Pharmacokinetics of vitamin C: insights into the oral and intravenous administration of ascorbate

There is a strong advocacy movement for large doses of vitamin C. Some authors argue that the biological half-life for vitamin C at high plasma levels is about 30 minutes, but these reports are the subject of some controversy. NIH researchers established the current RDA based upon tests conducted 12 hours (24 half lives) after consumption. The dynamic flow model refutes the current low-dose recommendations for dietary intakes and links Pauling's mega-dose suggestions with other reported effects of massive doses of ascorbate for the treatment of disease. Although, a couple of controlled clinical studies conducted at The Mayo Clinic did not support a significant benefit for terminal cancer patients after 10 grams of once-a-day oral vitamin C, other clinical trials have demonstrated that ascorbate may indeed be effective against tumors when administered intravenously. Recent studies confirmed that plasma vitamin C concentrations vary substantially with the route of administration. Only by intravenous administration, the necessary ascorbate levels to kill cancer cells are reached in both plasma and urine. Because the efficacy of vitamin C treatment cannot be judged from clinical trials that use only oral dosing, the role of vitamin C in cancer treatment should be reevaluated. One limitation of current studies is that pharmacokinetic data at high intravenous doses of vitamin C are sparse, particularly in cancer patients. This fact needs prompt attention to understand the significance of intravenous vitamin C administration. This review describes the current state-of-the-art in oral and intravenous vitamin C pharmacokinetics. In addition, the governmental recommendations of dose and frequency of vitamin C intake will also be addressed.

Vesicular transport of Fe and interaction with other metal ions in polarized Caco2 Cell monolayers

Two aspects of the mechanisms by which iron is absorbed by the intestine were studied in the Caco2 cell model, using 59Fe(II)-ascorbate. Data showing the importance of vesicular processes and cycling of apotransferrin (apoTf) to uptake and overall transport of Caco2 cell monolayers (or basolateral 59Fe release) were obtained by comparing effects of: a) adding apoTf to the basal chamber; b) adding vesicular transport inhibitors; or c) cooling to 4°C. These showed that apoTf may be involved in as much as half of Fe transfer across the basolateral membrane, and that vesicular processes may also play a role in non-apoTf-dependent Fe transport. Studies were initiated to examine potential interactions of other metal ions with Fe(II) via DMT1. Kinetic data showed a single, saturable process for uptake of Fe(II) that was pH dependent and had a Km of 7 ìM. An excess of Mn(II) and Cu(I) over Fe(II) of 200: 1 (ìM: ìM) in 1 mM ascorbate markedly inhibited Fe uptake. The kinetics were not competitive. Km increased and Vmax decreased. We conclude that vesicular transport, involving endo- and exocytosis at both ends of the enterocyte, is a fundamental aspect of intestinal iron absorption and that DMT1 may function as a transporter not just for divalent but also for monovalent metal ions.

Efecto de la administración oral de ácido ascórbico sobre la sensibilidad a la insulina y el perfil de lípidos en individuos con obesidad / Effect of the oral administration of ascorbic acid on lipid profile and insulin sensitivity in obese people

Objetivo. Determinar el efecto de la administración oral de un suplemento farmacológico de Ácido Ascórbico (AA) sobre la sensibilidad a la insulina y el perfil de lípidos en individuos obesos. Diseño de la investigación y métodos. Se realizó un ensayo clínico doble ciego en 16 voluntarios masculinos obesos, con índice de masa corporal (IMC) entre 30 y 40 kg/m 2 , sin enfermedad agregada. Ocho fueron asignados al azar a recibir 1g oral de AA diario por 4 semanas y el resto a recibir placebo por el mismo tiempo. Se determinaron colesterol total, colesterol de las lipoproteínas de alta densidad (HDL), triglicéridos, glucosa, creatinina y ácido úrico séricos, tanto antes como después de la intervención farmacológica. El colesterol de las lipoproteínas de baja densidad (LDL) y los triglicéridos de las lipoproteínas de muy baja densidad (VLDL) se estimaron con fórmulas. Se realizó una prueba de supresión a la insulina modificada con octreótido y se calculó el estado estacionario de la glucosa (EEG) para estimar la sensibilidad a la insulina antes y después de la intervención. Resultados. No existió diferencia significativa en las características clínicas entre ambos grupos, así mismo, fueron similares en su perfil metabólico y en el EEG antes de la intervención. No se presentaron diferencias significativas en el perfil metabólico y en la sensibilidad a la insulina, estimada mediante el EEG, entre antes(AU) y después de la intervención, tanto en el grupo de AA como en el de placebo. Conclusión. La administración oral de AA no modificó la sensibilidad a la insulina, ni el perfil de lípidos en individuos obesos.

