ReviewVitamin D metabolism and cardiovascular risk factors in postmenopausal women
Introduction
Vitamin D is, in fact, a group of molecules that function as hormones. There are two different forms important in humans: ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3). Vitamin D2 is synthesized by plants. Vitamin D3 is considered the sunshine vitamin because the major source of human vitamin D is endogenous synthesis under ultraviolet (UV) B exposure. In short, the skin transforms a derivative of cholesterol – dehydrocholesterol – normally found in the skin into vitamin D3. The liver, kidneys and other tissues further activate this molecule into 25-hydroxyvitamin D (25(OH)D)1 or calcidiol and the biological main active hormonal form 1,25-dihydroxyvitamin D (1,25(OH)2D) or calcitriol [1]. Recent studies have shown that sunshine levels in far from equator countries are so weak during the winter months that the body makes little to no vitamin D at all, leading to widespread deficiencies of the vitamin. Increased skin pigmentation also reduces the effect of ultraviolet B radiation [2]. Changes in lifestyle, such as working indoors, wearing occlusive clothing, and increasing the use of sunscreen creams, have increased the number of individuals with low vitamin D levels. Vitamin D is also an essential micronutrient found in foods like eggs, liver, fortified milk and orange juice, cod liver oil, sardines, salmon, other oily fish, some cereals, mushrooms, egg yolk, beef liver, cheese and others.
Serum 25(OH)D levels are the best indicator of vitamin D status, although some controversy remains regarding “normal” and “abnormal” values. Optimal levels of 25(OH)D should be at least in the range of 30–50 ng/ml, and possibly higher to maintain general health [3], [4]. It is well established that 25(OH)D serum levels below 5–7 ng/ml induce osteomalacia, serum levels below 10–12 ng/ml induce secondary hyperparathyroidism and osteoporosis, and serum levels above 18–20 ng/ml are usually considered normal or adequate. Low vitamin D levels are associated to a high prevalence of secondary hyperparathyroidism [5], [6]. Aside of this endocrine feedback mechanism, mild degrees of vitamin D insufficiency seems to alter many cell processes since the adequate cell active vitamin D (1,25(OH)2D) level depends on the precursor concentration (25(OH)D). It seems quite plausible that vitamin D insufficiency should be placed at 25(OH)D serum levels below 30 ng/ml (or 75 nmol/l). A level less than 20 ng/dl indicates deficiency. However, definitions of vitamin D deficiency and insufficiency are hampered by the fact that large interlaboratory differences exist in assays for serum 25(OH)D [5]. In addition, there are differing recommendations on defining 25(OH)D deficit since there is not a consensus for its cut-off value for general health [3], [4], [7], [8]. Neither is there any consensus on the serum concentration of 25(OH)D required to maintain the cardiovascular health.
Vitamin D is a regulator of calcium homeostasis, and helps maintain normal cell function in many organs and tissues. When vitamin D receptor (VDR) or 25(OH)D 1α-hydroxylase – the rate-limiting enzyme responsible for the synthesis of 1,25(OH)2D – calcium homeostasis is impaired, leading to hypocalcemia and secondary hyperparathyrodism which induce bone alterations. However, the broad VDR distribution suggests that the vitamin D endocrine system might have additional functions on the immune system, cardiovascular system, and reproductive system, depending on the individual genetic background [3], [7], [8], [9], [10]. Cardiovascular disease (CVD) is the leading cause of death among postmenopausal women in Western countries. Although causes are unclear, there are several risk factors including increased age, gender, heredity and race, cigarette smoking, high blood cholesterol, high blood pressure (BP), physical inactivity, obesity and overweight, diabetes mellitus, and individual response to stress. The influences of ovarian hormones as well as adipocyte factors, leptin, and ghrelin have been reviewed in relation to the menopause transition [11], [12], [13], [14]. Low bone mineral density (BMD) has been reported associated to both a high risk of cardiovascular disease that is proportional to the severity of osteoporosis at the time of the diagnosis [15], and non-cause-specific and cardiovascular mortality [16]. Insufficiency of vitamin D is common among postmenopausal women and is associated with osteoporosis [4]. Low 25(OH)D levels have been also associated with cardiovascular disease events [17]. My objective is to review the evidence published during the recent years concerning vitamin D and cardiovascular risk factors in postmenopausal women.
Section snippets
The metabolic syndrome, other risk conditions and vitamin D
The metabolic syndrome or syndrome X is a clustering of metabolic abnormalities that increases the risk of developing atherosclerotic disease and type 2 diabetes with subsequent complications including acute ischemic heart disease (IHD) and stroke [18], [19]. There are currently two major definitions for metabolic syndrome provided by the International Diabetes Federation (IDF) and the US National Institute of Health Third Adult Treatment Panel (ATPIII) [19], [20]. The revised ATPIII and IDF
Experimental evidence on vitamin D metabolism and the cardiovascular system
The action of the vitamin D endocrine system is mediated by both genomic and non-genomic pathways. The former is activated by the binding of 1, 25(OH)2D3 to a specific cytosolic/nuclear VDR, whereas non-genomic pathways are activated via a putative membrane vitamin D receptor and might be responsible for rapid effects of vitamin D [86].
Vitamin D and cardiovascular disease
Low vitamin D levels may favour the metabolic syndrome, insulin resistance, glucose and lipoprotein alterations, hypertension, and endothelial dysfunction which are related to the cardiovascular disease (Fig. 1). Different geographic, epidemiological, and clinical classical studies have suggested that there are excess of cardiovascular risk factors in individuals with insufficient or low vitamin D serum levels [112], [113], [114]. The results from the WHI cohort suggest a lack of effect on
Final remarks
There is a general consensus among health researchers and practitioners held that the primary function of vitamin D is in helping the body to maintain a healthy level of calcium in the blood, primarily for proper bone health throughout an individual's lifetime. But research is showing that this important vitamin is playing a much larger role in the overall health of the body. Insufficiency of vitamin D has been associated with a large number of chronic conditions such as muscleskeletal
Conflict of interest
None.
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