Effects of an Elderberry-Based Functional Beverage on Exercise Performance, Muscle Structure, and the Gut-Muscle Axis

NCT ID: NCT07054671

Last Updated: 2025-07-08

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-11-01
• Study Completion Date: 2027-10-01

Brief Summary

Introduction: Increasing sedentary lifestyle, microbiota imbalance and exercise-induced muscle fatigue are among the main causes of metabolic stress and performance decline, even in young individuals. The potential effects of functional foods-particularly polyphenol and anthocyanin-rich beverages-on both gut microbiota and muscle performance have attracted attention in recent years. In this context, intervention studies focused on the gut-muscle axis represent a promising and valuable area of research.

Objective: This study aims to investigate the effects of a functional beverage enriched with anthocyanins and polyphenols -extracted from Sambucus nigra L. (black elderberry)- combined with a regular exercise program on muscle performance, muscle morphology, fatigue level, and gut microbiota composition in healthy individuals.

Method: This 12-week double-blind, randomized, placebo-controlled trial will include participants adhering to a berry-free diet. Participants will be randomly assigned to two groups: the intervention group will consume a functional elderberry beverage formulated with high-purity anthocyanins obtained via supercritical CO₂ extraction; the control group will receive a placebo beverage with matched taste and energy content but without active compounds. Both groups will engage in a structured combined exercise program (3 days/week). Pre- and post-intervention assessments will include gut microbiota profiling (16S rRNA sequencing), short-chain fatty acid analysis, systemic biomarkers, muscle morphology (via ultrasound), exercise performance, and body composition. Mediator analyses will be used to explore the role of the gut-muscle axis in the observed effects.

Unique value: This project represents one of the few human-based intervention studies systematically evaluating the interaction between functional beverages, exercise, and microbiota through the lens of muscle fiber-type-specific adaptations. Furthermore, by integrating mediator analyses and multi-level outcome measures, the study aims to elucidate the physiological relevance of the gut-muscle axis in a holistic manner. The development, standardization, and sensory evaluation of the elderberry-based beverage also contribute valuable insights to functional product innovation.

Detailed Description

In modern times, the increasing prevalence of sedentary lifestyles, age-related decline in muscle function, and gut dysbiosis have been shown to negatively affect both metabolic health and muscular performance. These problems are not only observed in the elderly population but also in physically active young individuals, manifesting as exercise-induced fatigue, reduced performance, and impaired immune function. Sustaining muscle performance is closely related not only to physical fitness but also to maintaining gut microbiota balance and controlling inflammation.

The health effects of functional foods have become a focal point in multidisciplinary research in recent years. In this context, developing functional beverages rich in bioactive compounds such as polyphenols, flavonoids, and anthocyanins offers new research opportunities, particularly in the fields of exercise physiology and immune response. This study aims to evaluate the effects of an anthocyanin-enriched functional beverage derived from Sambucus nigra L. (elderberry) on muscle performance, fatigue, and the gut-muscle axis in healthy individuals participating in a combined exercise protocol.

Elderberry is a bioactive source noted for its high anthocyanin content, showing antioxidant and anti-inflammatory effects, and its potential to positively modulate gut microbiota. Since anthocyanins are only minimally absorbed in the small intestine, a large proportion reaches the colon, where they are fermented by the gut microbiota into various phenolic acids. This fermentation process may support the proliferation of beneficial species such as Bifidobacterium and Lactobacillus, while reducing pathogenic species such as Clostridium perfringens. Furthermore, elderberry polyphenols may promote the growth of anti-inflammatory species like Akkermansia muciniphila and Faecalibacterium prausnitzii. These microbial changes-especially the increase in short-chain fatty acids (SCFAs), particularly butyrate-have been associated with improved immune response, gut barrier integrity, and muscle metabolism. In vivo studies have shown that anthocyanin supplementation enhances microbial diversity and stimulates SCFA production, thereby helping to suppress inflammation. Within the so-called "gut-muscle axis," SCFAs-especially butyrate-play roles in muscle protein synthesis, mitochondrial function, and inflammation regulation. Some animal studies have also shown that modulation of microbiota composition via probiotics and polyphenol supplementation positively affects muscle mass and endurance.

Therefore, the researchers hypothesize that the elderberry-based beverage may reduce exercise-induced muscle fatigue and enhance performance not only through systemic antioxidant mechanisms but also by regulating gut microbiota. Consequently, this study will also assess how the microbiota changes induced by the beverage affect muscle metabolism.

A combined exercise protocol (2 days of resistance + 1 day of endurance) has been chosen, as it is an effective model for stimulating both cardiorespiratory capacity and muscle function. The literature highlights that endurance training improves mitochondrial biogenesis, oxidative capacity, and lactate clearance, whereas resistance training increases muscular strength and hypertrophy. It has been demonstrated that combined protocols are more effective for improving metabolic health and functional capacity.

