The 2011 study by Mursu et al. is an excellent example of how confounding variables can mask actual results. It was an observational study conducted by assessing 38772 older women from Iowa.
The study was based on self-administered questionnaires, and the women were between 55-69 years of age. And it ran from 1986 until 2008, with reporting happening in 86, 97 and 2004. The queries included data from 15 supplements, including vitamins, iron, calcium, copper, iron, magnesium, selenium and zinc.
The researchers have used three statistical models. In the first model, they considered raw data with minimum adjustment (only age and energy intake). More parameters were added, such as education, place of residence, diabetes, blood pressure, BMI, physical activity, and smoking, in the second model. The final one has, in addition to the others, alcohol, vegetable, and fruit intake.
The minimally adjusted model showed a lower mortality risk with vitamin B-complex, vitamins C, D, and E, and calcium. One could observe several confounding variables that differentiated supplement takers from non-takers. The supplement users, on average, were non-smokers, had a lower intake of energy, were more educated, were more physically active, and had lower BMI and waist-to-hip ratio.
The refinements, model 2, showed only calcium had some beneficial effect on lowering mortality, whereas the other supplements had minimal impact. Further adjustment of non-nutritional factors turned things further: multivitamins, B6, folic acid, copper, iron, magnesium, and zinc contributed to an increase in mortality rate compared to the non-takers of supplements.
Marsu et al.; Arch Intern Med., 2011, 171(18): 1625–1633