The Effect of Vitamin D Supplementation on Cardiovascular Risk Factors (D-COR)

The Effect of Vitamin D Supplementation on Cardiovascular Risk Factors in Subjects With Low Serum 25-hydroxyvitamin D Levels

Six-hundred subjects with vitamin D deficiency will be randomized to vitamin D 3000 IU per day versus placebo for 4 months, with effects on cardiovascular risk factors as main endpoint

Vitamin D is a hormone with effects not only on the skeleton, but on most tissues in the body. Lack of vitamin D is associated with cardio-vascular disease (CVD) and type 2 diabetes, and also with risk factors for these diseases like hypertension, dyslipidemia, insulin resistance, and endothelial dysfunction. However, intervention studies with vitamin D have been inconclusive regarding diseases and risk factors. Most of these studies were done in white, Western populations in subjects fairly vitamin D sufficient, and accordingly, no benefits were to be expected. Also, in many studies the doses of vitamin D have been too low, and the studies underpowered. To firmly establish the role of vitamin D regarding CVD risk factors we will in the present study include 600 subjects with vitamin D deficiency (serum 25-hydroxyvitamin D (25(OH)D) < 30 nmol/L) and randomize to high dose vitamin D (3000 IU per day) versus placebo for four months. The subjects will be recruited based on 25(OH)D measurements in the forthcoming 7th survey in the Tromsø study where more than 20 000 subjects are expected to attend. If our hypotheses are correct and the vitamin D supplement has a positive effect, this will be of great importance not only in countries with low sun exposure, but particularly for subjects in developing countries where vitamin D deficiency is highly prevalent.

vitamin D, blood pressure, serum lipids, glucose metabolism, muscle function, arterial stiffness, depression, psoriasis, sleep, bone density

placebo capsules (identical looking to the vitamin D capsules) will be given once a week for 4 months

Change from baseline in hand-grip, quadriceps and biceps muscle strength measured by hand held dynamometry .

Change from baseline in arterial stiffness and endothelial function evaluated with pulse wave velocity

Change from baseline in arterial stiffness and endothelial function evaluated with augmentation index (AIX)

Change from baseline in arterial stiffness and endothelial function evaluated with the subendocardial viability ratio (SEVR)

Change from baseline in bone mass density measured with dual energy x-ray absorptiometry (DEXA) at the lumbar spine and hip

Change from baseline in the bone turnover marker serum collagen type 1 cross-linked C-telopeptide (CTX-1)

Change from baseline in the glycosylation marker the receptor for advanced glycosylation end products (s-RAGE)

Change from baseline in psoriasis Activity in subjects with psoriasis evaluated with the Self-Administered Psoriasis Area Severity Index (SAPASI)

Change from baseline in psoriasis Activity in subjects with psoriasis, evaluated with the Dermatological Life Quality Index (DLQI)

Change from baseline in psoriasis Activity in subjects with psoriasis, evaluated with the Psoriasis Area Severity Index (PASI)

Change from baseline in sleep pattern evaluated with the Tromsø Study 7th Survey sleep pattern questionnaire

Change from baseline in insulin resistance evaluated with the homeostasis model assessment (HOMA) index based on fasting serum glucose and serum insulin

Change from baseline in proteomic profile with relative quantification in adipose tissue biopsies with the use of Liquid chromatography mass spectrometry Technology (LC-MS/MS)

Change from baseline in metabolomic profile with relative quantification in adipose tissue biopsies with the use of Liquid chromatography mass spectrometry Technology (LC-MS/MS)

Inclusion Criteria: participated in The 7th survey in The Tromsø study vitamin D deficiency Exclusion Criteria: primary hyperparathyroidism granulomatous disease reduced kidney function systolic blood pressure > 174 mmHg diastolic blood pressure > 104 mmHg diabetes renal stones last 5 years use of solarium on regular basis planned holidays in tropical areas clinical depression clinical signs of vitamin D deficiency (muscle weakness) use of vitamin D supplements serious illness

Jorde R, Kubiak J, Svartberg J, Fuskevag OM, Figenschau Y, Martinaityte I, Grimnes G. Vitamin D supplementation has no effect on cognitive performance after four months in mid-aged and older subjects. J Neurol Sci. 2019 Jan 15;396:165-171. doi: 10.1016/j.jns.2018.11.020. Epub 2018 Nov 17.