Calcium

Calcium is the fifth most abundant element in the earth's crust and is therefore widespread in waters, rocks, soils and living organisms. 

In animal foods, calcium is readily available in milk and dairy products in significant amounts, while other animal foods do not contribute significantly to dietary intake. Depending on the degree of hardness, drinking water can also supply considerable amounts of calcium and contribute to meeting daily requirements. 

Some vegetables such as kale, fennel and broccoli as well as various nuts such as almonds, Brazil nuts and hazelnuts are also considered rich in calcium. The following rule can be used for a rough estimate of the calcium content of vegetable foods: leaves > stems > roots > seeds. However, the usability of calcium from plants is limited because compounds such as phytates, oxalates and dietary fibers inhibit absorption. Cooking, watering and blanching can further reduce the calcium content of vegetables. 

The availability of dietary calcium is also impaired by phosphorus and fat. On the other hand, vitamin D, some sugars (lactose, inulin), amino acids and fruit acids promote the absorption of calcium into the body. 

Calcium absorption in the duodenum and jejunum is predominantly achieved by an active, transepithelial process, where the mineral is passed through the membranes of the intestinal cells with the aid of a calcium-binding protein (calbindin). Vitamin D, which induces the formation of calbidine, is of central importance for this process. In the absence of vitamin D, calcium can also diffuse passively through the intestinal wall, but this process is insufficient to meet demand (1). Calcium is absorbed better at lower doses (below 500 mg) and should be taken between meals for optimal absorption (1). 

Most calcium (99%) is stored in the bone as a structural agent. In serum, ionized calcium is the predominant form of the mineral in addition to albumin-bound calcium. The calcium concentration of the plasma is kept within a relatively narrow range (2.20 – 2.65 mmol/l). Regulation takes place via several hormone systems. The mobilization of calcium from the skeletal system is promoted by the parathyroid hormone and inhibited by calcitonin and estrogens. In order to counteract bone reabsorption during the night, intake of calcium in the evening is advised (2). 

The biological availability of mineral compounds poses a general challenge for both dietary and therapeutic supplementation. Citrate compounds of calcium demonstrate much better absorptionin clinical trials than, for example, corresponding carbonates (3) (4). Calcium citrate also provides alkaline equivalents that neutralize excess acids in the blood (2). Acidosis promotes the physicochemical release of alkaline bone minerals, which can lead to a decrease in bone density (5). In addition, citrate compounds counteract the risk of stone formation (6)

Adequate dietary intake of calcium is often not achieved. Both the German and Austrian Nutrition Reports identify calcium as a "high-risk nutrient" for which there is an urgent need for action in health policy (7). The results of the 2012 German National Nutrition Survey confirm earlier data. Calcium intake in all age groups is below the recommended intake. The average calcium intake in middle aged groups is higher than in children/youth and seniors (8). 

The consequence of inadequate calcium supply is suboptimal bone density, which manifests itself in premature onset of osteoporotic changes in old age. An insufficient calcium status (hypocalcemia) detected in the serum requires an investigation of differential diagnoses (parathyroid hormone, vitamin D metabolites), since the causes can be manifold. According to the nutrition report 2012, the average calcium intake in all population groups in Austria is far below the recommended values. Women average of 860 mg and men 891 mg of the recommended 1000 mg of calcium per day (adults between 18 and 64 years). is the inadequacy is even clearer for children: 86.1% of girls and 77.5% of boys do not reach the recommended level of 1200 mg/day. The same applies to vitamin D, which is closely related to calcium metabolism (7) (9). Vitamin D promotes the absorption of calcium in the intestine and increases storage in the bone structure. 

Calcium is particularly important in periods of bone formation. The highest bone density and bone mass are reached by approximately the age of 30 (Peak Bone Mass, PMB). Afterwards, the bone continuously loses mass, which increases the risk of bone fractures. An inadequate calcium supply, especially in connection with a marginal vitamin D status in younger years, leads to an increased risk of osteoporosis in old age. Targeted supplementation in adolescents and young adults can not only increase peak bone mass, but also reduce the occurrence of fractures caused by overloading (fatigue fracture) (10). Targeted substitution of calcium and vitamin D is generally considered an effective measure for building and maintaining bone mass (11) (12). 

