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Biomedical subjects

Satoshi Sasaki

Publications and source records attributed to Satoshi Sasaki.

At least 73 records · Page 4Linked to original sources

Dietary exposure to cadmium at close to the current provisional tolerable weekly intake does not affect renal function among female Japanese farmers.

Dietary cadmium (Cd) exposure and renal tubular function were investigated in 1381 female farmers from five districts in Japan (Japanese Multi-centered Environmental Toxicant Study project; JMETS). Dietary Cd exposure of the five populations was assessed from the individual Cd concentrations of the rice consumed by the study participants and the quantities of rice consumed daily. The populations showed a sequential difference in dietary Cd exposure, ranging from a level as low as that of the general Japanese population to one close to the current provisional tolerable weekly intake (PTWI). The levels of urinary Cd excretion, an indicator of Cd accumulation in the kidneys, increased along the same sequential pattern as dietary Cd exposure. However, no differences were observed among the populations in levels of urinary alpha 1-microglobulin and beta 2-microglobulin excretion, which are indicators of renal tubular function. These results indicate that the current PTWI is sufficient to prevent Cd-induced renal dysfunction among the general population.

Adult↗

Long-term vitamin C supplementation has no markedly favourable effect on serum lipids in middle-aged Japanese subjects.

Antioxidant vitamins have been reported to be associated with an improvement in blood lipid profiles, but results are not consistent. The present study was designed to determine whether long-term vitamin C supplementation could alter serum lipid concentrations in subjects who completed a 5-year population-based double-blind intervention trial. A total of 439 Japanese subjects with atrophic gastritis initially participated in the trial using vitamin C and beta-carotene to prevent gastric cancer. Before and upon early termination of beta-carotene supplementation, 134 subjects dropped out of the trial; finally, 161 subjects assigned to the high-dose group (500 mg vitamin C/d) and 144 subjects assigned to the low-dose group (50 mg vitamin C/d) were studied. No favourable effect of vitamin C supplementation on serum concentrations of total cholesterol, HDL- and LDL-cholesterol, and triacylglycerol was observed, although high-dose vitamin C supplementation increased serum vitamin C concentrations substantially. Among women, the mean change in serum triacylglycerol decreased (-0.12 mmol/l, 95 % CI -0.32, 0.09) in the high-dose group, but increased (+0.12 mmol/l, 95 % CI 0.03, 0.22) in the low-dose group. In addition, the mean change in serum triacylglycerol among women with hypertriacylglycerolaemia was statistically significant (-1.21, 95 % CI -2.38, -0.05) after high-dose vitamin C supplementation. The 5-year vitamin C supplementation had no markedly favourable effects on the serum lipid and lipoprotein profile. However, our present results do not preclude the possibility that vitamin C supplementation may decrease triacylglycerol concentrations among women with hypertriacylglycerolaemia.

Adult↗

Underreporting of energy intake among Japanese women aged 18-20 years and its association with reported nutrient and food group intakes.

OBJECTIVES: To evaluate the ratio of energy intake to basal metabolic rate (EI/BMR) among young female Japanese adults, and to compare the lifestyle and dietary characteristics between relatively low and high reporters. DESIGN: Dietary intakes were assessed over a 1-month period with a validated, self-administered, diet history questionnaire, and lifestyle variables were assessed by a second questionnaire designed for this survey. The ratio of EI/BMR was calculated from reported energy intake and estimated basal metabolic rate. SUBJECTS: In total, 1889 female Japanese university students aged 18-20 years who were enrolled in dietetics courses. RESULTS: Ninety-five per cent of the subjects were classified into a non-obese group (body mass index (BMI) <25 kg m(-2); mean+/-standard deviation (SD): 20.8+/-2.6 kg m(-2)). EI/BMR was 1.43+/-0.40 (mean+/-SD). Sixty-eight per cent of the subjects showed an EI/BMR level below the possibly balanced value of 1.56, 37% showed EI/BMR below the minimum survival value of 1.27 and 2% of the subjects showed EI/BMR exceeding the maximum value for a sustainable lifestyle of 2.4. BMI, body weight and BMR decreased significantly with the increase in EI/BMR (P<0.001). The percentage of energy from carbohydrate was significantly higher, whereas those from fat and protein were significantly lower, among the lower EI/BMR groups. As for food groups, a significantly declining trend from the lowest to the highest EI/BMR groups was observed for cereals. CONCLUSION: Underreporting, rather than overreporting, of energy intake was predominant in this relatively lean Japanese female population. BMI was the most important factor affecting the reporting accuracy of energy intake.

Adolescent↗

Onset symptoms and tumor locations as prognostic factors of pancreatic cancer.

