Calcium and Cardiovascular Risk Updates: The Bare Bones
By Luke Fortney, MD
Family and Integrative Medicine, Sauk Prairie Healthcare, River Valley Clinic, Spring Green, WI
Dr. Fortney reports no financial relationships relevant to this field of study.
SUMMARY POINTS
- Calcium is an essential part of a healthful diet, and research updates in the past year confirm recommendations that adults receive 1,000 mg per day.
- Serum vitamin D levels in the range of 40-80 ng/mL promote and are essential for efficient calcium absorption in the gut.
- From a cardiovascular perspective, calcium supplementation is safe, but excessive doses (> 2,500 mg per day) should be avoided, particularly among men and women with active cardiovascular disease and increased cardiovascular risk factors.
- Caution should be used in elderly women with history of stroke because of the increased risk of dementia by avoiding excessive calcium intake (> 1,000 mg/day).
- Calcium supplement selection should be based on cost, accessibility, and patient preference, noting that most forms of calcium supplements are absorbed relatively equally as long as it is taken with food at ≤ 500 mg at different times of the day.
Calcium is a well-known, little-maligned substance that has a long and important history in terms of health and disease. Interestingly, it is the fifth most common mineral on Earth, and is a vital component of both plant and animal life. Although nearly all the calcium in the body (> 99%) is retained in the bones and teeth, it plays a significant role in the function and diseases of the muscles (skeletal and smooth), nerves, cardiovascular, gastrointestinal, and renal systems. As a nutrient, it is one of the most recognized by the public for its use for osteoporosis and bone health, where it continues to be a grade A evidence-based recommendation for healthy bones when accompanied by exercise.1 However, its association with cardiovascular disease risk is a more recent example of the growing understanding of calcium’s role in our health. A number of recent updates over the past year (cardiovascular disease risk in particular) are noteworthy.
Brief History and Background
Osteoporosis (from the Greek word for “porous bones”) is the most commonly recognized disease associated with calcium deficiency and poor absorption/malnutrition. Long recognized by anthropologists who studied the remains of ancient civilizations, these early observations showed that loss of bone density and other associated structural changes were the first associations between chronic malnutrition and osteoporosis.2 However, it wasn’t until the mid-20th century that Fuller Albright, MD, made the link between a postmenopausal state and osteoporosis from a modern medical standpoint (hence, the Fuller Albright Award, which has been presented by the American Society for Bone and Mineral Research every year since 1981). Subsequently, bisphosphonate medications were discovered in the 1960s to help minimize osteoclast destruction of the skeletal system.
Although calcium plays a role in nearly every aspect of human metabolism, 99% of calcium deposits reside in the bones and teeth. However, with age — as well as with a host of other health problems, including alcoholism, anorexia, tobacco use, hyperthyroidism, malnutrition, and kidney disease — bone density decreases through a combination of accelerated bone loss and decreased bone repair. Women are most at risk because of lowered levels of estrogen after menopause. For these reasons, osteoporosis remains the top cause of bone fracture in the elderly.3
Although the underlying pathophysiology and risks associated with osteoporosis are relatively well understood, many questions remain in terms of prevention and treatment of advanced disease.
Calcium and the Heart
It would seem a simple conclusion that if osteoporosis and its sequelae are characterized by loss of bone mineralization (calcium in particular), then the logical solution would be to consume more calcium. However, like many things medical, it hasn’t been that straightforward.
For the past several decades, the standard recommendation for women of all ages has been to consume higher amounts of calcium, but research has been mixed regarding benefits in preventing and treating osteoporosis and osteopenia. Furthermore, the question of harm increasingly has come into play, with a body of literature revealing an association between coronary artery calcium deposition and cardiovascular disease.
