Nutritional neuropathies.

Neuropathies associated with nutritional deficiencies are routinely encountered by the practicing neurologist. Although these neuropathies assume different patterns, most are length-dependent, sensory axonopathies. Cobalamin deficiency neuropathy is the exception, often presenting with a non-length-dependent sensory neuropathy. Patients with cobalamin and copper deficiency neuropathy characteristically have concomitant myelopathy, whereas vitamin E deficiency is uniquely associated with a spinocerebellar syndrome. In contrast to those nutrients for which deficiencies produce neuropathies, pyridoxine toxicity results in a non-length-dependent sensory neuronopathy. Deficiencies occur in the context of malnutrition, malabsorption, increased nutrient loss (such as with dialysis), autoimmune conditions such as pernicious anemia, and with certain drugs that inhibit nutrient absorption. When promptly identified, therapeutic nutrient supplementation may result in stabilization or improvement of these neuropathies.

Relación entre niveles de vitamina D y perfil lipídico en embarazadas de alto riesgo / Relationship between level of vitamin D and lipid profile in high risk pregnant women

En la Argentina, las embarazadas presentan alta prevalencia (80%) de hipovitaminosis D y de sobrepeso u obesidad (27,4%). Ambas condiciones pueden aumentar la morbimortalidad materno-fetal. Bajos niveles de vitamina D se han relacionado con aumento del colesterol total, LDL, triglicéridos (Tg) y descenso de HDL. Objetivo: evaluar los niveles de 25-hidroxivitamina D (25OHD) y su relación con el perfil lipídico en pacientes embarazadas de alto riesgo. Materiales y métodos: estudio de corte transversal entre septiembre de 2016 y abril de 2017. Se excluyeron pacientes que recibieron suplementos de vitamina D, con disfunción tiroidea no compensada, malabsorción, insuficiencia cardíaca, renal o hepática y dislipidemia familiar. Niveles circulantes de 25OHD < 30 ng/ml se consideraron hipovitaminosis. Resultados: se evaluaron 86 embarazadas de 29,3 ± 7,1 años durante la semana 28 ± 6,5. El IMC pregestacional fue 28,3 ± 6,5 kg/m2 y la ganancia de peso 7 ± 4,3 kg. Perfil lipídico: colesterol total 240 ± 54 mg/dl; LDL 156 ± 54 mg/dl; HDL 66 ± 15 mg/dl; Tg 204 ± 80 mg/dl. La media de 25OHD fue de 23,8 ± 9 ng/ml, con una prevalencia de hipovitaminosis D de 77,9 %. Las pacientes con hipovitaminosis D presentaron mayores valores de colesterol total y LDL (p < 0,05), con tendencia no significativa a presentar mayores valores de Tg. Conclusión: en embarazadas de alto riesgo se observó una alta prevalencia de hipovitaminosis D, asociada con mayores concentraciones de colesterol total y LDL. (AU)

In Argentina, pregnant women have a high prevalence (80 %) of hypovitaminosis D and verweight/obesity (27.4%), conditions that can increase maternal-fetal morbidity and mortality. Low levels of 25-hydroxyvitamin D (25OHD) have been linked to an increase in total cholesterol, LDL cholesterol, triglycerides (TG) and a decrease in HDL cholesterol. Objective: to evaluate the levels of vitamin D and its relationship with the lipid profile in high risk pregnant patients. Materials and methods: cross-sectional study between September 2016 and April 2017. Patients who received vitamin D supplements or had non-compensated thyroid dysfunction, malabsorption, heart failure, renal or hepatic failure, or familial dyslipidemia were excluded. Hypovitaminosis D was defined as a circulating level of 25OHD < 30 ng/ml. Results: We assessed 86 women of 29.3 ± 7.1 years during pregnancy week 28 ± 6.5. Pre-gestational BMI was 28.3 ± 6.5 kg/m2. Their weight gain was 7 ± 4.3 kg. Lipid profile: total cholesterol 240 ± 54 mg/dl; LDL cholesterol 156 ± 54 mg/dl; HDL cholesterol 66 ± 15 mg/dL; TG 204 ± 80 mg/dl. The mean 25OHD level was 23.8 ± 9 ng/ml, with a 77.9 % prevalence of hypovitaminosis D. Patients with hypovitaminosis D had higher values of total cholesterol and LDL cholesterol (p<0.05), and a non-significant trend toward higher triglyceridemia. Conclusion: A high prevalence of hypovitaminosis D, associated with high total and LDL cholesterol was found in high risk pregnant women. (AU)

