Summary : The consumption of calcium helps to reduce the risk of suffering from osteoporosis, hypertension, cancer, kidney stones and obesity. Studies have shown that calcium supplementation increases or prevents the loss of bone mass, which is vital for the prevention of osteoporosis. Studies have also shown the positive impact of calcium in the regulation of blood pressure and in the prevention of colon, breast and ovarian cancer, possibly through its participation in cell division. A diet high in calcium helps prevent kidney stones by decreasing oxalate absorption and recently, it has been suggested that it can also help in weight control, decreasing lipogenesis and increasing lipolysis. The protective effect of calcium is evident in the recommended levels of calcium intake for most of the population, that is, between 1000 and 1300 mg of calcium per day.
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Summary : Intake of dietary calcium decreases the risk of osteoporosis, hypertension, cancer, kidney stones, and obesity. Studies have shown that calcium supplementation increases bone mass and prevents its loss, which is crucial in the prevention of osteoporosis. Likewise, studies have confirmed the impact of calcium in the regulation of blood pressure and in the prevention of colon, mammary and ovary cancer, possibly through its action in cellular division. A diet rich in calcium can also help against kidney stones by reducing oxalate absorption, and recently, it has been suggested that a diet rich in calcium can help in weight management, reducing lipogenesis and increasing lipolysis. The protective effects of calcium are seen within the levels actually recommended for the population, which are between 1000 and 1300 mg per day of calcium.
Introduction
Calcium is a nutrient that is involved in the prevention of chronic diseases, such as osteoporosis, high blood pressure, colon, breast and ovarian cancer, kidney stones and obesity. The association between calcium and these diseases has its explanation in the variety of functions that this nutrient fulfills in the organism. Calcium is the most abundant mineral in the human body where it forms part of the teeth and bones, where it represents up to 40% of the mineral content. Calcium is also considered a second messenger, because it acts both as a signal transmitter from outside the cell inward, as an activator of proteins involved in this process. In this way, calcium is found involved in the secretion of hormones, in the mediation of dilation and muscular and vascular contraction, as well as in neural conduction.
The following is a review of the evidence of the role of calcium in chronic diseases such as osteoporosis, arterial hypertension, cancer, renal lithiasis, and obesity.
Calcium and osteoporosis
99% of calcium is found in bones and only 1% in blood, muscle, and other tissues. However, this small fraction has priority and the calcium contained in the bones constitutes a great reservoir from which it can be extracted at any time to keep the serum level of calcium constant if the dietary intake is low. If calcium intake is persistently low, the bones become increasingly fragile, which can lead to osteoporosis.
Osteoporosis is a chronic, multifactorial disease that can progress silently for decades until a fracture occurs. It is characterized by a low bone density and by a deterioration of the bone microarchitecture (1), which produces a greater vulnerability to suffer fractures, mainly in the wrist, hip and spine (2,3).
In the world more than 200 million people have osteoporosis, and according to projections, the number of hip fractures a year will increase from 1.66 million in 1990 to 6.26 million in 2050 (4). In Venezuela, the magnitude of the problem is not well known. According to a report in 1980, the incidence of hip fractures in> 45 years was 348 and 834 (5), and in 1988 the incidence in> 80 years was 193 and 381 (6), per 100,000 inhabitants, in men and women, respectively (5).
Osteoporosis is a juvenile disease, since it is in adolescence when most of the bone mass is acquired, which will determine if the person will be at risk of fractures in the coming years. Thus, at 17 years of age the female adolescent has acquired 90% of her bone mass, at 19.8 years 95% and at 22.1 years 99% of her bone mass (7). That is to say, after the age of 22, the woman basically has already formed her bone mass. Although the process of bone mass acquisition is 60-80% determined by the genetics of the individual, there are modifiable factors that affect this process, such as calcium intake, physical activity and lifestyle, among which, the Calcium intake is the one that has the greatest effect (8). If in adolescence the individual does not consume an adequate intake of calcium, it will not reach the maximum peak of bone mass and the individual will enter the adult stage with a bone density lower than its genetic potential (dotted line, Figure 1 ). When the period of rapid loss of bone mass begins, which corresponds to menopause, this individual could have fractures. The development of bone mass up to the maximum peak potential protects against osteoporosis, since there is an inverse relationship between bone mineral density and the incidence of fractures (9,10).
