BACKGROUND: This Rapid Practice Guideline provides an evidence-based recommendation to address the question: in adults with sepsis or septic shock, should we recommend using or not using intravenous vitamin C therapy?
METHODS: The panel included 21 experts from 16 countries and used a strict policy for potential financial and intellectual conflicts of interest. Methodological support was provided by the Guidelines in Intensive Care, Development, and Evaluation (GUIDE) group. Based on an updated systematic review, and the grading of recommendations, assessment, development, and evaluation approach, we evaluated the certainty of evidence and developed recommendations using the evidence-to-decision framework. We conducted an electronic vote, requiring >80% agreement among the panel for a recommendation to be adopted.
RESULTS: At longest follow-up, 90 days, intravenous vitamin C probably does not substantially impact (relative risk 1.05, 95% confidence interval [CI] 0.94 to 1.17; absolute risk difference 1.8%, 95% CI -2.2 to 6.2; 6 trials, n = 2148, moderate certainty). Effects of vitamin C on mortality at earlier timepoints was of low or very low certainty due to risk of bias of the included studies and significant heterogeneity between study results. Few adverse events were reported with the use of vitamin C. The panel did not identify any major differences in other outcomes, including duration of mechanical ventilation, ventilator free days, hospital or intensive care unit length of stay, acute kidney injury, need for renal replacement therapy. Vitamin C may result in a slight reduction in duration of vasopressor support (MD -18.9 h, 95% CI -26.5 to -11.4; 21 trials, n = 2661, low certainty); but may not reduce sequential organ failure assessment scores (MD -0.69, 95% CI -1.55 to 0.71; 24 trials, n = 4002, low certainty). The panel judged the undesirable consequences of using IV vitamin C to probably outweigh the desirable consequences, and therefore issued a conditional recommendation against using IV vitamin C therapy in sepsis.
CONCLUSIONS: The panel suggests against use of intravenous vitamin C in adult patients with sepsis, beyond that of standard nutritional supplementation. Small and single center trials on this topic should be discouraged.

BACKGROUND: Vitamin C is a life saving molecule. Vitamin C based breeding is need of the hour in order to provide humans an immunity boosting supplement in the form of fresh food.
RESULTS: Multiple interactions of Anatolian Mediterranean environment were studied with cultivars (\'Calinda\', \'Rubygem\', \'Sabrina\', and \'Sahara\') and fruit maturity stages. Genetic expression of six vitamin C related genes was estimated showing significantly higher expression in open field. Cultivar \'Calinda\' performed better in organic acids but poor in firmness. Cultivar \'Sabrina\' showed highest fruit firmness but lower commercially desired fruit quality characters. Cultivar \'Sahara\' performed best for vitamin C and fruit redness, and was high in fruit size, weight, and organic acids. Chroma trends indicated simultaneous accumulation of vitamin C and anthocyanins in strawberry fruits. Transition stage of fruits was found most critical for metabolite regulation and sensitive to environmental changes. Fruits of cultivar \'Sahara\' at \'Red\' maturity stage expressed highest vitamin C levels (138.03 mg/100 g FW) whereas \'Turning\' fruits of cultivar \'Sabrina\' had lowest vitamin C content (27.80 mg/100 g FW). All studied vitamin C related genes indicate highest genetic expression for cultivar \'Sahara\', except for genes FaVTC2 and FaMDHAR which exhibit highest genetic expression for cultivar \'Rubygem.\'
CONCLUSIONS: Two-way and three-way interactions between cultivars, environments, and maturity stages were significant for vitamin C and fruit quality regulation under Mediterranean climate. This indicates an absolute requisite of studying combined influences in actual field, rather than single factor, controlled, or lab experiments. Correlation analysis showed that vitamin C content in a fruit is a complex subject and mainly depends on fruit color, size, and firmness. Principal Component Analysis validated that cultivar \'Sahara\' is a promising candidate for vitamin C based breeding in strawberry.

Background Impaired endothelial function is thought to contribute to the increased cardiovascular risk associated with above-normal blood pressure (BP). However, the association between endothelial function and BP classified by 2017 American College of Cardiology/American Heart Association guidelines is unknown. Our objective was to determine if endothelial function decreases in midlife/older adults across the 2017 American College of Cardiology/American Heart Association guidelines BP classifications and identify associated mechanisms of action. Methods and Results A retrospective analysis of endothelial function (brachial artery flow-mediated dilation) from 988 midlife/older adults (aged 50+ years) stratified by BP status (normal BP; elevated BP; stage 1 hypertension; stage 2 hypertension) was performed. Endothelium-independent dilation (sublingual nitroglycerin), reactive oxygen species-mediated suppression of endothelial function (∆brachial artery flow-mediated dilation with vitamin C infusion), and endothelial cell and plasma markers of oxidative stress and inflammation were assessed in subgroups. Compared with normal BP (n=411), brachial artery flow-mediated dilation was 12% (P=0.04), 15% (P<0.01) and 20% (P<0.01) lower with elevated BP (n=173), stage 1 hypertension (n=248) and stage 2 hypertension (n=156), respectively, whereas endothelium-independent dilation did not differ (P=0.14). Vitamin C infusion increased brachial artery flow-mediated dilation in those with above-normal BP (P≤0.02) but not normal BP (P=0.11). Endothelial cell p47phox (P<0.01), a marker of superoxide/reactive oxygen species-generating nicotinamide adenine dinucleotide phosphate oxidase, and circulating interleukin-6 concentrations (P=0.01) were higher in individuals with above-normal BP. Conclusions Vascular endothelial function is progressively impaired with increasing BP in otherwise healthy adults classified by 2017 American College of Cardiology/American Heart Association guidelines. Impaired endothelial function with above-normal BP is mediated by excessive reactive oxygen species signaling associated with increased endothelial expression of nicotinamide adenine dinucleotide phosphate oxidase and circulating interleukin-6.

