The Effect of High Dose Intravenous Vitamin C During Radiotherapy on Breast Cancer Patients' Neutrophil-Lymphocyte Ratio.

Background: Breast cancer is very common, and the incidence is growing every year. Most breast cancers are treated with radiation after surgery. As a side effect of radiation therapy, inflammation, as well as the neutrophil-lymphocyte ratio (NLR), level increases. However, high NLR levels act as independent prognostic factors for increased mortality in all cancers. In this study, the authors investigated whether administration of vitamin C, which is effective in suppressing inflammation, may help to reduce high levels of NLR produced by radiation therapy. Methods: This study was performed retrospectively among 424 patients who were diagnosed with breast cancer and were treated with postoperative radiotherapy at Kosin University Gospel Hospital from January 2011 to December 2017. Among them, 354 patients received radiation therapy without vitamin C (the control group), and 70 experimental patients received vitamin C intravenously twice a week for at least 4 weeks during radiation therapy. The experimental group was divided into two groups according to the dose administrated: a low-dose vitamin C group (less than 1 g/kg, 52 patients) and a high-dose vitamin C group (more than 1 g/kg, 18 patients). The authors conducted three NLR measurements: before and after radiation therapy and at 3 months after radiation therapy; the authors then compared the change in NLR over time between the groups using repeated measures analysis of variance. Results: In the control group and the low-dose vitamin C-administered group, NLR was increased at the endpoint compared to before the radiotherapy, whereas NLR values in the high-dose vitamin C group were 8.4 ± 1.7, 5.9 ± 1.3, and 4.3 ± 1.5, showing a continuous decrease and a statistically significant difference (pinteraction = 0.033). These results were similarly observed in models adjusted by the patient's age and American Joint Committee on Cancer stage, with borderline significance (pinteraction = 0.065). Conclusions: Elevated NLR, a measure of systemic inflammation, has been associated with higher mortality cancer patients, including breast cancer patients. In this observational study, NLR was significantly decreased during radiation therapy in patients administered high-dose vitamin C.

Can Current Recommendations on Sun Exposure Sufficiently Increase Serum Vitamin D Level?: One-Month Randomized Clinical Trial.

BACKGROUND: Lack of sunlight exposure is the primary reason for the worldwide epidemic of vitamin D deficiency. Although recommended sunlight exposure guidelines exist, there is no evidence regarding whether current guidelines are optimal for increasing vitamin D levels among individuals with vitamin D deficiency. METHODS: Sixty Korean adults aged 20-49 years with serum 25-hydroxyvitamin D (25[OH]D) levels of < 20 ng/mL were randomly assigned to three groups: sunlight exposure (n = 20), vitamin D supplementation groups (n = 20), and daily living (n = 20) for 1 month. The sunlight exposure group had sunlight exposure on 20% to 30% of their body surface areas for 30-60 minutes per day, 3 times a week during the summer season. Vitamin D supplementation was prescribed with 800 IU/day of vitamin D. The serum levels of 25(OH)D were measured at baseline and at 1-month follow-up examinations. RESULTS: The largest change in serum 25(OH)D was observed among the vitamin D supplementation group (+3.5 ng/mL, P < 0.001). The sunlight exposure group showed a slight increase in serum 25(OH)D level, but the absolute increase was less than one-third that of the vitamin D supplementation group (+0.9 ng/mL, P = 0.043). Only two participants in the sunlight exposure reached serum concentrations of 25(OH)D ≥ 20 ng/mL at follow-up. The daily living group showed no difference in vitamin D levels (-0.7 ng/mL, P = 0.516). CONCLUSION: Sunlight exposure was not sufficient to overcome vitamin D insufficiency or deficiency in the current study subjects. Effectiveness of current sunlight exposure guidelines among various populations should be reassessed in larger clinical studies. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0002671.

Effect of High-dose Vitamin C Combined With Anti-cancer Treatment on Breast Cancer Cells.

BACKGROUND/AIM: The anti-cancer effect of high doses of intravenous vitamin C (high-dose vitamin C) remains controversial despite growing evidence that high-dose vitamin C exerts anti-tumorigenic activity by increasing the amount of reactive oxygen species in cancer cells without meaningful toxicities. Therefore, this study attempted to demonstrate the in vitro anti-cancer activity of high-dose vitamin C in combination with conventional treatment in breast cancer. MATERIALS AND METHODS: The pro-apoptotic effects of high-dose vitamin C (1.25 to 20 mM) with or without anti-cancer agents (eribulin mesylate, tamoxifen, fulvestrant, or trastuzumab) were estimated using an MTT assay to measure the cell viability of a variety of breast cancer cell lines (MCF7, SK-BR3, and MDA-MB-231), as well as normal breast epithelial cells (MCF10A). RESULTS: High-dose vitamin C (≥10 mM) significantly decreased cell viability of all breast cancer cell lines, particularly of MCF-7 cells. The catalase activities of MCF7 and MDA-MD-231 cells were also lower than those of MCF10A cells. Moreover, cell viability of both MCF7 and MDA-MD-231 cells was decreased further when combining high-dose vitamin C and eribulin mesylate, and this was also true for MCF-7 cells when combining high-dose vitamin C with tamoxifen or fulvestrant and for SK-BR3 cells when combining high-dose vitamin C with trastuzumab in comparison with chemotherapy or endocrine therapy alone. CONCLUSION: Combining high-dose vitamin C with conventional anti-cancer drugs can have therapeutic advantages against breast cancer cells.

