Effects of Resveratrol Supplementation Combined With a Low-Calorie Diet in Postmenopausal Women With Obesity and Knee Osteoarthritis (ERSOKO)

Effects of Resveratrol as an Adjunct to a Low-Calorie Diet in Postmenopausal Women With Obesity and Knee Osteoarthritis: A Randomized Controlled Trial

Obesity is a major modifiable risk factor for knee osteoarthritis and is associated with chronic low-grade inflammation, pain, functional impairment, and cartilage degradation. Weight reduction is recommended as a core component of osteoarthritis management, while resveratrol has demonstrated anti-inflammatory and chondroprotective properties in experimental and clinical studies. However, the potential additional benefit of resveratrol supplementation when combined with dietary intervention remains uncertain.

This randomized controlled trial evaluated the effects of 150 mg/day trans-resveratrol supplementation as an adjunct to a low-calorie diet in postmenopausal women with obesity and knee osteoarthritis. Ninety-seven participants were randomized to receive either a low-calorie diet alone or the same diet combined with resveratrol for 10 days. Outcomes included pain intensity, functional status, urinary C-terminal telopeptide of type II collagen (CTX-II), anthropometric parameters, body composition, metabolic markers, lipid profile, and inflammatory biomarkers.

Study Overview

• Status: Completed
• Conditions: Obesity (Disorder); Knee Osteoarthritis (Knee OA)
• Intervention / Treatment: Behavioral: Low-Calorie Diet; Dietary supplement: Trans-resveratrol extract from Polygonum Cuspidatum

Detailed Description

Obesity is a major modifiable risk factor for knee osteoarthritis and contributes not only to increased mechanical loading of the joints but also to chronic low-grade systemic inflammation, metabolic dysfunction, and cartilage degradation. Postmenopausal women represent a particularly vulnerable population because obesity and menopause-related hormonal changes may accelerate the development and progression of osteoarthritis. Current clinical guidelines recommend weight management as a core component of osteoarthritis treatment, particularly in patients with obesity.

Resveratrol is a naturally occurring polyphenolic compound found in grapes, berries, peanuts, and other plants. Experimental studies have demonstrated anti-inflammatory, antioxidant, and chondroprotective properties of resveratrol. Potential mechanisms include modulation of inflammatory signaling pathways, reduction of oxidative stress, inhibition of cartilage matrix degradation, and protection of chondrocyte viability. Although several clinical studies have investigated the effects of resveratrol in metabolic disorders and osteoarthritis, its efficacy as an adjunct to dietary intervention remains insufficiently characterized.

The purpose of this randomized controlled trial was to evaluate whether supplementation with trans-resveratrol provides additional clinical and metabolic benefits when combined with a low-calorie diet in postmenopausal women with obesity and knee osteoarthritis.

Eligible participants were postmenopausal women with obesity (body mass index ≥30 kg/m²) and radiographically confirmed knee osteoarthritis of Kellgren-Lawrence grade II or III. Participants were recruited during inpatient treatment at the Nutrition Clinic of the Federal Research Centre of Nutrition, Biotechnology and Food Safety. After baseline assessment, participants were randomized in a 1:1 ratio to receive either a low-calorie diet alone or the same low-calorie diet combined with trans-resveratrol supplementation.

All participants received a standardized low-calorie diet providing approximately 1700 kcal per day for 10 consecutive days. The diet was based on moderate energy restriction with reduced fat and carbohydrate intake and exclusion of added sugars. Participants assigned to the intervention group additionally received 150 mg/day of trans-resveratrol throughout the intervention period.

Assessments were performed at baseline and at the end of the intervention period. Clinical outcomes included pain intensity measured by the Visual Analog Scale (VAS), functional status assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the Lequesne Algofunctional Index (LAI). Anthropometric measurements included body weight, body mass index, waist circumference, and hip circumference. Body composition was evaluated using multifrequency bioelectrical impedance analysis. Laboratory assessments included markers of carbohydrate metabolism, lipid metabolism, systemic inflammation, and routine biochemical parameters. Cartilage degradation was evaluated by measurement of urinary C-terminal telopeptide of type II collagen (CTX-II).

The primary objective of the study was to evaluate the effect of resveratrol supplementation on osteoarthritis-related outcomes and cartilage degradation markers when added to a low-calorie diet. Secondary objectives included assessment of changes in anthropometric parameters, body composition, metabolic indicators, lipid profile, and systemic inflammation.