OBJECTIVE: Maintaining proper nutrition during pregnancy is crucial for pregnant women and especially for who have been diagnosed with type 1 diabetes mellitus (T1DM) or who develop gestational diabetes mellitus (GDM).
METHODS: To measure differences in vitamin and mineral intakes among women with normal pregnancies, pregnant women with GDM, and pregnant women with pre-gestational T1DM; and to assess the women\'s dietary intakes in comparison with Polish nutritional guidelines. The analysis was conducted among 83 pregnant women (29 GDM patients, 26 T1DM patients and 28 normal pregnancy participants) from whom we collected seven-day 24-hour dietary records during the second part of their pregnancies.
RESULTS: There were no statistically significant differences observed for most of the vitamin and mineral intakes across the three groups. However, we did observe a significant difference in the vitamin C and calcium intakes between groups. The mean vitamin C and calcium intakes were significantly higher in the control group than among the diabetic patients. Insufficient dietary calcium intakes were found among 52.3% of the GDM patients and 61.6% of the T1DM participants, while only 28.6% of the normal pregnancy patients experienced a calcium deficiency. The highest incidence of inadequate intake in each of the GDM, T1DM and control groups was observed for vitamin D (100%, 100%, 100%), folate (97.7%, 100%, 100%), iron (97.7%, 100%, 100%), and iodine (97.7%, 92.4%, 85.7%), respectively.
CONCLUSIONS: Diet alone may not be enough to provide adequate levels of vitamins and minerals for most micronutrients. Supplement use reduces the risk of inadequate intake for many micronutrients, but diet-related issues during pregnancy and pregnancy diagnosed with diabetes remain, and they deserve to be addressed during public health interventions.

Inappropriate dietary intake and poor nutritional status are reported to be associated with metabolic syndrome and psychopathology in patients with schizophrenia. We hypothesized that inappropriate dietary habits and insufficient dietary intake of specific nutrients are associated with schizophrenia. To test the hypothesis, we assessed the dietary habits and nutritional intake of patients with schizophrenia and then developed suitable dietary guidelines. In total, 140 subjects (73 controls and 67 patients with schizophrenia from community mental health centers) were included, and dietary intakes were analyzed using a semi-quantitative food frequency questionnaire. As a result, the proportion of overweight or obese patients was significantly higher in schizophrenia subjects (64.2%) compared with control subjects (39.7%) (P=.004). The male schizophrenia patients had significantly lower dietary intakes of protein, polyunsaturated fatty acids (PUFAs), vitamin K, niacin, folate, and vitamin C than the male control subjects. In all multiple logistic regression models, subjects with the \"low\" dietary intake of protein, n-3 PUFAs, niacin, folate, and vitamin C had a significantly higher odds ratios for schizophrenia compared with those with the \"high\" dietary intake category of each nutrient. Therefore, maintenance of a healthy body weight and sufficient dietary intake of protein, PUFAs, niacin, folate, and vitamin C are recommended for Korean patients with schizophrenia.

BACKGROUND: To reach nutritional standards, human milk has to have 2g/dL of protein. In 2013, Lafeber stated that when human milk is fortified up to 2g/dL, it may increase its osmolality up to 500 mOsm/kg. He also warned that care must be taken when adding a drug or vitamins to human milk.
OBJECTIVE: We studied, for the first time, the impact of adding multivitamins (ADEC) on human fortified milk osmolality.
METHODS: The osmolality of 36 pasteurized, fortified human milk samples was measured. The amount of milk required as a solvent to maintain osmolality below 500 mOsm/kg was then determined.
RESULTS: The osmolality of 2mL of fortified human milk reached up to 750 mOsm/kg when the multivitamins ADEC was added. The osmolality decreased proportionately as the solution was diluted and if vitamins are added in two half-doses each time. It is only with 20mL of milk that the osmolality lowers to its initial rate of 430 mOsm/kg. The stronger the milk\'s fortification is, the greater impact it has on the milk\'s osmolality.
CONCLUSIONS: New nutritional recommendations for premature infants are needed. In the meantime, when the fortified milk intake is under 20mL, it is preferable to extend parenteral intakes with fat-soluble vitamins or reduce doses of vitamins in milk. Also, we should use enriched human milk as a fortifier and be cautious with indiscriminate fortification or when adding drugs and electrolyte solutions.

