NCT07461402

Plant Protein With Ashwagandha-Rhodiola for Sleep Quality

Effects on Sleep Quality and Bioelectrical Parameters of Cellular Health After Administration of a Plant Protein Supplement Combined With Ashwagandha and Rhodiola

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 100 (actual)
• Sponsor: Universidad Pablo de Olavide · Academic / Other
• Sex: All
• Age: 35 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

This study evaluates whether a combination of plant protein with adaptogenic herbs (ashwagandha and rhodiola) can improve sleep quality in middle-aged adults with sleep disturbances. One hundred participants aged 35-70 years with sleep problems will be randomly assigned to receive either the active intervention or placebo for 30 days. The active group will receive 27 grams per day of plant protein (pea, rice, and hemp isolate) combined with 300 mg of Rhodiola rosea and 500 mg of Withania somnifera (ashwagandha KSM-66®) in tablet form. The placebo group will receive maltodextrin and placebo capsules that look identical. Sleep quality will be measured daily using a validated Sleep Quality Questionnaire (SQQ) that assesses difficulty falling asleep, daytime sleepiness, and overall sleep quality. Body composition and cellular health will also be measured using bioimpedance analysis at the beginning and end of the study. The primary hypothesis is that the combination of plant protein with ashwagandha and rhodiola will produce greater improvements in sleep quality compared to placebo. The study will also evaluate the safety and tolerability of this nutritional intervention.

Detailed description

BACKGROUND AND RATIONALE Sleep disturbances affect 30-40% of the adult population worldwide and are associated with serious health consequences including insulin resistance, weight gain, and increased cardiovascular risk. While pharmaceutical sleep medications (benzodiazepines and hypnotics) are commonly prescribed, they have significant limitations including potential for addiction, adverse side effects, and disruption of natural sleep architecture. Natural alternatives are increasingly sought. Protein supplementation may influence sleep through multiple mechanisms: proteins provide tryptophan (a precursor to serotonin and melatonin), help stabilize nocturnal blood glucose levels, and can generate bioactive peptides with sedative properties. However, studies on protein and sleep have shown mixed results. Adaptogens are medicinal plants that help the body adapt to stress. Ashwagandha (Withania somnifera) has been extensively studied and shown to improve sleep quality, reduce sleep latency, and decrease nighttime awakenings, likely through modulation of the hypothalamic-pituitary-adrenal (HPA) axis and GABAergic effects. Rhodiola rosea, another well-characterized adaptogen, has demonstrated stress-resilience enhancement and neuroprotective effects. This study is the first to investigate the combined effects of plant protein with both ashwagandha and rhodiola on sleep quality, hypothesizing a synergistic multimodal effect. STUDY DESIGN This is a randomized, double-blind, placebo-controlled, parallel-group clinical trial conducted at three sites in Spain (Pozoblanco, Seville, and Yecla). The study was approved by the Research Ethics Committee of the Virgen Macarena and Virgen del Rocío University Hospitals (Code: 2061-N-21) on June 21, 2021, and is conducted in accordance with the Declaration of Helsinki. PARTICIPANTS One hundred adults aged 35-70 years with sleep disturbances will be recruited and randomized 1:1 to intervention (VERUM, n=50) or placebo (PLACEBO, n=50) groups. Key inclusion criteria include experiencing sleep disturbances, willingness to consume the plant protein supplement, and ability to provide informed consent. Exclusion criteria include known allergies to study ingredients, current use of sleep medications, serious medical conditions, and pregnancy or lactation. INTERVENTION VERUM Group: Participants will receive plant protein powder (27 g/day containing pea, rice, and hemp protein isolate) plus two tablets daily containing Rhodiola rosea (300 mg) and Withania somnifera KSM-66® (500 mg) for 30 consecutive days. PLACEBO Group: Participants will receive maltodextrin powder (matched for appearance and taste) plus placebo capsules (identical in appearance) for 30 consecutive days. All participants and investigators will be blinded to group assignment throughout the study period. OUTCOME MEASURES Primary Outcome: Sleep quality will be assessed using the validated Sleep Quality Questionnaire (SQQ), completed daily by participants. The SQQ evaluates three domains: * Sleep Difficulty subscale (range 0-16) * Daytime Sleepiness subscale (range 0-24) * Total Sleep Score (range 0-40) Higher scores indicate worse sleep quality. Secondary Outcome: Phase angle, a bioelectrical parameter reflecting cellular health and membrane integrity, will be measured using bioimpedance analysis (BIA-TELELAB) at baseline (Day 0) and end of intervention (Day 30). STATISTICAL ANALYSIS Sleep quality data will be analyzed using longitudinal mixed models to account for repeated daily measurements. Phase angle will be analyzed using non-parametric tests. Effect sizes will be calculated using Cohen's d. The significance level will be set at α = 0.05. Analysis will include all participants who complete outcome assessments. PROPOSED MECHANISMS The proposed mechanisms of action include: (1) tryptophan provision for serotonin/melatonin synthesis, (2) HPA axis modulation and cortisol reduction, (3) GABAergic effects, (4) nocturnal glycemic stabilization, and (5) enhanced stress resilience through adaptogenic pathways. SAMPLE SIZE JUSTIFICATION A sample size of 100 participants (50 per group) was determined to provide adequate statistical power to detect clinically meaningful differences in sleep quality measures between groups, accounting for an estimated dropout rate of 20-30%. SAFETY MONITORING Participants will be monitored for adverse events throughout the study. Any adverse events will be recorded and reported according to institutional and regulatory requirements.

