Orotic acid salts as sources of orotic acid and various minerals added for nutritional purposes to food supplements

,

doi:10.2903/j.efsa.2009.1187

Cited by 7 publications

(6 citation statements)

References 30 publications

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“…Historically, OTA was incorrectly thought to be a vitamin and therefore often referred to as “vitamin B13” . The substance is used as a food supplement and shows therapeutic effects such as increase in cognitive performance and learning potential, cardioprotection, and the reduction of serum lipids . A monohydrate (Hy1), , dimethyl sulfoxide monosolvate (S DMSO ), and anhydrous form are known, and both the anhydrate and monohydrate are commercially available …”

Section: Introductionmentioning

confidence: 99%

Structural Properties, Order–Disorder Phenomena, and Phase Stability of Orotic Acid Crystal Forms

et al. 2016

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Orotic acid (OTA) is reported to exist in the anhydrous (AH), monohydrate (Hy1), and dimethyl sulfoxide monosolvate (SDMSO) forms. In this study we investigate the (de)hydration/desolvation behavior, aiming at an understanding of the elusive structural features of anhydrous OTA by a combination of experimental and computational techniques, namely, thermal analytical methods, gravimetric moisture (de)sorption studies, water activity measurements, X-ray powder diffraction, spectroscopy (vibrational, solid-state NMR), crystal energy landscape, and chemical shift calculations. The Hy1 is a highly stable hydrate, which dissociates above 135 °C and loses only a small part of the water when stored over desiccants (25 °C) for more than one year. In Hy1, orotic acid and water molecules are linked by strong hydrogen bonds in nearly perfectly planar arranged stacked layers. The layers are spaced by 3.1 Å and not linked via hydrogen bonds. Upon dehydration the X-ray powder diffraction and solid-state NMR peaks become broader, indicating some disorder in the anhydrous form. The Hy1 stacking reflection (122) is maintained, suggesting that the OTA molecules are still arranged in stacked layers in the dehydration product. Desolvation of SDMSO, a nonlayer structure, results in the same AH phase as observed upon dehydrating Hy1. Depending on the desolvation conditions, different levels of order–disorder of layers present in anhydrous OTA are observed, which is also suggested by the computed low energy crystal structures. These structures provide models for stacking faults as intergrowth of different layers is possible. The variability in anhydrate crystals is of practical concern as it affects the moisture dependent stability of AH with respect to hydration.

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Section: Introductionmentioning

confidence: 99%

Structural Properties, Order–Disorder Phenomena, and Phase Stability of Orotic Acid Crystal Forms

et al. 2016

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“…A number of creatine salts have been marketed as sources of creatine for dietary supplements including creatine citrate (including di- and tri- forms) [ 172 , 173 , 174 ]; creatine maleate, creatine fumarate, creatine tartrate [ 31 ]; creatine pyruvate [ 32 , 174 , 175 , 176 ]; creatine ascorbate [ 33 ]; and creatine orotate [ 30 , 176 , 177 ], among others. Some creatine salts are less stable when compared to CrM.…”

Section: Some Evidence To Support Bioavailability Efficacy and Safetymentioning

confidence: 99%

“…The rationale was to provide a means of increasing creatine and ascorbic acid availability to improve exercise capacity while supporting the immune system [ 33 ]. However, we are not aware of any pharmacokinetic or exercise related studies to test this hypothesis and benefits would seemingly be similar and more effectively dosed by co-ingestion of CrM and vitamin C. Finally, there has been interest in tri-creatine orotate (CO) as a creatine salt (71% creatine by molecular weight) and a few raw material suppliers offer CO as a source of creatine to manufacturers [ 30 , 176 , 177 ]. Supplement companies who sell creatine orotate claim it provides creatine and orotic acid that is purported to aid in the production of carnosine in the muscle, and therefore improves muscle-buffering capacity.…”

