scholarly journals Vitamin A intake forms resistance to hypervitaminosis A and affects the functional activity of the liver

2021 ◽  
Author(s):  
Anatoliy Bozhkov ◽  
Igor Ionov ◽  
Natalia Kurguzova ◽  
Anna Novikova ◽  
Оleg Katerynych ◽  
...  
Keyword(s):  
Vitamin A ◽  
Functional Activity ◽  
Hypervitaminosis A

The Reversibility of the Effect of Hypervitaminosis A on Embryonic Limb Bones Cultivated in vitro

Development ◽  
1955 ◽  
Vol 3 (4) ◽  
pp. 355-365
Author(s):  
M. A. Herbertson
Keyword(s):  
Vitamin A ◽  
Direct Effect ◽  
Functional Activity ◽  
Vitamin A Deficiency ◽  
The Body ◽  
Long Bone ◽  
Hypervitaminosis A ◽  
Limb Bones ◽  
Embryonic Limb

The skeleton of young animals is profoundly affected by an abnormal amount of vitamin A in the body. In vitamin A deficiency changes in the functional activity of the osteoblasts and osteoclasts allow bone to be deposited in places where it would normally be removed, so producing excessive thickening of certain parts of the skeleton (Mellanby, 1938, 1939). Conversely, excessive vitamin A causes osteoporosis and spontaneous fractures, although the formation of new bone is not inhibited (Strauss, 1934; Wolbach & Bessey, 1942; Irving, 1949). Recent experiments have shown that the vitamin has a direct effect on skeletal tissues grown in vitro. Fell & Mellanby (1952) cultivated the long-bone rudiments of embryonic chicks and mice in medium containing vitamin A in concentrations similar to those found in the blood of animals suffering from hypervitaminosis A; in such explants the cartilage matrix lost its metachromasia and gradually disappeared (chicks, mice) while bone (mice) was rapidly resorbed.

The Need to Consider Context in the Evaluation of Anti-infectious and Immunomodulatory Effects of Vitamin A and its Derivatives

2019 ◽  
Vol 20 (8) ◽  
pp. 871-878 ◽  
Author(s):  
Pedro Xavier-Elsas ◽  
Bruno M. Vieira ◽  
Daniela Masid-de-Brito ◽  
Monica G. Barradas ◽  
Maria I.C. Gaspar-Elsas
Keyword(s):  
Vitamin A ◽  
Clinical Presentation ◽  
Infectious Agents ◽  
Hypervitaminosis A ◽  
General Role ◽  
Significant Toxicity ◽  
Vast Literature ◽  
Gut Mucosa ◽  
Anti Inflammatory ◽  
Pathogen Exposure

Vitamin A and its derivatives (retinoids) act as potent regulators in many aspects of mammalian reproduction, development, repair, and maintenance of differentiated tissue functioning. Unlike other vitamins, Vitamin A and retinoids, which have hormonal actions, present significant toxicity, which plays roles in clinically relevant situations, such as hypervitaminosis A and retinoic acid ("differentiation") syndrome. Although clinical presentation is conspicuous in states of insufficient or excessive Vitamin A and retinoid concentration, equally relevant effects on host resistance to specific infectious agents, and in the general maintenance of immune homeostasis, may go unnoticed, because their expression requires either pathogen exposure or the presence of inflammatory co-morbidities. There is a vast literature on the roles played by retinoids in the maintenance of a tolerogenic, noninflammatory environment in the gut mucosa, which is considered by many investigators representative of a general role played by retinoids as anti-inflammatory hormones elsewhere. However, in the gut mucosa itself, as well as in the bone marrow and inflammatory sites, context determines whether one observes an anti-inflammatory or proinflammatory action of retinoids. Both interactions between specialized cell populations, and interactions between retinoids and other classes of mediators/regulators, such as cytokines and glucocorticoid hormones, must be considered as important factors contributing to this overall context. We review evidence from recent studies on mucosal immunity, granulocyte biology and respiratory allergy models, highlighting the relevance of these variables as well as their possible contributions to the observed outcomes.

scholarly journals CFTR Modulator Therapy with Lumacaftor/Ivacaftor Alters Plasma Concentrations of Lipid-Soluble Vitamins A and E in Patients with Cystic Fibrosis

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 483
Author(s):  
Olaf Sommerburg ◽  
Susanne Hämmerling ◽  
S. Philipp Schneider ◽  
Jürgen Okun ◽  
Claus-Dieter Langhans ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Vitamin E ◽  
Vitamin A ◽  
Clinical Chemistry ◽  
Pancreatic Insufficiency ◽  
Plasma Concentrations ◽  
Plasma Vitamin ◽  
Hypervitaminosis A ◽  
Cholesterol Ratio ◽  
Fat Soluble Vitamins