• Study Type: Interventional
• Enrollment (Actual): 97
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Russia
  • Moscow, Russia, 115446
    • Department of Cardiovascular Pathology and Diet Therapy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Postmenopausal women aged 45-75 years.
• Diagnosed knee osteoarthritis.
• Obesity, defined as BMI ≥30 kg/m².
• Ability to comply with the study protocol and dietary recommendations.
• Written informed consent to participate in the study.

Exclusion Criteria:

• Allergy or intolerance to grapes, wine, peanuts, resveratrol, or supplement components.
• Acute infectious or inflammatory disease at screening.
• Unstable or exacerbated chronic disease requiring treatment changes or hospitalization.
• Malignancy within the past 5 years.
• Chronic liver disease, including hepatitis or cirrhosis.
• Major cardiovascular event within the past 6 months.
• Alcohol abuse or dependence.
• Severe psychiatric disorder or cognitive impairment limiting protocol adherence.
• Use of resveratrol-containing supplements or investigational products within the past 6 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Low-Calorie Diet; Participants received a standardized low-calorie diet providing approximately 1700 kcal/day for 10 consecutive days during inpatient treatment. The diet included moderate energy restriction through reduced fat and carbohydrate intake, exclusion of added sugars, restriction of animal fats and sodium, and inclusion of dietary fiber sources such as vegetables, fruits, and cereals.	Behavioral: Low-Calorie Diet; A standardized low-calorie diet providing approximately 1700 kcal/day for 10 days. The diet was designed to achieve moderate energy restriction and was administered under inpatient supervision.
Experimental: Low-Calorie Diet Plus Resveratrol; Participants received the same standardized low-calorie diet as the control group and additionally received trans-resveratrol supplementation at a dose of 150 mg/day for 10 consecutive days during inpatient treatment.	Dietary supplement: Trans-resveratrol extract from Polygonum Cuspidatum; Participants received 150 mg/day of trans-resveratrol (>99% purity) administered once daily with a meal for 10 days in addition to a standardized low-calorie diet.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urinary CTX-II	Change in urinary C-terminal telopeptide of type II collagen concentration corrected for urinary creatinine.	Baseline and Day 10
WOMAC Score	Change in Western Ontario and McMaster Universities Osteoarthritis Index total score.	Baseline and Day 10
Pain Intensity (VAS)	Change in pain intensity measured by Visual Analog Scale.	Baseline and Day 10
hsCRP	high-sensitivity C-reactive protein; measured in mg/L	Baseline and Day 10

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body weight	Change from baseline in body weight (kg)	Baseline and Day 10
BMI	Body Mass Index; calculated as weight in kg divided by height in meters squared	Baseline and Day 10
Fat mass	measured in kg or % of total body mass; bioelectrical impedance analysis	Baseline and Day 10
HOMA-IR	Homeostatic Model Assessment for Insulin Resistance; calculated as fasting insulin (μU/mL) × fasting glucose (mmol/L) / 22.5	Baseline and Day 10
Total cholesterol	Total cholesterol (measured in mg/dL or mmol/L)	Baseline and Day 10
LDL-C	LDL-C (low-density lipoprotein cholesterol; measured in mg/dL or mmol/L)	Baseline and Day 10
HDL-C	HDL-C (high-density lipoprotein cholesterol; measured in mg/dL or mmol/L)	Baseline and Day 10
Triglycerides	Triglycerides (measured in mg/dL or mmol/L)	Baseline and Day 10

Collaborators and Investigators

• Sponsor: Federal State Budgetary Scientific Institution "Federal Research Centre of Nutrition, Biotechnology

Study record dates

Study Major Dates

• Study Start (Actual): March 20, 2017
• Primary Completion (Actual): July 13, 2018
• Study Completion (Actual): September 10, 2018

Study Registration Dates

• First Submitted: June 3, 2026
• First Submitted That Met QC Criteria: June 3, 2026
• First Posted (Actual): June 8, 2026

Study Record Updates

• Last Update Posted (Actual): June 8, 2026
• Last Update Submitted That Met QC Criteria: June 3, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Inflammation; Obesity; Knee Osteoarthritis; Resveratrol; Postmenopausal Women; Low-Calorie Diet
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Pathologic Processes; Nutrition Disorders; Arthritis; Joint Diseases; Rheumatic Diseases; Overnutrition; Body Weight; Osteoarthritis; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Osteoarthritis, Knee; Inflammation; Therapeutics; Diet, Food, and Nutrition; Physiological Phenomena; Nutritional Physiological Phenomena; Diet Therapy; Nutrition Therapy; Diet; Energy Intake; Caloric Restriction
• Other Study ID Numbers: 03022017N1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No