SUPPORTING RESEARCH & PUBLICATIONS

This page highlights selected scientific research related to the individual ingredients found in Cloudcraft. Our goal is to provide an overview of the current evidence supporting the role these naturally occurring ingredients may play in sleep, recovery, and overall wellness.

Nutritional science and electrolyte research are continually evolving. While some ingredients have been extensively studied over many decades, others have a more limited body of evidence, including relatively few high-quality randomized controlled trials. As new research emerges, our understanding of these ingredients and their potential benefits may change.

The studies referenced on this page evaluate individual ingredients and, unless otherwise stated, do not assess the Cloudcraft formulation as a whole. Because ingredients may interact synergistically, the effects of the complete formula may differ from those observed in studies of individual compounds.

The information presented is intended for educational purposes only and should not be interpreted as medical advice, a guarantee of results, or evidence that every individual will experience the same outcomes. Individual responses to dietary supplements can vary based on numerous factors, including overall health, lifestyle, and medical conditions.

These statements have not been evaluated by the U.S. Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

Back to Ingredients

Amino Acids

What is it?

Glycine is a non-essential amino acid. This refers to an amino acid that is synthesized naturally within the body, rather than an “essential amino acid” which is not synthesized within the body and must be consumed.4

Key findings in literature:

Core body temperature.1, 2

Glycine passively crosses the blood brain barrier and acts on NMDA receptors in the suprachiasmatic nucleus in the hypothalamus.
Activation of these receptors leads to peripheral vasodilation, which results in decreased core body temperature.
There is a strong relationship between core body temperature, circadian oscillation, and sleep.
Core body temperature naturally drops at the onset of sleep, continues to decrease during sleep, and gradually rises during waking period.

Muscle tone.2, 4

Glycine acts as an inhibitory neurotransmitter in the brainstem and spinal cord, where it activates glycinergic premotor neurons resulting in muscle atonia during REM sleep.

Additional findings in literature:

Inflammation.3, 4

Suppresses cytokines in macrophages, T-cells, and neutrophils.
Can inhibit the production of pro-inflammatory cytokines.
Can increase the mRNA expression of other anti-inflammatory cytokines.

Metabolism.

Clinical studies have evaluated the effects of higher circulating glycine concentrations on metabolic conditions such as diabetes.
Glycine acts as a secretagogue of glucagon-like peptide-1 (GLP-1) and insulin.

References:

What is it?

Taurine, also known as 2-aminoethanesulfonic acid or tauric acid, is one of the most abundant amino acids in the brain and spinal cord, leukocytes, heart and muscle cells, and the retina. It is naturally synthesized within the liver, therefore it is known as a nonessential amino acid. However, the rate of biosynthesis is low. Levels of taurine have also been found to decrease as we age. In humans, taurine is mainly obtained from diet. Although it is most well-known for its inclusion in many energy drinks, taurine is present in several foods such as milk, shellfish, fish, turkey, and chicken.1, 2, 3, 4

Key findings in literature:

GABA.1

The primary mechanism of taurine in regards to sleep appears to be its weak agonistic effect on GABA receptors.
GABA acts as the primary inhibitory neurotransmitter in the brain and spinal cord.

Antioxidant.1, 2, 4

Neutralizes hypochlorous acid, which is a neutrophil oxidant. The product of the neutralizing reaction, taurine chloramine, also interferes with the inflammatory process.
Stabilizes intracellular levels of antioxidant enzymes like superoxide dismutase (SOD) and glutathione.

Additional findings in literature:

Cardiovascular.3, 4

Modulator of calcium and potassium channels. Impacts cardiac electrical activity, vascular tone, myocardial contractility and relaxation.
Studies have evaluated the association between taurine and left ventricular function, as well as exercise tolerance.

Metabolism.2

Some studies have evaluated the association between taurine and insulin sensitivity, as well as triglyceride levels.

Exercise.

This is one of the reasons Taurine is frequently associated with energy drinks.
Studies have evaluated the association between taurine supplementation and lactic acid levels during exercise.

References:

What is it?

L-theanine is a water-soluble, non-proteinogenic amino acid found predominantly in green tea.2 It is able to cross the blood-brain barrier, and influences several different neurotransmitters.

