Calcium

What is calcium?

Calcium is a mineral that is essential for human health (1).

What does calcium do in the body?

Calcium plays a role in many bodily functions, including:

1. Bone formation 

Calcium binds with other minerals to form a hard tissue called hydroxyapatite, which is a major component of bones and teeth (1, 2).

2. Muscle function

By binding to troponin (a protein complex found in muscle), calcium ions allow actin and myosin (the proteins responsible for muscle contraction) to interact (3, 5).

3. Blood clotting 

Calcium is required for the binding of cell membrane phospholipids with blood clotting proteins, which allows platelets to clump together (5, 6).

4. Nerve transmission

Action potentials (nerve impulses) stimulate nerve cells to release calcium ions, which triggers the release of neurotransmitters (7).

5. Cell signaling

Increases in calcium concentration within cells can activate enzymes, which play important roles in cell metabolism (8, 9).

How is calcium absorbed?

Most dietary calcium is bound to other substances, such as oxalic acid or phytic acid (1).

In order to be absorbed, it must be broken down into ionized (free) calcium by stomach acid (10).

About 90% of calcium absorption occurs in the small intestine, via one of the following modes of transport (10, 11, 12):

1. Transcellular (through cells)

• Requires active transport
• Takes place mainly in the duodenum.
• Regulated by calcitriol (the active form of vitamin D).
• The main mode of transport when calcium intake is low.

2. Paracellular (between cells)

• Occurs through passive diffusion.
• Takes place throughout the small intestine.
• The main mode of transport when calcium intake is normal or low.

A very small proportion (less than 10%) of calcium is absorbed in the large intestine via active transport (11).

On average, about 30% of dietary calcium is absorbed (1).

How is calcium transported throughout the body?

In the blood (serum), calcium exists in 3 different forms (13):

1. Ionized (free) (45%)
2. Bound to protein (mainly albumin) (45%)
3. Bound to other molecules (10%)

More than 99% of total body calcium is stored in the bones, where it serves as a reservoir for the body’s calcium needs (1).

The remaining 1% is found in tissues (such as muscle) and extracellular fluid (serum) (1).

Serum calcium levels are tightly regulated by parathyroid hormone (PTH), calcitriol (vitamin D3), and calcitonin (3).

How is calcium excreted?

Calcium is excreted via urine, feces, and other bodily fluids, such as sweat (1).

About 2% of the calcium filtered by the kidneys is excreted in urine, while the rest is reabsorbed (1).

Any unabsorbed dietary calcium is excreted in the feces (1).

How can you test calcium levels?

1. Total calcium blood test

A total calcium test measures both free and protein-bound calcium in the blood.

The normal range is around 8.6-10.2 mg/dL (2.15-2.54 mmol/L) (14).

If albumin is low, total calcium levels will be falsely low, so the following equation is used to calculate a “corrected” calcium level (14, 15):

Corrected calcium (mg/dL) = total calcium (mg/dL) = 0.8 x [4 – serum albumin (g/dL)]

2. Ionized calcium blood test

Only ionized (free) calcium is physiologically active, so measuring it can provide a more accurate picture of calcium metabolism (16, 17).

The normal range is 4.69-5.65 mg/dL (1.17-1.41 mmol/L) (18).

However, because blood levels of calcium are so tightly regulated, these tests are not a good marker of overall calcium status (3).

3. DEXA scan

Because the majority of calcium is found in bone, measuring bone density can provide better information about calcium status (19).

This is typically done using dual-energy X-ray absorptiometry (DEXA) (20).

How common is calcium deficiency?

It is estimated that 3.5 billion people worldwide are at risk of calcium deficiency (21).

Populations most at risk include the following (22):

• Low-income
• Minorities
• Older adults
• Overweight/obese
• Teenagers

Why might you be deficient in calcium?

1.Diet 

• Low intake of calcium-rich foods (1)

2. Nutrient deficiencies

• Vitamin D deficiency (12)
• Magnesium deficiency (23, 24)

3. Lifestyle factors

• Smoking (25)

4. Malabsorptive conditions

• Celiac disease (26, 27)
• Chronic pancreatitis (28)
• Inflammatory bowel disease (29, 30)

5. Hormonal imbalances

• Hypoparathyroidism (31)

6. Interactions with medications

• Anticonvulsants (carbamazepine, phenobarbital, phenytoin) (32, 33, 34)
• Bisphosphonates (35)
• Glucocorticoids (36, 37)
• Loop diuretics (38, 39)

What are the signs and symptoms of calcium deficiency?

Acute hypocalcemia (low blood calcium) can lead to (3):

• Depression
• Difficulty swallowing
• Fainting
• Fatigue
• Heart failure
• Irritability
• Numbness and tingling
• Seizures
• Tetany (muscle spasms)
• Wheezing

Long-term hypocalcemia can lead to (3):

• Brittle nails
• Cataracts
• Coarse hair
• Dental problems
• Dry skin
• Itchy skin
• Psoriasis

What diseases or conditions are linked to calcium deficiency?

