Krill Oil and Metformin in Women With PCOS and Metabolically Unhealthy Obesity

NCT07604870 | Completed Phase 2

• 1 other identifier: FU_MAcik_PCOS_KO_2023
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

This open-label, randomized, parallel-group pilot trial investigated the effects of krill oil, metformin, and their combination on adipokine profiles, cardiometabolic risk markers, and serum fatty acid composition in women with polycystic ovary syndrome (PCOS) and metabolically unhealthy obesity (MUO). Eligible women aged 19-40 years with PCOS according to Rotterdam criteria and MUO based on combined NCEP ATP-III/IDF criteria were allocated to three 8-week interventions: continuation of standard metformin therapy (MET), krill oil supplementation alone (KO), or metformin plus krill oil (METKO). Metformin users were stratified and randomized 1:1 to MET or METKO, while metformin-naive participants were assigned to KO. Krill oil (Superba Boost, Aker BioMarine) was administered at 2,000 mg/day (approximately 400 mg EPA and 240 mg DHA) and metformin at 1,000 mg/day. Primary outcomes were changes in serum adiponectin and neuregulin-4 (NRG-4) measured by ELISA. Secondary outcomes included anthropometric indices, fasting glucose, insulin, HOMA-IR, lipid profile, reproductive hormones, and detailed serum fatty acid profiling by GC-MS, as well as Mediterranean Diet Adherence Screener (MEDAS) scores. The trial aimed to provide preliminary evidence on whether adding krill oil to metformin therapy offers broader metabolic benefits than either intervention alone in women with PCOS and MUO.

Conditions

Polycystic Ovary Syndrome; Obesity, Metabolic

Keywords

krill oil; PCOS; omega-3 fatty acids; adipokine; metformin

Outcome Measures

Primary Outcomes (2)

• Change in Serum Adiponectin Level

  Change in serum adiponectin concentration measured by ELISA at baseline and after 12 weeks of intervention. Adiponectin is an anti-inflammatory adipokine associated with insulin sensitivity and metabolic health.

  8 weeks (Baseline and Week 8)

• Change in Serum Neuregulin-4 (NRG-4) Level

  Change in serum neuregulin-4 (NRG-4) concentration measured by ELISA at baseline and after 12 weeks of intervention. NRG-4 is a novel adipokine linked to lipid metabolism, brown adipose tissue activity, and cardiometabolic health.

  8 weeks (Baseline and Week 8)

Secondary Outcomes (2)

• Change in Insulin Resistance (HOMA-IR)

  8 weeks (Baseline and Week 8)

• Change in Lipid Profile (Total Cholesterol, LDL-C, HDL-C, Triglycerides)

  8 weeks (Baseline and Week 8)

Study Arms (4)

Metformin Group (MET)

EXPERIMENTAL

Participants received Metformin Hydrochloride 1000 mg/day (single daily oral dose) for 8 weeks. No dietary supplement was added in this group.

Drug: Metformin Hydrochloride 1000 MG

Krill Oil Group (KO)

EXPERIMENTAL

Participants received Krill Oil 2 g/day (1 g twice daily, orally) for 8 weeks. No pharmaceutical agent was administered in this group.

Dietary Supplement: Krill Oil

Metformin + Krill Oil Group (METKO)

EXPERIMENTAL

Participants received Metformin Hydrochloride 1000 mg/day (single daily oral dose) combined with Krill Oil 2 g/day (1 g twice daily, orally) for 8 weeks.

Drug: Metformin Hydrochloride 1000 MG; Dietary Supplement: Krill Oil

Control Group

NO INTERVENTION

Participants received no intervention during the 8-week study period. They continued their habitual lifestyle without any dietary supplementation or pharmaceutical treatment.

Interventions

Metformin Hydrochloride 1000 MG DRUG

Metformin Hydrochloride 1000 mg/day (single daily oral dose) for 8 weeks. Metformin is a biguanide antidiabetic drug that improves insulin sensitivity and reduces hepatic glucose production. Used as standard treatment for PCOS-related insulin resistance and metabolic dysfunction.

Metformin + Krill Oil Group (METKO); Metformin Group (MET)

Krill Oil DIETARY_SUPPLEMENT

Krill Oil 2 g/day (1 g twice daily, oral administration) for 8 weeks. Krill oil is a marine-derived omega-3 fatty acid supplement rich in EPA, DHA, and phospholipids with antioxidant astaxanthin. It has anti-inflammatory, lipid-modulating, and insulin-sensitizing properties relevant to PCOS and metabolic obesity management.

Krill Oil Group (KO); Metformin + Krill Oil Group (METKO)

Eligibility Criteria

• Age: 19 Years - 40 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Female sex, aged 19-40 years
• Diagnosis of Polycystic Ovary Syndrome (PCOS) according to Rotterdam criteria (at least 2 of 3: oligo/anovulation, clinical/biochemical hyperandrogenism, polycystic ovaries on ultrasound)
• Metabolically Unhealthy Obesity (MUO) defined by combined NCEP ATP-III/IDF criteria (waist circumference \>88 cm plus ≥2 metabolic risk factors)
• BMI ≥ 30 kg/m2
• Willingness to provide written informed consent

You may not qualify if:

• Type 1 or Type 2 diabetes mellitus
• Thyroid disorders (uncontrolled hypo- or hyperthyroidism)
• Renal or hepatic disease
• Cardiovascular disease
• Use of oral contraceptives, insulin sensitizers, lipid-lowering drugs, or omega-3 supplements in the past 3 months
• Pregnancy or lactation
• Allergy to fish or seafood (krill oil contraindication)
• Participation in another clinical trial
• Smokers or alcohol users

Sponsors & Collaborators

• Firat University: lead

Study Sites (1)

Firat University, Faculty of Health Sciences, Department of Nutrition and Dietetics

Elâzığ, 23119, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Polycystic Ovary Syndrome; Obesity

Interventions

Metformin

Condition Hierarchy (Ancestors)

Ovarian Cysts; Cysts; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, PhD, RD, Associate Professor

Study Record Dates

• First Submitted: May 17, 2026
• First Posted: May 22, 2026
• Study Start: March 1, 2023
• Primary Completion: April 30, 2024
• Study Completion: April 30, 2024
• Last Updated: May 22, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

TU (1)