OBJECTIVES: The prognosis of pancreatic carcinoma is generally very poor and difficult to predict. The aim of this study was to quantitate prognosis with the onset symptoms. METHODS: Survival curves and clinicopathological findings of 209 patients with pancreatic cancer admitted to our hospital between 1992 and 1998 were retrospectively analyzed with reference to their onset symptoms (eg, abdominal pain, back pain, jaundice, general fatigue, nausea) and tumor location (eg, head, body, tail). The interval from the onset symptoms to the patient's first medical treatment and laboratory data of the patients were also reviewed. Univariate and multivariate analyses were performed using Cox proportional hazards regression model. RESULTS: The patients who had initially had jaundice had a significantly shorter interval between onset symptoms and first medical treatment and a significantly better prognosis than other patients. The patients who initially had back pain had a significantly poorer rate survival rate. Onset symptoms had a significant correlation with tumor location, which is a significant prognostic factor, but remained a significant prognostic factor with multivariate analysis. CONCLUSIONS: The onset symptom of patients with pancreatic carcinoma closely correlates with prognosis.

Carcinoma, Pancreatic Ductal↗

Transgene of MIF induces podocyte injury and progressive mesangial sclerosis in the mouse kidney.

BACKGROUND: Recent evidence suggests that macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that plays a pathogenic role in glomerulonephritis. Renal expression of MIF is up-regulated in infiltrating and intrinsic renal cells, which include glomerular epithelial cells. The aim of the current study was to further clarify the role of MIF produced by podocytes in the process of renal disease. METHODS: We generated transgenic mice carrying a murine MIF cDNA driven by cytomegalovirus enhancer and beta-actin/beta-globin promoter, a hybrid promoter transactivated in podocytes in vivo. RESULTS: MIF expression was markedly up-regulated in podocytes in neonatal and adult transgenic kidneys. A longitudinal study of the MIF transgenic mice demonstrated a progressive matrix increase in mesangium accompanied by collagen IV accumulation, representing no significant glomerular cell hypercellularity. The glomeruli in transgenic kidney were not accompanied by influx of macrophages and T cells at the early stage of disease progression. Although a significant number of the mice showing higher expression of MIF died from renal failure at 8 weeks, most of them survived with significant proteinuria and progressive renal failure. Podocytes of transgenic mice frequently underwent characteristic ultrastructural changes, such as cell flattening, contracted foot processes, and villous transformation. In addition, immunohistochemical expression of synaptopodin, an actin-associated protein distributed in differentiated podocyte foot process, was significantly attenuated in transgenic kidney. CONCLUSION: Our results indicate that podocyte-expressed MIF could induce an injury of podocytes themselves, thereby accelerating the progression of glomerulosclerosis and leading to end-stage renal failure.

Animals↗

Oscillatory reaction using immobilized catalase.

Oscillation is found in many biological systems, and among them the enzymatic oscillatory reaction has been well studied using an enzyme solution. We show in this study for the first time that oscillation occurs when catalase is immobilized to controlled pore glass (CPG). The oscillatory wave mode changes with the distance among the CPG, electrode, or dialysis membrane. The lower substrate concentration results in oscillation with a longer period. This tendency agrees with a previous study using an enzyme solution. Furthermore, we show that the oscillation occurs when no dialysis membrane is used. These results show the wider applicability of the system to analysis or novel device fabrication.

Catalase↗

Sleeping habit and other life styles in the prime of life and risk for ossification of the posterior longitudinal ligament of the spine (OPLL): a case-control study in Japan.

BACKGROUND: Although the average age of onset of ossification of the posterior longitudinal ligament of the spine (OPLL) is at around 50 years, the onset of the symptoms is insidious and the progression is very slow. The etiology of OPLL has not been elucidated in detail. Previous studies have suggested that a high-salt diet and low consumption of animal protein, glucose intolerance and high body mass are risk factors for OPLL. However, there is little information about the relationship between OPLL and life styles in the prime of life (between 30 and 50 years). METHODS: To facilitate early prediction and prevention of OPLL, we analyzed life styles such as sleeping habit, physical exercise, smoking, alcohol drinking and hangover in subjects in the prime of life. Self-administered questionnaires were obtained from patients with OPLL and their sex- and age-matched controls. Sixty-nine patients diagnosed with OPLL within 3 years previously and 138 sex- and age-matched controls without backbone diseases, randomly selected from participants in a health checkup in a local town, were enrolled. RESULT: Moderate amount of sleep (6-8 hours vs. 5 hours or shorter and 9 hours or longer; odds ratio [OR] = 0.18, 95% confidence interval [CI] = 0.06, 0.54) and a regular sleeping habit (i.e., going to bed and getting up at regular time) (OR=0.44, 95% CI=0.22, 0.90) were associated with a decreased risk of OPLL even after adjusting for other factors. On the other hand, moderate physical exercise (once a week or more v.s. less than once a week: OR=0.97, 95% CI=0.42, 2.26), smoking (OR=1.41, 95% CI=0.67, 2.97), drinking (OR=1.08, 95% CI=0.53, 2.20) and hangover (OR=1.12, 95% CI=0.43, 2.94) in the prime of life showed no correlation with risk of OPLL. CONCLUSION: Good sleeping habits in the prime of life may decrease the risk of OPLL.

