# Calcium Orotate Monohydrate **Canonical URL:** https://ingredients.hermeticasuperfoods.com/ingredients/calcium-orotate-monohydrate **Data Source:** Hermetica Superfoods Ingredient Encyclopedia **Updated:** 2026-04-03 **Evidence Score:** 2 / 10 **Category:** Mineral **Also Known As:** Calcium orotate hydrate, Calcium 2,4-dioxo-1,2,3,4-tetrahydropyrimidine-6-carboxylate monohydrate, Calcium salt of orotic acid monohydrate, Orotate calcium monohydrate, Ca orotate monohydrate, Calcium oroticum monohydratum ## Overview Calcium Orotate Monohydrate is a calcium salt of orotic acid (pyrimidine-2,4-diol-6-carboxylic acid) combined with one water molecule, theorized to enhance cellular calcium delivery via orotate's membrane transport properties. Unlike inorganic calcium salts, the orotate carrier molecule is proposed to facilitate intracellular uptake, though no controlled human clinical trials have confirmed this mechanism or any health benefit. ## Health Benefits • No clinically proven health benefits - no human trials found in available research • Classified as a natural health product ingredient providing orotic acid - regulatory status only • Theoretical calcium supplementation potential - no clinical evidence available • No documented therapeutic effects - absence of RCTs or meta-analyses • Safety and efficacy remain unestablished - requires clinical investigation ## Mechanism of Action Calcium Orotate Monohydrate dissociates in the gastrointestinal tract to release calcium ions and orotic acid (vitamin B13 precursor). The orotate anion is theorized to pass through cell membranes by piggybacking on orotic acid transport channels involved in pyrimidine biosynthesis, potentially increasing intracellular calcium availability compared to carbonate or citrate salts. However, no peer-reviewed pharmacokinetic studies have measured plasma calcium AUC, bioavailability ratios, or receptor-level activity specific to this monohydrate salt form in humans. ## Clinical Summary As of available research, no published human clinical trials have investigated Calcium Orotate Monohydrate specifically for any health outcome, including bone density, [cardiovascular](/ingredients/condition/heart-health) function, or muscle physiology. The broader category of calcium orotates has minimal human trial data, with most theoretical claims originating from Hans Nieper's largely unverified clinical observations from the 1970s–1980s. Regulatory bodies such as Health Canada classify it solely as a natural health product ingredient supplying calcium and orotic acid, without approving therapeutic claims. The absence of randomized controlled trials, dose-response data, and safety endpoints makes evidence-based recommendations impossible at this time. ## Nutritional Profile Calcium Orotate Monohydrate is a calcium salt of orotic acid (pyrimidine-2,4(1H,3H)-dione-6-carboxylic acid) with one water molecule of crystallization. Molecular formula: C5H4CaN2O4·H2O; molecular weight approximately 228.19 g/mol. Elemental calcium content: approximately 17.6% by weight, meaning a 100 mg dose delivers roughly 17-18 mg elemental calcium. Orotic acid content: approximately 78% by weight. As a mineral salt, it contains no macronutrients (zero protein, fat, or carbohydrate contribution at supplemental doses), no dietary fiber, and negligible caloric value. The orotic acid component is a naturally occurring pyrimidine precursor involved in endogenous pyrimidine biosynthesis pathways. Bioavailability: calcium orotate is theorized to cross cell membranes more readily than inorganic calcium salts (e.g., calcium carbonate ~40% elemental calcium, calcium citrate ~21%) due to the lipophilic character of the orotate carrier molecule, but this claim lacks robust human pharmacokinetic data. Comparative elemental calcium content is lower than calcium carbonate and calcium citrate per unit weight. No significant vitamin content. No fiber. No notable secondary bioactive compounds beyond the orotate anion itself. Water molecule contributes negligible mass at supplemental doses. ## Dosage & Preparation No clinically studied dosage ranges are available for calcium orotate monohydrate in any form. No standardization details or recommended doses have been established through clinical research. Consult a healthcare provider before starting any new supplement. ## Safety & Drug Interactions No formal human safety trials exist for Calcium Orotate Monohydrate, but calcium supplementation in general carries risks of hypercalcemia at doses exceeding 2,500 mg elemental calcium per day, presenting as nausea, constipation, and impaired kidney function. Orotic acid at high doses has demonstrated hepatotoxic and lipogenic effects in animal models, raising theoretical concern for liver stress, though the doses used in those studies far exceed typical supplement amounts. Calcium ions can reduce absorption of tetracycline antibiotics, fluoroquinolones, bisphosphonates, levothyroxine, and iron supplements when taken concurrently. Pregnancy and lactation safety has not been studied for this specific salt form; standard calcium needs during pregnancy (1,000–1,300 mg/day elemental calcium) should be met through clinically validated forms under medical supervision. ## Scientific Research No human clinical trials, randomized controlled