MAGNESIUM OROTATE & OROTIC ACID
Written by Slawomir (“Swavak”) Gromadzki, MPH
Magnesium orotate is a complex consisting of magnesium bound to orotic acid. It is regarded by some as the most easily absorbable form of magnesium and more beneficial to the heart than other types. According to Dr. Edward Group, “If you need magnesium supplementation magnesium orotate is the best you can get”. Some experts suggest that orotic acid has the ability to carry magnesium across cell membranes, producing higher concentration of magnesium in cells. Because magnesium orotate is not very soluble in water, it does not dissociate in the GI tract. This means that, unlike many other forms of magnesium, is does not cause diarrhoea. Instead, it delivers magnesium directly to the cells, thus smaller quantities of elemental magnesium are required to be effective. Magnesium orotate doesn’t have a laxative effect.
The effects of magnesium orotate include: improved survival of heart tissue damaged by lack of oxygen (>), improved survival of heart cells after heart attacks (>), reduction of premature heartbeats & arrhythmias (>), increase in exercise capacity (>,>), lowered LDL, increased HDL cholesterol & reduced plaque formation in atherosclerosis (>,>), correction of magnesium deficiency (>), reduction in calcification of damaged heart tissue (>), improvement in skin appearance (>).
The mechanism for these benefits is believed to involve an improved availability of DNA & RNA precursors needed for repair of damaged heart tissue, and an increase in the synthesis of glycogen and ATP, required for the recovery of the heart muscle (>).
Do you complain about muscle, stomach and menstrual crumps, spastic colon, difficulty sleeping (even though you feel exhausted), low mood, irritability, feeling anxious without reason, tiredness, poor memory, sugar & salt cravings, or constipation? Well, if you do maybe it’s time to start being very serious about considering Magnesium deficiency. According to Dr. Norman Shealy, “Every known illness is associated with a magnesium deficiency. Magnesium deficiency may be responsible for more diseases than any other nutrient.” Magnesium is present in all cells in our body as they constantly require this mineral for a normal function. Magnesium is so important for preserving our health because it is involved in over 600 reactions, including DNA repair, converting food into energy (metabolism & body weight), contracting and relaxing muscles, regulating neurotransmitters and hormones, and hundreds of other health-sustaining functions. Even serotonin (the strongest antidepressant and feel-good hormone) and glutathione (body’s most powerful antioxidant) require Magnesium for their synthesis. Unfortunately, due to soil depletion, deprived of magnesium refined diet, emotional stress and other factors, millions suffer from Magnesium deficiency without even knowing it. In addition, magnesium deficiency is often misdiagnosed because it does not show up in blood tests as only 1% of the body’s Magnesium is stored in the blood.
Excellent sleep & relaxation aid
Magnesium enables us to control stress and is vital in our body for proper functioning of the nervous system and brain, promoting good mood and improves our sleep paterns. It’s been suggested that this is because Magnesium is involved in the synthesis and function of GABA and serotonin, neurotransmitters known to be most effective in calming the brain and promoting relaxation. That is why Dr. Berzin calls Magnesium “the nature’s anti-anxiety drug”.
Necessary for strong bones & teeth
Not too many people realise that Magnesium is more important for strong bones than calcium. Too much calcium without magnesium causes bones to become brittle, because without magnesium calcium can’t be used to strengthen bones. Instead, it tends to be deposited in kidneys and arteries leading to kidney stones and arteriosclerosis.
Helps relax all muscles, blood vessels, promotes heart health & normal blood pressure
Since lack of Magnesium leads to spasms and dysfunction of various muscles, including uterus, heart, stomach, colon, Magnesium supplementation is often the best and sometimes even only way to relax these muscles. Magnesium supports normal blood pressure and heart muscle function. Since Magnesium is involved in neurotransmitter function and regulating the constriction and relaxation of blood vessel found in the brain its deficiency is believed to contribute to migraines.