Rationale: Cystic fibrosis (CF), caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, leads to impaired pancreatic function and therefore reduced intestinal absorption of lipids and fat-soluble vitamins especially in patients with CF developing pancreatic insufficiency (PI). Previous studies showed that CFTR modulator therapy with lumacaftor-ivacaftor (LUM/IVA) in Phe508del-homozygous patients with CF results in improvement of pulmonary disease and thriving. However, the effects of LUM/IVA on plasma concentration of the lipid soluble vitamins A and E remain unknown. Objectives: To investigate the course of plasma vitamin A and E in patients with CF under LUM/IVA therapy. Methods: Data from annual follow-up examinations of patients with CF were obtained to assess clinical outcomes including pulmonary function status, body mass index (BMI), and clinical chemistry as well as fat-soluble vitamins in Phe508del-homozygous CF patients before initiation and during LUM/IVA therapy. Results: Patients with CF receiving LUM/IVA improved substantially, including improvement in pulmonary inflammation, associated with a decrease in blood immunoglobulin G (IgG) from 9.4 to 8.2 g/L after two years (p < 0.001). During the same time, plasma vitamin A increased significantly from 1.2 to 1.6 µmol/L (p < 0.05), however, levels above the upper limit of normal were not detected in any of the patients. In contrast, plasma vitamin E as vitamin E/cholesterol ratio decreased moderately over the same time from 6.2 to 5.5 µmol/L (p < 0.01). Conclusions: CFTR modulator therapy with LUM/IVA alters concentrations of vitamins A and vitamin E in plasma. The increase of vitamin A must be monitored critically to avoid hypervitaminosis A in patients with CF.

scholarly journals South African preschool children habitually consuming sheep liver and exposed to vitamin A supplementation and fortification have hypervitaminotic A liver stores: a cohort study

2019 ◽  
Vol 110 (1) ◽  
pp. 91-101 ◽  
Author(s):  
Martha E van Stuijvenberg ◽  
Muhammad A Dhansay ◽  
Jana Nel ◽  
Devika Suri ◽  
Michael Grahn ◽  
...  
Keyword(s):  
South Africa ◽  
Preschool Children ◽  
Vitamin A ◽  
Total Serum ◽  
High Dose ◽  
Serum Retinol ◽  
Hypervitaminosis A ◽  
Total Liver ◽  
Before And After ◽  
Retinyl Esters

ABSTRACT Background In some regions, multiple vitamin A (VA) interventions occur in the same target groups, which may lead to excessive stores. Retinol isotope dilution (RID) is a more sensitive technique than serum retinol to measure VA status. Objective We evaluated VA status before and after a high-dose supplement in preschool children living in a region in South Africa with habitual liver consumption and exposed to VA supplementation and fortification. Methods After baseline blood samples, subjects (46.7 ± 8.4 mo; n = 94) were administered 1.0 μmol [14,15]-13C2-retinyl acetate to estimate total liver retinol reserves by RID with a follow-up 14-d blood sample. Liver intake was assessed with a frequency questionnaire. In line with current practice, a routine 200,000 IU VA capsule was administered after the RID test. RID was repeated 1 mo later. Serum retinyl esters were evaluated using ultra-performance liquid chromatography. Results At baseline, 63.6% of these children had hypervitaminosis A defined as total liver retinol reserves ≥1.0 μmol/g liver, which increased to 71.6% after supplementation (1.13 ± 0.43 to 1.29 ± 0.46 μmol/g; P < 0.001). Total serum VA as retinyl esters was elevated in 4.8% and 6.1% of children before and after supplementation. The odds of having hypervitaminosis A at baseline were higher in children consuming liver ≥1/mo (ratio 3.70 [95% CI: 1.08, 12.6]) and in children receiving 2 (4.28 [1.03, 17.9]) or 3 (6.45 [0.64, 65.41]) supplements in the past 12 mo. Total body stores decreased after the supplement in children in the highest quartile at baseline compared with children with lower stores, who showed an increase (P = 0.007). Conclusions In children, such as this cohort in South Africa, with adequate VA intake through diet, and overlapping VA fortification and supplementation, preschool VA capsule distribution should be re-evaluated. This trial was registered at https://clinicaltrials.gov/ct2/show/NCT02915731 as NCT02915731.

