Metagenics CalmX Raspberry or Tropical Powder
Directions: Metagenics CalmX
Add 2 level scoops (12.7g) to 200 mL of water, twice daily.
Clinical Benefits: Metagenics CalmX
- Provides 350 mg of highly bioavailable Meta Mag® magnesium to be of benefit during stress. Magnesium, B vitamins, vitamin C and zinc are all nutrients required to be able to cope with stress effectively and may be depleted in chronic stress.4 The adrenergic effects of stress induce a shift of magnesium to the extracellular space, increasing urinary excretion and depleting body stores (Figure One). Magnesium deficiency adversely affects excitatory neurotransmitters such as serotonin and acetylcholine and is associated with stress.
- A double-blind, placebo controlled trial using 6.0 g of taurine per day investigated its impact on stress symptoms and biochemistry. This study showed taurine to inhibit the stress-induced release of adrenaline.8 Magnesium, B vitamins, vitamin C and zinc are required to regulate the stress response as co-factors in neurotransmitter synthesis.
- Zinc is essential in modulating the stress response.9 Zinc levels have been found to be deficient in people with generalised anxiety disorder.10 Exposure to acute stress increases serum glycocorticoids and induces metallothionein synthesis which consequently decreases serum zinc.11
Figure One: Magnesium and the Stress Response.
Ingredients: Metagenics CalmX
|Each 12.7 g dose contains:|
|Magnesium amino acid chelate (Meta Mag® - Magnesium bisglycinate)||3.5g|
|Calcium ascorbate dihydrate||605mg|
|Equivalent Ascorbic acid (Vitamin C)||500mg|
|Thiamine hydrochloride (Vitamin B1)||25mg|
|Equivalent Riboflavin sodium phosphate||34mg|
|Riboflavin (Vitamin B2)||25mg|
|Nicotinamide (Vitamin B3)||25mg|
|Calcium pantothenate (Vitamin B5)||25mg|
|Pyidoxal 5-phosphate monohydrate (Vitamin B6)||25mg|
|Zinc amino acid chelate (Meta Zn® - Zinc bisglycinate)||50mg|
Metagenics CalmX is free from animal products, dairy protein, lactose, eggs, gluten, wheat, nuts, yeast and soy protein.
Metagenics CalmX is free from artificial colours, sweeteners, flavours and preservatives. Sweetened with steviol glycosides. Contains 362 mg of potassium per 11.9 g dose.
Excipients: Metagenics CalmX
Citric acid, Colloidal anhydrous silica, Flavour, Hypromellose, Malic acid, Silicon dioxide, Steviol glycosides and Tartaric acid.
Warnings: Metagenics CalmX
Not all cautions and contraindications are listed. For full details, references or more information contact HealthMasters in Australia by email: firstname.lastname@example.org
Storage: Metagenics CalmX
Store below 30° C
Magnesium Bisglycinate: Metagenics CalmX
Metagenics CalmX contains evidenced-based ingredients to support the natural metabolic pathways for gamma-aminobutyric acid (GABA) production and activity, indicated to promote relaxation during times of stress. MetaMag Magnesium bisglycinate is scientifically designed to provide a highly bioavailable form of magnesium. Magnesium may act as a GABA receptor agonist and also has a binding site on the glutamate receptors helping to regulate the activity of this main excitatory neurotransmitter.1 Glycine functions as an inhibitory neurotransmitter in the nervous system while glutamine is a precursor to GABA production.2 Pyridoxal (vitamin B6) is a cofactor for the enzyme Glutamate decarboxylase that synthesises GABA from glutamate.4 Zinc also has a binding site on the glutamate receptor and may act as a modulator for both excitatory and inhibitory neurotransmission.5
Magnesium is predominantly located intra-cellular in bone, muscles and non-muscular soft tissues while only 1% of total magnesium is found in serum and red blood cells. Magnesium needs to be consumed in the diet regularly to prevent the risk of magnesium deficiency and due to the increased consumption of processed foods; magnesium intake in the western world is decreasing. Magnesium is a cofactor in more than 300 enzymatic reactions, critically stabilising enzymes, including many ATP-generating reactions. ATP metabolism, muscle contraction and relaxation, normal neurological function and release of neurotransmitters are all magnesium dependent.6 While evidence generally does not support the use of magnesium for skeletal muscle cramps with many studies producing null effect7,8, there is evidence to suggest oral magnesium supplementation can improve anaerobic metabolism in athletes, decreasing lactate production9 and improving physical performance in healthy elderly women involved in an exercise program.10
Magnesium may function as a GABA receptor agonist promoting the effects of GABA. Further, in the central nervous system (CNS), magnesium ions block NMDAR channels at resting membrane potentials. The binding site for magnesium ions is deep within the channel. This block is voltage-dependent but ion flux occurs when the membrane potential is depolarized. NMDAR receptors are glutamate-binding sites, being the major excitatory neurotransmitter in the CNS.11 See Figure 1.
