Evaluation of the Effect of a Seaweed Flour- and Leucine-Enriched Food on Metabolic and Inflammatory Status in Older Adults With Probable Sarcopenia or Sarcopenia

Evaluation of the Effect of a Seaweed Flour- and Leucine-Enriched Food on Metabolic and Inflammatory Status in Older Adults With Probable Sarcopenia or Sarcopenia: A Prospective, Controlled, Randomized, Double-Blind, Three-Arm Parallel Clinical Trial

Sarcopenia and probable sarcopenia are associated with loss of muscle strength, functional impairment, frailty, and an increased risk of adverse outcomes in older adults. In short-term interventions, structural or functional changes may be modest, whereas certain serum biomarkers of metabolic-nutritional response may be more sensitive. In this protocol version, serum transthyretin (TTR) has been selected as the primary outcome, without assuming that it represents, by itself, a direct measure of muscle mass or overall clinical efficacy.

Study Overview

• Status: Not yet recruiting
• Conditions: Sarcopenia in Elderly
• Intervention / Treatment: Dietary supplement: Standard chocolate-flavored cake; Dietary supplement: Leucine-Enriched Chocolate Cake; Dietary supplement: Leucine Plus Seaweed Flour-Enriched Chocolate Cake

Detailed Description

Sarcopenia is a progressive skeletal muscle disorder associated with aging and an increased risk of disability, hospitalization, dependency, and mortality. Contemporary consensus definitions identify low muscle strength as the primary characteristic of the condition, while muscle quantity or quality and physical performance are used to support the diagnosis and determine its severity.

In older adults, anabolic resistance reduces the muscle's responsiveness to habitual dietary protein intake. Leucine has been proposed as an amino acid capable of stimulating key anabolic pathways and therefore represents a plausible candidate for short-term nutritional interventions. In turn, Durvillaea incurvata flour provides bioactive compounds and dietary fiber with potential antioxidant and anti-inflammatory properties, although clinical evidence supporting its use in sarcopenia remains limited.

From a methodological perspective, a 28-day follow-up period may be sufficient to detect early metabolic and nutritional responses, but it may be insufficient to demonstrate robust clinical changes in muscle strength, muscle mass, or physical performance. For this reason, serum TTR has been selected as the primary short-term response outcome in the present protocol.

The selection of serum TTR as the primary outcome requires careful interpretation. Serum TTR levels may be influenced by protein-energy intake, liver function, inflammatory status, and intercurrent clinical conditions. Accordingly, in this protocol, serum TTR will not be interpreted as a direct surrogate of muscle mass or as a stand-alone measure of clinical efficacy. Rather, it will be considered a serum marker of early metabolic and nutritional response, whose interpretation will be complemented by functional, body composition, inflammatory, and safety-related outcomes.

This study is therefore designed as an exploratory, randomized proof-of-concept trial to determine whether the combination of leucine and seaweed flour improves serum TTR and whether this response is accompanied by consistent secondary changes in muscle strength, mobility, body composition, and the metabolic-inflammatory profile.

• Study Type: Interventional
• Enrollment (Estimated): 102
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: María S Mariotti Celis, Ph D; Phone Number: +56 9 82332421; Email: mmariotti@uft.cl

Study Locations

• Chile
  • Santiago, Chile, 8010000
    • Universidad Finis Terrae
    • Contact: Cristian R Encina Acosta, Ph D; Phone Number: +56 9 62240100; Email: cencinaa@uft.edu
    • Contact: Conrado S Camilo Manriquez; Phone Number: +56 9 77508471; Email: ccamilo@uft.cl

