GATA1 controls numbers of hematopoietic progenitors and their response to autoimmune neuroinflammation.

GATA-binding factor 1 (GATA1) is a transcription factor that governs the development and function of multiple hematopoietic cell lineages. GATA1 is expressed in hematopoietic stem and progenitor cells (HSPCs) and is essential for erythroid lineage commitment; however, whether it plays a role in hematopoietic stem cell (HSC) biology and the development of myeloid cells, and what that role might be, remains unclear. We initially set out to test the role of eosinophils in experimental autoimmune encephalomyelitis (EAE), a model of central nervous system autoimmunity, using mice lacking a double GATA-site (ΔdblGATA), which lacks eosinophils due to the deletion of the dblGATA enhancer to Gata1, which alters its expression. ΔdblGATA mice were resistant to EAE, but not because of a lack of eosinophils, suggesting that these mice have an additional defect. ΔdblGATA mice with EAE had fewer inflammatory myeloid cells than the control mice, suggesting that resistance to EAE is caused by a defect in myeloid cells. Naïve ΔdblGATA mice also showed reduced frequency of CD11b+ myeloid cells in the blood, indicating a defect in myeloid cell production. Examination of HSPCs revealed fewer HSCs and myeloid cell progenitors in the ΔdblGATA bone marrow (BM), and competitive BM chimera experiments showed a reduced capacity of the ΔdblGATA BM to reconstitute immune cells, suggesting that reduced numbers of ΔdblGATA HSPCs cause a functional deficit during inflammation. Taken together, our data show that GATA1 regulates the number of HSPCs and that reduced GATA1 expression due to dblGATA deletion results in a diminished immune response following the inflammatory challenge.

Effect of micro-osteoperforations on the gene expression profile of the periodontal ligament of orthodontically moved human teeth.

OBJECTIVES: This study aimed to evaluate the effect of micro-osteoperforations (MOPs) on the gene expression profile of the periodontal ligament (PDL) of orthodontically moved teeth. MATERIALS AND METHODS: Fifteen participants were randomly assigned into two groups: tooth movement only (Tr1, n = 7) and tooth movement supplemented with MOPs (Tr2, n = 8). In each subject, orthodontic tooth movement (OTM) was performed on premolar in one side, while no force was applied on contralateral premolar (Unt, n = 15). Seven days after loading, premolars were extracted for orthodontic reasons. RNA extraction from PDL and subsequent RNA-sequencing were performed. False discovery rates (Padj < 0.05) and log2 fold change (+ / - 1.5) thresholds were used to identify sets of differentially expressed genes (DEGs) among the groups. DEGs were analyzed with gene ontology enrichment, KEGG, and network analysis. RESULTS: Three hundred thirty-one DEGs were found between Tr1 and Unt, and 356 between Tr2 and Unt. Although, there were no significantly DEGs between Tr2 and Tr1, DEGs identified exclusively in Tr1 vs. Unt were different from those identified exclusively in Tr2 vs. Unt. In Tr1, genes were related to bone metabolism processes, such as osteoclast and osteoblast differentiation. In Tr2, genes were associated to inflammation processes, like inflammatory and immune responses, and cellular response to tumor necrosis factor. CONCLUSIONS: MOPs do not significantly alter the PDL gene expression profile of orthodontically moved human teeth. This study provides for the first time evidence on the whole PDL gene expression profiles associated to OTM in humans. Novel biomarkers for OTM are suggested for additional research. Clinical relevance The identified biomarkers provide new insights into the molecular mechanisms that would occur when OTM is supplemented with MOPs. These markers are expected to be useful in the near future for the application of personalized strategies related to the OTM.

Carcinogénesis Oral y Epigenética / Oral Carcinogenesis and Epigenetics

A pesar de que los procesos epigenéticos son estudiados ampliamente de forma general, no se habían relacionado, hasta ahora, a las alteraciones genéticas más tradicionales asociadas en la etiopatogenia del cáncer oral. La visión de carcinogénesis tradicional y la de la epigenética convergen en las mismas vías moleculares involucradas en el desarrollo del cáncer, potenciándose durante el proceso de carcinogénesis oral. A continuación se realizará una revisón de las siguientes vías moleculares VEGF-C /VEGFR; HB-EGF /EGFR; Wnt /B-catenina y las ciclinas, desde un punto de vista genético y epigenético para establecer su conexión durante el proceso de carcinogénesis oral.

