Vitamin requirements during stem cell transplantation: a systematic review.

Patients undergoing stem cell transplantation (SCT) are at high risk of malnutrition during the acute post-transplantation period. This systematic review aimed to collate and analyse the evidence for vitamin requirements post-SCT. A systematic search of five databases was conducted to include studies published until March 2021. The review utilised the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) framework. Inclusion criteria consisted of adults undergoing SCT who received vitamin supplementation or had their vitamin levels monitored up to 100 days post-SCT. Studies with paediatric patients or those that looked at vitamin derivates such as folinic acid were excluded. Main outcomes included vitamin deficiency and relevant clinical outcomes. Eleven studies (n = 11) were eligible for inclusion with five rated as neutral quality and six as positive quality. Five studies focused on allogenic SCT, two on autologous SCT and the remaining included a mix of both. Eight studies monitored vitamins levels post-SCT, and seven studies provided vitamin supplementation. Three studies (one provided supplementation) found a high prevalence of vitamin D deficiency (23-60%) prior to SCT. Findings indicate an unclear association between vitamin deficiency and post-SCT complications including acute graft-versus-host-disease, oral mucositis, and mortality. The GRADE certainty of evidence across these outcomes was low or very low. It is unclear if supplementation is needed during SCT, though assessing vitamin D levels prior to transplant should be considered. Further large observational studies or randomised control trials are required to establish vitamin requirements and guide supplementation protocols during SCT.

The Impact of Antiepileptic Drugs on Vitamin Levels in Epileptic Patients.

BACKGROUND: The impact of antiepileptics on serum vitamin levels is controversial and uncertain. With no clear conclusions on the impact of antiepileptics on serum levels of vitamins, there is a need for further clinical studies in order to ascertain the impact of old and newer antiepileptic drugs on serum levels of vitamins in epileptic patients, thus accomplishing a suitable usage of vitamins supplementation. OBJECTIVE: The intention of the present research is to confirm the hypothesis of whether or not vitamin levels are altered with antiepileptic drugs. The study also aims to reveal which vitamin levels are particularly more altered, are vitamin levels affected by gender and the type and number of antiepileptics used. METHODS: The present research was piloted in collaboration with the Department of Neurology in Qilu Hospital of Shandong University. A total of 63 serum samples of epileptic patients receiving antiepileptics as monotherapy or polytherapy were requested for analysis of nine vitamin serum levels. Total nine vitamins (B1, B2, B6, B9, B12, A, C, D and E) in epileptic patients receiving antiepileptic drugs were analyzed. The serum results of all vitamins were compiled and evaluated with SPSS. RESULTS: It was alarmingly found that serum levels of vitamin D were particularly very low in almost all (90%) epileptic patients in this study. Notably, serum levels of vitamin C and vitamin B1 were also below reference range in 72% and 46% epileptic patients, respectively. The remaining vitamins were almost in reference range for most of the patients. In our study, mean and frequency of vitamin D, C and B1 levels do not vary too much among different gender groups. The patients receiving newer antiepileptic drugs displayed a slightly increased serum vitamin D levels in comparison to the patients receiving older antiepileptic drugs. We found low vitamin D, C and B1 serum levels in patients who were on monotherapy as in comparison with patients on polytherapy. CONCLUSION: The most significant and surprising finding of this study revealed that serum vitamin D levels in particular were very low in almost all patients and in some patients' vitamin B1 serum levels were also below the reference range. More importantly, it is first time reported here that vitamin C serum levels were also below reference range in the majority of these Chinese epileptic patients. It is recommended that all these vitamins should be regularly monitored in addition to therapeutic drug monitoring of antiepileptic drugs. Additional clinical trials are required for further evaluation. It is also recommended that epileptic patients with low serum levels of these vitamins may be prescribed vitamins supplementations with antiepileptic drugs in order to control their seizures more effectively and efficiently.

Impact of opioids on oxidative status and related signaling pathways: An integrated view.

