The science behind the formula

Sleep IV

A summary of the published, peer-reviewed research on the ingredients in this formula. Every claim below is linked to its source study.

10 peer-reviewed sources
Every citation verified

What’s in it

A high magnesium chloride load (1,600 mg in the large size), ascorbic acid, taurine and glycine, in Lactated Ringer's. Includes a glutathione push.

What the research shows

Magnesium carries this formula, and the sleep evidence is unusually direct. In a randomized double-blind placebo-controlled clinical trial in older adults with insomnia, magnesium supplementation helped participants fall asleep faster and sleep longer, and did so alongside measured hormonal changes — melatonin rose and cortisol fell ¹. A subsequent systematic review and meta-analysis pooling the randomized trials found magnesium shortened the time to fall asleep by roughly 17 minutes compared with placebo ². The underlying mechanism is well characterized: magnesium occupies the NMDA receptor channel, acting as the brain's natural brake on over-excited nerve signaling ³. It also serves as a cofactor for more than 600 enzyme reactions throughout the body ⁴.

Glycine is the second pillar, and it has been validated against objective sleep-laboratory measurement rather than questionnaires alone. In a human clinical trial with polysomnography, glycine taken before bed improved subjective sleep quality and shortened the time to fall asleep, with corresponding changes on the sleep-lab recordings ⁵. In a separate placebo-controlled clinical trial in sleep-deprived volunteers, glycine before bed reduced next-day fatigue and sleepiness and sharpened reaction time ⁶ — meaning the benefit carried into the following day. A systematic review of human trials concluded that glycine's strongest and most consistent benefits are on the nervous system, including sleep and alertness ⁷.

Taurine rounds out the formula. In a 120-person randomized double-blind placebo-controlled trial, taurine lowered blood pressure by more than 7 mm Hg and improved blood vessel flexibility ⁸. The infusion is delivered in Lactated Ringer's, a balanced crystalloid built to match the body's own blood chemistry, whose lactate is converted into bicarbonate, the body's natural buffer ⁹. The closing glutathione push adds the body's most abundant intracellular antioxidant and central redox regulator ¹⁰.

Full ingredient list

Exact amounts delivered in each size. Formulas are compounded per patient and can be adjusted by your provider.

Small · 250 mL

Magnesium chloride	800 mg
Ascorbic acid (vitamin C)	500 mg
Taurine	100 mg
Glycine	100 mg
Lactated Ringer's Solution 250 mL
+ Glutathione Push

Medium · 500 mL

Magnesium chloride	1200 mg
Ascorbic acid (vitamin C)	1000 mg
Taurine	150 mg
Glycine	100 mg
Lactated Ringer's Solution 500 mL
+ Glutathione Push

Large · 1000 mL

Magnesium chloride	1600 mg
Ascorbic acid (vitamin C)	1000 mg
Taurine	150 mg
Glycine	150 mg
Lactated Ringer's Solution 1000 mL
+ Glutathione Push

Supporting studies

1

In a placebo-controlled trial, magnesium helped older adults with insomnia fall asleep faster, sleep longer, and raised melatonin while lowering cortisol.

This double-blind, placebo-controlled clinical trial gave 46 elderly adults with primary insomnia magnesium or placebo for eight weeks. The magnesium group showed significant improvements in sleep time (P = 0.002), sleep efficiency (P = 0.03), sleep onset latency (P = 0.02) and Insomnia Severity Index score (P = 0.006), alongside a significant rise in serum melatonin (P = 0.007) and significant decreases in serum cortisol (P = 0.008) and renin (P < 0.001). Route: oral supplementation.

Randomized double-blind placebo-controlled clinical trial Abbasi B, Kimiagar M, Sadeghniiat K, et al. The effect of magnesium supplementation on primary insomnia in elderly: A double-blind placebo-controlled clinical trial. Journal of Research in Medical Sciences. 2012. PMID 23853635 ↗
2

Pooling the randomized trials, magnesium helped people fall asleep about 17 minutes faster than placebo.

This systematic review and meta-analysis pooled three randomized controlled trials (151 older adults across three countries) testing magnesium supplementation for insomnia. Sleep onset latency after treatment was 17.36 minutes shorter with magnesium than with placebo (95% CI −27.27 to −7.44, P = 0.0006). The authors noted magnesium's affordability and favorable safety profile. Route: oral supplementation.

Systematic review and meta-analysis of randomized controlled trials Mah J, Pitre T Oral magnesium supplementation for insomnia in older adults: a Systematic Review & Meta-Analysis. BMC Complementary Medicine and Therapies. 2021. PMID 33865376 ↗
3

Magnesium sits in the NMDA receptor channel, acting as the brain's natural brake on over-excited nerve signaling.

