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The effect of fish oil versus krill oil intervention on clinical symptoms and cardiometabolic risk factors in patients with major depressive disorder: A randomized placebo-controlled double-blind trial.

  • 2025-07
  • Journal of affective disorders 380
    • Murat Açik
    • Funda Pınar Çakiroğlu
    • Atilla Tekin
    • Aslı Egeli

Study Design

Type
Randomized Controlled Trial (RCT)
Sample size
n = 57
Population
57 adults diagnosed with MDD
Methods
randomized study, allocated to receive krill-oil (520 mg EPA + DHA), fish-oil (600 mg EPA + DHA), or a placebo (soybean-oil) daily for 8 weeks
Duration
8 weeks

Background

This study aimed to compare the effects of krill- and fish-oil interventions on clinical symptoms and metabolic risk factors in individuals with MDD.

Methods

In this randomized study, 57 adults diagnosed with MDD were allocated to receive krill-oil (520 mg EPA + DHA), fish-oil (600 mg EPA + DHA), or a placebo (soybean-oil) daily for 8 weeks. Anthropometric measurements, depression anxiety stress-21 (DASS-21) scale, and Hamilton depression rating scale (HDRS) were performed at baseline and 4 and 8 weeks. In addition, venous blood samples were collected at baseline and post-intervention to evaluate lipid and glycemic profiles, including fasting glucose, HbA1c, cholesterol, triglycerides, LDL-c, and HDL-c levels.SPSS and R Studio software programs were used for statistical analysis.

Results

A total of 50 participants completed the study, with 17 in each intervention group and 16 in the placebo. The mean HDRS scores decreased significantly in both the krill-oil (8.5 ± 1.2) and fish-oil groups (10.0 ± 1.2) compared to the placebo (p < 0.001), indicating clinical symptom improvement. Furthermore, the interaction effect of group-by-time was found to be statistically significant (η2p = 0.273;ptime×group < 0.001). Anxiety and distress scores decreased to similar levels after the post-intervention compared to baseline in krill- and fish-oil groups. Krill- and fish-oil supplementation increased plasma HDL-c and uric acid levels, but the group-by-time interaction effect was only observed at the HDL-c level (η2p = 0.238;ptime×group = 0.002). The mean HbA1c rates and plasma triglyceride levels of krill-oil recipients were lower after the post-intervention.

Conclusion

Krill- and fish-oil could be considered as a safe and effective adjuvant treatments for depression. However, there was no evidence of apparent superiority over each other.

Research Insights

  • Fish Oil→Increased High-Density Lipoprotein Cholesterol

    Krill- and fish-oil supplementation increased plasma HDL-c and uric acid levels, but the group-by-time interaction effect was only observed at the HDL-c level (η2p = 0.238; p_time×group = 0.002).

    Effect
    Beneficial
    Effect size
    Small
    Dose
    600 mg EPA + DHA daily
  • Fish Oil→Increased Uric Acid

    Krill- and fish-oil supplementation increased plasma HDL-c and uric acid levels, but the group-by-time interaction effect was only observed at the HDL-c level

    Effect
    Neutral
    Effect size
    Small
    Dose
    600 mg EPA + DHA daily
  • Fish Oil→Reduced Anxiety

    Anxiety and distress scores decreased to similar levels after the post-intervention compared to baseline in krill- and fish-oil groups.

    Effect
    Beneficial
    Effect size
    Moderate
    Dose
    600 mg EPA + DHA daily
  • Fish Oil→Reduced Blood Cholesterol

    Venous blood samples were collected...to evaluate...cholesterol... (No significant effect reported for this outcome)

    Effect
    Neutral
    Effect size
    Small
    Dose
    600 mg EPA + DHA daily
  • Fish Oil→Reduced Depression Symptoms

    The mean HDRS scores decreased significantly in both the krill-oil (8.5 ± 1.2) and fish-oil groups (10.0 ± 1.2) compared to the placebo (p < 0.001)

    Effect
    Beneficial
    Effect size
    Large
    Dose
    600 mg EPA + DHA daily
  • Fish Oil→Reduced Distress Symptoms

    Anxiety and distress scores decreased to similar levels after the post-intervention compared to baseline in krill- and fish-oil groups.

    Effect
    Beneficial
    Effect size
    Moderate
    Dose
    600 mg EPA + DHA daily
  • Fish Oil→Reduced Fasting Glucose

    Venous blood samples were collected...to evaluate...fasting glucose... (No significant effect reported for this outcome for either intervention)

    Effect
    Neutral
    Effect size
    Small
    Dose
    600 mg EPA + DHA daily
  • Fish Oil→Reduced Hemoglobin A1c

    The mean HbA1c rates and plasma triglyceride levels of krill-oil recipients were lower after the post-intervention. (No significant change reported for fish oil on these outcomes)

    Effect
    Neutral
    Effect size
    Small
    Dose
    600 mg EPA + DHA daily
  • Fish Oil→Reduced LDL Cholesterol

    Venous blood samples were collected...to evaluate...LDL-c... (No significant effect reported for this outcome)

    Effect
    Neutral
    Effect size
    Small
    Dose
    600 mg EPA + DHA daily
  • Fish Oil→Reduced Triglyceride Levels

    The mean HbA1c rates and plasma triglyceride levels of krill-oil recipients were lower after the post-intervention. (No significant change reported for fish oil on these outcomes)

    Effect
    Neutral
    Effect size
    Small
    Dose
    600 mg EPA + DHA daily
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