VITAMIN A POISONING

PEDIATRICS ◽  
1951 ◽  
Vol 7 (3) ◽  
pp. 372-385
Author(s):  
DONALD GRIBETZ ◽  
SAMUEL H. SILVERMAN ◽  
ALBERT E. SOBEL
Keyword(s):  
Vitamin A ◽  
Experimental Studies ◽  
Plasma Vitamin ◽  
Hypervitaminosis A ◽  
Total Vitamin ◽  
Toxic Factor ◽  
Vitamin Intake ◽  
First Case ◽  
Alcohol Fraction ◽  
Clinical Literature

Two cases of hypervitaminosis A have been presented together with a review of experimental and clinical literature. The first case presented the highest reported fasting plasma vitamin A level, the increase being chiefly due to a high vitamin A alcohol fraction. This elevated level of alcoholic vitamin A probably denotes large stores of vitamin A in the liver and data have been given to show that it is a better index of hypervitaminosis A than is the total vitamin A level. In addition, evidence has been presented that the toxic factor in hypervitaminosis A is the permanent elevated plasma vitamin A level. The similarity between the experimental studies in animals and the observations in the authors' first case has been shown. The important points necessary for making a diagnosis of hypervitaminosis A have been discussed and several similar conditions have been differentiated. It cannot be emphasized too strongly that excess vitamin intake may be as dangerous as a deficient intake.

Vitamin A Acid and Hypervitaminosis A

Nature ◽  
1960 ◽  
Vol 188 (4751) ◽  
pp. 672-673 ◽  
Author(s):  
J. N. THOMPSON ◽  
G. A. J. PITT
Keyword(s):  
Vitamin A ◽  
Hypervitaminosis A ◽  
Vitamin A Acid

scholarly journals Multiple Vaccinations and the Enigma of Vaccine Injury

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 676
Author(s):  
Anthony R. Mawson ◽  
Ashley M. Croft
Keyword(s):  
Retinoic Acid ◽  
Vitamin A ◽  
Neurodevelopmental Disorders ◽  
Vaccine Safety ◽  
Mass Vaccination ◽  
Adverse Outcomes ◽  
Interactive Effects ◽  
Hypervitaminosis A ◽  
Ear Infections ◽  
The Impact

A growing number of vaccines are administered at the same time or in close succession, increasing the complexity of assessing vaccine safety. Individual vaccines are assumed to have no other effect than protection against the targeted pathogen, but vaccines also have nonspecific and interactive effects, the outcomes of which can be beneficial or harmful. To date, no controlled trials and very few observational studies have determined the impact of vaccination schedules on overall health. The balance of the risks and benefits from mass vaccination therefore remains uncertain. Recent studies worryingly suggest links between multiple vaccinations and increased risks of diverse multisystem health problems, including allergies, infections, and neuropsychiatric or neurodevelopmental disorders. Here, we propose that, in susceptible persons, multiple vaccinations activate the retinoid cascade and trigger apoptotic hepatitis, leading to cholestatic liver dysfunction, in which stored vitamin A compounds (retinyl esters and retinoic acid) enter the circulation in toxic concentrations; this induces endogenous forms of hypervitaminosis A, with the severity of adverse outcomes being directly proportional to the concentration of circulating retinoids. In very low concentrations, vitamin A and its major metabolite retinoic acid contribute to immune function and to the process of immunization, whereas excess vitamin A increases the risk of adverse events, including common “side-effects” as well as chronic adverse outcomes. The increasing rates of allergy, ear infections, and neurodevelopmental disorders (NDDs) in countries with high rates of vaccination could be related to mass vaccination and to its impact on liver function and vitamin A metabolism, collectively representing endogenous manifestations of hypervitaminosis A. Further studies of health outcomes in vaccinated and unvaccinated groups are urgently needed, to increase understanding of the pathophysiology and treatment of vaccine injury, to identify the risk factors and screen for vaccine injury, to inform public health policy on potential hazards related to vaccination schedules, and to optimize the safety and benefits of vaccines.

scholarly journals Retinol isotope dilution accurately predicts liver reserves in piglets but overestimates reserves in lactating sows

2019 ◽  
Vol 244 (7) ◽  
pp. 579-587 ◽  
Author(s):  
Jesse Sheftel ◽  
Rebecca L Surles ◽  
Sherry A Tanumihardjo
Keyword(s):  
Vitamin A ◽  
Isotope Dilution ◽  
Equilibration Time ◽  
Serum Retinol ◽  
Retinyl Acetate ◽  
Hypervitaminosis A ◽  
Post Dose ◽  
Human Infants ◽  
Lactating Women ◽  
Lactating Sows

