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Calcium citrate tetrahydrate

Also known as: Calcium citrate, Ca₃(C₆H₅O₇)₂·4H₂O, Calcium citrate tetrahydrate

Overview

Calcium citrate tetrahydrate is a calcium salt of citric acid, chemically identified as Ca₃(C₆H₅O₇)₂·4H₂O. While not naturally abundant, it is synthesized for use as a dietary supplement to provide bioavailable calcium. Its primary application is to prevent or treat calcium deficiency, support bone mineral density, and reduce the risk of osteoporosis, particularly in populations with increased calcium needs such as postmenopausal women and older adults. A key characteristic of calcium citrate tetrahydrate is its superior solubility and absorption compared to calcium carbonate, especially in individuals with low stomach acid. Unlike calcium carbonate, it can be taken with or without food, making it a more versatile option. Extensive research, including numerous randomized controlled trials and meta-analyses, supports its efficacy and bioavailability, particularly when combined with vitamin D for optimal bone health.

Benefits

Calcium citrate tetrahydrate offers several evidence-based benefits, primarily due to its enhanced bioavailability. It improves calcium absorption by approximately 22% to 27% compared to calcium carbonate, regardless of food intake, which is crucial for maintaining bone mineral density and reducing bone loss in at-risk populations like postmenopausal women. This superior absorption is particularly beneficial for individuals with achlorhydria or those taking acid-reducing medications, as gastric acid levels do not significantly impact its absorption. Furthermore, calcium citrate is less likely to cause gastrointestinal side effects such as constipation, which are common with calcium carbonate. It also does not exacerbate kidney stone risk and may even be preferable for individuals prone to nephrolithiasis. Clinical studies and meta-analyses consistently show statistically significant improvements in calcium absorption and bone health markers with calcium citrate supplementation, especially when combined with vitamin D. While bone health improvements require consistent, long-term supplementation (months to years), the enhanced absorption provides a clinically meaningful advantage.

How it works

Calcium citrate tetrahydrate functions by dissociating in the gastrointestinal tract, releasing calcium ions. These calcium ions are then absorbed primarily in the small intestine through both active transport and passive diffusion mechanisms. Once absorbed, calcium ions are critical for bone mineralization, forming a key component of hydroxyapatite crystals within the bone matrix. Beyond bone health, calcium also plays vital roles in various physiological processes, including neuromuscular function, blood clotting, and vascular contraction. The absorption process involves specific calcium channels and transporters, such as TRPV6 and calbindin, located in the enterocytes. A significant advantage of calcium citrate is its solubility, which is less dependent on gastric acid, allowing for better absorption even in individuals with low stomach acid or when consumed without food. Each unit of calcium citrate tetrahydrate provides approximately 21% elemental calcium by weight.

Side effects

Calcium citrate tetrahydrate is generally considered safe and well-tolerated when taken within recommended dosages. Common side effects, occurring in less than 5% of users, are typically mild gastrointestinal discomforts such as bloating or gas, which are less frequent and severe compared to those associated with calcium carbonate. Uncommon side effects (1-5%) may include rare instances of constipation or mild nausea. Very rare side effects (less than 1%) can include hypercalcemia, which usually only occurs with excessive intake. Calcium citrate may interact with certain medications, potentially interfering with the absorption of antibiotics like tetracyclines and fluoroquinolones if taken simultaneously; therefore, a separation of dosing times is often recommended. Contraindications for calcium citrate use include pre-existing hypercalcemia, severe renal impairment, or a known hypersensitivity to calcium citrate. It is particularly noted as a preferred calcium supplement for individuals with reduced gastric acid production or those on acid-suppressing medications due to its superior absorption profile under these conditions.

Dosage

For optimal absorption, a minimum effective dose of 500 mg elemental calcium per single serving is typically recommended. The optimal total daily calcium intake, combining dietary sources and supplements, should generally not exceed 1000–1200 mg for most adults. Supplementation should be adjusted to meet individual needs while staying within this range. Single doses exceeding 500 mg elemental calcium may lead to reduced absorption efficiency. The maximum safe total daily intake is generally considered to be around 1500 mg; exceeding this amount may increase the risk of adverse effects, such as hypercalcemia or, in men, a potential increased risk of prostate cancer. Calcium citrate can be taken with or without food, although taking it with meals may help minimize any mild gastrointestinal discomfort. When calculating dosage, it's important to remember that calcium citrate tetrahydrate provides approximately 21% elemental calcium by weight. Co-supplementation with vitamin D is highly recommended, as vitamin D sufficiency significantly enhances calcium absorption and optimizes bone health benefits.

FAQs

Is calcium citrate better absorbed than calcium carbonate?

Yes, calcium citrate is absorbed 22–27% better than calcium carbonate, especially on an empty stomach or in individuals with low stomach acid.

Can calcium citrate be taken without food?

Yes, unlike calcium carbonate, calcium citrate does not require food for optimal absorption, making it a flexible option for supplementation.

Does calcium citrate cause constipation?

Calcium citrate is less likely to cause constipation compared to calcium carbonate, making it a more tolerable option for many individuals.

How long does it take to see benefits?

Bone health improvements typically require several months to years of consistent supplementation, often combined with vitamin D, for noticeable effects.

Is calcium citrate safe for people with kidney stones?

Calcium citrate does not increase kidney stone risk and may be a safer choice than other calcium forms for individuals prone to stones.

Research Sources

https://pubmed.ncbi.nlm.nih.gov/17507729/ – This review summarized calcium supplementation forms, recommending calcium citrate for individuals with low stomach acid or on acid-reducing drugs. It emphasized a maximum single dose of 500 mg elemental calcium for optimal absorption and highlighted the importance of vitamin D co-supplementation. The review cited evidence supporting calcium citrate’s better absorption and tolerability compared to calcium carbonate.
https://utsouthwestern.elsevierpure.com/en/publications/meta-analysis-of-calcium-bioavailability-a-comparison-of-calcium- – This meta-analysis quantitatively compared calcium citrate and calcium carbonate absorption, finding calcium citrate superior by 22–27% regardless of food intake. It included randomized controlled trials with adequate sample sizes and proper controls, providing statistically significant results (p < 0.05).
https://ods.od.nih.gov/factsheets/Calcium/HealthProfessional/ – This authoritative summary, based on systematic reviews and meta-analyses, confirmed calcium citrate’s better absorption profile and safety. It recommended calcium citrate for individuals with low gastric acid and emphasized vitamin D co-administration. It also noted the typical elemental calcium content differences and dosing guidelines.
https://www.wbcil.com/blog/citrate-vs-citrate-malate-the-ultimate-showdown-for-bone-strength/ – This source discusses the differences between calcium citrate and calcium citrate malate, highlighting the benefits of citrate forms for bone strength. It suggests that calcium citrate is a good option for those seeking bone health support.