Journal of Steroid Biochemistry and Molecular Biology 200 (2020) 105668
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Editorial
Diverse functions of vitamin D in health and disease
The 8th International Vitamin D Conference was held in Jamia
Hamdard Campus, New Delhi on September 15–16, 2018 with a focus
on Food Fortification. The organizers were Afrozul Haq, Seyed
Ehtesham Hasnain, and Mohammed S. Razzaque. This Special Issue
attempts to summarize the proceedings based on various presentations
made at this conference. This meeting was focused on a wide array of
vitamin D functions, ranging from skeletogenesis to pregnancy to sepsis
to tumorigenesis. A total of 20 papers explained how impaired vitamin
D function could be the cause or the consequence of various human
diseases. Connection of vitamin D with various inflammatory, in-
fectious and neoplastic diseases would enhance our understanding of
the adequate clinical use of vitamin D supplements, and would reduce
the abuse of vitamin D supplement consumption in health and diseases.
Traditionally, vitamin D is believed to be involved in calcium meta-
bolism and bone growth and maintenance [1–4].
In this Special Issue, multiple papers explained the roles and reg-
ulations of vitamin D in non-skeletal diseases. Although safe sunlight
exposure is the best source of vitamin D [2], However, its deficiency is
widespread and most prevalent in regions with limited sunlight ex-
posure. In addition to the region, other factors, including race, climate,
and culture could also limit sunlight exposure to influence vitamin D
metabolism. The impaired autocrine, paracrine and endocrine functions
of vitamin D are linked to many acute and chronic illnesses [5–7]; some
of which are detailed in this Special Issue.
Jan et al. while comprehensively describing the vitamin D for-
tification status in India, highlight that despite India being mostly
sunny land, vitamin D inadequacy is widespread. The authors re-
commended the consumption of vitamin D-rich foods; including milk,
cheese, and other dairy products. The need for fruit drinks and staple
food fortification with vitamin D to decrease vitamin D deficiency in
various age groups was also advised [8].
Maurya and colleagues summarized the utility of nanotechnology
that offers various microencapsulation techniques such as liposome,
solid-lipid particles, nanostructured lipid carriers, emulsion, etc. for the
fortification purposes, including vitamin D fortification [9]. The au-
thors then explained the development of a phase inversion based na-
noemulsion fabrication process for the encapsulation of vitamin D.
After performing physicochemical stability of encapsulated vitamin D,
and the sensory evaluation, the authors recommend that their gener-
ated encapsulated vitamin D could be used for beverage fortification
[10] and also yogurt-based popular Indian drink (lassi) [11].
Tsuprykov and colleagues detailed why measuring free 25-hydro-
xyvitamin D [25(OH)D] might be superior over the total 25(OH)D, in
estimating the vitamin D status during pregnancy. Their results showed
that free 25(OH)D levels had better correlations with gestational age,
bone and lipid metabolism biomarkers than total 25(OH)D levels.
Although, the investigators pointed out that for observing on tissues
https://doi.org/10.1016/j.jsbmb.2020.105668
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T
capable of megalin/cubilin-mediated 25(OH)D-vitamin D-binding pro-
tein up-taking, measuring the total 25(OH)D might be superior over
free 25(OH)D [12]. In a comparative study conducted on pregnant
women in Mongolia and Boston by Bromage and colleagues, the serum
level of 25(OH)D in Mongolian third-trimester pregnant women was
found to be severely low. The authors recommend a combined ap-
proach of fortified food and supplementation for Mongolian women
during pregnancy [13]. In a separate study conducted on 51 women
(mean age: 44 ± 12 years) with chronic widespread pain, Kenis-Coskun
and colleagues have reported that the vitamin D replacement therapy
did not significantly change ‘Cutaneous Silent Period’ latency and
duration; the authors concluded that vitamin D replacement could not
modify the spinal inhibitory pathways that are involved in the forma-
tion of the Cutaneous Silent Period [14].
