Krill oil may be beneficial for osteoarthritis Original paper

Osteoarthritis is a health condition resulting from a degradation of articular cartilage, a type of connective tissue in joints that separates bones and creates a smooth surface on which they can move. As this cartilage wears down, adjacent bones rub together, resulting in joint pain, stiffness, and reduced mobility, with commonly affected areas being the knees, hands, and hips.

A healthy knee vs. a knee with osteoarthritis

Although osteoarthritis has historically been considered to be the result of mechanical stress (i.e., wear and tear), there is growing evidence that inflammatory processes may also be an important driver of the disease.^[1][2] As a result, there is interest in strategies capable of inhibiting such inflammation.

One intervention that could be helpful for this purpose is supplementation with the long-chain fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) because these fatty acids exhibit some anti-inflammatory effects.^[3] Although fish oil is a common source of EPA and DHA, krill oil seems to contain these fats in a more bioavailable form (i.e., more of the molecules exist as phospholipids instead of triglycerides).^[4] Additionally, krill oil contains astaxanthin, a red-orange pigment molecule with proposed, though not well-studied, anti-inflammatory effects.^[5]

This 6-month randomized controlled trial (RCT) examined the effect of krill oil supplementation on joint pain in 235 people (ages 40–65) with osteoarthritis of the knee. The participants were assigned to take either 4 grams of krill oil (supplying 600 mg of EPA, 280 mg of DHA, and 450 μg of astaxanthin) or a placebo daily. None of the participants had severe osteoarthritis according to X-ray analysis.

The primary outcome was knee pain, assessed using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) questionnaire. Secondary outcomes included knee joint stiffness (assessed using WOMAC) and physical function of the knee (assessed using WOMAC), serum lipids, inflammatory markers (i.e., hsCRP, TNF-a, and IL-6), omega-3 index (the percentage of EPA+DHA in red blood cell lipid membranes), and adverse effects. The outcomes were assessed after 3 months and 6 months.

Additionally, because krill oil is hypothesized to benefit osteoarthritis by reducing inflammation, an exploratory analysis was performed to assess the effect of krill oil on knee pain according to inflammatory status. Specifically, participants were categorized as having levels of hsCRP (a marker of inflammation) that were low (less than 1 mg/L), medium (1–3 mg/L), or high (more than 3 mg/L).

Knee pain, knee stiffness, and physical function of the knee all improved in the krill oil group compared to the placebo group at 6 months, but not at 3 months. The percent changes in knee parameters after 6 months were as follows (decreases indicate improvement):

• Knee pain: −44% (krill oil), −30% (placebo),
• Knee stiffness: −41% (krill oil), −23% (placebo)
• Knee physical function: −40% (krill oil), −26% (placebo)

In subgroup analysis, krill oil improved knee pain compared to placebo among participants with high inflammation, whereas there was no clear reduction in pain in participants with medium and low inflammation.

Krill oil did not affect any of the inflammatory markers. Additionally, hsCRP levels were not affected by krill oil regardless of baseline hsCRP levels.

Krill oil resulted in a relative increase in the omega-3 index of +3.11% after 3 months and +3.22% after 6 months compared to the placebo group. The omega-3 index in the krill oil group was 6.0% at baseline, 8.9% at 3 months, and 9% at 6 months.

The krill oil group had higher fasting glucose levels after both 3 and 6 months, high LDL levels after 3 months, and lower uric acid after 6 months compared to the placebo group. Adverse events did not different between groups. Use of nonsteroidal anti-inflammatory drugs (NSAIDs) did not differ between groups.

Swisse Wellness Pty Ltd., a supplement company that sells krill oil supplements, funded and helped design and implement this study.

The krill oil group experienced increases in glucose and LDL (the latter transiently) and a decrease in uric acid. These findings were part of a very large number of secondary analyses, meaning that they are likely to have been chance findings. Additionally, the changes seen were fairly small.

The study claims the krill oil supplement provided 450 mg of astaxanthin, but this appears to be a typo, and the intended value was 450 μg. This is because 450 mg is far more astaxanthin than is naturally found in krill oil, and online information about the specific supplement used indicates it would have instead provided close to 450 μg of astaxanthin.

A few other clinical trials of note have also looked at whether marine oils can improve either osteoarthritis or knee pain in general:

• A 16-week RCT from 2020 assessed the effects of fish oil among older people with osteoarthritis and overweight or obesity.^[6] A total of 41% of participants reported pain predominantly in the knees. Compared to placebo, the fish oil supplement (supplying 2,000 mg of DHA and 400 mg of EPA per day) led to improvements in both chronic and present pain intensity.

• A 30-day RCT from 2016 looked at the effects of krill oil (supplying 240 mg of EPA and 110 mg of DHA per day) among 50 people with knee pain.^[7] Compared to a placebo, krill oil supplementation improved knee pain and knee range of motion. Of note, CRP levels at the start of the study were low (less than 1 mg/L) in all but two participants. The participants in this trial were not necessarily diagnosed with osteoarthritis.

• The findings of a 2-year RCT from 2016 suggest that more isn’t always better when it comes to omega-3s for osteoarthritis. In the trial, 202 people (average age of 61) with knee osteoarthritis were assigned to take fish oil in either a low dose (450 mg of EPA+DHA) or high dose (4,500 mg of EPA+DHA). Both groups experienced improvements in knee pain and function during the trial, compared to the start of the trial, but these improvements were actually greater in the low-dose fish oil group, though the difference between groups was very small.

A commonly proposed mechanism by which krill oil, and omega-3s in general, benefit osteoarthritis is by reducing inflammation. It’s therefore notable that in the trial under review, supplementation with krill oil did not lower any of the assessed inflammatory markers (hsCRP, IL-6, and TNF-a). At first glance, this could mean that any benefits are unrelated to inflammation. However, it’s also possible that omega-3s alter different inflammatory pathways than those assessed. Other inflammation-related molecules both implicated in osteoarthritis and potentially reduced by omega-3s include prostaglandin E2 (PGE2), leukotriene B4 (LTB4), and matrix metalloproteinases (MMPs).^[8] Alternatively, one RCT found that improvements in osteoarthritis pain from supplementation with fish oil were correlated with improvements in a marker of blood vessel (specifically small artery) function.^[6]

An important consideration is whether the effects of krill oil on knee parameters were clinically, rather than just statistically, significant. A common way to assess this is to determine the minimum clinically important difference (MCID), a measure of the smallest improvement an individual would consider both noticeable and important. Previous research has estimated that the MCID for osteoarthritis is around 17% for pain, 10% for stiffness, and 12% for physical function.^[9] This trial found that, on average, krill oil improved pain by 14%, improved stiffness by about 18%, and improved physical function by 14% compared to placebo after 6 months of supplementation.

Finally, krill oil can be compared to NSAIDs, which are commonly taken to manage pain due to osteoarthritis. In terms of percent pain improvements, the effects of krill oil after 6 months appear to be similar to daily use of either celecoxib,^[10][11][12] ibuprofen,^[13][14][15] or naproxen.^[16][17] However, these comparisons between NSAIDs and krill oil should be viewed with caution because existing NSAID trials typically involved participants who were older and had higher levels of pain.