trials, or meta-analyses for calcium orotate monohydrate were found in the available research. The current evidence base consists only of chemical characterization data without any clinical outcome studies or PubMed-indexed trials. ## Historical & Cultural Context No historical or traditional medicinal uses are documented for calcium orotate monohydrate in the provided research. The compound appears to be a modern synthetic creation without traditional usage history. ## Synergistic Combinations Insufficient evidence to recommend synergistic combinations ## Frequently Asked Questions ### What is calcium orotate monohydrate and how does it differ from calcium carbonate? Calcium Orotate Monohydrate is a calcium salt bound to orotic acid with one water molecule of crystallization, whereas calcium carbonate is an inorganic salt containing approximately 40% elemental calcium. The orotate form is theorized to use orotic acid's pyrimidine transport pathways for improved cellular uptake, but no comparative bioavailability studies in humans have confirmed superior absorption over calcium carbonate or citrate. ### Is there any clinical evidence that calcium orotate monohydrate works? No peer-reviewed, controlled human clinical trials have been published specifically on Calcium Orotate Monohydrate. The theoretical benefits of orotate-bound calcium originate primarily from Hans Nieper's uncontrolled clinical reports in the 1970s, which have not been replicated in modern randomized trials. Regulatory agencies do not recognize therapeutic claims for this ingredient beyond its function as a calcium source. ### How much elemental calcium does calcium orotate monohydrate provide per dose? Calcium Orotate Monohydrate has a molecular weight of approximately 260 g/mol, with elemental calcium comprising roughly 15–16% by weight, making it one of the lower-density calcium sources compared to calcium carbonate (~40%) or calcium citrate (~21%). A 500 mg dose of the compound would therefore deliver approximately 75–80 mg of elemental calcium, meaning users targeting 1,000 mg of daily elemental calcium would need substantially higher gram-level doses. ### Can calcium orotate monohydrate interact with medications? Calcium ions released from Calcium Orotate Monohydrate can chelate and reduce the oral bioavailability of several drug classes, including tetracycline and fluoroquinolone antibiotics, bisphosphonates such as alendronate, levothyroxine, and non-heme iron supplements. A minimum separation of 2–4 hours between calcium supplementation and these medications is generally recommended. The orotic acid component has not been studied for drug interactions in humans, but theoretically could affect pyrimidine metabolism pathways relevant to fluorouracil or methotrexate therapy. ### Is calcium orotate monohydrate safe to take daily? Daily safety data specific to Calcium Orotate Monohydrate does not exist in published human research. General tolerable upper intake levels for elemental calcium are set at 2,500 mg/day for adults aged 19–50 by the Institute of Medicine, above which hypercalcemia, nephrolithiasis, and vascular calcification risk increase. High-dose orotic acid supplementation has caused fatty liver changes in rodent models, so until human safety studies are conducted, caution is warranted with prolonged high-dose use. ### What is orotic acid and why is it included in calcium orotate monohydrate supplements? Orotic acid is an organic compound naturally involved in nucleotide synthesis and cellular metabolism. In calcium orotate monohydrate, orotic acid serves as the carrier molecule for calcium, though no clinical evidence demonstrates that the orotic acid component provides additional health benefits beyond theoretical metabolic support. The compound is marketed as a natural health product ingredient, but its therapeutic significance remains unestablished in human research. ### How does calcium orotate monohydrate absorption compare to other calcium supplementation forms? While calcium orotate monohydrate is theorized to have superior bioavailability due to its organic acid chelation, no clinical studies directly compare its absorption rates to calcium carbonate, citrate, or other established forms. Without human trials measuring serum calcium levels or urinary excretion, claims about enhanced bioavailability remain speculative. Evidence-based calcium forms like citrate and carbonate have documented absorption data from multiple clinical trials. ### Who should avoid calcium orotate monohydrate or use it with caution? Given the absence of clinical safety data, calcium orotate monohydrate should be used cautiously by pregnant women, nursing mothers, children, and individuals with kidney disease or hypercalcemia until safety is established. People taking bisphosphonates, tetracycline antibiotics, or other medications sensitive to calcium supplementation should consult a healthcare provider, as calcium orotate may interact similarly to other calcium forms. Individuals with rare genetic disorders affecting nucleotide metabolism should seek medical guidance before use. --- *Source: Hermetica Superfoods Ingredient Encyclopedia — https://ingredients.hermeticasuperfoods.com* *License: CC BY-NC-SA 4.0 — Attribution required. Commercial use: admin@hermeticasuperfoods.com*