Summary
Systemic lupus erythematosus is an autoimmune disease, meaning that the immune system mistakenly starts to target tissues and organs as if they are pathogens. Because of this, tissues and organs such as skin, blood vessels, lungs and kidneys can become severely damaged. The anti-inflammatory nature of Omega-3 fatty acids and their metabolites have sparked interest in their potential beneficial role in lupus. Indeed, research shows that Omega-3 fatty acids EPA and DHA have positive effects in people with this disease, with regard to levels of inflammation as well as quality of life.
 
Introduction
Systemic lupus erythematosus (SLE) is the most prevalent form of the four kinds of lupus, affecting 20 to 150 people per 100.000. Lupus is a chronic autoimmune disease, meaning that the body’s own immune system malfunctions and starts targeting certain organs or tissues, causing damage and impairing healthy functioning. Commonly affected tissues and organs are the skin, musculoskeletal system, cardiovascular system, central nervous system, lungs and kidneys. In brief, certain cells of our immune system (B cells and T cells) normally scan for pathogens (such as viruses or bacteria) and start an inflammatory reaction once they find these pathogens. Antibodies are then produced against these specific pathogens, so that the immune system can recognize and dispose of them. In SLE, our B and T cells can lose their ability to differentiate between pathogens and some of our own cells. Because of this, the B and T cells can start an inflammatory reaction and produce antibodies against our own cells, telling our immune system to target and dispose of them. This faulty immune reaction can occur in response to many different cell types, causing unique symptom profiles that can greatly vary per patient. For example, when the skin is affected, symptoms commonly include rashes, alopecia (causing hair loss) and sores. When the central nervous system is affected, symptoms such as cognitive impairment, depression and headaches can occur. On top of this, persons with lupus typically alternate between periods of remission and flare-ups, during which fatigue, fever and weight loss are commonly reported. These flare-ups can be caused by triggers such as intense sun exposure or viral infections, but can also occur without any clear causative factor. Taken together, these factors can make (early) diagnosis very difficult.
Risk factors for SLE include sex (women are affected more often), age, racial/ethnic background and presence of autoimmune diseases in a person’s family. Even with improved modern techniques for early detection and treatment, SLE has 10-year mortality rate of 10%. Moreover, the quality of life for SLE patients is negatively affected not only during flare-ups, but due to (permanent) organ damage as well. Up to half of SLE patients develop lupus nephritis (LN), a condition wherein inflammation in the kidneys causes a severe decrease in kidney function, which has a relatively high mortality rate. Additionally, common comorbidities in persons with SLE are atherosclerosis (plaque buildup in blood vessels, causing them to thicken and narrow) and coronary artery disease (a condition wherein blood vessels supplying oxygen to the heart muscles are damaged). It has been speculated that drugs commonly given to treat SLE such as glucocorticosteroids are risk factors for development of these cardiovascular conditions. Thus, it is clear that more approaches to provide adequate disease management are required.
As inflammation plays a central role in the disease process of SLE, it only makes sense that the role of Omega-3 fatty acids in SLE have been investigated, due to their anti-inflammatory properties. Both observational and intervention studies have been carried out to clarify what role Omega-3 fatty acids such as EPA and DHA play in SLE; results from these studies point towards positive effects in terms of countering inflammation, vascular health and quality of life.
 
Research findings
Researchers of the Karolinska institute in Sweden set out to establish the links between intake of Omega-3 fatty acids, SLE disease severity and atherosclerosis (Elkan et al. 2012). They recruited 114 adult patients with SLE and 122 healthy individuals matched on basis of age and sex. In the SLE group, the researchers assessed disease activity by means of the Systemic Lupus Activity Measure (SLAM) scoring system and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Organ damage in the SLE group was determined according to the Systemic Lupus International Collaborating Clinics damage index. Blood samples were taken to examine markers of inflammation and cardiovascular health. Abdominal fat samples were collected to assess fatty acid composition, including Omega-3 fatty acids. Scans of arteries in the neck were made to assess presence of plaques as indicator of atherosclerosis levels.  Finally, by means of a food frequency questionnaire, the dietary intake of, amongst others, Omega-3 fatty acids EPA and DHA was assessed in both groups. Strikingly, it was found that the SLE group consumed less polyunsaturated fatty acids than the control group, including (anti-inflammatory) Omega-3 and (pro-inflammatory) Omega-6 fatty acids. As expected, higher levels of dietary intake of DHA and EPA were associated with higher levels of DHA and EPA in abdominal fat samples in both groups. Interestingly, the researchers reported that higher levels DHA in abdominal fat samples were associated with lower SLE disease activity, according to both the SLAM and SLEDAI scoring system. The same was true for EPA, though only for the SLEDAI scoring system. Then, looking at the plaques in neck arteries, the researchers found that SLE patients had higher occurrence of plaques than their control counterparts. In agreement with their findings on EPA and DHA and SLE disease activity, the researchers reported that SLE patients with higher levels of EPA and DHA in their abdominal fat samples showed less plaques in their neck arteries. Accordingly, higher levels of abdominal fat EPA and DHA in SLE patients were correlated with higher levels of ApoA1 in blood samples, which is a protective marker against atherosclerosis. No associations between abdominal fat levels of EPA or DHA and the SLE index organ damage scores were found, though higher levels of (pro-inflammatory) Omega-6 fatty acids in these samples were associated with more damage. Overall, these researchers provided convincing evidence for the positive role of EPA and DHA dietary intake with regard to SLE disease activity and atherosclerosis.
 