Figure 1. Neurotransmitter signalling12
Glycine functions as one of the major inhibitory neurotransmitters in the CNS with a high density of glycine containing neurons being found in spinal cord and brain stem. When glycine binds to its receptor it opens the anion channel allowing an influx of chloride ions into the postsynaptic neuron causing hyperpolarization that raises the threshold for neuronal firing and thereby inhibits the postsynaptic neuron.2,13
Glutamine and glutamate are amino acids. Several studies show that concentrations of serum glutamine in the body are diminished during times of physical or psychological stress and further that patients presenting with exhaustion, anxiety, sleeplessness and lack of concentration have low serum glutamate concentration. Glutamine and glutamate synthesis occur interchangeably (see figure 2). Glutamine converts to glutamate using NADPH as a cofactor and glutamate is a precursor for GABA production using vitamin B6 as a cofactor.15-19
Figure 2. GABA is synthesized from Glutamine and Glutamate20
Pyridoxal 5-Phosphate (Vitamin B6)
Pyridoxine is the cofactor required by Glutamate decarboxylase to convert glutamate to GABA in the CNS.4 See Figure 2.
Approximately 10% of total zinc in the brain is located in synaptic vesicles of certain glutamatergic neurons.5 Zinc may modulate neurotransmission mediated via both excitatory and inhibitory amino acid receptors at specific synapses for example the NMDA glutamate receptor is directly inhibited by zinc whereas GABA release from the presynapse can be potentiated (see Figure 1).28
- To naturally increase GABA production to induce relaxation
- Helps relieve symptoms of nervous tension, stress and mild anxiety
- For the symptomatic relief of stress disorders.
- Herbal blend which helps relieve stress of study or work
- May help reduce the frequency of migraines.
Who will benefit:
- Those with symptoms of anxiety and nervous tension
- Those who are experiencing mild stress and associated disorders
- Those who are experiencing stress associated with work and/or study
- Those with magnesium deficiency
- Those who are experiencing frequent migraines
- Those who wish to improve their cognitive performance and mood.
- Held K, Antonijevic IA, Künzel H, et al. Oral Mg(2+) supplementation reverses age-related neuroendocrine and sleep EEG changes in humans. Pharmacopsychiatry 2002;35(4):135-143
- Legendre P. The glycinergic inhibitory synapse. Cell. Mol. Life Sci 2001;58:760–793
- Kimura K1, Ozeki M, Juneja LR, et al. L-Theanine reduces psychological and physiological stress responses. Biol Psychol 2007;74(1):39-45
- Qu K, Martin DL, Lawrence C. Motifs and structural fold of the cofactor binding site of human glutamate decarboxylase. Protein Sci 1998;7:1092-1105.
- Takeda A, Minami A, Seki Y, et al. Differential effects of zinc on glutamatergic and GABAergic neurotransmitter systems in the hippocampus. J Neurosci Res 2004; 15;75(2):225-9.
- Jahnen-Dechent W, Ketteler M. Magnesium basics. Clin Kidney J 2012;5 (1);i3–i14.
- Nygaard IH, Valbo A, Oethick SV, et al. Does oral magnesium substitution relieve pregnancy-inducede leg cramps? Eur J Obstet Gynecol Reprod Biol 2008;141:23-6.
