Hypervitaminosis A Following the Ingestion of Fish Liver: Report on 3 Cases from the Poison Control Center in Marseille.

In European countries, vitamin A toxicity is most often the result of an excessive intake of vitamin supplements and rarely the consequence of the ingestion of a large carnivorous fish liver. We report 3 cases of vitamin A poisoning after fish liver ingestion in mainland and overseas France. The patients were a 12-y-old girl, a 36-y-old pregnant woman, and a 62-y-old man. They experienced headache, nausea, emesis, and desquamation. Laboratory examination showed a high serum retinol level in the girl. The woman's pregnancy progressed to a miscarriage. This case series shows that this kind of poisoning is not restricted to the polar regions. In patients presenting with flushing combined with signs of intracranial hypertension, accurate questioning of the patient's diet is crucial to avoid misdiagnosis and unnecessary examinations. Pregnant women or women of child-bearing age should be informed of the risk to pregnancy in the case of excessive fish liver ingestion.

Hypervitaminosis A is associated with immunological non-response in HIV-1-infected adults: a case-control study.

For people living with HIV, determinants of immunological non-response (INR) to combined antiretroviral therapy (cART) have not been fully elucidated. In a case-control study, we evaluated the influence of the nutritional and antioxidant status in HIV-1 adults whose cART was initiated between January 2001 and December 2013. Cases had persistent CD4 counts < 350/µL vs. > 350/µL for controls, after at least 2 years of cART with persistent viral loads (VL) < 50 copies/mL. Twelve cases and twenty-eight control subjects with the same CD4 count at cART initiation were compared for their nutritional and antioxidant status after age adjustment at dosage assessment. Patients were predominantly male (70%), Caucasian (82%) and at AIDS stage (62%). The median age was 53, and the median CD4 count was 245/mm3 for cases and 630/mm3 for controls after a median time of 7 years on cART. Despite higher energy intakes in cases, anthropometric data was comparable between groups who had similar vitamins B9/B12/C/D/E, zinc, citrulline and glutamine levels. Nine cases (75%) and 8 controls (29%) had hypervitaminosis A (> 2.70 µmol/L) (p = 0.030). Cases had lower erythrocyte resistance when exposed to a controlled free radical attack (p = 0.014). Most cases had hypervitaminosis A and altered antioxidant capacities that could affect immunological response. Wide-scale studies are required, but in the meantime, screening of their vitamin A status must be encouraged in these patients.

Long-term dietary intake of excessive vitamin A impairs spermatogenesis in mice.

Vitamin A and its derivatives contribute to many physiological processes, including vision, neural differentiation, and reproduction. Vitamin A deficiency causes early cessation of spermatogenesis, characterized by a marked depletion of germ cells. However, there has been no clear understanding about the role of chronic intake of vitamin A excess (VAE) in spermatogenesis. The objective of this study was to investigate whether chronic intake of VAE diet causes arrest of spermatogenesis. To examine the effects of VAE on spermatogenesis, we used ICR male mice fed with control (AIN-93G purified diet: 4 IU/g) diet or VAE (modified AIN-93G diet with VAE: 1,000 IU/g) diet for 7 weeks (from 3 to 10 weeks of age). At 10 weeks of age, the retinol concentration in the testes of VAE mice was significantly higher than that of control mice. Testicular cross sections from control mice contained a normal array of germ cells, while the seminiferous tubules from VAE mice exhibited varying degrees of testicular degeneration. Daily sperm production in VAE testes was dramatically decreased compared to that in control testes. Sperm viability, motility, and morphology were also impaired in VAE mice. Furthermore, we examined the effects of VAE on the expression of genes involved in retinoid signaling and spermatogenesis to determine the underlying molecular mechanisms. Therefore, we are the first to present results describing the long-term dietary intake of VAE impairs spermatogenesis using a mouse model.

High provitamin A carotenoid serum concentrations, elevated retinyl esters, and saturated retinol-binding protein in Zambian preschool children are consistent with the presence of high liver vitamin A stores.