Since the early days of X-ray technology, arterial calcium deposits have been observed. In the 1950s, when heart disease became more recognized as a significant cause of mortality in the United States, the association between arterial calcium and cardiovascular disease became more widely known, thanks to numerous publications about the growing ability to detect these calcifications with radiography.4
Fast-forward to today: Advances in CT technology using 256- and 320-slice scanners have led to the development of sensitive and accurate arterial calcium scoring in preventive cardiology, which is now used to help make treatment decisions for patients who have or are at risk for heart disease. This technological advancement is helpful in a clinical setting, given the fact that catheter-based angiography is expensive and carries some risk of serious complications because of its invasive nature (the more invasive the procedure, the higher the risks). From a risk/benefit perspective, up to half of all elective catheter-based interventions reveal no or insignificant coronary artery disease.5 Although it is now clear that calcium is a marker for diseased arteries,4 how and when to use this technology and how to interpret it clinically remain unclear. The United States Preventive Services Task Force concluded that the evidence currently is insufficient to fully assess the benefits and harms of coronary artery calcification scoring.6 From a cardiology perspective, CT angiography is a helpful tool in determining appropriate care and treatment in symptomatic patients who are at intermediate risk for coronary artery disease.7
Do No Harm
The question then looms, to what extent (if at all) does dietary/supplemental calcium intake factor into the risk/benefit discussion for 1) treating/preventing osteoporosis, and 2) contributing/advancing cardiovascular disease? This is especially pressing given that the top cause of death among women in the United States is heart disease (22.4%), while unintentional injuries (falls, fractures) ranks sixth at 3.8%.8
Although calcium remains a top-tier, grade A evidence-based part of osteoporosis treatment, questions have emerged regarding the possible contribution to coronary calcium deposits and advancing coronary artery disease. Three studies published in 2016 shed more light on the conflicting evidence regarding potential cardiovascular risks associated with high levels of calcium intake. The first by Chung et al reanalyzed two separate systemic reviews to examine the effects of supplemental calcium ingestion on cardiovascular disease among healthy adults.9 The study authors reviewed more than 50 years of data (randomized, controlled; prospective cohort; and nested case-control studies) from Medline, Cochrane, and Embase registries dating from 1966 to 2016. Of the 37 high-quality publications selected, there were no statistically significant differences for risk of cardiovascular disease events (e.g., heart attack, stroke, etc.) or death between groups taking calcium supplementation (with or without vitamin D, notably) compared to those receiving placebo. Furthermore, the cohort trials did not show any significant relationship between total/dietary/supplemental calcium dose ingestion and cardiovascular mortality. However, the authors did observe “highly inconsistent dose-response relationships between calcium intake and risks for total stroke or stroke mortality.” That being said, this latter finding was notably limited by a number of potential confounding factors that largely involved imprecise measures of calcium exposure, particularly regarding “very high” calcium intake that went beyond the upper limits of recommended intake. In short, from an overall cardiovascular perspective, it appears that calcium intake is not a significant player in terms of harm to the cardiovascular system, but when looking specifically at stroke the picture is less clear at both high and low levels of calcium intake. Specifically, two studies showed that dietary calcium intake > 1,000 mg per day was associated with an increase in stroke in both men and women (relative risk [RR], 1.09; 95% confidence interval [CI], 0.99-1.21 for men; and RR, 1.13; CI, 1.02-1.26 for women). However, the authors concluded that, overall, risk estimates, even if statistically significant, were small (± 10% RR) and were not considered clinically significant. Of note, none of the three cohort studies (two in Asia and one in Finland) showed any significant associations between dietary calcium intake and risk for stroke in men or women.
