Sleep is a physiological brain state characterized by altered consciousness, reduced responsiveness to environmental stimuli, and defined autonomic, motor, and postural features 1. It comprises two primary phases—REM (Rapid Eye Movement) and NREM (Non-Rapid Eye Movement) —which alternate cyclically throughout the sleep period. During REM sleep, sympathetic nervous system activation leads to elevated body temperature, increased blood flow and pressure, and an accelerated heart rate 2. Sleep is essential for restorative processes, energy conservation, and physiological protection, whereas sleep deprivation can significantly impair daily functioning—socially, somatically, psychologically, and cognitively 3. Disruptions in sleep may compromise various brain functions, resulting in diminished learning performance, slower reaction times, heightened seizure risk, irritability, and depressive symptoms 4.

In clinical practice, sleep-related complaints are exceedingly common and typically include difficulties initiating or maintaining sleep, nocturnal awakenings, early morning awakenings, non-restorative sleep, abnormal nocturnal behaviors, daytime fatigue or sleepiness, impaired concentration, emotional lability, anxiety, depression, and musculoskeletal pain 3. Consequently, there is a pressing need for safe and effective therapies capable of mitigating stress-related physiological dysregulation and enhancing sleep quality 5.

Sleep disorders are primarily diagnosed through overnight, in-laboratory polysomnography—which simultaneously records EEG, EOG, chin and limb EMG, airflow, respiratory movements, ECG, and oximetry 6. However, this gold-standard methodology requires specialized infrastructure, trained personnel, and substantial financial investment, limiting its feasibility in many research and clinical contexts. As an alternative, validated subjective instruments such as the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS) offer reliable and accessible means of assessing sleep disturbances.

The PSQI, developed by Buysse et al. (1989), encompasses both quantitative and qualitative aspects of sleep across seven components—subjective quality, latency, duration, efficiency, disturbances, medication use, and daytime dysfunction—yielding a global score ranging from 0 to 21; scores above 5 indicate clinically significant sleep disturbance 78. In our study, the ILIB group demonstrated a meaningful reduction in PSQI scores from 10.24 at baseline to 6.47 post-treatment.

The ESS, originally developed by Johns (1989; 1991; 2000), measures daytime sleepiness through eight common scenarios rated from 0 to 3, with total scores above 10 indicating excessive daytime sleepiness. In our sample, ESS change was non-significant, possibly reflecting the absence of primary hypersomnolence and the predominance of nocturnal symptoms, which are more effectively detected by the PSQI.

Among promising non-pharmacological interventions, photobiomodulation (PBM) has gained attention for its diverse physiological effects, non-invasive nature, and absence of significant side effects. PBM utilizes LED or laser light sources (600–1100 nm) to stimulate cellular pathways—including nucleic acid and protein synthesis, enzyme activation, and cell cycle regulation—while enhancing mitochondrial redox balance, primarily through cytochrome c–mediated ATP production and downstream signaling activation 910111213. Systematic reviews have supported PBM’s neuroprotective, anti inflammatory, vasodilatory, and anti-stress effects, although protocol variability remains a limitation and calls for greater standardization 141315.

Modified Intravascular Laser Irradiation of Blood (ILIB), often referred to as non-invasive ILIB, involves the transcutaneous irradiation of large superficial arteries to achieve systemic effects via in situ blood irradiation 161718. This approach has been shown to positively modulate microcirculation, blood viscosity, immune function, and oxidative stress, while also stimulating rheological parameters and vascular wall components associated with improved hemodynamics and metabolic homeostasis 192021. However, existing clinical trials reveal heterogeneity in dosing and administration, highlighting the need for standardized treatment protocols 1920.

