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Calcium Orotate- An Overview of Its Bioavailability, Health Benefits, and Clinical Applications
Published on: April 19, 2024

The Science Behind Calcium Orotate – What Research Says

Calcium orotate (CaOr) is a calcium supplement gaining traction due to purported high bioavailability and potential benefits for bone health [1]. It comprises elemental calcium bound to orotic acid (OA), a natural precursor in pyrimidine synthesis, crucial for cellular function. Proponents theorize this unique structure enhances calcium absorption by the body.

Chemical Composition: CaOr possesses the molecular formula C10H6CaN4O8 with a molecular weight of 350.25 g/mol [2]. It is 4-Pyrimidinecarboxylic acid, 1,2,3,6-tetrahydro-2,6-dioxo-, calcium salt (2:1). Its structure consists of two key components.

Specification (composition wise) is here:

  • Calcium Ion (Ca2+): This positively charged cation provides the essential mineral for bone health and various physiological processes.
  • Orotic Acid (OA): This negatively charged organic molecule (C5H4N2O4) acts as a chelator, binding to the Ca2+

Calcium orotate dihydrate is a specific form of calcium orotate that contains additional water molecules bonded to the core calcium orotate structure.

Properties:

  • Appearance: White crystals or crystalline powder [1].
  • Solubility: Very easily soluble in water. This high-water solubility could contribute to its potential for good absorption [3].
  • Potential Advantages in human body: It’s also known as
    Uracil-4-carboxylic acid calcium salt is often considered advantageous [4] due to several reasons.
  • Bioavailability: Bioavailability is a crucial factor when considering calcium supplements, as it reflects the proportion of calcium absorbed and utilized by the body. It is generally considered more soluble than some other calcium salts, such as carbonate or phosphate.

This improved its solubility might suggest easier absorption in the digestive system. Its absorption rate reflects its higher bioavailability compared to other forms of calcium supplements.  While calcium orotate absorption rate is promoted as having near-perfect (around 90-95%) compared to common forms like calcium citrate or carbonate (20-45%) [5].

Calcium orotate Calcium Carbonate Calcium Citrate
Bioavailability 90-95% 20-40% 22% to 49%.
Calcium Content 10-11% 40% 21%
Calcium Orotate properties
  1. Enhanced Cellular Uptake: Orotic acid, a component of CaOr, may facilitate calcium’s passage through cell membranes [6]. This can improve the delivery of calcium to various tissues and cells throughout the body.
  2. Potential for Balanced Mineral Absorption: The purported higher absorption of calcium orotate suggests it might have less impact on magnesium and phosphorus homeostasis compared to other supplements [7]. Some calcium forms, like carbonate, can bind to magnesium in the digestive tract, hindering its absorption [8].
  3. Improved Gastrointestinal Tolerance: Research is ongoing regarding the effectiveness of calcium orotate in treatment for various conditions, but it is generally considered safe for most adults when taken at recommended doses [9]. The chelation between calcium and orotic acid might enhance absorption and potentially reduce gastrointestinal irritation as well as side effects compared to larger calcium molecules found in carbonate or some citrate forms [10]. This could make calcium orotate a more tolerable option for individuals with sensitive stomachs. Calcium orotate treats calcium level as it maintains optimal calcium levels in the body.
  4. Bone Health Support: It usesinclude treating and preventing calcium deficiency, a condition that can lead to weak bones and other health problems. Some studies on calcium orotate uses suggest it might be beneficial for bone health in conditions like osteoporosis, but more research is needed for confirmation [11]. CaOr in treatment may be a potential option for supporting bone health due to its chelation property. However, controlled clinical trials investigating its impact on bone mineral density (BMD) are scarce. One small study in postmenopausal women with osteopenia did observe a modest increase in BMD with calcium orotate supplementation. Along with calcium orotate in treatment, maintaining a healthy diet rich in calcium and vitamin D is crucial for optimal bone health [12].
  5. Healthcare professionals might consider calcium orotate usesfor pregnant or lactating women who need additional calcium orotate supplements. The National Institutes of Health (NIH) recommends that pregnant women consume 1,000 milligrams (mg) of calcium daily. This helps with fetal bone development and prevents complications for the mother like calcium citrate, calcium carbonate, and calcium lactate are well-established and generally safe forms of calcium for pregnant women. Calcium orotate with vitamin D3 tablets during pregnancy can be a helpful combination, but it’s important to consult a doctor before starting them. Calcium is essential for fetal bone development, and vitamin D3 aids in calcium absorption. While calcium orotatein pregnancy is generally considered safe, exceeding recommended dosages can be harmful. There are lots of calcium orotate brands available for dietary supplements and may provide options for those seeking to supplement with calcium orotate.
  6. Calcium Orotate might improve calcium absorption and reduce inflammation, potentially aiding cartilage healing in Costochondritis. However, more research is required to validate this theory. Costochondritis is inflammation in the cartilage connecting your ribs to your breastbone, causing chest pain.

