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

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Abstract

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.

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Acknowledgments

We acknowledge PNKDIET, SLU, Spain, for providing free of charge the diet of the ketogenic phases in both groups and oral supplementation of DHA or placebo.

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Authors and Affiliations

  1. Department of Endocrinology and Nutrition, School of Medicine, Center of Investigation of Endocrinology and Nutrition, Hospital Clinico Universitario Valladolid, University of Valladolid, C/los perales 16, 47130, Simancas, Spain

    Daniel de Luis & Olatz Izaola

  2. Department of Biochemistry and Molecular Biology, School of Biology, University of Barcelona, Barcelona, Spain

    Joan Carles Domingo

  3. Division of Endocrinology, Department of Medicine, Complejo Hospitalario Universitario de Santiago, Santiago de Compostela University and CIBER Fisiopatología Nutrición y Obesidad, Santiago De Compostela, Spain

    Felipe F. Casanueva

  4. Division of Endocrinology, Complejo Hospitalario Universitario de Ferrol and Coruña University, Ferrol, Spain

    Diego Bellido

  5. Medical Department Pronokal Group, PronokalGroup, Barcelona, Spain

    Ignacio Sajoux

Authors
  1. Daniel de Luis
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  2. Joan Carles Domingo
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  3. Olatz Izaola
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  4. Felipe F. Casanueva
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  5. Diego Bellido
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Correspondence to Daniel de Luis.

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Glossary

12-HETE

15-Hydroxyicosatetraenoic acid

12-LOX

12-Lipoxygenase

14-HDOHE

14-Hydroxy docosahexaenoic acid

14-HDHA

14-Hydroxy docosahexaenoic acid

15-HETE

15-Hydroxyicosatetraenoic acid

15-LOX

12-Lipoxygenase

17-HDOHE

17-Hydroxy docosahexaenoic acid

17-HDHA

17-Hydroxy docosahexaenoic acid

4-HDOHE

4-Hydroxy docosahexaenoic acid

4-HDHA

4-Hydroxy docosahexaenoic acid

5-HETE

5-Hydroxyicosatetraenoic acid

5-LOX

5-Lipoxygenase

7-HDOHE

7-Hydroxy docosahexaenoic acid

7-HDHA

7-Hydroxy docosahexaenoic acid

7RMAR1

Nuclear matrix-associated protein RMAR1

7SMAR1

Nuclear matrix-associated protein SMAR1

8-HETE

8-Hydroxyicosatetraenoic acid

AA

Arachidonic acid

ADO

Available data only

AIFAI

Anti-inflammatory fatty acid index

ANCOVA

Analysis of covariance

BHT

Butylhydroxytoluene

BMI

Body mass index

CHOL

Cholesterol

COX

Cyclooxygenase

CRP

C-reactive protein

DHA

Docosahexaenoic acid

DPA

Docosapentaenoic acid

EPA

Eicosapentaenoic acid

FAME

Fatty acid methyl ester

GCMS

Gas chromatograph/mass spectrometer

HDL

High-density lipoprotein

HOMA-IR

Homeostatic model assessment of insulin resistance

HPLC

High-performance liquid chromatography

IL6

Interleukin 6

K2-EDTA

K2-Ethylenediaminetetraacetic acid

LC

Liquid chromatography

LDL

Low-density lipoprotein

LM

Lipid mediators

LOX

Lipoxygenase

LTB4

Leukotriene B4

MAR1

Nuclear matrix-associated protein MAR1

MS

Mass spectrometry

MUFA

Monounsaturated fatty acid

NS

Not significant

PD1

Programmed cell death protein 1

PGE2

Prostaglandin E2

PnK

Pronokal

PUFA

Polyunsaturated fatty acid

RBC

Red blood cell

RVD2

7(S), 16(R), 17(S)-resolvin D2

SD

Standard deviation

SFA

Saturated fatty acid

SPM

Proresolution lipid mediators

TNF

Tumor necrosis factor

TXB2

T-box transcription factor

VLKD

Very low-calorie ketogenic diet

WC

Waist circumference

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de Luis, D., Domingo, J.C., Izaola, O. et al. Effect of DHA supplementation in a very low-calorie ketogenic diet in the treatment of obesity: a randomized clinical trial. Endocrine 54, 111–122 (2016). https://doi.org/10.1007/s12020-016-0964-z

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  • DOI: https://doi.org/10.1007/s12020-016-0964-z

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