Photo source: Why Hip Fractures In The Elderly Are Often A Death Sentence, The Conversation.

Lots of people are taking lots of vitamin D. Can you take too much? I happened across:

Is High Dose Vitamin D Harmful?, Calcified Tissue International, February 2013

With the potential to minimize the risk of many chronic diseases and the apparent biochemical safety of ingesting doses of oral vitamin D several-fold higher than the current recommended intakes, recent research has focussed on supplementing individuals with intermittent, high-dose vitamin D.

However, two recent randomized controlled trials (RCTs) both using annual high-dose vitamin D reported an increase, rather than a decrease, in the primary outcome of fractures.

Results from observational, population-based studies with evidence of a U- or J-shaped curve are also presented as these findings suggest an increased risk in those with the highest serum 25D levels.

Here are those two RCTs:

Effect Of Annual Intramuscular Vitamin D On Fracture Risk In Elderly Men And Women–a Population-Based, Randomized, Double-Blind, Placebo-Controlled Trial, Rheumatology, December 2007

Annual High-Dose Oral Vitamin D And Falls And Fractures In Older Women A Randomized Controlled Trial, JAMA 2010

The first one was out of the UK:

Randomized, double-blind, placebo-controlled trial of 300,000 IU intramuscular (i.m.) vitamin D2 (ergocalciferol) injection or matching placebo every autumn over 3 years. 9440 people (4354 men and 5086 women) aged 75 yrs and over were recruited from general practice registers in Wessex, England.

The vitamin D group showed an almost 50% increased risk of hip and femur (thigh bone) fractures compared with placebo group. Fracture risks were higher in women:

When the genders were analysed separately, the tendency for an increase in fracture risk was particularly observed among women, in whom there was a 59% increase in hazard at the proximal femur or distal forearm (wrist) among those treated with vitamin D compared with placebo (P = 0.003).

The second one was out of Australia:

Double-blind, placebo-controlled trial of 2256 community-dwelling women, aged 70 years or older … randomly assigned to receive cholecalciferol (vitamin D3, 500 000 IU, oral) or placebo each autumn to winter for 3 to 5 years.
…
Participants receiving annual high-dose oral cholecalciferol experienced 15% more falls and 26% more fractures than the placebo group. Women not only experienced excess fractures after more frequent falls but also experienced more fractures that were not associated with a fall.

I thought that the delivery method (very high dose once a year) might be having an effect. They think not:

The evidence of harm relating to high-dose vitamin D centers on the findings of two RCTs that used annual high-dose vitamin D (Table 3), although results from RCTs using lower, more frequent dosing regimens have not been consistently clear. The different forms of the vitamin used in the studies and the different delivery modes demonstrate that the adverse outcomes are not restricted to one form of the vitamin.

The mechanism for these increased falls and fractures isn’t understood. Sanders et al. speculates that vitamin D supplementation may result in a “decline in muscle strength” (there are vitamin D receptors in muscle). It may also impact the central nervous system (there are vitamin D receptors in CNS and the brain) affecting balance and coordination.

From Concluding Summary:

In addition to evidence from enzyme kinetics relating to vitamin D metabolism [44], there is now high-level RCT evidence that vitamin D supplementation has potential toxicities other than simply hypercalcemia/-uria.
…
Emerging evidence from both observational studies and RCTs suggests that there should be a degree of caution about recommending high serum 25(OH)D concentrations for the entire population.

Some notes about doses:

• They defined high-dose as: “High dose refers to an intermittent bolus dose of at least 20,000 IU or a daily dose of 4,000 IU.”
• 4000 IUs is 100 micrograms.
• Conversion: 1 µg (microgram) = 40 IU (international units)
• For comparison, 2000 IU a day is 60,000 IU a month is 720,000 IU a year is more than the 300,000 and 500,000 IU/year used in these trials.
• “Peak 25(OH)D levels from these studies tend to be around 120-140 nmol/L (48-56 ng/ml).”
• Conversion: One nmol/L is equal to 0.4 ng/mL, and 1 ng/mL is equal to 2.5 nmol/L.

So, high-dose vitamin D could be acting in the brain? Affecting balance and coordination? Isn’t that the last thing we need?