serum pro-inflammatory cytokines such as interleukin-1 beta, a dangerous cell-signaling molecule involved in a host of degenerative diseases. That meant that the anti-inflammatory effects and reduction in joint symptoms were attributable to a different mechanism than what is commonly seen with fish oil supplementation, in which inflammatory cytokine levels drop dramatically.23-25
This is a highly significant result: it demonstrates how krill oil works in synergy with fish oil to attack inflammation on multiple levels and optimize arthritis control. Based on his study, supplementing with both of these natural products (krill and fish oil) provides the best opportunity to combat inflammation on multiple levels and maximize joint and total body benefits.
Potent Anti-Arthritis Effects Observed in Humans
Human studies of krill oil in arthritis and other joint-health conditions are even more compelling.
In one study, the effect of a krill oil extract on patients with arthritis and chronic inflammation was evaluated.1
One group received 300 mg/day of krill oil, and the other group received placebo. At days 7, 14, and 30, C-reactive protein (CRP, a measure of inflammation) and the widely used WOMAC arthritis score were determined.
The WOMAC score assesses levels of pain and stiffness in patients with osteoarthritis. After just 7 days of supplementation, CRP was significantly reduced by 19.3% in the krill-supplemented group, while it rose by 15.7% in the placebo group.1 CRP dropped an additional 30% and 31% at days 14 and 30, respectively, in the krill arm of the study, while it rose by 32% at day 14 in the placebo group.
Of greater clinical significance for the arthritis sufferers, WOMAC severity scores dropped significantly on all three parameters: pain, stiffness, and functional impairment.1 These improvements were not just temporary, but were sustained, with patients continuing to experience greater relief at each time point. No significant improvements were seen in the placebo recipients (See table 1 below).
In breaking news, a second, still more compelling clinical trial has just been completed, with an even more effective krill oil formulation.2 The new formulation contains several valuable additional ingredients along with purified krill oil. Together, these compounds were found to augment krill oil’s clinical effectiveness in treating joint pain.
Hyaluronic Acid Blocks Cartilage Destruction
Hyaluronic acid (HA) is a naturally occurring polysaccharide that is a major component of joint and connective tissue.26 In joints, its natural function is to lubricate and cushion the joint lining from repeated impacts and microscopic trauma.27 It is also involved in wound repair and regeneration.26
Hyaluronic acid fights arthritis via multiple mechanisms, most notably by inhibiting the enzyme MMP-13, which is a key element in the joint destruction seen in osteoarthritis.7 MMP-13 (which stands for matrix metalloproteinase-13) dissolves cartilage, leaving the joint space unprotected and vulnerable to friction and traumatic injury.5,28 By inhibiting MMP-13, hyaluronic acid quenches the joint degradation and slows the painful and destructive progress of arthritis.7
Hyaluronic acid is now in widespread clinical use for treatment of knee osteoarthritis, where it is administered by direct injection into the joint.27,29,30 Recent studies have demonstrated significant improvement in arthritis sufferers’ quality of life when hyaluronic acid from natural sources is administered orally.29
One potential problem with orally administered hyaluronic acid is bioavailability. Hyaluronic acid is a very large molecule that is not readily absorbed from the intestinal tract by itself, limiting how much is available to help heal damaged joint tissues.26 But when hyaluronic acid is provided in a mixture rich in phospholipids, as found in krill oil, absorption is markedly improved, with blood levels significantly exceeding those obtained when hyaluronic acid is administered alone.31
Astaxanthin Adds Anti-Inflammatory Potency
A second additional component of a new joint health formulation is astaxanthin, a naturally occurring carotenoid pigment found abundantly in ocean-dwelling algae.32 Krill avidly consume these algae and accumulate high concentrations of astaxanthin. Unfortunately, standard processing practices destroy astaxanthin, depleting it from the finished krill oil product.3,4 However, this new formulation of krill and hyaluronic acid is further enriched with natural astaxanthin to maximize its therapeutic effect and enhance its stability.2
Astaxanthin is a powerful antioxidant and natural anti-inflammatory agent.4,32,33 It is widely studied for its beneficial effects on chronic inflammatory conditions such as arthritis.32,34
Astaxanthin exerts its anti-inflammatory effects via multiple pathways, always an important plus for natural supplements over single-targeted drugs. First, its antioxidant powers reduce levels of tissue oxidation that lead to inflammation.35,36 Astaxanthin also downregulates production and activity of several enzymes that manufacture inflammatory cytokines.36,37 Importantly, astaxanthin also reduces inducible nitric oxide synthase (iNOS), which is known to be an important inflammatory trigger in osteoarthritis.37,38
Astaxanthin has additional, direct benefits on joint health. It inhibits apoptosis, the programmed cell death that underlies many chronic, inflammatory diseases.39 Apoptosis is a significant cause of cartilage loss in osteoarthritis.40,41 And like hyaluronic acid, astaxanthin inhibits the destructive enzyme MMP-13, thereby preventing the joint degradation seen in osteoarthritis.28
Clinical Benefits Accrue from Natural Krill Oil Formulation
A new, multi-component, multi-targeted krill oil formulation with hyaluronic acid and astaxanthin has proven benefits on joint health. In a recently completed clinical trial, the formulation was compared with both a placebo and a “positive control” consisting of a glucosamine/chondroitin supplement.2 Two separate measures of joint pain were used, the standard WOMAC score, and also a patient-driven Visual Analogue Scale to maximize validity. A total of 107 people with joint pain completed the study in June, 2011.