Long-term calcium deficiency is linked with the following conditions:

1. Rickets

Rickets is a bone disease characterized by defective mineralization of the growth plates in children, which leads to softening of the bones and deformities (such as bowed legs) (40, 41).

It can be caused by a calcium deficiency, but more often it is the result of inadequate vitamin D (42, 43).

2. Osteomalacia

Softening of the bones (also known as osteomalacia) is the result of poor mineralization of existing bone, usually caused by calcium and/or vitamin D deficiency (40).

It can cause muscle weakness, bone pain, and fractures (44).

3. Osteoporosis

When calcium intake is low, the body pulls calcium from the bones in order to maintain serum levels (45).

Over time, It is thought that this leads to osteoporosis, a condition in which bone density is reduced and the risk of fractures increases (45, 46).

4. Hypertension

Several studies have shown a link between low calcium intake and increased risk for hypertension (47, 48).

It’s unclear exactly why this might occur, but many scientists believe the mechanism is related to calcium’s ability to increase smooth muscle tone in blood vessels (49).

5. Type 2 diabetes

Research shows an association between low calcium intake and increased risk of type 2 diabetes (50, 51). 

It has been suggested that calcium plays a role in glucose homeostasis because insulin secretion is dependent upon intracellular calcium levels (51, 52).

6. Colorectal cancers

Higher dietary calcium intake has been linked with lower colorectal risk (53, 54, 55).

One study found that each 300 mg/day increase in total calcium intake was associated with an 8% reduced risk (56).

It’s unclear exactly how this might happen, but some studies have found that calcium reduces cell proliferation by regulating cell signaling (57).

7. Obesity

Some studies have shown a link between low calcium intake and increased body weight (58, 59, 60).

It is thought that dietary calcium intake may play a role in fat metabolism by altering the calcium levels in adipose cells (61, 62).

Other studies have produced conflicting results, so more research is needed (63, 64, 65).

How much calcium do you need each day?

The Recommended Dietary Allowance (RDA) for calcium is listed below (66):

• Birth to 6 months: 200 mg (this is technically the adequate intake, not an RDA)
• 7-12 months: 260 mg (this is technically the adequate intake, not an RDA)
• 1-3 years old: 700 mg
• 4-8 years old: 1,000 mg
• 9-13 years old: 1,300 mg
• 14-18 years old: 1,300 mg
• 19-30 years old: 1,000 mg
• 31-50 years old: 1,000 mg
• Males 51-70 years old: 1,000 mg
• Females 51-70 years old: 1,200 mg
• >70 years old: 1,200 mg
• Note: Requirements do not increase during pregnancy or breastfeeding.

Is there such a thing as calcium toxicity?

Yes, very high levels of calcium in the blood (known as hypercalcemia) can lead to kidney problems and calcium deposits in soft tissues (67, 68).

However, this is usually caused by hyperparathyroidism rather than excessive calcium intake (67).

The tolerable upper intake level for calcium (listed below) is based on the amount that increases the risk for kidney stones, although recent research suggests this probably isn’t a concern (67, 69, 70):

• 0-6 months: 1,000 mg
• 6-12 months: 1,500 mg
• 1-8 years old: 2,500 mg
• 9-18 years old: 3,000 mg
• 19-50 years old: 2,500 mg
• 51+ years old: 2,000 mg

How much calcium is required to replete a deficiency?

Acute hypocalcemia requires treatment with intravenous calcium gluconate until serum levels normalize (71).

Chronic calcium deficiency is typically treated with doses ranging from 1,000 to 3,000 mg/day of supplemental calcium (72).

What are the best food sources of calcium?

Dairy-based calcium food sources (73):

• Low-fat yogurt: 448 mg per cup
• Parmesan cheese: 331 mg per ounce
• Goat’s milk: 327 mg per cup
• Fat-free or skim milk: 306 mg per cup
• Whole milk yogurt: 296 mg per cup
• Reduced fat (2%) milk: 286 mg per cup
• Whole milk: 276 mg per cup
• Greek yogurt: 263 mg per cup
• Ricotta cheese: 257 mg per ½ cup
• Swiss cheese: 221 mg per ounce
• Provolone cheese: 212 mg per ounce
• Cheddar cheese: 202 mg per ounce
• Blue cheese: 148 mg per ounce
• Mozzarella cheese: 141 mg per ounce
• Feta cheese: 138 mg per ounce
• American cheese: 118 mg per slice
• Cottage cheese: 103 mg per ½ cup
• Ice cream: 85 mg per ½ cup 

Non-dairy calcium food sources (73):