Clinical studies and trials

  • This API has shown promise in several clinical applications related to bone health and degenerative bone diseases. Notably, it has been used effectively for the recalcification of malignant bone tumors, which potentially prevents further metastases. In a specific study, it achieved successful recalcification in 10 out of 13 subjects. Additionally, an oral dose of approximately 600 mg daily has been found to reverse bone loss in cancer patients undergoing radiological therapy, a result substantiated by X-ray images taken before and after the treatment [13].
  • Further research indicates that it may also be beneficial in managing joint diseases, including arthritis and spondylitis. Given these outcomes, it could potentially play a role in mitigating degenerative bone changes associated with osteoarthritis. These findings suggest a valuable therapeutic role for calcium orotate in the treatment and prevention of various bone-related conditions [14].
  • It has demonstrated efficacy in the management of chronic, aggressive hepatitis. In a study, complete remissions were observed in 14 patients who were administered 3 grams of calcium orotate daily over a period of two years. It is noteworthy that four of these patients also required adjunctive cortisone therapy, albeit at reduced dosages. The optimal therapeutic effect of it was generally realized after a treatment duration ranging from 9 to 18 months, with no significant benefits noted before this period. These findings suggest that it could be a valuable addition to the treatment regimen for chronic hepatitis, particularly in cases where standard therapies are insufficient or require supplementation [15].

Is calcium Orotate the best form of Calcium?

  • Calcium Orotate Vs Calcium Acetate:
    Calcium acetate is commonly prescribed to chronic kidney disease patients to lower high phosphorus levels in the body by promoting a balance between calcium and phosphorus. 16 Calcium orotate on the other hand is reasonably considered to be well integrated.
  • Calcium orotate Vs Calcium Carbonate
    Calcium carbonate is a cost-effective supplement, while CaOr is considered for its high absorption qualities. Relatively, Calcium aspartate is highly bioavailable. 17  Calcium carbonate requires the absorption of stomach acid, which can cause upset stomach. Calcium orotate, on the other hand, improves absorption even without optimal stomach acid. When considering calcium orotate vs citrate, or even calcium orotate vs calcium citrate malate, it’s important to note that while all these forms are effective, the orotate form tends to be more efficient in lower doses.
  • Calcium hydroxide vs calcium orotate
    Calcium hydroxide is primarily used in industrial applications and less bioavailable for bone health, compared to the highly absorbable calcium orotate.
  • Calcium orotate and calcium Gluconate
    Calcium gluconate offers moderate bioavailability. It is usually used in medical settings for immediate mineral replenishment. While calcium orotate is used for bone health, calcium gluconate shines in a specific role – regulating elevated phosphate levels in patients with kidney disease.
  • Calcium oxide vs calcium orotate
    Calcium oxide is more caustic and less suited for dietary supplementation than calcium orotate.

 

Calcium Form Primary Benefits Usage
Calcium orotate High bioavailability, superior cellular absorption, direct cellular uptake Sustained bone health, cellular health
Calcium aspartate High bioavailability Efficient absorption by the body
Calcium carbonate Low bioavailability General supplementation
Calcium citrate malate Excellent absorption Preferred for those with digestive issues
Calcium hydroxide Used in industrial applications, less bioavailable Not suited for bone health supplementation
Calcium gluconate Moderate bioavailability Medical settings for immediate replenishment
Calcium oxide Less suited for dietary supplementation Rarely used in dietary supplements

Wrapping up!