New approaches to cope with possible harms of low-dose environmental chemicals.

Low-dose environmental chemicals including endocrine-disrupting chemicals can disturb endocrine, nervous and immune systems. Traditional chemical-focused approaches, strict regulation and avoidance of exposure sources, can help protect humans from individual or several chemicals in the high-dose range, but their value in the low-dose range is questionable. First, exposure sources to problematic environmental chemicals are omnipresent, and many common pollutants present no safe level. In this situation, the value of any effort focusing on individual chemicals is very limited. Second, critical methodological issues, including the huge number of environmental chemicals, biological complexity of mixtures and non-linearity, make it difficult for risk assessment-based regulation to provide reliable permissible levels of individual chemicals. Third, the largest exposure source is already internal; human adipose tissue contains the most complex chemical mixtures. Thus, in the low-dose range, a paradigm shift is required from a chemical-focused to a human-focused approach for health protection. Two key questions are (1) how to control toxicokinetics of chemical mixtures to decrease their burden in critical organs and (2) how to mitigate early harmful effects of chemical mixtures at cellular levels. Many lifestyles can be evaluated for these purposes. Although both the chemical-focused and human-focused approaches are needed to protect humans, the human-focused holistic approach must be the primary measure in the low-dose range of environmental chemicals.

Judicial Precedent-Based Clinical Practice Guidelines of Propofol in Sedative Esthetic Surgery.

BACKGROUND: Propofol is has been widely used for sedation in the field of esthetic surgery because of its favorable pharmacokinetic profile. Propofol sedation-induced side effects are rare. However, when present, they can be serious. The number of malpractice claims associated with propofol sedation has increased in recent years. This study aims to show which procedures lead to the most claims in the field of esthetic surgery through a review of Korean precedents. METHODS: Thirteen precedent cases of propofol sedation in the field of esthetic surgery were collected between 2000 and 2016. We analyzed the type of procedure, administration route, anesthesia provider, complications, timing of damaging events, average indemnification, plaintiff's (patients) winning rate, ratio and the reason of limitation of liability and the key factors affecting the judgement in these cases. RESULTS: Most plaintiffs were women, and in most cases (11/13, 73.3%), the times of the damaging events were in maintenance and the anesthesia provider was the surgeon. The most common complication related to propofol sedation was hypoxic brain damage. Among the 13 cases, 12 were won by the plaintiff. The mean claim settlement was 339,455,814 KRW (USD 301,792.15). The key factors affecting the judgement were administration method and staff, monitoring method, preparation of emergency kit, response to emergencies, transfer to a higher-level hospital, detailed medical recording about event and informed consent. CONCLUSION: The number of claims owing to propofol sedation after esthetic surgery is increasing. Close monitoring during the operation, immediate reaction to an event and thorough medical records were main key factors that influenced the judgement. Preoperative explanation about the possibility of complications was important. The findings will help surgeons achieve high patient satisfaction and reduce liability concerns. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Common presence of non-transferrin-bound iron among patients with type 2 diabetes.

OBJECTIVE: Recently, we reported increased cardiovascular disease mortality among supplemental vitamin C users with type 2 diabetes in a prospective cohort study. Because vitamin C may cause oxidative stress in the presence of redox active iron, we hypothesized that non-transferrin-bound iron (NTBI), a form of iron susceptible to redox activity, may be present in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: We measured serum NTBI levels using high-performance liquid chromatography in 48 patients with known diabetes (at least 5 years duration since diagnosis), 49 patients with newly diagnosed diabetes, and 47 healthy control subjects (frequency matched on age and sex). RESULTS: NTBI was commonly present in diabetes: 59% in newly diagnosed diabetes and 92% in advanced diabetes. Mean NTBI values varied significantly between the three groups, with the highest values being observed in patients with known diabetes and the lowest in the control subjects (0.62 +/- 0.43 vs. 0.24 +/- 0.29 vs. 0.04 +/- 0.13 micromol/l Fe). Serum total iron or percent transferrin saturation were very similar among the three groups, yet NTBI was strongly associated with serum total iron (r = 0.74, P < 0.01) and percent transferrin saturation (r = 0.70, P < 0.01) among the patients with known diabetes. CONCLUSIONS: Consistent with our hypothesis, these data demonstrate the common existence of NTBI in type 2 diabetic patients with a strong gradient with severity. Prospective cohort studies are required to clarify the clinical relevance of increased NTBI levels.