• Sardines: 351 mg per 3.75-ounce tin 
• Rhubarb: 348 mg per cooked cup
• Collard greens: 266 mg per cooked cup
• Spinach: 245 mg per cooked cup
• Winged beans: 244 mg per cooked cup
• Pink salmon: 233 mg per 3-ounce portion (canned with bones)
• Black-eyed peas: 211 mg per cooked cup
• Mackerel: 203 mg per 3-ounce portion (canned with bones)
• Turnip greens: 197 mg per cooked cup
• Natto: 182 mg per 3-ounce portion
• Agar seaweed: 175 mg per ounce (dried)
• Bok choy: 158 mg per cooked cup
• Dandelion greens: 147 mg per cooked cup
• White beans: 131 mg per cooked cup
• Baked beans: 126 mg per cooked cup
• Poppy seeds: 126 mg per tablespoon 
• Teff: 123 mg per cooked cup
• Amaranth: 116 mg per cooked cup
• Okra: 123 mg per cooked cup
• Anchovies: 104 mg per 2-ounce can
• Mustard greens: 104 mg per cooked cup
• Blackstrap molasses: 100 mg per tablespoon
• Edamame: 98 mg per cup
• Kale: 94 mg per cooked cup
• Sesame seeds: 88 mg per tablespoon
• Chia seeds: 86 mg per tablespoon
• Almonds: 75 mg per ounce
• Oranges: 60 mg per orange

Foods fortified with calcium (73):

• Tofu, firm, prepared with calcium: 861 mg per ½ cup
• Orange juice, fortified: 500 mg per cup
• Plant-based milks, fortified: 300-450 mg per cup
• Breakfast cereals, fortified: 100-1,000 mg per cup

Which conditions might benefit from calcium supplementation?

1. Hypoparathyroidism

Parathyroid hormone deficiency (hypoparathyroidism) is commonly caused by head and neck surgery and can lead to dangerously low serum calcium levels.

Most patients require calcium supplementation (1000-3000 mg/day), as determined by their physician (74).

2. Preeclampsia

Significantly lower serum calcium levels have been found in women with preeclampsia, a complication of pregnancy that results in high blood pressure and (if untreated) organ damage (75).

Strong evidence suggests that calcium supplementation (1,000-2,000 mg/day) reduces the risk and/or severity of preeclampsia women with low calcium intake (<600 mg/day) (76, 77, 78, 79).

3. Premenstrual Syndrome (PMS)

Research has shown that some symptoms of PMS (such as mood swings, bloating, appetite changes, and fatigue) are alleviated by calcium supplementation (500-1,200 mg/day) when taken for at least 2 months (80, 81, 82, 83, 84, 85).

The mechanism for this effect is unclear, but one study found low calcium levels in women with PMS (86).

4. Colorectal cancer

A small number of trials have found a reduced colorectal cancer risk with calcium supplementation (1200-1600 mg/day) (87, 88).

In addition, a recent study found a link between higher calcium intake after diagnosis and lower risk of death in patients with colorectal cancer (89).

More high-quality studies are needed before any recommendations can be made.

5. Osteoporosis?

Calcium supplementation (1,000-1,200 mg/day) is often recommended for the management of osteoporosis in postmenopausal women (90, 91).

Unfortunately, the evidence supporting this recommendation is weak and inconsistent (92, 93, 94, 95, 96).

A recent meta-analysis found that increased calcium intake from dietary and/or supplemental sources increased bone mineral density by only 0.7-1.8%, which is unlikely to make much of a difference in fracture risk (91).

Supplementing with vitamin D, however, might improve the effectiveness of calcium in reducing fracture risk (95, 97).

What are the different forms of supplemental calcium?

The most popular forms of supplemental calcium include the following:

1. Calcium carbonate

The most common and least expensive supplemental form is calcium carbonate, which contains 40% elemental calcium (98).

Absorption of calcium carbonate is similar to that of milk and calcium-fortified orange juice (99).

2. Calcium citrate

Another popular form is calcium citrate, which contains 21% elemental calcium (98).

When taken on an empty stomach, the bioavailability of calcium citrate is similar to that of calcium carbonate (98).

Under any of the following conditions, calcium citrate is BETTER absorbed than calcium carbonate (98):

• When taken with meals
• In patients with low stomach acid
• In patients taking proton-pump inhibitors (PPIs) and H2 blockers

3. Calcium citrate-malate

One of the newer forms is calcium citrate-malate, which contains 24% elemental calcium (100).

Its bioavailability (36-44%) is similar to calcium carbonate, but some people prefer it because it doesn’t have the soapy flavor or chalky mouthfeel that is common with calcium carbonate (100, 101, 102).

4. Microcrystalline hydroxyapatite

The form of calcium found in bone is called microcrystalline hydroxyapatite, and supplements containing this form are usually derived from bovine bones (98, 103).