Although epigenetic processes are widely studied, no one has related them to the classical genetic processes in oral cancer etiopathogenesis. The traditional carcinogenesis and epigenetic views converge in the same molecular pathways involved in cancer development, enhancing this process. This review will approach the VEGF-C/VEGFR, HB-EGF/EGFR, Wnt /B-catenin, and cyclins molecular pathways from the genetic and epigenetic views to establish their connection during the oral cancer process.

Constrained chromatin accessibility in PU.1-mutated agammaglobulinemia patients.

The pioneer transcription factor (TF) PU.1 controls hematopoietic cell fate by decompacting stem cell heterochromatin and allowing nonpioneer TFs to enter otherwise inaccessible genomic sites. PU.1 deficiency fatally arrests lymphopoiesis and myelopoiesis in mice, but human congenital PU.1 disorders have not previously been described. We studied six unrelated agammaglobulinemic patients, each harboring a heterozygous mutation (four de novo, two unphased) of SPI1, the gene encoding PU.1. Affected patients lacked circulating B cells and possessed few conventional dendritic cells. Introducing disease-similar SPI1 mutations into human hematopoietic stem and progenitor cells impaired early in vitro B cell and myeloid cell differentiation. Patient SPI1 mutations encoded destabilized PU.1 proteins unable to nuclear localize or bind target DNA. In PU.1-haploinsufficient pro-B cell lines, euchromatin was less accessible to nonpioneer TFs critical for B cell development, and gene expression patterns associated with the pro- to pre-B cell transition were undermined. Our findings molecularly describe a novel form of agammaglobulinemia and underscore PU.1's critical, dose-dependent role as a hematopoietic euchromatin gatekeeper.

Evaluation of exosome derivatives as bio-informational reprogramming therapy for cancer.

Exosomes are nanoparticle sized (100 ± 50 nm) extracellular vesicles (ECVs) that play important roles in cell-to-cell communication. They do this by utilizing their natural ability to shuttle signaling molecules across the cellular microenvironment and promote paracrine signaling. Currently, exosomes are being explored for their potential as therapeutic agents for various degenerative diseases including cancer. The rationale behind their therapeutic ability is that they can transfer signaling biomolecules, and subsequently induce metabolic and physiological changes in diseased cells and tissues. In addition, exosomes can be used as a drug delivery system and may be very effective at reducing toxicity and increasing bioavailability of therapeutic molecules and drugs. Although exosomes were first believed to be a waste product of the cell, current research has demonstrated that these particles can serve as modulators of the immune system, act as cancer biomarkers, cause re-differentiation of cancer cells, and induce apoptosis in diseased cells. Extensive research has been performed specifically using amniotic fluid-derived extracellular vesicles, named "cytosomes". While the use of cytosomes in clinical application is still in the early stages, researchers have shown great potential for these EVs in regenerative medicine as immune modulators, in controlling microbial infection and by inducing tissue repair through the activation of endogenous, tissue-specific stem cells. This review emphasizes the capabilities of specific subsets of extracellular vesicles that can potentially be used for cancer therapy, principally as a source of bi-informational reprogramming for malignant cells.

Impact of Intravenous Vitamin C and Endolaser Therapies on a Pediatric Brainstem Glioma Case.

Pediatric cases of a brainstem glioma are one of the most difficult tumors to treat. In children, this type of cancer is perhaps the most dreaded of cancers due to its poor prognosis, yet it remains an area of intense research. In the case presented herein, conventional chemotherapy and radiotherapy treatments were not showing any improvement. The patient was then treated with high-dose intravenous vitamin C (IVC) and endolaser therapy. A significant reduction in glioma's size was achieved in 2 months with this adjunct therapy. These results present a possibility of decreasing brainstem glioma progression with adjuvant IVC and endolaser therapy.

Metabolic Correction in Patients Sample with Diabetes: Clinical Outcomes and Costs Reductions.

