Why your vitamin D supplements might not be working

The study, published in the December issue of The American Journal of Clinical Nutrition, adds clarity to long-standing debates about vitamin D’s links to colorectal cancer and other diseases. These questions have gained attention due to mixed results from major studies, including the VITAL trial. The new findings also reinforce earlier research from 2013 by the same team, which found that people with low magnesium intake often had low vitamin D levels as well.

New Evidence of a Regulating Effect

Beyond confirming earlier observations, the trial uncovered an additional insight. Magnesium did not simply raise vitamin D across the board. Instead, it appeared to act as a regulator, lowering vitamin D levels in participants whose levels were already high. This is the first clinical evidence suggesting magnesium may help optimize vitamin D levels rather than just increase them, which could be important for reducing disease risk linked to vitamin D imbalance.

Qi Dai, MD, PhD, Ingram Professor of Cancer Research and lead author of the study, explained that the healthiest vitamin D range appears to fall in the middle of a U-shaped curve. Previous observational studies have linked this middle range to the lowest risk of cardiovascular disease.

Vitamin D Research Remains Mixed

Despite earlier findings, vitamin D did not show a clear link to cardiovascular disease in the recent VITAL trial. Dai and co-author Martha Shrubsole, PhD, a research professor of Medicine in the Division of Epidemiology, are now examining whether magnesium could help explain these inconsistent results. Their work is part of the ongoing Personalized Prevention of Colorectal Cancer Trial.

“There’s a lot of information being debated about the relationship between vitamin D and colorectal cancer risk that is based upon observational studies versus clinical trials,” Shrubsole said. “The information is mixed thus far.”

Why Magnesium May Matter More Than Expected

The researchers turned their attention to magnesium after noticing that vitamin D supplements do not work equally well for everyone. Some people fail to raise their vitamin D levels even when taking high doses.

“Magnesium deficiency shuts down the vitamin D synthesis and metabolism pathway,” Dai said.

The study included 250 adults considered at higher risk for colorectal cancer, either due to known risk factors or because they had previously had a precancerous polyp removed. Participants received either magnesium supplements or a placebo, with dosages tailored to their usual dietary intake.

Magnesium Deficiency Is Common in the U.S.

Shrubsole noted that vitamin D insufficiency is widely recognized as a public health concern in the United States, and many patients are advised to take supplements based on blood test results.

“Vitamin D insufficiency is something that has been recognized as a potential health problem on a fairly large scale in the U.S.,” Shrubsole said. “A lot of people have received recommendations from their health care providers to take vitamin D supplements to increase their levels based upon their blood tests. In addition to vitamin D, however, magnesium deficiency is an under-recognized issue. Up to 80 percent of people do not consume enough magnesium in a day to meet the recommended dietary allowance (RDA) based on those national estimates.”

Food Sources of Magnesium

Shrubsole emphasized that magnesium intake in the study matched RDA guidelines and suggested that diet is the best way to increase magnesium levels. Foods rich in magnesium include dark leafy greens, beans, whole grains, dark chocolate, fatty fish such as salmon, nuts and avocados.

Additional Vanderbilt co-authors on the study include Xiangzhu Zhu, MD, Hui Nian, PhD, Harvey Murff, MD, MPH, Reid Ness, MD, MPH, Douglas Seidner, MD and Chang Yu, PhD.