Micronutrient Depletion in Heart Failure: Common, Clinically Relevant and Treatable.

Heart failure (HF) is a chronic condition with many imbalances, including nutritional issues. Next to sarcopenia and cachexia which are clinically evident, micronutrient deficiency is also present in HF. It is involved in HF pathophysiology and has prognostic implications. In general, most widely known micronutrients are depleted in HF, which is associated with symptoms and adverse outcomes. Nutritional intake is important but is not the only factor reducing the micronutrient availability for bodily processes, because absorption, distribution, and patient comorbidity may play a major role. In this context, interventional studies with parenteral micronutrient supplementation provide evidence that normalization of micronutrients is associated with improvement in physical performance and quality of life. Outcome studies are underway and should be reported in the following years.

Prolonging healthy aging: Longevity vitamins and proteins.

It is proposed that proteins/enzymes be classified into two classes according to their essentiality for immediate survival/reproduction and their function in long-term health: that is, survival proteins versus longevity proteins. As proposed by the triage theory, a modest deficiency of one of the nutrients/cofactors triggers a built-in rationing mechanism that favors the proteins needed for immediate survival and reproduction (survival proteins) while sacrificing those needed to protect against future damage (longevity proteins). Impairment of the function of longevity proteins results in an insidious acceleration of the risk of diseases associated with aging. I also propose that nutrients required for the function of longevity proteins constitute a class of vitamins that are here named "longevity vitamins." I suggest that many such nutrients play a dual role for both survival and longevity. The evidence for classifying taurine as a conditional vitamin, and the following 10 compounds as putative longevity vitamins, is reviewed: the fungal antioxidant ergothioneine; the bacterial metabolites pyrroloquinoline quinone (PQQ) and queuine; and the plant antioxidant carotenoids lutein, zeaxanthin, lycopene, α- and ß-carotene, ß-cryptoxanthin, and the marine carotenoid astaxanthin. Because nutrient deficiencies are highly prevalent in the United States (and elsewhere), appropriate supplementation and/or an improved diet could reduce much of the consequent risk of chronic disease and premature aging.

Treatment of Vitamin and Mineral Deficiencies After Biliopancreatic Diversion With or Without Duodenal Switch: a Major Challenge.

BACKGROUND: Vitamin and mineral deficiencies are a major concern after biliopancreatic diversion (BPD) and BPD with duodenal switch (BPD/DS). Evidence-based guidelines how to prevent or how to treat deficiencies in these patients are currently lacking. The aim of the current study is to give an overview of postsurgical deficiencies and how to prevent and treat these deficiencies. METHODS: Retrospective evaluation of a 1-year structured monitoring and treatment schedule for various deficiencies in 34 patients after BPD or BPD/DS. RESULTS: Patients were introduced into the program 12-90 months after surgery. Vitamin B1, B6, B9, and B12 deficiencies could be prevented by mean daily doses of 2.75 mg, 980 µg, 600 µg, and 350 µg, respectively. However, many patients continued to develop deficiencies of vitamin A, D, iron, calcium, and zinc despite major dose adjustments. Current observations suggest that at least total daily doses of 200 mg Fe in premenopausal women and 100 mg in men, 100 mg of Zinc, 3000 mg of calcium, and weekly doses of at least 50,000 IU solubilized vitamin A and vitamin D are needed to prevent the occurrence of major deficiencies. CONCLUSION: Exceptionally high supplementation doses are needed to prevent and treat vitamin and mineral deficiencies in patients after BPD or BPD/DS. Further refinement and simplification of treatment schedules is needed. Focus on improvement of compliance to treatment is recommended.