Diabetes is a leading cause of mortality and morbidity worldwide. Diabetes complications produce profound impact on patient's quality of life and represent very significant economic cost to patients, their family, the government and society as a whole. Metabolic correction has been proposed as an efficient method to improve clinical outcomes and reduce costs in diabetes. Metabolic correction is a concept that supports health maintenance and promotes the healing processes by improving the body's biochemical-physiological mechanisms. This is done by helping activate the metabolic enzymes necessary to facilitate key physiological pathways. A group of 50 patients followed a simple metabolic correction strategy based on hydration, diet, and magnesium supplementation during a 6 months period. Outcomes measures included laboratory testing, anthropometric measures and medication use including its related costs. Patients had an average weight loss of 9.4 lbs (↓5.0%) from baseline at month 3 and 12 lbs (↓6.4%) at month 6. Waist circumference decreased on average 3.7 inches (↓9.0%) from baseline at month 3 and had further decrease to 5.5 inches (↓13.4%) from baseline at month 6. Laboratory testing of average triglycerides decreased from a baseline of 156.9 to 116.7 (↓25.6%) at month 3 and maintained a reduction of ↓24.2% by month 6. Total cholesterol concentration decreased from a baseline of 181.1 mg/dL to 173.9 (↓4.0%) in month 3 and to 171.1 (↓5.5%) at month 6. Average HgA1c decreased from baseline of 7.17 to 6.52 (↓9.1%) at month 3 and maintained 6.52 at months 6. The atherogenic index decreased from 4.18 at baseline to 3.85 at month 3 (↓7.9%) and then 3.47 (17.0%) at month 6. Medication use and cost was quantified in various ways. The average baseline monthly diabetes medication cost per patient of $124.10 was reduced to $ 78.23 (↓36.7% reduction) at month 3 and to $62.80 (↓49.4% reduction) at month 6. A simple and well structured metabolic correction program that includes a significant educational component, dietary modifications and dietary supplement intake was able to maintain or improve vital signs, anthopometric and laboratory measurements that correlate with improved clinical diabetes and cardiovascular health. This outcome was achieved while decreasing the use medications at month 3 and 6 at significant cost savings.

Metabolic Correction as a tool to improve diabetes type 2 management.

Diabetes Mellitus type 2 (DM2) is a metabolic disease that develops by a decrease in sensitivity of insulin receptors as an effect of the disruption certain metabolic functions in the processing of glucose. DM2 patients have, uncontrolled glucose levels, and commonly have problems with obesity and cardiovascular disease. Patients are treated with standard diet, insulin, diabetic oral agents and antihypertensive drugs, but this approach does not completely stops tissue deterioration since it does not address the metabolic root of the disease. Metabolic correction is proposed as a suitable adjunct treatment to improve clinical outcomes. Metabolic correction is based on diet modification, proper hydration and scientific supplementation directed to improve cellular biochemistry and metabolic efficiency. In addition, other possible benefits may include reduction in medication use, disease complications and medical costs. To test the results of a metabolic correction program, 25 patients with DM2 participated in an education program about adequate food consumption that promoted control of blood glucose levels. Anthropometric measurements and blood tests were performed during a 13 week program based on a low carbohydrate diet, proper hydration and magnesium supplementation. The metabolic correction program implemented by a proprietary educational system resulted in significant reductions in glucose, triglycerides, cholesterol, weight and waist circumference. Improvements in these values could represent an important reduction of coronary heart disease risk factors as well as other chronic degenerative diseases. In addition there was medication dosage reduction in one or more medications in 21 of the 25 participating patients, which suggest that the program has the potential to improve health outcomes and reduce health care costs.

[Metabolic correction: a biochemical option against diseases]. / Corrección metabólica: Una opción bioquímica contra las enfermedades.