Studies in adolescents and children (11-14) and adults (15-18) have shown that calcium supplementation increases bone mass. Supplementation in identical twins (6-14 years) with 1612 mg / d of calcium significantly increased bone density compared to the group with a 908 mg / d calcium intake (12). Studies in American girls and Chinese children showed that calcium supplementation for 18 months resulted in a significant additional increase in density and total bone content over the control group (11,13). In adolescent girls, an increase of 35 g more in bone mineral content was observed with the supplementation of dairy products during one year compared with the control group (14). These effects are maintained only if the high calcium intake is constant, and not as a short intervention, since after one year of the intervention, the differences in bone density disappeared (19). It has been observed that if daily calcium intake remains high throughout childhood and adolescence, this results in high bone density of the radius in post-menopausal women.
Transversal and intervention studies in adults report a positive relationship between calcium intake and bone mass. A meta-analysis of 33 studies evidenced a significant correlation between calcium intake and bone density (21). It was concluded that the intake of 1 g / d of calcium can prevent the loss of 1% of bone / year in most regions of the body. In the first years of post-menopause, bone mass does not respond as much to calcium supplementation, since it is a stage of rapid bone resorption, however, if it favors those women with more than 5 years postmenopausal (22). In the elderly it has also been observed that the intervention with calcium favors the reduction of the fracture index (18).
Calcium and high blood pressure
High blood pressure is a public health problem that affects 20% -23% of adults in Venezuela (23). Blood pressure levels predict the mortality and morbidity of cardiovascular diseases (CVD), so any factor that lowers blood pressure is important at the population level.
After 20 years of controversy, the evidence confirms the positive impact of calcium and calcium-rich foods in the regulation of blood pressure, through 2 lines of research:
1. Epidemiological studies: The first study that systematically investigated the relationship between calcium and blood pressure was an epidemiological analysis of the relationship of 17 nutrients with blood pressure in Americans (24). Low calcium intake was the most consistent factor in individuals with hypertension and it was determined that high calcium intake was associated with low blood pressure and a low absolute risk of hypertension. Several meta-analyzes have shown a significant decrease in blood pressure with a high calcium intake (25-28). One of these analyzes showed that calcium from food was more effective in reducing blood pressure compared to supplements (29). In children this protective effect has also been seen, and it was determined that for each 100 mg increase in calcium intake, the systolic pressure was decreased by 2.27 mm Hg (30).
2. Clinical studies: There have been numerous studies, some have used calcium supplements as the source of the nutrient and other foods. Supplementation of 1 g / d of calcium for several weeks (31) or days (32) resulted in a significant decrease in blood pressure. It was recently observed that those with low habitual calcium intake benefited more from calcium supplementation (33), although not all studies show this (34,35). The results with the use of supplementation are not consistent, possibly to the use of a single isolated nutrient. This is why several studies have investigated the impact of calcium-rich foods, which are also good sources of magnesium and potassium, in blood pressure. In hypertensive patients, a 9-8% decrease in blood pressure was observed with the consumption of dairy products and calcium fortified juice for 6 weeks, compared with the control group. The "DASH" study (37) investigated the effect of 3 diets on blood pressure: 1) diet high in saturated fat and low in calcium (450 mg / d calcium); 2) diet rich in fruits and vegetables but low in calcium (450 mg / d calcium); and 3) diet rich in fruits and vegetables and dairy products low in saturated fat "combined diet" (1240 mg / d calcium). The combined diet significantly reduced blood pressure compared to the other two diets.
