Phosphate Dysregulation and Metabolic Syndrome.

Phosphorus is one of the most abundant minerals in the human body. It is essential for almost all biochemical activities through ATP formation, intracellular signal transduction, cell membrane formation, bone mineralization, DNA and RNA synthesis, and inflammation modulation through various inflammatory cytokines. Phosphorus levels must be optimally regulated, as any deviations may lead to substantial derangements in glucose homeostasis. Clinical studies have reported that hyperphosphatemia can increase an individual's risk of developing metabolic syndrome. High phosphate burden has been shown to impair glucose metabolism by impairing pancreatic insulin secretion and increasing the risk of cardiometabolic disorders. Phosphate toxicity deserves more attention as metabolic syndrome is being seen more frequently worldwide and should be investigated further to determine the underlying mechanism of how phosphate burden may increase the cardiometabolic risk in the general population.

Zinc and its role in vitamin D function.

Zinc is an essential mineral with an important relationship with vitamin D. Studies have found that reduced blood zinc levels could predict vitamin D deficiency in adolescent girls, while zinc supplementation increased vitamin D levels in postmenopausal women. In vitro studies using human peritoneal macrophages have found that zinc induced the release of calcitriol (1,25-dihydroxycholecalciferol). Zinc also acts as a cofactor for vitamin D functions, as the transcriptional activity of vitamin D-dependent genes relies on zinc to exert pleiotropic functions, including mineral ion regulation. Vitamin D could also induce zinc transporters to regulate zinc homeostasis. Together, zinc and vitamin D in adequate concentrations help maintain a healthy musculoskeletal system and beyond; however, deficiency in either of these nutrients can result in various disorders affecting almost all body systems. This brief article will focus on the role of zinc in vitamin D functions.

Laughter therapy: A humor-induced hormonal intervention to reduce stress and anxiety.

Prolonged pharmacological interventions have detrimental health consequences by developing drug tolerance or drug resistance, in addition to adverse drug events. The ongoing COVID-19 pandemic-related stress has adversely affected the emotional and mental health aspects around the globe. Consequently, depression is growing during the COVID-19 pandemic. Besides specific pharmacological interventions, which if prolonged have detrimental health consequences, non-pharmacological interventions are needed to minimize the emotional burden related to the COVID-19 pandemic. Laughter therapy is a universal non-pharmacologic approach to reduce stress and anxiety. Therapeutic laughter is a non-invasive, cost-effective, and easily implementable intervention that can be used during this pandemic as a useful supplementary therapy to reduce the mental health burden. Laughter therapy can physiologically lessen the pro-stress factors and increase the mood-elevating anti-stress factors to reduce anxiety and depression. In this ongoing stressful period of the COVID-19 pandemic, keeping necessary social distancing, it is important to create a cheerful environment that will facilitate laughter among the family, neighbor, and community to cope with the stresses of the COVID-19 pandemic.

COVID-19 pandemic: Can zinc supplementation provide an additional shield against the infection?

Coronavirus disease-19 (COVID-19)-induced severe acute respiratory syndrome is a global pandemic. As a preventive measure, human movement is restricted in most of the world. The Centers for Disease Control and Prevention (CDC), the National Institutes of Health (NIH), along with the World Health Organization (WHO) have laid out some therapeutic guidelines for the infected patients. However, other than handwashing and vigilance surrounding commonly encountered oronasal symptoms and fever, no universally available prophylactic measure has yet been established. In a pandemic, the accessibility of a prophylactic biologically active substance is crucial. Ideally, it would be something readily available at a low price to a larger percentage of the population with minimal risk. Studies have demonstrated that zinc may reduce viral replication and increase immune responses. While consuming zinc (within the recommended upper safety limits), as a prophylactic might provide an additional shield against the initiation and progression of COVID-19 would need clinical studies, the potential clearly exists. Even after vaccination, low zinc status may affect the vaccination responses.