Emerging clinical evidence supports both PBM and ILIB as potential interventions for improving sleep outcomes. A recent randomized, sham-controlled trial applying red/near-infrared PBM to the neck region demonstrated enhanced subjective relaxation and sleep quality in individuals with subjective cognitive decline 2223. Another study utilizing 830 nm laser irradiation of the palm in night-shift nurses reported significant improvements in PSQI and Athens Insomnia Scale (AIS) scores, with benefits sustained one month post-intervention 24. Additionally, ILIB has been shown to reduce pain and enhance daily functioning—including sleep—in individuals recovering from COVID-19 25. A notable case report described an improvement in PSQI score from 12 to 7 in a patient with Guillain–Barré syndrome following ILIB 26. A systematic review further suggests that ILIB effectively modulates inflammatory markers and promotes tissue repair in animal models 20.

Taken together, accumulating evidence from 2022 to 2025 reinforces the potential of PBM—and transcutaneous ILIB in particular—to improve sleep quality by enhancing sleep latency, efficiency, and subjective well-being. Nevertheless, rigorous randomized controlled trials employing standardized dosing parameters and objective biomarkers—such as polysomnography and oxidative stress markers—are essential to confirm efficacy and elucidate underlying mechanisms. Accordingly, the present clinical trial aims to assess the impact of transcutaneous ILIB compared to sham treatment on perceived sleep quality, as measured by the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS).

This study was conducted as a randomized, double-blind clinical trial in accordance with international standards outlined in the CONSORT (Consolidated Standards of Reporting Trials) statement for randomized controlled trials. The trial protocol was developed following the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines and was registered on ClinicalTrials.gov under the identifier NCT05415163. Ethical approval was granted by the Research Ethics Committee of Universidade Nove de Julho (CAAE: 54691921.4.0000.5511), under opinion number 5.305.314, in compliance with the guidelines for research involving human participants.

Between June 2022 and September 2022, 97 participants were identified for eligibility, and 72 were randomized to receive Modified Intravascular Laser Irradiation of Blood (ILIB) (n = 36) or Modified Intravascular Laser Irradiation of Blood Sham (n = 36). A total of 67 participants completed the study and had their data analyzed. 5 participants who did not complete the study had 5 absences, attending only the first session and not completing the 6 sessions stipulated for our study, so their data were not analyzed.

Due to the number of patients affected with sleep disorders added to the costs and side effects of medications, it is extremely necessary to find new therapeutic approaches or alternative treatments that present good results, greater ease of use, good patient acceptance, all with lower cost and reduced side effects. Thus, the Modified Intravascular Laser Irradiation of Blood (ILIB) technique emerges as a promising approach. In the present study, we investigated whether Modified Intravascular Laser Irradiation of Blood (ILIB) would influence the sleep quality of patients with compromised sleep, through a randomized controlled clinical trial.

The present study is pioneering in the evaluation of the use of Vascular Photobiomodulation FBMV specifically on sleep quality as a complementary treatment, following rigorous methodology in relation to patient selection, randomization of groups, confidentiality of active or placebo group allocation, masking of application, and control of losses.

Positive results after evaluating the scores of the study variables may suggest that, in a systemic way through the application of FBM, we can observe effects already described for local photobiomodulation.

This effect of the therapy observed on sleep quality also seems to be related to effects of ILIB such as antioxidant, immunological, and hormonal action with direct reflections on the quality of life and sleep regulation, as researchers cite that the equipment that performs Modified Intravascular Laser Irradiation of Blood (ILIB) emits a luminous energy that activates the regulation and neuro-humoral synchronization and cellular modulation with antioxidant, metabolic, immunological, antispasmodic, sedative, healing, analgesic, anti-inflammatory effects, and increased blood circulation. It has a central effect stimulating the limbic system and hypothalamus, as well as a hormonal effect regulating sleep, mood, and normalizing endorphins and serotonin, generating well-being and improving quality of life 27162817293031.