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.

Vitamin Supplementation in the Elderly.

Vitamin supplementation is fairly common among the elderly. Supplements are often used to prevent disease and improve health. In the United States, the use of dietary supplements has continued to increase over the last 30 years, and more than half of adults report using one or more dietary supplements. Epidemiologic evidence suggests that a diet rich in fruits and vegetables does have a protective effect on health. However, clinical trials on the use of vitamin supplements for promotion of health and prevention of disease have failed to demonstrate the strong associations seen in observational studies.

[Effects of dietary fibers on hepatocyte apoptosis in rats with alimentary polyhypovitaminosis].

The effect of dietary fibers (DF) of wheat bran on hepatocyte apoptosis in rats adequately provided with vitamins or insufficiently supplied with vitamins has been investigated. 48 male Wistar rats (initial body mass--58.1 +/- 0.5 g) were randomly divided into 6 groups and fed with semi-synthetic diet, containing 100% or 20% of vitamin mixture (Vit) with or without addition of DF in the dose corresponding to the upper allowable level of its consumption (5% of diet mass) for 4 weeks. The animals of the 1 group received 100% of vitamin mixture (100% Vit); 2 group--100% Vit + DF; 3 group--20% of vitamin mixture with full exclusion of vitamins E, B1 and B2 (20% Vit); 4 group--20% of vitamin mixture and DF (20% Vit + DF). The next 5 days rats from vitamin-deficient groups were fed with diets supplemented with 80% of vitamins from their content in control group: (5 group--20% Vit + 80% Vit; 6 group--20% Vit + DF + 80% Vit). The suspension of hepatocytes was received by Becton Dickinson Medimachine System (USA). Hepatocyte apoptosis was assessed by the method of flow cytometry using Beckman Coulter FC 500 (USA) cytometer by stained cells with Annexin V-FITC/ 7-Amino-Actinomycin D Kit (Beckman Coulter, USA). In rats fed complete semi-synthetic diet supplemented with DF (100% Vit + DF) the hepatocyte apoptosis was higher by 22% (p < 0.10) than that in rats of control group (4.99 +/- 1.82%). In rats fed diets with low vitamin content (groups: 20% Vit and 20% Vit + DF) the hepatocyte apoptosis was significantly higher (p < 0.05) than that in the control group and reached 7.03 +/- 1.74 and 7.26 +/- 1.13% accordingly. Normalization of vitamin content in the diets of rats from deficient groups during 5 days had no effect on the severity of apoptosis regardless from presence (8.02 +/- 2.18%) or absence of the DF (8.04 +/- 1.66%). Adding DF in dose corresponding to the upper allowable level of consumption, on the background of adequate vitamin content in the diet is accompanied by a tendency to develop hepatocyte apoptosis, which may be the result of a direct action of short chain fatty acids generated from the DF and the deterioration of vitamin sufficiency.

[Vitamins and oxidative stress].

The central and local stress limiting systems, including the antioxidant defense system involved in defending the organism at the cellular and systemic levels from excess activation response to stress influence, leading to damaging effects. The development of stress, regardless of its nature [cold, increased physical activity, aging, the development of many pathologies (cardiovascular, neurodegenerative diseases, diseases of the gastrointestinal tract, ischemia, the effects of burns), immobilization, hypobaric hypoxia, hyperoxia, radiation effects etc.] leads to a deterioration of the vitamin status (vitamins E, A, C). Damaging effect on the antioxidant defense system is more pronounced compared to the stress response in animals with an isolated deficiency of vitamins C, A, E, B1 or B6 and the combined vitamins deficiency in the diet. Addition missing vitamin or vitamins restores the performance of antioxidant system. Thus, the role of vitamins in adaptation to stressors is evident. However, vitamins C, E and beta-carotene in high doses, significantly higher than the physiological needs of the organism, may be not only antioxidants, but may have also prooxidant properties. Perhaps this explains the lack of positive effects of antioxidant vitamins used in extreme doses for a long time described in some publications. There is no doubt that to justify the current optimal doses of antioxidant vitamins and other dietary antioxidants specially-designed studies, including biochemical testing of initial vitamin and antioxidant status of the organism, as well as monitoring their change over time are required.

