2. Sources of Calcium
Calcium intake is usually associated with the intake of dairy products such as milk, yogurt and cheese, as they are rich sources of calcium. Calcium-rich foods are dairy products, especially hard cheese that can provide 1 g of calcium per 100 g, whereas milk and yogurt can provide between 100 mg to 180 mg per 100 g. Cereals usually have around 30 mg per 100 g, however if they are fortified, the amount can reach 180 mg per 100 g. Nuts and seeds are also rich in calcium, especially almonds, sesame and chia that can provide between 250 to 600 mg per 100 g. Vegetables rich in calcium are kale, broccoli and watercress, which provide between 100 and 150 mg per 100 g [5
]. However, the impact that these foods have on total calcium intake depends on the population food consumption patterns. Whereas dairy products represent around 14% of total dietary energy intake in developed countries, they represent only around 4% of total energy intake in developing countries [6
]. In this way, some Asian countries have higher proportion of total calcium intake from non-animal foods such as vegetables, legumes and grains than from dairy products, though they also have a much lower calcium intake [6
]. In the United states and in Holland, 72 and 58% of calcium supply come from dairy products, respectively, whereas in China, only around 7% of total calcium intake comes from dairy products, while most comes from vegetables (30.2%) and legumes (16.7%) [7
] Fortified foods such as cereals and juices can additionally become important sources of calcium.
Supplements are also a great dietary source of calcium for some populations. Some calcium supplements, available with no prescription, have up to 1000 mg of calcium per tablet, which represents the nutritional requirements for most adults. However, the use of supplements also varies between countries. In the United States and Canada, around 40% of the adult population was reported to have taken calcium supplements in the month before the interview, and this figure increased to 70% in the older women group [3
]. On the other hand, in Argentina and in Holland, very few women reported taking calcium supplements, even during pregnancy [5
3. Calcium Recommendations
Calcium requirements are high during all stages of life [13
]. Dietary reference values for individuals over 19 years of age vary from 1000 mg to 1300 mg, depending on the reference guidelines [1
] (Table 1
The dietary reference values are established to account for the needs of growth, development, functioning and health maintenance [15
]. The requirements are calculated on the basis of a selected health outcome. The USA Institute of Medicine (IOM) conducted a review to assess the effect of calcium on health so as to update the dietary reference intakes for calcium in 2010 [2
]. The review finally recommended to base the requirements for calcium on its effects on bone health and concluded that the evidence of the effect of calcium on cancer, cardiovascular disease, diabetes and autoimmune disorders was inconsistent, inconclusive as to causality and insufficient to inform nutritional requirements [7
]. Besides, in order to establish calcium intake upper limits, the review evaluated the following clinical outcomes: all-cause mortality, cancer (incidence and mortality), soft tissue calcification, renal outcomes and adverse events reported in RCTs. No evidence of association was found in this report for mortality, soft tissue or cancer. An increased risk of renal stone [Hazard Ratio 1.17 (95% CI 1.02–1.34)] was reported in only one trial in women aged 50 to 79 years who received vitamin D3 400 IU supplements in combination with 1000 mg of calcium supplements [17
]. Of the 63 included RCTs, 10 reported adverse events, mainly related to higher gastrointestinal discomfort in the groups receiving calcium and or Vitamin D supplements. The upper limit was set to 2500 mg/day for people aged 19 to 50 years and to 2000 mg/day for older people.
During pregnancy, most guidelines acknowledge the increased demand of calcium; however, while some guidelines increase recommendations up to 1300 mg/day to achieve a positive balance, other guidelines state that metabolic adaptations during pregnancy compensate the required calcium demand [2
]. The IOM set in 2010 the dietary intake upper limit for pregnant women to 3000 mg/day for those aged 14 to 18 years and to 2500 for older ones [7
], whereas the FAO/WHO recommendation of 2001 acknowledged that the risk of kidney stones from dietary hypercalciuria might be negligible and set the upper limit to 3000 mg/day independent of age. Since 2013, WHO recommends that all pregnant women from areas of low dietary calcium intake receive calcium supplementation from 1500 to 2000 mg/day from 20 weeks´ gestation, as evidence from randomized control trials shows a reduction of the risk of preeclampsia [21
5. Calcium and Blood Pressure
Epidemiological studies associated dietary calcium with blood pressure in deprived communities of Guatemala [3
]. This population, with poor food intake and limited access to prenatal care, had an incidence of preeclampsia and eclampsia comparable to that of populations with higher resources [32
]. Despite having a diet short on nutrients, they had a relatively high intake of calcium. Their diet is based on corn tortillas prepared according to the Mayan tradition that consists of cooking corn with limestone and leave it to soak overnight in hot water [3
]. In this way, the grains of corn increase their calcium content, improving their nutritional value. After milling, the flour obtained from grains that underwent this process had an average of 196 mg of calcium per 100 g, while corn flour commonly contains between 10 and 15 mg of calcium per 100 g.