Section: No Evidence To Support Bioavailability Efficacy and Safetymentioning

confidence: 99%

“…However, as of this writing, we are aware of no data showing bioavailability and/or efficacy of CO supplementation [ 216 ]. The European Food and Safety Authority has also expressed concerns about the potential cancerogenic effects of orotic acid [ 176 , 177 ]. Therefore, CO does not seem to be a good alternative for CrM in dietary supplements particularly when co-ingestion of effective doses of CrM and beta alanine would seeming be more effective.…”

Section: No Evidence To Support Bioavailability Efficacy and Safetymentioning

confidence: 99%

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Bioavailability, Efficacy, Safety, and Regulatory Status of Creatine and Related Compounds: A Critical Review

Kreider

Jäger²,

Purpura³

2022

Nutrients

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In 2011, we published a paper providing an overview about the bioavailability, efficacy, and regulatory status of creatine monohydrate (CrM), as well as other “novel forms” of creatine that were being marketed at the time. This paper concluded that no other purported form of creatine had been shown to be a more effective source of creatine than CrM, and that CrM was recognized by international regulatory authorities as safe for use in dietary supplements. Moreover, that most purported “forms” of creatine that were being marketed at the time were either less bioavailable, less effective, more expensive, and/or not sufficiently studied in terms of safety and/or efficacy. We also provided examples of several “forms” of creatine that were being marketed that were not bioavailable sources of creatine or less effective than CrM in comparative effectiveness trials. We had hoped that this paper would encourage supplement manufacturers to use CrM in dietary supplements given the overwhelming efficacy and safety profile. Alternatively, encourage them to conduct research to show their purported “form” of creatine was a bioavailable, effective, and safe source of creatine before making unsubstantiated claims of greater efficacy and/or safety than CrM. Unfortunately, unsupported misrepresentations about the effectiveness and safety of various “forms” of creatine have continued. The purpose of this critical review is to: (1) provide an overview of the physiochemical properties, bioavailability, and safety of CrM; (2) describe the data needed to substantiate claims that a “novel form” of creatine is a bioavailable, effective, and safe source of creatine; (3) examine whether other marketed sources of creatine are more effective sources of creatine than CrM; (4) provide an update about the regulatory status of CrM and other purported sources of creatine sold as dietary supplements; and (5) provide guidance regarding the type of research needed to validate that a purported “new form” of creatine is a bioavailable, effective and safe source of creatine for dietary supplements. Based on this analysis, we categorized forms of creatine that are being sold as dietary supplements as either having strong, some, or no evidence of bioavailability and safety. As will be seen, CrM continues to be the only source of creatine that has substantial evidence to support bioavailability, efficacy, and safety. Additionally, CrM is the source of creatine recommended explicitly by professional societies and organizations and approved for use in global markets as a dietary ingredient or food additive.

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“…Orotic acid is another bioactive component of milk that improves the condition of the heart muscle, and its main source is ruminant milk (Czauderna et al, 2021). Sheep's milk contains more orotic acid (20-400 mg/ml) than human milk (less than 2 mg/l) (Aguilar et al, 2009). A diet rich in orotic acid may be important for patients at increased risk of lifestyle-related cardiovascular disorders (Czauderna et al, 2021).…”

Section: Importance In the Prevention Of Heart And Circulatory System...mentioning

confidence: 99%

The role of sheep’s milk bioactive substances in the prevention of metabolic and viral diseases

Flis¹,

Szczecina²,

Molik³

2022

J. Anim. Feed Sci.

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Orotic acid salts as sources of orotic acid and various minerals added for nutritional purposes to food supplements

Cited by 7 publications

References 30 publications

Structural Properties, Order–Disorder Phenomena, and Phase Stability of Orotic Acid Crystal Forms

Structural Properties, Order–Disorder Phenomena, and Phase Stability of Orotic Acid Crystal Forms

Bioavailability, Efficacy, Safety, and Regulatory Status of Creatine and Related Compounds: A Critical Review

The role of sheep’s milk bioactive substances in the prevention of metabolic and viral diseases

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