Helps maintain normal blood glucose levels
Since Magnesium helps convert sugar to energy it helps our body to maintain normal blood sugar levels. In addition, studies demonstrated that oral Magnesium supplementation improves insulin sensitivity in people with insulin resistance and high blood sugar levels.
Magnesium Orotate vs other forms
Magnesium Orotate is a complex consisting of Magnesium bound to orotic acid. It is regarded as the most easily absorbable form of magnesium. According to Dr. Edward Group, “If you need magnesium supplementation magnesium orotate is the best you can get”. Some experts suggest that orotic acid has the ability to carry magnesium across cell membranes, producing higher concentration of magnesium in cells.
MAGNESIUM OROTATE (OROTIC ACID) SAFETY
Unfortunately, although Magnesium Orotate appears to be perfectly safe if used in recommended dosages, yet in EU countries (including UK), it is forbidden to be sold as a nutritional supplement.
Magnesium orotate consists of two ingredients, magnesium and orotic acid (the carrier of magnesium).
According to some found on the internet articles, it is not magnesium itself but rather orotic acid (carrier of magnesium in Magnesium Orotate) that is the cause of safety concerns. However, magnesium supplements containing orotic acid should be regarded as safe as their concentration of orotic acid is much lower than the recommended upper safe limit.
For instance, a Magnesium Orotate supplements usually contain 500mg of magnesium orotate per tablet and the dosage is 1 to 2 tablets per day (500-1000mg per day). Since about 85% of magnesium orotate is orotic acid, the maximum daily dosage (2 a day) should contain about 850mg of orotic acid, which is still much lower than its upper safe limit. The safe daily intake for orotic acid is 50mg per 1 kg of body weight per day which for an average 70kg body would be about 3500mg per day (50 x 70 = 3500). Therefore, since the daily intake of orotic acid per maximum daily dosage of 2 tablets of magnesium orotate is 850mg (425 per recommended 1 tablet) it is still much lower than safe upper daily intake of 3500mg per day.
In addition, although excess of orotic acid, like in case of many other good compounds including vitamins and minerals, can be harmful, the normal intake has been shown to be very beneficial and even essential (required by human body for proper function).
The EFSA Panel addressing the safety of Magnesium Orotate doesn’t seem to prohibit the supplemental use of this type of magnesium but only expresses concern about its safety in the context of the amounts exceeding the upper safe limits: “The Panel concludes that in the light of the tumour-promoting effect of orotic acid in animal experimentation, the small margin of safety to this effect from foreseeable exposure, and the absence of any relevant studies on genotoxicity and of any developmental studies, the use of orotate as a source of the eight other minerals and choline at the proposed levels of use is of safety concern.”
According to the research there is “no observed adverse effect of 50mg/kg body weight/day, while the lowest observed effect level at 100mg/kg bw/day. [>]
POSSIBLE BENEFITS OF MAGNESIUM OROTATE BASED ON SCIENTIFIC RESEARCH
“For those seeking optimal cardiovascular health and for those with failing hearts and blocked arteries, magnesium orotate can be a miracle nutrient backed by a substantial, positive history in experimental and clinical medicine… The clinical effects of magnesium orotate include: improved survival of heart tissue damaged by oxygen starvation, reduction of premature heartbeats,[>] increase in exercise capacity,[>,>] correction of magnesium depletion,[>] improvements in skin appearance,[>] and reduction in calcification of damaged heart tissue. [>] The mechanism for these benefits is suspected to involve an improved availability of DNA and RNA precursors needed for repair of damaged tissue, and an increase in the synthesis of glycogen and ATP, both of which provide energy to and help recovery of the heart muscle.” [>]
“Magnesium orotate dihydrate (MO) has the sum formula C10H6MgN4O8 x 2H2O and a MG of 370.52. The salt is poorly soluble in water and hence does not bind gastric acid nor does it exhibit noteworthy laxative effects upon oral administration in contrast to easily dissociable Mg salts. As a source of magnesium (Mg), MO is indicated for the oral treatment of extracellular Mg deficiency. Orotic acid (OA), the second active ingredient of MO, is a key intermediate in the biosynthetic pathway of pyrimidines and is shown to improve the energy status of injured myocardium by stimulating, a.o., the synthesis of glycogen and ATP. Myocardial energy-rich phosphate levels are decreased during hypoxic conditions; subsequently, intracellular Mg is depleted and lost via the urine. Since binding sites for Mg (ATP) are provided by OA it can be classified as “Mg-fixing agent”. Accordingly MO is also indicated for the treatment of Mg depletion as convincingly shown in animal experiments and also in coronary heart patients undergoing e.g. aortocoronary bypass surgery.” [>]
OROTIC ACID BENEFITS
OA is also a normal part of the diet, being found in milk and dairy products, and it is converted to uridine for use in the pyrimidine salvage pathway predominantly in liver, kidney and erythrocytes.
