{"id":53334,"date":"2023-12-31T10:22:50","date_gmt":"2023-12-31T10:22:50","guid":{"rendered":"https:\/\/biomedpharmajournal.org\/?p=53334"},"modified":"2024-10-07T10:09:52","modified_gmt":"2024-10-07T10:09:52","slug":"cardio-metabolic-indices-in-relation-to-serum-vitamin-d-levels-among-middle-aged-adults","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol16no4\/cardio-metabolic-indices-in-relation-to-serum-vitamin-d-levels-among-middle-aged-adults\/","title":{"rendered":"Cardio-Metabolic Indices in Relation to Serum Vitamin D Levels among Middle-Aged Adults"},"content":{"rendered":"\n<p class=\"wp-block-paragraph\"><strong>Introduction<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Vitamin deficiencies are an important health concern because they contribute to the pathogenesis, development, mortality, and morbidity loads of many chronic diseases, including cardiovascular diseases (CVD); it is a significant public health issue. Globally, CVDs account for more than 40% of all deaths, making them one of the main causes of illness and death<sup>1<\/sup>. Vitamin D (25(OH)D), acts as a steroid hormone<sup>2<\/sup>. 25(OH)D has a role in several human organ developments, including calcium homeostasis, bone formation, cardiovascular control, and muscular and brain activity among others<sup>3<\/sup>. Its deficiency is an autonomous risk feature for cardiovascular disease development<sup>4,5<\/sup>. One of the multifactorial properties of vitamin D is to regulate blood pressure by suppressing renin synthesis and thereby renin-angiotensin system (RAS), and it outperforms in anti-inflammatory, anti-hypertrophic, anti-thrombotic, and anti-diabetic properties. It also regulates the traditional cardiovascular risk elements. These elements regulate the progress of diseases including hypertension, metabolic disease, and malignancy, infectious and autoimmune illnesses, which are the main reasons for disease and death in advanced countries<sup>6,7<\/sup>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The\ndilemma about 25(OH)D deficiency among different communities persists due to\nunavailable resources from different races. According to Holick et al., across\nall civilizations and age categories, more than 80% of the world&#8217;s population\nhas a lower serum concentration of 25(OH)D<sup>8<\/sup>. However, a number of\nresearch<sup>9-11<\/sup> reported a greater incidence rate of serum 25(OH)D\ninsufficiency in the global populace. Epidemiological studies have stated the\nconnection between a low concentration of 25(OH)D and various disease states.\nAccording to the prospective studies<sup>12\u201315<\/sup>, low\n25(OH)D can accentuate the severity of cardio-metabolic risk factors<sup>16,17<\/sup>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">By\nkeeping global population risk in mind, the risk of CVD can be deaccelerated by\nimplementing a treatment to overcome vitamin D deficiency<sup>18<\/sup>. Though\nmiddle-aged adults are more prone to CVD as well as hypovitaminosis D, the\naccuracy of data that could establish the relation between 25(OH)D deficiency\nand cardio-metabolic risk elements is limited. Therefore, the current study attempted to investigate the relationship\nbetween serum vitamin D concentration and cardio-metabolic risk elements in the\nmiddle-aged populace.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Materials and Methods<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">It was observational research. A total of 100 subjects both male and female, between the age of 45 and 65, were enrolled in the study. Study subjects were selected from the patients undergoing routine checkups in the Medicine Department at the tertiary care Hospital, Deralakatte, Mangalore, Karnataka, India. &nbsp;<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Volunteers\nwere chosen based on the inclusion criterion of age group 45 to 65 years and volunteers\nwith vitamin D levels (30-100 ng\/ml). Patients with hypertension, Diabetic Mellitus,\nChronic Kidney disease, Liver Cirrhosis, acute inflammatory-infectious illness,\nand patients who were on vitamin D supplements were not considered for the\nstudy. <\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The\nInstitutional Ethical Committee approved the study after scrutinizing it in\ndetail. A comprehensive medical history was taken from all subjects. BMI, fat\npercentage, and waist-hip ratio were calculated by using standard techniques<sup>19<\/sup>. The following indices, including HRV, mean\nblood pressure, pulse pressure, and Resting Heart Rate (RHR), were used to\nassess cardiovascular risk factors.