There are many herbs and nutraceuticals that can help improve sleep quality. Certainly, your patients are aware of these, and many are experimenting with them, in their quest for better sleep.

But it is essential to understand the biological foundations of sleep in order to know how herbs and nutraceuticals can optimize the quantity and quality of sleep.

Sleep is regulated by the circadian rhythm, an internal 24-hour clock synchronized by light and darkness, which governs melatonin production in the pineal gland. Melatonin signals the body to prepare for sleep, coordinating the transition between wakefulness and rest.

Sleep itself cycles through distinct stages, including light sleep, deep non-REM sleep, and REM sleep, each playing a unique role in physical restoration, memory consolidation, and emotional regulation. Nutrients and botanical compounds that influence these processes, whether by supporting melatonin synthesis, modulating neurotransmitters, or reducing stress hormones, can help optimize sleep architecture and promote more restorative rest.

It is essential to understand the biological foundations of sleep in order to know how herbs and nutraceuticals can optimize the quantity and quality of sleep.

This mechanistic insight underscores the potential for targeted nutraceutical interventions to address specific disruptions within the sleep cycle, moving beyond simply increasing total sleep time to enhancing sleep quality at a physiological level.

Sleep for Body & Mind

Sleep plays a central role in restorative processes essential for optimal daytime performance, brain plasticity, and the preservation of cognitive functions such as emotional regulation and mental health. These benefits are linked to neuronal reorganization, growth, and repair that occur during deep sleep phases.

Unfortunately, a substantial proportion of the US population experiences sleep disturbances. No doubt you are seeing this in your practice. Weary of pharmaceutical fixes, people increasingly turns to herbal and natural supplements for relief (Brinkman et al., 2023; Yeom & Cho, 2024).

While many supplements are available, most base their claims on subjective reports of sleep quality. This makes it difficult for healthcare professionals to recommend products with confidence. While subjective experience is important, from a scientific viewpoint subjective measures may not truly align with objective outcomes. The need for solutions supported by both subjective and objective evidence has grown among consumers and clinicians alike.

Melatonin: Widely Used, Variable Quality

Melatonin is a very popular sleep supplement among consumers worldwide. Global sales of melatonin products topped $1.5 billion several years ago. While this neurohormone can be helpful in some cases of sleep disturbance, it is also problematic.

Most melatonin on the consumer market is produced synthetically, others are sourced from genetically-modified organisms and phyto melatonin-rich extracts. These alternatives face cost, scalability, and consumer acceptance challenges.

While many sleep supplements are available, most base their claims on subjective reports of sleep quality. This makes it difficult for healthcare professionals to recommend products with confidence.

Quality variability is also a concern with off-the-shelf retail melatonin products. Studies looking at actual melatonin content in consumer supplements show a shockingly wide range, going from 83 to 478 percent of the labeled amount. Contamination is also a problem with some products (Arnao et al., 2023). There are some porcine-derived melatonin products on the market, but these will be problematic for many people who have religious or ethical objections to pork-based ingredients.

Widespread consumer use, coupled with spotty regulatory oversight, have led many concerned medical professionals to calls for stricter regulation of melatonin, including reclassification of the ingredient as a prescription-only product. Melatonin is, in fact, classified as a prescription drug in some European countries.

While melatonin has clinical utility, especially for circadian rhythm disorders, its variability and potential safety concerns limit its appeal as a long-term solution for sleep problems.

Holixer: A Standardized Botanical Approach

Holixer is a hydroalcoholic extract of the herb Ocimum tenuiflorum, known colloquially as Holy Basil or Tulsi. This plant is an aromatic perennial native to Southeast Asia, and it has a long and venerable history of medicinal use in Ayurveda and other systems of traditional Asian medicine.

The Holixer extract is manufactured in a GMP-certified facility and standardized to at least 5% Ocimum Bioactive Complex (OBC). This is verified using high performance liquid chromatography (HPLC). Unlike the many other Holy Basil extracts on the market which are standardized only to triterpene content, Holixer is developed using Bioactive Optimization Technology, which integrates phytochemical profiling with biological validation to target specific health outcomes.