Retinol isotope dilution (RID) is used to estimate total body vitamin A (VA) stores in groups to assess VA status. Metabolic differences during lactation may affect RID calculations as currently applied. We evaluated the time required for isotopic equilibration between serum and liver retinol in piglets, and the utility of milk retinol isotopic enrichment as a proxy for serum in lactating sows. Piglets ( n = 24) and sows ( n = 6) were fed 1.75 or 20 µmol 13 C2-retinyl acetate, respectively. Piglets ( n = 5 or 7) were killed on d 0, 4, 7, or 14. Blood and milk were collected at d 0, 0.5, 1, 2, 4, 7, 10, 14, and 21 before the sows were killed to collect liver. Retinol 13 C-enrichment was determined by gas chromatography-combustion-isotope ratio mass spectrometry. Equilibration time and RID-predicted liver VA reserves were calculated. In piglets, serum and liver retinol 13 C-enrichment differed significantly in individuals at d 4 and 7 ( P = 0.008, 0.03) but not d 14 ( P = 0.06); however, mean values were not different by d 4 ( P = 0.62). Current RID equations accurately predicted VA deficiency (means ≤0.027 µmol/g liver) in the piglets. In sows, milk and serum retinol 13 C-enrichment reached equilibrium between 2 and 7 d post-dose. After correcting for dose lost to milk, RID equations predicted higher liver stores than measured values even though the serum to liver atom % was 1.00 ± 0.01 at kill. In VA deficient infants, a shorter period may be accurate in population-level RID studies when using appropriate assumptions. In lactating women, the RID may have decreased accuracy due to variable losses of tracer in milk. Furthermore, assumptions about storage and loss of the dose in milk must be evaluated in lactating women considering the observed discrepancy between predicted and measured stores. Impact statement Vitamin A (VA) deficiency and hypervitaminosis A have been reported in groups of people worldwide. Conventional biomarkers of VA deficiency (e.g. serum retinol concentration, dose response tests) are not able to distinguish between sufficiency and hypervitaminosis A. Retinol isotope dilution (RID) predictions of VA status have been validated in humans and animal models from deficiency through toxicity; however, RID during life stages with unique issues related to isotopic tracing, such as infancy and lactation, requires further evaluation. This study investigated RID in piglets and lactating sows as models for human infants and women. In piglets, RID successfully determined VA deficiency (confirmed with liver analysis), and that the tracer mixes quickly. Conversely, in lactating sows, although serum and milk enrichments were similar, traditional RID equations overestimated VA stores, likely due to losses of tracer and higher extrahepatic VA storage than predictions. These data inform researchers about the challenges of using RID during lactation.

scholarly journals Rubella Virus Infection, the Congenital Rubella Syndrome, and the Link to Autism

2019 ◽  
Vol 16 (19) ◽  
pp. 3543 ◽  
Author(s):  
Anthony R. Mawson ◽  
Ashley M. Croft
Keyword(s):  
Virus Infection ◽  
Vitamin A ◽  
Liver Dysfunction ◽  
Signs And Symptoms ◽  
First Trimester ◽  
Congenital Rubella Syndrome ◽  
Hypervitaminosis A ◽  
Background Rate ◽  
Rubella Infection ◽  
Congenital Rubella

Rubella is a systemic virus infection that is usually mild. It can, however, cause severe birth defects known as the congenital rubella syndrome (CRS) when infection occurs early in pregnancy. As many as 8%–13% of children with CRS developed autism during the rubella epidemic of the 1960s compared to the background rate of about 1 new case per 5000 children. Rubella infection and CRS are now rare in the U.S. and in Europe due to widespread vaccination. However, autism rates have risen dramatically in recent decades to about 3% of children today, with many cases appearing after a period of normal development (‘regressive autism’). Evidence is reviewed here suggesting that the signs and symptoms of rubella may be due to alterations in the hepatic metabolism of vitamin A (retinoids), precipitated by the acute phase of the infection. The infection causes mild liver dysfunction and the spillage of stored vitamin A compounds into the circulation, resulting in an endogenous form of hypervitaminosis A. Given that vitamin A is a known teratogen, it is suggested that rubella infection occurring in the early weeks of pregnancy causes CRS through maternal liver dysfunction and exposure of the developing fetus to excessive vitamin A. On this view, the multiple manifestations of CRS and associated autism represent endogenous forms of hypervitaminosis A. It is further proposed that regressive autism results primarily from post-natal influences of a liver-damaging nature and exposure to excess vitamin A, inducing CRS-like features as a function of vitamin A toxicity, but without the associated dysmorphogenesis. A number of environmental factors are discussed that may plausibly be candidates for this role, and suggestions are offered for testing the model. The model also suggests a number of measures that may be effective both in reducing the risk of fetal CRS in women who acquire rubella in their first trimester and in reversing or minimizing regressive autism among children in whom the diagnosis is suspected or confirmed.

Sign in / Sign up

Export Citation Format

Share Document