RICHMOND HILL, ONT. — Large, vulnerable segments of the population, including children, pregnant women, the elderly and prediabetics would benefit from vitamin D supplementation, according to a wide-ranging scientific study published last month.

The authors of the study, “Vitamin D for the Prevention of Disease: An Endocrine Society Clinical Practice Guideline,” included brief discussions of food fortification, including the fortification of flour, as a possible path toward reaching the individuals who would benefit from greater vitamin D intake.

The 30-page study was published in June in The Journal of Clinical Endocrinology & Metabolism. A team of researchers who authored the article was led by Marie B. Demay, an endocrinologist associated with Massachusetts General Hospital and Harvard Medical School in Boston. Numerous other US states and institutions were represented among the contributors as were researchers from Brazil, Ireland, The Netherlands and New Zealand.

Questions of whether to increase intake of vitamin D in the diet and by how much have been swirling around the scientific community for well over a decade. In 2010, the Institute of Medicine of the National Academies recommended raising the daily allowance for vitamin D to 600 IU from 200 and the upper limit tolerance to 4,000 from 2,000.

In 2012, the North American Millers’ Association began conducting technical studies around the fortification of flour with vitamin D, and the group submitted a draft petition to the Food and Drug Administration, allowing the addition of 80 IU of vitamin D per 30 grams of whole grain and enriched flour. The initiative never moved forward. Other industry actions include, in the 2000s, Lallemand launched a yeast with naturally higher vitamin D content, and more recently, in 2023, the FDA okayed a petition by Kellogg Co. to increase fortification of cereal and allow fortification of grain-based bars.

Over this period, promising research findings suggesting vitamin D may be beneficial were accompanied by other data showing little benefit for most individuals. Hopes vitamin D would prove a panacea for conditions ranging from cancer to depression were dashed.

In an article in Scientific American published earlier this year chronicling the rise and fall of vitamin D mania, the writer Christie Aschwanden concluded, “When scientists tried administering it as a means to prevent or treat those problems, the wonder supplement failed miserably.” 

While perhaps not a miracle drug, Aschwanden said studies have found vitamin D provides numerous benefits.

Because intake of vitamin D has been linked to the prevention or reduction of risk of many diseases, the group of scientists led by Demay participating in the study posed a series of questions related to the use of vitamin D and vitamin D testing to lower the disease risk. Scientific studies related to the vitamin were assessed using the agreed upon questions as guide.

Explaining their work, the authors said associations with vitamin D have been demonstrated in studies between vitamin D and a “variety of common disorders, including musculoskeletal, metabolic, cardiovascular, malignant, autoimmune, and infectious diseases. Although a causal link between serum 25(OH)D (the principal circulating form of vitamin D) concentrations and many disorders has not been clearly established, these associations have led to widespread supplementation with vitamin D and increased laboratory testing for 25(OH)D in the general population. The benefit-risk ratio of this increase in vitamin D use is not clear, and the optimal vitamin D intake and the role of testing for 25(OH)D for disease prevention remain uncertain.”

In assessing research regarding vitamin D, the panel of researchers gave higher prioritization to studies conducted as randomized placebo-controlled trials in general populations, but such studies were not always available. The paper suggested considerable additional scientific research is needed to more accurately understand the need for vitamin D in the diet.

“The panel suggests empiric vitamin D supplementation for children and adolescents aged 1 to 18 years to prevent nutritional rickets and because of its potential to lower the risk of respiratory tract infections; for those aged 75 years and older because of its potential to lower the risk of mortality; for those who are pregnant because of its potential to lower the risk of preeclampsia, intra-uterine mortality, preterm birth, small-for-gestational-age birth, and neonatal mortality; and for those with high-risk prediabetes because of its potential to reduce progression to diabetes,” the researchers concluded.

Additionally, the panel said individuals older than 50 years who need vitamin D should receive administration daily rather than in high doses.

Because most natural foods are not rich sources of vitamin D, supplementation should be achieved through “a combination of fortified foods and supplements that contain vitamin D,” the researchers said.

Children: from bone health to immunity

Addressing individually the various population groups it explored, the researchers said many children around the world are deficient in vitamin D. The prevalence is significantly higher in northern Europe, they said.