Human development and its physiology depends on a number of complex biochemical body processes, many of which are interactive and codependent. The speed and the degree in which many physiological reactions are completed depend on enzyme activity, which in turn depends on the bioavailability of co-factors and micronutrients such as vitamins and minerals. To achieve a healthy physiological state, organism need that biochemical reactions occur in a controlled and specific way at a particular speed and level or grade fully completed. To achieve this, is required an optimal metabolic balance. Factors such as, a particular genetic composition, inadequate dietary consumption patterns, traumas, diseases, toxins and environmental stress all of these factors rising demands for nutrients in order to obtain optimal metabolic balance. Metabolic correction is a biochemical and physiological concept that explains how improvements in cellular biochemistry of an organism can help the body achieve metabolic and physiological optimization. We summarize the contribution of several pioneers in understanding the role of micronutrients in health management. The concept of metabolic correction is becoming a significant term due to the presence of genetic variants that affect the speed of reactions of enzymes, causing metabolic alterations that enhance or promote the state/development of multiple diseases. Decline in the nutritional value of the food we eat, the increase in demand for certain nutrients caused by normal development, diseases and medications induce, usually, nutrients consumption. These nutritional deficiencies and insufficiencies are causing massive economic costs due to increased morbidity and mortality in our society. In summary, metabolic correction improves the enzymatic function, which favors the physiological normal functions, thus, contributing to improving health and the welfare of the human being. The purpose of this paper is to describe and introduce the concept of optimal metabolic correction as a functional cost-effective mechanism against disease, in addition, to contribute to diseases prevention and regeneration of the body and health.

Metabolic correction: a functional biochemical mechanism against disease--Part 2: mechanisms and benefits.

A healthy physiology depends on a plethora of complex interdependent biochemical reactions. In order for these reactions to occur suitably, the enzymes and cofactors that regulate their flow must be present in the proper balance. The term metabolic correction is used to describe a biochemical-physiological process that improves cellular biochemistry as a means to an individual's achieving metabolic or physiological optimization. Part 2 discusses how metabolic correction, through the increase of cofactors, can supply unmet enzyme needs and compensate for nutritional deficiencies induced by improper nutritional intake or by the increased demand for nutrients caused by genetics, health conditions, medications, or physical or environmental stressors. Nutrient insufficiencies are causing an increase in morbidity and mortality, at great cost to our society. In summary, metabolic correction improves enzymatic function and satisfies the increasing demand for nutrients. Metabolic correction can have a significant impact on the reduction of morbidity and mortality and their financial cost to our society and contribute to improving health and well-being.

Metabolic correction: a functional biochemical mechanism against disease--Part 1: concept and historical background.

Human physiology depends on countless biochemical reactions, numerous of which are co-dependent and interrelated. The speed and level of completion of reactions usually depend on the availability of precursors and enzymes. The enzymatic activity depends on the bioavailability of micronutrient cofactors such as vitamins and minerals. In order to achieve a healthy physiological state, the organism requires that biochemical reactions occur at a controlled rate. To achieve this state it is required that metabolic reactions reach what can be considered an optimal metabolic equilibrium. A combination of genetic makeup, dietary patterns, trauma, disease, toxins, medications, and environmental stressors can elevate the demand for the nutrients needed to reach this optimal metabolic equilibrium. In this, part 1, the general concept of metabolic correction is presented with an elaboration explaining how this concept is increasing in importance as we become aware of the presence of genetic variants that affect enzymatic reactions causing metabolic disturbances that themselves favor or promote the disease state. In addition, part 1 reviews how prominent scientists have contributed in fundamental ways to our understanding of the importance of micronutrients in health and disease and in the development of the metabolic correction concept.

Alcohol consumption and smoking and their associations with socio-demographic characteristics, dietary patterns, and perceived academic stress in Puerto Rican college students.