During growth phases, bone size, stability and density increase continuously. By the age of 20, approx. 90 % of the maximum bone mass is deposited. If peak bone mass is already low in young adults, the natural degradation processes caused by age very quickly lead to osteoporosis. Therefore, supplementation of nutrients that promote bone health is appropriate at an early age, especially in children and adolescents with poor diets. In older people, therapeutic intervention attempts to reduce the rate of bone degradation and to improve and maintain stability. The benefit of supplements in this indication framework has been established and is no longer questioned.

According to WHO, osteoporosis is one of the ten most common diseases worldwide. The main victims are post-menopausal women and people over 70 years of age. In Germany, each year approximately 2.8 million vertebral fractures and 1,300,000 femoral neck fractures are caused by osteoporotic changes in bone stability. For those affected, osteoporosis is synonymous with a loss of quality of life, including disability, immobility and loss of independence. One-year mortality after fractures of the hip joint is around 25%. Osteoporosis is a systemic skeletal disease characterized by a reduction in bone mass and disorders in the microarchitecture of bone tissue with increased tendency to fracture. Osteopenia is a preclinical, incipient osteoporosis without fractures. Osteoporosis is a multifactorial disease, which can be caused by genetic influences as well as by malnutrition, physical inactivity and hormonal disorders. Nutritive calcium deficiency is the main pathogenic factor for insufficient bone stability, but other nutrients are essential for sustainable skeletal development and the maintenance of bone mass (2). 

The prevalence of osteoporosis and fractures of fragility increases in women and men over the age of 60 and increases exponentially after the age of 75. An adequate intake of calcium and vitamin D can at least partially prevent the occurrence of bone fractures in existing osteoporosis (13). Evidence-based data show that a daily intake of 700-800 mg calcium and 400 I.U. vitamin D (= 10µg vitamin D) is a cost-effective and safe method to reduce fracture frequency in the elderly (14). This also applies to men, who are less frequently affected by osteoporosis than women (> 50 %) with 15 - 25 % risk, but in whom the mortality rates associated with fractures are about three times higher than in women (15). Calcium and vitamin D supplementation can also reduce bone loss in postmenopausal women (16).

The processus alveolaris maxillae, which forms the basic framework for the dental alveoli, is also affected by osteoporotic changes. It is now established that the loss of bone mass in the jaw correlates with periodontosis and resulting loss of teeth (17). A deterioration in skeletal bone mass, especially after menopause, is also reflected in a loss of mass of the alveolar bones and a decrease in tooth retention capacity (18). In menopausal women with diagnosed osteoporosis, there is also a marked reduction in the height of the alveolar crest between alveloli(19). Therefore, targeted, long-term supplementation with micronutrients for the dietary treatment of osteoporosis also strengthens the periodontium and can effectively counteract osteoporosis-related tooth loss (20). Conversely, women who do not supplement calcium are 54% more likely to develop periodontal disease than women who take additional calcium daily (21). 

Calcium, and its antagonist magnesiu,m stabilize the excitation potential in the heart muscle. Both hypocalcemia and hypomagnesemia can lead to cardiac arrhythmia, tachycardia and changes in the cardiac signal system. Through appropriate supplementation, the electrolyte balance can be harmonized and normal, effective neuromuscular activity and function of the heart muscle is ensured (23). A reduced calcium outflow from the endoplasmic reticulum also appears to play a significant role in heart failure, although the underlying cause is still unclear (24). A heart muscle spasm, which can lead to angina pectoris and heart attack, is associated with an unbalanced calcium/magnesium ratio. Cardiac arrhythmias respond well to calcium and magnesium (25). 
Hypertensive patients often have low plasma calcium concentrations. A slight reduction in blood pressure has been achieved by supplementation in intervention studies (1). 