The interaction of calcium with other nutrients seems to be important in the control of blood pressure, such as the salt-calcium interaction. In black hypertensive patients consuming a diet low / high in calcium / sodium, an increase in blood pressure and in the levels of parathyroid hormone (PTH) was observed, especially in black individuals, which was abolished with the high diet in calcium (38). This racial difference was also found in girls when consuming a diet low (800 mg / d) or high (> 1300 mg / d) in calcium and low (1 g / d) or high (3.86 g / d) in sodium for 3 weeks (39). The urinary excretion of sodium ( Figure 2 ) and calcium excretion ( Figure 3 ) was significantly lower in black girls in the high sodium / low calcium combination, but when calcium was added to the diet, the racial differences disappeared. These racial differences may be the result of some mutation in the channels of calcium and sodium regulation at the renal level, which may be present in other groups with a high incidence of hypertension (40-42).
The mechanism by which calcium and sodium affect blood pressure is altering their regulatory systems (43). In the case of sodium, the renin-aldosterone system and in the case of calcium, vitamin D and PTH. These hormones in turn regulate free calcium in the cytosol, which participates as a second messenger in various reactions. A high level of free calcium in the cytoplasm increases smooth muscle contraction, catecholamine secretion and central nervous system activity and therefore increases blood pressure. A high intake of calcium keeps low free calcium in the cytoplasm because vitamin D and PTH do not increase, so blood pressure does not increase either.
Calcium is also involved in the prevention of pregnancy-induced hypertension (HIE). In Guatemala, a low incidence of eclampsia has been found and is explained by the high calcium intake (44). However, in Colombia and India a high incidence of eclampsia has been observed and in these populations it has been determined that the calcium intake is 250-350 mg / d. In Ecuador it was observed that supplementation with 2 g / d of calcium reduced blood pressure in pregnant adolescents (45). In a meta-analysis of 14 randomized studies with calcium supplementation in 2459 pregnant women, a significant decrease in blood pressure was observed (26).
Calcium and cancer
Cancer is the third cause of death worldwide. In the year 2000, around 7 million people died of cancer, which represents 12% of all deaths (46). Among the different types of cancer, colon cancer is the third cause of death and breast cancer is the fifth cause. In Venezuela in 2000 there were 922 cases and 499 people died of colon cancer, 442 cases and 282 people died of ovarian cancer, and 3400 cases and 1068 people died of breast cancer (47).
Epidemiological studies have shown that a high calcium intake decreases the risk of colon cancer and its recurrence. In studies with more than 100 thousand subjects it was determined that the intake of 1200 mg / d of calcium was associated with a lower risk and incidence of colon cancer (48), both in men (49) and in women (50). Longitudinal studies with numerous subjects with or without a history of colon cancer show that the consumption of more than 2 daily servings of calcium protects against recurrent colon cancer (51), especially if low-fat dairy products are consumed (52). which results in a low relative risk of colon cancer (53). However, not all studies have found this relationship (54,55).
Clinical studies have found a decrease in the proliferative activity of colonic cells with calcium intake (56,57). In subjects with a history of colorectal adenoma, supplementation with 1200 mg / d of calcium decreased the risk of recurrence by 19% (58).
The mechanism by which calcium seems to protect against colon cancer lies in the participation of calcium in cell division and in the regulation of cell proliferation and differentiation. A low level of intracellular ionized calcium contributes to cell proliferation while high concentrations decrease the proliferation of colonic cells (59). Alternatively, calcium precipitates bile and fatty acids in faeces (60), which are potentially toxic, whereas insoluble calcium salts are less toxic to the colonic mucosa. Calcium supplementation reduces the concentration of faecal bile acids (61). However, not all studies have shown these benefits (62-64).
Regarding breast cancer, it was found that a high consumption of dairy products was related to a low relative risk in young women (65), but not in post-menopausal women (66). In Uruguay it was found that low-fat dairy products, especially fermented products (yogurt), were linked to a lower risk of cancer, while high-fat dairy products (chocolate and yellow cheese) were at higher risk (67) .
Calcium intake has also been associated with the prevention of ovarian cancer. In women, a low relative risk was observed with a high consumption of low-fat dairy products versus those with low consumption (68), although others did not achieve this effect (69).
To observe the protective effect of calcium in cancer, it is not necessary to consume levels higher than those recommended for the general population, since studies have shown that higher levels of calcium (> 1200 mg / d) do not produce additional benefits (48 ).