[Colon lactoflora of rats with alimentary polyhypovitaminosis and modified fat component of diet].

The examination was carried out on male Wistar rats with an initial weight 97-121 g. Influence of vitamin provision and composition of fat component in semisynthetic diet on the condition of lactoflora population of intestine were studied. The deficiency of vitamins was caused by fivefold decrease of amount of vitamin mixture added to the feed and by elimination of vitamin E from this mixture. The modification of fat component was made by substitution of sunflower oil for linseed oil in equal amount (the ratio of vegetable oil and animal fat (lard) was 1:1). Duration of the first phase of the experiment was 28 days. Vitamin deficiency in rats, receiving feed with sunflower oil, was accompanied by significant decrease of vitamins A, E, B1 and B2 in the liver, but did not affect the quantity of lactobacilli in caecum content of rats. Enrichment of the diet deficient in vitamins with polyunsaturated omega 3 fatty acids was associated with a statistically significant increase in number of lactobacilli in the intestine compared with the control group (9.78+/-0.08 opposite 8.82+/-0.33 Ig CFU/g, p=0.018) and group of rats with vitamin deficiency (9.03+/-0.18 Ig CFU/g p = 0.006). On the second stage, replenishment of vitamin deficiency was carried out in the next 14 days by increasing the amount of vitamin mixture to 70 and 200% of vitamin content from a diet in control group. The replenishment has not affected the number of caecum lactobacilli irrespectively of the dose of vitamins and fatty component.

[Effect of dietary fat on vitamin status of rats].

The influence of low (1%) and high (31%) diet fat content (sunflower-seed oil and lard 1:1 at a ratio of 1:1) on vitamin A, E, B1 and B2 status of growing Wistar rats (8 rats per group) with initial body weight 80-100 g has been investigated. The semi-synthetic diet contained vitamin mixture in doses covering the physiological requirement of these animals. The increase of fat content (31%) in the diet due to the presence of vitamin E in sunflower-seed oil automatically lead to 1,7-fold increase consumption of this vitamin compared to the control group. Diet fat content did not affect the level of vitamins B1 and B2 in rat liver. Excessive intake of fat and vitamin E for 6 weeks did not influence on the content of blood plasma vitamin E and rat liver vitamin A occurs at the same time, while significant 1,9 fold elevation of liver vitamin E level and 26 per cent increase of blood plasma vitamin A concentration. The almost complete exclusion of fat from the diet had no effect on blood plasma level of alpha-tocopherol and retinol, but resulted in a significant decrease of vitamins A and E content in rat liver by 40 per cent, indicating a deterioration of sufficiency with these fat-soluble vitamins. The analysis of the results obtained in this investigation and literature data have suggested that under excessive as well as under decreased consumption of fat there is a risk of the development of polyhypovitaminosis. Vitamin complex supplementation is required to prevent a possible worsening of vitamin status under diets with modified fatty component.

Use of chitosan in the treatment of obesity: evaluation of interaction with vitamin B12.

Is well known that obesity has increased significantly in recent times and therefore many dietary supplements, synthetic or natural, have been proposed in order to prevent and/or to treat obesity or overweight. Chitosan, a polysaccharide with ability to act as a carrier and to absorb fat, has been used for this purpose. However, interactions with other molecules present in the body may also occur and, therefore, the purpose of this study was to evaluate interactions of chitosan with vitamin B12. Spectroscopic properties of vitamin B12 (acid aqueous solution) were monitored in the absence and the presence of chitosan in order to evaluate possible interactions between the two. Results showed that the rigid micro-environment generated by chitosan solution modifies the photophysical properties of vitamin B12. Thus, chitosan is able to eliminate vitamin B12 and, based on this information, some care must be taken during prolonged treatment with chitosan.

