Assessment of the Effects and Safety of Spermidine Supplementation on Blood Lipids and Body Weight in Overweight or Obese Individuals With Hyperlipidemia

Assessment of the Effects and Safety of Spermidine Supplementation on Blood Lipids and Body Weight in Overweight or Obese Individuals With Hyperlipidemia: A Randomized, Double-Blind, Placebo-Controlled Trial

Evaluate the effect of spermidine supplementation on lipid profile changes in individuals with overweight or obesity accompanied by hyperlipidemia. Analyze the impact of spermidine on metabolic parameters and assess the safety of spermidine supplementation, including liver and kidney function, gastrointestinal reactions, and other adverse effects.

Study Overview

• Status: Recruiting
• Conditions: Hyperlipidemia; Obesity & Overweight
• Intervention / Treatment: Drug: Spermidine; Drug: Placebo

Detailed Description

This is a single-center, randomized, double-blind, placebo-controlled, parallel-group trial designed to evaluate the efficacy and safety of spermidine supplementation in overweight or obese adults with hyperlipidemia.

A total of 50 eligible participants will be randomly assigned in a 1:1 ratio to either the experimental group (spermidine capsule 10 mg/day) or the control group (placebo capsule, identical in appearance, packaging, and taste). Randomization will be performed by a third-party statistician using a computer-generated random number table with variable block sizes. Allocation concealment will be ensured through sequentially numbered, opaque, sealed envelopes. All outcome assessors, investigators, and participants will be blinded to group assignment throughout the study.

The intervention period lasts 1 month. Participants in the experimental group will take 2 capsules (10 mg total) of spermidine (extracted from North American high-selenium wheat germ, 100:1 concentration process) orally per day after breakfast. The placebo group will receive an identical regimen of microcrystalline cellulose capsules. During the trial, all participants will receive standardized dietary advice designed to avoid high-polyamine foods (e.g., natto, fermented soy products, mushroom, germ products) and maintain stable total energy intake without overeating. They will also be advised to avoid new nutritional supplements and any other weight-loss interventions. Weekly telephone follow-ups will monitor compliance and dietary/exercise logs. Compliance will be assessed by pill counts of returned capsules, with <80% adherence defined as protocol deviation.

Assessments are scheduled at baseline (Day 0) and at study end (Month 1). Baseline evaluations include anthropometric measurements, blood biochemistry, stool sample collection, and questionnaire assessments. At Month 1, all baseline measurements will be repeated, and adverse events will be recorded and assessed for causality using the Naranjo scale. Safety monitoring includes liver and kidney function tests and documentation of gastrointestinal or other adverse reactions throughout the trial.

Primary outcome is the change in triglycerides (TG) from baseline to 1 month. Secondary outcomes include changes in LDL, total cholesterol, weight, BMI, body fat percentage, waist-to-hip ratio, fasting glucose, liver/kidney function parameters, and adverse event rates. Statistical analyses will follow the intention-to-treat principle using SAS 9.4. Primary analysis will employ two independent sample t-tests or Mann-Whitney U tests for between-group comparisons.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Bu Le; Phone Number: +86 17701621016; Email: geyingjun@hotmail.com

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200072
      • Recruiting
      • Shanghai Tenth People's Hospital
      • Contact: Bu Le; Phone Number: +86 17701621016; Email: geyingjun@hotmail.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Males or females aged 18 to 65 years.
• BMI ≥ 24 kg/m², without severe chronic diseases.
• Not currently using glucose-lowering or lipid-lowering medications.
• Dyslipidemia defined as triglycerides ≥ 1.7 mmol/L or total cholesterol ≥ 5.2 mmol/L.
• No active weight loss or weight gain diet within the past 1 month.
• No special dietary pattern changes (e.g., ketogenic, vegan, high-protein, meal replacement, intermittent fasting) within the past 1 month.
• No use of supplements that may affect polyamine intake (e.g., germ, yeast, fermented extracts, nutritional powders) within the past 2-4 weeks.
• Willing and able to provide signed informed consent.

Exclusion Criteria:

