The Effects of Calcium Supplementation on the Human Body

Charlie Ryan

Abstract: The usage of calcium supplementation for the purpose of treating or preventing Osteoporosis has been studied to determine its efficacy and harmful side effects. The purpose of this article is to review these studies and call for further research into the effects of calcium supplements.

Calcium plays a number of important roles in physiology, pathology, and especially as a structural component for bones.1 It is used in the processes of blood-clotting, muscle contraction, regulation of heart rhythms, and nerve functions.2 The body can attain calcium by either ingesting it through food and supplements or by removing calcium from the bones.2 The loss of bone mineral density (BMD) and the loss of muscle function are major causes of osteoporotic fractures, which are associated with disability, increased morbidity and a twenty percent increased mortality.3 Osteoporosis remains a common problem. Approximately forty percent of women aged fifty are expected to have an osteoporotic fracture in the remainder of their life.4 For years, a certain calcium and Vitamin D balance has been considered necessary for maintaining a healthy bone metabolism and for treating, as well as preventing, osteoporosis.3 There has been evidence that supplemental approaches to calcium, especially for those who receive inadequate amounts of it, may benefit bone mass and reduce fracture risk.5 Recent studies have, however, questioned the efficacy of calcium supplements.3 Moreover, further evidence suggests possible gastrointestinal side effects, increased risk of kidney stones, and potential negative cardiovascular effects from calcium supplementation.3 Efficacy of Calcium Supplements: As a person ages, bones go through a remodeling process where they are repeatedly broken down and built up. 2 Osteoblast bone cells will continuously build bone up while osteoclast bone cells will constantly break bone down if calcium is needed in other parts of the body. 2 A typical healthy person will produce more bone than they lose until about the age of thirty, when they will have a negative calcium balance which can lead to bone loss and thus higher fragility in bones.2 Figure 1 depicts the negative feedback loop of calcium in the body.

Figure 1: A visual depiction of how the body regulates calcium levels. Note the effects of calcium levels on osteoclasts.2

Several studies have been performed to determine whether calcium supplementation has been shown to reduce the risk of osteoporotic fractures. Its effects when combined with Vitamin D supplemental intake may differ, as having

an adequate amount of Vitamin D is helpful for calcium absorption in the body.3 In their meta-analysis, the DIPART Investigator group viewed 68,500 patients from seven individual randomized controlled trials.5 For trials including the combined use of calcium and vitamin D supplements, there appeared to be a modest reduction in all fractures [Hazard Ratio (HR)–the ratio of hazard rates in the treated versus control group– 0.92 (95 % Confidence Interval (CI) 0.86, 0.99)] and hip fractures [HR 0.83 (95 % CI 0.69, 0.99)].5 This meta-analysis included individuals both in a community setting and in a nursing-home setting, indicating that there is an association between calcium supplements and reduced osteoporotic fractures in an average person’s environment.5 In order to determine whether calcium supplementation alone would differ from calcium supplementation combined with vitamin D supplementation, Tang et. Al. performed a meta-analysis separating the two approaches and comparing their results among seventeen trials.5 The authors of the meta-analysis took a sensitivity analysis comparing the effects of either approach.5 The relative risk of fracture for calcium and vitamin D supplements was 0.87 (95 % CI 0.77, 0.97) and, for calcium alone, it was 0.90 (95 % CI 0.80, 1.00). 5 Given the margin of error, there was no significant difference between the two types of therapies; however the reduced risk of fracture with calcium alone was borderline statistically significant. In a separate meta-analysis of random clinical trials conducted by members of the Department of Orthopaedic Surgery in China, the use of supplements that included calcium with or without vitamin D compared with a placebo or no treatment revealed that there was no significant association between calcium supplements and a reduced risk of bone fractures.4 As such, their findings do not support the use of calcium supplements for community dwelling people, including those at higher ages who have the highest risk of Osteoporosis.4 In contrast, the metaanalysis done by Iacopo Chiodini and Mark J Bolland suggests that calcium supplements, specifically those combined with vitamin D supplements, lead to an increase in BMD and to a reduction of total fracture risk by fifteen percent and hip fracture risk by thirty percent.3 Therefore, without taking into account the possible adverse effects of calcium supplements, they claim that their findings suggest that only those who suffer from insufficient calcium uptake should take calcium supplements and that the evidence does not justify the use of population-level usage of calcium supplements, nor the prescribing of them to those who experience normal levels of calcium intake. 3 A similar review from the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) and the International Foundation for Osteoporosis (IOF) reflected this conclusion. 5