BACKGROUND: Opioids produce reactive oxygen species (ROS) which are highly reactive molecules that damage cells and tissues, and are suggested to contribute to the opioid use disorders. Thus, antioxidant supplementation might improve the disturbance in redox (oxidation-reduction) homeostasis. However, randomized trials on antioxidant therapy have not shown beneficial effects. OBJECTIVES: The purpose of this review is to shed lights on the oxidative changes resulting from opioid use and to highlight the unanswered questions regarding oxidative profile in an effort to provide a comprehensive view of different aspects of an efficient antioxidant therapy in clinical settings. METHODS: The studies were identified and gathered from the PubMed database over the past 16 years (2000-2016). Our search results were limited to articles in English, both animals and human and in vitro and in vivo studies. A total of 50 full text articles were reviewed and summarized. RESULTS: Opioids elevate the level of ROS and decrease the function of enzymatic antioxidants such as superoxide dismutase, catalase, and glutathione peroxidase. They increase the risk of vitamin deficiency and modify gene expression of target cells through ROS production. The effects of opioids on their target cells are exerted through different way and various mechanisms. CONCLUSION: Opioids modulate the redox homeostasis; therefore, understanding the profile of oxidative changes in individuals with opioid use disorder could be of significant benefits in the clinical setting, to help with selection of an efficient antioxidant therapy and diminishing oxidative damage.

[Proton pump inhibitor - side effects and complications of long-term proton pump inhibitor administration]. / Protonenpumpenhemmer ­ Nebenwirkungen und Komplikationen der langfristigen Protonenpumpenhemmereinnahme.

Proton Pump Inhibitors are among the most common drugs taken. The indication is for treatment of heartburn, reflux disease, prophylaxis and treatment of peptic ulcers, in combination with NSAIDs and steroids as well as H. pylori-eradication. PPI's are widely used, even with non-specific symptoms. This certainly has to do with good tolerability and a previously considered low side effect profile. At the moment, there is growing evidence that the long-term intake of PPI's may not be as safe as assumed. In addition to interactions with some drugs, including platelet aggregation inhibitors, recent studies have shown an increased risk of myocardial infarction, interstitial nephritis, chronic renal injury, infections, vitamin deficiencies and electrolyte shifts as well developing dementia.

Expression of kyphosis in young pigs is induced by a reduction of supplemental vitamin D in maternal diets and vitamin D, Ca, and P concentrations in nursery diets.

Kyphosis is an idiopathic disease characterized by abnormal, outward spinal curvature. A spontaneous outbreak and subsidence of kyphosis over a 4-mo period in the University of Wisconsin Swine Research and Teaching Center herd coincided with an accidental omission of vitamin D(3) in 1 of 2 premixes used in sow diets. This controlled experiment was conducted to determine whether vitamin D deletion from premixes used in sow diets would induce kyphosis in their offspring. Crossbred (Landrace × Large White), multiparous sows (n = 8) were fed corn-soybean meal diets supplemented with either 325 IU vitamin D(3)/kg (+D) or 45 IU vitamin D(3)/kg (-D) diet from breeding through lactation. The vitamin D concentrations duplicated formulations of diets fed during the earlier spontaneous outbreak. At weaning (approximately 4 wk), pigs were fed diets devoid of supplemental vitamin D and formulated to supply either 120% of the Ca and P requirements (HCaP) or 80% of the Ca and P requirements (LCaP) until wk 9. At wk 9, all pigs were fed the HCaP diet until wk 13. No evidence of kyphosis was observed in pigs at weaning. Pigs produced by -D sows and fed LCaP diets exhibited a 17% incidence (4/23 pigs) of kyphosis at wk 9. At wk 13, the incidence of kyphosis had increased to 32% (6/19 pigs). Unexpectedly at wk 13, pigs produced by +D sows and fed LCaP diets exhibited a 26% incidence (5/19 pigs) of kyphosis. None of the pigs fed HCaP diets from wk 4 to 13 displayed kyphosis, regardless of maternal diets. Evidence of kyphosis was detected at a younger age if pigs were produced by sows fed -D diets. Whole body and femur bone mineral content determined with dual energy X-ray absorptiometry were reduced (P < 0.05) in pigs fed LCaP vs. HCaP diets, but pigs produced by -D sows were more severely affected. Femur bending moments were reduced (P < 0.05) at wk 9 and 13 in pigs fed LCaP vs. HCaP diets. At wk 13, pigs produced by -D sows and fed LCaP diets had reduced (P < 0.05) bone mineral density and femur yield bending moment compared with pigs from +D sows fed LCaP diets. In conclusion, the 20 to 30% incidence of kyphosis induced by altering vitamin D, Ca, and P concentrations in maternal and nursery diets mimics the incidence observed in spontaneous outbreaks in afflicted herds. A reproducible vitamin D-induced kyphosis in young pigs offers a suitable model to study skeletal tissue characteristics, fetal skeletal tissue development, and potential treatments for pigs and human patients afflicted by this disease.

[The impact of medication on vitamins and trace elements]. / Statut en vitamines et en oligoéléments: impact des médicaments.