• Diagnosis of acute or severe gastrointestinal disease
• Concurrent participation in any other weight-loss therapy
• Current use of hypoglycemic or lipid-lowering medications
• Participation in any other clinical trial within one month prior to signing the informed consent form
• Pregnancy, lactation, or planning a pregnancy during the trial period
• Known allergy to cellulose or wheat
• History of cancer
• Renal insufficiency, indicated by abnormal serum creatinine levels
• Hepatic impairment, defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 × upper limit of normal (ULN), or total bilirubin (TBIL) >3 × ULN
• Any other condition deemed by the investigator as inappropriate for trial participation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Trial group (spermidine); Spermidine capsules 10 mg/day	Drug: Spermidine; Spermidine (10 mg/day) administered as two oral capsules taken after breakfast. The spermidine is extracted from North American high-selenium wheat germ using a 100:1 concentration process. Each capsule contains 5 mg of spermidine, with a total daily dose of 10 mg. The intervention duration is 1 month.
Placebo Comparator: Control group (placebo); Placebo 10 mg/day	Drug: Placebo; Placebo capsules are identical in appearance, color, size, packaging, and taste to the spermidine capsules. Each capsule is filled with microcrystalline cellulose and contains no active ingredients. Participants will take two placebo capsules orally after breakfast daily for a duration of 1 month. The placebo is packaged and blinded by an independent pharmacy according to a randomization code to ensure double-blind implementation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Triglycerides (TG)	Change in fasting serum triglycerides (TG) from baseline (Day 0) to the end of the 1-month intervention period. Blood samples are collected after an overnight fast and analyzed using standard enzymatic methods. TG level is measured in mmol/L. This is the primary efficacy outcome of the study.	Baseline and 1 month post-treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Three-Factor Eating Questionnaire - Revised 21-item(TFEQ-R21)	The Three-Factor Eating Questionnaire-Revised 21-item (TFEQ-R21) is a validated instrument assessing eating behaviors across three domains: cognitive restraint, uncontrolled eating, and emotional eating. The questionnaire consists of 21 items scored on a 4-point Likert scale, yielding a total score ranging from 21 to 84, or standardized scores from 0 to 100. Higher scores indicate greater levels of the respective eating behavior, with higher uncontrolled and emotional eating scores reflecting more dysfunctional eating patterns.	Baseline and 1 month post-treatment
Alanine Aminotransferase	Change in serum alanine aminotransferase (ALT) levels from baseline (Day 0) to 1 month post-treatment (Month 1). Blood samples are collected after an overnight fast and analyzed using standard enzymatic methods. ALT is measured in U/L and serves as a safety indicator of liver function.	Baseline and 1 month post-treatment
Fasting Blood Glucose	Change in fasting blood glucose levels from baseline (Day 0) to 1 month post-treatment (Month 1). Blood samples are collected after an overnight fast and analyzed using standard glucose oxidase or hexokinase methods. Fasting blood glucose is measured in mmol/L.	Baseline and 1 month post-treatment
Low-Density Lipoprotein Cholesterol	Change in serum low-density lipoprotein cholesterol (LDL-C) levels from baseline (Day 0) to 1 month post-treatment (Month 1). Blood samples are collected after an overnight fast and analyzed using standard enzymatic or homogeneous direct methods. LDL-C is measured in mmol/L.	Baseline and 1 month post-treatment
Physical Activity Intensity	Physical activity levels (including intensity) were assessed using the short form of the International Physical Activity Questionnaire (IPAQ).	Baseline and 1 month post-treatment
Total Cholesterol (TC)	Change in serum total cholesterol (TC) levels from baseline (Day 0) to 1 month post-treatment (Month 1). Blood samples are collected after an overnight fast and analyzed using standard enzymatic methods (cholesterol oxidase-peroxidase method). TC is measured in mmol/L.	Baseline and 1 month post-treatment
Creatinine	Change in serum creatinine levels from baseline (Day 0) to 1 month post-treatment (Month 1). Blood samples are collected after an overnight fast and analyzed using standard enzymatic or Jaffé methods. Creatinine is measured in μmol/L or mg/dL and serves as a safety indicator of renal function.	Baseline and 1 month post-treatment
Body Weight	Body weight (kg) will be measured using a calibrated body composition scale.	Baseline and 1 month post-treatment
Body Fat Percentage	Body fat percentage(%) will be assessed using a body composition scale based on bioelectrical impedance analysis.	Baseline and 1 month post-treatment
Waist Circumference	Waist circumference(cm) will be measured at the midpoint between the lowest rib and the iliac crest using a standardized measuring tape.	Baseline and 1 month post-treatment
Hip Circumference	Hip circumference(cm) will be measured at the level of the greatest posterior protuberance of the buttocks using a standardized measuring tape.	Baseline and 1 month post-treatment
Body Mass Index (BMI)	BMI(kg/m²) will be calculated as body weight (kg) divided by height squared (m²).	Baseline and 1 month post-treatment

Collaborators and Investigators

• Sponsor: Shanghai 10th People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2026
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): January 31, 2027

Study Registration Dates

• First Submitted: April 7, 2026
• First Submitted That Met QC Criteria: June 22, 2026
• First Posted (Actual): June 23, 2026

Study Record Updates

• Last Update Posted (Actual): June 23, 2026
• Last Update Submitted That Met QC Criteria: June 22, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nutrition Disorders; Metabolic Diseases; Overnutrition; Body Weight; Dyslipidemias; Lipid Metabolism Disorders; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight; Obesity; Hyperlipidemias; Organic Chemicals; Amines; Biogenic Amines; Polyamines; Putrescine; Biogenic Polyamines; Spermidine
• Other Study ID Numbers: Spermidine

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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