To evaluate not only general muscle hypertrophy but also fiber-type-specific physiological adaptations, three muscle groups will be assessed: quadriceps, soleus (Type I fiber dominant), and gastrocnemius (Type II fiber dominant). These muscles were selected based on their well-defined morphological and metabolic profiles in the literature, allowing for indirect assessment of anthocyanins and polyphenols on mitochondrial function and oxidative stress. This makes the study one of the few human-based interventions that systematically investigates the effects of functional foods on exercise physiology with a muscle fiber-type-specific approach.

This study is among the few examples in the literature that evaluate functional beverages not only at the bioactive compound level but also in the context of exercise physiology and microbiota interaction. Most current research focuses on the short-term effects of polyphenol supplementation or isolated microbiota outcomes. However, this project aims to evaluate the holistic effects of a polyphenol/anthocyanin-rich functional beverage on both performance physiology and gut microbiota. Furthermore, the mediating role of the gut-muscle axis will be explored through quantitative measurements. This approach introduces a new methodological framework for both bioactive food development and microbiota-based exercise science. To date, there has been no human-based randomized controlled trial combining exercise, microbiota, and functional beverage interventions in the same design.

Conditions

Exercise; Anthocyanins; Muscle Size

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: NONE

Study Groups

Elderberry Beverage Group

Participants will consume an anthocyanin-rich elderberry-based functional beverage daily for 12 weeks while following a combined exercise protocol (2 days resistance + 1 day endurance training per week).

Intervention;

• Dietary Supplement (Elderberry-Based Functional Beverage)
• A polyphenol and anthocyanin-rich beverage formulated from Sambucus nigra L., consumed once daily.

Group Type: EXPERIMENTAL

Elderberry-Based Functional Beverage

Intervention Type: DIETARY_SUPPLEMENT

A polyphenol- and anthocyanin-rich beverage derived from Sambucus nigra L., administered once daily for 12 weeks as a dietary supplement.

Placebo Beverage Group

Participants will consume a placebo beverage that is matched in color and taste but does not contain polyphenols or anthocyanins, while following the same combined exercise protocol.

Intervention:

• Type: Placebo (Placebo Beverage)
• A non-bioactive beverage matched for flavor and appearance, consumed once daily.

Group Type: PLACEBO_COMPARATOR

Placebo Beverage

Intervention Type: DIETARY_SUPPLEMENT

A placebo beverage that mimics the elderberry drink in color and flavor but contains no polyphenols or bioactive compounds. Consumed once daily for 12 weeks.

Interventions

Elderberry-Based Functional Beverage

A polyphenol- and anthocyanin-rich beverage derived from Sambucus nigra L., administered once daily for 12 weeks as a dietary supplement.

Intervention Type: DIETARY_SUPPLEMENT

Placebo Beverage

A placebo beverage that mimics the elderberry drink in color and flavor but contains no polyphenols or bioactive compounds. Consumed once daily for 12 weeks.

Intervention Type: DIETARY_SUPPLEMENT

Other Intervention Names

1

Eligibility Criteria

Inclusion Criteria

• Engaging in regular physical activity at least 2 days per week
• Body Mass Index (BMI) between 18.5 and 29.9 kg/m²
• No use of antibiotics, probiotics, or prebiotics within the past 3 months
• No history of chronic illness or autoimmune disorders
• Physically able and eligible to participate in exercise training
• Willingness to participate and provide written informed consent

Exclusion Criteria

• Pregnancy or breastfeeding
• Known food allergies
• Regular use of medications such as corticosteroids, NSAIDs, or immunosuppressants
• Professional-level athletes
• All participants will be instructed to avoid consuming any products containing berries (fresh, frozen, dried, jam, juice, or supplements) during the intervention period. A "berry-free diet" will be implemented as part of the study protocol. At baseline, a short Food Frequency Questionnaire (FFQ) will be administered to assess participants' berry consumption habits over the past month. The FFQ will include 10 commonly consumed berries in Türkiye: strawberry, raspberry, blackberry, blueberry, elderberry, mulberry, redcurrant, blackcurrant, aronia, and goji berry. Each item will be scored on a scale from 0 (never) to 4 (daily), and the total score will represent the individual's berry consumption score. Participants with a total baseline score of ≥10 will be excluded to minimize confounding from prior polyphenol exposure. The FFQ will only be used to assess baseline habits and ensure compliance with the berry-free protocol; it will not be used in primary outcome analyses.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Burdur Mehmet Akif Ersoy University

OTHER

Sponsor Role: lead

Responsible Party

Gul Akduman

Research Assistant, Department of Nutrition and Dietetics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

MAKU Department of Nutrition and Dietetics

Burdur, , Turkey (Türkiye)

Countries

Turkey (Türkiye)

Central Contacts

Gul Akduman, Dr.

Role: CONTACT

gakduman@gmail.com

+905380458382

Facility Contacts

Gul Akduman, Dr.

Role: primary

gakduman@gmail.com

+905380458382

Other Identifiers

MAKU-AKDUMAN-3501-2025

Identifier Type: -

Identifier Source: org_study_id