BACKGROUND: The objective was to develop an index based on the Dutch Guidelines for a healthy Diet of 2006 that reflects dietary quality and to apply it to the Dutch National Food Consumption Survey (DNFCS) to examine the associations with micronutrient intakes.
METHODS: A total of 749 men and women, aged 19-30 years, contributed two 24-hour recalls and additional questionnaires in the DNFCS of 2003. The Dutch Healthy Diet index (DHD-index) includes ten components representing the ten Dutch Guidelines for a Healthy Diet. Per component the score ranges between zero and ten, resulting in a total score between zero (no adherence) and 100 (complete adherence).
RESULTS: The mean ± SD of the DHD-index was 60.4 ± 11.5 for women and 57.8 ± 10.8 for men (P for difference = 0.002). Each component score increased across the sex-specific quintiles of the DHD-index. An inverse association was observed between the sex-specific quintiles of the DHD-index and total energy intake. Calcium, riboflavin, and vitamin E intake decreased with increasing DHD-index, an inverse association which disappeared after energy adjustment. Vitamin C showed a positive association across quintiles, also when adjusted for energy. For folate, iron, magnesium, potassium, thiamin, and vitamin B6 a positive association emerged after adjustment for energy.
CONCLUSIONS: The DHD-index is capable of ranking participants according to their adherence to the Dutch Guidelines for a Healthy Diet by reflecting variation in nine out of ten components that constitute the index when based on two 24-hour recalls. Furthermore, the index showed to be a good measure of nutrient density of diets.

OBJECTIVE: Gastric cancer is a major health burden in the Asia-Pacific region but consensus on prevention strategies has been lacking. We aimed to critically evaluate strategies for preventing gastric cancer.
METHODS: A multidisciplinary group developed consensus statements using a Delphi approach. Relevant data were presented, and the quality of evidence, strength of recommendation, and level of consensus were graded.
RESULTS: Helicobacter pylori infection is a necessary but not sufficient causal factor for non-cardia gastric adenocarcinoma. A high intake of salt is strongly associated with gastric cancer. Fresh fruits and vegetables are protective but the use of vitamins and other dietary supplements does not prevent gastric cancer. Host-bacterial interaction in H. pylori infection results in different patterns of gastritis and differences in gastric acid secretion which determine disease outcome. A positive family history of gastric cancer is an important risk factor. Low serum pepsinogens reflect gastric atrophy and may be useful as a marker to identify populations at high risk for gastric cancer. H. pylori screening and treatment is a recommended gastric cancer risk reduction strategy in high-risk populations. H. pylori screening and treatment is most effective before atrophic gastritis has developed. It does not exclude the existing practice of gastric cancer surveillance in high-risk populations. In populations at low risk for gastric cancer, H. pylori screening is not recommended. First-line treatment of H. pylori infection should be in accordance with national treatment guidelines.
CONCLUSIONS: A strategy of H. pylori screening and eradication in high-risk populations will probably reduce gastric cancer incidence, and based on current evidence is recommended by consensus.

The 22 supersetnd Hohenheim Consensus Workshop took place in at the University of Stuttgart-Hohenheim. The subject of this conference was vitamin C and its role in the treatment of endothelial dysfunction. Scientists, who had published and reviewed scientific and regulatory papers on that topic were invited, among them basic researchers, toxicologists, clinicians and nutritionists. The participants were presented with eleven questions, which were discussed and answered at the workshop, with the aim of summarising the current state of knowledge. The explicatory text accompanying the short answers was produced and agreed on after the conference and was backed up by corresponding references. The therapeutic relevance of administration of the physiological antioxidant vitamin C in high parenteral doses in Endothelial Dependent Pathophysiological Conditions (EDPC) was discussed. Endothelial dysfunction is defined as including disturbed endothelial dependant relaxation of resistance vessels, breakdown of the microvascular endothelial barrier and/or loss of anti-adhesive function. It occurs in severe burn injury, intoxications, acute hyperglycemia, sepsis, trauma, and ischemic-reperfusion tissue injury and is induced by oxidative stress. Reduced plasma ascorbate levels are a hallmark of oxidative stress and occur in severe burns, sepsis, severe trauma, intoxication, chemotherapy/radiotherapy and organ transplantation. Vitamin C directly enhances the activity of nitric oxide synthase, the acyl CoA oxidase system and inhibits the actions of proinflammatory lipids. There is experimental evidence that parenteral high-dose vitamin C restores endothelial function in sepsis. In vitro, supraphysiological concentrations (> 1mM) of ascorbate restore nitric oxide bioavailability and endothelial function. Only parenterally, can enough vitamin C be administered to combat oxidative stress. There is no evidence that parenteral vitamin C exerts prooxidant effects in humans. Theoretical concerns in relation to competitive interactions between vitamin C and glucose cellular uptake are probably only relevant for oxidised vitamin C (dehydroascorbate).

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