Latent acidosis triggers a variety of metabolic and endocrine abnormalities. It leads to a loss of nitrogen, which can impair protein metabolism. Endocrine systems are also directly and indirectly affected. For example, in acidosis there is a decrease in IGF-1 levels due to a reduction in the sensitivity of peripheral growth hormones and a mild form of primary hypothyroidism and hyperglucocorticoidism (26). Several studies have shown that latent acidosis can have a negative effect on bone health. It is believed that this effect is due to the physicochemical release of bone minerals when the intracellular pH decreases (27). Chronic acidosis leads to a negative calcium balance and an increased loss of bone density. In contrast, it was shown that an increase in the supply of alkalizing potassium compounds leads to higher axial and peripheral bone density and correlates with a lower rate of bone turnover (28). Hypercalciuria caused bya negative calcium balance in bone metabolism can also increase a tendency toward kidney stones (29). Clinical studies confirm the observations of many therapists that there is a connection between latent acidosis and chronic inflammatory diseases. Reduced alkaline buffer reserves correlate with higher levels of inflammatory biomarkers (30). An increased intake of alkaline substances also demonstrated good results as an adjuvant therapeutic measure. For example, supplementation with alkalising mineral compounds significantly reduced disease activity and pain in patients with rheumatoid arthritis(31). Decreased alkaline buffer reserves correlate with the occurrence of insulin resistance in diabetes mellitus type 2 diseases (32) and with elevated blood pressure values (33). An increased acid load leads to an increased risk of high blood pressure (34).

The recommended intake of 1000 mg per day for pregnant women is no higher than for women who are not pregnant, but inadequate calcium intake during pregnancy increases the risk of gestosis and eclampsia (1). Calcium supplementation can significantly reduce this risk (35). During pregnancy, approximately 30 g of calcium is mobilized from the maternal bone system (28) to meet the unborn child's calcium requirements and ensure sufficient mineralization of the skeleton. The increased release of calcium leads to bone loss rates of 4.8 to 5.1% during pregnancy and is therefore similar to those during menopause (36). Particularly in the case of aversion to milk and dairy products, lactose intolerance, low molecular weight heparin therapy or chronic autoimmune diseases, calcium supply should be regarded as critical, so supplementary intake is advisable (37). In women with low calcium intake, additional calcium supplementation during pregnancy is also associated with a lower risk of hypertension (37). Studies also show that additional calcium intake reduces lead levels increased by bone resorption and subsequently fetal lead exposure (38). 

The relative risk of pregnancy-induced hypertension and pre-eclampsia is significantly increased in pregnant women with low calcium intake and in certain subgroups (adolescents, existing hypertension, previous pre-eclampsia). A systematic review evaluating 12 studies on calcium supplementation and pre-eclampsia prevention showed that pregnant women with an increased risk of pre-eclampsia and women with a low calcium intake can benefit from supplementation of at least 1 g/d (35). 

Studies document that both calcium and magnesium have a soothing effect in PMS. In a recent review, the evaluation of randomized controlled trials confirmed that taking calcium improves the symptoms of PMS (39). Magnesium also has an effect. Women suffering from PMS are often diagnosed with low intracellular magnesium levels. In a pilot study, 3 months of magnesium supplementation at 250 mg/d resulted in a highly significant 35% improvement in symptoms (40). This confirms previous clinical data in which supplemental magnesium intake led to an improvement in mood swings and other PMS symptoms according to the Menstrual Distress Questionnaire Score (41).

Epidemiological data show that a high calcium intake can reduce the risk of colon cancer. It has been experimentally demonstrated that calcium inhibits the growth of colon carcinomas and inhibits cell proliferation of the colonic mucosa and the formation of colorectal adenomas. In addition to the ability to form insoluble lime soaps with fatty and bile acids, a direct effect of calcium on tumor cells is also discussed (1).