Bioavailability of iron bis-glycinate chelate in water

Iron amino acid chelate is being increasingly considered in programs for iron fortification of foods. The bioavailability of iron bis-glycinate chelate given in water was studied using a double-isotopic method in a group of 14 women. Iron absorption from aqueous solutions of 15 mg/L of elemental iron as either iron bis-glycine chelate or ferrous ascorbate was not significantly different (34.6 and 29.9 respectively). Standardized iron absorption of the iron bis-glycinate was 46.3 (standardized to 40 absorption of the reference dose). There was a significant correlations between (ln) iron absorption of iron bis-glycinate chelate with (ln) serum ferritin (r = -0.60, p < 0.03) and with (ln) iron absorption from ferrous ascorbate (r = 0.71, p < 0.006), suggesting that iron bis-glycinate chelate absorption is indeed regulated by the iron stores of the body.

Radicales libres y antioxidantes en la prevención de enfermedades, III: evidencias clínico epidemiológicas de los riesgos y beneficios asociados al consumo de antioxidantes en la prevención de enfermedades cardiovasculares / Free radicals and antioxidants in disease prevention, III: clinical and epidemiological evidences of the risks and benefits associated with antioxidant consumption in cardiovascular disease prevention

La presente actualización constituye la tercera parte de una serie de artículos publicados en esta revista sobre radicales libres y antioxidantes en nutrición, salud y patologá humana. En los artículos referidos, los autores han realizado una detallada descripción y discusión de los principales mecanismos de generación de radicales libres en el organismo, de sus acciones tanto biológicas como deletéreas, y de aquellos mecanismos de defensa antioxidante encargados de la remoción de dichas especies radicalarias. De estas revisiones se ha desprendido que, si bien la formación controlada de radicales libres es un evento continuo de carácter fisiológico, la existencia de un desbalance a favor de la generación de especies radicalarias respecto a la velocidad con que dichas especies son removidas (estrés oxidativo) puede conducir a la oxidación masiva de susbtratos biológicos. Se estableció que si bien el estrés oxidativo per se no es sinonimo de daño, la cronicidad de este evento a nivel celular/tisular puede estar involucrado en la etiogénesis y/o en el desarrollo de numerosas patologías entre las que destacan las enfermedades cardiovasculares y diversos tipos de cáncer. Esto último ha constituido la base racional para intentar establecer asociaciones entre el nivel de ingesta de antioxidantes dietarios y la prevención de dichas enfermedaes. En esta tercera revisión, centrándose en enfermedades cardiovasculares, los autores han intentado recoger en forma concisa las princiipales evidencias científicas, de carácter epidemiológico y clínico, en torno a los potenciales beneficios y riesgos asociados al consumo de antioxidantes (ya sea dietario o como suplemento)

Efecto de la suplementación de las vitaminas C y E en la dieta del pollo de engorda sobre los parámetros productivos y la respuesta inmune / Effect of vitamin C and E supplementation in the diet of broilers chicks on performance and immune response