In a retrospective analysis of 268 children, Zhang et al. have shown
that vitamin D deficiency was associated with a movement disorder and
nervous system abnormalities in the majority of the analyzed pediatric
group of patients [15]. In a separate study conducted on a much
younger cohort of 150 healthy children, aged between 1 and 23
months, Akrour-Aisso and colleagues showed that two doses of vitamin
D supplementation, the first dose of 200,000 IU at 1 month and the
second dose of 200,000 IU at 6 months, resulted in a higher serum level
of 25(OH)D, as compared to the non-supplemented Algerian children
[16].
Al-Daghri and colleagues showed that in their cohort oral vitamin D
supplementation was not only superior to vitamin D fortified milk in
improving vitamin D status but could also reduce the incidence of
metabolic syndrome in Arab adolescents and such a reduction in the
incidence of metabolic syndrome could likely be a dose-dependent
phenomenon [17]. Chen et al. described the results of the meta‐analysis
on the effect of vitamin D on vascular stiffness and concluded that
correction of vitamin D deficiency by using nutritional vitamin D could
improve arterial stiffness [18]. Authors, however, emphasized the need
for further Randomized Controlled Trials to determine whether such
improvement of arterial stiffness could translate into the reduction of
cardiovascular mortality in vitamin D deficient individuals. Patel and
co-workers discussed the utility of monitoring serum 25(OH)D in pa-
tients with breast cancer [19a]. This study aimed to investigate circu-
latory 25(OH)D in relation to breast cancer risk and its association with
various clinicopathological parameters in the Indian population. A total
of 297 subjects, comprising of 157 controls and 140 breast cancer pa-
tients were enrolled for the study. The prevalence of severe and mod-
erate 25(OH)D deficiency was higher in breast cancer patients as
compared to controls. Mean values of 25(OH)D were lower in breast
cancer patients as compared to controls in mild, moderate and severe
deficient groups (p = 0.07, p = 0.003, and p = 0.001). Moreover,
25(OH)D was significantly lower in postmenopausal breast cancer
Editorial
patients as compared to premenopausal breast cancer patients, parti-
cularly in a severely deficient group. The levels of 25(OH)D were lower
in ER and PR negative receptor status as compared to the positive re-
ceptor in severe deficient category (p = 0.06 and p = 0.09 respec-
tively). Whereas, the mean values of 25(OH)D were lower in HER 2
negative receptor status as compared to positive receptor status in the
moderate deficient category (p = 0.09). The results of this study in-
dicate that 25(OH)D deficiency might be associated with an increased
risk of breast cancer. Moreover, severe 25(OH)D deficiency was asso-
ciated with aggressive behavior of breast cancer.
Panda and colleagues described the susceptibility to tuberculosis in
80 active tuberculosis patients, along with 75 household contacts and
70 healthy controls and reported reduced serum levels of vitamin D in
active tuberculosis patients as compared to healthy controls [20]. The
investigators also found significantly lower Vitamin D Receptor (VDR)
and inducible nitric oxide synthase (iNOS) mRNA levels in active tu-
berculosis patients compared to household contacts and healthy con-
trols. Further studies to determine the beneficial effects of vitamin D
supplementation in the prevention and treatment of tuberculosis are
warranted.
In an in vitro study, using primary human skeletal muscle myoblasts,
Montenegro et al. showed that vitamin D could inhibit myoblast pro-
liferation, but could enhance the differentiation, by altering the ex-
pression of myogenic regulatory factors [21]. The investigators also
found that protein synthesis signaling improved in myotubes after vi-
tamin D treatment in the presence of insulin, and concluded an additive
effect of vitamin D on insulin responsiveness and protein synthesis. In a
separate in vivo study, conducted on adult C57BL/6 male mice, Maia-
Ceciliano and co-workers showed that fructose consumption with vi-
tamin D deficiency could induce steatosis and liver fibrosis; vitamin D
supplementation reduced the adverse effects of the fructose consump-
tion in the studied animals [22]. Since fructose is added to soft drinks
and processed food, and is a major cause of organ damage, efforts to
reduce such organ damage by maintaining optimal vitamin D status
would be a useful clinical approach. Human relevance and benefits of
such therapeutic practice, however, need further clinical validations.
