Minerals

Synergist compounds that support nutrient transport and utilization, cytokine and eicosanoid modulation, neurotrophin factors, redox reactions, cholesterol regulation, and much more..

Magnesium Glycinate

Magnesium Glycinate Common Names

Magnesium Glycinate | Magnesium Diglycinate | Magnesium Bisglycinate | Magnesium | Glycine

Top Benefits of Magnesium Glycinate

  • Supports cellular energy*
  • Supports cardiovascular function*
  • Supports brain function*
  • Supports musculoskeletal health*
  • Supports healthy gut microbiota*

What Is Magnesium Glycinate?

Magnesium glycinate is a chelated form of the mineral magnesium. It is made from one magnesium bound to two glycines. Both are involved in supporting efficient cellular function. Magnesium is one of the most abundant minerals in the body and is vital for the functioning of all living cells. It’s used in more than 300 enzymes. ATP (i.e., cellular energy) occurs complexed with ATP, so all enzymes utilizing or synthesizing ATP require magnesium. The same is true for enzymes that synthesize DNA and RNA, magnesium is always involved. Magnesium also plays a large role in breaking down sugars (glycolysis). Because magnesium supports the electrical functions of cells (i.e., it’s an electrolyte), muscle and nerve function rely on magnesium. Glycine was discovered in the early 1800’s. It’s name comes from the Greek word for sweet, because glycine has a sweet taste similar to sugar. Glycine is a conditional amino acid. While we can make glycine inside the body (i.e., it’s non-essential), there are circumstances where the amount we make and what we get in the diet appear to be insufficient to optimize functional health. Glycine is used to make many proteins in the body. An example is glutathione, which functions as part of cellular antioxidant defenses and detoxification. Glycine is also used in the brain as a neurotransmitter and throughout the body to make collagen. Collagen proteins are the best dietary source of glycine.  

Neurohacker’s Magnesium Glycinate Sourcing

Magnesium glycinate is used when there’s a role for both magnesium and glycine in the formula. For example, both support healthy cellular energy function. Magnesium is involved in making and using ATP and glycine supports building the antioxidant molecule glutathione, so boosts antioxidant defenses.

Magnesium glycinate has higher bioavailability than other more traditional forms of magnesium supplementation, because the two glycines act as a carrier and allow for efficient absorption (1)

Magnesium glycinate sourcing is focused on ensuring it is non-GMO, gluten-free and vegan.

Magnesium Glycinate Dosing Principles and Rationale

The Recommended Dietary Allowances for magnesium in adults varies from 310 to 420 depending upon age and gender. A majority of Americans of all ages fall somewhat short of this amount. Supplying even a low dose of magnesium can help close the gap. Magnesium glycinate contains about 14% elemental magnesium by mass (the other 86% is glycine), so the complex provides far more glycine than magnesium. An average adult requires about 15 grams of glycine daily. About 2-3 grams is made in the body; diet must provide the rest. (2) Magnesium glycinate is generally considered to be dose-dependent (see Neurohacker Dosing Principles) in the range it’s commonly dosed. We generally dose it in small amounts to augment dietary intake of both magnesium and glycine.

Magnesium Key Mechanisms

Metabolism and energy generation

  • Magnesium is required for the synthesis of ATP by ATP synthase in mitochondria  (3, 4)
  • Magnesium forms a complex with ATP (MgATP) that is required for many rate-limiting metabolic enzymes (5)
  • Regulates rate-limiting enzymes involved in carbohydrate and lipid metabolism (5, 6)
  • Regulates rate-limiting enzymes involved protein and nucleic acid synthesis (5, 6)
  • Regulates insulin sensitivity (7, 8)

Cell signaling

  • Supports cellular sodium and potassium influx and efflux (5)
  • Slows calcium entry into cells so supports balanced calcium signaling (5, 6)
  • Required for protein phosphorylation (enzyme activation) (5, 6)
  • Required for the activity of adenylate cyclase - cyclic adenosine monophosphate (cAMP) synthesis (9)

Cell structure

  • Stabilizes proteins, nucleic acids, chromosomes, and biological membranes (5)

Cardiovascular function

  • Supports cardiac muscle contraction and heart rhythm (6, 10)
  • Supports vascular tone (6, 10)
  • Supports platelet function (6, 11)

Brain function

  • Required for neurotransmitter release and normal neurological function (6)
  • Supports the activity of the glutamate N-methyl-D-aspartate (NMDA) receptor (12)