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria

• Age between 60 and 80 years at the time of enrollment.
• Ability to understand the study procedures and provide written informed consent.
• SARC-F score ≥4 during screening.
• Reduced muscle strength defined as handgrip strength <27 kg in men or <16 kg in women; alternatively, a time >15 seconds on the five-repetition chair stand test when handgrip dynamometry cannot be validly performed or is contraindicated.
• Availability to attend study visits and comply with daily consumption of the study product for 28 days.
• Willingness to provide fasting blood samples at the Day 0 and Day 28 visits. Exclusion Criteria
• Cognitive impairment according to the abbreviated Mini-Mental State Examination (MMSE), using the operational cutoff approved for the study (≤13 points).
• Clinically significant chronic liver disease, clinically significant chronic kidney disease, nephrotic syndrome, active cancer or recent oncological treatment, or any condition that may substantially affect serum TTR levels or increase participant risk.
• Acute infection, acute inflammatory condition, or clinical decompensation at baseline that may interfere with the interpretation of serum TTR measurements.
• Uncontrolled diabetes mellitus or any metabolic condition that, in the investigator's judgment, may increase the risks associated with the intervention.
• Food allergy or intolerance to any component of the study product, including gluten, egg, milk, or other specific cake ingredients.
• Use of leucine, HMB, or protein supplements within the previous 3 months.
• Chronic use of systemic corticosteroids, immunosuppressive agents, or other therapies that may significantly alter the metabolic response under study.
• Untreated thyroid disease or any other unstable endocrine disorder.
• Clinically significant edema, severe dehydration, or any condition that may compromise the validity of bioelectrical impedance measurements.
• Any medical, functional, social, or cognitive condition that may limit safe participation or adherence to the study protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control chocolate cake; One daily serving of standard chocolate-flavored cake without added leucine or seaweed flour for 28 consecutive days	Dietary supplement: Standard chocolate-flavored cake; Participants will consume one standard chocolate-flavored cake serving daily for 28 days, without added leucine or seaweed flour.; Other Names: Cake
Active Comparator: Leucine-enriched chocolate cake; One daily serving of standard chocolate-flavored cake supplemented with 3 g of leucine for 28 consecutive days	Dietary supplement: Leucine-Enriched Chocolate Cake; Participants will consume one chocolate-flavored cake serving supplemented with 3 g of leucine daily for 28 days.; Other Names: Leucin
Experimental: Leucine and Durvillaea incurvata Flour-Enriched Chocolate Cake; One daily serving of standard chocolate-flavored cake supplemented with 3 g of leucine and 3 g of Durvillaea incurvata flour for 28 consecutive days.	Dietary supplement: Leucine Plus Seaweed Flour-Enriched Chocolate Cake; Participants will consume one chocolate-flavored cake serving supplemented with 3 g of leucine and 3 g of Durvillaea incurvata flour daily for 28 days.; Other Names: Seaweed

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in fasting serum transthyretin concentration at day 28.	Fasting serum transthyretin (TTR; prealbumin) concentration (mg/dL) measured using Human Transthyretin/Prealbumin ELISA Kit (NBP2-60516, Bio-Techne, Novus Biologicals). The outcome is the change from Day 0 to Day 28 according to the Statistical Analysis Plan.	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in handgrip strength at day 28.	Handgrip strength (kg) measured by dynamometry under standardized conditions. The operational measure, such as the best of three valid attempts.	28 days
Change from baseline in 4-meter gait speed at day 28.	Usual gain speed (m/s) calculated from the 4-meter walk test under standardized condition.	28 days
Change from baseline in appendicular muscle mass index at day 28.	Appendicular skeletal muscle mass index (kg/m2) measured calculated as appendicular skeletal muscle mass divided by height squared	28 days
Percentage (%) of prescribed study product serving consumed during the intervention.	Adherence calculated from returned product counts and participant self-report as number of consumed servings divided by the number of prescribed servings.	28 days
Number of participants with adequate adherence during the intervention.	Participants who consume at least 80% of prescribed study product serving during the 28-day intervention.	28 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with any adverse event.	Number of participants with at least one adverse event recorded from through the day 28 visit, regardless of relationship to the intervention.	28 days
Number of participants with serious adverse events.	Number of participants with at least one serious adverse event, as defined by applicable ethical and regulatory criteria	28 days
Number of participants with treatment-related adverse events	Number of participants with at least one adverse event assessed by the investigator as possibly, probably, or definitely related to the assigned study product.	28 days
Number of participants with gastrointestinal intolerance symptoms.	Number of participants reporting gastrointestinal symptoms such as nausea, abdominal pain, bloating, diarrhea, constipation, vomiting, or other symptoms recorded in the tolerability form.	28 days
Number of participants who discontinue the study product due to an adverse event.	Number of participants who permanently stop consuming the assigned study product because of an adverse event.	28 days
Change from baseline in serum TNF-alpha concentration at day 28.	Fasting serum TNF-alpha concentration (pg/mL) measured using Human TNF-alpha ELISA Kit.	28 days
Change from baseline in serum OX-SR1 concentration	Fasting serum OX-SR1 concentration (pg/mL) measured using Human Oxidative Stress Responsive (OXSR1) ELISA Kit	28 days
Change from baseline in fasting insulin concentration at day 28.	Fasting serum insulin (uUI/mL) measure using the validated assay.	28 days
Change from baseline in total cholesterol concentration at day 28	Fasting serum total cholesterol concentration (mg/dL) measured using the laboratory method.	28 days
Change from baseline in LDL cholesterol concentration at day 28.	Fasting serum LDL cholesterol concentration (mg/dL) measured using the laboratory method.	28 days
Change from baseline in HDL cholesterol concentration at day 28.	Fasting serum HDL cholesterol concentration (mg/dL) measured using the laboratory method.	28 days
Change from baseline in triglyceride concentration at day 28.	Fasting serum triglyceride concentration (mg/dL) measured using the laboratory method.	28 days
Change from baseline in serum glucose concentration at day 28.	Fasting serum glucose concentration (mg/dL) measured using the laboratory method	28 days
Change from baseline in serum total protein concentration at day 28.	Fasting serum total protein concentration (mg/dL) measured using the laboratory method.	28 days
Change from baseline in serum total bilirubin concentration at day 28.	Fasting serum total bilirubin concentration (U/L) measured using the laboratory method.	28 days
Change from baseline in serum albumin concentration at day 28.	Fasting serum albumin concentration (g/dL) measured using the laboratory method.	28 days
Change from baseline in serum globulin concentration at day 28.	Fasting serum globulin concentration (g/dL) measured using the laboratory method.	28 days

