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Life Extension Magazine November 2011

Krill Oil Optimizes Multimodal Arthritis Control

By Jason Ramirez
Krill Oil Optimizes Multimodal Arthritis Control

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

Rapid Relief from Joint Pain

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.

Exciting Findings in Animal Studies

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).

TABLE 1. Krill Oil Progressively Improves WOMAC Arthritis Scores1

Study Day

Improvement in Pain

Improvement in Stiffness

Improvement in Function

7 29% 20% 23%
14 26% 26% 29%
30 38% 39% 36%

Improvements in arthritis scores were progressive in krill oil-supplemented patients, showing significant gains at each successive day of evaluation.

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 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

Krill Oil and Fish Oil: Different Mechanisms, Greater Benefit

Krill oil and fish oil are both healthful marine oils from ocean-dwelling animals. Both are rich in the beneficial fats known as omega-3 fatty acids, and both fight inflammation in your body.

What distinguishes krill oil from fish oil? Why is it essential for some people to supplement with both?

Despite their apparent similarities, there are three important differences between these two marine oil products, differences that you need to understand in order to optimize your fight against dangerous inflammatory processes.

  1. The first point of differentiation is intended benefit and dosage. Fish oil is widely recognized for promoting cardiovascular health and favorably affecting blood lipids. Fish oil taken in sufficient doses lowers triglycerides and favorably modifies other vascular risk factors such as small, dense LDL.17-20 Optimal doses for most people of EPA is 1,400 mg and DHA is 1,000 mg. Krill oil also provides EPA and DHA (in the phospholipid forms), but it does not provide them in levels high enough for optimal cardiovascular protection.
  2. The second point of differentiation is the site of action of the two marine oils. Fish oils favorably modulate inflammatory cytokines circulating in the blood, thereby reducing total body inflammation (that’s in part how they exert their beneficial cardiovascular effects).21 Krill oil, on the other hand, has beneficial effects locally in the joint. In one study, krill oil, but not fish oil, reduced 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.16 In that same study, fish oil, but not krill oil, modulated blood levels of inflammatory cytokines. This study provides a neat picture of the complementary nature of these two marine oils.
  3. Purified fish oil concentrates are a more cost-effective way of obtaining high doses of EPA/DHA required to protect against a wide range of degenerative disorders. Just 300 mg a day of krill oil has been shown to relieve joint pain, whereas 2,400 mg of EPA/DHA are needed each day to provide the systemic benefits of EPA and DHA omega-3s. For comparison, one would need to take approximately 30 softgels containing about 300 mg of krill oil to obtain similar amounts of DHA as found in just two purified and concentrated fish oil softgels.

Taken together, these three important points of distinction explain why it’s essential to continue supplementation with high-dose fish oil to maintain optimal cardioprotection and generalized protection from inflammation and to add krill oil to manage pain and prevent joint destruction.

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 Adds Anti-Inflammatory Potency

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

What You Need to Know: Krill Oil
  • Conventional medicine has failed to effectively alleviate arthritis symptoms.
  • Available treatments do not safely inhibit pro-inflammatory factors in the body, including specific proteins, cell-signaling molecules, enzymes, and immune cells.
  • Krill oil suppresses the activity of C-reactive protein, a contributor to arthritic inflammation, by as much as 50%.
  • 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 reported a 55% pain reduction in under three months, with 63% entirely pain-free.

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).

TABLE 2. Advanced Krill Oil Formulation Superior to Standard Therapy Alone2


Drop in WOMAC Score

Drop in VAS Score

Study Day Krill Oil Glucosamine/Chondroitin Krill Oil Glucosamine/Chondroitin  
7 N/A N/A 17% 11%


14 35% 20% 29% 19%  
28 44% 31% 39% 32%  
56 55% 35% 55% 35%  

Percent drop in pain scores using standard WOMAC and patient-driven Visual Analogue Scale scales for subjects receiving advanced krill oil formula or standard glucosamine/chondroitin therapy.

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.

How Astaxanthin Suppresses Inflammatory Fires

Astaxanthin is a natural carotenoid with anti-inflammatory benefits. It acts by at least four distinct mechanisms.35

First it reduces oxidant-provoked cell death35 and mitochondrial dysfunction,42 two basic triggers of inflammation. Astaxanthin then enhances natural cellular antioxidant function and decreases formation of reactive oxygen species (ROS) and their lipid oxidation byproducts, both additional inflammation triggers.35

Astaxanthin also suppresses activity of caspase-3,35 a protein necessary to produce the cell death by apoptosis that is a feature of osteoarthritis.43 Finally, astaxanthin reduces release of inflammatory cytokines such as IL-1, IL-6, and TNF-alpha.35


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.

If you have any questions on the scientific content of this article, please call a Life Extension® Health Advisor at


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