The demand for pharmaceutical-grade calcium orotate API is expected to rise in the coming years due to its potential health benefits. Calcium orotate emerges as a promising contender for promoting bone health and potentially mitigating calcium deficiency. When formulating dietary supplements, choosing a reliable supplier of high-quality calcium orotate API is crucial for product safety and efficacy. Research into the effectiveness of calcium orotate API for specific health conditions is ongoing, with promising results in some areas.

Why choose WBCIL?

WBCIL takes pride in its high-purity calcium orotate production process. We are API manufacturing company in India working as its source. We prioritize quality by directly reacting orotic monohydrate, a single-water molecule form of orotic acid, with a carefully chosen calcium salt. This controlled reaction ensures optimal yield and exceptional purity in the final API product. Our commitment to quality sets WBCIL apart, offering you the best CaOr available. Choose West Bengal Chemical Industries Limited to get calcium orotate API with high quality.

References
  1. Calcium Orotate Tablet – Uses, Side Effects, and More, WebMD. https://www.webmd.com/drugs/2/drug-59689/calcium-orotate-oral/details.
  2. National Center for Biotechnology Information. “PubChem Compound Summary for CID 89722, Calcium orotate” https://pubchem.ncbi.nlm.nih.gov/compound/Calcium-orotate.
  3. Jahan SM, Islam HM, Khan MR, Hossain A, Kayesh R, Asma Rahman. A simple reversed phase HPLC method for quantitative estimation of calcium orotate and its degradation products in solid dosage form. J Res Anal. 2016; 2(4): 108-112. https://www.researchgate.net/publication/313859127_A-Simple-Reversed-Phase-HPLC-Method-for-Quantitative-Estimation-of-Calcium-Orotate-and-Its-Degradation-Products-in-Solid-Dosage-Form
  4. Group, DC, Calcium Orotate: How It Compares to Other Calcium Supplements, Global Healing, https://explore.globalhealing.com/calcium-orotate/
  5. Tello, Carlos. Calcium Salts: Citrate vs Carbonate vs Orotate & Others. September 9, 2021. https://supplements.selfdecode.com/blog/calcium-salts/
  6. Brosnan ME, Brosnan JT. Orotic acid excretion and arginine metabolism. J Nutr. 2007 Jun;137(6 Suppl 2):1656S-1661S. https://pubmed.ncbi.nlm.nih.gov/17513443/#:~:text=Increased%20orotic%20acid%20excretion%20is,arginase%20deficiency%20who%20exhibit%20hyperargininemia.
  7. Sakhaee K, Bhuket T, Adams-Huet B, Rao DS. Meta-analysis of calcium bioavailability: a comparison of calcium citrate with calcium carbonate. Am J Ther. 1999 Nov;6(6):313-21. doi: 10.1097/00045391-199911000-00005. PMID: 11329115. https://pubmed.ncbi.nlm.nih.gov/11329115/#:~:text=Results%3A%20Calcium%20absorption%20from%20calcium,and%20by%2021.6%25%20with%20meals.
  8. Michelle Gordon-Releford, Alternative calcium options instead of milk, Michigan State University Extension, October 18, 2018. https://www.canr.msu.edu/news/alternative_calcium_options_instead_of_milk
  9. Said SA, Abdullah ME. Effect of antacids on activity of oral hypoglycemics. J Pharm Sci. 1981 Jun;70(6):621-4. doi: 10.1002/jps.2600700612. PMID: 7252803. https://pubmed.ncbi.nlm.nih.gov/7252803/#:~:text=The%20antacids%20reduced%20the%20hypoglycemic,antacids%20with%20acetohexamide%20and%20tolazamide.
  10. Calcium Supplements for Osteoporosis, Health Wellness Prevention. https://health.umms.org/2022/07/26/calcium-supplements-for-osteoporosis/
  11. Institute of Medicine (US) Committee to Review Dietary Reference Intakes for Vitamin D and Calcium; Ross AC, Taylor CL, Yaktine AL, et al., editors. Dietary Reference Intakes for Calcium and Vitamin D. Washington (DC): National Academies Press (US); 2011. https://www.ncbi.nlm.nih.gov/books/NBK56070/
  12. Nieper A. Recalcification of bone metastases by calcium diorotate. Agressologie. 1970;11(6):495-500. PMID: 5502790. https://oawhealth.com/2018/08/13/orotates-and-mineral-transporters-fact-or-fiction/
  13. Nieper HA. ANTI-INFLAMMATORY AND IMMUNE-INHIBITING EFFECTS OF CALCIUM OROTATE ON BRADYTHROPHIC TISSUES. Agressologie. 1969 Jan 1;10(4):349. https://oawhealth.com/2018/08/13/orotates-and-mineral-transporters-fact-or-fiction/
  14. Nieper HA. The curative effect of a combination of Calcium-orotate and Lithium orotate on primary and secondary chronic hepatitis and primary and secondary liver cirrhosis. From lecture Intl Acad of Prevent Med, Washington, DC March. 1974;9. https://oawhealth.com/2018/08/13/orotates-and-mineral-transporters-fact-or-fiction/
  15. Taksande SR, Worcester EM. “Calcium supplementation in chronic kidney disease.” Expert Opin Drug Saf. 2014;13(9),1175-85.
Frequently Asked Questions on: The Science Behind Calcium Orotate – What Research Says
Is calcium orotate the best form of calcium?