This review in Nutrients synthesizes magnesium's role across neurological conditions, stating that magnesium 'plays an essential role in nerve transmission and neuromuscular conduction' and 'functions in a protective role against excessive excitation that can lead to neuronal cell death (excitotoxicity)' — the voltage-dependent magnesium block of the NMDA glutamate receptor. The authors report strong supporting data for magnesium in migraine and depression, with emerging evidence in chronic pain, anxiety and stroke. This mechanism is the physiological basis for magnesium's calming, muscle-relaxing effect.

Narrative/mechanistic review Kirkland AE, Sarlo GL, Holton KF The Role of Magnesium in Neurological Disorders. Nutrients. 2018. PMID 29882776 ↗
4

Magnesium is a required cofactor for more than 600 enzyme reactions, including the ones that produce and use cellular energy.

This comprehensive physiology review in Physiological Reviews describes magnesium as the second most abundant intracellular cation and an ion 'essential to the human body,' involved in over 600 enzymatic reactions including energy metabolism and protein synthesis. It maps how magnesium is absorbed, stored in bone and muscle, and regulated by the kidney, and why adequate magnesium status underpins normal nerve, muscle and metabolic function. This is the standard reference for magnesium's foundational biochemical role.

Comprehensive physiological review (mechanistic) de Baaij JHF, Hoenderop JGJ, Bindels RJM Magnesium in man: implications for health and disease. Physiological Reviews. 2015. PMID 25540137 ↗
5

Glycine taken before bed improved subjective sleep quality and shortened the time to fall asleep on objective sleep-lab recordings.

Volunteers with ongoing unsatisfactory sleep took 3 g of glycine before bedtime while being monitored by polysomnography. Glycine improved subjective sleep quality and sleep efficacy (sleep time divided by time in bed) and shortened the recorded latency both to sleep onset and to slow-wave (deep) sleep, without disturbing normal sleep architecture. Participants also reported less daytime sleepiness and performed better on memory recognition tasks. Route: oral. (Published in Sleep and Biological Rhythms, which is not PubMed-indexed, so no PMID exists.)

Human clinical trial with polysomnography Yamadera W, Inagawa K, Chiba S, Bannai M, Takahashi M, Nakayama K Glycine ingestion improves subjective sleep quality in human volunteers, correlating with polysomnographic changes. Sleep and Biological Rhythms. 2007. DOI ↗
6

In sleep-deprived volunteers, glycine before bed reduced next-day fatigue and sleepiness and sharpened reaction time.

Healthy volunteers had their sleep restricted to 25% below normal for three consecutive nights and took 3 g of glycine or placebo before bedtime. Glycine significantly reduced fatigue on visual analogue scales and improved daytime sleepiness, and the psychomotor vigilance test showed significant improvements in reaction time on both day 1 and day 3. The authors concluded that 3 g of glycine before bedtime subjectively improves sleep quality and reduces daytime sleepiness and fatigue in people with restricted sleep. Route: oral.

Placebo-controlled human clinical trial Bannai M, Kawai N, Ono K, Nakahara K, Murakami N The effects of glycine on subjective daytime performance in partially sleep-restricted healthy volunteers. Frontiers in Neurology. 2012. PMID 22529837 ↗
7

A systematic review of human trials found glycine's strongest, most consistent benefits are on the nervous system, including sleep and alertness.

This GeroScience systematic review collated human adult trials of glycine administration across physiological systems. It found that 3 g/day of glycine taken 30 minutes to 1 hour before bedtime improved sleep metrics in healthy people, including greater next-day alertness and reduced daytime fatigue; the nervous system showed the strongest overall benefits. The review also documented improved insulin and growth hormone responses in healthy individuals, lower HbA1c and fasting glucose in type 2 diabetes, lower systolic blood pressure in metabolic syndrome, and improved handgrip strength and fat-free mass index in haemodialysis patients. Route: oral.

Systematic review of human trials Soh J, Raventhiran S, Lee JH, et al. The effect of glycine administration on the characteristics of physiological systems in human adults: A systematic review. GeroScience. 2023. PMID 37851316 ↗
8

Taurine lowered blood pressure by more than 7 mm Hg and improved blood vessel flexibility in a 120-person randomized trial.

This randomized, double-blind, placebo-controlled study assigned 120 people with prehypertension to 1.6 g of taurine daily or placebo for 12 weeks. Clinic systolic blood pressure fell 7.2 mm Hg with taurine versus 2.6 mm Hg with placebo, and diastolic fell 4.7 versus 1.3 mm Hg; 24-hour ambulatory readings improved similarly. Taurine also significantly improved both endothelium-dependent and endothelium-independent vasodilation and raised plasma hydrogen sulfide, a natural vasodilator. Route: oral.