It has been shown to have similar effects on bone turnover as calcium carbonate and calcium citrate (104). 

However, it does appear to produce smaller increases in serum calcium levels, which may lower the risk of arterial calcification and potential negative consequences like CVD (103, 104).

What calcium supplements are recommended?

Calcium + Co-nutrients:

• Pure Encapsulations Calcium K/D 180’s
  • 1,000 IU vitamin D3, 100 mcg vitamin K1, 400 mg di-calcium malate, 30 mcg vitamin K2 (MK-7) per two capsules
  • Other ingredients: vegetarian capsule (cellulose, water)
• Thorne Advanced Bone Support
  • 1,000 IU vitamin D3, 300 mg dicalcium malate, 100 mg dimagnesium malate, 20 mg vitamin B6 (as pyridoxal 5′-phosphate), 100 mcg folate (as L-5-MTHF), 50 mcg vitamin B12 (as methylcobalamin), and 3 mg boron (as boron glycinate complex) per two capsules
  • Other ingredients: hypromellose (derived from cellulose) capsule, medium chain triglyceride oil

Calcium-Containing Multivitamin:

• Thorne Basic Nutrients V
  • 120 mg calcium citrate, 90 mg calcium malate per six capsules
  • Other ingredients: hypromellose (derived from cellulose) capsule, microcrystalline cellulose, calcium laurate, silicon dioxide

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How does calcium interact with other nutrients?

1. Vitamin D

Calcium absorption is optimized when vitamin D binds to the vitamin D receptor (VDR) in intestinal cells (105).

There is also evidence that high calcium intake increases the half-life of vitamin D, allowing it to remain in circulation for longer periods (105).

2. Vitamin K

By interacting with proteins that regulate calcium deposition, vitamin K optimizes the utilization of calcium in the body and prevents vascular calcification (106, 107).

3. Phosphorus

A high phosphorus, low calcium diet increases PTH and urinary calcium excretion (108).

Based on this observation, some experts have suggested a dietary calcium:phosphorus ratio of 1.3:1 (109). 

However, this is controversial, and more research is needed to fully explain the relationship between calcium and phosphorus (109).

4. Sodium

Excess dietary sodium increases urinary calcium excretion, but the body compensates for the loss by increasing vitamin D synthesis that leads to enhanced calcium absorption (110, 111) 

5. Potassium

Studies show that potassium supplementation reduces urinary calcium excretion (112, 113, 114).

However, this reduced excretion may be offset by a reduction in intestinal absorption of calcium, which results in no net changes in calcium balance (115).

6. Protein 

There is some evidence that dietary protein increases urinary calcium excretion, but the research is conflicting, and some studies have shown an increase in calcium absorption with higher protein diets (1, 116, 117, 118).

7. Caffeine

Caffeine has been shown to increase urinary calcium excretion (119).

However, the effect is very small, and caffeine intake <400 mg/day is unlikely to interfere with calcium homeostasis as long as overall calcium intake is adequate (120).

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Are there any potential side effects or precautions with supplementation?

1. Increased cardiovascular disease risk

Some evidence suggests that taking calcium supplements may increase the risk of heart disease and stroke (121, 122).

However, research is conflicting, and the overall quality of evidence is low (123, 124, 125, 126).

Larger trials focusing specifically on the effect of calcium supplements on CVD risk are needed before any conclusions can be made (127).

A few studies have found no increased risk if calcium and vitamin D are supplemented together, but this needs more research (128, 129).

2. Increased prostate cancer risk

Several studies have found a link between very high calcium intake (>2000 mg/day) and increased prostate cancer risk (130, 131). 

However, the research is conflicting, and a recent meta-analysis found that high intake of calcium from DAIRY products (but not supplemental or nondairy dietary calcium) increased the risk of prostate cancer (132, 133, 134).

3. Impaired iron and zinc absorption

Taking calcium supplements (or consuming dairy products) with meals reduces iron absorption by as much as 60% but does not appear to reduce plasma ferritin levels over time (135, 136, 137, 138, 139, 140).

One study found that zinc absorption was reduced by 50% when 469 mg of calcium was given with a meal, but further research has shown no significant effects on zinc balance (135, 141, 142, 143, 144).

4. Impaired drug absorption

When taken together, calcium supplements can interfere with the absorption of the following drugs:

• Antibiotics (fluoroquinolone and tetracycline) (145, 146)
• Bisphosphonates (147)
• Levothyroxine (148, 149)

5. Constipation

Studies regarding calcium supplements and constipation are conflicting, possibly due to the wide range of doses used (150, 151, 152, 153).

Taking smaller doses (500 mg/day) doesn’t seem to influence stool frequency or form in healthy women (151).

Note:

It was once thought that calcium supplementation increased the risk for kidney stones, but newer research suggests the opposite may be true (69, 70, 154, 155, 156, 157).