The results were impressive.
WOMAC scores measured on days 14, 28, and 56 of the study demonstrated a progressive drop in pain severity.2 When the effect of the placebo was controlled for, the krill oil formulation vividly outperformed the glucosamine/chondroitin positive control as well, achieving a 55% reduction in WOMAC pain score reduction by day 56 (See table 2 below).
Particularly impressive was the proportion of subjects who became entirely pain-free, attaining a WOMAC score of less than 10. A total of 63% of subjects reached this milestone by the end of the study.2 And an impressive 30% were pain-free already by day 14.
Scores on the Visual Analogue Scale measurement showed strikingly similar improvements, decreasing in a linear fashion from day 7 through day 56 (Table 2). A total of 68% of subjects reported themselves to be pain-free by the end of the study, consistent with the WOMAC scores.
Statistical analysis of the mean WOMAC and Visual Analogue Scale pain scores further demonstrated the superiority of the advanced krill oil formulation. The krill oil-supplemented group had a significantly higher mean treatment effect than either the glucosamine/chondroitin group or the placebo group.2
In conclusion, the krill oil supplement, enhanced with hyaluronic acid, astaxanthin, and additional antioxidant stabilizers proved clinically superior, not only to a placebo control, but to an active glucosamine/chondroitin supplement. The beneficial effects grew linearly, continuing to increase over time right up until the study’s termination at 8 weeks. With two-thirds of the multi-supplemented (krill oil-hyaluronic acid-astaxanthin) patients attaining a pain-free status in that time period, this advanced triple ingredient formula has much to offer for those suffering from debilitating joint pain.
Conventional medicine has failed to effectively alleviate arthritis symptoms because the available treatments do not safely inhibit pro-inflammatory factors in the body.
Krill oil reduces infiltration of inflammatory cells into the joint and joint-lining tissues, a vital effect in reducing the pain, swelling, and loss of function in arthritis. Hyaluronic acid and astaxanthin operate via distinct but similar mechanisms to suppress pro-inflammatory agents.
In a study combining krill oil with hyaluronic acid and astaxanthin, subjects in the active group reported a 55% pain reduction in less than three months, with 63% entirely pain-free.
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1. Deutsch L. Evaluation of the effect of Neptune Krill Oil on chronic inflammation and arthritic symptoms. J Am Coll Nutr. 2007 Feb;26(1):39-48.
2. Valensa. FlexPro MD Clinical Trial Overview and Results. (Data on File.) 2011.
3. Tou JC, Jaczynski J, Chen YC. Krill for human consumption: nutritional value and potential health benefits. Nutr Rev. 2007 Feb;65(2):63-77.
4. Krill oil. Monograph. Altern Med Rev. 2010 Apr;15(1):84-6.
5. Li NG, Shi ZH, Tang YP, et al. New hope for the treatment of osteoarthritis through selective inhibition of MMP-13. Curr Med Chem. 2011;18(7):977-1001.
6. Sawitzke AD, Shi H, Finco MF, et al. Clinical efficacy and safety of glucosamine, chondroitin sulphate, their combination, celecoxib or placebo taken to treat osteoarthritis of the knee: 2-year results from GAIT. Ann Rheum Dis. 2010 Aug;69(8):1459-64.