Key findings in literature:

Sleep1, 2, 3

Studies suggest that it exerts its relaxant effect by upregulating GABA receptors and antagonizing glutamate receptors.
It may reverse some of caffeine’s effects by decreasing its inhibition of GABA receptors and decreasing expression of glutamate receptors.
Caffeine induces insomnia through inhibition of GABAA and GABAB receptors, whereas L-theanine increases their expressions and directly stimulates GABAA receptors.
Some studies show influence on delta brain waves, which are high-amplitude slow brain waves that correlate with sleep intensity and dominate NREM sleep.
Other studies show influence on alpha brain waves, which are associated with a relaxed state as well as selective attention and mental readiness. Essentially a state of “calm attention”.4
Studies suggest that L-theanine administration also promotes brain serotonin and dopamine levels.

Antioxidant.3

Increases activity of antioxidant enzymes such as SOB and CAT.
Malondialdehyde (MDA) is an end product of lipid peroxidation and has been used as a biomarker to measure oxidative stress. This has been shown to decrease with L-theanine intake.

Additional findings in literature:

Cognitive function.

Several studies have evaluated effects on cognition, attention, and memory - potentially enhanced by more restful sleep.4, 5

References:

Botanicals & Fruit Extracts

What is it?

Tart cherry (Prunus Cerasus) is a substantial source of polyphenolic compounds including anthocyanins, flavonoids, and phenolic acids. The market for tart cherries, primarily Montmorency cherries, has skyrocketed in the last decade due to agricultural improvements and literature suggesting various health benefits. These are sour cherries rather than sweet, and contain higher levels of anthocyanins and phytochemicals.

Anthocyanins are a class of water-soluble flavonoids and are responsible for the colors red, purple, and blue in fruits and vegetables.

Key findings in literature:

Sleep.1, 2

Tart cherries are high in melatonin, serotonin, and tryptophan. There is an average of 2.1 - 13.5 ng/g of melatonin in tart cherries.
Melatonin serves as a signal of darkness that promotes sleep. Concentration of melatonin increases in darkness, then falls when exposed to light to promote wakefulness.
The suprachiasmatic nucleus (SCN) in the hypothalamus regulates melatonin synthesis and secretion. In pineal cells, tryptophan undergoes hydroxylation and decarboxylation to make serotonin. N‐acetyltransferase shifts serotonin into N‐acetylserotonin, which is methylated by hydroxylindole‐O‐methyltransferase to produce melatonin (Masters et al. 2014; Poza et al.).
There have been many studies delving into the association between tart cherries and sleep. This systematic review from 2025 describes some of them.1Jack N Losso et al evaluated sleep time and efficiency when supplementing with tart cherry juice.Howatson et al. 2012 evaluated metrics like total sleep time, time in bed, and sleep efficiency. They also compared melatonin levels to baseline and placebo.Simper et al. 2019 evaluated total time in bed and wake after sleep onset.

Recovery.3, 4, 5

Various studies have evaluated associations with rest, recovery, muscle soreness, and inflammation in athletes receiving tart cherry supplementation.

Additional findings in literature:

Antioxidant/Inflammation.7, 8, 9

Inflammation and oxidative stress are common drivers of many chronic illnesses.
This review from 2025 seeks to identify possible antioxidant and antiinflammatory properties of tart cherry concentrate. These suspected properties are most likely due to its high quantities of phytochemicals like anthocyanins, polyphenols, and vitamins.7
Anthocyanins can scavenge free radicals as strong antioxidants, and reduce certain blood biomarkers involving blood lipids. In research, anthocyanins exhibit effects that promote general and metabolic health through their antioxidant, anti-inflammatory, and epigenetic properties.Anthocyanins can downregulate inflammatory gene expression to control the transactivation of relative transcription factors.

Cognitive function.6

This randomized controlled trial evaluated cognitive performance after tart cherry supplementation. They also evaluated impact on perceptions of fatigue and alertness, as well as regulation of plasma amino acids.

References:

What is it?1, 2

Acerola fruit, sometimes known as Barbados cherry or West Indian cherry, is one of the richest natural sources of ascorbic acid (Vitamin C) and contains a plethora of phytonutrients like carotenoids, phenolics, anthocyanins, and flavonoids. It has become very prevalent in countries such as Brazil due to suspected antioxidant and antiinflammatory properties. Vitamin C is a water-soluble vitamin which humans do not synthesize naturally, making it an essential dietary component. Vitamin C is important for numerous processes such as biosynthesis of collagen, L-carnitine, and some neurotransmitters. Vitamin C deficiency results in a serious medical condition called scurvy, and although rare in developed countries, some populations are at risk for other reasons. This includes people who smoke or are exposed to secondhand smoke, and individuals with limited food variety.