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">To assess HRV\ncomponents, like TP, HF, LF, and Very Low Frequency (VLF) characteristics, Lead\nII ECG data with a sampling frequency of 1000Hz was collected for 5 minutes\nwhile the participant remained supine. The amount of HF power spectrum (0.15 to\n0.4 Hz) was used to determine whether there had been any cardio-vagal changes.\nThe LF power spectrum, which mainly reflects the cardio-sympathetic nervous\nsystem activity, was in the range of 0.04 to 0.15 Hz. Additionally, the LF\/HF\nratio depicts the sympathovagal balance<sup>20<\/sup>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">2 ml of Venous blood was drawn with all precautions from\nthe median cubital vein for Vitamin D assessment. The sample was centrifuged to\nobtain serum and then vitamin D concentrations were analysed using an ELISA kit\n(Krishgen Biosystems, India) as per instructions given by the manufacturer.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Statistical Evaluation<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The\nstatistical data analysis was done using IBM SPSS software version 22.0. The\nlink between vitamin D levels and markers of cardiometabolic risk was evaluated\nusing Pearson&#8217;s correlation test. Statistics considered P values under 0.05 to\nbe significant.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Results and Discussion<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Table 1 displays descriptive statistics\n(Mean and SD) of&nbsp; the study population.\nThe &nbsp;mean age of the study population is\n52.36\u00b15.83 years. The mean\nVitamin D level of the study population is&nbsp;\n28.58\u00b111.47 ng\/dl. The cardiovascular &nbsp;parameters included are blood pressure,\nresting heart rate and indices of heart rate variability. Body mass index,\nwaist circumferences and percent fat considered as metabolic parameters in this\nstudy. &nbsp;<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Table 2 indicates the inference\nstatistics of the study results. Analysis shows a significant &nbsp;inverse relationship between vitamin D and\ncardiometabolic indices such as LF\/HF ratio the &nbsp;measure of sympathovagal balance (p=0.039),\nRHR (p=0.06), and WC (p=0.000). However, the HRV\nindices namely TP, HF and LF in absolute units were not statistically\nsignificant associated with the level of vitamin D. <\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Vitamin\nD has roles in pathogenesis, progression, and consequences on mortality and\nmorbidity of many chronic diseases, including cardiovascular disorders, which are\nsignificant public health issues. The current investigation&#8217;s objective was to\nascertain if a middle-aged person&#8217;s low serum vitamin D levels were related to indicators\nof cardio-metabolic risk variables.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The\nfindings of the study showed that waist circumference, an indicator of central\nobesity was significantly negatively correlated with serum Vitamin D levels. Also,\na negative association was found between LF\/HF indices of HRV, a surrogate of\nsympathovagal balance, and serum Vitamin D levels. However, no relationship was\nfound between serum 25(OH)D insufficiency and SBP, DBP, and BMI among middle-aged\nadults. Further, the study&#8217;s findings also revealed that there was no\nconclusive association of absolute power of HF and LF indices of HRV with concentrations\nof serum 25(OH)D.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">&nbsp;Analysis of the data revealed that statistically\nsignificant increase in waist circumference in decreased vitamin D concentrations\nindicating a greater proportion of abdominal fat (fig.1). According to previous\nresearch, greater abdominal fat storage is a risk element for CVD<sup>21<\/sup>.\nAbdominal obesity is linked to a slew of negative health consequences<sup>22<\/sup>.