Longitudinal associations between body mass index and serum carotenoids: the CARDIA study.

Cross-sectional studies report an inverse association between BMI and serum carotenoid concentration. The present study examined the prospective association between BMI and the serum concentration of five carotenoids in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Serum carotenoids (alpha-carotene, beta-carotene, beta-cryptoxanthin, zeaxanthin/lutein, lycopene), BMI, dietary intake, physical activity and dietary supplement use were measured at years 0 and 7 in 3071 black and white male and female participants, who were either persistent smokers or non-smokers. Among non-smokers, year 0 BMI predicted year 7 serum carotenoid levels: obese subjects (BMI > or =30 kg/m2) had an average concentration of the sum of four carotenoids (alpha-carotene +beta-carotene + zeaxanthin/lutein+beta-cryptoxanthin) that was 22 % lower than the concentration among subjects with a BMI of less than 22 kg/m2. In contrast, the sum of carotenoids among smokers was only 6 % lower. Relationships between BMI and serum lycopene were weak. The change from year 0 to year 7 in serum carotenoids, except for lycopene, was inversely associated with the change in BMI among non-smokers but not among smokers. Parallel findings were observed for BMI and serum gamma-glutamyl transferase level. In summary, the observation that BMI predicted the evolution of serum carotenoids during a 7-year follow-up among young non-smoking adults is consistent with the hypothesis that carotenoids are decreased in protecting against oxidative stress generated by adipose tissue, while smokers maintain a minimal level of serum carotenoids independent of adiposity. The results for lycopene were, however, discordant from those of the other carotenoids.

[Relationships among Oxidative Stress Markers, Life Style Factors and Biochemical Findings.].

BACKGROUND: In many studies, oxidative stress markers have been employed to serve as a measure of a disease process or to reflect oxidative status. These oxidative stress markers must have some degree of predictive validity, but full substantiation of this relation is still lacking. This paper presents data on levels of three biomarkers, oxidized low-density lipoproteins (LDL), carbonyl, and 8-hydroxy-2'-deoxyguanosine (8-OHdG), and a number of life style factors associated with oxidative stress in healthy adults. METHODS: For 237 healthy adults aged 40-60 years, a number of life style factors, biochemical characteristics and oxidative status were evaluated. Markers of oxidative stress were measured by an ELISA method. RESULTS: Waist-hip ratio and use of vitamin supplement were associated with serum oxidized LDL (P<0.05). Body mass index and stress had a relationship (P<0.05) with protein carbonyl. Creactive protein was related to serum oxidized LDL (P<0.01). There was no correlation among three oxidative stress markers, oxidized LDL, carbonyl, and 8-OHdG. CONCLUSIONS: The oxidative stress markers used in this study could not be regarded as a general estimate of the healthy individual oxidative status. Further studies focusing on the development of biomarkers to reflect changes in the oxidative status under normal, non-pathological conditions in humans will be required.

Interaction among heme iron, zinc, and supplemental vitamin C intake on the risk of lung cancer: Iowa Women's Health Study.

Redox-active iron present at physiological levels in the pulmonary epithelial lining fluid may lead to damage of lung tissue under some circumstances. For example, factors that increase potential for oxidative stress, such as higher intake of heme iron or higher intake of vitamin C in the presence of high intake of iron, might increase the risk of lung cancer, whereas higher intake of the antioxidant zinc might decrease that risk. During 16 yr of follow-up, 34,708 postmenopausal women, aged 55-69 yr at baseline who completed a food-frequency questionnaire for the Iowa Women's Health Study, were followed for 700 incident lung cancers. When subjects were stratified by intake of vitamin C supplements, among women who took vitamin C supplements of >500 mg/day, after adjusting for age, total energy intake, cigarette smoking, alcohol consumption, and dietary zinc or dietary heme iron intake, relative risks across categories of dietary heme iron intake were 1.0, 0.85, 0.93, 1.32, 1.70, and 3.77 (P for trend = 0.05; P for interaction = 0.08), whereas corresponding figures for dietary zinc intake were 1.0, 1.15, 0.71, 0.84, 0.61, and 0.11 (P for trend = 0.12; P for interaction = 0.04). The strength of the associations of heme iron and zinc intake with lung cancer appeared to be stronger with increasing levels of vitamin C supplement intake. Our results suggest that high dietary heme iron intake may increase the risk of lung cancer, whereas high dietary zinc may decrease the risk of lung cancer among postmenopausal women who consume high-dose vitamin C supplements. This finding may be of particular importance to smokers, for whom vitamin C supplementation is a common recommendation.