Collaborators and Investigators

• Sponsor: Finis Terrae University

Publications and helpful links

General Publications

• Chen LK, Woo J, Assantachai P, Auyeung TW, Chou MY, Iijima K, Jang HC, Kang L, Kim M, Kim S, Kojima T, Kuzuya M, Lee JSW, Lee SY, Lee WJ, Lee Y, Liang CK, Lim JY, Lim WS, Peng LN, Sugimoto K, Tanaka T, Won CW, Yamada M, Zhang T, Akishita M, Arai H. Asian Working Group for Sarcopenia: 2019 Consensus Update on Sarcopenia Diagnosis and Treatment. J Am Med Dir Assoc. 2020 Mar;21(3):300-307.e2. doi: 10.1016/j.jamda.2019.12.012. Epub 2020 Feb 4.
• Shenkin A. Serum prealbumin: Is it a marker of nutritional status or of risk of malnutrition? Clin Chem. 2006 Dec;52(12):2177-9. doi: 10.1373/clinchem.2006.077412. No abstract available.
• Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyere O, Cederholm T, Cooper C, Landi F, Rolland Y, Sayer AA, Schneider SM, Sieber CC, Topinkova E, Vandewoude M, Visser M, Zamboni M; Writing Group for the European Working Group on Sarcopenia in Older People 2 (EWGSOP2), and the Extended Group for EWGSOP2. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing. 2019 Jan 1;48(1):16-31. doi: 10.1093/ageing/afy169.
• Calvani R, Marini F, Cesari M, Tosato M, Anker SD, von Haehling S, Miller RR, Bernabei R, Landi F, Marzetti E; SPRINTT consortium. Biomarkers for physical frailty and sarcopenia: state of the science and future developments. J Cachexia Sarcopenia Muscle. 2015 Dec;6(4):278-86. doi: 10.1002/jcsm.12051. Epub 2015 Jul 7.
• Beaudart C, Alcazar J, Aprahamian I, Batsis JA, Yamada Y, Prado CM, Reginster JY, Sanchez-Rodriguez D, Lim WS, Sim M, von Haehling S, Woo J, Duque G; Global Leadership Initiative in Sarcopenia (GLIS) group. Health outcomes of sarcopenia: a consensus report by the outcome working group of the Global Leadership Initiative in Sarcopenia (GLIS). Aging Clin Exp Res. 2025 Mar 22;37(1):100. doi: 10.1007/s40520-025-02995-9.

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: June 18, 2026
• First Submitted That Met QC Criteria: July 1, 2026
• First Posted (Actual): July 8, 2026

Study Record Updates

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

More Information

Terms related to this study

• Keywords: older adults; Sarcopenia; Seaweed; Inflammatory status
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Muscular Atrophy; Atrophy; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Sarcopenia; Amino Acids, Peptides, and Proteins; Amino Acids; Amino Acids, Essential; Amino Acids, Branched-Chain; Leucine
• Other Study ID Numbers: 25-124

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