Calming IV

Full ingredient list

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

Supporting studies

• 1

  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 ↗

• 2

  Magnesium produced a clinically meaningful drop in both depression and anxiety scores within two weeks.

  This randomized crossover clinical trial enrolled 126 adults with mild-to-moderate depression in outpatient primary care, comparing six weeks of magnesium chloride (248 mg elemental magnesium daily) against no treatment. Magnesium produced a net improvement of −6.0 points on the PHQ-9 depression scale (95% CI −7.9 to −4.2, P < 0.001) and −4.5 points on the GAD-7 anxiety scale (95% CI −6.6 to −2.4, P < 0.001). Effects appeared within two weeks and held regardless of age, sex, baseline severity, or concurrent antidepressant use; the supplement was well tolerated. Route: oral magnesium chloride — the same magnesium salt used in our infusions.

  Randomized clinical trial (crossover) Tarleton EK, Littenberg B, MacLean CD, Kennedy AG, Daley C Role of magnesium supplementation in the treatment of depression: A randomized clinical trial. PLoS One. 2017. PMID 28654669 ↗

• 3

  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 ↗

• 4

  Across 34 randomized double-blind trials, magnesium lowered both systolic and diastolic blood pressure.

  This meta-analysis pooled 34 randomized, double-blind, placebo-controlled trials in 2,028 participants, with a median dose of 368 mg magnesium per day over a median of three months. Magnesium reduced systolic blood pressure by 2.00 mm Hg (95% CI 0.43–3.58) and diastolic blood pressure by 1.78 mm Hg (95% CI 0.73–2.82), and raised serum magnesium. The authors concluded that 300 mg/day for one month is sufficient to elevate serum magnesium and reduce blood pressure. Route: oral supplementation.

  Meta-analysis of randomized double-blind placebo-controlled trials Zhang X, Li Y, Del Gobbo LC, et al. Effects of Magnesium Supplementation on Blood Pressure: A Meta-Analysis of Randomized Double-Blind Placebo-Controlled Trials. Hypertension. 2016. PMID 27402922 ↗

• 5

  Intravenous magnesium is established hospital medicine: in the largest trial ever run, IV magnesium sulfate cut the risk of eclamptic seizures by 58%.

  The Magpie Trial randomized 10,141 pregnant women with pre-eclampsia across 175 hospitals in 33 countries to intravenous magnesium sulfate (loading dose plus 24 hours of maintenance infusion) or placebo. Eclampsia occurred in 0.8% of the magnesium group versus 1.9% of the placebo group — a 58% relative risk reduction, or 11 fewer cases per 1,000 women — and placental abruption was also reduced (RR 0.67). This trial is the reason IV magnesium is on the WHO Essential Medicines List and is given by infusion in hospitals worldwide.

  Large multicenter randomized placebo-controlled trial (intravenous) Altman D, Carroli G, Duley L, et al. (Magpie Trial Collaboration Group) Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate? The Magpie Trial: a randomised placebo-controlled trial. The Lancet. 2002. PMID 12057549 ↗

• 6

  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 ↗

• 7

  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 ↗

• 8

  Glycine acts as a direct anti-inflammatory and cell-protective agent by calming immune cells and stabilizing cell membranes.

  This review in Current Opinion in Clinical Nutrition and Metabolic Care summarizes evidence that L-glycine is anti-inflammatory, immunomodulatory and cytoprotective. Glycine acts on inflammatory cells such as macrophages to suppress activation, opening a glycine-gated chloride channel that hyperpolarizes and stabilizes the cell membrane and blunts inflammatory signaling. Documented protective effects span ischemia-reperfusion and cold-storage injury in liver, kidney, heart, intestine and skeletal muscle, along with suppression of arthritis and protection against gastric ulceration. Evidence base is largely mechanistic and preclinical.

  Mechanistic review (preclinical evidence) Zhong Z, Wheeler MD, Li X, et al. L-Glycine: a novel antiinflammatory, immunomodulatory, and cytoprotective agent. Current Opinion in Clinical Nutrition and Metabolic Care. 2003. PMID 12589194 ↗

• 9

  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 ↗

• 10

  Vitamin B6 in its active P5P form is the required cofactor for more than 140 biochemical reactions, including the synthesis of serotonin, dopamine and GABA.