- Garrison SR, Birmingham CL, Koehler BE, et al. The effect of magnesium infusion on rest cramps: a randomized controlled trial. J Gerontol A Biol Sci Med Sci 2011;66:661-6.
- Setaro L, Santos-Silva PR, Nakano EY, et al. Magnesium status and the physical performance of volleyball players: effects of magnesium supplementation. J Sports Sci 2014;32:438-45.
- Veronese N, Berton L, Carraro S, et al. Effect of oral magnesium supplementation on physical performance in healthy elderly women involved in a weekly exercise program: a randomized controlled trial. Am J Nutr 2014;100:974-81.
- Monaghan DT, Jane DE. Pharmacology of NMDA receptors. In: Van Dongen AM, editor. Biology of the NMDA receptor. Boca Raton (FL): CRC Press/Taylor & Francis; 2009. Chapter 12.
- Gecz, J. Glutamate receptors and learning and memory. Nat. Genet 2010;42:925
- Berger AJ, Dieudonne S, Ascher P. Glycine uptake governs glycine site occupancy at NMDA receptors of excitatory synapses. J. Neurophysiol 1998;80: 3336–3340.
- Hubner CA, Stein V, Hermans-Borgmeyer I, et al. Disruption of KCC2 reveals an essential role of K-Cl cotransport already in early synaptic inhibition. Neuron 2001;30:515–524.
- Chen SW, Kong WX, Zhang YJ, et al. Possible anxiolytic effects of taurine in the mouse elevated plus-maze. Life Sci 2004;75(12):1503-1511.
- Hertz L, Kvamme E, McGeer, EG, et al. Glutamine, Glutamate, and Gaba in the Central Nervous System. Alan R Liss Inc. New York; 1983.
- Bowtell JL, Gelly K, Jackman ML, et al. Effect of oral glutamine on whole body carbohydrate storage during recovery from exhaustive exercise. J.Appl Physiol 1999:1770-1777.
- Welbourne TC. Increased plasma bicarbonate and growth hormone after an oral glutamine load. Am J Clin Nutr 1995;61(5):1058-1061.
- Hasler G, Van der Veen JW, Tumonis, T, et al. Reduced Prefrontal Glutamate/Glutamine and Aminobutyric Acid Levels in Major Depression Determined Using Proton Magnetic Resonance Spectroscopy. Arch Gen Psych 2007;64 (2):193-200.
- Owens DF, Krieg Stein AR. Is there more to GABA than synaptic inhibition? Nat. Rev. Neurosci 2002;3:715
- Kakuda T, Nozawa A, Sugimoto A, et al. Inhibition by Theanine of binding of [3H]AMPA, [3H]Kainate and [3H]MDL 105,519 to glutamate receptors. Biosci Biotechnol Biochem 2002;66:2683-86.
- Kimura R, Murata T. Influence of alkylamides of glutamic acid and related compounds on the central nervous system I. Central depressant effect of theanine. Chem Pharm Bull 1971;19:1257–1261.
- Nathan PJ, Lu K, Gray M, et al.; The neuropharmacology of L-theanine (N-ethyl-L-glutamine): a possible neuroprotective and cognitive enhancing agent. J Herb Pharmacother 2006;6(2):21-30.
- Heese T, Jenkinson J, Love C, et al.& Anxiolytic effects of L-theanine - a component of green tea - when combined with midazolam, in the male Sprague-Dawley rat. AANA J 2009;77(6):445-449.
- Ito K, Nagato Y, Aoi N, et al. Effects of L-theanine on the release of alpha brain waves in human volunteers. Nippon Nogeikagaku Kaishi 1998;72:153-157.
- Lu K., Gray MA, Oliver C, et al. The acute effects of L-theanine in comparison with alprazolam on anticipatory anxiety in humans. Hum Psychopharmacol 2004;19(7):457-465.
- Lardner AL. Neurobiological effects of the green tea constituent Theanine and its potential role in the treatment of psychiatric and neurodegenerative disorders. Nutr Neurosci 2014;17:145-55.
- Smart TG, Hosie AM, Miller PS. Zn2+ ions: modulators of excitatory and inhibitory synaptic activity. Neuroscientist 2004;10(5):432-42.