Key findings in literature:

Vitamin C.1

As previously mentioned, Acerola fruit is one of the richest natural sources of vitamin C. Its vitamin C content far exceeds other fruits such as oranges and lemons.
Vitamin C is an essential micronutrient, a vitamin that humans do not synthesize naturally and must consume. While it is naturally synthesized in most plants and animals, humans lack a functional enzyme called l-gulono-1,4,-lactone oxidase, which catalyzes the final step in ascorbic acid synthesis. It is important for many physiological functions and the primary reason for acerola’s health benefits.
The vitamin C of Acerola may be better absorbed by humans than synthetic vitamin C.
Researchers have evaluated the association between vitamin C and sleep quality.Zhang et al. conducted a cohort study involving nearly 70,000 participants in the UK, which evaluated the association between higher levels of vitamin C intake and sleep disorders.Otocka-Kmiecik et al. provided a literature overview of vitamin C and its relationship with both physical activity and sleep.4
There is a growing body of evidence linking free radical formation and oxidative stress with sleep disorders. Hence, vitamins with antioxidant and antiinflammatory properties are suspected to promote sleep quality and restorative sleep.4

Additional findings in literature:

Antioxidant/Inflammation:

Researchers have evaluated the association between vitamin C intake and general, cardiovascular, immune, and ocular health. Some studies have also evaluated the effect on duration of the common cold.2
As an antioxidant, vitamin C provides protection against oxidative stress-induced cellular damage by scavenging of reactive oxygen species, vitamin E-dependent neutralization of lipid hydroperoxyl radicals, and by protecting proteins from alkylation by electrophilic lipid peroxidation products.5
Vitamin C also plays a role in the function of endothelial nitric oxide synthase (eNOS) by recycling the eNOS cofactor, tetrahydrobiopterin, which is relevant to arterial elasticity and blood pressure regulation.5
Vitamin C promotes hydroxylation and subsequent degradation of hypoxia-inducible factor (HIF-1). HIF-1 is a transcription factor that regulates many genes responsible for tumor growth.5

References:

What is it?1, 3

Saffron is a medicinal and culinary plant originally cultivated in the Middle East and Mediterranean. It is derived from the flower of Crocus Sativus, most commonly from the stigma of the plant. The major products of saffron are crocins and crocetin (carotenoids), and pirocrocin and safranal which give its taste and aroma. It also contains small amounts of thiamine and riboflavin. Saffron has been studied in regard to potential effects on mental, sexual, cardiovascular, and skin health. Researchers have evaluated antioxidant, antiinflammatory, and anti-carcinogenic properties. Because of these many proposed health benefits, it has become a popular and potentially valuable supplement worldwide.

Key findings in literature:

Sleep.1, 2

A systematic review conducted in 2023 examined 5 randomized controlled trials. They evaluated the association between saffron and sleep duration and quality.1
Another RCT by Taherzadeh et. al evaluated intranasal administration of a preparation containing saffron oil (as well as violet and lettuce seeds oil). They measured improvements in insomnia based on ISI and PSQI scores.2
The primary mechanism of action is thought to be saffron’s antagonistic effect on NMDA receptors, resulting in decreased excitability.
Saffron supplementation may also impact melatonin concentrations. Concentration and release of melatonin may be a downstream effect of its antiinflammatory effects. For example, inflammatory cytokines such as interleukin-1β and interferon-γ can impact the release of melatonin.
Proposed effects on mood and inflammation may further promote restful sleep.

Additional outcomes supported by research:

Antioxidant/Inflammation.3, 7, 10

Saffron’s constituents display antioxidant and antiinflammatory properties. Crocin appears to have the most significant effects, followed by safranal.
Crocin combats reactive oxygen species and suppresses pro-inflammatory cytokine secretion. It scavenges free radicals, mainly superoxide anions, therefore defending against oxidative stress.7, 10
Crocin has also been shown to alter DNA transcription factors called NF-κB in the cell nucleus. These factors have downstream effects involving inflammation in various organ systems including the respiratory, nervous, gastrointestinal cardiovascular, urogenital, and musculoskeletal systems.7
Studies have also evaluated impact on ocular, metabolic, and cognitive health.3, 7

Mood.4, 5, 6

Some data suggests that saffron may exert properties that regulate mood. The mechanism for this effect is thought to be inhibition of synaptic serotonin reuptake, resulting in more circulating serotonin in the brain.