One exception from a more recent small Swedish study found an association of dementia among elderly women with previous history of stroke who regularly consumed supplemental calcium. In this study, 98 women with history of stroke were treated with daily calcium supplementation compared to 602 women with stroke history who were not given calcium. Those treated with calcium (1,000 mg per day) were at increased risk of developing dementia (mixed and vascular type), with an odds ratio of 2.10 and a confidence interval 1.01-4.37. Since calcium plays a central role in cell death by activating proteases that degrade critical proteins that maintain cell membrane integrity and function, the study authors hypothesized that calcium supplementation may potentiate adverse changes in vessel cell membranes that accelerate atherosclerosis and its end result of ischemia and hypotension seen in stroke and myocardial infarction.10
Ultimately, the review by Chung et al offered two significant insights: 1) To date, there are no data on the health effect of very high calcium intake levels (> 2,500 mg per day); and 2) Given the conflicting conclusions from several meta-analyses on calcium (which have contributed to confusion among healthcare providers and patients in determining what form and how much calcium to take on a daily basis), the authors recommended that all published data be made publicly available for future meta-analyses and reviews.9
Interestingly, whether calcium supplementation (with or without vitamin D) is beneficial or detrimental to vascular health still is not known definitively. In recognition of the absence of information, the National Osteoporosis Foundation and the American Society for Preventive Cardiology convened an expert panel to evaluate the effects of dietary (and supplemental) calcium on cardiovascular disease based on currently available research. As a result, this panel found that there is moderate-quality (level B) evidence that calcium with or without vitamin D intake from food or supplements ultimately has no relationship — positive or negative — to the risk for cardiovascular disease among generally healthy adults.11 In light of this, the National Academy of Medicine has established the tolerable upper limit of intake of 2,000-2,500 mg per day as safe from a cardiovascular standpoint at this time, noting the need for further research.
Calcium, the Supplement
The big question is what forms of calcium are best? In an ideal world, calcium obtained through good nutrition and food would be sufficient for most healthy people. According to the National Institutes of Health’s resource on osteoporosis, nearly all forms of calcium supplements are absorbed relatively equally as long as it is taken with food at ≤ 500 mg at different times of the day.12
Furthermore, there are several different kinds of calcium available in calcium supplements. Each type contains different amounts of mineralized or elemental calcium (the essential part). Calcium orotate has a reputation for being the highest quality calcium given its easy absorption, but it may not be the most practical, cost-effective, or easily available for most people and ultimately doesn’t appear to matter in terms of long-term outcomes. Other more commonly available and practical calcium supplements include the following:13
- Calcium orotate (90% elemental calcium)
- Calcium carbonate (40% elemental calcium)
- Calcium citrate (21% elemental calcium)
- Calcium lactate (13% elemental calcium)
- Calcium gluconate (9% elemental calcium)
How much actual daily calcium a person requires depends on age, gender, and health status. As mentioned earlier, upper recommended daily limits have been established based on current (although incomplete) research. (See Table 1.)
Table 1: Recommended Dietary Allowance (RDA) of Calcium for Adults |
||
|
Men |
Daily RDA |
Daily upper limit |
|
19-50 years |
1,000 mg |
2,500 mg |
|
51-70 years |
1,000 mg |
2,500 mg |
|
71 and older |
1,200 mg |
2,000 mg |
|
Women |
Daily RDA |
Daily upper limit |
|
19-50 years |
1,000 mg |
2,500 mg |
|
51 and older |
1,200 mg |
2,000 mg |
|
SOURCE: Committee to Review Dietary Reference Intakes for Vitamin D and Calcium, Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: National Academy Press, 2010 |
||
Calcium and the Diet
Similar to vitamins and essential amino acids and fatty acids, the body doesn’t produce calcium, which must be obtained through the diet. The first step for addressing adequate calcium intake is to make sure that vitamin D levels are adequate. Vitamin D has a complex metabolic journey in the body, with important enzymatic steps in the liver, kidneys, skin, and gut. Calcium requires vitamin D for proper absorption in the brush border cells of the small intestine by upregulating transcription/translation of cellular proteins that bind, carry, and transfer calcium. Without it (or in low/insufficient levels < 20 ng/mL), calcium absorption is inhibited. At levels of 40-80 ng/mL, vitamin D is considered “sufficient” and is the target range for most people, according to the Vitamin D Council, the Endocrine Society, and the Institute of Medicine, among others.14
Dairy has long been the preferred and recommended source of calcium for most people, but the reality is that dairy is greatly lacking in most American diets. Calcium-deficient groups can include people who eat a vegetarian/vegan diet, people with gut absorption problems (lactose intolerance, celiac disease, short bowel syndrome, inflammatory bowel disease, etc.), postmenopausal women, and various other chronic diseases. However, the first step to adequate calcium intake always starts with a generally well-balanced diet that includes calcium-rich foods. Examples include oatmeal (and other whole grains), sardines, salmon, soybeans (and other beans/legumes), nuts/seeds, fortified orange juice, broccoli (and other dark leafy greens), and fortified rice/almond/coconut/soy milk.
