Consumer confusion over vitamin D and calcium seems likely to grow, following claims from the Women's Health Initiative (WHI) trial about their effect on bone health that oppose other studies.
The combination of vitamin D and calcium has long been recommended to reduce the risk of bone fracture for older people, particularly those at risk of or suffering from osteoporosis, which is estimated to affect about 75m people in Europe, USA and Japan.
Use of these supplements is widely accepted by the general public, with calcium reported to be the biggest seller in the US supplements industry. Annual sales were about $993m (€836m) in 2004, according to the Nutrition Business Journal.
The new study poses a challenge to this acceptance by concluding that calcium and vitamin D supplements did not reduce the risk of fractures in post-menopausal women, but in fact the results were skewed by poor compliance.
Published in the New England Journal of Medicine (Vol 354, pp 669-683), the study followed 36,282 post-menopausal women with an average age of 62 at the start of the trial. Volunteers were randomly assigned to receive 1000mg of elemental calcium in the carbonate form and 400 IU of vitamin D3 per day, or a placebo.
After an average of seven years follow-up, the scientists reported: "Among healthy postmenopausal women, calcium with vitamin D supplementation resulted in a small but significant improvement in hip bone density, and did not significantly reduce hip fracture."
Such a generalisation is somewhat misleading however. If one looks just at the 59 per cent of the participants who actually adhered to the supplementation programme (assuming 80 per cent or more compliance with taking the supplements), the data do, in fact, highlight the benefits of dual vitamin D-calcium supplementation.
The number of fractures in this compliant group was 29 per cent lower than in those taking the placebo. This indicates that supplementation with calcium and vitamin D did significantly reduce the risk of hip fracture, as has been reported by other studies, but only if taken regularly.
The bone mineral density (BMD) of the entire intervention group increased by 0.86 per cent after six years, and for those followed-up for nine years, BMD increased by 1.06 per cent.
The strengths of this study lie in the large-scale, randomised, double-blind, placebo-based design. However the authors recognise that adherence to an intervention using a free-living population is difficult.
Indeed, even though those in the placebo group was not given calcium supplements by the researchers, they were free to use supplements on their own. Sixty-four per cent of the placebo group had a daily calcium intake of at least 800 mg from diet and supplements, and 42 per cent were consuming at least 400 IU of vitamin D.
This suggests that the intervention and control groups were very similar. With both groups consuming calcium and vitamin D, this could explain why the incidence of overall fractures was less than envisaged - the actual hip fracture rate was more than half that projected by the researchers.
"The lower-than-projected hip-fracture rate reduced the power of the study to approximately 48 per cent," wrote the research team, led by Rebecca Jackson from Ohio State University.
In an accompanying editorial, Joel Finkelstein from the Massachusetts General Hospital rightly points out: "There were several aspects of the study design and characteristics of the study population that may have reduced the chances of detecting a benefit of calcium and vitamin D."
It should be noted that many of the women were also involved in the other arms of the WHI trial, with 69 per cent of the women enrolled on the Dietary Modification trial, 54 per cent enrolled on the Hormone Therapy trial, and 14 per cent enrolled on both.
"The use of hormone-replacement therapy (HRT) among post-menopausal women has declined dramatically [HRT is known to be potent against bone resorption and weakening and can reduce bone fracture]. Thus, the widespread use of HRT in the current study limits the ability to generalise the results," he said.
Another limitation is that the dose of vitamin D might have been too small to initiate a response for all participants. Other studies have reported no effect with 400 IU, but benefits have been reported for trials using doses of 600 IU or more.
However it seems plausible that the dose was not as significant a factor as adherence to the program. The data clearly show that women who regularly took the vitamins had a 29 per cent reduction in hip fractures.
Finkelstein finishes a well-balanced editorial by concluding: "It seems reasonable that women consume the recommended daily levels of calcium and vitamin D through diet, supplements, or both. But one message is clear: calcium with vitamin D supplementation by itself is not enough to ensure optimal bone health."
This statement was echoed by Roger Francis, Professor of Geriatric Medicine at the University of Newcastle, who told NutraIngredients.com: "This study shows that vitamin D and calcium supplementation would not work as a public health measure, because vitamin D-calcium trials have notoriously poor adherence."
Professor Francis pointed out however that an earlier French study (Scand J Rheumatol Suppl 1996 Vol 103, pp 75-78) reported that calcium and vitamin D supplements given to elderly women significantly reduced the risk of hip fracture. This sample population was much older than the WHI population.
The current EU recommended daily intake of calcium is 800mg, with an upper safe limit of 2500mg. Vitamin D has a RDI of 400 IU, although campaigners are calling for an increase to 1000 IU, half the upper safe limit recommended by the EU and US.
In the US, the DRI (dietary reference intake) for calcium is 1000mg for adults aged 19 to 50, and 1200mg from 51 to 70. For vitamin D it is five micrograms per day, rising to 10 after the age of 50.
According to the International Osteoporosis Foundation, the total direct cost of osteoporotic fractures is €31.7 billion ($37.6) in Europe, and $17.5 (€14.7) billion in the US (2002 figure).