Cardiovascular.3, 8, 9

Data suggests that saffron may promote cardiovascular health by inhibiting malondialdehyde (MDA) production, decreasing tumor necrosis factor-alpha (TNF-α).3
Crocetin may have an impact on cholesterol and vascular reactive acid substances.3
Saffron may exhibit antihypertensive effects via inhibition of the renin-angiotensin (RAS) system.3
Crocetin appears to influence insulin sensitivity and fasting plasma glucose.3

References:

Cellular Nutrients

What is it?

Myo-Inositol is a carbohydrate that is intrinsically synthesized via the kidneys, and to a lesser extent the brain and liver. Deficiencies have been observed in some mammals. Furthermore, there are various lifestyle habits that have been shown to increase the need for myo-inositol.1

Key findings in literature:

Lifestyle habits.1

Studies have demonstrated that the need for myo-inositol is increased with higher caffeine intake (especially coffee), increasing age, sugar/refined carbohydrate intake, and insulin resistance.
Foods containing myo-inositol tend to be consumed less often. This includes liver, grains, seeds, and beans. Tissues highest in myo-inositol are no longer regularly consumed by humans, such as kidneys, brain, and blood cells.

Additional findings in literature:

Cholesterol.1

Studies have evaluated the association between myo-inositol supplementation and hyperlipidemia & hypertriglyceridemia.
Studies have also evaluated effects on liver triglyceride accumulation and and myocardial cholesterol accumulation. Buildup of cholesterol in the myocardium may increase risk of left ventricular stiffness and heart function.

Metabolism.2

Studies have commented on associations between myo-inositol and glucose absorption in the duodenum, as well as glucose uptake in muscles.
Glucose can impair cellular uptake of myo-inositol by competitively inhibiting sodium ion-coupled transporters.
Insulin-resistant states are found to promote urinary losses of myo-inositol primarily due to glucose-mediated inhibition of myo-inositol reabsorption in the kidneys.
Metabolic abnormalities may increase risk of myo-inositol deficiency.

Other.4, 5

Some studies have evaluated the association between myo-inositol and reproductive function.

References:

What is it?

Phosphatidylcholine (PC) is the most abundant phospholipid in all mammalian cell membranes. It predominantly resides on the outer leaflet of the plasma membrane bilayer, with its partner Phosphatidylethanolamine (PE) predominantly residing on the inner layer. PC is critical for maintaining cell structure and facilitating cell signaling and transport across the membrane. It is required for assembly and secretion of lipoproteins, which are complexes of proteins and lipids that transport lipids in circulation.

Key findings in literature:

Performance and recovery.

PC biosynthesis is important for maintenance of the phospholipid composition of mitochondrial membranes in muscle, and defects in this biosynthesis pathway can result in muscle pathology.1
Supplies of PC are needed to support membrane expansion as the cells grow, for membrane renewal, and for the regeneration of the cells' membrane system following damage.3
PC:PE ratio is reduced in response to acute as well as long-term physical exercise.2
Prolonged intense exercise appears to reduce circulatory choline concentrations. This is important because choline is a precursor both for phosphatidylcholine as well as for acetylcholine, an important neurotransmitter that plays a role in bodily functions such as muscular contraction.
Some studies have evaluated the effect of PC supplementation on performance in a variety of sporting activities. The proposed mechanism is prevention of diminished choline levels.
Total sleep deprivation (TSD) has also been shown to decrease the expression of PC.10

Cognitive function.