Observational studies also reported an inverse association between water hardness and cardiovascular diseases [33
]. Water hardness is determined by minerals in water, firstly calcium and secondly magnesium [36
]. In 1972, the WHO published a general review of these findings [37
]. However, later studies showed a weak or inconsistent relationship, possibly because the contribution of calcium from hard water to the total calcium intake was considerably smaller in the populations examined or because more significant risk factors of cardiovascular disease than that of a low dietary calcium intake existed [33
Studies in animals and humans have shown an inverse relationship between calcium intake and blood pressure [38
]. Normotensive rats fed a free-calcium diet significantly increased their systolic blood pressure (SBP) between 15 to 35 mmHg in comparison with rats fed a normal calcium diet [38
]. On the other hand, normotensive and hypertensive rats supplemented with calcium had significantly lower values of SBP [42
]. A systematic review has shown that calcium supplementation reduces SBP in normotensive adults by 1.14 mmHg (95% CI: −2.01 to −0.27) with doses of calcium of 1000 to 1500 mg/day and by 2.79 mmHg (95% CI: −4.71 to −0.86) with doses of calcium equal to or over 1500 mg/day [46
]. In this review, it was found that calcium supplementation had the greatest effect in young adults of less than 35 years, as their systolic blood pressure was reduced by 2.11 mmHg (95% CI: −3.58 to −0.64). A similar systematic review in hypertensive adults found that calcium supplementation reduced SBP by −1.86 mm Hg (95% CI: −2.91 to −0.81) and diastolic BP (DBP) by −0.99 mm Hg (−1.61 to −0.37). However, higher reductions were found in people with a relatively low calcium intake (less or equal to 800 mg/day), in which calcium supplementation reduced SBP by −2.63 (−4.03 to −1.24) and DBP by −1.30 (−2.13 to −0.47) [47
]. Another similar systematic review also showed that calcium supplementation as compared to control induced a statistically significant reduction of SBP (mean difference: −2.5 mmHg, 95% CI: −4.5 to −0.6, I2
= 42%) but not of DBP (mean difference: −0.8 mmHg, 95% CI: −2.1 to 0.4, I2
= 48%) [48
A systematic review that included 13 RCTs and 15730 pregnant women estimated that calcium supplementation compared to placebo reduced the high blood pressure relative risk (RR) to 0.65, (95% CI: 0.53 to 0.81) and, although with low quality of evidence, also the risk of preeclampsia by 55%, with RR 0.45, (95% CI: 0.31 to 0.65) [49
]. In populations with low calcium intake below 800 mg/day, the effect was even higher (RR 0.36, 95% CI: 0.20 to 0.65). A recent RCT has shown a reduction in the incidence of preeclampsia of 34% (RR 0.66, 95% CI: 0.44–0.98) in women supplemented with 500 mg/day of calcium before and in early pregnancy, comparing groups of women with good adherence to supplement intake, either calcium or placebo [50
]. Both groups received calcium supplementation corresponding to 1.5 g/day after 20 weeks´ gestation.
From the above information, it can be concluded that adequate calcium intake has many health benefits besides its favourable effects on bone health, and action should be taken to ensure an adequate calcium intake (Table 2
). The effect of calcium supplementation on pregnancy outcomes is the one with more evidence as it received more research attention. However, the effect of calcium supplementation on lowering blood pressure, particularly at an early age, is also very important for its impact on the prevention of cardiovascular complications later in life. Further studies are required to better understand the modeling effect of calcium intake during pregnancy on progeny blood pressure.
Other benefits of adequate calcium intake have been reported, such as higher bone mineral accretion at early ages and prevention of osteoporosis and colorectal cancer.
Many of the reported deleterious effects of calcium supplementation were recently reviewed, and previous results were questioned. A recent meta-analysis showed no effect on coronary heart disease or all-cause mortality risk in postmenopausal women supplemented with calcium. Long-term calcium supplementation did not show a detriment to iron status. The effect of calcium intake on renal stones formation was shown to be contradictory, and new evidence shows that a diet with an adequate calcium intake actually prevents the formation of calcium stones.
Of concern are the calcium resorption outcomes reported in the follow-up of Gambian women that had received calcium supplementation during pregnancy. Whereas other trials have shown opposite results to those of the Gambian study, more research on the effects of calcium supplementation on bone health after lactation is required to better understand these particular findings.
All this evidence suggests that every subject should attain an adequate calcium intake. Inequities in calcium intake are striking. Strategies to improve calcium intakes should be evaluated according to the target population.
Individuals with low calcium intake should be counselled on the importance of calcium intake and guided on achieving an adequate intake, especially if belonging to high-risk groups such as children, adolescents and women (with emphasis on the reproductive period). Populations at risk of low calcium intake should be identified, and strategies should be designed according to each particular situation.