Muscle function

  • Required for muscle contraction (6, 13)
  • Supports muscle strength (14, 15)

Skeletal system

  • Supports bone metabolism/remodeling by calcium absorption (5)
  • Supports calcitonin and parathyroid hormone activity (5)
  • Supports bone formation (5)

Gut microbiota

  • Supports the composition of the gut microbiota (16–18)

Glycine Key Mechanisms

Structure and Function Roles

  • Plays an essential role in protein synthesis, especially collagen synthesis (19) 
  • Providing flexibility to active sites in many enzymes (20)
  • Supports cell membrane function to promote balanced immunity and inflammatory responses (21)

Protein Precursor

  • Precursor for synthesis of glutathione (22–24)
  • Precursor for synthesis of creatine (25)
  • Precursor for synthesis of porphyrins and heme (26)
  • Precursor for synthesis of purines (27)

Brain and Nervous System Function

  • Acts as a neurotransmitter (i.e., has its own neurotransmission system) (28–31)
  • Supports healthy glutaminergic neurotransmission (32)
  • Supports restful sleep (33, 34)

Longevity / Hallmarks of Aging

  • Supports reduced glycation end products (i.e., sugar-protein cross links) (35–38)
  • Supports growth hormone secretion (39)

Nutrient Synergies

  • N-Acetyl-Cysteine - For glutathione synthesis (40–42)

REFERENCES

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2. E. Meléndez-Hevia, P. De Paz-Lugo, A. Cornish-Bowden, M. L. Cárdenas, J. Biosci. 34, 853–872 (2009).
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4. A. U. Igamberdiev, L. A. Kleczkowski, Front. Plant Sci. 6, 10 (2015).
5. S.-M. Glasdam, S. Glasdam, G. H. Peters, Adv. Clin. Chem. 73, 169–193 (2016).
6. W. Jahnen-Dechent, M. Ketteler, Clin. Kidney J. 5, i3–i14 (2012).
7. M. Barbagallo, L. J. Dominguez, Arch. Biochem. Biophys. 458, 40–47 (2007).
8. M. de L. Lima et al., Diabetes Res. Clin. Pract. 83, 257–262 (2009).
9. S. Y. Cech, W. C. Broaddus, M. E. Maguire, Mol. Cell. Biochem. 33, 67–92 (1980).
10. B. M. Altura, B. T. Altura, Magnesium. 4, 226–244 (1985).
11. M. Shechter et al., Am. J. Cardiol. 84, 152–156 (1999).
12. J. P. Ruppersberg, E. v. Kitzing, R. Schoepfer, Seminars in Neuroscience. 6, 87–96 (1994).
13. J. D. Potter, S. P. Robertson, J. D. Johnson, Fed. Proc. 40, 2653–2656 (1981).
14. L. R. Brilla, T. F. Haley, J. Am. Coll. Nutr. 11, 326–329 (1992).
15. L. J. Dominguez et al., Am. J. Clin. Nutr. 84, 419–426 (2006).
16. E. K. Crowley et al., Mar. Drugs. 16 (2018), doi:10.3390/md16060216.
17. B. Pyndt Jørgensen et al., Acta Neuropsychiatr. 27, 307–311 (2015).
18. G. Winther et al., Acta Neuropsychiatr. 27, 168–176 (2015).
19. M. D. Shoulders, R. T. Raines, Annu. Rev. Biochem. 78, 929–958 (2009).
20. B. X. Yan, Y. Q. Sun, J. Biol. Chem. 272, 3190–3194 (1997).
21. Z. Zhong et al., Curr. Opin. Clin. Nutr. Metab. Care. 6, 229–240 (2003).
22. S. C. Lu, Biochim. Biophys. Acta. 1830, 3143–3153 (2013).
23. A. Ruiz-Ramírez, E. Ortiz-Balderas, G. Cardozo-Saldaña, E. Diaz-Diaz, M. El-Hafidi, Clin. Sci. . 126, 19–29 (2014).
24. M. F. McCarty, J. H. O’Keefe, J. J. DiNicolantonio, Ochsner J. 18, 81–87 (2018).
25. J. T. Brosnan, R. P. da Silva, M. E. Brosnan, Amino Acids. 40, 1325–1331 (2011).
26. G. Layer, J. Reichelt, D. Jahn, D. W. Heinz, Protein Sci. 19, 1137–1161 (2010).
27. J. M. Berg, T. J. Tymoczko, L. Stryer, Biochemistry. New York: WH Freeman (2002).
28. J. W. Johnson, P. Ascher, Nature. 325, 529–531 (1987).
29. H. Betz, B. Laube, J. Neurochem. 97, 1600–1610 (2006).
30. F. Zafra, C. Giménez, IUBMB Life. 60, 810–817 (2008).
31. A. A. Ghavanini, D. A. Mathers, H.-S. Kim, E. Puil, J. Neurophysiol. 95, 3438–3448 (2006).
32. S. F. Traynelis et al., Pharmacol. Rev. 62, 405–496 (2010).
33. W. Yamadera et al., Sleep Biol. Rhythms. 5, 126–131 (2007).
34. M. Bannai, N. Kawai, K. Ono, K. Nakahara, N. Murakami, Front. Neurol. 3, 61 (2012).
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36. S. Ramakrishnan, K. N. Sulochana, R. Punitham, Indian J. Biochem. Biophys. 34, 518–523 (1997).
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38. F. Bahmani, S. Z. Bathaie, S. J. Aldavood, A. Ghahghaei, Mol. Vis. 18, 439–448 (2012).
39. K. Kasai, M. Kobayashi, S. I. Shimoda, Metabolism. 27, 201–208 (1978).
40. S. Xie, L. Tian, J. Niu, G. Liang, Y. Liu, Effect of N-acetyl cysteine and glycine supplementation on growth performance, glutathione synthesis, and antioxidative ability of grass carp, Ctenopharyngodon idella. Fish Physiology and Biochemistry. 43 (2017), pp. 1011–1020.
41. K. A. Cieslik et al., J. Gerontol. A Biol. Sci. Med. Sci. 73, 1167–1177 (2018).
42. S. Xie, W. Zhou, L. Tian, J. Niu, Y. Liu, Fish Shellfish Immunol. 55, 233–241 (2016).