BACKGROUND: Biomarkers of micronutrient status are needed to best define deficiencies and excesses of essential nutrients. OBJECTIVE: We evaluated several supporting biomarkers of vitamin A status in Zambian children to determine whether any of the biomarkers were consistent with high liver retinol stores determined by using retinol isotope dilution (RID). DESIGN: A randomized, placebo-controlled, biofortified maize efficacy trial was conducted in 140 rural Zambian children from 4 villages. A series of biomarkers were investigated to better define the vitamin A status of these children. In addition to the assessment of total-body retinol stores (TBSs) by using RID, tests included analyses of serum carotenoids, retinyl esters, and pyridoxal-5'-phosphate (PLP) by using high-pressure liquid chromatography, retinol-binding protein by using ELISA, and alanine aminotransferase (ALT) activity by using a colorimetric assay. RESULTS: Children (n = 133) were analyzed quantitatively for TBSs by using RID. TBSs, retinyl esters, some carotenoids, and PLP differed by village site. Serum carotenoids were elevated above most nonintervened reference values for children. α-Carotene, ß-carotene, and lutein values were >95th percentile from children in the US NHANES III, and 13% of children had hypercarotenemia (defined as total carotenoid concentration >3.7 µmol/L). Although only 2% of children had serum retinyl esters >10% of total retinol plus retinyl esters, 16% of children had >5% as esters, which was consistent with high liver retinol stores. Ratios of serum retinol to retinol-binding protein did not deviate from 1.0, which indicated full saturation. ALT activity was low, which was likely due to underlying vitamin B-6 deficiency, which was confirmed by very low serum PLP concentrations. CONCLUSIONS: The finding of hypervitaminosis A in Zambian children was supported by high circulating concentrations of carotenoids and mildly elevated serum retinyl esters. ALT-activity assays may be compromised with co-existing vitamin B-6 deficiency. Nutrition education to improve intakes of whole grains and animal-source foods may enhance vitamin B-6 status in Zambians.

A Case Report of Acute Vitamin A Intoxication due to Ocean Perch Liver Ingestion.

BACKGROUND: Chronic vitamin A intoxication is well known; however, there are few reports of acute vitamin A intoxication due to the ingestion of food rich in vitamin A, particularly in adults. CASE REPORT: We report a case of a 27-year-old man presenting with chief complaints of flushing, headache, nausea, and joint pain. He had consumed 800 g of grilled ocean perch liver the day before and had experienced numbness shortly after. Although physical examination revealed only facial flushing, we suspected acute vitamin A intoxication due to his diet history. On day 2 after ingestion, his serum retinol levels were elevated at 1577 ng/mL, which confirmed vitamin A intoxication. He returned for follow-up on day 4 after ingestion, by which time his presenting symptoms had improved, but he had developed desquamation of his facial skin. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Emergency physicians should consider acute vitamin A intoxication in the differential diagnosis of patients with headache, flushing, desquamation, nausea, and vomiting of unknown etiology. Complete diet histories and checking vitamin A levels are essential for diagnosis. This report highlights the diagnostic difficulties associated with vitamin A intoxication and the importance of an accurate diet history.

Retinoids, race and the pathogenesis of dengue hemorrhagic fever.

Dengue hemorrhagic fever (DHF) is the most significant mosquito-borne viral disease worldwide in terms of illness, mortality and economic cost, but the pathogenesis of DHF is not well understood and there is no specific treatment or vaccine. Based on evidence of liver involvement, it is proposed that dengue virus and retinoids interact to cause cholestatic liver damage, resulting in the spillage of stored retinoids into the circulation and in an endogenous form of hypervitaminosisis A manifested by the signs and symptoms of the disease, including: fever, severe joint and bone pain, capillary leakage, thrombocytopenia, headache, and gastrointestinal symptoms. While retinoids in low concentration are essential for numerous biological functions, they are prooxidant, cytotoxic, mutagenic and teratogenic in higher concentration, especially when unbound to protein, and an endogenous form of vitamin A intoxication is recognized in cholestasis. The model tentatively explains the observations that 1) repeat infections are more severe than initial dengue virus infections; 2) the incidence of denue has increased dramatically worldwide in recent decades; 3) DHF is less prevalent in people of African ancestry than those of other racial backgrounds; and 4) infants are protected from dengue. The retinoid toxicity hypothesis of DHF predicts the co-existence of low serum concentrations of retinol coupled with high concentrations of retinoic acid and an increased percentage of retinyl esters to total vitamin A. Subject to such tests, it may be possible to treat DHF effectively using drugs that target the metabolism and expression of retinoids.

Mefloquine use, psychosis, and violence: a retinoid toxicity hypothesis.

