SLEEPING TROUBLES? THESE SUPPLEMENTS COULD HELP (EVIDENCE-BASED)



I am no chemist, but I find it fascinating that so much pharmaceutical R & D money is spent on figuring out patentable chemical compounds that help enhance the activity of inhibitory neurotransmitters (ex. GABA) when we already have nutritional supplements that do the same thing (and tend to do it with fewer adverse side effects!).


There are several nutritional supplements that are regularly used to enhance sleep. I’ve organized them into the following 6 categories…


* Soft tissue-relaxing minerals (ex. magnesium, potassium)

* Vitamins (ex. vitamin D3, activated vitamin B6 [p5p])

* Inhibitory neurotransmitters (ex. 5-HTP, GABA)

* Neurotransmitter helpers (ex. taurine, glycine, inositol, theanine)

* Botanicals (ex. chamomile, lavender, valerian, Montmorency cherry)

* Hormones (ex. melatonin)


MY TOP 4 SLEEP SUPPLEMENTS:

MAGNESIUM, VITAMIN D, 5-HTP & GABA

So which of these sleep supplements are my favorites? With the caveat that every person is in a unique biological condition (and what’s best for one person may not be best for another), my 4 favorites are magnesium (either citrate or glycinate), vitamin D3, 5-HTP and GABA…


MAGNESIUM

Why magnesium? Roughly 60-70% of Americans are deficient in magnesium (an essential macro-mineral), and aside from improving sleep it has a whole host of additional benefits, including promoting healthy bones and teeth, muscle relaxation, nervous system support, cardiovascular health (especially helpful for arrhythmias and preventing progression of atherosclerosis via calcium : magnesium balance), endocrine functioning and digestive system health (helps promote regular BMs). [27-28]



VITAMIN D3

Why vitamin D3? At least 40% of the US population is deficient in vitamin D, and several studies have linked vitamin D deficiency to higher risks of various sleep disorders. Note that scientific evidence suggests that a 25(OH) vitamin D3 blood reading of 60-80ng/ml is needed for optimal sleep effects (which is notably higher than the 20-30ng/ml baseline threshold often used to diagnose vitamin D deficiency). This may indicate the need for higher dose vitamin D supplementation (equal to or even more than 10,000 IU/day). [29-34]



5-HTP

5-Hydroxy Tryptophan, a form of tryptophan, which is one of the 9 protein building amino acids in humans. Tryptophan is a serotonin precursor and as a supplement is used to increase serotonin activity in the body and brain (which has a calming, sedating effect). 5-HTP supplements are somewhat notorious for causing nausea (especially at higher dosages), so for those considering 5-HTP I’d recommend starting at a lower dose (ex. 50mg) and looking for products that have an enteric coating. [35-39]



GABA

GABA (or more formally, gamma aminobutyric acid) is an amino acid-like compound created from glutamic acid (a non-essential amino) and vitamin B6. There are four major neurotransmitters that regulate mood: serotonin, dopamine, norepinephrine and… GABA! And GABA is THE major inhibitory neurotransmitter of the brain, where it occurs in some 30-40% of all synapses there. Of all the neurotransmitters, GABA is second in prevalence only to glutamate, the brain’s major excitatory neurotransmitter. [40-42]


OTHER SUPPLEMENTS WITH A TRACK RECORD

OF SUPPORTING SLEEP…


POTASSIUM CITRATE

Like magnesium, potassium is a major mineral that assists in soft tissue relaxation. And like magnesium, many Americans (>90%) are deficient in potassium. Potassium also helps support cardiovascular and renal functioning. Potassium would likely make it into my top 3-4 sleep supplements save for the fact that sometimes it can actually increase energy levels (it is an important electrolyte after all). A 2019 study of 292 hypertensive patients found that low blood serum levels of potassium negatively impacted quality of sleep in study participants. [43]



ACTIVATED VITAMIN B6 (P5P)

More formally pyridoxal 5 phosphate, p5p (or P-5-P) is an important neurotransmitter co-factor and helps with the conversion of amino acids into neurotransmitters (ex. aids in the conversion of tryptophan to serotonin). While sometimes taken as a sleep aid, P-5-P is also used to treat carpal tunnel and trigger finger, peripheral neuropathy, neuralgia (general nerve pain) and seizures. Clinical research looking at vitamin B6 and sleep is scarce, but a 2007 study found that vitamin B6 strengthened melatonin biosynthesis (melatonin playing a crucial role in sleep quality). [44]