Clinical trials have shown that Holixer improves sleep stability and continuity by modulating NREM sleep microarchitecture and reducing sleep fragmentation. In particular, it increases the A1 subtype of the cyclic alternating pattern (CAP A1), an EEG biomarker reflective of deep NREM sleep and increased restorative function (Ferri et al., 2008).

Holixer has undergone comprehensive safety testing, including a 90-day oral toxicity study, as well as assessments of mutagenicity and genotoxicity, all confirming a favorable profile. It is self-affirmed GRAS in the US, registered with the Therapeutic Goods Administration in Australia, and under review with regulatory agencies in Canada, Korea, and Japan.

Melatonin vs Holixer

Endogenous melatonin regulates circadian rhythm but also influences metabolism, reproductive function, and neuroplasticity (Givler et al., 2023; Amaral & Neto, 2018). Exogenous melatonin supplementation can improve sleep latency and REM parameters but may cause metabolic effects in young adults and delayed puberty onset in children (Neubauer, 2020; Boafo et al., 2019). A lack of consistent dosing and quality control further complicates use of melatonin in clinical settings.

Holixer, by contrast, is an adaptogenic herb that supports neuroendocrine-immune balance. It reduces stress-induced sleep disturbances by antagonizing CRF1 receptors and lowering cortisol release, while also activating endogenous melatonin receptors, and inhibiting orexin pathways that promote wakefulness. These combined mechanisms of action lead to improvements in both subjective sleep quality and objective measures such as CAP stability.

Synergistic Benefits

Melatonin remains a useful option for specific populations, including older adults with sleep-wake phase disorders, shift workers, travelers with jet lag, and children with autism spectrum or ADHD. In these contexts, combining low-dose melatonin with Holixer may offer synergistic benefits.

Holixer is an adaptogenic herb that supports neuroendocrine-immune balance. It reduces stress-induced sleep disturbances by antagonizing CRF1 receptors and lowering cortisol release, while also activating endogenous melatonin receptors, and inhibiting orexin pathways.

Melatonin primarily improves sleep macrostructure by reducing latency and aligning circadian rhythm, while Holixer optimizes sleep microarchitecture, reduces stress-driven arousal, and enhances restorative sleep. Together, they address both structural and regulatory aspects of sleep, potentially allowing for lower melatonin doses and minimizing long-term side effects.

For healthcare professionals seeking evidence-based, plant-derived solutions for sleep management, Holixer offers a clinically validated option that addresses both physiological stress and sleep microarchitecture. While melatonin remains a valuable tool for certain cases, the quality and safety issues highlight the need for alternatives or complementary strategies.

The combined use of melatonin and Holixer, tailored to patient needs, represents a promising approach for improving both the quality and continuity of sleep, ultimately supporting cognitive performance and overall well-being.

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Suresh Lakshmikanthan, PhD, B.Pharm, is the Chief Business Officer at Natural Remedies, where he leads global business strategy and operations across the company’s pharmaceutical and nutraceutical divisions. With more than two decades of international experience, he is focused on advancing innovation and sustainable practices in botanical product development. Dr. Suresh has been a driving force in establishing Natural Remedies Human Health as a globally recognized, integrated herbal nutraceutical company.

He earned his Bachelor of Pharmacy from  Dr. M.G.R. Medical University, India. He also holds a PhD in International Business and Leadership and an MBA in International Business. He has authored research papers on international business and leadership, and his work continues to shape the intersection of global business strategy and botanical science.

About Natural Remedies: With a history dating back to 1950, Natural Remedies is an internationally recognized botanical healthcare company focused on combining traditional herbal wisdom with modern science. The company develops clinically supported, high-quality botanical branded ingredients used in health and wellness products around the world. Its team of 45+ scientists has published more than 230 research papers in peer-reviewed journals. Natural Remedies is committed to safety, sustainability, and innovation across its entire supply chain. All its ingredients are certified kosher and halal.