7. Campo GM, Avenoso A, Nastasi G, et al. Hyaluronan reduces inflammation in experimental arthritis by modulating TLR-2 and TLR-4 cartilage expression. Biochim Biophys Acta. 2011 Sep;1812(9):1170-81.
8. Sawitzke AD, Shi H, Finco MF, et al. The effect of glucosamine and/or chondroitin sulfate on the progression of knee osteoarthritis: a report from the glucosamine/chondroitin arthritis intervention trial. Arthritis Rheum. 2008 Oct;58(10):3183-91.
9. Clegg DO, Reda DJ, Harris CL, et al. Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. N Engl J Med. 2006 Feb 23;354(8):795-808.
10. Jerosch J. Effects of glucosamine and chondroitin sulfate on cartilage metabolism in OA: outlook on other nutrient partners especially omega-3 fatty acids. Int J Rheumatol. 2011;2011:969012.
11. Kamarul T, Ab-Rahim S, Tumin M, Selvaratnam L, Ahmad TS. A preliminary study of the effects of glucosamine sulphate and chondroitin sulphate on surgically treated and untreated focal cartilage damage. Eur Cell Mater. 2011;21:259-71; discussion 70-1.
12. Gruenwald J, Petzold E, Busch R, Petzold HP, Graubaum HJ. Effect of glucosamine sulfate with or without omega-3 fatty acids in patients with osteoarthritis. Adv Ther. 2009 Sep;26(9):858-71.
13. Abeywardena MY, Patten GS. Role of omega-3 longchain polyunsaturated fatty acids in reducing cardio-metabolic risk factors. Endocr Metab Immune Disord Drug Targets. 2011 Sep 1;11(3):232-46.
14. Kalogeropoulos N, Panagiotakos DB, Pitsavos C, et al. Unsaturated fatty acids are inversely associated and n-6/n-3 ratios are positively related to inflammation and coagulation markers in plasma of apparently healthy adults. Clin Chim Acta. 2010 Apr 2;411(7-8):584-91.
15. Ulven SM, Kirkhus B, Lamglait A, et al. Metabolic effects of krill oil are essentially similar to those of fish oil but at lower dose of EPA and DHA, in healthy volunteers. Lipids. 2011 Jan;46(1):37-46.
16. Ierna M, Kerr A, Scales H, Berge K, Griinari M. Supplementation of diet with krill oil protects against experimental rheumatoid arthritis. BMC Musculoskelet Disord. 2010;11:136.
17. Griffin BA. The effect of n-3 fatty acids on low density lipoprotein subfractions. Lipids. 2001;36 Suppl:S91-7.
18. Kelley DS, Siegel D, Vemuri M, Mackey BE. Docosahexaenoic acid supplementation improves fasting and postprandial lipid profiles in hypertriglyceridemic men. Am J Clin Nutr. 2007 Aug;86(2):324-33.
19. Sanchez-Muniz FJ, Bastida S, Viejo JM, Terpstra AH. Small supplements of N-3 fatty acids change serum low density lipoprotein composition by decreasing phospholid and apolipoprotein B concentrations in young adult women. Eur J Nutr. 1999 Feb;38(1):20-7.
20. Cottin SC, Sanders TA, Hall WL. The differential effects of EPA and DHA on cardiovascular risk factors. Proc Nutr Soc. 2011 May;70(2):215-31.
21. Duda MK, O’Shea KM, Tintinu A, et al. Fish oil, but not flaxseed oil, decreases inflammation and prevents pressure overload-induced cardiac dysfunction. Cardiovasc Res. 2009 Feb 1;81(2):319-27.
22. Ierna M, Kerr A, Scales H, Berge K, Griinari M. Supplementation of diet with krill oil protects against experimental rheumatoid arthritis. BMC Musculoskelet Disord. 2010;11:136.
23. James M, Proudman S, Cleland L. Fish oil and rheumatoid arthritis: past, present and future. Proc Nutr Soc. 2010 Aug;69(3):316-23.
24. Kolahi S, Ghorbanihaghjo A, Alizadeh S, et al. Fish oil supplementation decreases serum soluble receptor activator of nuclear factor-kappa B ligand/osteoprotegerin ratio in female patients with rheumatoid arthritis. Clin Biochem. 2010 Apr;43(6):576-80.
25. Wann AK, Mistry J, Blain EJ, Michael-Titus AT, Knight MM. Eicosapentaenoic acid and docosahexaenoic acid reduce interleukin-1beta-mediated cartilage degradation. Arthritis Res Ther. 2010;12(6):R207.