Conditions

• Sleep Quality
• Sleep Disorders
• Insomnia

Interventions

Type	Name	Description
DIETARY_SUPPLEMENT	Plant Protein Supplement	Plant-based protein powder supplement containing 27 grams per day of a proprietary blend of three protein sources: pea protein isolate, rice protein isolate, and hemp protein isolate. The powder is mixed with water or beverage of choice and consumed once daily for 30 consecutive days. This protein blend provides essential and branched-chain amino acids, including tryptophan (precursor to serotonin and melatonin), which may influence sleep quality through neurotransmitter synthesis and nocturnal glycemic stabilization.
DIETARY_SUPPLEMENT	Rhodiola rosea Extract	Rhodiola rosea extract supplement in tablet form containing 300 milligrams per day. One or two tablets taken daily with meals for 30 consecutive days. Rhodiola rosea is an adaptogenic herb that helps the body manage stress through modulation of the hypothalamic-pituitary-adrenal (HPA) axis. It enhances stress resilience and has neuroprotective effects. May synergistically improve sleep quality when combined with other adaptogens and protein supplementation.
DIETARY_SUPPLEMENT	Ashwagandha KSM-66	Withania somnifera (Ashwagandha) KSM-66® extract supplement in tablet form containing 500 milligrams per day. One or two tablets taken daily with meals for 30 consecutive days. Ashwagandha is an adaptogenic herb that modulates the hypothalamic-pituitary-adrenal (HPA) axis, reduces cortisol levels, and has gamma-aminobutyric acid (GABA) receptor effects. Extensively studied for improving sleep quality, reducing sleep latency, and decreasing nighttime awakenings.
DIETARY_SUPPLEMENT	Placebo	Placebo intervention consisting of two components: (1) Maltodextrin powder matched to the active protein powder in appearance, taste, texture, color, and packaging, mixed with water or beverage, consumed once daily; and (2) Inert placebo capsules identical in appearance, size, color, shape, and packaging to the active adaptogen tablets, taken with meals. All placebo products contain no active ingredients and are consumed for 30 consecutive days. Participants, care providers, investigators, and outcomes assessors are blinded to treatment assignment.

Timeline

• Start date: 2025-11-01
• Primary completion: 2025-12-02
• Completion: 2025-12-04
• First posted: 2026-03-10
• Last updated: 2026-03-10

Locations

1 site across 1 country: Spain