\nIncreased waist circumference, a marker of abdominal fat, was found to be\nsignificantly predicted by low 25(OH)D status. This may imply that 25(OH)D insufficiency\nand the risk of cardio-metabolic disease are associated with obesity <sup>23<\/sup>.\nAdditionally, abdominal fat has been linked to higher cardiovascular disease\nrisks, including high insulin levels, high blood pressure and heart disease<sup>24<\/sup>,\nwhich could impact circulating concentrations of 25(OH)D.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Receptors\nof Vitamin D present in adipose tissue are responsible for the synthesis of\n1,25-dihydroxy vitamin D to an active form of vitamin D<sub>3<\/sub>. It\nsuggests that vitamin D may be entangled in the control of adipose tissue<sup>25<\/sup>.\nAlso, according to previous research 25(OH)D may have anti-obesity benefits by\nregulating the gene expression of adipocyte differentiation, lipolysis, and\nlipogenesis<sup>26<\/sup>. Other elements, including enhanced parathormone\nconcentrations, have been connected to both decreased vitamin D concentration\nand a higher risk of obesity. . Though there are studies indicating obesity and vitamin D association<sup>27,28<\/sup>\n&nbsp;&nbsp;there is lack of studies on association of\nvitamin D and cadiometabolic disease especially in middle aged population\ntherefore, findings of this study would be additional contribution to the field\nof metabolic and cardiac diseases.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">A significant inverse relationship &nbsp;between HRV parameters and vitamin D levels shows that low concentrations of 25(OH)D resulted in a decrease in &nbsp;variability of heart rate indicating altered autonomic cardiac autonomic modulation. (Table 2). A significant negative association of LF\/HF ratio with vitamin D showing sympathetic dominance is significantly linked with decreased concentrations of serum 25(OH)D. In current research, the association of LF\/HF ratio with low 25(OH)D levels indicates that serum insufficiency can alter cardiovascular risk. Studies have consistently shown that LF\/HF ratio is a surrogate of cardiac sympathovagal balance. Further, relation of sympathetic dominance with cardiovascular morbidity is well documented. Therefore in this study we have included LF\/HF ratio as one of the indices for diseases of cardiovascular risks. Studies have consistently shown that LF\/HF ratio is a surrogate of cardiac sympathovagal balance<sup>29,30<\/sup>. Further, relation of sympathetic dominance with cardiovascular morbidity is well documented. Therefore, in this study we have included LF\/HF ratio as one of the indices of cardiovascular risks.&nbsp; &nbsp;&nbsp;&nbsp;<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">LF\/HF ratio, which is negatively correlated with vitamin D levels, cardiac autonomic dysfunction, and low blood 25(OH)D levels are coupled, which could start the pathophysiological process that raises cardiovascular disease risk in people with 25(OH)D insufficiency. Hence, this study concludes that the greater cardiac sympathovagal balance seen in subjects with low serum 25(OH)D concentrations could be attributed to cardio metabolic disorders. <\/p>\n\n\n\n<p class=\"wp-block-paragraph\"> <strong>Table 1 presents the population&#8217;s descriptive data. (N=100).<\/strong> &nbsp;<\/p>\n\n\n<table style=\"width: 95%;\" border=\"1\" cellspacing=\"0\" cellpadding=\"4\">\n<tbody>\n<tr>\n<td width=\"321\">\n<p style=\"text-align: center;\"><strong>Parameters<\/strong><\/p>\n<\/td>\n<td width=\"458\">\n<p style=\"text-align: center;\"><strong>Mean \u00b1 SD<\/strong><strong style=\"font-size: inherit; font-family: inherit;\">&nbsp;<\/strong><\/p>\n<\/td>\n<\/tr>\n<tr>\n<td width=\"321\">\n<p style=\"text-align: center;\">Age (years)<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"458\">\n<p>52.36 \u00b1 5.83<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"321\">\n<p>BMI (kg\/m<sup>2<\/sup>)<\/p>\n<\/td>\n<td width=\"458\">\n<p style=\"text-align: center;\">24.96 \u00b1 3.58<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td width=\"321\">\n<p style=\"text-align: center;\">Waist Circumference (Cm)<\/p>\n<\/td>\n<td width=\"458\">\n<p style=\"text-align: center;\">85.07 \u00b1 11.305<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td