Elsevier

Maturitas

Volume 62, Issue 3, 20 March 2009, Pages 248-262
Maturitas

Review
Vitamin D metabolism and cardiovascular risk factors in postmenopausal women

https://doi.org/10.1016/j.maturitas.2008.12.020Get rights and content

Abstract

Objectives

The purpose of this review is to focus on the association of vitamin D and cardiovascular risk factors in postmenopausal women.

Methods

Review of the relevant literature and results from recent clinical studies as well as critical analysis of published results concerning the association of vitamin D and cardiovascular risk factors in postmenopausal women obtained from both a PubMed and individual searches.

Results and discussion

Both basic science and clinical studies support the protective role of vitamin D on cardiovascular health, although there are controversial results in the literature. Hypovitaminosis D is associated with disturbed glucose metabolism and pancreatic β-cell dysfunction, lipoprotein alterations, hypertension, overweight and obesity. The evidence highlights the importance of improving vitamin D status in the general population for the prevention of adverse long-term health risks, including cardiovascular health. The optimal vitamin D dose remains to be determined. However, correction of low vitamin D itself does not guarantee the prevention of these conditions.

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.

References (126)

  • K. Tai et al.

    Glucose tolerance and vitamin D: effects of treating vitamin D deficiency

    Nutrition

    (2008)
  • W.G. John et al.

    Hypovitaminosis D is associated with reductions in serum apolipoprotein A-I but not with fasting lipids in British Bangladeshis

    Am J Clin Nutr

    (2005)
  • G.C. Major et al.

    Supplementation with calcium + vitamin D enhances the beneficial effect of weight loss on plasma lipid and lipoprotein concentrations

    Am J Clin Nutr

    (2007)
  • L.D. Carbone et al.

    25-Hydroxyvitamin D, cholesterol, and ultraviolet irradiation

    Metabolism

    (2008)
  • R. Krause et al.

    Ultraviolet B and blood pressure

    Lancet

    (1998)
  • R. Scragg et al.

    Serum 25-hydroxyvitamin D, ethnicity, and blood pressure in the Third National Health and Nutrition Examination Survey

    Am J Hypertens

    (2007)
  • S.E. Judd et al.

    Optimal vitamin D status attenuates the age-associated increase in systolic blood pressure in white Americans: results from the third National Health and Nutrition Examination Survey

    Am J Clin Nutr

    (2008)
  • H.M. Macdonald et al.

    Vitamin D status in postmenopausal women living at higher latitudes in the UK in relation to bone health, overweight, sunlight exposure and dietary vitamin D

    Bone

    (2008)
  • J. Wortsman et al.

    Decreased bioavailability of vitamin D in obesity

    Am J Clin Nutr

    (2000)
  • E.T. Aasheim et al.

    Vitamin status in morbidly obese patients: a cross-sectional study

    Am J Clin Nutr

    (2008)
  • J.I. Botella-Carretero et al.

    Vitamin D deficiency is associated with the metabolic syndrome in morbid obesity

    Clin Nutr

    (2007)
  • C. Mathieu et al.

    The coming of age of 1,25-dihydroxyvitamin D(3) analogs as immunomodulatory agents

    Trends Mol Med

    (2002)
  • I. Kowalska et al.

    Insulin resistance, serum adiponectin, and proinflammatory markers in young subjects with the metabolic syndrome

    Metabolism

    (2008)
  • J.B. Richards et al.

    Higher serum vitamin D concentrations are associated with longer leukocyte telomere length in women

    Am J Clin Nutr

    (2007)
  • S.S. Schleithoff et al.

    Vitamin D supplementation improves cytokine profiles in patients with congestive heart failure: a double-blind, randomized, placebo-controlled trial

    Am J Clin Nutr

    (2006)
  • F.R. Pérez-López

    Vitamin D: the secosteroid hormone and human reproduction

    Gynecol Endocrinol

    (2007)
  • M.F. Holick

    Vitamin D deficiency

    N Engl J Med

    (2007)
  • P. Lips et al.

    A global study of vitamin D status and parathyroid function in postmenopausal women with osteoporosis: baseline data from the multiple outcomes of raloxifene evaluation clinical trial

    J Clin Endocrinol Metab

    (2001)
  • L. Rejnmark et al.

    Plasma 1,25(OH)2D levels decrease in postmenopausal women with hypovitaminosis D

    Eur J Endocrinol

    (2008)
  • Pérez-López FR, Chedraui P, Haya J. Vitamin D acquisition and breast cancer risk. Reprod Sci...
  • T.G. Marshall

    Vitamin D discovery outpaces FDA decision making

    Bioessays

    (2008)
  • M. Rees et al.

    Primary prevention of coronary heart disease in women

    Menopause Int

    (2008)
  • G.L. Burke et al.

    The impact of obesity on cardiovascular disease risk factors and subclinical vascular disease: the Multi-Ethnic Study of Atherosclerosis

    Arch Intern Med

    (2008)
  • L.B. Tankó et al.

    Relationship between osteoporosis and cardiovascular disease in postmenopausal women

    J Bone Miner Res

    (2005)
  • R. Vieth et al.

    Inaccuracies in relating 25-hydroxyvitamin D to ischemic heart disease

    Eur J Epidemiol

    (2003)
  • S.M. Grundy et al.

    Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement

    Circulation

    (2005)
  • Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III)....
  • E.S. Ford et al.

    Prevalence of the metabolic syndrome among US adults: findings from the Third National Health and Nutrition Examination Survey

    J Am Med Assoc

    (2002)
  • P.W. Wilson et al.

    Clustering of metabolic factors and coronary heart disease

    Arch Intern Med

    (1999)
  • A.G. Bertoni et al.

    Insulin resistance, metabolic syndrome, and subclinical atherosclerosis: The Multi-Ethnic Study of Atherosclerosis (MESA)

    Diabetes Care

    (2007)
  • E. Oda

    The metabolic syndrome as a concept of adipose tissue disease

    Hypertens Res

    (2008)
  • E.S. Ford et al.

    Concentrations of serum vitamin D and the metabolic syndrome among U.S. adults

    Diabetes Care

    (2005)
  • J.P. Reis et al.

    Relation of 25-hydroxyvitamin D and parathyroid hormone levels with metabolic syndrome among US adults

    Eur J Endocrinol

    (2008)
  • E. Hyppönen et al.

    25-Hydroxyvitamin D, IGF-1, and metabolic syndrome at 45 years of age. A cross-sectional study in the 1958 British Birth Cohort

    Diabetes

    (2008)
  • R. Scragg et al.

    Serum 25-hydroxyvitamin D, diabetes, and ethnicity in the Third National Health and Nutrition Examination Survey

    Diabetes Care

    (2004)
  • A.G. Need et al.

    Relationship between fasting serum glucose, age, body mass index and serum 25 hydroxyvitamin D in postmenopausal women

    Clin Endocrinol (Oxf)

    (2005)
  • G. Targher et al.

    Serum 25-hydroxyvitamin D3 concentrations and carotid artery intima-media thickness among type 2 diabetic patients

    Clin Endocrinol (Oxf)

    (2006)
  • S. Liu et al.

    Dietary calcium, vitamin D, and the prevalence of metabolic syndrome in middle-aged and older U.S. women

    Diabetes Care

    (2005)
  • A.G. Pittas et al.

    Vitamin D and calcium intake in relation to type 2 diabetes in women

    Diabetes Care

    (2006)
  • A.G. Pittas et al.

    The role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis

    J Clin Endocrinol Metab

    (2007)
  • Cited by (0)

    View full text