TAURINE

Technically an amino sulfonic acid, taurine is non protein-building but is nonetheless important in the body, where it has inhibitory neurotransmitter capabilities. A “Swiss Army Knife” amino acid, taurine is taken as a supplement for a variety of reasons, including cardiovascular health (arrhythmia, aFib, hypertension), ear issues (tinnitus), eyesight (taurine is abundant in the retina), liver support (helps thin bile) and exercise recovery. As far as sleep is concerned, clinical research is limited, but a 2010 study showed that supplementing with taurine had positive effects on sleep. [45]


GLYCINE

Glycine is a conditionally essential amino acid that also has inhibitory neurotransmitter effects (which produces a calming, sedating effect). A 2018 study made the case that the average 150lb adult has a 10g/day glycine deficiency which, among other things, may adversely affect sleep quality. Additionally, glycine also plays an important role in digestive health, and is regularly used to help heal and support the intestines. The clinical data on glycine and sleep is moderately robust- several studies have shown that glycine supplementation is a safe and effective tool for improving sleep quality. [46-48]


INOSITOL (VITAMIN B8)

All major neurotransmitters — dopamine, norepinephrine, serotonin, acetylcholine, and GABA — rely on inositol to relay messages, and low levels of inositol can disrupt the function of dopamine and serotonin. Additionally, inositol provides some liver support as well. While the clinical research looking specifically at inositol and sleep is somewhat scant, there are studies showing the benefits of supplemental inositol, such as a 2020 study of 60 pregnant women that found that "myo-inositol supplementation can improve global sleep quality, subjective sleep quality and sleep duration." [49]



L-THEANINE

L-theanine is an amino acid analogue of L-glutamine (a conditionally-essential amino acid) and glutamic acid/L-glutamate (a non-essential amino acid) that’s naturally found in high amounts in green tea, especially Matcha (powdered green tea). When taken as a supplement, l-theanine tends to have an interesting calming/focusing/relaxing effect, which some call a “zen-like” effect. For this reason it is commonly taken as a subtle energizing supplement (powder often mixed in morning coffee) AND as a sleep aid.


The clinical data on l-theanine is compelling- several studies have demonstrated l-theanine’s positive effect on sleep quality. A 2019 study found that l-theanine supplementation improved several sleep quality markers, including a reduction in sleep disturbances and the use of sleep medication. A 2017 study showed that 8 weeks of l-theanine supplementation is safe and has multiple beneficial effects on depressive symptoms, including sleep disturbances. Finally, a 2015 study showed that l-theanine improves sleep quality, not through sedation, but rather through anxiolysis, which is a reduction in anxiety. [50-52]


CHAMOMILE, LAVENDER & VALERIAN

Next to melatonin, these botanicals might be the recognized natural sleep aids. Commonly taken in either tea or pill form, I think all 3 of these are fine sleep-assisting botanicals, but I do believe the other supplements mentioned above will be more effective for the majority of people. While several other plant extracts show up in the clinical literature when it comes to sleep (kava kava, hops, lemon balm and others), valerian, lavender and chamomile tend to get the most attention. A 2020 review found that, while there is some conflicting evidence, valerian and lavender in particular were effective sleep aids for improving quality of sleep, sleep latency (the amount of time it takes to fall asleep) and total sleep time. [53]



MONTMORENCY TART CHERRY JUICE CONCENTRATE

A good natural source of melatonin, Montmorency cherry juice concentrate is used as a sleep aid and to help with gout and joint pain. While tasty, I don’t recommend it as often as some of the supplements above due to the notable amount of carbohydrates it provides (20-25g per ounce). There are several published scientific studies showing the benefits of tart cherries on sleep, such as a 2012 study that showed that consumption of tart cherry juice increased melatonin levels in the body, and improved sleep markers such as total sleep time and sleep efficiency. A 2019 pilot study showed that cherry juice increased sleep time and efficiency, and a 2010 study showed that tart cherry juice has modest beneficial effects on sleep in older adults with insomnia. [54-56]


MELATONIN

Perhaps the first supplement most people associate with sleep, melatonin is an important hormone produced by the pineal gland that helps regulate sleep/wake cycles. As we discussed above, melatonin levels can be dysregulated due to a lack of early and midday sunlight exposure and/or excessive artificial light exposure, especially at night.



