Developing Effective Products for Relaxation and Sleep

Insomnia is the most common sleep complaint. About one-third of Americans suffer from insomnia, and at least 10 percent have an ongoing problem with it. Prescriptions for pharmaceutical sleep aids are on the rise, yet these drugs do little or nothing to address the underlying problems or to support healthy sleep. Although many natural options exist to support sleep—from melatonin to botanical nervines to adrenal support—formulators often fail to create targeted, effective products. Achieving the right balance of ingredients in a formula is an art, but it must be guided by science.

Normal sleep is viewed by many as a little more than a divider between days. But sleep is much more than that: it is a critical daily restorative period during which the body rebuilds itself: growth hormone levels rise, cells regenerate, systems rejuvenate themselves, experiences are processed into memory and dreams occur. During normal sleep, the brain’s biological sleep clock, in response to patterns of light and darkness, regulates key processes in the body, such as hormone levels, body temperature and sleep patterns.

Disruptions to normal sleep can easily be glossed over, particularly in the young. Over time, however, chronic sleep disruptions can set the stage for chronic fatigue, depression and disease. Most adults need seven to nine hours of sleep every night to feel their best. Teens need about nine to nine-and-a-half hours of sleep per night. Elderly individuals, who tend to sleep less, commonly have more difficulty falling asleep at night, particularly if they take frequent catnaps during the day. Thirteen percent of men and 36 percent of women over the age of 65 years take more than 30 minutes to fall asleep.

Insomnia is when the quality of sleep is perceived to be inadequate to restore you, despite having had ample opportunity to sleep. The result is distress or disruption to your ability to function during the day (e.g., difficulty concentrating, memory problems, trouble coping with minor annoyances, and decreased pleasure in family and social relationships). Like fatigue or fever, insomnia is a symptom, not a disease. Many medical conditions can cause insomnia, however, so these should be thoroughly investigated, particularly in severe cases. Insomniacs are more than twice as likely as the general population to have a fatigue-related motor vehicle accident, and people who get less than five hours of sleep per night have a higher mortality rate than the general population.

Formulating for Sleep and Relaxation: What’s the Target?

There is not simply one kind of insomnia, so it does not make sense that there should be just one kind of sleep formula. Several classes of natural agents (mostly botanical) can be considered when crafting a sleep formula, depending on the target user. While there may be some overlap among ingredients, it is important to know by what mechanisms ingredients work, what their effective doses are, and what evidence exists to support their inclusion in a formula. Actions of botanical medicines that can affect the sleep cycle include nervine, sedative, adaptogen, anxiolytic, antispasmodic, analgesic, anti-inflammatory, and even actions on secondary systems whose symptoms can contribute to insomnia, i.e., antitussive, carminative, etc. Promoting relaxation and relieving insomnia is not simply about inducing drowsiness at bed time. Formulators should identify a specific approach to sleep restoration and formulate products that can complement one another. Consider, for example, two directions for sleep formula development that overlap with other categories: stress management and inflammation.

Stress and Sleep: The Adrenal Connection

Sleep deprivation is one of the most reliable and severe stress-inducers. Stress and insomnia can set up a vicious cycle. Chronic stress can cause insomnia. Insomnia, over the long-term, deprives the individual of adequate rest and renewal, leading to fatigue. To continue functioning, stimulants such as caffeine are used. However, caffeine impairs appropriate perception of rest requirements and the adrenal glands’ response to stress, while also disrupting sleep. Stress is modulated in part by the hypothalamic-pituitary-adrenal (HPA) axis. Chronic stress, as manifested in Selye’s classic General Adaptation Syndrome, is a major contributor to both HPA axis dysfunction and insomnia. Adaptogens are a class of botanical medicines that stabilize physiological processes and promote homeostasis, for example, decreased cellular sensitivity to stress. Adaptogenic herbs not only help reverse HPA axis dysfunction, but they can clear the way for nervines and or even anti-inflammatories to do a better job. The best-studied adaptogens include Rhodiola (Rhodiola rosea), Ashwagandha (Withania somnifera), maca (Lepidium meyenii), Eleuthero (Eleutherococcus senticosus) and Holy Basil (Ocimum sanctum).

Cytokines and Sleep: Inflammation and Insomnia Mutually Reinforce Each Other

Inflammation is another multi-system process that may contribute to sleep problems. Sleep, like stress and other complex biological processes, is influenced by cytokines and their effector molecules. Affector molecules that are particularly important in proper sleep regulation include nitric oxide, prostaglandins and adenosine. There is overwhelming evidence linking sleep deprivation to elevated levels of interleulin-1 (IL1) and tumor necrosis factor alpha (TNF-a). These elevations, in turn, are linked to symptoms associated with sleep deprivation, such as sensitivity to kindling and pain stimuli; cognitive, memory and performance impairments; depression; sleepiness; and fatigue. Chronic sleep loss is associated with pathologies such as metabolic syndrome, chronic inflammation and cardiovascular disease. Thus, conditions associated with elevated IL1 and/or TNF-a may disrupt sleep, and normalizing these cytokines may help improve insomnia. The supplement formulator’s materials kit contains many botanical agents capable of modulating cytokines. Ashwagandha, astragalus (Astragalus membranaceus), Holy Basil, maitake (Grifola frondosa), oats (Avena sativa), Jamaica dogwood (Piscidia erythrina) and, of course, turmeric (Curcuma longa) are all known to have effects on cytokines. Turmeric, specifically, has been shown to down-regulate IL-1 and TNF-a, among other cytokines.

A formulator must be guided by clinical evidence from the medical literature when it comes to determining dose for optimal efficacy and support of label claims. A formula should not try to do too much. When it has a focus—such as on nervine activity or adaptogenic actions—there is a better chance of efficacy and clearer purpose to support claims and other marketing imperatives.

Jeremy Appleton, N.D., is a licensed naturopathic physician, author, product development professional and educator. An industry veteran, Dr. Appleton currently works as director of scientific affairs at Nature's Way. He has been on faculty at Bastyr University and the National College of Natural Medicine. Dr. Appleton is the author of several books and hundreds of articles on natural medicine, and is an expert in assessing safety, efficacy and claims for dietary supplements.

Looking for more information on Sleep Support Products?

Jeremy Appleton, N.D., will speak on “Developing Effective Products for Relaxation and Sleep" as part of the Natural Products INSIDER track in the SupplySide West Education Program. His session will take place on Tuesday, Oct. 6, from 1 to 1:50 p.m. at Mandalay Bay in Las Vegas. Visit http://west.supplysideshow.com/edu-more.aspx for more information and to get registered.