width=\"321\">\n<p style=\"text-align: center;\">Fat (%)<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"458\">\n<p>28.25 \u00b1 8.42<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td width=\"321\">\n<p style=\"text-align: center;\">RHR (bpm)<\/p>\n<\/td>\n<td width=\"458\">\n<p style=\"text-align: center;\">80.84 \u00b1 3.96<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"321\">\n<p>SBP (mmHg)<\/p>\n<\/td>\n<td width=\"458\">\n<p style=\"text-align: center;\">140.88 \u00b1 10.2<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td width=\"321\">\n<p style=\"text-align: center;\">DBP (mmHg)<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"458\">\n<p>81.90 \u00b1 6.46<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"321\">\n<p>TP (ms<sup>2<\/sup>)<\/p>\n<\/td>\n<td width=\"458\">\n<p style=\"text-align: center;\">9218 \u00b1 1966<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td width=\"321\">\n<p style=\"text-align: center;\">LF (ab) (ms<sup>2<\/sup>)<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"458\">\n<p>2187 \u00b1 6405<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"321\">\n<p>HF (ab) (ms<sup>2<\/sup>)<\/p>\n<\/td>\n<td width=\"458\">\n<p style=\"text-align: center;\">1551.6 \u00b1 3382.4<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td width=\"321\">\n<p style=\"text-align: center;\">LF\/HF<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"458\">\n<p>1.98 \u00b1 1.95<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"321\">\n<p>Vitamin D (ng\/ml)<\/p>\n<\/td>\n<td width=\"458\">\n<p style=\"text-align: center;\">28.58 \u00b1 11.47<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<p>Data is represented as Mean \u00b1 SD.<\/p>\n<p>Abbreviations: Total Power (TP), Low Frequency (LF), High Frequency (HF), and LF\/HF: Low Frequency High Frequency Ratio, Resting heart rate (RHR). Systolic blood pressure -SBP, and diastolic blood pressure &#8211; DBP.<\/p>\n\n\n<p class=\"wp-block-paragraph\"><strong>Table 2: displays the relationship between concentrations of 25(OH)D and cardiometabolic parameters. (N= 100)<\/strong>.<\/p>\n\n\n<table style=\"width: 95%;\" border=\"1\" cellspacing=\"0\" cellpadding=\"4\">\n<tbody>\n<tr>\n<td rowspan=\"2\" width=\"186\">\n<p><strong>&nbsp;<\/strong><\/p>\n<p style=\"text-align: center;\"><strong>Cardio-metabolic indices<\/strong><\/p>\n<\/td>\n<td style=\"text-align: center;\" colspan=\"2\" width=\"543\">\n<p><strong>Vitamin D Levels<\/strong><\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"189\">\n<p><strong>R-value<\/strong><\/p>\n<\/td>\n<td width=\"354\">\n<p style=\"text-align: center;\"><strong>P value<\/strong><\/p>\n<\/td>\n<\/tr>\n<tr>\n<td width=\"186\">\n<p style=\"text-align: center;\">TP (ms<sup>2<\/sup>)<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"189\">\n<p>-.091<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"354\">\n<p>.371<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"186\">\n<p>LF (ab) (ms<sup>2<\/sup>)<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"189\">\n<p>-.43<\/p>\n<\/td>\n<td width=\"354\">\n<p style=\"text-align: center;\">.677<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td width=\"186\">\n<p style=\"text-align: center;\">HF (ab) (ms<sup>2<\/sup>)<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"189\">\n<p>-.004<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"354\">\n<p>.972<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"186\">\n<p>LF\/HF<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"189\">\n<p>-.209<\/p>\n<\/td>\n<td width=\"354\">\n<p style=\"text-align: center;\">.039*<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td width=\"186\">\n<p style=\"text-align: center;\">SBP (mmHg)<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"189\">\n<p>-.002<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"354\">\n<p>.984<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"186\">\n<p>DBP (mmHg)<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"189\">\n<p>-.111<\/p>\n<\/td>\n<td width=\"354\">\n<p style=\"text-align: center;\">.275<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td width=\"186\">\n<p style=\"text-align: center;\">RHR (bpm)<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"189\">\n<p>-.275<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"354\">\n<p>0.06**<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"186\">\n<p>BMI (kg\/m<sup>2<\/sup>)<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"189\">\n<p>0.16<\/p>\n<\/td>\n<td width=\"354\">\n<p style=\"text-align: center;\">.878<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td width=\"186\">\n<p style=\"text-align: center;\">Waist Circumference (Cm)<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"189\">\n<p>-.416<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"354\">\n<p>.000**<\/p>\n<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"186\">\n<p>Fat (%)<\/p>\n<\/td>\n<td style=\"text-align: center;\" width=\"189\">\n<p>2.73<\/p>\n<\/td>\n<td width=\"354\">\n<p style=\"text-align: center;\">0.06<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<p>The correlation test was used to analyse the data.<\/p>\n<p>&#8220;r&#8221; stands for correlation strength.<\/p>\n<p>** Correlation is significant at the 0.01 level (2-tailed).<\/p>\n<p>* Correlation is significant at the 0.05 level (2-tailed).<\/p>\n<p>Abbreviations: Total Power (TP), Low Frequency (LF), High Frequency (HF), and LF\/HF: Low Frequency High Frequency Ratio, Resting heart rate (RHR). Systolic blood pressure &#8211; SBP, and diastolic blood pressure &#8211; DBP.<\/p>\n<table style=\"width: 70%;\" border=\"1\" cellpadding=\"5\">\n<tbody>\n<tr>\n<td><img decoding=\"async\" class=\"alignnone size-thumbnail wp-image-53339\" src=\"https:\/\/biomedpharmajournal.org\/wp-content\/uploads\/2023\/11\/Vol16No4_Car_Sum_fig1-150x150.jpg\" alt=\"\" width=\"150\" height=\"150\" srcset=\"https:\/\/biomedpharmajournal.org\/staging\/wp-content\/uploads\/2023\/11\/Vol16No4_Car_Sum_fig1-150x150.jpg 150w, https:\/\/biomedpharmajournal.org\/staging\/wp-content\/uploads\/2023\/11\/Vol16No4_Car_Sum_fig1-256x256.jpg 256w, https:\/\/biomedpharmajournal.org\/staging\/wp-content\/uploads\/2023\/11\/Vol16No4_Car_Sum_fig1.jpg 713w\" sizes=\"(max-width: 150px) 100vw, 150px\" \/><\/td>\n<td>\n<p><strong>Figure 1: <\/strong><strong>The graph displays a negative association between waist circumference and vitamin D.<\/strong><\/p>\n<p><\/p>\n<p><a href=\"https:\/\/biomedpharmajournal.org\/wp-content\/uploads\/2023\/11\/Vol16No4_Car_Sum_fig1.jpg\" target=\"_blank\" rel=\"noopener noreferrer\">Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n<p class=\"wp-block-paragraph\"><strong>Limitations<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">A\nbetter understanding of the association of Vitamin D with cardio-metabolic\nindices would have been established by estimating the lipid profile in this\nstudy population as well as assessing central obesity using sensitive methods.&nbsp; <\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Conclusion<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The\nfindings of this study conclude that lower serum concentrations of 25(OH)D are associated\nwith central obesity as well as cardiac sympathetic dominance, therefore a low\nlevel of vitamin D might increase the risk for cardiovascular diseases.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Acknowledgments<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">We\nthank the study participants&nbsp; for\nparticipation in this study and Nitte (Deemed to be University), for funding\nthis study.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Conflict\nof Interest<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The authors\ndeclare no conflict of interest.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Funding\nSources<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Financial support was received from Nitte (Deemed to be\nUniversity). Grant number is N\/RG\/NUFR2\/KSHEMA\/2020\/11<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>References<\/strong><\/p>\n\n\n\n<ol class=\"wp-block-list\"><li>Voutilainen S, Nurmi T, Mursu J, Rissanen TH. Carotenoids and cardiovascular health. Am J Clin Nutr 2006; 83 (6): 1265-71.<br><a rel=\"noreferrer noopener\" aria-label=\"CrossRef (opens in a new tab)\" href=\"https:\/\/doi.org\/10.1093\/ajcn\/83.6.1265\" target=\"_blank\">CrossRef<\/a><\/li><li>Holick, M.F. Vitamin D deficiency.&nbsp;<em>N. Engl. J. 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