Lessons From the WHI, Part 2: Calcium, Vitamin D, and Low-Fat Diet

Henry R. Black, MD; Rebecca D. Jackson, MD


July 08, 2014

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Editor's Note: This is part 2 of Dr. Black's interview with Dr. Rebecca Jackson on the Women's Health Initiative (WHI) studies.

Part 1, on the hormone therapy findings, is available here.

Part 3, on the cost-effectiveness of the estrogen and progestin arm, is available here.

And part 4, in which Dr. Jackson reminisces on paying it forward and the rewards of working on an important clinical trial, is available here.

Henry R. Black, MD: Hi. I'm Dr. Henry Black, Adjunct Professor of Medicine at the New York University Langone School of Medicine. I am here today with my colleague, Dr. Rebecca Jackson, from the Ohio State University.

I was the principal investigator at one of the 40 sites for the WHI when I was at Rush University in Chicago, and Dr. Jackson has been there ever since -- about 20 years now. How about the dietary intervention study? What was that design, and what did that show?

Rebecca D. Jackson, MD: The dietary intervention study was designed to answer the question of whether low-fat dietary modification reduced the risk for breast cancer,[1] and then secondarily to look at cardiovascular disease[2] and other cancers.[3] The hypothesis came from the fact that dietary fats are a precursor to the development of estrogens, and that by lowering dietary fat, estrogen levels would be lower as well, and that might have a preventive effect on the development of breast cancer. In this trial, we took women who had an average dietary intake of about 32% of their calories from fat and randomly assigned them to maintain their usual diet or to reduce their fat intake to less than 20% of their total daily calories. That is hard to do, and the women didn't quite achieve that. There was a certain level of recidivism with time, and fat intake crept up slightly, but there was still a significant 6%-8% decrement in exposure to fat over the length of the trial, which went on for an average duration of 7.5-8 years.[4]

We found a trend for a nonstatistically significant reduction in the risk for breast cancer[1] and other estrogen-related cancers, such as ovarian cancer.[3] There was no significant impact on colorectal cancer.[5] The intervention was a reduction in total fat intake and not necessarily saturated fat or cholesterol. There was a nonsignificant trend towards reduction in cardiovascular disease, but this was not the same dietary intervention that we would typically recommend for lipid management in cardiovascular disease. There was no significant impact on fractures.[6] All of these trials considered the big 5 diseases that occur in aging. We did not look at cognitive impairments or other outcomes in this trial.

Dr. Black: As I recall, it took an army of expert nutritionists and multiple visits to achieve that. Is that likely to be practical?

Dr. Jackson: We learned a lot of things that have now moved into the mainstream of nutritional teaching and how we work with patients in continuing to add dietary influence. We used both individual counseling sessions and group sessions to change diets. A critical element is self-monitoring -- having women write down what they were eating, paying attention to that, and working on reducing the fat in their diets. We know from this and many other nutritional studies that self-monitoring is a critically important tool. If people record what they eat, they are aware of what they are doing and are able to make the necessary modifications.

A second great innovation that came out of WHI within the dietary modification trial was the use of motivational interviewing. This involved working with women in this trial and using this technique to help them maintain those dietary changes. This is now in the mainstream of clinical nutrition in the ways that we help people -- whether it is in diabetes or in lipid management -- to maintain dietary changes.

Dr. Black: How about the calcium and vitamin D trial? Tell us about that.

Dr. Jackson: The calcium and vitamin D was the third randomized trial. This was designed to look at the use of calcium plus vitamin D supplementation. In this trial, we used the most commonly prescribed calcium at that time, which was calcium carbonate, 1000 mg daily with 400 units of vitamin D3 vs placebo. A lot of data[7] from multiple trials in the osteoporosis world suggested that there was a significant improvement in the rates of decline in bone density associated with calcium supplementation, but no definitive trials had shown whether calcium plus vitamin D significantly reduced the risk for fractures.

Secondarily, emerging data[8] from observational studies suggested that calcium specifically (because it binds bile acids) might have an impact on reducing the risk for the development of polyps and, subsequently, colorectal cancer. Those were the primary hypotheses. This trial showed that there was a small but nonstatistically significant reduction in the rate of hip fractures associated with calcium plus vitamin D supplementation.[9] In secondary analyses, however, in women over the age of 60 years and those who were compliant with taking the study medication (meaning that they took more than 80% of the prescribed pills), there was a significant reduction in hip fractures. This helped to inform the use of calcium as a foundation but not as a treatment for all fractures because it had no impact on total fractures, only a trend towards a reduction in hip fractures.

[Editor's note: The findings for the incidence of colorectal cancer showed no effect for daily supplementation of calcium with vitamin D at 7 years.][10]


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