The main role of vitamin D is to regulate blood levels of minerals such as calcium, phosphorus, and, to a lesser extent, magnesium. Thus, vitamin D is vital for bone health and growth, and its deficiency leads to two well-known skeletal disorders: rickets in children and osteomalacia in adults [8].
Besides this important physiological role,
vitamin D plays a complex role in numerous biological processes that regulate
the immune system, inflammatory pathways and many vital cellular processes [9].
An insufficient vitamin D level has been
identified as a worldwide health problem, especially in Middle Eastern
countries [10, 11]. Risk factors include advanced age (especially if
institutionalised), African American race, obesity, limited sun exposure,
diabetes and chronic illnesses [12, 13]. Recent evidence has linked vitamin D
deficiency with many adverse health outcomes such as hypertension, type II
diabetes, cancer [14] and many autoimmune diseases (e.g. type I diabetes in
children and multiple sclerosis) [15].
Hypovitaminosis D has also been linked to respiratory
problems (e.g. higher frequency of asthma exacerbations and tuberculosis
reactivation) [16]. It may even have an influence on certain neonatal
conditions such as the risk of small for gestational age births and neonatal
hypocalcaemia [17].
Vitamin
D may affect different biological mechanisms, including insulin sensitivity,
the renin-angiotensin-aldosterone system (and consequently, blood pressure),
inflammatory cytokines, and vascular muscle contractility and response to
injury [18]. In the recent literature, studies investigating the effects of the
vitamin D level on the fasting lipid profile have given conflicting
results.
In this retrospective study, we investigated
the relationship between 25(OH) D3 levels and fasting serum lipid profile
parameters in Jordanian adults.
Methods
Our study was approved by the ethics committee
of the Royal Medical Services, Amman, Jordan.
This
study was carried out on 762 patients. All were attending the internal medicine
clinics at King Hussein Medical Centre during the period from 1 January 2017 to
1 February 2018.In the Royal Medical Services, patients at the age of 14 years
are no longer treated at the pediatric clinic.
They are treated in adult clinics instead. This is why we included patients
starting from the age of 14 year in this adult cohort.
After an overnight fast of 10–12 hours, a
single venous blood sample was collected from each patient into gel separator
yellow top tubes between 8:00 and 10:00 am. The samples were allowed to clot
for 15–30 minutes at room temperature, then were centrifuged at 4000 g for 10
minutes and immediately analyzed for lipid profile parameters and 25(OH) D3
levels. The fully automated analysis for all the parameters in our study was
carried out in the clinical chemistry laboratory at the Princess Iman Centre
for Research and Laboratory Sciences. Serum 25(OH) D3 levels were measured
using a Cobas e411 auto-analyzer (Roche Diagnostics GmbH, Mannheim, Germany). Although
1,25(OH)2D3 is the
most potent form, 25(OH)D3 levels
are not influenced by parathyroid hormone and therefore reflect vitamin D
status more accurately. The triglycerides (TG), total cholesterol, low-density
lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol
levels were measured using a Cobas 501 auto-analyzer (Roche Diagnostics GmbH,
Mannheim, Germany). In our center, the reference ranges for the lipid profile
parameters are: total cholesterol, 150–200 mg/dL; TGs, 50–200 mg/dL; HDL
cholesterol, 35–65 mg/dL; and LDL cholesterol, 50–150 mg/dL. There is a slight
variation from universal values. Recently, the National Lipid Association and
the National Cholesterol Education Program defined desirable
levels as total cholesterol < 200 mg/dL, TGs < 150 mg/dL, LDL < 100
mg/dL (with the range between 100 and 129 mg/dL termed above desirable) and HDL
> 40 mg/dL for females and >50 mg/dL for males.
Statistical analysis
Based on the serum lipid levels (total
cholesterol, triglycerides, HDL cholesterol and LDL cholesterol), subjects were
divided into two groups: those with normal levels, and those with high levels.
With regard to the serum 25(OH) D3 level, the subjects were divided into three
groups: the vitamin D deficiency group [25(OH)D3< 20
ng/mL], the insufficiency group [25(OH)D3 20–30
ng/mL] and the sufficiency group [25(OH)D3> 30
ng/mL]. The management and statistical analysis of the data were performed
using the software SPSS 20.0 for Windows (SPSS Inc., Chicago, IL, USA) and the
Microsoft Excel 2007 program. All variables were presented as means and
standard deviation (SD), and a P-value < 0.05 was considered to be
statistically significant.
Results
The study included 762 patients with a mean
age of 48.85 years (range, 14–92 years) and a female predominance: 473 (62%)
were female and 289 (38%) were male. We divided our study subjects into three
groups according to their 25(OH) D3 levels, as shown in (Table I).
Table I:
25(OH) D3 levels in all 762 subjects
Discussion
In the
present study, serum vitamin D level was positively correlated with all lipid
profile parameters which is partly beneficial in terms of higher HDL levels,
and partly harmful in terms of higher total cholesterol, LDL and TGs. Wang et
al. and Jorde et al. have shown the same effect of vitamin D on total cholesterol
and LDL in women [33, 34]. In our study, however, no significant differences
were found between men and women. A pilot study conducted on Hispanic/Latino
adults suggested a positive association between vitamin D and lipids (results
similar to our study), although the sample size of their study was small [42].
Glueck et al. found in a group of hyperlipidemia patients that serum vitamin D
level was a significant independent positive determinant of HDL, but a negative
one for the other lipid parameters [41].Studies in the literature vary in their
results; some found no clinical impact of vitamin D deficiency on lipids in
older women and no effect on TGs in patients with type II diabetes [32, 43].
Others even found an inverse correlation. Jorde and Grimnes observed that serum
25(OH) D was positively associated with a favorable lipid profile [30]. Vitamin
D was inversely related to TG levels in Saudi postmenopausal women and in
Iranian type 2 diabetic patients, in addition to LDL in another Japanese study
[31, 39, and 40].
Aside from observational studies and reviews,
some interventional studies failed to support a protective effect of vitamin D
supplementation on cardiovascular health [35–37]. Heikkinen et al. even
demonstrated adverse effects on the lipid profile [38]. This supports our
findings regarding total cholesterol, LDL and TGs.
One of the limitations of this study was its
retrospective nature. It was difficult to determine the subjects’ past medical
history and their medication history. It was limited to a correlation between
laboratory figures only; more clinical laboratory correlation is needed to
better assess the association between dyslipidaemia and vitamin D deficiency. Well-designed
prospective, placebo-controlled randomised interventional studies are needed to
determine the effects of vitamin D supplementation. Case-control studies could be performed to
include variables such as season of the year, smoking status, medication use,
vitamin D intake, calcium intake, visceral fat area and cardiorespiratory
fitness.
Conclusion:
Our
present study showed a direct positive association between 25(OH)
D3 level and total cholesterol, TGs, LDL and HDL. This raises the question as
to whether hypovitaminosis D presents a potential risk factor for
cardiovascular disease by reducing HDL or a beneficial effect by lowering total
cholesterol, TGs and LDL.
Abbreviations:
|
1,25(OH)2D3
|
1,25-dihydroxyvitamin D3
|
|
25(OH)D3
|
|
25-hydroxyvitamin D3
|
|
HDL
|
|
High-density lipoprotein
|
|
LDL
|
|
Low-density lipoprotein
|
|
TGs
|
|
Triglycerides
|
|
|
|
|
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