Mefloquine use has been linked to severe gastrointestinal and neuropsychiatric adverse effects, including cognitive disturbances, anxiety, depression, psychosis, and violence. The adverse effects of the drug are thought to result from the secondary consequences of hepatocellular injury; in fact, mefloquine is known to cause a transient, anicteric chemical hepatitis. However, the mechanism of mefloquine-associated liver damage and the associated neuropsychiatric and behavioral effects of the drug are not well understood. Mefloquine and other 8-amino-quinolines are the only antimalarial drugs that target the liver-stage malaria parasites, which selectively absorb vitamin A from the host. Vitamin A is also stored mainly in the liver, in potentially poisonous concentrations. These observations suggest that both the therapeutic effectiveness of mefloquine and its adverse effects are related to the ability of the 8-aminoquinolines to alter the metabolism of retinoids (vitamin A and its congeners). Several lines of evidence support the hypothesis that mefloquine neurotoxicity and other adverse effects reflect an endogenous form of hypervitaminosis A due to a process involving: mefloquine-induced dehydrogenase inhibition; the accumulation of retinoids in the liver; retinoid-induced hepatocellular damage; the spillage of stored retinoids into the circulation; and the transport of these compounds to the gut and brain in toxic concentrations. The retinoid hypothesis could be tested clinically by comparing cases of mefloquine toxicity and untreated controls in terms of retinoid profiles (retinol, retinyl esters, percent retinyl esters, and retinoic acid). Subject to such tests, retinoid profiling could provide an indicator for assessing mefloquine-associated adverse effects.

Individualized vitamin A supplementation for patients with cystic fibrosis.

BACKGROUND & AIMS: To determine the vitamin A status and appropriate supplementation dosage of cystic fibrosis (CF) patients who received vitamin A supplementation based on annual serum retinol measurements. METHODS: Vitamin A food intake, supplementation dosage, and serum retinol levels were obtained for 32 CF patients >4 years of age (4.3-27.3 years old) who had pancreatic insufficiency and mild-to-moderate lung disease (percent predicted of forced expiratory volume in 1 s > 40%). These measurements were compared with the dietary reference intake for healthy children and adults (D-A-CH dietary recommendations), US and German CF recommendations, and serum retinol concentrations from National Health and Nutrition Examination Survey (NHANES) data. RESULTS: Total vitamin A intake from food and supplementation was 315% ± 182% of D-A-CH recommendations, with 65% from supplements. The range of the prescribed vitamin A supplementation dosage was 0-20,000 IU/day (median 5500 IU), and it was consistent with CF recommendations in 28% of participants. A quarter of all patients did not need any vitamin A supplementation. The total vitamin A intake exceeded the recommended upper limit of intake in 69% of subjects. The mean (range) serum retinol was 38.6 µg/dl (22.1-59.1 µg/dl). All subjects had serum retinol levels above 20 µg/dl and below 72 µg/dl (95th percentile of NHANES reference range). CONCLUSION: Individualized vitamin A supplementation of 0-20,000 IU/day based on annual serum retinol measurements may prevent deficiency and high serum retinol levels, but it may lead to vitamin A intake above the tolerable upper intake level.

Vitamin A: too much of a good thing?

UNLABELLED: Vitamin A has the unique distinction of being readily available over the counter, yet conferring significant toxic and teratogenic potential. Although vitamin A deficiency is relatively rare in the United States, globally it is the most common cause of blindness. The following is a review of the various forms and derivatives of vitamin A and their associations with potential adverse perinatal outcomes. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After participating in this CME activity, physicians should be better able to identify sources of Vitamin A, distinguish between toxic and non toxic forms of Vitamin A and counsel patients regarding the dosages of Vitamin A that are tolerable during pregnancy.

Acute vitamin A toxicity: a report of three paediatric cases.

The following report describes three paediatric cases of vitamin A toxicity secondary to carnivorous fish liver ingestion. Further discussion of vitamin A toxicity and management of toxicity is included.

Vitamin A intoxication from reef fish liver consumption in Bermuda.

We report three historical cases of severe vitamin A intoxication in anglers who had consumed reef fish liver caught in Bermuda. The subsequent analyses of 35 fish livers from seven different fish species revealed that very high concentrations of vitamin A exist in tropical fish liver, even in noncarnivorous fish species. Large variations in concentrations were observed between specimens and between species. The angling population and (especially) pregnant women should be advised of this potential health threat.

