order po1 Whether calcium supplements can be

Whether calcium supplements can be beneficial or harmful to the health of people is still controversial. Although the effects of calcium supplements or casual calcium uptake on health outcomes have been systematically reviewed [99], the risks of calcium supplements for cardiovascular diseases have not been completely understood [116]. High calcium intake can slightly improve BMD in children and pregnant woman. There is no consistent conclusion between calcium intake and cardiovascular diseases, except blood pressure. Similarly, although some studies show that people with high calcium intake has lower chance of overweight and obesity [117], the relationship between calcium and obesity is still controversial. Calcium supplementation in diets can contribute to the reduced rate of bone loss and fracture incidence in elders; however, it can also increase the risks of acute gastrointestinal events, kidney stone, and cardiovascular diseases such as myocardial infarction and stroke [118,119]. Based on the meta-analysis, only 10% fracture incidence is reduced due to the calcium supplementation, but the incidences of myocardial infarction and stroke are increased up to 27%–31% and 12%–20%, respectively [119]. Moreover, high calcium intake for men also has the potential for the risk of advanced and fatal prostate cancer [17,120,121].
Conclusion
Conflict of interest
Acknowledgements This work is financially supported by the National Natural Science Foundation of China (No. 31571228), Chutian Scholar Program from Education Department of Hubei Province and Innovative Start-up Foundation from Wuhan Sports University to NC.
Introduction Experimental evidence has shown that elevated concentration of uric acid, otherwise known as hyperuricaemia, leads to the deposition of monosodium urate monohydrate crystals in tissue, especially joints, thereby resulting in gouty arthritis or uric order po1 nephrolithiasis [1,2]. Gout is a chronic inflammatory arthritis characterized by elevated concentration of uric acid in body fluids, resulting from the over-activity of xanthine oxidase (XO) [3]. It is also characterized with severe and episodic painful inflammation [4]: erythema and swelling [5]. Epidemiological studies have shown that the overall burden of the disease is increasing globally [2]. It is more prevalent in men above 30 years of age and in women older than 50 years [2,6]. Moreover, it has the propensity to reduce the quality of life of these individuals [7]. In addition to gouty arthritis, hyperuricaemia is also a well-established causative factor for uric acid kidney stones and acute kidney failure [8]. Recent epidemiologic studies have also implicated chronic mild hyperuricaemia in the development of interstitial nephritis and progressive renal failure [9]. Furthermore, it is an independent risk factor for metabolic syndrome, cardiovascular disease, hypertension, obesity, obstructive sleep apnea, stroke, vascular dementia, and preeclampsia [10]. Xanthine oxidase (XO) (EC 1.1.3.22) catalyzes the oxidation of hypoxanthine to xanthine and subsequently to uric acid [11] in the purine nucleotides catabolism. Its re-oxidation involves molecular oxygen which acts as electron acceptor, and during this reaction, superoxide radical (O2−) and hydrogen peroxide (H2O2) are produced [12]. The O2− is transformed into H2O2 and O2 either spontaneously or by the catalytic action of superoxide dismutase. Thus, the over-activity of XO leads to the deposition of uric acid in the susceptible tissues, and this triggers the inflammatory pathways with a concomitant release of reactive oxygen species. Hence, gouty arthritis and other inflammatory diseases associated with hyperuricaemia are characterized by oxidative stress. The kidney, liver and lungs are three major organs in mammals involved in metabolism and excretion, and previous studies have reported XO activity in the tissues of these organs [6,13,14]. Functionally, in these organs materials are chemically biotransformed and the metabolic wastes, such as carbon dioxide, water, salt, urea and uric acid, are removed from the body.