- Gröber U. Magnesium. In: Gröber U., editor. Micronutrients: Metabolic Tuning-Prevention-Therapy. 1st ed. MedPharm Scientific Publishers; Stuttgart, Germany: 2009:159–166.
- Foca FJ. Motor and sensory neuropathy secondary to excessive pyridoxine ingestion. Arch Phys Med Rehabil 1985;66(9):634-6.
- Dalton K, Dalton MJ. Characteristics of pyridoxine overdose neuropathy syndrome. Acta Neurol Scand 1987;76(1):8-11.
Technical Information: Metagenics CalmX
META MAG MAGNESIUM, TAURINE AND GLUTAMINE FOR STRESS
Magnesium, taurine and glutamine are key nutrients to reduce the effects of physical and psychological stress on the body. In addition, sufficient amounts of B group vitamins are important for the production of stress-response hormones. Magnesium, in particular, plays a pivotal role in a number of functions in the human body, many of which are brain related. For example, magnesium can reduce the effect of Nmethyl-D-aspartate (NMDA) receptor stimulation, by acting as a voltage-gated antagonist at the glutamate NMDA receptor (Figure 1). With chronic stress increasing the hypothalamic NMDA receptor expression, deficiency of magnesium can impact mood with symptoms such as depression, apathy and/or anxiety. Furthermore, studies have demonstrated increased rates of depression in individuals with lower levels of serum zinc; with an inverse relationship seen between lowered zinc status and higher depressive scores. Potassium citrate and glutamine, which enhance the acid-alkaline balance of the body, may also be beneficial for low-grade metabolic acidosis.
Figure 1: Magnesium reduces the effect of NMDA receptor stimulation by acting as a voltage-gated antagonist at the glutamate NMDA receptor in the brain.
Nutrients That May Assist
- Magnesium - Magnesium amino acid chelate (Meta Mag® - Magnesium bisglycinate)
- Potassium - Potassium citrate
- Vitamin C - Calcium ascorbate dihydrate
- Vitamin B1 - Thiamine hydrochloride
- Vitamin B2 - Riboflavin sodium phosphate
- Vitamin B3 - Nicotinamide
- Vitamin B5 - Calcium pantothenate
- Vitamin B6 - Pyridoxal 5-phosphate monohydrate
- Zinc - Zinc amino acid chelate (Meta Zn® - Zinc bisglycinate)
- Nervous system support
- Reduce stress and anxiety
- Supporting healthy mood
*Dosing regimens should be determined by appropriate assessment and monitoring.
BACKGROUND TECHNICAL INFORMATION
Magnesium, the Mental Mineral
Magnesium regulates neuronal excitability and membrane fluidity and is arguably the most important micronutrient in relation to nerve and mental function. Magnesium is a cofactor for more than 300 enzymatic reactions in the body1,2 and with many of magnesium’s enzymatic processes being brain-related, deficiency has been associated with a large range of symptoms. These include personality changes such as apathy, depression, confusion, agitation, and delirium.3 Furthermore, low magnesium status has been correlated with other mental health disorders including anxiety,4 psychosis,5 and stress-related conditions such as phobias, tics, obsessive compulsive and dissociative disorders, hyperexcitability, hyper emotivity and other negative emotional states.6
Magnesium deficiency is common, with a recent Australian Health Survey finding 72% of 14-18 year old females, and an average of just under 40% of all Australian adults consuming inadequate amounts of magnesium daily.7 In addition, dietary factors such as high intakes of fat, calcium, coffee and strong tea can worsen magnesium status, by either reducing absorption or enhancing elimination.8
‘Magnesium deficiency has been associated with a large range symptoms and personality changes such as apathy, depression, confusion, agitation and delirium.’
It has been well-established that amino acid chelates offer the best form of delivery for most minerals. Of these, magnesium bisglycinate (Meta Mag) is the most efficient way to present high dose magnesium (regarding absorption and utilisation), due to glycine being the smallest amino acid.9,10 Glycine allows the chelate to be effectively absorbed through amino acid channels for complete utilisation once within the body.11 The combination of minerals with amino acids also mimics the natural delivery of minerals from plant and animal sources,12 therefore delivering them the way they are generally found in nature.