OBJECTIVE: College students often use different strategies, such as consuming alcohol and smoking, to cope with stress. We examined the associations between self-perceived academic stress, alcohol consumption, smoking, and dietary patterns in graduate students. METHODS: A representative stratified sample of 275 students from each school of the Medical Science Campus of the University of Puerto Rico (UPR-MSC) completed a 48-item questionnaire that solicited the following: socio-demographic data, estimates of self-perceived stress, estimates of the frequency of alcohol consumption and the type(s) of alcohol consumed, details regarding smoking habits, and information associated with diet (i.e., dietary patterns). Fisher's exact test and the Chi2 test were used to assess the associations between the different study variables. RESULTS: Only 3% were considered smokers (defined as > 1 cigarettes per day), with the greatest number of smokers among those aged 21-30 y (p<0.05). Smoking habits was not associated with academic load/stress or with dietary pattern. Most smokers reported that their main reason for using cigarettes was to cope with stress. About 70% of the students were considered drinkers (defined as > 0 drink/day), with a higher proportion found among women (63.5%), among those aged 21-30 years (90.6%), and among those with a low or moderate household income (p<0.05). Alcohol intake was significantly associated with academic stress, with a greater proportion of drinkers reporting experiencing moderate levels of academic stress (p<0.05), but it was not associated with dietary patterns or academic load (p>0.05). Most subjects classified as drinkers reported that alcohol consumption was not (in their experience) an effective strategy for the management of stress (81%). CONCLUSION: Alcohol consumption was only associated with academic stress. No associations were found between smoking habits and academic stress/load and dietary patterns.

Non-medical use of prescription drugs and its association with socio-demographic characteristics, dietary pattern, and perceived academic load and stress in college students in Puerto Rico.

OBJECTIVE: Stress can have deleterious effects on health and academic performance. Common stress-relieving activities among college students include the non-medical use of prescription drugs (NMUPD). The aim of this study was to determine the associations between self-perceived academic load and stress, NMUPD (stimulants, depressants, and sleeping medication), and dietary pattern in college students in PR. METHODS: A questionnaire to evaluate academic load and stress, NMUPD, and dietary pattern was used on a representative sample of 275 first- and second-year students from one campus. RESULTS: In total, 27.6% reported NMUPD in the past 6 months, with higher use among students aged 21-30 years (93.4%) than in those aged 31-53 years (6.6%; p=0.062). Those with high levels of stress had higher NMUPD (42.1%) than did those with low (26.3%) or moderate (31.6%) stress levels, after controlling for age and sex (p=0.03). Among those who reported NMUPD over the previous 6 months, 74% reported that such use was effective as a coping strategy, and 35% reported that it helped them to improve academic performance. Although no significant association was found between NMUPD and dietary pattern, 57% of the participants reported that their appetites decreased when they engaged in NMUPD. CONCLUSION: To our knowledge, this is the first study that has associated self-perceived academic load and stress, NMUPD, and dietary pattern among college students in Puerto Rico. NMUPD's prevalence was 27.6%, which prevalence appeared to be higher in students aged 21-30 years than in those of any other age. High levels of stress were significantly related to high NMUPD in this sample.

Caffeinated-beverage consumption and its association with socio-demographic characteristics and self-perceived academic stress in first and second year students at the University of Puerto Rico Medical Sciences Campus (UPR-MSC).

OBJECTIVE: To determine the association between caffeinated-beverage consumption, self-perceived academic load, and self-perceived stress levels in first and second year students at UPR-MSC. METHODS: A descriptive epidemiological study was performed using a self-administered anonymous questionnaire given to a representative stratified sample of 275 students. Questions included information regarding socio-demographic characteristics, academic load and stress indicators, and caffeinated-beverage consumption. Chi2 was used to assess the associations between these variables. RESULTS: Most participants were women (68%), aged 21-30 years (88%), with low annual household incomes (43%). Most perceived their academic loads as being heavy (68%), and most perceived their academic stress levels as being moderate (37%). Academic load was significantly correlated with stress level (p<0.001). About 88% of the participants reported consuming caffeinated beverages; of those, 87% drank soft drinks, 83% drank coffee, 56% drank hot chocolate, 40% drank tea, and 29% drank energy drinks, all of which were--according to the participants (54%)--used mainly to stay awake. Soft drinks and coffee intake increased in periods of high stress, and many (49%) reported that these beverages were useful for coping with stress. Energy drinks, in particular, were consumed more often by men compared to women (p<0.05). None of these beverages were significantly associated with academic stress or load. CONCLUSION: Consuming caffeinated beverages is a popular practice among participants in this sample, with soft drinks and coffee being the ones that are the most frequently consumed. No associations were found between the consumption of caffeinated beverages and academic stress or load.

Alteration of ganglioside biosynthesis responsible for complex hereditary spastic paraplegia.