Phosphatidylcholine is required for membrane synthesis and maintenance of neuronal synaptic function.
Ylilauri et al. presented a prospective analysis that evaluated dietary intakes of choline and phosphatidylcholine, and their association with performance in cognitive tests assessing verbal fluency and memory.5
In general there are not many studies demonstrating a direct link between PC and improved neurocognitive function. However, it is already stated that supplementation with PC likely influences choline levels.Studies have evaluated the effects of higher choline levels and choline intake on cognitive performance.7, 8
Studies have demonstrated that individuals with certain neurocognitive disorders have reduced choline in plasma and cerebrospinal fluid.4
Data also indicates that PC composition of the neuronal membrane is critical to inhibiting amyloid-beta (Aβ) aggregation, which is a principal component of senile plaques found in individuals with certain neurocognitive disorders. This is important for protecting the neuron from plaque formation and Aβ toxicity.6

Additional findings in literature:

Liver health.1, 9, 10

Lower PC:PE ratio has been linked to the development of some liver diseases.
PC is a critical component for the assembly of very low density lipoproteins (VLDL), which are responsible for transporting triglycerides out of the liver.9
Sleep deprivation significantly decreases the hepatic phosphatidylcholine expression and sharply increases the oxidative stress in hepatocytes.10

References:

What is it?

Phosphatidylserine (PS) is an anionic phospholipid found in cell membranes and accounts for approximately 10-15% of the total phospholipid content in the human cerebral cortex. It plays a major role in the regulation of membrane signaling pathways, neuroinflammation, neurotransmission, and synaptic refinement.

Key findings in literature:

Sleep.

Cortisol is a glucocorticoid hormone produced via the adrenal cortex in response to stress. Its release is mediated by the hypothalamic-pituitary-adrenal (HPA) axis and follows a circadian rhythm - morning peak, slow decline throughout the day, and low or undetectable amounts at night.10
In response to acute stressors, the hypothalamus secretes corticotropin–releasing hormone (CHR), which triggers the release of adrenocorticotropic hormone (ACTH) from the pituitary gland. ACTH then promotes the release of cortisol from the adrenal cortex.12
Deregulated cortisol concentrations have been correlated with diminished sleep quality and insomnia.10, 11
Studies have evaluated the association between PS supplementation and basal cortisol concentrations, as well as regulation of the circadian rhythm of salivary cortisol.2
Researchers have proposed effects on ACTH and cortisol responses to acute physical and mental stress.12

Cognitive function.1, 2, 3, 4

Studies have evaluated the association between PS supplementation and neurocognition. Some metrics have included memory storage, learning, and retrieval.2
Intake of exogenous PS may promote the activity of protein kinase C, a family of enzymes that act as regulators in cellular signaling.1
Exogenous PS may also promote glucose metabolism in the brain cortex.1
PS can promote normalization of NMDA receptors, mediating excitatory transmission essential for cognitive function.1
PS has been shown to impact the metabolic levels of dopamine and serotonin which appear to be lower in individuals with neurocognitive diseases.1
PS has been shown to positively affect the release of choline.1

Additional findings in literature:

Stress & Recovery.

Studies have been conducted in chronically stressed populations, indicating that individuals within these populations may exhibit suppressed cortisol stress responses. Researchers have evaluated the effects of PS on regulation of these stress responses.5
A publication in 2018 evaluated 18 elite shooters supplemented with PS. They measured cortisol levels, neurotransmitter concentrations, and subjective mood scores.9
The Strength and Conditioning Journal evaluated PS benefits in athletes, primarily associated with “overtraining syndrome” (OTS).OTS is an unwanted training effect that occurs with inadequate recovery for the training stimulus. It can have many detrimental effects on body functions.6Findings suggest that the athletes who will benefit most from supplemental PS are individuals who (a) have high amounts of additional nonexercise stress, (b) have reoccurring illnesses, (c) have a low stress capacity, (d) are prone to OTS or have experienced an episode of OTS, (e) are likely to become glycogen depleted, (f) engage in high volumes of aerobic training, (g) are vegetarian/vegan, (h) have a poor diet, (i) participate in additional sports or training, (j) engage in long or multiple competitive seasons, and (k) those who do not acquire enough sleep.6
Studies have evaluated the relationship between elevated levels of circulating cortisol and testosterone levels.7
Furthermore, researchers have evaluated the effects of PS supplementation on plasma cortisol concentrations, and secondarily on testosterone levels.8

References:

What is it?

Vitamin B6, pyridoxine, is a water-soluble vitamin important for many physiological processes. It is involved with the metabolism of proteins, carbohydrates, and lipids. It plays a role in cognitive development through biosynthesis of neurotransmitters and amino acid maintenance. It is also involved in gluconeogenesis, immune function, and hemoglobin formation. Pyridoxal 5’ phosphate, also known as P5P or PLP, is the active coenzyme form of vitamin B6.

