New sleep-enhancing nutraceutical blend falls short in clinical trial

By Hugo Francisco de SouzaApr 10 2024Reviewed by Benedette Cuffari, M.Sc.

In a recent study published in Scientific Reports, researchers evaluate the efficacy of a novel nutraceutical formulation containing L-theanine supplemented with valerian, saffron, and lemon balm extracts to improve sleep quality.

Study: Effect of a nutraceutical combination on sleep quality among people with impaired sleep: a randomised, placebo-controlled trial. Image Credit: Stock-Asso / Shutterstock.com

The dangers of sleep deprivation and the potential for nutraceuticals

Over the past several decades, an unprecedented rise in the incidence and prevalence of chronic and non-communicable diseases, especially cardiovascular diseases (CVDs), cancers, and mental health conditions, has been observed. In addition to diet, sleep is the most commonly cited risk factor in most non-transmissible diseases.

Sleep represents a human biological process responsible for energy saving and restoration, tissue growth and repair, and memory consolidation. Sleep has also been associated with the breakdown and removal of noxious metabolites, including beta-amyloid.

To date, sleep has been found to be closely linked to social, environmental, physiological, and individual factors. Each of these factors can significantly alter the sleep experience, which leads to almost half of all humans receiving insufficient quality or duration of sleep.

Nevertheless, sleep disorders have been successfully managed in the past, often through clinical interventions, including health behavioral modifications and pharmacotherapy. Nutraceutical products derived from plants and plant extracts have also been used, given their relative safety and low cost compared to pharmacotherapeutic interventions.

L-theanine, a tea derivative, has been shown to improve relaxation, sleep quality, mood, and cognitive performance. Likewise, lemon balm (Melissa officinalis) extracts appear to enhance sleep quality in patients with insomnia. Valerian (Valeriana officinalis) and saffron (Crocus sativus) extracts have similarly been tested and found to have significant positive effects on sleep with minimally adverse side effects.

About the study

The present study aims to assess the effects of a nutraceutical comprised of L-theanine, lemon balm, valerian, and saffron extracts administered over a six-week period in individuals with poor sleep quality. The randomized, double-blind, and placebo-controlled study was conducted in Bogota, Colombia, between December 2022 and June 2023.

All study participants were 18 years of age and older with Pittsburgh sleep quality scores (PSQIs) exceeding five and were not receiving treatment for their condition. Individuals with severe and pre-existing mental health conditions, those consuming over 400 mg of caffeine per day, daily smokers, and individuals with frequent and occupation-related sleep deprivation were excluded from the study.

Data collection included sociodemographic, anthropometric, and medical histories of all participants. Blood pressure and heart rate metrics were collected using a sphygmomanometer and pulse oximeter.

Study participants were also required to complete PSQI and the SF-36 quality of life questionnaires and provide blood and saliva samples. Blood samples were used to identify and quantify plasma glucose, lipid profiles, liver enzymes, creatinine, urea, bilirubin, and thyroid-stimulating hormone. Saliva samples were used to quantify the expression of cortisol.

Study outcomes, dosage adherence, and any adverse effects were reported by each enrolled participant in a health diary throughout the six-week-long intervention.

Study findings

Of the 193 candidates initially screened, 67 met the study inclusion criteria and were included in the analysis. Three participants eventually declined to complete the study, thus resulting in a final dataset of 64 participants, 35 and 29 of whom were randomized to receive the nutraceutical formulation and placebo, respectively.

No statistically significant improvements in sleep quality were observed between case and control cohorts. The primary outcome, referred to as a change in sleep efficiency, showed no change between the cohorts despite significant improvements in PSQI scorers across both cohorts. In fact, within-group improvements were observed across both groups, with these effects more distinct in the placebo group, both in sleep duration and PSQI/Sf-36 scores.

Multiple factors can explain the results of our study, in which the intervention and placebo group experienced similar improvements in key sleep outcomes. Many effective interventions for sleep disturbances are behavioural in nature, including relaxation training, stimulus control therapy, sleep restriction therapy, sleep hygiene, paradoxical intention therapy, cognitive restructuring, and many others."

Conclusions

Despite each of its constituents having been proven effective in improving sleep quality in isolation, the combination of nutraceuticals developed in the current study did not significantly change sleep quality. Behavioral and cognitive factors may play a role in this observation; therefore, additional research is needed before nutraceuticals can supplement or even replace their synthetic alternatives in treating sleep disorders.