Hereditary spastic paraplegias (HSPs) form a heterogeneous group of neurological disorders. A whole-genome linkage mapping effort was made with three HSP-affected families from Spain, Portugal, and Tunisia and it allowed us to reduce the SPG26 locus interval from 34 to 9 Mb. Subsequently, a targeted capture was made to sequence the entire exome of affected individuals from these three families, as well as from two additional autosomal-recessive HSP-affected families of German and Brazilian origins. Five homozygous truncating (n = 3) and missense (n = 2) mutations were identified in B4GALNT1. After this finding, we analyzed the entire coding region of this gene in 65 additional cases, and three mutations were identified in two subjects. All mutated cases presented an early-onset spastic paraplegia, with frequent intellectual disability, cerebellar ataxia, and peripheral neuropathy as well as cortical atrophy and white matter hyperintensities on brain imaging. B4GALNT1 encodes ß-1,4-N-acetyl-galactosaminyl transferase 1 (B4GALNT1), involved in ganglioside biosynthesis. These findings confirm the increasing interest of lipid metabolism in HSPs. Interestingly, although the catabolism of gangliosides is implicated in a variety of neurological diseases, SPG26 is only the second human disease involving defects of their biosynthesis.

Dietary patterns and their association with sociodemographic characteristics and perceived academic stress of college students in Puerto Rico.

OBJECTIVE: University students face academic responsibilities that may produce stress, which may lead to changes in dietary patterns (DPs). These changed patterns can become dysfunctional, often resulting in a negative impact on the health of the stressed student. Little is known about DPs in college students in Puerto Rico (PR). The purpose of this study was to describe the DPs of college students in PR and the association of these patterns with socio-demographic characteristics and perceived academic stress. METHODS: This retrospective epidemiological study investigated self-reported DPs in a representative sample of 275 college students, in relation to socio-demographic characteristics, body composition (BC), and perceived academic stress; a Diet Quality Index was developed using the USDA Food Patterns for 2010 to determine whether their DPs were adequate or inadequate. RESULTS: Most of the participating students were female (67.6%), ranged from 21 to 30 years old (88%), lived in low household incomes (42.7%), and had healthy weights (56.4%). Most of the students perceived the stress levels as being moderate (60.7%). Most had diets that were below the dietary recommendations for grains, fruits, vegetables, dairy products, and protein, whereas fat consumption was adequate. Overall, most had inadequate DPs (62%). DP was significantly associated with age (p < 0.05); older students had better DPs than did younger students. In terms of the different schools (p < 0.05), those students from the School of Medicine and those from the School of Public Health had better DPs than did the students from the other schools. DP was not associated with income, gender, BMI, stress level, or course load. CONCLUSION: The majority of the students had inadequate DPs, which inadequacy was associated with both the age of the student and the school that he or she attended.

Physical activity and its associations with sociodemographic characteristics, dietary patterns, and perceived academic stress in students attending college in Puerto Rico.

OBJECTIVE: The academic environment usually generates stress in students. Increasing physical activity (PA) is one of the stress-coping strategies for students; however, students usually reduce their PA while enrolled in college. OBJECTIVE: To determine the association between PA, self-perceived academic load and stress, and dietary patterns in students attending college in Puerto Rico. METHODS: A proportional stratified sample of 275 students from UPR-MSC completed a self-administered questionnaire on socioeconomic status, academic load and stress, body composition, dietary patterns, and PA. Chi2 was used to assess the association between variables. RESULTS: Most of the participants were female (68%), were aged 21 to 30 years (88%), and had low annual household incomes ($0-$24,999) (43%). Women reported higher levels of stress (p < 0.001) than did men. Overweight and obesity was found in 35.4%, while most students reported a light PA level (46.5%), which was higher among women (p < 0.001). During periods of greater stress, most students increased sedentary activities (68%), and -30% reported a decrease in moderate and vigorous activities; however, 60% reported that PA was an effective coping strategy and 66% would use it again. There was a negative association between PA and stress: those with higher levels of stress had lower PA levels (p = 0.06). No significant associations were found between PA and the others variables studied (p > 0.05). CONCLUSION: Most students reported sedentary lifestyles during periods of greater stress. High level of stress were positively associated with a light PA level.

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.