A Narrative Review of the Evidence for Variations in Serum 25-Hydroxyvitamin D Concentration Thresholds for Optimal Health

Abstract

Vitamin D3 has many important health benefits. Unfortunately, these benefits are not widely known among health care personnel and the general public. As a result, most of the world’s population has serum 25-hydroxyvitamin D (25(OH)D) concentrations far below optimal values. This narrative review examines the evidence for the major causes of death including cardiovascular disease, hypertension, cancer, type 2 diabetes mellitus, and COVID-19 with regard to sub-optimal 25(OH)D concentrations. Evidence for the beneficial effects comes from a variety of approaches including ecological and observational studies, studies of mechanisms, and Mendelian randomization studies. Although randomized controlled trials (RCTs) are generally considered the strongest form of evidence for pharmaceutical drugs, the study designs and the conduct of RCTs performed for vitamin D have mostly been flawed for the following reasons: they have been based on vitamin D dose rather than on baseline and achieved 25(OH)D concentrations; they have involved participants with 25(OH)D concentrations above the population mean; they have given low vitamin D doses; and they have permitted other sources of vitamin D. Thus, the strongest evidence generally comes from the other types of studies. The general finding is that optimal 25(OH)D concentrations to support health and wellbeing are above 30 ng/mL (75 nmol/L) for cardiovascular disease and all-cause mortality rate, whereas the thresholds for several other outcomes appear to range up to 40 or 50 ng/mL. The most efficient way to achieve these concentrations is through vitamin D supplementation. Although additional studies are warranted, raising serum 25(OH)D concentrations to optimal concentrations will result in a significant reduction in preventable illness and death.

Effect of Cholecalciferol Supplementation on the Clinical Features and Inflammatory Markers in Hospitalized COVID-19 Patients: A Randomized, Open-Label, Single-Center Study

“…Recently published systematic reviews and meta-analyses have demonstrated that vitamin D insufficiency and deficiency are highly prevalent in patients with moderate and severe COVID-19 [1,17]. At present, there are sufficient data to demonstrate that a low serum 25(OH)D concentration increases the disease severity and risk of death in patients with COVID-19 [10,18]. A study conducted in the United States showed that patients with a positive SARS-CoV-2 test and a 25(OH)D concentration of 15 ng/mL compared to 40 ng/mL had a 20% greater risk of hospitalization (p = 0.009) and an increased risk of mortality by 53% (p = 0.001) [19].…”

Suboptimal Consumption of Relevant Immune System Micronutrients Is Associated with a Worse Impact of COVID-19 in Spanish Populations

“…In addition, low circulating levels of 25-hydroxyvitamin D are associated with increased incidence and severity of disease triggered by SARS-CoV-2 [ 32 , 33 , 34 , 35 ]. Moreover, plasma concentrations of 25-hydroxyvitamin D above 30 ng/mL are associated with lesser risk for cardiovascular disease and all-cause mortality rate, pointing out that vitamin D supplementation is the most efficient way to accomplish these concentrations [ 36 ]. In this context, a randomized controlled trial carried out on health workers with the aim of analyzing the reduction in the severity of COVID-19 according to the dose of vitamin D3 (cholecalciferol) supplementation for three months showed the need for high doses of supplementation [ 37 ].…”

Malnutrition in Older Adults—Effect on Falls and Fractures: A Narrative Review

“…These doses are also recommended for the treatment of vitamin D deficiency, but higher vitamin D doses (e.g., 6000 IU per day) may be used for the first 4 to 12 weeks of treatment if a rapid correction of vitamin D deficiency is clinically indicated before continuing with a maintenance dose of 800 to 2000 IU per day. Treatment success may be evaluated after 6 to 12 weeks in certain risk groups (e.g., patients with malabsorption syndromes) via measurement of serum 25(OH)D, with an aim to target concentrations of 30 to 50 ng/mL (75 to 125 nmol/L) [ 36 , 37 ].…”