Studies have shown that magnesium bisglycinate is absorbed into enterocytes intact.13 Magnesium then dissociates from glycine within the enterocyte and is delivered rapidly into the blood stream.14 Not only is intestinal uptake (bioavailability) greater with magnesium bisglycinate compared to other forms of magnesium (Figure 2), studies have also shown faster absorption. For example, magnesium bisglycinate was absorbed at a rate 228% higher than that of magnesium chloride in a study carried out on a group of athletic females.15
Figure 2: Intestinal uptake rate of different magnesium types.16
Nervous System Support
Magnesium supplementation has been shown to affect all elements of the body’s reactions to stress, exerting a neuroprotective effect. For example, in the event of deficiency, magnesium repletion reverses the increased stress sensitivity, with pharmacological loading of magnesium inducing resistance to neuropsychological stressors such as glutamate excitotoxicity.17
Glutamate is an excitatory neurotransmitter important for brain function and development; however, an excess of glutamate can result in neurotoxicity.
With the ability to inhibit the release of excitatory neurotransmitters, magnesium acts as a voltage-gated antagonist at the glutamate, NMDA receptor.18 When the NMDA receptor is over-activated, it can result in increased cell death and increased excitotoxicity which ultimately results in neurological changes. For example, low levels of magnesium has been associated with hippocampal atrophy, with supplementation demonstrating the ability to boost brain derived neurotrophic factor (BDNF) and promote hippocampal neurogenesis.19 Psychological stress is one of the states that can result in the release of glutamate (which exerts excitatory effects), and appears to be mediated, at least in part, via glucocorticoids, which can both increase glutamate levels and contribute to the neuronal damage.20
In a state of deficiency, the neuronal requirements for magnesium may not be met, causing the neuronal damage which can result in low mood.21 Acute stress has been associated with increased plasma magnesium levels due to the release of stress hormones (catecholamines and corticosteroids), and increased urinary excretion.22 This is due to the body shifting magnesium from the intracellular to extracellular space as a protective mechanism to reduce the effects of stress.23 For example, by limiting the rate of inflammation and oxidation experienced at times of stress, as well as supporting extra neurotransmitter requirements.
With extended periods of stress resulting in progressively deficient magnesium levels, a vicious cycle can develop where stress increases cellular magnesium losses, thus resulting in an exaggerated stress response.24 Moreover, magnesium deficiency is itself a stress to the body, as it has been linked to promoting catecholamine release, promoting pro-inflammatory factors, and disrupting sleep patterns.25 Therefore, it is suitable to say that magnesium deficiency is both a cause and a consequence of stress.
The anxiolytic effects of magnesium are similarly attributed to the reduction of glutamate activity, and the increased actions of the gamma aminobutyric acid (GABA)-ergic systems26 (Figure 3). This results in a soothing effect on the entire stress response system,27 as GABA acts as the body’s primary calming influence, working to control and balance the effects of glutamate.
Magnesium ions regulate calcium ions as part of nerve cell conduction activity,28 (Figure 4) with magnesium deficiency causing NMDA-coupled calcium channels to be biased towards opening, leading to further neuronal injury and neurological dysfunction.29 This results in glutamate-induced neuro-excitotoxicity, which may manifest as anxiety and other mood and behavioural disorders.30
Figure 3: Magnesium’s mechanism of action in anxiety and panic.39
Taurine, (otherwise known as 2-aminoethane sulfonic acid), has modulatory effects on the magnitude of the stress response in the brain. Taurine has been described as a unique psychopharmacological compound,31 which can act as a neuromodulator, an osmoregulator, a regulator of cytoplasmic calcium levels, a neuroprotectant, and a trophic factor in development.32 It is involved in the regulation of calcium movement during depolarisation as well as in maintaining the structural integrity of the neuronal membrane.33 Animal studies indicate taurine exerts anxiolytic34 and antidepressant-like effects, with no alteration of locomotor activity.35
Taurine is found abundantly in the brain.36 It has been shown to act as an inhibitory neurotransmitter or neuromodulator; (thus protecting against glutamate excitotoxicity) and may directly interact at the glutamate NMDA receptor to suppress glutamatergic transmission.37 Furthermore, taurine is reported to be supportive when treating addictions, due to its ability to decrease extracellular basal levels of dopamine as well as prevent acute increases in the synaptic levels of dopamine within the nucleus accumbens;38 the area of the brain involved in reward, motivation and impulsivity.