Our results showed that treatment with ILIB promoted improvement in the scores evaluated on the Epworth Sleepiness Scale (ESS) and on the Pittsburgh Sleep Quality Index (PSQI). This result leads us to suggest that ILIB modulates the homeostasis of the organism through its systemic action. The literature points out that the mechanism of action of FBM is based on the absorption of photons by cellular chromophores, the most described being the enzyme cytochrome c oxidase, which is part of the mitochondrial respiratory chain. The absorption of energy delivered by light sources initially generates an increase in ATP production and electron transport, which will lead to the activation of many signaling pathways that will subsequently activate transcription factors related to the production of key proteins in the regulation of cellular metabolism and the inflammatory response. 32

A recent pilot study investigating the effects of Intravenous Laser Irradiation of Blood (ILIB) in long COVID patients with persistent neurological symptoms provides valuable insight into the broader therapeutic potential of ILIB, particularly regarding sleep quality. In this study, patients underwent a series of 30 ILIB sessions, resulting in significant improvements in both cognitive function and sleep quality, as evidenced by enhanced scores on the Montreal Cognitive Assessment (MoCA) and the Athens Insomnia Scale (AIS) post-treatment. These clinical outcomes were paralleled by molecular findings, including upregulation of mitochondrial electron transport and oxidative phosphorylation pathways, alongside downregulation of immune and inflammatory responses. Notably, modulation of the glutathione metabolism pathway suggested a reduction in oxidative stress, a mechanism closely linked to sleep regulation and neuroprotection. The observed amelioration of insomnia symptoms in this cohort supports the hypothesis that ILIB may exert beneficial effects on sleep quality through the attenuation of neuroinflammation and oxidative imbalance. These findings align with the objectives of the present study, reinforcing the rationale for exploring ILIB as a non-pharmacological intervention to improve sleep quality, and underscore the need for further research in larger, controlled populations to validate these preliminary results. 33

The systemic physiological effects of ILIB, such as reduced oxidative stress and improved microcirculation, may directly influence the neural circuits of sleep-wake regulation. Specifically, enhanced metabolic homeostasis might modulate the activity of the ventrolateral preoptic area (VLPO)—a key sleep-promoting nucleus—or the ascending reticular activating system (ARAS). The complex, systemic nature of sleep regulation necessitates therapeutic approaches that target multiple physiological pathways, akin to the multifactorial engineering solutions required in other complex systems 34.

The observed improvement in sleep quality may be related to ILIB’s documented antioxidant, immunological, and hormonal effects, with direct reflections on the quality of life and sleep regulation.

The results from this sample suggest that ILIB may provide benefits for sleep, particularly regarding sleep time per night and the quality of rest

Considering that this study is pioneering in the use of Modified Intravascular Laser Irradiation of Blood (ILIB) specifically for the treatment of sleep quality, the data are interesting and promote the stimulation of future investigations, mainly in relation to the mechanisms involved, better dosimetry and application time, in addition to the possibility of conducting studies with greater investment in marker analysis and the use of polysomnography.

The sample size of this study allows us to understand that Modified Intravascular Laser Irradiation of Blood (ILIB) seems to present benefits for the sleep of patients, in relation to sleep time per night, quality of rest after sleep, tiredness during the day, difficulty waking up or falling asleep, and score on the questionnaires. It is a cost-effective equipment, simple application technique, and accessible for use in the hospital, clinical, and domestic environment, and does not require complex structure and prerequisites for its handling.

This study has limitations that should be considered. First, it relied solely on subjective self-report measures (PSQI and ESS); while validated, these do not provide the objective physiological data offered by polysomnography or actigraphy. Second, the relatively short-term nature of the intervention and follow-up leaves the long-term durability of the treatment effects unknown. Finally, the sample consisted of adults with self-reported poor sleep, which may limit the generalizability of the findings to clinical populations with diagnosed insomnia disorders or severe comorbidities.

The results of the present randomized clinical trial showed that the use of Modified Intravascular Laser Irradiation of Blood (ILIB) can be presented as a therapeutic alternative for compromised sleep. Through the results, it was possible to observe positive effects on sleep quality, sleep latency, and control of daytime sleepiness demonstrated through a significant decrease in the scores of the PSQI questionnaires. Thus, we can conclude that Modified Intravascular Laser Irradiation of Blood (ILIB) is a safe technique and that it emerges as a therapeutic possibility for contributing to sleep quality, the data are promising and promote the stimulation of future investigations, mainly in relation to the mechanisms involved, better dosimetry and application time, in addition to the possibility of conducting studies with greater investment in biomarker analysis and the use of polysomnography.