Epidemiological studies have shown that vitamin or trace-element deficiencies are frequent in the general population. Food intake can be incriminated, but various drugs may also precipitate micronutrient deficits. Indeed, the consequences of pharmacotherapy on micronutrients are yet modestly explored in clinical practice settings. We aim at sensitizing physicians on the impact of frequently used drugs on vitamins and trace-elements. High risk populations for micronutrient deficiencies and indications for substitution are discussed.

Oral treatment with amitriptyline induces coenzyme Q deficiency and oxidative stress in psychiatric patients.

Amitriptyline is a commonly prescribed tricyclic antidepressant, which has been shown to impair mitochondrial function and increase oxidative stress in a variety of in vitro assays. Coenzyme Q(10) (CoQ(10)), an essential component of the mitochondrial respiratory chain and a potent antioxidant, has been proposed as a mitochondrial dysfunction marker. In order to evaluate the putative mitochondrial toxicity of amitriptyline, we have analyzed CoQ(10) and ATP levels, oxidative damage and mitochondrial mass in peripheral blood cells from control healthy volunteers and psychiatric patients with depressive episodes treated or non-treated with amitriptyline. In patients not following amitriptyline treatment, CoQ(10) and ATP levels and mitochondrial mass were reduced when compared to normal individuals while lipid peroxidation was clearly increased. All these alterations were aggravated in patients following oral amitriptyline therapy. These results suggest that mitochondrial dysfunction could be involved in the pathophysiology of depression and may be worsened by amitriptyline treatment. CoQ(10) supplementation is postulated to counteract the adverse effects of amitriptyline treatment in psychiatric patients.

Intake of medication and vitamin status in the elderly.

BACKGROUND/AIMS: An inadequate vitamin status is associated with higher morbidity and frailty in the elderly and might be due to medication. This study aimed to evaluate the status of several vitamins in relation to regular intake of medication in this population. METHODS: A total of 102 non-institutionalized subjects aged 70-90 years were recruited. Plasma levels of vitamins A, D, E, K and C were determined by HPLC. The functional parameters of vitamins B(1), B(2) and B(6), i.e. the activities of the erythrocyte enzymes transketolase, glutathione reductase and glutamic oxaloacetic transaminase were analyzed photometrically; plasma folate and vitamin B(12) were determined by RIA. RESULTS: The status of vitamins A, E and C was generally satisfactory. Eighty-eight percent and 42% of participants were deficient in vitamins D and K, respectively, as were 29% in B(6); up to 10% were deficient in vitamins B(1), B(2), B(12) and folate. A considerable percentage of participants was, however, at risk for vitamin deficiencies (vitamins B(1), B(6), B(12) and folate: 20-30%; vitamin B(2): 60%). Regular intake of maximally 2 drugs per day was not adversely related to the status of several vitamins; intake of ≥ 3 drugs per day was significantly negatively associated with the status of vitamins D, K, B(6) and folate. CONCLUSION: Daily intake of ≥ 3 drugs was found to be adversely associated with the status of some vitamins in the elderly. Hence, the medication schedule and nutritional status of these subjects should be monitored closely to ensure that the daily micronutrient requirement is fulfilled.

Deficiencies in fat-soluble vitamins in long-term users of somatostatin analogue.

BACKGROUND: Somatostatin analogues are administered to control hormone hypersecretion in acromegaly and carcinoid patients. Somatostatin analogues can increase fat in the stools, which can lead to loss of fat-soluble vitamins. The effect of long-term somatostatin analogue use on vitamin levels remains unknown. AIM: To investigate the prevalence of fat-soluble vitamin deficiencies in long-term somatostatin analogue users. METHODS: All acromegaly and carcinoid patients using somatostatin analogues for ≥ 18 months visiting the University Medical Center Groningen between December 2008 and April 2009 were eligible. Vitamin levels of fat-soluble vitamins in blood, clinical and vitamin-dependent laboratory parameters were collected. RESULTS: In all, 19 acromegaly and 35 carcinoid patients were included. Twelve patients experienced steatorrhoea; two carcinoid patients experienced night blindness. Forty-two (78%) were deficient for one or more vitamins, and 32% (n = 17) had multiple deficiencies. Deficiencies for vitamin A, D, E, K1 and E in erythrocytes occurred in 6%, 28%, 15%, 63% and 58% of the patients. Prevalence of vitamin D, E and K1 deficiencies was similar in both patient groups. Treatment duration did not influence vitamin levels. The length of intestinal resection and age correlated negatively with vitamin A levels. CONCLUSIONS: Fat-soluble vitamin deficiencies are frequent during long-term somatostatin analogue treatment. Therefore, fat-soluble vitamins should be monitored in these patients.