Figure 4: The role of magnesium in regulating calcium ion flow and neurotransmission.40
Zinc is required throughout the human body for a myriad of chemical reactions necessary for normal body functioning.41 For example, it is well-established that zinc supplementation provides antidepressant-like effects, with zinc deficient diets associated with low moods.42 Zinc has been shown to increase BDNF, which is recognised as a target implicated in the aetiology of depression.43 It has been demonstrated that BDNF plays a significant role in supporting patients with low mood, with a meta-analysis showing depressive patients have decreased serum and plasma BDNF levels.44 Zinc is highly concentrated in the synaptic vesicles of specific neurons, and regulates the release of neurotransmitters. The neurons that contain zinc are known as zinc-enriched neurons (ZEN), with cerebellar ZEN primarily associated with GABA neurotransmission, which produces a calming effect by balancing over-excitability. In other regions, ZEN are found in glutamate-producing neurons.45 Furthermore, zinc has been shown to increase synaptic dopamine levels, thereby allowing dopamine to stay and engage with receptors longer within the synapse, and is considered an important regulator of dopamine transporter function.46
Additionally, zinc also acts as an inhibitory neuromodulator of glutamate release, regulating NMDA receptors.47 The areas of the brain in which functional and structural changes occur in the course of low mood are areas of particularly high concentration of glutamatergic neurons sequestering zinc, and the subsequent NMDA receptors are characterised by a high degree of susceptibility to the inhibitory effects of zinc.48 This reflects a further need for sufficient zinc to reduce the excitotoxicity associated with the pathophysiology of mood disorders.
‘It has been well-established that zinc supplementation provides antidepressant-like effects, with zinc deficient diets associated with low moods.’
Moreover, deficiency of thiamine has been associated with decreased glutamate uptake in the brain and increased levels in the cerebrospinal fluid.49 Up to 85% of thiamine content in meat and vegetables is lost with cooking and processing, and there is significant loss with refining of grains.50
L-Glutamine is the most abundant extracellular amino acid and is the precursor for the neurotransmitters glutamate and GABA. It is quantitatively the most important fuel for intestinal tissue, while other functions include its role as a precursor for glutathione production, neurotransmitter synthesis, and its function in controlling acid-base balance.51
Glutathione is the most important intracellular antioxidant, protecting cellular organelles, including the nucleus and DNA, from oxidative damage.
Vitamin C (ascorbic acid) is required for the synthesis of neurotransmitters (including noradrenaline and serotonin), as well as the synthesis and catabolism of tyrosine.52 Vitamin C is maintained at elevated levels in the central nervous system and may act as a neuromodulator, facilitating the release of neurotransmitters and inhibiting glutamate binding to receptors.53 Additionally, the antioxidant properties of vitamin C can assist in reducing reactive oxygen species (ROS), which have been shown to be subsequently increased due to chronic stress.54 The presence of ROS may result in oxidative damage in the central nervous system, which has been demonstrated to play a role in the development of depressive symptoms.
‘Vitamin B6 is a fundamental nutrient for the production of many neurotransmitters.* Deficiency is often associated with psychological disturbances such as mood alterations.’
There are many forms of vitamin C, with calcium ascorbate being the calcium mineral salt of ascorbic acid. This form is buffered and less acidic than ascorbic acid itself. Therefore, it is better tolerated by those who may experience abdominal pain or diarrhoea with ascorbic acid.55
Riboflavin sodium phosphate (vitamin B2, also known as flavin monucleotide or FMN), and its derivative flavin adenine dinucleotide (FAD), functions as a coenzyme for a wide variety of different reactions in intermediary metabolism in the body.56 In particular, rib