REFERENCES
- Weaver CM, Gordon CM, Janz KF, et al. The National Osteoporosis Foundation’s position statement on peak bone mass development and lifestyle factors: A systematic review and implementation recommendations. Osteoporos Int 2016:27:1281-1386.
- Hirata K; Morimoto I. Vertebral Osteoporosis in Late Edo Japanese. Anthropol Sci 1994;102:345-361.
- National Institute of Arthritis and Musculoskeletal and Skin Diseases. Osteoporosis. Available at: https://www.niams.nih.gov/health_info/Osteoporosis/default.asp. Accessed Jan. 15, 2017.
- Selby JB, Morris PB. Coronary artery calcification on CT scanning. theheart.org. Medscape. Available at: http://emedicine.medscape.com/article/352189-overview. Accessed Jan. 15, 2017.
- Patel MR, Peterson ED, Dai D, et al. Low diagnostic yield of elective coronary angiography. N Engl J Med 2010:362:886-865.
- U.S. Preventive Services Task Force. Final Recommendation Statement. Coronary Heart Disease: Screening Using Non-Traditional Risk Factors. Available at: https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/coronary-heart-disease-screening-using-non-traditional-risk-factors. Accessed Jan. 15, 2017.
- Lin EC, Bredeweg RP, Sicuro PL. Coronary CT Angiography. Theheart.org. Medscape. Available at: http://emedicine.medscape.com/article/1603072-overview#a3. Accessed Jan. 15, 2017.
- Centers for Disease Control and Prevention. Health Equity – Women’s Health. Available at: https://www.cdc.gov/women/lcod/2013/index.htm. Accessed Jan. 15, 2017.
- Chung M, Tang AM, Fu Z, et al. Calcium intake and cardiovascular disease risk: An updated systematic review and meta-analysis. Ann Intern Med 2016;165:856-866.
- Kern J, Kern S, Blennow K, et al. Calcium supplementation and risk of dementia in women with cerebrovascular disease. Neurology 2016;87:1674-1680.
- Kopecky S, Bauer DC, Gulati M, et al. Lack of evidence linking calcium with or without vitamin D supplementation to cardiovascular disease in generally healthy adults: A clinical guideline from the National Osteoporosis Foundation and the American Society for Preventive Cardiology. Ann Intern Med 2016;165:867-868.
- NIH Osteoporosis and Related Bone Diseases National Resource Center. Calcium and Vitamin D: Important at Every Age. Available at: https://www.niams.nih.gov/health_info/bone/bone_health/nutrition/. Accessed Jan. 15, 2017.
- Brigham and Women’s Hospital. All About Calcium Supplements. Available at: http://www.brighamandwomens.org/Patients_Visitors/pcs/nutrition/services/healtheweightforwomen/special_topics/intelihealth1004.aspx?subID=submenu10. Accessed Jan. 15, 2017.
- Vitamin D Council. I tested my vitamin D level. What do my results mean? Available at: https://www.vitamindcouncil.org/i-tested-my-vitamin-d-level-what-do-my-results-mean/. Accessed Jan. 15, 2017.
Calcium plays a significant role in the function and diseases of the muscles (skeletal and smooth), nerves, cardiovascular, gastrointestinal, and renal systems. As a nutrient, it is one of the most recognized by the public for its use for osteoporosis and bone health. However, its association with cardiovascular disease risk is a more recent example of the growing understanding of calcium’s role in our health. A number of recent updates over the past year (cardiovascular disease risk in particular) are noteworthy.
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