I am not a huge fan of supplemental melatonin for a couple reasons. First, I think there are safer and more effective ways of boosting endogenous melatonin levels than taking the hormone itself. Second, I think that most melatonin dosages are too high (5-20mg). For those interested in consuming melatonin for sleep I’d suggest they start with a much smaller dose (300mcg an hour before bed) and titrate up as needed/tolerated. Other researchers have come to similar conclusions, such as the authors of a 2014 study in the journal Drugs & Aging. [57]


Of all sleep supplements, melatonin has the most robust clinical data examining its use. The American Academy of Family Physicians considers melatonin the first line therapy for the treatment of insomnia, and dozens of studies have found that melatonin, at proper doses, prevents side effects of jet lag, improves insomnia, synchronizes circadian rhythms (helpful for blindness and shift workers), and improves sleep onset, duration and quality. Melatonin is also a relatively potent antioxidant and free radical scavenger and is sometimes taken for immune support, cancer and neurodegenerative diseases (including Alzheimer’s). [58-62]


BOTTOM LINE

Sleep-supporting supplements can be an important and difference-making tool in the battle for better sleep. While vitamin D is one of my top tier sleep supplements, when the body needs to physically relax (or muscle tightness, cramps or restless legs are at work), magnesium and potassium are two of my favorite supplements. When the issue is more cerebral and anxiety or an over-active mind is at work, 5-HTP and GABA are often my two supplements of choice.


While sleeping troubles and disorders can be due to only 1 factor (ex. vitamin D deficiency for instance), often they’re multifactorial and warrant a holistic, multi-intervention approach. Check out the image below and consider the 12 factors that often play a significant role in sleep quality. Are there areas you could improve on?



SOURCES

27 www.ncbi.nlm.nih.gov/pmc/articles/PMC8053283/ (2021 study; “RCT evidence may support oral magnesium supplements (less than 1 g quantities given up to three times a day) for improved sleep parameters after magnesium supplementation for insomnia symptoms.”)

28 www.ncbi.nlm.nih.gov/pmc/articles/PMC3703169/ (2012; 46 elderly adults taking 500mg mag over 8 weeks; “Supplementation of magnesium appears to improve subjective measures of insomnia such as ISI score, sleep efficiency, sleep time and sleep onset latency, early morning awakening, and likewise, insomnia objective measures such as concentration of serum renin, melatonin, and serum cortisol, in elderly people.”)

29 www.ncbi.nlm.nih.gov/pmc/articles/PMC7334763/ (2020 study; “A meta-analysis including 9 studies (6 cross-sectional, 2 case-control, and 1 cohort studies) aimed at clarifying the association between vitamin D and sleep disorder risk. Overall, the study concluded that vitamin D deficiency is associated with a higher risk of sleep disorders including poor sleep quality, short sleep duration, and sleepiness. Moreover, there is an association between serum vitamin D levels and obstructive sleep apnea syndrome.”)

30 https://pubmed.ncbi.nlm.nih.gov/28475473/ (2018; 89 participants; “This study shows that the use of vitamin D supplement improves sleep quality, reduces sleep latency, raises sleep duration and improves subjective sleep quality in people of 20-50 year-old with sleep disorder.”)

31 www.ncbi.nlm.nih.gov/pmc/articles/PMC6213953/ (2018; meta-analysis suggests vit D deficiency associated w/ higher risk of sleep disorders)

32 www.ncbi.nlm.nih.gov/pubmed/22699141/ (2013; vitamin D supplementation in ppl w/ chronic pain effective in improving pain levels, sleep & QoL)

33 www.ncbi.nlm.nih.gov/pubmed/22583560 (2012; sleep disorders linked to vit D deficiency; 25(OH) vitamin D3 blood levels of 60-80 ng/ml needed for optimal sleep [notably higher than the 20-30 ng/ml baseline])

34 www.vitamindcouncil.org/what-is-the-upper-limit-and-noael-and-are-they-justified/#.XQy-T-hKhPY

35 www.ncbi.nlm.nih.gov/pmc/articles/PMC7334763/ (2020 study; “it has been indicated that supplementation of tryptophan (1 g or more) produces an increase in subjective sleepiness and a decreased time to sleep especially in subjects with mild insomnia. A random double-blind experiment on healthy adults suggested that tryptophan consistently reduced sleep latency which is associated with blood levels.”)

36 www.ncbi.nlm.nih.gov/pmc/articles/PMC6520871/ (2019 study; “Dietary tryptophan has been shown to improve sleep… Tryptophan depletion studies have demonstrated decreased tryptophan plasma concentrations affected sleep fragmentation (arousal index (events/h)), REM sleep latency (the interval between first epoch of stage 2 and the first epoch of REM sleep), and REM density (the cumulated duration of each REM burst divided by the duration of each REM sleep period) compared to baseline and placebo.”)

37 www.ncbi.nlm.nih.gov/pmc/articles/PMC4728667/ (2016; review of 5-HTP, tryptophan, serotonin and effects on mood, cognition and sleep found 5-HTP supplementation can have positive effects on sleep quality)

38 www.ncbi.nlm.nih.gov/pmc/articles/PMC4523676/ (2015 study; “Significantly reduced sleep latency and increased subjective ratings of sleepiness in healthy adults during the day have been reported in a number of uncontrolled and controlled studies (with tryptophan).”)