COVID-19 Pandemic: Can Maintaining Optimal Zinc Balance Enhance Host Resistance?

The novel coronavirus disease 2019 (COVID-19) is now officially declared as a pandemic by the World Health Organization (WHO), and most parts of the world are taking drastic measures to restrict human movements to contain the infection. Millions around the world are wondering, if there is anything that could be done, other than maintaining high personal hygiene, and be vigilant of the symptoms, to reduce the spread of the disease and chances of getting infected, or at least to lessen the burden of the disease, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The National and International health agencies, including the National Institutes of Health (NIH), the Centers for Disease Control and Prevention (CDC), and the WHO have provided clear guidelines for both preventive and treatment suggestions. In this article, I will briefly discuss, why keeping adequate zinc balance might enhance the host response and be protective of viral infections.

Effects of sunlight exposure and vitamin D supplementation on HIV patients.

Unlike many vitamins derived predominantly from food sources, vitamin D is produced endogenously in the skin upon exposure to sunlight. Ethnicity, skin pigmentation, socioeconomic status, geographic location, climate and sunscreen; all of these factors contribute to the amount of insolation for any given individual. Insufficient insolation creates the prerequisites for vitamin D deficiency. This is particularly true in HIV-infected individuals, who are highly vulnerable to vitamin D insufficiency/deficiency, as it plays a huge role in the musculoskeletal and cardiovascular systems. Antiretroviral therapy may also be a factor in vitamin D deficiency. Today, as the issues of preventing common skeletal and non-skeletal diseases with HIV-infected people are becoming highly relevant, the maintenance of vitamin D levels through exposure to sunlight or supplementation appears to be an effective and safe solution. This review focuses on studies concerning the potential role of vitamin D supplementation through adequate sunlight exposure or dietary intake in HIV-infected people. The biology and epidemiology of HIV infection, as well as the issues related to vitamin D deficiency, its status on immune function, the effect of vitamin D against HIV disease progression and other health aspects of this vitamin, are briefly explained.

Oral manifestations of magnesium and vitamin D inadequacy.

Adequate nutrition is essential for maintaining good oral health. Minerals such as magnesium, calcium, and phosphorus found in the diet constitute the main structural components of the tooth. Their inadequacy leads to absorption impairment, increased bleeding tendency, bone resorption, looseness, and premature tooth loss. Inadequacy of those essential minerals is associated with delayed tooth eruption and with enamel or dentin hypoplasia. Taking calcium without magnesium results in soft dental enamel, which cannot resist the acids causing tooth decay. In addition to magnesium, calcium, and phosphorus, adequate vitamin D is needed to maintain optimal oral health. Vitamin D exerts anti-inflammatory effects and helps in calcium absorption and bone remodeling. Moreover, adequate vitamin D status could reduce formation of dental caries by delaying its onset and progression. Here we summarize the oral manifestations of vitamin D and magnesium inadequacy.

Procalcitonin as a biomarker for critically ill patients with sepsis: Effects of vitamin D supplementation.

Early diagnosis of sepsis is often difficult in clinical practice, whilst it can be vital for positive patient outcomes in sepsis management. Any delay in diagnosis and treatment may lead to significant organ failure and can be associated with elevated mortality rates. Early diagnosis and effective management of sepsis can allow for prompt antibiotic therapy and a potential reduction in mortality; it can also minimize the unnecessary use of antibiotics. Furthermore, vitamin D supplementation, which is commonly used in the intensive care units to reduce mortality, may interfere with the ability to use procalcitonin (PCT) as a means of assessing clinical progression. This paper aims to explore the diagnostic and prognostic value of serum levels of PCT as an early marker of sepsis and to assess whether it can be used as a guide for using antibiotic therapy. Several serum-based biomarkers such as C-reactive protein, lactate, presepsin, and cytokines, such as interleukin-1 (IL-1), and IL-6 have been evaluated as early indicators of sepsis but none have been proven sensitive and/or specific enough to make a definitive diagnosis. Finally the potential benefits and disadvantages of using serum levels of PCT to diagnose and monitor patients with sepsis and septic shock will be briefly discussed.