Species identification and vitamin A level in lutjanid fish implicated in vitamin A poisoning.

One outbreak of food poisoning associated with ingestion of the liver of a large lutjanid fish was investigated in this study. The symptoms in three patients primarily included headache, nausea, vomiting, fever, vertigo, and visual disorientation and later included peeling of the skin. The species of fish implicated in this incident was Etelis carbunculus (family Lutjanidae) as determined by direct sequence analysis and PCR plus restriction fragment length polymorphism analysis for detection of the cytochrome b gene. Subsequently, several specimens of E. carbunculus of different body weights were collected, and the level of vitamin A in the muscle and liver was determined by high-performance liquid chromatography. The average level of vitamin A in E. carbunculus muscle was 12 +/- 2 IU/g and that in the liver was 9,844 +/- 7,812 IU/g. Regression models indicate that E. carbunculus with higher body weight and liver weight will have higher levels of vitamin A levels in the liver.

Hypervitaminosis A in experimental nonhuman primates: evidence, causes, and the road to recovery.

One of the great underlying assumptions made by all scientists utilizing primate models for their research is that the optimal nutritional status and health of the animals in use has been achieved. That is, no nutrient deficiency or excess has compromised their health in any detectable way. To meet this assumption, we rely on the National Research Council's (NRC's) nutritional recommendations for nonhuman primates to provide accurate guidance for proper dietary formulations. We also rely on feed manufacturers to follow these guidelines. With that in mind, the purpose of this commentary is to discuss three related points that we believe have significant ramifications for the health and well being of captive primates as well as for their effective use in biomedical research. First, our laboratory has shown that most experimental primates are likely in a state of hypervitaminosis A. Second, it is apparent that many primate diets are providing vitamin A at levels higher than the NRC's recommendation. Third, the recommendation itself is based on inadequate information about nutrient needs and is likely too high, especially when compared with human requirements.

Hypervitaminosis a in pediatric hematopoietic stem cell patients requiring renal replacement therapy.

BACKGROUND: Chronic renal failure patients have been known to develop vitamin A toxicity, but a descriptive study of hypervitaminosis A in patients with acute renal failure (ARF) has not yet been published. The authors observed hypervitaminosis A in pediatric hematopoietic stem cell transplant (HSCT) patients. METHODS: All HSCT patients admitted between January 2001 and May 2006 who experienced ARF, received renal replacement therapy (RRT), and had a vitamin A level drawn were included in this retrospective, descriptive study. Molar ratios of vitamin A and retinol-binding protein (RBP) were calculated to more accurately assess vitamin A status. Nineteen patients met the criteria for this study. RESULTS: At initial testing (generally between days 6 and 10 after initiation of RRT), 17 of the 19 patients had abnormally elevated vitamin A levels for their age. Molar ratios of vitamin A to RBP were elevated in 6 patients at initial testing. Prescribed vitamin A intake information (parenteral and enteral) was available for most patients; all but 3 had an average daily intake greater than 2000 IU/kg over the 30 days prior to RRT initiation. Many patients had symptoms possibly related to vitamin A toxicity, although interpretation of hair, skin, and liver abnormalities are difficult to ascertain in HSCT patients. Seven patients had other findings that may have been associated with vitamin A toxicity. CONCLUSION: Children undergoing HSCT who receive nutrition support (predominantly parenteral nutrition), experience ARF, and require RRT are at risk for hypervitaminosis A and toxicity.

Risk of vitamin A toxicity from candy-like chewable vitamin supplements for children.

Numerous vitamin supplements are available over-the-counter to the general public. Some such supplements are available as candy-like chewable preparations to encourage consumption by children. We report 3 cases of overdose of such preparations. Each patient had taken an estimated 200,000 to 300,000 IU of vitamin A. Their circulating vitamin A (retinol and retinyl palmitate) concentrations were monitored over a 6-month period. There were no clinical or biochemical complications noted. However, there were marked increases in both retinol and retinyl palmitate concentrations above age-related reference ranges. In particular, it took 1 to 3 weeks for the serum retinol concentrations to peak and many months for them to normalize. Parents should be warned about the dangers of excessive vitamin consumption. Clinicians should be aware of the late peak in serum retinol concentrations, which may lead to late complications of vitamin A overdose.