Even though the importance of vitamin D for the prevention of rickets, a bone disease affecting children, has been known for decades, the researchers said the condition currently is on the rise in high-income countries.

The authors took a deep look, too, at the evidence vitamin D may help prevent respiratory infections in children, noting such illnesses are very common and that pneumonia is “the most common infectious cause of death in the first five years of life.”

The researchers also were interested in the role, possibly long-lasting, vitamin D may play in immunity.

“Childhood offers a unique window of opportunity to train the immune system,” the study said. “Thus, inadequate vitamin D status in childhood may affect disease vulnerability throughout the lifespan.”

Based on its work, the group concluded vitamin D supplementation would be beneficial for many and that undesirable effects are “likely to be trivial for all.”

“An additional study suggested that universal vitamin D supplementation via flour fortification would be cost-saving, while targeted supplementation of children would be cost-effective,” the study said.

Benefits for healthy adults prove elusive

For adults under 50, though, the researchers said controlled studies have found no benefits from vitamin D supplementation when it comes to the prevention of respiratory infections.

As individuals age, vitamin D status may decrease for various reasons, including reduced intake of dairy and fish and increased weight, as well as lower sun exposure/reduced biosynthesis capacity, the researchers said. The decrease is “most marked above age 75 years,” they added.

The strongest case for supplementation among adults between the ages of 50 and 74 appears to be reducing the risk of bone fractures.

“The period between 50 and 74 years of age corresponds to a time of bone loss related to menopause and normal aging, decreasing muscle function, and increasing fall risk, all predisposing to increased risk of fractures,” the authors said. “Importantly, some studies suggest that these risks can be attenuated by vitamin D and calcium.”

The review of studies showed a modest reduction in the risk of bone fractures from vitamin D supplementation. For a range of other negative outcomes studied extensively, research has found no benefit from vitamin D supplementation. These include cancer, cardiovascular disease and kidney stones. While raising questions about whether the studies should be considered definitive, the researchers do not recommend comprehensive supplementation for adults between 18 and 74 beyond the recommendation of the Institute of Medicine.

Studies a mixed bag for seniors

While recommending vitamin D supplementation for adults 75 years and older, the authors warned that it is not clear that supplementation will reduce the risk of falls, fractures and respiratory disease among the elderly. On the other hand, the researchers cited data showing supplementation “probably results in a slight decrease in all-cause mortality,” among this group.

Numerous factors point to the importance of vitamin D for pregnant women, beginning with the dependence of the fetus on maternal circulation of the vitamin for placental metabolism and transfer of vitamin D metabolites, the study said. Low levels of vitamin D are associated with several life-threatening neonatal conditions, including cardiomyopathy.

The researchers said eight studies suggest vitamin D intake may reduce the risk of preeclampsia. It also may slightly reduce the risk of stillborn births and neonatal mortality and also may lower the risk of pre-term birth, low birthweight and gestational diabetes.

How much vitamin D is needed during pregnancy and when is not fully understood, the authors said.

“Accordingly, preconception or pregnancy-specific recommendations for vitamin D are not universal, nor is there a consensus on the dosage of vitamin D or 25(OH)D level required to support a healthy pregnancy,” they said.

Solid evidence for prediabetics

The importance of addressing prediabetes and the role vitamin D may play were emphasized in the study.

“In the United States, more than one in three adults 18 years and older have prediabetes, and only about 20% of these individuals have been informed of their prediabetes status by a health care professional,” the study said.

To reduce this population’s risk of developing diabetes, “intensive lifestyle changes focused on weight loss and increased physical activity” often are emphasized and are effective, the authors said.

“However, these lifestyle modifications are challenging to maintain over the long term,” they added.

Several studies over the past 10 years have addressed the role of vitamin D in “attenuating the progression” of adults with prediabetes to diabetes, the researchers said. For their analysis, the group looked at 15 randomized controlled trials.

Studies showed a 15% reduction in new-onset diabetes among subjects taking vitamin D versus placebo. In other studies, subjects taking vitamin D experienced a reduction in blood sugar, versus subjects taking a placebo.