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



Potassium as Tripotassium Citrate

Potassium Citrate Common Names

Tripotassium Citrate | Potassium | Citrate | Citric Acid

Top Benefits of Potassium Citrate

  • Supports electrolyte balance*
  • Supports cellular energy*
  • Supports neuronal function*
  • Supports muscle function*

What Is Potassium Citrate?

Tripotassium citrate is a chelated form of the mineral potassium, with three potassium ions bound to a single citrate molecule. Both molecules are involved in supporting efficient cellular energy production. Potassium is one of the most abundant minerals in the body and is vital for the functioning of all living cells. Its main role is as an intracellular electrolyte (sodium is the main extracellular electrolyte). Potassium is needed for electrolyte balance, which supports the electrical functions of cells. Citrate is a salt of citric acid, a compound that was first identified in lemon juice, but is found in all citrus fruits. Citrate is an intermediate in the citric acid cycle (also called the Krebs cycle), a circular pathway that helps turn food into energy (i.e., ATP) and build important biomolecules. Adding intermediates like citrate into this cycle helps upregulate the flux (i.e., the cycle can essentially spin faster). Citrate is also a vital component of bone. 

Neurohacker’s Potassium Citrate Sourcing

We opt to use the citrate sale of potassium, instead of a different form of potassium, when both potassium and citrate play a role supporting pathways or processes in a formulation.

Potassium citrate sourcing is focused on ensuring it is non-GMO, gluten-free and vegan.

Tripotassium Citrate Dosing Principles and Rationale

Tripotassium citrate is used primarily as a source of citrate, an important Krebs cycle and mitochondrial nutrient. We dose it in small amounts to augment dietary intake. The adequate intake (AI) for potassium in adults is 3400 mg for men and 2600mg for women. Supplements will typically contain 99 mg or less per serving because of certain FDA constraints with potassium dosing. This amount would not be sufficient to correct issues with potassium intake.