Neurologic complications of bariatric surgery.

With the rapid rise in the number of bariatric surgeries performed for morbid obesity, several short- and long-term neurologic complications of this procedure have been identified. These complications affect various levels of the neuraxis, and most are likely secondary to deficiency of essential minerals and vitamins. We report on 3 patients who developed unusual and severe neurologic deficits after undergoing bariatric surgery, including Wernicke encephalopathy, acute and rapidly progressive polyneuropathy, myelopathy, and visual deficits. Two developed clinical features of Parkinsonism, a complication not previously reported in this patient population. None of our patients had attended a nutrition clinic postoperatively. All 3 had a rapid weight loss and intractable vomiting preceding the development of neurologic symptoms, and all were found to have significant vitamin deficiencies. Replacement of vitamins resulted in a slow and variable degree of neurologic recovery. Patients undergoing bariatric surgery should have close monitoring of their nutritional status postoperatively. Routine supplementation of vitamins and minerals may be a cost-effective strategy for preventing neurologic complications in these patients.

Homocysteine, vitamin determinants and neurological diseases.

This review focuses on the putative role of hyper-homocysteinemia in the pathogenesis of different diseases affecting the nervous system, including stroke, Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis and amyotrophic lateral sclerosis. However, a firm pathogenic role of homocysteine in these diseases has never been established. Lowering plasma homocysteine levels trough vitamin therapy failed to prevent vascular diseases. Conversely, normalization of hyper-homocysteinemia caused improvement in patients with cognitive impairment. B vitamin deficiency is the main determinant of homocysteine levels. However, it has been hypothesized that homocysteine might be a mere marker of vitamin deficiency or an indicator of disease rather than a risk factor. A more consistent use of thresholds to define deficiency is needed to recommend routine screening, monitoring and supplementation of B vitamins to ameliorate the prognosis of the above mentioned disorders. To date, data are insufficient to firmly establish which one of the hypotheses made is correct and the question concerning the real meaning of hyper-homocysteinemia in the pathology of the nervous system still remains an intriguing medical dilemma.

Nutritional deficiencies in obesity and after bariatric surgery.

The presence of nutritional deficiencies in overweight and obesity may seem paradoxical in light of excess caloric intake, but several micronutrient deficiencies appear to be higher in prevalence in overweight and obese adults and children. Causes are multifactorial and include decreased consumption of fruits and vegetables, increased intake of high-calorie, but nutritionally poor-quality foods, and increased adiposity, which may influence the storage and availability of some nutrients. As the obesity epidemic continues unabated and the popularity of bariatric surgery rises for severely obese adults and adolescents, medical practitioners must be aware of pre-existing nutritional deficiencies in overweight and obese patients and appropriately recognize and treat common and rare nutritional deficiencies that may arise or worsen following bariatric surgery. This article reviews current knowledge of nutritional deficits in obese and overweight individuals and those that commonly present after bariatric surgery and summarizes current recommendations for screening and supplementation.

Effects of instant coffee consumption on oxidative DNA damage, DNA repair, and redox system in mouse liver.

To examine the effects of instant coffee consumption on cancer risk, we analyzed the oxidative DNA damage levels and the DNA repair and redox systems in the livers of coffee-fed mice. Three-week-old male ICR mice were fed with/without 0.1% (w/v) instant coffee solution. At 2, 4, and 8 mo, the levels of 8-hydroxydeoxyguanosine (8-OH-dG), a major form of oxidative DNA damage, and the expression of mouse 8-OH-dG repair-associated genes and redox system-associated genes, the SOD activity, and the LPO level were analyzed. Simultaneously, half of the mice were fed a low vitamin (LV) diet (autoclaved diet) to disturb the defense system against oxidative stresses. As a result, the 8-OH-dG level was increased in the livers of LV diet (+ water)-fed mice for 8 mo, in comparison to those of the 0 M control mice and normal diet (+ water)-fed mice. However, no significant differences between water drinking and coffee drinking were observed, in terms of the 8-OH-dG level. In addition, the 8-OH-dG repair-associated gene expression, the SOD activity, and the LPO level also showed no significant differences between water drinking and coffee drinking in all mouse groups. On the other hand, among the redox system-associated genes, only the expression of GPx1 was changed. These results suggest that instant coffee consumption has little, if any, effect on the risk of liver cancer due to oxidative stresses.