26. Volpi N, Schiller J, Stern R, Soltes L. Role, metabolism, chemical modifications and applications of hyaluronan. Curr Med Chem. 2009;16(14):1718-45.
27. Altman RD. Status of hyaluronan supplementation therapy in osteoarthritis. Curr Rheumatol Rep. 2003 Feb;5(1):7-14.
28. Bikadi Z, Hazai E, Zsila F, Lockwood SF. Molecular modeling of non-covalent binding of homochiral (3S,3’S)-astaxanthin to matrix metalloproteinase-13 (MMP-13). Bioorg Med Chem. 2006 Aug 15;14(16):5451-8.
29. Kalman DS, Heimer M, Valdeon A, Schwartz H, Sheldon E. Effect of a natural extract of chicken combs with a high content of hyaluronic acid (Hyal-Joint) on pain relief and quality of life in subjects with knee osteoarthritis: a pilot randomized double-blind placebo-controlled trial. Nutr J. 2008;7:3.
30. Petrella RJ. Hyaluronic acid for the treatment of knee osteoarthritis: long-term outcomes from a naturalistic primary care experience. Am J Phys Med Rehabil. 2005 Apr;84(4):278-83; quiz 84, 93.
31. Huang SL, Ling PX, Zhang TM. Oral absorption of hyaluronic acid and phospholipids complexes in rats. World J Gastroenterol. 2007 Feb 14;13(6):945-9.
32. Yuan JP, Peng J, Yin K, Wang JH. Potential health-promoting effects of astaxanthin: a high-value carotenoid mostly from microalgae. Mol Nutr Food Res. 2011 Jan;55(1):150-65.
33. Serebruany V, Malinin A, Goodin T, Pashkow F. The in vitro effects of Xancor, a synthetic astaxanthine derivative, on hemostatic biomarkers in aspirin-naive and aspirin-treated subjects with multiple risk factors for vascular disease. Am J Ther. 2010 Mar-Apr;17(2):125-32.
34. Nakao R, Nelson OL, Park JS, Mathison BD, Thompson PA, Chew BP. Effect of astaxanthin supplementation on inflammation and cardiac function in BALB/c mice. Anticancer Res. 2010 Jul;30(7):2721-5.
35. Chan KC, Mong MC, Yin MC. Antioxidative and anti-inflammatory neuroprotective effects of astaxanthin and canthaxanthin in nerve growth factor differentiated PC12 cells. J Food Sci. 2009 Sep;74(7):H225-31.
36. Kim YJ, Kim YA, Yokozawa T. Protection against oxidative stress, inflammation, and apoptosis of high-glucose-exposed proximal tubular epithelial cells by astaxanthin. J Agric Food Chem. 2009 Oct 14;57(19):8793-7.
37. Choi SK, Park YS, Choi DK, Chang HI. Effects of astaxanthin on the production of NO and the expression of COX-2 and iNOS in LPS-stimulated BV2 microglial cells. J Microbiol Biotechnol. 2008 Dec;18(12):1990-6.
38. Schmidt N, Pautz A, Art J, et al. Transcriptional and post-transcriptional regulation of iNOS expression in human chondrocytes. Biochem Pharmacol. 2010 Mar 1;79(5):722-32.
39. Kim JH, Choi W, Lee JH, et al. Astaxanthin inhibits H2O2-mediated apoptotic cell death in mouse neural progenitor cells via modulation of P38 and MEK signaling pathways. J Microbiol Biotechnol. 2009 Nov;19(11):1355-63.
40. van den Berg WB. Osteoarthritis year 2010 in review: pathomechanisms. Osteoarthritis Cartilage. 2011 Apr;19(4):338-41.
41. Zamli Z, Sharif M. Chondrocyte apoptosis: a cause or consequence of osteoarthritis? Int J Rheum Dis. 2011 May;14(2):159-66.
42. Wolf AM, Asoh S, Hiranuma H, et al. Astaxanthin protects mitochondrial redox state and functional integrity against oxidative stress. J Nutr Biochem. 2010 May;21(5):381-9.
43. Thomas CM, Fuller CJ, Whittles CE, Sharif M. Chondrocyte death by apoptosis is associated with the initiation and severity of articular cartilage degradation. Int J Rheum Dis. 2011 May;14(2):191-8.