Resetting the Circadian Architecture: How Restorative Sleep and Autonomic Stress Regulation Extend Biological Healthspan

Nutraceuticals World (NW): How does sleep relate to biological aging? What does the science show?

Pavitra Viswanath, PhD, Director of Clinical Affairs, Saanroo: Healthy sleep quantity and quality are key to optimal mental and physical health. Cumulative scientific evidence points to a role for sleep loss and sleep disturbances as contributors to early disease onset and shortened survival. 

NW: What should product developers consider when targeting sleep latency, stress regulation, restorative sleep, and overall sleep quality?

Viswanath: Product developers should consider the pathways that bring in a good quality of sleep. A starting point is sleep latency. This is the time taken to fall fully asleep after going to bed. This is a key factor in determining sleep duration, restorative sleep, and sleep quality. Factors that increase sleep latency are pain, inflammation, stress, anxiety, and a host of other minor factors. These lead to disturbed sleep, lethargy, and impaired cognition upon awakening. There are ingredients available in the industry that cater to this aspect of sleep. 

A key example is Levagen+, a highly bioavailable form of Palmitoylethanolamide which has been shown in a gold-standard, double-blind, randomized, placebo-controlled human clinical study to have the following benefits:

• Significant reduction in sleep onset latency (time to fall asleep), especially in individuals with difficulty falling asleep;
• Faster time to feel fully awake and improved cognitive performance on waking, indicating that there is better sleep-to-function transition. No drowsiness, showing that it’s non-sedative.

These are key issues in improving sleep quality and active wakefulness after a good night’s sleep. 

Ingredients like Affron brand Saffron extract and Lavender Oil are good ingredients for developing sleep formulas.

NW: What role does the endocannabinoid system (ECS) play in stress regulation and sleep support?

Viswanath: The endocannabinoid system (ECS) helps control the sleep-wake cycle and promotes deep non-rapid eye movement (NREM) sleep. It aligns with your internal biological clock, helping manage when you feel alert or tired. 

The body produces its own cannabinoids, called endocannabinoids (such as anandamide and 2-arachidonoylglycerol). Higher levels of endocannabinoids encourage NREM sleep and help stabilize sleep patterns.

Palmitoylethanolamide has been shown to help protect and elevate anandamide (AEA) levels in the body. This biochemical teamwork is recognized in pharmacology as a primary component of the “entourage effect.”

Levagen+, a brand of PEA, would again be an ideal tool to leverage this beneficial mechanism of action related to the body’s need for sleep.

NW: How can product formulators deliver non-sedative sleep products that promote restorative sleep while supporting next-day cognitive clarity?

Viswanath: One of the key issues with sleep formulas is that they contain substances that give a sedative effect. One common ingredient in sleep formulas is Valerian Root Extract. Individuals consuming Valerian Root are strongly advised not to drive or operate heavy machinery due to its powerful central nervous system sedative properties. Because Valerian interacts with brain chemicals to promote relaxation and sleep, it can mimic the cognitive and physical impairments caused by prescription sedatives, directly threatening road safety.

So one needs to be aware of these side effects associated with sleep formulas and to design formulas containing non-sedative ingredients with proven mechanisms of action that support healthy sleep.

NW: What’s missing in today’s marketplace of sleep solutions? What opportunities do you see for future innovation?

Viswanath: Opportunities we see for future innovations are to develop non-sedative solutions with proven mechanisms of action for promoting healthy sleep levels. Format versatility and delivery systems would be key cogs in the wheel for developing new formulations.

Speaking of format versatility, the Compressible Powdered Oils (CPO_ technology and the LipiSperse Lipid dispersion technology, developed by Pharmako Biotechnologies, Australia, are excellent delivery systems that enhance the bioavailability and versatility of ingredients and formulations.

Levagen+ of Saanroo, described above, is powered by the LipiSperse delivery system to increase bioavailability. The CPO technology converts Lavender Oil into a compressible and tablettable, free-flowing powder. Lavender oil has a sleep claim with EFSA in the EU and is well known for promoting restful sleep. The CPO technology allows the oil to be formulated as a powder with a 50% oil load.