Periodontal diseases and adverse pregnancy outcomes: Is there a role for vitamin D?

Studies have shown a relationship between maternal periodontal diseases (PDs) and premature delivery. PDs are commonly encountered oral diseases which cause progressive damage to the periodontal ligament and alveolar bones, leading to loss of teeth and oral disabilities. PDs also adversely affect general health by worsening of cardiovascular and metabolic diseases. Moreover, maternal PDs are thought to be related to increasing the frequency of preterm-birth with low birth weight (PBLBW) in new-borns. Prematurity and immaturity are the leading causes of prenatal and infant mortality and is a major public health problem around the world. Inflamed periodontal tissues generate significantly high levels of proinflammatory cytokines that may have systemic effects on the host mother and the fetus. In addition, the bacteria that cause PDs produce endotoxins which can harm the fetus. Furthermore, studies have shown that microorganisms causing PDs can get access to the bloodstream, invading uterine tissues, to induce PBLBW. Another likely mechanism that connects PDs with adverse pregnancy outcome is maternal vitamin D status. A role of inadequate vitamin D status in the genesis of PDs has been reported. Administration of vitamin D supplementation during pregnancy could reduce the risk of maternal infections and adverse pregnancy outcomes. As maternal PDs are significant risk factors for adverse pregnancy outcome, preventive antenatal care for pregnant women in collaboration with the obstetric and dental professions are required.

Effects of vitamin D status on oral health.

Normal humans of all ages have the innate ability to produce vitamin D following sunlight exposure. Inadequate vitamin D status has shown to be associated with a wide variety of diseases, including oral health disorders. Insufficient sunlight exposure may accelerate some of these diseases, possibly due to impaired vitamin D synthesis. The beneficial effects of vitamin D on oral health are not only limited to the direct effects on the tooth mineralization, but are also exerted through the anti-inflammatory functions and the ability to stimulate the production of anti-microbial peptides. In this article, we will briefly discuss the genesis of various oral diseases due to inadequate vitamin D level in the body and elucidate the potential benefits of safe sunlight exposure for the maintenance of oral and general health.

Calcium and vitamin D in human health: Hype or real?

The incidence and prevalence of vitamin D deficiency are increasing worldwide. It is estimated that over 50% of the world's population have low vitamin D (i.e., hypovitaminosis D; serum levels below 30 ng/mL). In vitamin D inadequacy, human physiological systems work inefficiently. In humans, 80% of the vitamin D is synthesized in the presence of ultraviolet rays from sunlight; for the rest, we rely on diet and nowadays, supplements. The latter becomes important when one is exposed to less than optimal amounts of sunlight, inability to generate vitamin D in the skin efficiently, and/or having conditions that lead to decreased intestinal absorption or increased catabolism of vitamin D. The normal serum 25-hydroxyvitamin D [25(OH)D] level is around 30 ng/mL (75 nmol/L) and the optimal range is between 30 and 60 ng/mL (75-150 nmol/L). In 2011, the Institute of Medicine (IOM) suggested that 600IU of vitamin D is adequate for people below age 71 who are not exposed to sunshine. Although this might be relevant to the ambulatory healthy white Caucasians to achieve serum 25(OH)D level of 20 ng/mL, but it is insufficient for other ethnic groups. Moreover, the IOM recommendations are not suitable for those who live outside North America. Vitamin D requirements are higher during adolescence, pregnancy and lactation, and in many other disease conditions. Most clinicians consider 30 ng/mL as the minimum serum level of 25(OH)D necessary to maintain good health. In the absence of sunlight exposure and with daily oral intake of 600IU vitamin D, very few people would reach serum 25(OH)D level above 30 ng/mL. While an additional daily intake of 1000IU of vitamin D are required for people with lighter-skin color, those with darker complexion and the elderly, require a minimum of 2000IU/day to maintain serum 25(OH)D levels over 30 ng/mL; 5000 IU/day supplement is considered as the safe daily upper limit of supplementation. Vulnerable groups such as the disabled and/or house-bound, obese, with gastrointestinal abnormalities and/or malabsorption syndromes, institutionalized people (e.g., nursing homes, prisons, etc.), and pregnant and lactating women need approximately 4000IU per day for optimal physiological activity. Vitamin D is essential for gastrointestinal calcium absorption, mineralization of osteoid tissue and maintenance of serum ionized calcium level. It is also important for other physiological functions, such as muscle strength, neuromuscular coordination, hormone release, subduing autoimmunity, and curtailing the development of certain cancers.