The marine algae Lithothamnium coralloides uses calcium and trace elements to build its structures. A standardized, branded, raw material (30 % calcium) of dried and ground lithothamnium coralloides is available in Austria and Germany under the brand name AlgaeCal®. Two clinical studies have shown that calcium from plant algae (in combination with vitamins and trace elements) can increase bone density (42). In a comparative study on osteoblasts, AlgaeCal® was clearly superior to the salt compounds calcium carbonate and calcium citrate (44).

Original Okinawa sango coral calcium contains only sango coral calcium from Okinawa and is obtained by grinding fossilised sea corals. Corals are mined in strict compliance with the guidelines for the protection and conservation of coral reefs. Only the fossil coral sediments discarded by the live coral are used for the preparations, the living coral reefs in Okinawa are not damaged. 
In contrast to commercially available coral calcium, original Okinawa sango coral powder is mined in a precisely defined underwater area in order to achieve a special mineral distribution. Corals growing just below the surface of the sea contain relatively high amounts of calcium. Fossil sango corals, on the other hand, provide calcium and magnesium in a physiological ratio of 2: 1 and are thus suitable for the targeted natural supplementation of both elements. In addition to calcium and magnesium, corals absorb other trace elements and minerals from seawater during their lifetime and incorporate them into their structures. This makes them a rich source of a wide variety of biologically important substances. Sango coral powder contains over 70 different trace elements, including aluminum, vanadium, tin and nickel, whose essentiality for humans is currently under discussion. Studies have also shown that coral calcium is absorbed much better by humans than other calcium compounds (45).

Calbon® N is a clinically tested premium quality raw material for nutritive cocomitant therapy in osteoporosis and osteopenia. Calbon® N contains standardized amounts of calcium and phosphorus bound in natural protein structures. Both elements are part of the hydroxyapatite of the bone and thus play a significant role in the development of the skeletal system. Clinical studies with protein-bound Ca/P complexes have shown that these have a better effect on bone density than calcium alone. 
The therapeutic efficacy of Calbon® N is confirmed in clinical studies. In a placebo-controlled double-blind study of post-menopausal women with osteopenia, a daily intake of 500mg of a standard calcium preparation was not found to stop bone density reduction. However, the administration of Calbon® N (500 mg/d, P 224 mg/d) increased the bone density in this group by 0.5 % compared to the initial value (46). 