Drug-induced nutrient deficiencies.

Good clinical care extends beyond mere diagnosis and treatment of disease to appreciation that nutrient deficiencies can be the price of effective drug therapy. The major risk factors for developing drug-induced nutrient deficiencies are lack of awareness by the prescribing physician and long duration of drug therapy. The field of pharmacogenomics has potential to improve clinical care by detecting patients at risk for complications from drug therapy. Further improvements in patient safety rely on physicians voluntarily reporting serious suspected adverse drug reactions.

The experimental induction of leukoencephalomyelopathy in cats.

Leukoencephalomyelopathy of undetermined etiology has been described in specific pathogen-free cats. A study was established to assess if the long-term feeding of a gamma-irradiated diet could induce this disease. Cats fed exclusively on diet irradiated at 25.7-38.1 kGy ("typical" dose) and 38.1-53.6 kGy (high-end dose), respectively, developed typical lesions with attendant, progressively severe ataxia between study days 140 and 174. The onset of ataxia at day 140 and the number of animals affected at this time were similar in animals fed each ration. A maximum ataxia "score" was first reached by an animal on the high-end dose diet on day 167 and by 2 cats fed the "typical-end" dose diet 21 days later. Ataxic cats and 1 animal euthanized on day 93 prior to the onset of ataxia exhibited varying degrees of Wallerian degeneration in the spinal cord and brain, similar to the spontaneous disease. The elevated total antioxidant status of spinal cord segments and hepatic superoxide dismutase concentration of cats fed typical and high-end treated diets suggested free-radical involvement in the pathogenesis. The significantly elevated peroxide concentrations of the irradiated diets (1,040% and 6,440% of untreated values) may have resulted in increased oxidative insult, a factor possibly exacerbated by the treated diets' reduced vitamin A content. This study has reproduced leukoencephalomyelopathy in cats similar to spontaneous outbreaks by feeding a gamma-irradiated dry diet with elevated peroxide and reduced vitamin A concentrations.

The effects of biotin supplementation on serum and liver tissue biotinidase enzyme activity and alopecia in rats which were administrated to valproic acid.

Valproic acid (VPA) is a widely used and well-tolerable antiepileptic drug in epileptic patients. However, VPA has many side effects dose-dependent or non-dose-dependent. It is reported that VPA treatment may lead to biotin deficiency and low serum and liver tissue biotinidase enzyme activity (BEA). Major clinical manifestations in biotin deficiency are seborrheic dermatitis, dry skin, fine and brittle hair, and alopecia. We aimed to investigate the effects of biotin supplementation on serum and liver tissue BEA and alopecia during VPA therapy. Rats were randomly divided into 4 groups, each consisted of 15 rats (VPA-B1, VPA-B2, VPA, and control). Except the control group, all groups were administrated VPA dose of 600 mg/kg/d per oral (PO) for 60 days with 12h intervals two divided doses. VPA-B1 was administrated biotin dose of 6 mg/kg/d and VPA-B2 was administrated biotin dose of 0.6 mg/kg/d. In the third week of the study, we determined alopecia in the study groups. Alopecia was seen in the subjects of 13.3% of VPA-B1 (n=2), 13.3% of VPA-B2 (n=2), and 40% of VPA (n=6). But statistical significant effect on alopecia by biotin supplementation was not able to be determined between the study groups. In the control group, alopecia was not observed. The ratios of alopecia in the study groups were statistically higher than the control group (p=0.028). Itchiness was more obvious in the study groups compared with the control group. Serum biotin levels of the biotin supplemented groups (VPA-B1 and VPA-B2) were higher than the other groups (VPA and control group). Serum biotin levels of the VPA group were lower than the control group. There were significant decreases in the levels of serum and liver tissue BEA of the study groups compared with the control group. In conclusion we showed that VPA usage reduced the serum and liver tissue BEA and impaired the biotin utilization by affecting the liver. Partial biotinidase deficiency may lead to alopecia. It might be prevented by biotin supplementation in the patients receiving VPA therapy. We considered that further studies are necessary to find out the effective and safe biotin dose.

Vitamins deficiency in developing chick during chromium intoxication and protection thereof.