Sunlight exposure: Do health benefits outweigh harm?

Vitamin D is a fat-soluble vitamin whose levels within the body are elevated following sunlight exposure. Numerous studies have shown that sunlight exposure can provide protection to a wide variety of diseases, ranging from different types of tumors to hypertension to type 1 diabetes to multiple sclerosis. Moreover, studies have shown that avoiding sunlight may influence the initiation and progression of some of these diseases. Avoidance of sunlight, coupled with the inclination towards consuming supplements, is becoming the primary choice to obtain vitamin D. The purpose of this article is to present evidences from published literature, to show that the expected benefits of vitamin D supplements are minimized by the potential risk of cardiovascular events and beyond. Since hypovitaminosis D status usually reflects reduced sunlight exposure, the obvious primary replacement should be safe sunlight exposure, and not exogenous supplements.

Can adverse effects of excessive vitamin D supplementation occur without developing hypervitaminosis D?

Vitamin D is a fat-soluble hormone that has endocrine, paracrine and autocrine functions. Consumption of vitamin D-supplemented food & drugs have increased significantly in the last couple of decades due to campaign and awareness programs. Despite such wide use of artificial vitamin D supplements, serum level of 25 hydroxyvitamin D does not always reflect the amount of uptake. In contrast to the safe sunlight exposure, prolonged and disproportionate consumption of vitamin D supplements may lead to vitamin D intoxication, even without developing hypervitaminosis D. One of the reasons why vitamin D supplementation is believed to be safe is, it rarely raises serum vitamin D levels to the toxic range even after repeated intravenous ingestion of extremely high doses of synthetic vitamin D analogs. However, prolonged consumption of vitamin D supplementation may induce hypercalcemia, hypercalciuria and hyperphosphatemia, which are considered to be the initial signs of vitamin D intoxication. It is likely that calcium and phosphorus dysregulation, induced by exogenous vitamin D supplementation, may lead to tissue and organ damages, even without developing hypervitaminosis D. It is needed to be emphasized that, because of tight homeostatic control of calcium and phosphorus, when hypercalcemia and/or hyperphosphatemia is apparent following vitamin D supplementation, the process of tissue and/or organ damage might already have been started.

Vitamin D, phosphate, and vasculotoxicity.

Vascular calcification is a complex process that results in the ectopic deposition of calcium-phosphate hydroxyapatite. Medial and intimal vascular calcification is frequently present in patients with diabetes mellitus and chronic kidney disease (CKD), and markedly increases the morbidity and mortality of these patients. Increased serum levels of calcium and phosphate, along with the use of active vitamin D metabolites, are commonly implicated in the evolvement of vascular wall mineralization in CKD patients. Because CKD patients have lower serum levels of vitamin D, they are routinely prescribed vitamin D supplements that exert a dualistic role that is both healthful and harmful in these patients, perhaps protecting bone health, but at the expense of promoting vascular pathology. This review briefly explains how reducing the phosphate burden in CKD patients could minimize vitamin-D-associated vascular wall calcification.