Key findings in literature:

Inflammation.

Researchers have evaluated the association between higher intake of vitamin B6 (and/or higher plasma concentration of P5P) and inflammatory markers. Some studies evaluated individual markers such as c-reactive protein (CRP), while other utilized an overall inflammation score (IS) that encompasses 13 different inflammatory markers.4
Another article commented on the relationship between vitamin B6 and interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in conditions of chronic inflammation.3

Cardiovascular.

Researchers have evaluated the association between vitamin B6 and cardiovascular health. For example, some studies evaluated homocysteine levels in patients supplementing with vitamin B6.1, 4
P5P plays an important role in the homocysteine pathway as a cofactor for enzymes responsible for homocysteine metabolism and breakdown.3
Homocysteine is an amino acid. Abnormally high concentrations of homocysteine are known to mediate cardiovascular problems due to adverse effects on cardiovascular endothelium and smooth muscle cells, resulting in alterations in arterial structure and function.2

Additional findings in literature:

Sleep.

Research evaluating the effects of vitamin B6 on sleep is limited. Some studies have evaluated the relationship between average P5P concentrations and sleep duration. Other studies have supplemented participants with products containing vitamin B6 and evaluated the effects on sleep quality and duration.5, 6, 7

Cognitive function.

Researchers have evaluated the association between vitamin B6 / P5P concentrations and memory test scores.1
An analysis of participants from the Boston Puerto Rican Health Study cohort evaluated cognitive function in individuals with higher plasma concentrations of P5P.8

References:

Electrolytes & Minerals

What is it? 1, 5, 9

Magnesium is an abundant and important mineral required for many important physiological functions. It is a cofactor in over 300 enzyme systems that regulate protein synthesis, muscle and nerve function, blood glucose control, and blood pressure regulation. It contributes to structural development of bone and plays a role in the active transport of calcium and potassium ions important to nerve impulse conduction, muscle contraction, and normal heart rhythm. As important as it is, magnesium is one of the most common deficiencies seen with the American diet.

Key findings in literature:

Sleep.2, 3, 9

Magnesium’s effect on sleep is thought to be due to its natural NMDA antagonist and GABA agonist properties, promoting relaxation.
Studies have evaluated effects of magnesium supplementation on improvements in subjective sleep measures such as sleep efficiency, sleep time and onset latency, and early morning awakening. Some studies also utilized objective measurements such as serum renin, melatonin, and serum cortisol.
Studies have evaluated the association between magnesium supplementation and serum cortisol concentrations. One proposed mechanism is NMDA antagonism resulting in reduction activity and secretion of adrenocorticotropin (ACTH) “stress hormone” from the pituitary gland.

Additional findings in literature:

Cardiovascular.

Clinical trials have evaluated the association between magnesium supplementation and blood pressure. There have also been findings to suggest effects on ischemic heart disease and stroke.2, 6
A prospective analysis conducted within the Nurses’ Health Study involving 88,375 female nurses looked at prevalence of sudden cardiac death in individuals with higher plasma concentrations and dietary intake of magnesium.7

Bone health.1

Magnesium is involved in bone formation and influences the activities of osteoblasts and osteoclasts.
It also affects concentrations of parathyroid hormone (PTH) and the active form of vitamin D, both of which are major regulators of bone homeostasis.
Studies have evaluated the association between lower serum levels of magnesium and osteoporosis. Some studies have also observed decreased bone loss in individuals supplementing with magnesium.

Migraines.1

Studies have evaluated the association between low magnesium levels and migraine headaches.
Several placebo-controlled trials have observed the effects of magnesium supplementation on frequency of migraines.
Magnesium deficiency may contribute to major elements of migraine development such as cortical spreading depression, nociceptor alteration and neurotransmitter release, vasoconstriction, and platelet hyperaggregation. 8

Metabolism.1

Studies have evaluated the association between dietary magnesium intake and metabolism, suggesting a role in glucose metabolism and insulin resistance.
Metabolic conditions may also promote increased urinary losses of magnesium.