In a study by Lozovoy and collaborators, the effects of supplementation of EPA and DHA on SLE disease activity were investigated in a group of 62 SLE patients (Lozovoy et al. 2015). Forty-one of these patients received 180mg EPA and 120mg DHA for a period of 4 months, the remaining 21 served as a control and did not receive any supplementation. At the start and end of the supplementation period, SLE activity was scored in all patients using the aforementioned SLEDAI. It was found that only in the group receiving EPA and DHA supplementation, a significant decrease in SLE activity occurred after 4 months. Moreover, the supplementation group showed higher levels of adiponectin and lower levels of leptin in their blood plasma. Adiponectin is a hormone that promotes fat breakdown for energy, leptin is a hormone that stimulates feeling hungry and increases when the body’s fat stores are decreasing. This indicates that the supplementation with EPA and DHA had a positive effect on the fat metabolism and SLE disease activity in SLE patients.
 
Salmon and colleagues investigated the Omega-3 index and the effects of krill oil concentrate supplementation in SLE patients (Salmon et al. 2024). The Omega-3 index is a measurement of the incorporation of the Omega-3 fatty acids DHA and EPA into cell membranes; the active compounds of krill oil concentrate are DHA and EPA. A group of 64 men and women with SLE were selected to receive daily supplementation for a period of 24 weeks in a double-blind clinical trial. Participants received either krill oil concentrate capsules (772mg EPA & 384mg DHA, 30 participants) or a vegetable oil capsules (placebo group, 34 participants). Throughout the study, the Omega-3 index was measured for all participants every 4 weeks. The treatment group showed a strong increase in their Omega-3 index during the 24 week supplementation period. In contrast, the placebo group showed no differences in their Omega-3 index. The SLE disease activity index was used to assess SLE activity at 4, 8, 16 and 24 weeks. Compared to the baseline, SLE patients with high disease activity showed a decrease in their indexed SLE activity scores at every measurement period, though the 24 week point was just shy of reaching statistical significance. This effect was not seen in the placebo group or in patients in the supplementation group with low SLE disease activity index scores at baseline.
 
Conclusion
Despite modern detection and treatment methods, up to 10% of persons with SLE die within 10 years after their diagnosis. Furthermore, patients can experience a severe drop in quality of life due to re-occurring disease flare-ups, but also due to (permanent) organ damage and poor cardiovascular health. Clinical studies have shown that supplementation of EPA and DHA brings about several positive health effects in SLE patients. Adequate intake of DHA and EPA is associated with a healthy  Omega-3 index and associated positive effects on cardiovascular health markers, as well as SLE disease activity. The studies discussed above emphasize the significant role that EPA and DHA can play in managing SLE. These findings highlight the potential for Omega-3 supplementation to be incorporated as part of the therapeutic approach to managing SLE. However, further research is needed to fully understand the long-term benefits and optimal dosages of Omega-3 fatty acids for SLE patients, particularly in relation to organ damage and cardiovascular health.
 
References
Elkan, A. C., C. Anania, T. Gustafsson, T. Jogestrand, I. Hafström, and J. Frostegård. 2012. ‘Diet and Fatty Acid Pattern among Patients with SLE: Associations with Disease Activity, Blood Lipids and Atherosclerosis’. Lupus 21(13):1405–11. doi: 10.1177/0961203312458471.

Lozovoy, Marcell Alysson Batisti, Andréa Name Colado Simão, Helena Kaminami Morimoto, Bruna Miglioranza Scavuzzi, Tathiana Veiga Mayumi Iriyoda, Edna Maria Vissoci Reiche, Rubens Cecchini, and Isaias Dichi. 2015. ‘Fish Oil N-3 Fatty Acids Increase Adiponectin and Decrease Leptin Levels in Patients with Systemic Lupus Erythematosus’. Marine Drugs 13(2):1071–83. doi: 10.3390/md13021071.

Salmon, Jane, Daniel J. Wallace, Violeta Rus, Addison Cox, Claire Dykas, Brooke Williams, Yunpeng Ding, Petter-Arnt Hals, Line Johnsen, and Peter E. Lipsky. 2024. ‘Correction of Omega-3 Fatty Acid Deficiency and Improvement in Disease Activity in Patients with Systemic Lupus Erythematosus Treated with Krill Oil Concentrate: A Multicentre, Randomised, Double-Blind, Placebo-Controlled Trial’. Lupus Science & Medicine 11(2):e001201. doi: 10.1136/lupus-2024-001201.