  This peer-reviewed review of vitamin B6 biology states that vitamin B6 'is an enzymatic co-factor required for more than 140 biochemical reactions' — roughly 4% of all classified enzyme activities — spanning transaminations, decarboxylations and amino acid metabolism. It further notes that 'VitB6 is required for the biosynthesis of several neurotransmitters like serotonin, dopamine, and gamma-aminobutyric acid (GABA).' Pyridoxal-5-phosphate (P5P) is the already-activated coenzyme form that these enzymes bind directly.

  Mechanistic review Hellmann H, Mooney S Vitamin B6: A Molecule for Human Health?. Molecules. 2010. PMID 20110903 ↗

• 11

  In a double-blind placebo-controlled crossover trial, inositol significantly reduced the frequency and severity of panic attacks with minimal side effects.

  Twenty-one patients with panic disorder, with or without agoraphobia, completed a randomized double-blind, placebo-controlled, four-week crossover trial of 12 g/day inositol. The frequency and severity of panic attacks and the severity of agoraphobia declined significantly more on inositol than on placebo, and side effects were minimal. The authors highlighted that inositol acts as a precursor to a cell-signaling second messenger rather than targeting neurotransmitter receptors directly, and noted its status as a naturally occurring dietary compound. Route was oral.

  Randomized controlled trial (double-blind, placebo-controlled crossover) Benjamin J, et al. Double-blind, placebo-controlled, crossover trial of inositol treatment for panic disorder. American Journal of Psychiatry. 1995. PMID 7793450 ↗

• 12

  In a double-blind placebo-controlled trial, inositol improved depression scores significantly more than placebo within four weeks, with no adverse effects on blood work or organ function.

  Twenty-eight depressed patients received either 12 g/day inositol (n = 13) or placebo (n = 15) for four weeks under double-blind conditions. Improvement on the Hamilton Depression Rating Scale was significantly greater for inositol than placebo at week 4. No changes were noted in blood chemistry, hematology, kidney or liver function. The authors framed inositol as a novel approach that supplies a second-messenger precursor rather than acting on neurotransmitters directly. Route was oral.

  Randomized controlled trial (double-blind, placebo-controlled) Levine J, et al. Double-blind, controlled trial of inositol treatment of depression. American Journal of Psychiatry. 1995. PMID 7726322 ↗

References

• 1Kirkland AE, Sarlo GL, Holton KF. The Role of Magnesium in Neurological Disorders. Nutrients. 2018. PMID 29882776 ↗
• 2Tarleton EK, Littenberg B, MacLean CD, Kennedy AG, Daley C. Role of magnesium supplementation in the treatment of depression: A randomized clinical trial. PLoS One. 2017. PMID 28654669 ↗
• 3de Baaij JHF, Hoenderop JGJ, Bindels RJM. Magnesium in man: implications for health and disease. Physiological Reviews. 2015. PMID 25540137 ↗
• 4Zhang X, Li Y, Del Gobbo LC, et al. Effects of Magnesium Supplementation on Blood Pressure: A Meta-Analysis of Randomized Double-Blind Placebo-Controlled Trials. Hypertension. 2016. PMID 27402922 ↗
• 5Altman D, Carroli G, Duley L, et al. (Magpie Trial Collaboration Group). Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate? The Magpie Trial: a randomised placebo-controlled trial. The Lancet. 2002. PMID 12057549 ↗
• 6Soh 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 ↗
• 7Bannai 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 ↗
• 8Zhong Z, Wheeler MD, Li X, et al. L-Glycine: a novel antiinflammatory, immunomodulatory, and cytoprotective agent. Current Opinion in Clinical Nutrition and Metabolic Care. 2003. PMID 12589194 ↗
• 9Sun 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 ↗
• 10Hellmann H, Mooney S. Vitamin B6: A Molecule for Human Health?. Molecules. 2010. PMID 20110903 ↗
• 11Benjamin J, et al. Double-blind, placebo-controlled, crossover trial of inositol treatment for panic disorder. American Journal of Psychiatry. 1995. PMID 7793450 ↗
• 12Levine J, et al. Double-blind, controlled trial of inositol treatment of depression. American Journal of Psychiatry. 1995. PMID 7726322 ↗