Potassium Citrate Key Mechanisms

  • Main positively charged ion in intracellular fluid (1, 2)
  • Along with sodium, potassium creates an electrochemical gradient across cell membranes known as the membrane potential (1, 2)
  • Essential for nerve impulse transmission, muscle contraction and heart function (2)
  • Potassium is required for the activity of a few enzymes including pyruvate kinase (catalyzes the final step of glycolysis) (3)
  • Supports insulin secretion (4)
  • Regulates blood flow and blood pressure (4, 5, 6)
  • Protects kidney function (7, 8)

References

1. J. M. Berg, J. L. Tymoczko, G. J. Gatto, L. Stryer, Eds., Biochemistry (W.H. Freeman and Company, 8th ed., 2015).
2. W. Boron, E. Boulpaep, Eds., Medical Physiology (Elsevier, 3rd ed., 2016).
3. M. J. Page, E. Di Cera, Physiol. Rev. 86, 1049–1092 (2006).
4. C. Ekmekcioglu, I. Elmadfa, A. L. Meyer, T. Moeslinger, J. Physiol. Biochem. 72, 93–106 (2016).
5. F. J. Haddy, P. M. Vanhoutte, M. Feletou, Am. J. Physiol. Regul. Integr. Comp. Physiol. 290, R546–52 (2006).
6. M. S. Stone, L. Martyn, C. M. Weaver, Nutrients. 8 (2016), doi:10.3390/nu8070444.
7. C. M. Weaver, Adv. Nutr. 4, 368S–77S (2013).
8. C. P. Kovesdy et al., J. Am. Soc. Hypertens. 11, 783–800 (2017).

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

Magnesium Threonate

Scientific Name:
Magnesium (2R,3S)-2,3,4-Trihydroxybutanate

Overview:
Magnesium threonate is a salt of magnesium and L-Threonate with neuroprotective and nootropic effects. Magnesium threonate can significantly improve memory and learning.

Scientific Name:
Magnesium (2R,3S)-2,3,4-Trihydroxybutanate

Mechanisms:

  • L-Threonate significantly enhances the bioavailability of magnesium[1]
  • Magnesium inhibits the activation of NMDA receptors and blocks calcium channels, decreasing neuronal hyperexcitation and excititoxicity[2,3]
  • Magnesium can greatly improve both short and long-term memory and delay age-related memory impairment[4]
  • Can have anxiolytic effects and improve sleep quality[5,6]
  • Improves synaptic activity and plasticity[7]
  • Improves glucose metabolism and energy production[8]
  • May increase cerebrospinal fluid in the brain[9]
References

[1] Slutsky I, et al (2010). Enhancement of learning and memory by elevating brain magnesium. Neuron. 2010 Jan 28;65(2):165-77. doi: 10.1016/j.neuron.2009.12.026
[2] Johnson JW and Ascher P. (1990). Voltage-dependent block by intracellular Mg2+ of N-methyl-D-aspartate-activated channels. Biophys J, 57(5):1085-90. doi: 10.1016/S0006-3495(90)82626-6
[3] Iseri LT & French JH (1984). Magnesium: nature’s physiologic calcium blocker. Am Heart J. 1984 Jul;108(1):188-93. doi: 10.1016/0002-8703(84)90572-6
[4] Billard JM (2006). Ageing, hippocampal synaptic activity and magnesium. Magnes Res, 19(3):199-215. doi: 10.1684/mrh.2006.0063
[5] Poleszak E, et al (2004). Antidepressant- and anxiolytic-like activity of magnesium in mice. Pharmacol Biochem Behav, 78(1):7-12. doi: 10.1055/s-2002-33195
[6] Held K, et al (2002). Oral Mg(2+) supplementation reverses age-related neuroendocrine and sleep EEG changes in humans. Pharmacopsychiatry, 35(4):135-43. doi: 10.1016/j.pbb.2004.01.006
[7] Slutsky I, et al (2004). Enhancement of synaptic plasticity through chronically reduced Ca2+ flux during uncorrelated activity. Neuron, 44(5):835-49. doi: 10.1016/j.neuron.2004.11.013
[8] Cinar V, et al (2008). The effect of magnesium supplementation on glucose and insulin levels of tae-kwan-do sportsmen and sedentary subjects. Pak J Pharm Sci, 21(3):237-40. PMID: 18614418
[9] Morris ME (1992). Brain and CSF magnesium concentrations during magnesium deficit in animals and humans: neurological symptoms. Magnes Res, 5(4):303-13. PMID: 1296767
[10] Köseoglu E, et al (2008). The effects of magnesium prophylaxis in migraine without aura. Magnes Res, 21(2):101-8. doi: 10.1684/mrh.2008.0132

Lithium Orotate

Scientific Name:
Lithium 1,2,3,6-Tetrahydro-2,6-dioxo-4-pyrimidinecarboxylate

Overview:
Lithium orotate is a salt of orotic acid and lithium with neuroprotective effects. Lithium orotate can improve mood and may help preserve cognitive function.