Another artificial ingredient that is added to soft drinks and pro-
cessed food is phosphate-based preservatives. In a large cohort of 8314
children (mean age of 9.9 ± 0.6 years), by using quantile regression
analysis, Goodson and colleagues have shown a statistically significant
correlation between the occurrence of gingivitis and calorie-adjusted
phosphate intake [23]. The salivary analysis in a subset of 744 children
showed a positive correlation between elevated calorie-adjusted phos-
phate intake and salivary Interleukin-1β concentration, but an inverse
association with salivary Interleukin-4 concentration. Such association
with either biomarker was not detected with sugar intake, suggesting a
harmful effect of excessive phosphate consumption in the evolvement
of gingivitis. Elevated dietary phosphate consumption may likely in-
fluence inflammatory diseases by dysregulating cytokines [23,24]. Of
relevance, vitamin D consumption was not associated with the occur-
rence of oral lesions in this study, though vitamin D could actively in-
fluence phosphate homeostasis.
Another mineral that is essential for vitamin D activation and
function is magnesium [25,26]. For exerting biological functions, the
storage form of vitamin D (inactive) needs to be converted to an active
form through various stages of activation process that are magnesium-
dependent. In an in-depth review, Erem et al. explained how magne-
sium could activate vitamin D, and summarized how optimal magne-
sium and vitamin D balance could improve skeletal health outcomes in
the elderly population [27]. Similar benefits of preserving optimal
magnesium status in maintaining healthy oral functions are also ex-
plained by Uwitonze et al. [28]. It is important to mention that, the
under-consumption of magnesium is widespread in the United States of
America and beyond, and is a health concern [25,26].
Although early diagnosis and treatment are vital for the survival of
sepsis patients, the early diagnosis of sepsis is a medical challenge. Wolf
2
Journal of Steroid Biochemistry and Molecular Biology 200 (2020) 105668
et al. discussed the potential benefits and challenges of using serum
levels of procalcitonin in the diagnosis and monitoring the patients with
sepsis and septic shock [29]. Since vitamin D supplementation is
commonly used in intensive care unit patients, the authors discussed
how such treatment might interfere with the ability to use procalcitonin
as a biomarker of evaluating clinical progression. Dr. Akimbekov and
colleagues have detailed the effects of sunlight exposure and vitamin D
supplementation on HIV patients [30]. Almost half of the HIV patients
around the globe have shown a low baseline level or serum 25(OH)D,
perhaps partly related to the increasing urbanization and decreasing
amounts of time spent under the sunlight, in general; HIV infection
itself is a risk factor for the premature development of many disorders,
where vitamin D deficiency can be a catalyst for these pathological
processes.
In summary the large volume and spread of research outcomes and
shreds of evidence presented in this special issue not only reiterate the
health value of Vitamin D, but some of these directly point to the im-
portance of supplementations in food and drinks. It is reasonable to
conclude that an adequate level of vitamin D is vital for the main-
tenance of normal health and reducing disease burdens.
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Editorial
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⁎
Corresponding author.
Journal of Steroid Biochemistry and Molecular Biology 200 (2020) 105668
[29] T.A. Wolf, S.J. Wimalawansa, M.S. Razzaque, Procalcitonin as a biomarker for
critically ill patients with sepsis: effects of vitamin D supplementation, J. Steroid
Biochem. Mol. Biol. 193 (2019) 105428.
[30] N. Akimbekov, R.A. Ortoski, M.S. Razzaque, Effects of sunlight exposure and vi-
tamin D supplementation on HIV patients, J. Steroid Biochem. Mol. Biol. 194
(2020).
Afrozul Haq*
Department of Food Technology, School of Interdisciplinary Sciences and
Technology, Jamia Hamdard, New Delhi, 110062, India
E-mail address: profafrozulhaq@jamiahamdard.ac.in.
Seyed E. Hasnain
JH Institute of Molecular Medicine, Jamia Hamdard, New Delhi, India and
Dr. Reddy’s Institute of Life Sciences, University of Hyderabad Campus,
Hyderabad, 500046, India
E-mail address: pstovc@jamiahamdard.ac.in.
Mohammed S. Razzaque
Department of Pathology, Lake Erie College of Osteopathic Medicine, Erie,
Pennsylvania, USA
E-mail address: mrazzaque@lecom.edu.