Biological Activity and Preparation Method of Calcium beta-hydroxy-beta-methylbutyrate

Calcium beta-hydroxy-beta-methylbutyrate, abbreviated as HMB-Ca with the chemical formula C₁₀H₁₈CaO₆, is a white powdered compound under ambient temperature and pressure, which is readily soluble in water but insoluble in ether-based organic solvents. Widely found in citrus fruits, cauliflower, and deep-sea fish, Calcium beta-hydroxy-beta-methylbutyrate is commonly used as a food additive in beverages, dairy products, sports nutrition foods, and related fields, with a recommended daily intake not exceeding 6 grams.

Figure1: Picture of Calcium beta-hydroxy-beta-methylbutyrate

Introduction

Calcium beta-hydroxy-beta-methylbutyrate is produced using sodium hypochlorite, diacetone alcohol, hydrochloric acid, ethyl acetate, ethanol, calcium hydroxide, and other primary raw materials through a series of processes including oxidative synthesis, acidification, extraction, neutralization, centrifugation, and drying. Initially approved as a novel food ingredient in 2011, Calcium beta-hydroxy-beta-methylbutyrate was permitted for use in sports nutrition foods and formula foods for special medical purposes. In 2017, its application scope was further expanded to include beverages, dairy products, cocoa products, chocolate and chocolate products, confectionery, baked goods, and other categories, with a maximum recommended daily intake of 3 grams. According to Announcement No. 1 issued in 2025, the maximum recommended daily intake of Calcium beta-hydroxy-beta-methylbutyrate has been adjusted to no more than 6 grams. Calcium beta-hydroxy-beta-methylbutyrate has been approved for use in multiple countries and regions including the European Union, the United States, Japan, Singapore, and others. It has a long history of application internationally, and its safety profile is widely recognized. [1]

Biological Activity

Calcium beta-hydroxy-beta-methylbutyrate exhibits functions such as promoting muscle growth and regulating cholesterol metabolism. Its preparation methods primarily include the haloform reaction process using diacetone alcohol as a raw material and a synthetic process involving peracetic acid solution, both of which are environmentally friendly. Capable of enhancing muscle growth, boosting immunity, reducing cholesterol and low-density lipoprotein (LDL) levels in the body to lower the risk of coronary heart disease and cardiovascular diseases, as well as improving nitrogen retention capacity and maintaining protein levels, Calcium beta-hydroxy-beta-methylbutyrate has broad applications. It is included in the Generally Recognized as Safe (GRAS) certification by the U.S. Food and Drug Administration and is suitable for formula foods for special medical purposes. [1]

Preparation Method

The preparation method of Calcium beta-hydroxy-beta-methylbutyrate belongs to the technical field of organic compound synthesis. Using 4-methyl-4-hydroxy-2-pentanone (diacetone alcohol) as the reaction raw material and water as the solvent, a haloform reaction is carried out with a NaOBr aqueous solution, followed by acidification and extraction with isobutanol. The HMB acid in the isobutanol extract is directly converted into its calcium salt with Ca(OH)₂ to produce Calcium beta-hydroxy-beta-methylbutyrate. This method offers advantages such as high product purity and minimal environmental pollution. Alternatively, peracetic acid solution is prepared by reacting glacial acetic acid, sulfuric acid, and hydrogen peroxide, followed by distillation under reduced pressure. The resulting peracetic acid solution is mixed with diacetone alcohol, and methyl acetate is added as a solvent for the reaction. After the reaction, distillation is performed to collect the fraction at 70°C, leaving β-hydroxy-β-methylbutyric acid solution as the residue. Water is then added to the residue, and sodium hydroxide solution is used to adjust the pH to 6.0–7.0. After heating and dissolution, the mixture is filtered, and calcium chloride is added to the filtrate under stirring. The pH is readjusted to 6.5–7.0, leading to the precipitation of Calcium beta-hydroxy-beta-methylbutyrate, which is then filtered and dried to obtain the final product. [2]

Applications

Calcium beta-hydroxy-beta-methylbutyrate is permitted for use in beverages, dairy products, cocoa products, chocolate and chocolate products, confectionery, baked goods, sports nutrition foods, and formula foods for special medical purposes. The recommended daily intake for this product is ≤6 g/day. According to the Generally Recognized as Safe (GRAS) designation by the U.S. Food and Drug Administration, Calcium beta-hydroxy-beta-methylbutyrate is approved for use in medical nutritional foods and special dietary products. [1]

Reference

[1] Song, Y.; Li, Y. H.; et al. Scientific consensus on the application of calcium β-hydroxy-β-methylbutyrate (CaHMB)[J]. Journal of Chinese Institute of Food Science and Technology, 2024, 24(6): 486-497.

[2] Wang, X. Z.; Tang, J.; Yang, F. Preparation method of calcium β-hydroxy-β-methylbutyrate (HMB-Ca): CN 02151042[P].

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