Effect of DHA supplementation in a very low-calorie ketogenic diet in the treatment of obesity: a randomized clinical trial

Endocrine. 2016 Oct;54(1):111-122. doi: 10.1007/s12020-016-0964-z. Epub 2016 Apr 27.


A VLCK diet supplemented with DHA, commercially available, was tested against an isocaloric VLCK diet without DHA. The main purpose of this study was to compare the effect of DHA supplementation in classic cardiovascular risk factors, adipokine levels, and inflammation-resolving eicosanoids. A total of obese patients were randomized into two groups: a group supplemented with DHA (n = 14) (PnK-DHA group) versus a group with an isocaloric diet free of supplementation (n = 15) (control group). The follow-up period was 6 months. The average weight loss after 6 months of treatment was 20.36 ± 5.02 kg in control group and 19.74 ± 5.10 kg in PnK-DHA group, without statistical differences between both groups. The VLCK diets induced a significant change in some of the biological parameters, such as insulin, HOMA-IR, triglycerides, LDL cholesterol, C-reactive protein, resistin, TNF alpha, and leptin. Following DHA supplementation, the DHA-derived oxylipins were significantly increased in the intervention group. The ratio of proresolution/proinflammatory lipid markers was increased in plasma of the intervention group over the entire study. Similarly, the mean ratios of AA/EPA and AA/DHA in erythrocyte membranes were dramatically reduced in the PnK-DHA group and the anti-inflammatory fatty acid index (AIFAI) was consistently increased after the DHA treatment (p < 0.05). The present study demonstrated that a very low-calorie ketogenic diet supplemented with DHA was significantly superior in the anti-inflammatory effect, without statistical differences in weight loss and metabolic improvement.

Keywords: DHA; Ketosis; PnK method; Pronokal method; Protein diet; Weight loss.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Blood Glucose
  • Caloric Restriction*
  • Diet, Ketogenic*
  • Dietary Supplements*
  • Docosahexaenoic Acids / therapeutic use*
  • Female
  • Humans
  • Insulin / blood
  • Insulin Resistance / physiology
  • Lipids / blood
  • Male
  • Middle Aged
  • Obesity / diet therapy*
  • Treatment Outcome
  • Triglycerides / blood


  • Blood Glucose
  • Insulin
  • Lipids
  • Triglycerides
  • Docosahexaenoic Acids