Calcium and kidney stones
The incidence of renal lithiasis varies by region, being low in Asia (1% -5%), average in Europe (5% -9%) and North America (12% -13%) and high in the Middle East (20%) ) (70). In Venezuela, there are no national data on the incidence of kidney stones.
Kidney stones are formed when the urine is concentrated and the substances that normally are in it crystallize, such is the case of oxalate and calcium; so the first therapeutic measure against kidney stones would involve a reduction in calcium intake, however, there is evidence to the contrary. A study with more than 45 thousand men showed that high calcium intake decreased the risk of presenting kidney stones in 34% (2), with a low relative risk in those with a high calcium intake compared with those who consumed <850 mg / d of calcium. In women it was also observed that a high calcium intake decreased the risk of kidney stones, but only if calcium came from food, since the use of calcium supplements was positively associated with the risk of kidney stones, especially those who consumed calcium. supplement without food (71). Foods rich in calcium (dairy products) may contain other substances that help reduce the risk.
It has been suggested that the mechanism by which calcium prevents kidney stones is in the interference of intestinal absorption of oxalate (72). Clinical studies show that calcium binds to oxalate at the intestinal level, making it less available for absorption, which leads to a lower oxalate content in the body and therefore to a lower excretion of oxalate in the urine (73,74 ). The high concentration of oxalate in the urine is what causes the calculation.
Calcium and obesity
Obesity is an epidemic worldwide. It is estimated that more than 1 billion people are overweight and at least 300 million people are obese (75). Recently, high calcium intake has been related to a decrease in body weight due to its relationship with the control of fat metabolism. The first study to demonstrate this association was an epidemiological study in women, where those with a high calcium intake (> 1300 mg / d calcium), presented a low relative risk (0.16) of having high body fat compared to those with an intake less than 300 mg / d of calcium (76). In young women it was observed that a high calcium intake with respect to total calories significantly decreased body fat (> 3 kg) compared to women with a low calcium / kcal intake (77). In children aged 5 to 6 years, there was also a significant decrease in body fat (2 kg) consuming 1200 mg / d versus those who consumed 500 mg / d (78) and in children aged 7 to 10 years it was determined that the low Ingestion in calcium was found to be one of the predictors of obesity (79).
Clinical studies have also shown this effect. The consumption of 2 cups of yogurt per day for 12 months resulted in a total decrease of 4.9 kg of body fat at the end of this period in obese (76). Obese subjects assigned to a diet exclusively based on dairy products lost 7.4 kg, while those with a mixed diet lost only 1.4 kg in 4 weeks (80). In a re-analysis of several studies in women it was determined that for every 1000 mg of difference in calcium intake there was 8 kg of difference in body weight (81).
The effect of calcium on weight control seems to be more effective with the consumption of dairy products compared to the use of calcium supplements, possibly due to the presence of other bioactive compounds, although there are no studies in humans (82). In obese mice, a greater decrease in body weight and fat mass was observed with a mixed diet based on dairy products versus the diet with calcium supplement (83).
The mechanism by which calcium influences weight control and body fat lies in the regulation of intracellular fat metabolism. Apparently, a diet low in calcium leads to a decrease in serum calcium, which increases intracellular calcium in the adipocytes, resulting in an increase in lipogenesis and decreased lipolysis, and therefore, fat accumulation. Conversely, a diet high in calcium suppresses intracellular calcium, increasing thermogenesis and reducing fat accumulation.
In conclusion, dietary calcium helps protect against chronic diseases such as osteoporosis, high blood pressure, cancer, kidney stones and obesity. Calcium from food, especially dairy products, seems to be more effective in preventing these diseases, possibly due to the interaction with other nutrients present in these foods. To observe the protective effect of calcium against these diseases, it is not necessary to recommend high calcium intakes, since its protective effect is evident at the levels recommended for most of the population, that is, between 1000 and 1300 mg of calcium per day. However, adequate calcium intake for preventive purposes should be maintained over time and not as a punctual intervention.