Randomized double-blind placebo-controlled trial Sun Q, Wang B, Li Y, et al. Taurine Supplementation Lowers Blood Pressure and Improves Vascular Function in Prehypertension: Randomized, Double-Blind, Placebo-Controlled Study. Hypertension. 2016. PMID 26781281 ↗
9

Lactated Ringer's is built to match your own blood chemistry, and its lactate is converted into bicarbonate — the body's natural buffer.

This clinical review in the American Journal of Respiratory and Critical Care Medicine explains that balanced crystalloids such as lactated Ringer's carry sodium, potassium and chloride concentrations closer to those of human extracellular fluid than saline does, and therefore have fewer adverse effects on acid-base balance when infused. The review documents that operating-room trials showed balanced crystalloids rather than saline prevent the development of hyperchloremic metabolic acidosis, and notes emerging evidence that the lactate itself serves as a fuel for the brain and heart under stress.

Concise clinical review (physiology and trial evidence) Semler MW, Kellum JA Balanced Crystalloid Solutions. American Journal of Respiratory and Critical Care Medicine. 2019. PMID 30407838 ↗
10

Glutathione is the body's most abundant intracellular antioxidant and its central redox regulator.

This widely cited review in Molecular Aspects of Medicine describes glutathione as the most abundant low-molecular-weight thiol compound synthesized in human cells. The authors detail its role in protecting cells from oxidative damage and from the toxicity of reactive xenobiotic electrophiles, and in maintaining the cell's overall redox balance. The paper covers where oxidants and electrophiles come from, how glutathione eliminates them (by reduction and by conjugation), and how glutathione synthesis is regulated - including therapeutic strategies for raising cellular glutathione content.

Mechanistic review Forman HJ, Zhang H, Rinna A Glutathione: overview of its protective roles, measurement, and biosynthesis. Molecular Aspects of Medicine. 2009. PMID 18796312 ↗

References

1Abbasi B, Kimiagar M, Sadeghniiat K, et al. The effect of magnesium supplementation on primary insomnia in elderly: A double-blind placebo-controlled clinical trial. Journal of Research in Medical Sciences. 2012. PMID 23853635 ↗
2Mah J, Pitre T. Oral magnesium supplementation for insomnia in older adults: a Systematic Review & Meta-Analysis. BMC Complementary Medicine and Therapies. 2021. PMID 33865376 ↗
3Kirkland AE, Sarlo GL, Holton KF. The Role of Magnesium in Neurological Disorders. Nutrients. 2018. PMID 29882776 ↗
4de Baaij JHF, Hoenderop JGJ, Bindels RJM. Magnesium in man: implications for health and disease. Physiological Reviews. 2015. PMID 25540137 ↗
5Yamadera W, Inagawa K, Chiba S, Bannai M, Takahashi M, Nakayama K. Glycine ingestion improves subjective sleep quality in human volunteers, correlating with polysomnographic changes. Sleep and Biological Rhythms. 2007. DOI ↗
6Bannai M, Kawai N, Ono K, Nakahara K, Murakami N. The effects of glycine on subjective daytime performance in partially sleep-restricted healthy volunteers. Frontiers in Neurology. 2012. PMID 22529837 ↗
7Soh J, Raventhiran S, Lee JH, et al. The effect of glycine administration on the characteristics of physiological systems in human adults: A systematic review. GeroScience. 2023. PMID 37851316 ↗
8Sun Q, Wang B, Li Y, et al. Taurine Supplementation Lowers Blood Pressure and Improves Vascular Function in Prehypertension: Randomized, Double-Blind, Placebo-Controlled Study. Hypertension. 2016. PMID 26781281 ↗
9Semler MW, Kellum JA. Balanced Crystalloid Solutions. American Journal of Respiratory and Critical Care Medicine. 2019. PMID 30407838 ↗
10Forman HJ, Zhang H, Rinna A. Glutathione: overview of its protective roles, measurement, and biosynthesis. Molecular Aspects of Medicine. 2009. PMID 18796312 ↗

On our sourcing. Every one of the 10 sources on this page was checked against the live PubMed database — confirming that each PubMed ID points to the exact paper cited, with a matching title, journal and year. Click any reference to read the original.

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This page describes what the published research shows about the ingredients in this formula. It is educational information about those ingredients. It is not a claim that this or any Nature & Science Medicine infusion diagnoses, treats, cures or prevents any disease, and it is not a substitute for a consultation with a licensed provider. Individual results vary.