1) Hahn, A. et al. 2006. Ernährung. Physiologische Grundlagen, Prävention, Therapie.
2) Gröber, U. 2006. Osteoporose – Risikomanagement mit Vitalstoffen. Zs f Orthomol Med. 1:6–12.
3) Kenny, A. M. et al. 2004. Comparison of the effects of calcium loading with calcium citrate or calcium carbonate on bone turnover in postmenopausal women. Osteoporosis International 15, Nr. 4 (January): 290–294. doi:10.1007/s00198-003-1567-0.
4) Walker, A. F. et al. 2003. Mg citrate found more bioavailable than other Mg preparations in a randomized, double-blind study. Magnes Res. 16(3):183-91.
5) Arnett, T. 2003. Regulation of bone cell function by acid–base balance. Proceedings of the Nutrition Society 62, Nr.02:511–520. doi:10.1079/pns2003268.
6) Gröber, U. 2002. Orthomolekulare Medizin. Ein Leitfaden für Apotheker und Ärzte.
7) Bundesministerium für Gesundheit und Frauen. 2012. Österreichischer Ernährungsbericht.
8) Max Rubner Institut für Ernährung und Lebensmittel. 2012 Ergebnisse der Nationalen Verzehrsstudie II – Basisauswertung II.
9) Gennari, C. 2001. Calcium and vitamin D nutrition and bone disease of the elderly. Public Health Nutrition 4, Nr. 2b. doi:10.1079/phn2001140.
10) Bouillon, R. 2008. How effective is nutritional supplementation for the prevention of stress fractures in female military recruits? Nature Clinical Practice Endocrinology & Metabolism 4, Nr.9:486–487. doi:10.1038/ncpendmet0897.
11) Rodríguez-Martínez, M. et al. 2002. Role of Ca(2+) and vitamin D in the prevention and treatment of osteoporosis. Pharmacol Ther. 93(1):37–49.
12) Cranney, A. et al. 2007. Effectiveness and safety of vitamin D in relation to bone health. Evid Rep Technol Assess (Full Rep). (158):1–235.
13) Robert Koch Institut; Statistisches Bundesamt. 2006. Gesundheit in Deutschland.
14) Rabijewski, M. et al. 2008. Pathogenesis, diagnosis and treatment of osteoporosis in men. Pol Merkur Lekarski. 24(139):76–80.
15) Shea, B. et al. 1998. Calcium supplementation on bone loss in postmenopausal women. The Cochrane Database of Systematic Reviews (February). doi:10.1002/14651858.cd004526.
16) Tezal, M. et al. 2000. The Relationship Between Bone Mineral Density and Periodontitis in Postmenopausal Women. Journal of Periodontology 71, Nr. 9: 1492–1498. doi:10.1902/jop.2000.71.9.1492.
17) Wactawski-Wende, J. 2001. Periodontal Diseases and Osteoporosis: Association and Mechanisms. Annals of Periodontology 6, Nr. 1: 197–208. doi:10.1902/annals.2001.6.1.197.
18) Wactawski-Wende, J. et al. 2005. The Association Between Osteoporosis and Alveolar Crestal Height in Postmenopausal Women. Journal of Periodontology 76, Nr. 11-s: 2116–2124. doi:10.1902/jop.2005.76.11-s.2116.
19) Krall, E. A. et al. 2001. Calcium and vitamin D supplements reduce tooth loss in the elderly. The American Journal of Medicine 111, Nr. 6: 452–456. doi:10.1016/s0002-9343(01)00899-3.
20) Nishida, M. et al. 2000. Calcium and the Risk For Periodontal Disease. Journal of Periodontology 71, Nr.7:1057–1066. doi:10.1902/jop.2000.71.7.1057.
21) Laver, D. R. et al. 2004. Luminal Ca2 –regulated Mg2 Inhibition of Skeletal RyRs Reconstituted as Isolated Channels or Coupled Clusters. The Journal of General Physiology 124, Nr.6:741–758. doi:10.1085/jgp.200409092.
22) Niestroj, I. 2000. Praxis der orthomolekularen Medizin. Physiologische Grundlagen, Therapie mit Mikro-Nährstoffen.
23) Kubalova, Z. et al. 2005. Abnormal intrastore calcium signaling in chronic heart failure. Proceedings of the National Academy of Sciences 102, Nr. 39: 14104–14109. doi:10.1073/pnas.0504298102.
24) Bo, S. et al. 2008. Role of dietary magnesium in cardiovascular disease prevention, insulin sensitivity and diabetes. Current Opinion in Lipidology 19, Nr. 1: 50–56. doi:10.1097/mol.0b013e3282f33ccc.
25) Wiederkehr, M. R. et al. 2004. Correction of metabolic acidosis improves thyroid and growth hormone axes in haemodialysis patients. Nephrology Dialysis Transplantation 19, Nr. 5: 1190–1197. doi:10.1093/ndt/gfh096.