Scientific Name:
Lithium 1,2,3,6-Tetrahydro-2,6-dioxo-4-pyrimidinecarboxylate

Mechanisms:

  • Lithium orotate provides lithium to the body[1]
  • Neuroprotective effects through inhibition of neuronal damaging proteins[3]
  • Increases the elimination of harmful toxic metals from the brain[4]
  • May increase gray matter[5]
  • Analgesic effect – decreases migraines[6]
References

[1] Smith DF & Schou M (1979). Kidney function and lithium concentrations of rats given an injection of lithium orotate or lithium carbonate. J Pharm Pharmacol, ;31(3):161-3. doi: 10.1111/j.2042-7158.1979.tb13461.x
[2] Oruch R, et al (2014). Lithium: a review of pharmacology, clinical uses, and toxicity. Eur J Pharmacol, 740:464-73. doi: 10.1016/j.ejphar.2014.06.042
[3] Vo TM, et al (2015). Is lithium a neuroprotective agent? Ann Clin Psychiatry, 27(1):49-54
[4] Moore GJ, et al (2000). Lithium-induced increase in human brain grey matter. Lancet, 356(9237):1241-2. doi: 10.1016/S0140-6736(00)02793-8
[5] Schettini G, et al (1992). Molecular mechanisms mediating the effects of L-alpha-glycerylphosphorylcholine, a new cognition-enhancing drug, on behavioral and biochemical parameters in young and aged rats. Pharmacol Biochem Behav, 43(1):139-51. doi: 10.1007/s10571-008-9343-5
[6] Oedegaard KJ, et al (2000). Are migraine and bipolar disorders comorbid phenomena?: findings from a pharmacoepidemiological study using the Norwegian Prescription Database. J Clin Psychopharmacol, 31(6):734-9. doi: 10.1097/JCP.0b013e318235f4e9

Zinc Picolinate

Scientific Name:
Zinc pyridine-2-carboxylate

Overview:
Zinc picolinate is an acid form of zinc with neuroprotective effects. Zinc picolinate helps improve memory and mood.

Scientific Name:
Zinc pyridine-2-carboxylate

Mechanisms:


    • Picolinate increases the absorption of the essential nutrient zinc[1]
    • Zinc is a potent antioxidant, an anti-inflammatory, and an immunity enhancer[2]
    • Is found in the cerebral cortex, pineal gland, and hippocampus and has a neuromodulatory function[3]
    • Zinc is as cofactor for many metalloproteins, namely the enzyme superoxide dismustase, an important endogenous antioxidant[4]
    • Activates neuronal potassium channels, inhibits NMDA glutamate receptors, and decreases glutamate release[5,6]
    • Increases serotonin uptake in some brain regions[7]
    • May increase the production of BDNF – neuronal growth and plasticity, improved spatial memory effect[5,6]
    • Inhibits glycogen synthase kinase-3β [8]
References

[1] Barrie SA, et al (1987). Comparative absorption of zinc picolinate, zinc citrate and zinc gluconate in humans. Agents Actions, 21(1-2):223-8. PMID: 3630857
[2] Chasapis CT, et al (2012). Zinc and human health: an update. Arch Toxicol, 86(4):521-34. doi: 10.1007/s00204-011-0775-1
[3] Popescu BF & Nichol H (2010). Mapping brain metals to evaluate therapies for neurodegenerative disease. CNS Neurosci Ther, 17(4):256-68. doi: 10.1111/j.1755-5949.2010.00149.x
[4] Oteiza PI (2012). Zinc and the modulation of redox homeostasis. Free Radic Biol Med, 53(9):1748-59. doi: 10.1016/j.freeradbiomed.2012.08.568
[5] Sensi SL, et al (2009). Zinc in the physiology and pathology of the CNS. Nat Rev Neurosci, 10(11):780-91. doi: 10.1038/nrn2734
[6] Sensi SL, et al (2011). The neurophysiology and pathology of brain zinc. J Neurosci, 31(45):16076-85. doi: 10.1523/JNEUROSCI.3454-11.2011
[7] Levenson CW (2006). Zinc: the new antidepressant? Nutr Rev, 64(1):39-42. doi: 10.1111/j.1753-4887.2006.tb00171.x
[8] Ilouz R, et al (2002). Inhibition of glycogen synthase kinase-3beta by bivalent zinc ions: insight into the insulin-mimetic action of zinc. Biochem Biophys Res Commun, 295(1):102-6. doi: 10.1016/S0006-291X(02)00636-8