Vitamin A toxicity presenting as bone pain

Baineni, Revanth; Gulati, Reena; Delhi, Cg Kumar

doi:10.1136/archdischild-2016-310631

Cited by 13 publications

(8 citation statements)

References 5 publications

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“…Due to the lack of 1,25(OH) 2 D 3 -mediated inhibition of RA-induced gene transcription in the T cells of the patient in the present study, it might be suggested that the patient has a functional hypervitaminosis A. Accordingly, despite normal serum levels of calcium, phosphate, alkaline phosphatase and parathyroid hormone, the patient’s main complains were bone pains and hair loss, classical signs of hypervitaminosis A ( 38 , 39 ). Further studies are required to test this hypothesis.…”

Section: Discussionmentioning

confidence: 51%

Impaired Vitamin D Signaling in T Cells From a Family With Hereditary Vitamin D Resistant Rickets

et al. 2021

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The active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), mediates its immunomodulatory effects by binding to the vitamin D receptor (VDR). Here, we describe a new point mutation in the DNA-binding domain of the VDR and its consequences for 1,25(OH)2D3 signaling in T cells from heterozygous and homozygous carriers of the mutation. The mutation did not affect the overall structure or the ability of the VDR to bind 1,25(OH)2D3 and the retinoid X receptor. However, the subcellular localization of the VDR was strongly affected and the transcriptional activity was abolished by the mutation. In heterozygous carriers of the mutation, 1,25(OH)2D3-induced gene regulation was reduced by ~ 50% indicating that the expression level of wild-type VDR determines 1,25(OH)2D3 responsiveness in T cells. We show that vitamin D-mediated suppression of vitamin A-induced gene regulation depends on an intact ability of the VDR to bind DNA. Furthermore, we demonstrate that vitamin A inhibits 1,25(OH)2D3-induced translocation of the VDR to the nucleus and 1,25(OH)2D3-induced up-regulation of CYP24A1. Taken together, this study unravels novel aspects of vitamin D signaling and function of the VDR in human T cells.

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Section: Discussionmentioning

confidence: 51%

Impaired Vitamin D Signaling in T Cells From a Family With Hereditary Vitamin D Resistant Rickets

et al. 2021

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“…A controlled clinical trial found that people who took 25,000 IU of vitamin A per day for a median of 3.8 years had 11% increase in triglycerides, 3% increase in total cholesterol and 1% decrease in high-density lipoprotein (HDL) cholesterol, unlike those who did not take vitamin A [23]. In a recent case report, a 4-year-old boy presented several bone pains due to vitamin A toxicity (600,000 IU every day for more than 3 months) [2]. In fact, it has been reported that excessive vitamin A intake can accelerate bone loss and risk of hip fracture, possibly due to vitamin A-induced osteoclasts stimulation, besides it inhibits new bone formation, increasing osteoporosis risk [24].…”

Section: Adverse Effects Of Antioxidantsmentioning

confidence: 99%

“…Jones redefined oxidative stress as a disruption of redox signaling and control [1]. However, a certain amount of oxidative damage takes place even under normal conditions, besides to be observed, a rise in damage rate with aging and disease processes, since antioxidant and repair mechanisms efficiency decreases [2]. On the other hand, oxidative/nitrosative stress (O and NS) has also been markedly implicated in the pathophysiology of many disorders [2].…”

Section: Introductionmentioning

confidence: 99%

“…However, a certain amount of oxidative damage takes place even under normal conditions, besides to be observed, a rise in damage rate with aging and disease processes, since antioxidant and repair mechanisms efficiency decreases [2]. On the other hand, oxidative/nitrosative stress (O and NS) has also been markedly implicated in the pathophysiology of many disorders [2]. Briefly, O and NS are defined as an imbalance between ROS production and ROS neutralizing/counteracting organic ability, through antioxidant and detoxifying mechanisms.…”

Section: Introductionmentioning

confidence: 99%

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Antioxidants: Positive or Negative Actors?

et al. 2018

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The term “antioxidant” is one of the most confusing definitions in biological/medical sciences. In chemistry, “antioxidant” is simply conceived “a compound that removes reactive species, mainly those oxygen-derived”, while in a cell context, the conceptual definition of an antioxidant is poorly understood. Indeed, non-clinically recommended antioxidants are often consumed in large amounts by the global population, based on the belief that cancer, inflammation and degenerative diseases are triggered by high oxygen levels (or reactive oxygen species) and that through blocking reactive species production, organic unbalances/disorders can be prevented and/or even treated. The popularity of these chemicals arises in part from the widespread public mistrust of allopathic medicine. In fact, reactive oxygen species play a dual role in dealing with different disorders, since they may contribute to disease onset and/or progression but may also play a key role in disease prevention. Further, the ability of the most commonly used supplements, such as vitamins C, E, selenium, and herbal supplements to decrease pathologic reactive oxygen species is not clearly established. Hence, the present review aims to provide a nuanced understanding of where current knowledge is and where it should go.

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“…These might include prevention and treatment of general malnutrition, prevention and treatment of infections, and supplementation of individuals with vitamin A when warranted. With regard to the use of VAS, as noted above, context matters and care should be taken to address all contingencies regarding vitamin A status including the potential for toxicity which, although rare, does happen ( 62–64 ).…”

Section: Current Status Of Knowledgementioning

confidence: 99%

Perspective: Integration to Implementation (I-to-I) and the Micronutrient Forum—Addressing the Safety and Effectiveness of Vitamin A Supplementation

Raiten

Darnton‐Hill

Tanumihardjo

et al. 2020

Advances in Nutrition

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An ongoing challenge to our ability to address the role of food and nutrition in health promotion and disease prevention is how to design and implement context-specific interventions and guidance that are safe, efficacious, and avoid unintended consequences. The integration to effective implementation (I-to-I) concept is intended to address the complexities of the global health context through engagement of the continuum of stakeholders involved in the generation, translation, and implementation of evidence to public health guidance/programs. The I-to-I approach was developed under the auspices of the Micronutrient Forum and has been previously applied to the question of safety and effectiveness of interventions to prevent and treat nutritional iron deficiency. The present article applies the I-to-I approach to questions regarding the safety and utility of large-dose vitamin A supplementation programs, and presents the authors’ perspective on key aspects of the topic, including coverage of the basic and applied biology of vitamin A nutrition and assessment, clinical implications, and an overview of the extant data with regard to both the justification for and utility of available intervention strategies. The article includes some practical considerations based on specific country experiences regarding the challenges of implementing vitamin A–related programs. This is followed by an overview of some challenges associated with engagement of the enabling communities that play a critical role in the implementation of these types of public health interventions. The article concludes with suggestions for potential approaches to move this important agenda forward.

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Vitamin A toxicity presenting as bone pain

Cited by 13 publications

References 5 publications

Impaired Vitamin D Signaling in T Cells From a Family With Hereditary Vitamin D Resistant Rickets

Impaired Vitamin D Signaling in T Cells From a Family With Hereditary Vitamin D Resistant Rickets

Antioxidants: Positive or Negative Actors?

Perspective: Integration to Implementation (I-to-I) and the Micronutrient Forum—Addressing the Safety and Effectiveness of Vitamin A Supplementation

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