Sunday, April 29, 2012

Calcium In, Calcium Out

Calcium Intake

Osteoporosis is thought to be due to a negative calcium balance. It’s suggested that a low dietary intake of calcium and/or low vitamin D levels reduces the amount of calcium absorbed, which then increases parathyroid hormone level to maintain calcium levels by through bone resorption.

While calcium deficiency may cause osteoporosis, randomised controlled trials of calcium supplements don't show too much benefit for fracture rates and have increased the number of cardiovascular events, but not total mortality.

Fracture Rates
Heart Attacks
Meta-Analysis of RCTs (institutionalised) [1]
Calcium and Calcium + Vitamin D

Meta-Analysis of RCTs (community) [1]
Calcium and Calcium + Vitamin D

Meta-Analysis of RCTs [2]
Calcium (women/men)

Meta-Analysis of RCTs [3]
Calcium and Calcium + Vitamin D

Meta-Analysis of RCTs [4]

* Non-significant

Calcium and calcium + vitamin D supplementation in studies that were institutionalised and/or had high compliance rates reduced fracture rates by 24% compared with only 6% in RCTs that were community based (low compliance). Other factors that influence the effect size of calcium supplementation include age and baseline dietary calcium intake. The studies with higher compliance do a better job of reflecting the actual effect of calcium supplementation, so I’ll rather use that data. The authors discuss that there seems to be some publication bias, but not enough to suggest calcium supplementation has no effect on fracture rates [1]. So I’m comfortable in concluding that calcium supplements seem to reduce overall fracture rates by approximately 20%.

However, it’s clear that the proposed mechanism that’s mentioned above (low calcium absorbed >> low serum calcium>> increase parathyroid hormone >> bone resorption) is hardly the full story. Calcium supplements raise serum calcium even more strongly than dietary calcium [5], but this only slows down bone loss, admittedly by about 50% [6]. While a 20% reduction in fractures sounds good, altogether this suggests that some other mechanism is being overlooked and perhaps calcium is simply covering up the problem.

* Elevated serum calcium levels and hyperparathyroidism are associated with an increased risk of cardiovascular disease, which may explain why calcium supplementation increases the risk [4]. The risk of supplemental calcium is related to kidney function. Food forms of calcium such as dairy and bone don’t elevate serum calcium as much as supplements do [5]

** The Women’s Health Initiative trial found that among people not taking calcium at randomisation, calcium and vitamin D supplementation reduced cancer by 14% [7]

*** Vitamin D supplementation of 700-1,000 IU reduces falls by 19% [8]

Calcium Out: The Dietary Acid-Base Theory of Osteoporosis

An alternative theory of osteoporosis is that high dietary acid loads (mainly from protein, particularly the sulphur amino acids, and phosphorus, both of which animal foods are rich in) cause the body acidic and then calcium (which is alkaline) is leeched from the bones and used to balance the acid load on the kidneys.  Vegetarians and vegans use this as an argument against meat, while early versions of Paleo used this as an argument against dairy.

However, contrary to the dietary acid-base theory of osteoporosis:

  • Calcium isn’t leeched due to lower renal pH
  • Calcium balance isn’t affected by minor physiological changes in pH (7.35-7.45)
  • Protein doesn’t decrease bone mineral density and low protein is not ideal for bone health
  • Alkaline diets and supplements don’t increase bone mineral density or markers of bone formation [9]

“A causal association between dietary acid load and osteoporotic bone disease is not supported by evidence and there is no evidence that an alkaline diet is protective of bone health.” [9]

Furthermore, high protein diets maintain calcium balance as they increase calcium absorption and excretion. There was no difference in bone resorption or bone formation biomarkers between the high protein and low protein diet. The high protein diet increased IGF-1 and decreased parathyroid hormone, which could suggest high protein diets promote bone health* [10]. Also in the Framingham study** found that those who ate the most protein had the highest bone mineral density [11]

A likely reason why dietary acid-base theories have little evidence to support them is because our body’s pH is tightly regulated between 7.38-7.42 (lower pH is more acidic, higher pH is more alkaline and a pH of 7 is neutral) and the main regulatory mechanisms don’t involve calcium.  To regulate pH we have the bicarbonate buffering system, which converts carbon dioxide (acidic) and water to carbonic acid (acidic), carbonic acid to bicarbonate (alkaline) and a hydrogen ion (acidic), and vice versa.

CO2 + H2O <> H2CO3 <> HCO3- + H+

From here, pH homeostasis is achieved in the short term by the lungs regulating the amount of CO2 in the bloodstream, and long term by the kidneys regulating the amount of bicarbonate and hydrogen ions (as well as other acidic and basic molecules) that are excreted and reabsorbed

Rather than pathologise the modest amount of protein in the SAD, it’s more informative to look at actual causes of acidity, which can arise from a defect in the regulatory systems – respiratory acidosis or metabolic acidosis due to poor kidney function – or other sources of metabolic acidosis where the regulatory systems being overwhelmed, such as ketoacidosis (due to insulin deficiency, not ketosis) and lactic acidosis (due to hypoxia or mitochondrial dysfunction)

* Seeing as the high protein diet lowered parathyroid hormone it seems likely that protein increases calcium absorption primarily and then increases calcium excretion simply because there’s excess calcium in the blood. If protein increased calcium absorption to compensate for increased calcium excretion/low serum calcium then parathyroid hormone would go up

** Data from the Framingham study suggests people with a more alkaline diet (more fruit, vegetables, potassium and magnesium) had higher bone mineral density and lower bone loss over time [11]. However, this (and similar findings) doesn’t prove the alkaline hypothesis, as the major confounding variable is that fruit and vegetables are healthy anyway, and potassium and magnesium intake could be markers of a better diet. There would need to be evidence for alkaline diets independent of the other biological effects of fruit, vegetables and alkaline supplements.

Further Reading:
(1) The Acid-Alkaline Myth: Part 1
(2) The Acid-Alkaline Myth: Part 2
(3) Calcium Supplements: Why You Should Think Twice
(4) Does Dairy Cause Osteoporosis?

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