39 www.ncbi.nlm.nih.gov/pubmed/9727088 (1998; 5-htp crosses blood-brain barrier & increases serotonin in CNS; supplementing w/ 5-htp shown to be effective in treating depression and insomnia, as well as fibro, binge eating & chronic headaches)

40 www.ncbi.nlm.nih.gov/pmc/articles/PMC7334763/ (2020 study; “There are many studies showing the sleep-promoting effect of GABA, for example, Byun et al. reported a study of 40 patients with insomnia receiving 4 weeks of GABA (300 mg/day) have decreased sleep latency and increased sleep efficacy.”)

41 www.ncbi.nlm.nih.gov/pmc/articles/PMC7527439/ (2020 study; “natural and biosynthetic GABA intake may have beneficial effects on stress and sleep.”)

42 www.ncbi.nlm.nih.gov/pmc/articles/PMC6031986/ (2018 study of 40 participants, 300mg/day, 4 weeks; “This study shows that treatment with unpolished-rice-germ-derived GABA improved not only the subjective sleep quality but also the objective sleep efficacy without severe adverse events.”)

43 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075976/ (2019 study of 292 hypertensive patients; "our findings provide evidence that hypokalemia [low potassium] may disturb the sleep architecture in hypertensive individuals.")

44 https://pubmed.ncbi.nlm.nih.gov/18250494/ (2007 rat study showing vitamin B6 positively impacts melatonin production)

45 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3630960/ (2010 study showing taurine had positive effects on sleep)

46 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4397399/ (2015; "the use of glycine as a therapeutic option for improving sleep quality is a novel and safe approach")

47 https://pubmed.ncbi.nlm.nih.gov/22293292/ (2012; glycine may promote sleep benefits in part thru lowering body temperature)

48 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3328957/ (2012; In several studies, ingestion of 3g of glycine was found to improve sleep quality)

49 https://pubmed.ncbi.nlm.nih.gov/32933356/ (2020; study of 60 pregnant women found that “myo-inositol supplementation can improve global sleep quality, subjective sleep quality, and sleep duration”)

50 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6836118/ (2019; “sleep quality problems (disturbances in sleep latency, sleep disturbance, and use of sleep medication) was greater in the L-theanine administration compared to the placebo administration”)

51 https://pubmed.ncbi.nlm.nih.gov/27396868/ (2017; “Our study suggests that chronic (8-week) l-theanine administration is safe and has multiple beneficial effects on depressive symptoms, anxiety, sleep disturbance and cognitive impairments”)

52 https://pubmed.ncbi.nlm.nih.gov/25759004/ (2015; “200 mg of L-theanine before bed may support improved sleep quality not by sedation but through anxiolysis.”)

53 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191368/ (2020 review of plant extracts such as valerian, lavender and chamomile and their effects on sleep)

54 https://pubmed.ncbi.nlm.nih.gov/22038497/ (2012; tart cherry juice improved melatonin levels and sleep quality)

55 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5617749/ (2019; cherry juice increased sleep time and sleep efficiency)

56 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3133468/ (2010; cherry juice has modest beneficial effects on sleep in older adults with insomnia

57 https://pubmed.ncbi.nlm.nih.gov/24802882/ (2014; “In older adults, we advise the use of the lowest possible dose of immediate-release formulation melatonin to best mimic the normal physiological circadian rhythm of melatonin and to avoid prolonged, supra-physiological blood levels.”)

58 https://www.ncbi.nlm.nih.gov/books/NBK534823/ (2021 stat pearls; “melatonin is considered the first-line pharmacologic therapy for the treatment of insomnia by the American Academy of Family Physicians”)

59 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4273450/ (2014 review; “The use of melatonin by healthy adults shows promise to prevent phase shifts from jet lag and improvements in insomnia”)

60 https://pubmed.ncbi.nlm.nih.gov/28460563/ (2017; “Melatonin has been shown to synchronize the circadian rhythms, and improve the onset, duration and quality of sleep.”)

61 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3656905/ (2013; “melatonin decreases sleep onset latency, increases total sleep time and improves overall sleep quality. The effects of melatonin on sleep are modest”)

62 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3593297/ (2013; “melatonin is used for the management of sleep disorders and jet lag, for the resynchronization of circadian rhythms in situations such as blindness and shift work, for its preventive action in the development of cancer, as additive therapy in cancer and as therapy for preventing the progression of Alzheimer’s disease and other neurodegenerative disorders.”)