Mood.3

Meta-analysis of randomized controlled trials (RCT) suggests that magnesium supplementation may have a beneficial effect on mood.
7 RCTs with sample size of 325 subjects included. Researchers evaluated several different subjective depression scores compared with placebo.
Theorized to affect mood disorders through a combination of antiinflammatory properties, sleep quality alteration, and neurotransmitter receptor alteration in the hippocampus.

Inflammation.

Some studies have evaluated the association between recommended daily amounts (RDA) of magnesium and inflammatory markers such as c-reactive protein (CRP).4

References:

What is it?

Zinc is an essential mineral that is involved in many aspects of cellular metabolism such as enzyme activation, immune function, wound healing, and cell signaling and division.

Key findings in literature:

NMDA.

Zinc is an antagonist of glutamatergic NMDA receptors, which in turn decreases excitation.

Sleep.

Zinc has long been considered a possible supplement for sleep disturbance, however further randomized controlled trials are needed to support its benefits.
Overall it is likely that glutamatergic NMDA antagonism decreases excitation and promotes sleep.
A systematic review investigated 8 studies from 2009 - 2022. Studies evaluated the association of zinc supplementation on sleep efficiency. One study in this review specifically looked at ICU nurses.2
Zinc is also needed for the synthesis of glutamate, GABA, and melatonin.
Studies have evaluated the association between zinc supplementation and insomnia in individuals with Alzheimer’s dementia. Alzheimer’s is associated with amyloid plaques forming in the brain, and these plaques are highly enriched with zinc. Many of these patients present with overall zinc deficiency because the amyloid plaques essentially immobilize the pool of zinc in the brain and reduce bioavailability to the neurons, similar to a negative feedback loop.3

Additional findings in literature:

General health.1

Results from clinical trials have been inconsistent, however many studies have demonstrated favorable outcomes in regard to zinc supplementation and duration of the common cold.
Observational studies have suggested that zinc supplementation may promote ocular health.
Some studies have suggested that zinc supplementation may promote metabolic health, i.e. cholesterol and insulin resistance.

Mood.4

Researchers have evaluated the association between zinc supplementation and mood disorders, again likely secondary to the modulation of NMDA receptors. Improvements in sleep quality may also improve depressive symptoms.

Deficiency.1

Certain populations are more at risk for zinc deficiency. This includes women who are pregnant or lactating, people following vegetarian or vegan diets, and people with gastrointestinal disorders.
Alcohol consumption can also lead to zinc deficiency. Ethanol consumption decreases intestinal absorption of zinc and increases urinary zinc excretion.

References:

What is it?1, 2

Potassium is an essential nutrient, and the most abundant intracellular cation. It is present in all body tissues and required for normal cellular function. While potassium requirements can vary based on a number of different factors, surveys have suggested that most recommendations for adequate intake are considerably higher than average intakes. A National Health and Nutrition survey in 2011-2012 demonstrated that less than 3% of the examined population were meeting the guidelines for adequate intake.

Key findings in literature:

Sweat loss.5, 6, 7

Potassium deficiency is known as hypokalemia.
While potassium can be lost from the body from various routes such as vomiting, diarrhea, and diuresis secondary to medications such as antihypertensives, a lesser thought of route is through sweat.
Some studies have shown that a large amount of potassium is lost via sweat, both during training in the heat and remaining stationary.
In many individuals it is likely that the daily losses of potassium in sweat and urine exceed dietary intake of potassium, resulting in a net negative.
Thus, potassium supplementation may play an important role in electrolyte replenishment. This is important both for those with physical careers and those working in excessive heat. In general it is important for most individuals considering many are likely not meeting the recommended adequate intake for potassium.

Sleep.8

A randomized controlled trial published in 2024 evaluated serum cortisol and melatonin levels in individuals supplementing with potassium.
This study also evaluated subjective improvements in sleep using the Insomnia Severity Index.
Results also showed possible benefits from supplementing with both potassium and magnesium, rather than one alone.

Additional findings in literature:

Cardiovascular.1, 3, 4

There is extensive literature evaluating the effects of higher potassium intake on cardiovascular health.
Higher potassium intake may provide cardiovascular benefits by increasing vasodilation and urinary sodium excretion, in turn leading to decreased plasma volume.
Some findings suggest that other mechanisms such as improved endothelial function and reduced free radical formation may be involved.