Deficiency of various vitamins in postnatally developing chick during chromium intoxication and their recovery during vitamins (B and E) and glutathione therapies has been investigated. Study was concentrated on liver, kidney, muscles and serum. Newly hatched chicks were reared in laboratory. They were treated with a daily dose of 10mg/kg/day potassium dichromate from 2nd to 8th day of their age. Thereafter, one group was sacrificed on 9th day. Second group was kept without intoxication for another 7 days and sacrificed on 16th day. Three groups of chromium pretoxicated animals were exposed to therapeutic agents like vitamins (B and E) and glutathione for another 7 days. These animals were sacrificed on 16th day of their age along with control. Study showed chromium intoxication decreases vitamins (B(1), B(2), B(6) and E) in all the tissues and serum. The maximum decrease was recorded in serum. The 7 days pretoxicated animals kept without any treatment for 7 days revealed a slow increase of vitamins with few exceptions. Nevertheless, the recovery of vitamins was quick and significant during vitamins and glutathione therapy and in some cases control level was achieved.

Effects of orlistat on fat-soluble vitamins in obese adolescents.

STUDY OBJECTIVES: To determine whether orlistat causes fat-soluble vitamin deficiencies in African-American and Caucasian adolescents. DESIGN: Prospective, open-label pilot study. SETTING: Warren Grant Magnuson Clinical Center of the National Institutes of Health. PATIENTS: Seventeen adolescents with body mass indexes above the 95th percentile for age, race, and gender who also had at least one obesity-related comorbid condition. INTERVENTION: Subjects received orlistat 120 mg 3 times/day and a daily multivitamin supplement containing vitamin A 5000 IU, vitamin D 400 IU, vitamin E 300 IU, and vitamin K 25 microg. MEASUREMENTS AND MAIN RESULTS: During 3-6 months of orlistat treatment, acute absorption of retinol (vitamin A) was not significantly altered, but absorption of alpha-tocopherol (vitamin E) was significantly reduced compared with baseline levels (p<0.001). Serum levels of vitamins A and E did not change significantly; however, there was a nonsignificant decrease in vitamin K. Mean vitamin D levels were significantly reduced compared with baseline (p<0.02) after 1 month of orlistat, despite multivitamin supplementation. CONCLUSION: It may be prudent to monitor vitamin D concentrations in adolescents who take orlistat, even when a multivitamin is prescribed.

The role of orlistat in weight management.

BACKGROUND: Most antiobesity drugs act centrally to reduce appetite or increase satiety. Orlistat is the first in a new class of drugs targeted at a single dietary component, in this case dietary fat. OBJECTIVE: To review the clinical actions and efficacy of orlistat and to discuss its place in overall weight management. DISCUSSION: Orlistat is best used in long term weight management as an adjunct to dietary modification and increased physical activity. The reduction in fat absorption results in a slow but sustained weight reduction and improved metabolic parameters such as reduced total, and LDL cholesterol. Side effects are minimised by maintaining a low fat diet.

Role of the ketogenic diet in children with intractable seizures.

OBJECTIVE: To provide a review of the mechanism of action, clinical efficacy, adverse effects, drug interactions, and therapeutic considerations associated with the use of a ketogenic diet to manage patients with intractable seizures. DATA SOURCES: A MEDLINE search from January 1966 to the present and relevant articles from journals were reviewed. DATA SYNTHESIS: The ketogenic diet has been used as a treatment modality since the early 1920s to control intractable seizures. The exact mechanism of action is unknown. Overall, uncontrolled clinical studies have reported that approximately one-third of patients with intractable seizures have become seizure-free on the ketogenic diet. Common adverse events attributed to the diet include dehydration, gastrointestinal symptoms, hypoglycemia, as well as carnitine and vitamin deficiencies. Cognitive effects, hyperlipidemia, impaired neutrophil function, urolithiasis, optic neuropathy, osteoporosis, and protein deficiency may also occur in some patients. Carbohydrate content and drug formulation in the selection of medications while on the diet are important. Acetazolamide, phenobarbital, and valproic acid have been reported to interact with the ketogenic diet. Medications that cause carnitine deficiency or influence carbohydrate metabolism should also be used with caution. The carbohydrate content of drugs in various therapeutic classes is presented to aid in the selection of the most appropriate drug and formulation for patients on the ketogenic diet. The success of the diet in controlling intractable seizures is related to the patient's close adherence to the diet. Minimizing carbohydrate ingestion from medications along with a multidisciplinary team approach to the selection and monitoring of the diet are important to the success of the ketogenic diet in controlling seizures. CONCLUSIONS: The ketogenic diet has shown promising results in controlling intractable seizures; however, carefully controlled clinical trials are needed to better assess the efficacy of the diet during its use and after discontinuation.