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DAYLIGHT: Vitamin D supplementation did not lower BP
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In vitamin D-deficient patients with prehypertension or stage 1 hypertension, vitamin D supplementation did not decrease BP levels.
“A large body of epidemiological and experimental evidence suggests that vitamin D deficiency may promote hypertension,” the researchers wrote. “This raises the possibility that vitamin D supplementation could be a simple intervention to reduce blood pressure, but data from prospective, randomized trials are limited.”
For the randomized, double blind, multicenter DAYLIGHT trial, researchers evaluated high-dose (4,000 IU/day) vs. low-dose (400 IU/day) vitamin D3 supplementation in 534 US adults (mean age, 38 years; 62% men; 46% white; 48% black) with prehypertension and untreated stage 1 hypertension plus vitamin D deficiency. Participants returned for follow-up visits every 2 months after randomization through September 2013. At each visit, four BP measurements and blood samples were taken. Researchers also collected 24-hour ambulatory BP measurements at baseline and 6 months. Seventy-two percent of participants completed the 6-month study, and 85% had at least one follow-up BP measurement.
At baseline, mean 24-hour systolic BP was 127 mm Hg and mean 24-hour diastolic BP was 78 mm Hg.
The primary endpoint was change in mean 24-hour ambulatory systolic BP. At 6 months, the researchers reported no significant difference in the primary endpoint compared with baseline. The mean change was –0.8 mm Hg for patients assigned high-dose vitamin D and –1.6 mm Hg for patients assigned low-dose vitamin D (P=.71).
No significant changes were reported from baseline to 6 months in mean 24-hour systolic BP (mean change, –1.2 mm Hg in high-dose group, –1 mm Hg in low-dose group; P=.43). The results demonstrated similar results for other secondary BP endpoints including clinic, daytime and nighttime BP measurements.
At baseline, the mean 25-hydroxyvitamin D level was 15 ng/mL, and about three-quarters of participants had levels <20 ng/mL. The mean vitamin D level at 2 months increased to 33 ng/mL in the high-dose group and 20 ng/mL in the low-dose group (P<.001), and levels remained consistent through 6 months.
In additional analyses, “even among individuals with large increases in 25-hydroxyvitamin D during the study, there was no discernible trend toward lower 24-hour blood pressure,” the researchers wrote.
Prespecified subgroup analyses revealed similar results.
Patients assigned both high- and low-dose vitamin D had a similar incidence of adverse events, and no serious adverse events were reported during the study period.
According to the researchers, these findings contradict a sizeable body of observational evidence suggesting a correlation between vitamin D status and hypertension.
“Added to the existing body of evidence from smaller randomized trials, our findings suggest that the association between vitamin D status and hypertension noted in observational studies is not causal,” the researchers wrote.
Disclosure: Two researchers report financial ties with DiaSorin Inc. and LabCorp Inc. The other researchers report no relevant financial disclosures.
Perspective
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Keith C. Ferdinand, MD, FACC, FAHA
DAYLIGHT, the largest prospective, randomized trial to test the effect of vitamin D supplementation on BP, significantly adds to our knowledge on the potential benefit or lack thereof of vitamin D supplementation in patients with hypertension. The DAYLIGHT evidence for lack of BP lowering with vitamin D is important, since large numbers of self-medicated patients and clinicians waste resources with unproven vitamin therapies, while underutilizing proven antihypertensive pharmacotherapy with evidence-based CVD outcome benefits.
At the same time, no clinical trial is perfect, and the decision to measure vitamin D levels and intervene if found to be deficient has to be based on more than one peer-reviewed report.
It is important to point out that in DAYLIGHT, the baseline BPs were approximately 130 mm Hg systolic/82 mm Hg diastolic, there was an apparent high degree of nonadherence, and the achieved vitamin D levels may have been inadequate for actual BP reduction for many volunteers, especially over the short term. These factors give us pause in closing the book on the potential benefits of vitamin D deficiency as either an ideological factor or potential source of therapeutic intervention, especially in older patients with more severe forms of hypertension and African Americans and other persons with dark skin living in Northern latitudes. In such patients, vitamin D deficiency may be a real factor in their disease.
In DAYLIGHT, there was no placebo arm and the 534 individuals were young. While 48% of participants were black, no subgroup benefits were observed. However, a recent large study by Forman et al with 283 black adults (median age, 51 years) reported significant BP lowering with vitamin D supplementation. In that randomized, placebo-controlled trial, cholecalciferol supplementation significantly lowered systolic BP with median 25-hydroxyvitamin D levels achieved at 3 months of 45.9 ng/mL, 34.8 ng/mL and 29.7 ng/mL, respectively, in participants assigned 4,000 IU/day, 2,000 IU/day and 1,000 IU/day, and vitamin D levels lessened but were still improved levels at 6 months (Forman JP. Hypertension. 2013;61:779-785).
Moreover, at the DAYLIGHT final visit, troubling proportions of individuals still had 25-hydroxyvitamin D <20 ng/mL, 21% in the high-dose arm and 48% in the low-dose arm. Higher doses, for a longer period of time, may yet show benefit. Recognizing the difficulty completing these types of clinical trials, it is unfortunate that approximately 20% of participants failed to complete the required follow-up visits, and an additional 10% were withdrawn early for meeting one of the exclusion criteria. The high drop out and apparent suboptimal patient adherence in DAYLIGHT should not deter a thoughtful clinician for considering appropriate detection and correction of insufficient vitamin D levels.
Although the adequate funding and design would be difficult to finalize, a larger, longer study, perhaps placebo-controlled, with more robust dosing and achieved vitamin D blood levels would be ideal.
The lack of conclusive data from DAYLIGHT does not confirm a lack of benefit. Clinicians who treat patients with hypertension, especially African Americans, may still consider documenting vitamin D status and advise supplementation when insufficient. An overenthusiastic interpretation of the negative findings from DAYLIGHT may have the unintended consequence of preventing thousands, if not more, of hypertensive black patients from a potentially low-cost, relatively safe intervention.
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