A GUIDE TO SUPPLEMENTS FOR INSOMNIA

Sleep duration and quality are closely connected with health. Reduced sleep is correlated with heart disease, stroke, decreased immune function, obesity, and death. The American Academy of Sleep Medicine and the Sleep Research Society recommend that adults get at least 7 hours of sleep per night (1).

Many people in the US turn to sleep supplements without a clear understanding of their mechanism or scientific data. While it is biologically plausible that some of these supplements can improve sleep, the very limited data on their sleep-inducing benefits makes it difficult to strongly recommend them. The information below is intended as a primer for patients currently using sleep supplements or considering their therapeutic benefits.

How Do Supplements Impact Insomnia?

Numerous supplements are used to treat insomnia including apigenin, GABA, glycine, magnesium L-threonate, and L theanine. These supplements commonly work through the GABA chemical pathway to quiet the mind and induce relaxation. The GABA pathway is also targeted by prescription anti-anxiety and insomnia medications such as Valium and Ambien.

Commonly Used Supplements

Apigenin

Recommended Dose: 50mg taken 30-60 minutes before bed

Apigenin is a type of flavonoid found in various plants including chamomile and celery. Its calming and sleep-inducing effects are attributed to its activation of GABA receptors in the brain. While there are anecdotal claims of Apigenin helping individuals, there is no compelling evidence showing the benefits of this agent in people with insomnia. A small study of 34 patients showed no difference between the study group and the control group (2).

Ashwagandha

Recommended Dose: 600mg taken 30-60 minutes before bed

Ashwagandha, an Ayurvedic herb, has been shown to improve sleep quality including sleep latency and sleep efficiency in a randomized, placebo-controlled trial with 80 patients (3). A Meta-analysis including 5 studies and 400 patients also demonstrated improved sleep quality and reduced anxiety. While the short-term data is encouraging, there is no safety data on long-term use (4).

GABA (Gamma-aminobutyric acid)

Recommended Dose: 100-300mg taken 30-60 minutes before bed

GABA is the main inhibitory neurotransmitter in the human brain. It has been shown to promote relaxation and improve sleep including decreased sleep latency in multiple studies. Of note, the results were inconsistent across studies and involved small numbers of patients, different formulations of GABA, and focused on different results (5,6).

Glycine

Recommended Dose: 2-3g per day taken 30-60 minutes before bed

Glycine is an amino acid, one of the building blocks of protein. It is found in meat, fish, eggs, dairy, and legumes. Research suggests that its temperature-lowering and sleep-inducing effects are mediated through the activation of the NMDA receptors in the suprachiasmatic nucleus, the body’s biological clock that regulates the sleep-wake cycle (7). Glycine facilitates the body’s decrease in core body temperature during its progression to sleep. An additional impact on sleep is due to increases in serotonin levels (8).

In human studies, glycine ingestion improved sleep quality and shortened latency to sleep onset and slow wave sleep without changing sleep architecture (9).

L-Theanine

Recommended dose: 50-400mg taken 30-60 minutes before bedtime

L-theanine is an amino acid found in green tea leaves. It works by influencing brain levels of serotonin and GABA. It has been studied for its potential to promote relaxation and improve sleep quality. Research suggests that L-theanine may help people relax before bedtime, fall asleep more easily, and experience deeper sleep (10). Of note, L Theanine is considered safe for long-term use and does not induce the daytime drowsiness associated with most sleep aids.

Magnesium L-Threonate –

Recommended Dose: 300-500mg taken 30-60 mins before bed

Magnesium is a mineral that supports multiple body functions including muscle and nerve function, blood glucose control, and bone health. Several studies have shown that magnesium L- threonate may increase sleep duration and quality. A double-blind, placebo-controlled trial showed magnesium increased sleep time and sleep efficiency and decreased sleep latency (11).

Magnesium L-threonate is considered better than other forms of magnesium for treating insomnia due to its unique ability to cross the blood-brain barrier, which allows it to increase magnesium levels in the brain.

Adverse effects of magnesium include gastrointestinal upset and headaches. It may also interact with medications for osteoporosis and diuretics.

Myo-inositol

Recommended Dose: 1000mg – 2000mg when awakened in the middle of the night to get back to sleep

In a single small study, Myo-inositol supplementation has been shown to increase sleep quality and duration in pregnant women (12). Mechanistically it has been associated with activation of the serotonin and orexin pathways in the brain and may quiet mental chatter that commonly interferes with sleep.

Phosphatidylserine

Recommended Dose: 400-600mg taken 30-60 minutes before bed

Phosphatidylserine is a phospholipid that plays a key role in cell membrane structure and function. It has stress-reducing benefits that make it a potential tool for insomnia, but it has not been formally studied.

Phosphatidylserine helps regulate cortisol, the stress hormone, a key factor in sleeplessness (13). Sleeplessness is often brought on by the mind processing the previous day or planning the next day. Our adrenal glands respond by releasing cortisol. This natural reaction to daily stress prevents people from falling back asleep when they wake up in the middle of the night.

Non-Supplement Sleep Practices:

1 Exercise every day

2 Find a consistent sleep time

3 Avoid liquids after 6 pm

4 Eat a light dinner without alcohol or caffeine

5 Make an agreement with yourself not to process thoughts from the previous day or plan the next day

Bradford Rabin MD aims to provide the best concierge physicians in the Bay Area for patients in Palo Alto, Menlo Park, Atherton, Los Altos, Portola Valley, Hillsborough, and Woodside.

1. Recommended Amount of Sleep for a Healthy Adult: A Joint Consensus Statement of the American Academy of Sleep Medicine and Sleep Research Society

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4434546/

2. The Therapeutic Potential of Apigenin

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6472148/

3. Clinical evaluation of the pharmacological impact of ashwagandha root extract on sleep in healthy volunteers and insomnia patients: A double-blind, randomized, parallel-group, placebo-controlled study

https://pubmed.ncbi.nlm.nih.gov/32818573/

4. Effect of Ashwagandha (Withania somnifera) extract on sleep: A systematic review and meta-analysis

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8462692/

5. Effect of oral γ-aminobutyric acid (GABA) administration on sleep and its absorption in humans

https://pubmed.ncbi.nlm.nih.gov/30263304/

6. Safety and Efficacy of Gamma-Aminobutyric Acid from Fermented Rice Germ in Patients with Insomnia Symptoms: A Randomized, Double-Blind Trial

https://pubmed.ncbi.nlm.nih.gov/29856155/

7. The Sleep-Promoting and Hypothermic Effects of Glycine are Mediated by NMDA Receptors in the Suprachiasmatic Nucleus

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4397399/

8. Oral administration of glycine increases extracellular serotonin but not dopamine in the prefrontal cortex of rats

https://pubmed.ncbi.nlm.nih.gov/21414089/

9. Glycine Ingestion Improves Subjective Sleep Quality in Human Volunteers, Correlating With Polysomnographic Changes