Autoimmune disease occurs when the immune system attacks self-molecules due to a breakdown of immunologic tolerance.¹ Although our scientific understanding of autoimmunity continues to evolve, both T helper 17 (Th17) and Th1 cells appear to play a role in the induction of organ-specific autoimmune disease,² including multiple sclerosis (MS)³ and Hashimoto’s thyroiditis.^4,5 Th17 cells orchestrate tissue inflammation by inducing pro-inflammatory cytokines (interleukin [IL]-6, IL-1 and tumour necrosis factor-alpha [TNF-α]) and chemokines that recruit Th1 cells to the target tissue.²

Inflammatory bowel disease (IBD) was originally thought to be primarily mediated by Th1 cells in Crohn’s disease or Th2 cells in ulcerative colitis, but it is now known that Th17 cells and their related cytokines are crucial mediators in both conditions.⁶ Additionally, Th17 cells are found to be present in the inflamed synovial tissue of patients with rheumatoid arthritis (RA) and have been associated with clinical parameters, such as disease activity score-28 (DAS-28), C-reactive protein (CRP) levels and presence of anti-citrullinated protein antibodies (ACPAs).^7,8 Other human evidence places Th17 in the midst of the inflammatory reaction in systemic lupus erythematous (SLE),⁹ supporting the theory that Th17 plays an important role both localised and systemic autoimmune conditions.

Although functional regulatory T cells (Tregs) also accumulate in the target tissue, they are not entirely effective due to the overwhelming amounts of pro-inflammatory cytokines that protect effector T cells from the suppressive effects of Treg cells.² Therefore, inhibiting Th17 cell function, enhancing Tregs and controlling tissue inflammation may provide the most effective approach to managing autoimmune disease, from development to progression.

Vitamin D¹⁰ and omega-3¹¹ have both been shown to promote Treg function while inhibiting Th17 and Th1 cell function. As such, the immunomodulatory effects of vitamin D (Figure 1) and omega-3s (Figure 2) make them ideal for preventing the immune dysregulation that incites autoimmune disease.

Figure 1. Immunomodulatory Effects of Vitamin D on Immune Cells¹²

Abbreviations: cluster of differentiation (CD), dendritic cell (DC), interferon gamma (IFN-γ), immunoglobulin (Ig), interleukin (IL), major histocompatibility complex class II (MHC II), natural killer (NK), natural killer T (NKT), T helper (Th), tumour necrosis factor-alpha (TNF-α), regulatory T cell (Treg)

Figure 2. Immunomodulatory Effects of Omega-3s on Immune Cells¹³

Abbreviations: immunoglobulin (Ig), T helper (Th), regulatory T cell (Treg)

The VITAL Trial

A randomised, double-blind, placebo-controlled trial, the VITAL trial, investigated whether vitamin D and omega-3s could reduce autoimmune disease risk.¹⁴ It involved 25,871 participants (mean age 67.1 years) who self-reported incidence of autoimmune diseases from baseline to a median of 5.3 years follow-up. Incidence was confirmed by extensive medical record review. The trial showed that vitamin D3 supplementation (2000 IU/day), with or without omega-3 fatty acids (1000 mg/day as fish oil, containing 460 mg of EPA and 380 mg of DHA), reduced autoimmune disease by 22%. Omega-3 fatty acid supplementation, with or without vitamin D, reduced the autoimmune disease rate by 15% (not statistically significant). However, when participants with probable autoimmune disease were included, omega-3 fatty acid supplementation reduced the rate by 18% compared with placebo and a significant interaction was found with time (p=0.04).

Subgroup analysis confirmed that those of a lower body mass index (BMI) seemed to benefit more from vitamin D treatment (p=0.02), and that those with a family history of autoimmune disease benefitted more from omega-3 fatty acids (p=0.03).¹⁴ The VITAL trial confirms that both vitamin D and omega-3s are important long-term nutritional considerations for the prevention of autoimmune disease.

Supportive Evidence From Data on Omega-3 Intake and Vitamin D Status

Moderate consumption of omega-3 rich oily fish has been associated with a reduced risk of RA in women,¹⁵ as well as lower concentrations of thyroid antibodies in pregnant women.¹⁶ Fatty fish intake has also been associated with decreased occurrence of MS.¹⁷

Various meta-analyses have consistently show negative or inverse associations between vitamin D status and autoimmune diseases, inclusive of correlations between vitamin D levels and Crohn’s disease severity,¹⁸ SLE risk and disease activity,¹⁹ RA risk and disease activity,²⁰ and disability in MS.²¹

Vitamin D and Omega-3s – From Plate to Prescription

Dysregulation of the immune cells, particularly Th17, is implicated in the autoimmune disease process. Through their actions on Th17 cells and Tregs in particular, vitamin D and omega-3s are well suited for preventing and managing autoimmune diseases. Human evidence suggests that, whether taken as supplements or included within the diet, especially in the form of oily fish, long-term consumption of either or both nutrients can benefit those who are predisposed to or suffering from autoimmune diseases.

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