Recent studies regarding the vascular and gastrointestinal side effects of calcium supplements have received more attention. Calcium deposition in the vasculature has been a consistent feature of vascular disease and has shown to have adverse effects in other soft tissues such as with an increased risk of developing kidney stones.1 In order to prevent this, there is a complex system of inhibitors that react with calcium when it reaches high levels, however, as the body ages, the effectiveness of this system declines, especially in the vascular system.1 Furthermore, some studies claim that blood calcium levels influence the development of vascular diseases.1 One recent meta-analysis of nine studies regarding the relationship between serum

calcium and mortality from vascular disease revealed that calcium seemed to be an independent predictor of myocardial infarction, which are commonly referred to as heart attacks. Moreover, this meta analysis demonstrated a hazard ratio (HR) of death of 1.13 (95% confidence interval [CI], 1.09 to 1.18) for each standard deviation increase in serum calcium (approximately 0.1 mmol/L). 1 Many other studies also attribute serum calcium and circulating calcium to vascular calcification, and one study even directly attributed calcium supplements with an increased risk of developing coronary artery calcification.1 Further research is need to better determine what extent calcium supplements affect serum calcium levels. Many studies focusing on the direct relationship between calcium supplements and vascular health have been performed. An example of which is presented in Figure 2.

Figure 2: Results of a meta-analysis revealing a significant difference between those who experienced a myocardial infarction after continuously taking calcium supplements and those who did not. In contrast to this however, a Women’s Health Initiative study found no association between calcium supplementation and coronary artery calcium.6 The European Prospective Investigation into Cancer and Nutrition Study did find an association between calcium supplementation among women and myocardial infarction (RR = 1.86; 95% CI = 1.17–2.96) but depicted no significant relationship between calcium supplementation and strokes or cardiovascular disease mortality.6 In one of the studies incorporating results from patient level data, Bolland found that treatment of one thousand people with calcium for five years would cause an additional fourteen myocardial infarctions, ten strokes, and thirteen deaths while preventing twenty-six fractures.7 Although Bolland claims that the increased risk of cardiovascular disease is modest, he believes it could become a large problem given the widespread usage of calcium supplements. 7

Conclusion: Given the contrasting data on the efficacy of calcium supplements in preventing bone fractures and the important link between blood calcium levels and vascular disease, this review recommends that further research be done in regard to the effects of calcium supplements. An important focus should be put on calcium supplements and how they affect serum calcium. It is important to note that many of these studies were likely exposed to confounding variables, so more direct experimental research within the bounds of ethical standards appears to be necessary.

1 Reid, Ian R. et al. "Calcium and Cardiovascular Disease." Endocrinology and Metabolism 32 (2017): 339 - 349. 2 The Nutrition Source. "Calcium." The Nutrition Source, Harvard T.H. Chan, www.hsph.harvard.edu/nutritionsource/calcium/ #:~:text=Calcium%20is%20a%20mineral%20mos t,heart%20rhythms%20and%20nerve%20function

s. Accessed 1 May 2022. 3 Chiodini, Iacopo, and Mark J. Bolland. "Calcium supplementation in osteoporosis: useful or harmful?" European Journal of Endocrinology, vol. 178, no. 4, Apr. 2018. European Society of Endocrinology, https://doi.org/10.1530/EJE-18-0113. Accessed 26 Apr. 2022. 4 Zhao, Jia-Guo et al. "Association Between Calcium or Vitamin D Supplementation and Fracture Incidence in Community-Dwelling Older Adults: A Systematic Review and Meta-analysis." JAMA 318 (2017): 2466–2482. 5 Harvey, Nicholas C. et al. "The role of calcium supplementation in healthy musculoskeletal ageing." Osteoporosis International 28 (2016): 447-462. 6 Waldman, Talya et al. "Calcium Supplements and Cardiovascular Disease." American Journal of Lifestyle Medicine 9 (2015): 298 - 307. 7 Bolland, Mark J. et al. "Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis." The BMJ 341 (2010): n. pag.