It has been found that orotic acid improves the metabolism of folic acid and vitamin B12. Orotic acid is found in milk produced by cows and other commercial dairy products derived from milk. The presence of orotate in mammals is important to the development of the central nervous system [>]. The importance of orotic acid in human metabolism can be witnessed in individuals afflicted with orotic aciduria. Orotic aciduria is detected in humans by virtue of affected individuals excreting excess orotic acid.
Recently, it was noted that the administration of orotic acid in humans improved the condition of hearts with hypertrophy. It was concluded that the positive effect of administering orotic acid to humans with hypertrophic hearts was caused by the release of pyrimidine nucleosides into the blood stream blocking adenine nucleotide depletion in the myocardium [>].
POSSIBLE SIDE EFFECTS
Orotic Acid: Why it is Important to Understand Its Role in Metabolism (1014)
Negative effects have also been observed with respect to orotic acid since insulin resistance and hypertension or fatty livers can be induced in rats when orotic acid is included in their diet [>].
The hypertension observed in orotic acid-fed rats was thought to be the result of impaired endothelial nitric acid synthesis [>].
With respect to gene transcription, it has been speculated that orotic acid may influence the synthesis of genes involved in cell proliferation in eukaryotes [>].
Share this article!
LÃffler M, Carrey EA, Zameitat E (2016) Orotate (orotic acid): An essential and versatile molecule. Nucleosides Nucleotides Nucleic Acids 35: 566-577.
Garavito MF, NarvÃ¡ez-Ortiz HY, Zimmerman BH (2015) Pyrimidine metabolism: Dynamic and versatile pathways in pathogens and cellular development. J Genet Genomics 42: 195-205.
LÃffler M, Carrey EA, Zameitat E (2015) Orotic acid, more than just an intermediate of pyrimidine de novo synthesis. J Genet Genomics 42: 207-219.
LÃffler M, Fairbanks LD, Zameitat E, Marinaki AM, Simmonds HA (2005) Pyrimidine pathways in health and disease. Trends Mol Med 11: 430-437.
Richards SM, Conyers RAJ, Fisher JL, Rosenfeldt FL (1997) Cardioprotection by orotic acid: Metabolism and mechanism of action. J Mol Cell Cardiol 29: 3239-3250.
Choi YJ, Yoon Y, Lee KY, Kang YP, Lim DK, et al. (2015) Orotic acid induces hypertension associated with impaired endothelial nitric oxide synthesis. Toxicol Sci 144: 307-317.
Santiago MF, West TP (2002) Control of pyrimidine formation in Pseudomonas putida ATCC 17536. Can J Microbiol 48: 1076-1081
Wang YM, Hu XQ, Xue Y, Li ZJ, Yanagita T, et al (2011) Study on possible mechanism of orotic acid-induced fatty liver in rats. Nutrition 27: 571-575.
Chu CP, West TP (1990) Pyrimidine biosynthetic pathway of Pseudomonas fluorescens. J Gen Microbiol 136: 875-880.
Any information or product suggested on this website is not intended to diagnose, treat, cure or prevent any medical condition. Never disregard medical advice or delay in seeking it because of something you have read on this website. Consult your primary healthcare physician before using any supplements or making any changes to your regime.
© 2016 Slawomir Gromadzki – All Rights Reserved