26) Arnett, T. 2008. Extracellular pH regulates bone cell function. J Nutr. 138(2):415S–418S.
27) New, S. A. et al. 2004 Lower estimates of net endogenous non-carbonic acid production are positively associated with indexes of bone health in premenopausal and perimenopausal women. AmJ Clin Nutr. 79:131-8.
28) Kenny, J. E., Goldfarb, D.S. 2010 Update on the pathophysiology and management of uric acid renal stones. Curr Rheumatol Rep. 12(2):125-9.
29) Farwell, W. R, Taylor, E. N.2010 Serum anion gap, bicarbonate and biomarkers of inflammation in healthy individuals in a national survey. CMAJ. 182(2):137-41.
30) Cseuz, R. M. et al. 2008. Basische Mineralstoffsupplementierung vermindert Schmerz bei Patienten mit Rheumatoider Arthritis: eine Pilot Studie. The Open Nutrition Journal. 100-105.
31) Farwell, W.R., Taylor, E. N. 2008. Serum bicarbonate, anion gap and insulin resistance in the National Health and Nutrition Examination Survey. Diabet Med. 25(7):798–804.
32) Taylor, E. N. et al. 2007. Serum anion gap and blood pressure in the national health and nutrition examination survey. Hypertension. 50(2):320-4.
33) Forman, J. P. et al. 2008. Association between the serum anion gap and blood pressure among patients at Harvard Vanguard Medical Associates. J Hum Hypertens. 22(2):122-5.
34) Hofmeyr, G. J. et al. 2007. Dietary calcium supplementation for prevention of pre-eclampsia and related problems: a systematic review and commentary. BJOG. 114(8):933-43.
35) Ettinger, A. et al. 2007. Dietary calcium supplementation to lower blood lead levels in pregnancy and lactation. J Nutr Biochem. 18(3):172–178.
36) Beinder E. 2007 Calcium-supplementation in pregnancy--is it a must? Ther Umsch. 64(5):243-7.
37) Ettinger, A. S. et al. 2009 Effect of calcium supplementation on blood lead levels in pregnancy: a randomized placebo-controlled trial. Environ Health Perspect. 117(1):26–31. Epub 2008 Sep 2.
38) Whelan, A. M. et al. 2009. Herbs, vitamins and minerals in the treatment of premenstrual syndrome: a systematic review. Can J Clin Pharmacol. 16(3):e407-29.
39) Quaranta, S. et al. 2007. Pilot study of efficacy and afety of a modified-release magnesium 250 mg tablet for the treatment of premenstrual syndrome. Clin Drug Investig. 27(1):51-8.
40) Facchinetti, F. et al. 1991. Oral magnesium successfully relieves premenstrual mood changes. Obstet Gynecol. 78(2):177-81.
41) Kaats, G. R. et al. 2011. A Comparative Effectiveness Study of Bone Density Changes in Women Over 40 Following Three Bone Health Plans Containing Variations of the Same Novel Plant-sourced Calcium. Int J Med Sci. 8(3):180–191.
42) Michalek, J. E. et al. 2011. Changes in total body bone mineral density following a common bone health plan with two versions of a unique bone health supplement: a comparative effectiveness research study. Nutrition Journal. 10: 32.
43) Adluri, R. S. et al. 2010 Comparative effects of a novel plant-based calcium supplement with two common calcium salts on proliferation and mineralization in human osteoblast cells. Mol Cell Biochem. 340(1–2):73-80.
44) Ishitani, K. et al. 1999. Calcium absorption from the ingestion of coral-derived calcium by humans. J Nutr Sci Vitaminol. 45(5):509-17. 
45) Calbon®-N prevents loss of Bone Mineral Density. University of Hull. SON.DSH_14.057.EN.03
46) Salamone, L.M. 1996. The association between vitamin D receptor gene polymorphisms and bone mineral density at the spine, hip and whole-body in premenopausal women. Osteoporos Int. 6(1):63-8. 

References Interaktionen
Stargrove, M. B. et al. Herb, Nutrient and Drug Interactions: Clinical Implications and Therapeutic Strategies, 1. Auflage. St. Louis, Missouri: Elsevier Health Sciences, 2008.
Gröber, U. Mikronährstoffe: Metabolic Tuning –Prävention –Therapie, 3. Auflage. Stuttgart: WVG Wissenschaftliche Verlagsgesellschaft Stuttgart, 2011.
Gröber, U. Arzneimittel und Mikronährstoffe: Medikationsorientierte Supplementierung, 3. aktualisierte und erweiterte Auflage. Stuttgart: WVG Wissenschaftliche Verlagsgesellschaft Stuttgart, 2014.