Scientific Opinion on the Tolerable Upper Intake Level of calcium

Elderly people who have a fracture are at high risk of another. Vitamin D and calcium supplements are often recommended for fracture prevention. We aimed to assess whether vitamin D3 and calcium, either alone or in combination, were effective in prevention of secondary fractures. In a factorial-design trial, 5292 people aged 70 years or older (4481 [85%] of whom were women) who were mobile before developing a low-trauma fracture were randomly assigned 800 IU daily oral vitamin D3, 1000 mg calcium, oral vitamin D3 (800 IU per day) combined with calcium (1000 mg per day), or placebo. Participants who were recruited in 21 UK hospitals were followed up for between 24 months and 62 months. Analysis was by intention-to-treat and the primary outcome was new low-energy fractures. 698 (13%) of 5292 participants had a new low-trauma fracture, 183 (26%) of which were of the hip. The incidence of new, low-trauma fractures did not differ significantly between participants allocated calcium and those who were not (331 [12.6%] of 2617 vs 367 [13.7%] of 2675; hazard ratio (HR) 0.94 [95% CI 0.81-1.09]); between participants allocated vitamin D3 and those who were not (353 [13.3%] of 2649 vs 345 [13.1%] of 2643; 1.02 [0.88-1.19]); or between those allocated combination treatment and those assigned placebo (165 [12.6%] of 1306 vs 179 [13.4%] of 1332; HR for interaction term 1.01 [0.75-1.36]). The groups did not differ in the incidence of all-new fractures, fractures confirmed by radiography, hip fractures, death, number of falls, or quality of life. By 24 months, 2886 (54.5%) of 5292 were still taking tablets, 451 (8.5%) had died, 58 (1.1%) had withdrawn, and 1897 (35.8%) had stopped taking tablets but were still providing data for at least the main outcomes. Compliance with tablets containing calcium was significantly lower (difference: 9.4% [95% CI 6.6-12.2]), partly because of gastrointestinal symptoms. However, potentially serious adverse events were rare and did not differ between groups. The findings do not support routine oral supplementation with calcium and vitamin D3, either alone or in combination, for the prevention of further fractures in previously mobile elderly people.

The impact of abdominal arterial calcific deposits on the prediction of cardiovascular disease (CVD) over a long follow-up interval deserves greater scrutiny. Lateral lumbar radiographs were studied as a predictor of incident coronary heart disease (CHD), CVD, and CVD mortality in 1049 men and 1466 women (mean age, 61 years) who were followed from 1967 to 1989. Anterior and posterior wall calcific deposits in the aorta at the level of the first through fourth lumbar vertebrae were graded according to increasing severity using a previously validated rating scale for abdominal aortic calcium (AAC) that ranges from 0 to 24 points. There were 454 cases of CHD, 709 cases of CVD, and 365 CVD deaths. Proportional hazards logistic regression was used to test for associations between AAC and later events after adjustment for age, cigarette use, diabetes mellitus, systolic blood pressure, left ventricular hypertrophy, body mass index, cholesterol, and HDL cholesterol. In comparisons with the lowest AAC tertile, the multivariate age-adjusted relative risks (RR) for CVD were increased in tertile 2 (men: RR, 1.33; 95% confidence interval [CI], 1.02 to 1.74; women: RR, 1.25; 95% CI, 0.95 to 1.65) and tertile 3 (men: RR, 1.68; 95% CI, 1.25 to 2.27; women: RR, 1.78; 95% CI, 1.33 to 2.38). Similar results were obtained with CHD and CVD mortality. AAC deposits, detected by lateral lumbar radiograms, are a marker of subclinical atherosclerotic disease and an independent predictor of subsequent vascular morbidity and mortality.

In older women and men, greater intakes of dietary calcium, potassium, and total fluid reduce the risk of kidney stone formation, while supplemental calcium, sodium, animal protein, and sucrose may increase the risk. Recently, phytate has been suggested to play a role in stone formation. To our knowledge, no prospective information on the role of dietary factors and risk of kidney stone formation is available in younger women. We prospectively examined, during an 8-year period, the association between dietary factors and the risk of incident symptomatic kidney stones among 96 245 female participants in the Nurses' Health Study II; the participants were aged 27 to 44 years and had no history of kidney stones. Self-administered food frequency questionnaires were used to assess diet in 1991 and 1995. The main outcome measure was an incident symptomatic kidney stone. Cox proportional hazards regression models were used to adjust simultaneously for various risk factors. We documented 1223 incident symptomatic kidney stones during 685 973 person-years of follow-up. After adjusting for relevant risk factors, a higher dietary calcium intake was associated with a reduced risk of kidney stones (P =.007 for trend). The multivariate relative risk among women in the highest quintile of intake of dietary calcium compared with women in the lowest quintile was 0.73 (95% confidence interval, 0.59-0.90). Supplemental calcium intake was not associated with risk of stone formation. Phytate intake was associated with a reduced risk of stone formation. Compared with women in the lowest quintile of phytate intake, the relative risk for those in the highest quintile was 0.63 (95% confidence interval, 0.51-0.78). Other dietary factors showed the following relative risks (95% confidence intervals) among women in the highest quintile of intake compared with those in the lowest quintile: animal protein, 0.84 (0.68-1.04); fluid, 0.68 (0.56-0.83); and sucrose, 1.31 (1.07-1.60). The intakes of sodium, potassium, and magnesium were not independently associated with risk after adjusting for other dietary factors. A higher intake of dietary calcium decreases the risk of kidney stone formation in younger women, but supplemental calcium is not associated with risk. This study also suggests that some dietary risk factors may differ by age and sex. Finally, dietary phytate may be a new, important, and safe addition to our options for stone prevention.