Does supplemental vitamin C increase cardiovascular disease risk in women with diabetes?

BACKGROUND: Vitamin C acts as a potent antioxidant; however, it can also be a prooxidant and glycate protein under certain circumstances in vitro. These observations led us to hypothesize that a high intake of vitamin C in diabetic persons might promote atherosclerosis. OBJECTIVE: The objective was to examine the relation between vitamin C intake and mortality from cardiovascular disease. DESIGN: We studied the relation between vitamin C intake and mortality from total cardiovascular disease (n = 281), coronary artery disease (n = 175), and stroke (n = 57) in 1923 postmenopausal women who reported being diabetic at baseline. Diet was assessed with a food-frequency questionnaire at baseline, and subjects initially free of coronary artery disease were prospectively followed for 15 y. RESULTS: After adjustment for cardiovascular disease risk factors, type of diabetes medication used, duration of diabetes, and intakes of folate, vitamin E, and beta-carotene, the adjusted relative risks of total cardiovascular disease mortality were 1.0, 0.97, 1.11, 1.47, and 1.84 (P for trend < 0.01) across quintiles of total vitamin C intake from food and supplements. Adjusted relative risks of coronary artery disease were 1.0, 0.81, 0.99, 1.26, and 1.91 (P for trend = 0.01) and of stroke were 1.0, 0.52, 1.23, 2.22, and 2.57 (P for trend < 0.01). When dietary and supplemental vitamin C were analyzed separately, only supplemental vitamin C showed a positive association with mortality endpoints. Vitamin C intake was unrelated to mortality from cardiovascular disease in the nondiabetic subjects at baseline. CONCLUSION: A high vitamin C intake from supplements is associated with an increased risk of cardiovascular disease mortality in postmenopausal women with diabetes.

A hypothesis: interaction between supplemental iron intake and fermentation affecting the risk of colon cancer. The Iowa Women's Health Study.

Fermentation in the large intestine can increase absorption of ferrous iron, which is the main form in supplements, because the solubility of ferrous iron is enhanced in the mildly acidic environments caused by fermentation. We therefore hypothesized that higher supplemental iron intake would increase the risk of colon cancer among those who consume large amounts of fermentable substrates, namely, dietary fiber and resistant starch. Among 34,708 postmenopausal women, supplemental iron was unrelated to proximal colon cancer in all women and to distal colon cancer among those consuming below the median of fermentable substrates. However, supplemental iron was positively associated with distal colon cancer among women who consumed above the median of fermentable substrates (P for interaction %lt; 0.01); the adjusted relative risks across categories of supplemental iron (0 g/day, 1-19 g/day, 20-49 g/day, and > or = 50 g/day) were 1.0, 1.24, 1.78, and 3.78 (P for trend < 0.01). This hypothesis needs confirmation in other cohort studies because, despite the significant trend, only nine cases were included in the top category of > or = 50 mg supplemental iron, and this finding could have arisen by chance.

Association between serum gamma-glutamyltransferase and dietary factors: the Coronary Artery Risk Development in Young Adults (CARDIA) Study.

BACKGROUND: Diet may be involved in the strong dose-response relation of gamma-glutamyltransferase (GGT) concentration with incident diabetes. OBJECTIVE: We examined dietary correlates of serum GGT activity. DESIGN: Study subjects were 3146 black and white men and women aged 17-35 y in 1985-1986. A diet history was taken at years 0 and 7. Food items were classified into alcohol; breaded, battered, or canned vegetables; fruit; fruit juice; refined grain; whole grain; dairy; legumes; meat; poultry; fish; fresh or frozen vegetables; nuts; and coffee. RESULTS: After adjustment for nondietary factors and other food groups, GGT was positively associated with alcohol consumption and meat intake. Geometric means of year 10 GGT across categories of alcohol consumption (0, 1-9, 10-19, 20-29, and > or = 30 g/d) were 17.7, 18.8, 20.4, 21.8, and 24.8 U/L (P for trend < 0.01); corresponding means across quintiles of meat intake were 19.2, 20.2, 20.5, 21.8, and 21.2 times/wk (P for trend < 0.01). GGT was inversely associated with fruit intake. Among possible meat constituents, dietary heme iron, but not saturated fat, was associated with GGT. Dietary constituents typical of plant foods showed an inverse association. In contrast, vitamin supplements were positively associated with GGT. CONCLUSIONS: Serum GGT activity increased in a dose-response manner as alcohol and meat consumption increased and fruit consumption decreased. Heme iron contained in meats and micronutrients contained in fruits may influence GGT metabolism. However, micronutrients taken as supplements had a positive association with GGT.