Efforts should be made to achieve calcium recommendations both at individual and global levels, and strategies will depend on the intake level of each population. Calcium intakes in low- and middle-income countries (LMICs) are extremely inadequate, and strategies should include the whole population; however, even in high income countries, certain population groups such as pregnant women often do not meet the recommendations, and strategies should probably be targeted specifically to those groups.
Supplementing with calcium individuals that already reach the requirements has been shown to be of no benefit. Even in the NICHD/NIH study that showed no overall effect of calcium supplementation in women with high basal intake (mean 1114 mg/day), there was a tendency towards a lower incidence of preeclampsia according to the quintiles of basal calcium intake [101
]. A decrease in preeclampsia incidence, although not statistically significant, was observed in women in the quintiles of calcium intake below the requirements [101
Another point to discuss regards the amount of calcium these strategies should provide to achieve an adequate intake. Theoretically, this amount should be determined after assessment of each specific population. A review of calcium intake during pregnancy showed an average difference in calcium intake of around 400–500 mg/day between LMICs and HICs. WHO guidelines recommend calcium supplementation of 1.5 to 2 g/day to pregnant women from populations with low basal intake; however, a newer review showed that supplementation with 500 mg/day of calcium during pregnancy had effects similar to those of supplementation with higher doses [102
There are three broad approaches to improve dietary calcium intake: one is a behavioural intervention that, although ideal, relies on personal habits and abilities, the second one is supplementation that targets individuals, and the third one is food fortification that aims at improving the dietary intake of a whole population. Recommendations to improve dietary calcium intake by increasing the consumption of calcium-rich foods and/or taking calcium supplements have been around for many years; however, these recommendations have shown little impact in LMICs.
Supplementation strategies, though well-evaluated in research studies, have many limitations for implementation in LMICs, such as end user costs, poor access to the health system and low long-term compliance. In addition, some deleterious effects discussed above, such as post-partum bone resorption, gastrointestinal discomfort and cardiovascular effects on adult women, as well as some drug interactions have been reported in subjects taking calcium supplements.
Food fortification looks like as a promising approach, since it can reach different age groups for a long period of time and, if properly designed, does not require changing the dietary habits or taking pills, which allows to reach populations outside the healthcare system.
The calcium dietary intake gap between LMICs and HICs is around 400–500 mg/day, a feasible amount to achieve with food fortification. Taking into account the benefits shown during pregnancy on mother and foetus and the benefits on bone mineral accretion and prevention of bone loss, it can be assumed that achieving an adequate calcium intake at population level would imply long-lasting benefits and will reduce the differences in many health outcomes between LMICs and HICs.
Food fortification has been used for more than 80 years [103
]. Mandatory food fortification has contributed to health improvement, lowering the incidence of goitre, beriberi and pellagra. Currently, more than 130 countries have mandatory micronutrient fortification of salt, and around 85 have mandatory micronutrient fortification of wheat flour. WHO evaluation of food fortification nutrition interventions recommends the fortification of maize flour with iron and folic acid and the fortification of salt with iodine and iron powders [104
]. Improved zinc, vitamin A, folic acid, vitamin D and calcium deficiencies at population level were also achieved by fortifying different staple foods. Besides fortification, the restoration of micronutrients naturally present in foods that are removed during industrialization processes, such as vitamin B complex in maize flour, is used. The restoration of calcium to wheat flour has been used in the UK since 1943. However, despite this vast experience, food fortification products are not always accessible to the low socioeconomic groups, and strategies should be developed to reach them [103
Most experiences include staple food fortification, as they are generally consumed in good amounts, and research is required to determine the best staple food to be fortified for each specific population. On the other hand, water fortification looks promising, since water is universally consumed and taking into account the global obesity figures water does not imply any change in energy intake.
Ecological studies have found an inverse relationship between water hardness and cardiovascular mortality [33
]. Calcium bioavailability from calcium-rich waters is similar to that of milk [13
]. Water fortification with calcium would in some way mimic the situation of populations drinking hard water. Although there are some studies on this topic, more research is required. Studies on water fortification include examples of fortification of public water supplies with fluoride to prevent dental cavities that have been implemented for more than 50 years in more than 25 countries; however, most evidence of its effects comes from observational studies [108
]. There are some studies in Asia regarding iodized water; however, as iodine has limited stability, this strategy is not always cost-effective [103
]. Iron and ascorbic acid water fortification to prevent iron deficiency anaemia has been explored and, although successful, is still being researched [112
It has been estimated that in LMICs, improved drinking water can reach the majority of urban areas (92%), and 70% of the urban population has access to piped water within their household. In contrast, in rural areas, only 25% of the population has access to this type of service [114
]. Research into the feasibility of calcium-fortified water deserves to be considered, taking into account different water supplies.