Bone health.1

Observational studies have evaluated the association between increased potassium consumption and bone mineral density.
This may be due to an effect on acid-base balance. Diets that are high in acid-forming foods, such as meats and cereal grains, contribute to metabolic acidosis and may have adverse effects on bone.
Clinical trials have primarily utilized alkaline potassium salts such as potassium bicarbonate and potassium citrate. These alkaline components may counter the effects of acid formation and help preserve bone tissue.

Kidney stones.1

Kidney stones most commonly contain calcium, generally in the form of calcium oxalate or calcium phosphate. Low potassium intake impairs calcium reabsorption within the kidney, resulting in increased urinary calcium excretion which can contribute to stone formation.
Potassium citrate is the most likely potassium salt to provide benefits. Citrate itself forms complexes with urinary calcium and increases urine pH, which inhibits the formation of calcium oxalate crystals.

Metabolism.1

Observational studies have suggested that individuals with lower potassium intakes may be at greater risk for metabolic conditions.
Another observational study from the Nurses’ Health study demonstrated an inverse relationship between serum potassium levels and fasting glucose.
Potassium is needed for insulin secretion from pancreatic cells.

References:

What is it?

Sodium is the most abundant extracellular cation and is vital for maintaining extracellular volume, electrolyte balance, and blood pressure. Deficiencies are not common in healthy populations, however low sodium (hyponatremia) can be extremely common in pathologic conditions such as burns and prolonged sweating.

Key findings in literature:

Hyponatremia.1, 2, 3

Sodium deficiency is known as hyponatremia.
Higher than recommended sodium intake has been shown to adversely affect health due to mechanisms such as increased blood volume and alteration of the renin-angiotensin system.
However, many studies have also demonstrated that lower than recommended sodium intake may also have deleterious effects.
Some studies have demonstrated that sodium restriction resulted in increased renin, aldosterone, and catecholamine activity.
It is thought that long-term sodium restriction could have a negative impact on lipid and glucose metabolism, potentially increasing risk of insulin resistance, hyperlipidemia, and lipid infiltration in arterial walls.
Current evidence indicates that 3 to 5 grams of dietary sodium is associated with the lowest cardiovascular risk, although the Dietary Guidelines for Americans (DGA) recommends 2.3 grams daily. The average daily consumption in the USA is about 3.3 grams.

Additional findings in literature:

Acid buffer.

Similar to potassium, sodium citrate may be a beneficial sodium salt in regards to supplementation.
Citrate can form complexes with urinary calcium which increases urine pH and inhibits formation of calcium crystals.
A randomized controlled trial in 2024 evaluated sodium citrate versus sodium bicarbonate in metabolic acidosis, noting similar outcomes but finding that some individuals taking sodium bicarbonate experienced more diarrhea and abdominal pain.4

References:

What is it?

Chloride is the most abundant ion in humans after sodium, and accounts for 70% of the total anions in extracellular fluid. It is vital for maintaining osmotic pressure, muscle movement, and acid-base balance in the body. Chloride is most commonly ingested in the form of sodium chloride (NaCl), which serves as a common additive in many food preparations.1 It can also be found in fresh fruits, vegetables, and red meats.

Key findings in literature:

Hypochloremia.

Chloride deficiency is known as hypochloremia.
Chloride loss, as well as sodium, is observed in patients with prolonged diarrhea, vomiting, or excessive sweating.1
Severe vomiting may lead to the most disproportionate loss of chloride since gastric chloride content is very high and gastric sodium content is relatively low.4
A study from 2018 evaluated sweat loss in athletes and demonstrated that total sweat sodium and chloride losses increased by approximately 150% with increased exercise intensity.2
Diuretics and high blood glucose levels can also cause hypochloremia.1
Past studies have shown that whole-body sweating rate and regional sweating rate increase proportionally with the rate of metabolic heat production.2

Additional findings in literature:

Brain health.3, 5

For decades, it has been well understood that neuronal excitability is primarily mediated through synaptic transmission of neurotransmitters such as glutamate and GABA.
A growing body of evidence highlights the role of intracellular chloride concentration as a fundamental regulator of neuronal function and key determinant of brain health.
An electrochemical gradient, coordinated through several chloride channels and transporters, governs GABA and glycine response polarity, neuronal excitability thresholds, and plasticity.

References:

Other References

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