The role of nutrients in the prevention and treatment of Alzheimer's disease: methodology for a systematic review.

There is a large body of existing data on nutrition in Alzheimer's disease (AD). We are conducting a systematic review of published scientific literature to determine the role of specific nutrients, both individually and in combination, in the prevention and treatment of AD. This will contribute towards a structured evidence base to help inform the clinical management of AD. The objective of the systematic review is to evaluate the strength of evidence from both observational cohort studies and randomized controlled trials on the role of fats, vitamins, antioxidants and other nutrients in the prevention and treatment of AD. We present here the methodology of our systematic review.

Vitamin D and parathyroid hormone in general populations: understandings in 2009 and applications to chronic kidney disease.

Vitamin D is now recognized as an important prohormone in health and disease. Its role in immunoregulation and cardiovascular and bone health has become topical in the lay press and the medical press in the past 5 yr. The target audience for this review includes the interested clinician and researchers. The prevalence of chronic kidney disease in the general population has further increased the interest and perhaps the applicability of findings of population studies. The basic physiology of vitamin D and receptor activation and biologic importance is reviewed, as well as various vitamin D analogues and nomenclature. Issues related to measurement of vitamin D and parathyroid hormone have the potential to complicate the clinical use of these tests and should be understood by all clinicians so as to ensure informed decision making and stimulate interest in participation in clinical trials. The epidemiology of vitamin D deficiency and supplementation in association with health status and disease status is reviewed, and issues related to association versus causation are highlighted. Some recommendations for pragmatic approaches and study design are suggested.

A semimechanistic-physiologic population pharmacokinetic/pharmacodynamic model for neutropenia following pemetrexed therapy.

PURPOSE: The objectives of these analyses were to (1) develop a semimechanistic-physiologic population pharmacokinetic/pharmacodynamic (PK/PD) model to describe neutropenic response to pemetrexed and to (2) identify influential covariates with respect to pharmacodynamic response. PATIENTS AND METHODS: Data from 279 patients who received 1,136 treatment cycles without folic acid or vitamin B12 supplementation during participation in one of eight phase II cancer trials were available for analysis. Starting doses were 500 or 600 mg pemetrexed per m2 body surface area (BSA), administered as 10-min intravenous infusions every 21 days (1 cycle). The primary analyses included 105 patients (279 cycles) for which selected covariates-including vitamin deficiency marker data (i.e., homocysteine, cystathionine, methylmalonic acid, and methylcitrate [I, II, and total] plasma concentrations)-were available. Classical statistical multivariate regression analyses and a semimechanistic-physiologic population PK/PD model were used to evaluate neutropenic response to single-agent pemetrexed administration. RESULTS: The timecourse of neutropenia following single-agent pemetrexed administration was adequately described by a semimechanistic-physiologic model. Population estimates for system-based model parameters (i.e., baseline neutrophil count, mean transit time, and the feedback parameter), which mathematically represent current understanding of the process and physiology of hematopoiesis, were consistent with previously reported values. The population PK/PD model included homocysteine, cystathionine, albumin, total protein, and BSA as covariates relative to neutropenic response. CONCLUSION: These results support the programmatic decision to introduce folic acid and vitamin B12 supplementation during pemetrexed clinical development as a means of normalizing patient homocysteine levels, thereby managing the risk of severe neutropenia secondary to pemetrexed administration. The current results also suggest that the addition of vitamin B6 supplementation to normalize patient cystathionine levels may further decrease the incidence of grade 4 neutropenia following pemetrexed administration. The results also suggest the use of folic acid as a means of lessening hematologic toxicity following administration of cytotoxic agents other than antifolates.