Se evaluó la adicción de las vitaminas C y E en el alimento de iniciación y finalización (1-28 y 29-56 días de edad) sobre los parámetros productivos y la respuesta inmune del pollo de engorda. Se seleccionaron 1,6000 pollos de estirpe Indian River X Peterson de la misma incubadora, que se distribuyeron en 4 tratamientos con 4 repeticiones de 100 pollos cada una. Los tratamientos fueron la dieta base o testigo o con suplementación entre de 200 ppm de vitamina C + 74,000 U.I. de vitamina E/ton. Los parámetros evaluados fueron los productivos, así como los perfiles inmunológicos a través de niveles de anticuerpos como una respuesta primaria y secundaria a glóbulos rojos de borrego (GRB), Brucella abortus (Ba) y a la vacuna de virus vivos modificado (VVM) y muerto de newcastle (VM). Los tratamientos fueron similares en cuanto a peso corporal, consumo de alimento, conversión alimenticia y mormalidad. En todos los antígenos usados para evaluar la respuesta primaria, el testigo presentó títulos menores mostrando diferencia significativa a los 21 días posinoculación; para GRB a favor de la adicción conjunta de vitamina C + E (5.6 vs 2.4), Ba (12.4 vs 0) y para VVM a favor de la adición de vitamina E (5.4 vs 4.4). La respuesta secundaria fue favorable para los tratamientos donde se administraron las vitaminas. Para GRB, hubo una diferencia a los 7 días posinoculación de la segunda aplicación a favor de la vitamina C + E (24 vs. 6.4); para Ba hubo una respuesta a los 7 días posinoculación de la primera aplicación a favor de la vitamina C (35.2 vs. 19.2) y para VM la respuesta secundaria fue mejor con vitamina C + E a los 7 días posinoculación de la segunda aplicación (7.8 vs. 6.4) y a los 14 días posinoculación (8.6 vs 7.0). Los resultados indican que las adiciones extras de las vitaminas C y E en dietas para pollo de engorda mejoran la respuesta inmunológica

Storage effect on juices and drinks with reference to some cariogenic factors

This work was carried out to study the effect of storage for a period of 5 months on total soluble solids [TSS], pH value, total acidity, vitamin C, sugar content, optical density in some juices and drinks, to avoid the cariogenic factors, such as sugar and acidity. The results showed that, total soluble solids were 3%, 4%, 8% and 10% in rosette plant, tamarind, guava and orange juices, respectively, while it was ranged between 17% to 18% for drinks and 10-12% for carbonated beverage, before storage. In general, TSS of drink and beverage products were higher than juices and were quite stable during storage period. pH value was slightly decreased in juices and drinks during storage period [5 months], while the total acidity was slightly increased, which ranged between 0.611 to 0.615 mg/100 g in juices and 0.365 to 0.380 mg/100 g in drinks, this is due to the formation of CO2 and/or to slight degradation or oxidation of some reducing sugars. Vitamin C and sugar content were decreased, this is due to the method of juice preparation and duration of storage. Vitamin C content in guava juice was 50-60 fold higher than other juices. Optical density change is an important quality attribute, some discoloration occurred for orange drinks, while the color of guava drink was stable. It was concluded that anthocyanin and carotene contents were decreased during the storage. Finally, storage at room temperature did not eliminate the all cariogenicity of studied juices, drinks and beverage, based on the changes in chemical composition. It is important to avoid frequent consumption of all these types of products in order to reduce the risk for dental caries

Effect of vitamins C and E intake on plasma lipid concentrations in rats

Changes in the plasma lipid levels were investigated among rats fed an atherosclerotic-promoting diet containing 0.5% cholesterol and rats fed the same diet with added vitamin C [ascorbic acid], vitamin E [a-tocopherol] and vitamins C + E from one to seven weeks. Total cholesterol [TC] and triglycerides [TG] were significantly increased in rats fed a hyperlipidemic diet from the third week to the seventh week, whereas high density lipoprotein cholesterol [HDL-C] was not affected. Rats supplemented with 5 mg vitamin C, 5 mg vitamin E or 5 mg vitamin C + 5 mg vitamin E per day for four to seven weeks showed significant decrease in the concentration of TC and TG. HDL-C was only affected at the seventh week with vitamin C alone, whereas it was significantly increased with vitamin E alone and vitamins C + E at five to seven weeks. However, supplementation of vitamins C, E or C + E for less than four weeks has no significant effect on plasma lipid concentrations. The antioxidant effect of vitamins C and E is probably a time-dependent process that significantly lowers plasma lipids between week four and week seven following administration of these vitamins. It is therefore suggested that the incidence of coronary heart disease [CHD] may be reduced in lowering plasma lipid levels by dietary supplementation of vitamins C or E