Calcium orotate is one of many calcium supplements available. It is commonly known its high bioavailability. However, whether it is the “best” form of calcium depends on various factors like health requirements, digestive tolerance, and specific health goals.

How much calcium is in calcium orotate?

Calcium orotate supplements typically contain a lower percentage of elemental calcium compared to other forms of calcium supplements. On average, about 10% of the weight of calcium orotate is elemental calcium. This means if a tablet contains 500 mg of calcium orotate, it would provide about 50 mg of actual calcium.

Is calcium orotate safe?

As top API manufacturer in India, we prioritize the safety and efficacy of our products. Calcium orotate is generally recognized as safe when used according to the recommended dosages. We adhere to stringent quality control standards during manufacturing to ensure that our products meet all regulatory safety requirements.

Is calcium orotate better than calcium citrate malate?

It is touted for its high bioavailability, while calcium citrate malate is well-absorbed and generally gentler on the digestive system.

Who is the manufacturer of calcium orotate API in India?

When it comes to best API manufacturers in India, West Bengal Chemical Industries Limited grabs top position.

What are the health benefits of calcium orotate?

Here are five benefits:
Bone health, heart function, nerve support, muscle function, cellular health.

Is orotic acid a vitamin?

No, Orotic acid is not a vitamin.

What is the history of calcium orotate?

In the 1950s, Dr. Hans Nieper, a German physician, developed calcium orotate. He believed orotic acid, a natural substance in the body, could improve mineral absorption. His research led to calcium orotate as a supplement, potentially offering better absorption and fewer side effects than traditional calcium. Since then, it’s been used in alternative medicine and supplements to support bone health and overall well-being.

What is the USP of calcium orotate?

The unique selling proposition (USP) of Calcium Orotate lies in its ability to increase the absorption and utilization of calcium by the body. This increased absorption of this chelated complex can improve bone health, cardiovascular support, and overall mineral balance. In addition, calcium orotate is often touted for its ability to reduce gastrointestinal side effects, making it desirable for individuals seeking an effective calcium supplement with reduced digestive discomfort.

Why is it better than other calcium APIs?

Calcium orotate, bound to orotic acid, is claimed to be better absorbed by the body than other calcium supplements. This chelation, the process of forming a complex with a metal ion, may increase bioavailability leading to maximum utilization in the body. Compared to other forms, calcium orotate’s chelation may ease digestion, potentially reducing bloating and constipation.


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