Activities of Daily Living↗

Prognostic significance of the intra-vessel tumor characteristics of invasive ductal carcinoma of the breast: a prospective study.

Invasive ductal carcinomas (IDCs) of the breast are composed of stroma-invasive tumors and tumors in vessels. The purpose of this study was to prospectively investigate whether the histological characteristics of the tumors in vessels were more significantly associated with the outcome of 393 IDC patients than well-known histological parameters. Multivariate analyses showed greater than six apoptotic figures in tumor cells in lymph vessels to be significantly associated with increased hazard rates (HRs) of tumor recurrence and death in IDC patients without nodal metastasis (P<0.05). Among IDC patients with nodal metastasis whose tumors were positive for estrogen receptors (ERs) or progesterone receptors (PRs) or both, greater than six apoptotic figures in tumor cells in lymph vessels and greater than four mitotic figures in tumor cells in lymph vessels significantly increased the HR of tumor recurrence and the HR of death, respectively (P<0.05). Among IDC patients with nodal metastases whose tumors were negative for ERs and PRs, multivariate analyses showed that greater than two apoptotic figures in the blood vessel tumor emboli significantly increased the HRs of tumor recurrence and death (P<0.005). We conclude that apoptotic figures and mitotic figures in tumor cells in vessels are very important prognostic indicators for patients with IDC of the breast.

Adult↗

Low body mass index is a risk factor for impaired endothelium-dependent vasodilation in humans: role of nitric oxide and oxidative stress.

OBJECTIVES: The purpose of this study was to evaluate the relationship between body mass index (BMI), including low BMIs, and endothelial function. BACKGROUND: Epidemiologic study has demonstrated that not only obesity but also a low BMI may be a risk factor for cardiovascular disease. METHODS: The forearm blood flow (FBF) response to acetylcholine (ACh) and isosorbide dinitrate (ISDN) was measured in 87 healthy young men (15 low BMI, 51 normal, 14 obese, and 7 extremely obese). RESULTS: Plasma concentrations of 8-hydroxy-2'-deoxyguanosine and serum concentrations of malondialdehyde-modified low-density lipoprotein were higher in low BMI, obese, and extremely obese subjects than in normal subjects and were similar among the low BMI, obese, and extremely obese groups. The FBF response to ACh was greater in the normal group than in the other groups (p < 0.001), and was lower in the extremely obese group as compared with the other groups (p < 0.001). The ACh-stimulated vasodilation was similar between the low BMI group and the obese group. The ISDN-stimulated vasodilation was similar in all four groups. There were no significant differences in ACh-stimulated vasodilation between the four groups after the nitric oxide (NO) synthase inhibitor NG-monomethyl-L-arginine infusion. Co-infusion of vitamin C augmented the FBF response to ACh in low BMI, obese, and extremely obese groups--but not in normal BMI group. CONCLUSIONS: These findings suggest that not only obesity but also a low BMI may be a risk factor for impaired endothelium-dependent vasodilation through the increased oxidative stress, leading to the reduced bioavailability of NO.

Acetylcholine↗

Soy, isoflavones, and breast cancer risk in Japan.

BACKGROUND: Although isoflavones, such as those found in soy, have been shown to inhibit breast cancer in laboratory studies, associations between consumption of isoflavone-containing foods and breast cancer risk have been inconsistent in epidemiologic studies. We evaluated the relationship between isoflavone consumption and breast cancer risk among women in the Japan Public Health Center-Based Prospective Study on Cancer and Cardiovascular Diseases (JPHC Study). METHODS: In January 1990, 21 852 Japanese female residents (aged 40-59 years) from four public health center areas completed a self-administered questionnaire, which included items about the frequency of soy consumption. Through December 1999 and 209 354 person-years of follow-up, 179 women were diagnosed with breast cancer. Cox proportional hazards regression was used to estimate the relative risks (RRs) and 95% confidence intervals (CIs) for breast cancer in relation to consumption of miso soup, soyfoods, and estimated isoflavones. All statistical tests were two-sided. RESULTS: Consumption of miso soup and isoflavones, but not of soyfoods, was inversely associated with the risk of breast cancer. The associations did not change substantially after adjustment for potential confounders, including reproductive history, family history, smoking, and other dietary factors. Compared with those in the lowest quartile of isoflavone intake, the adjusted RRs for breast cancer for women in the second, third, and highest quartiles were 0.76 (95% CI = 0.47 to 1.2), 0.90 (95% CI = 0.56 to 1.5), and 0.46 (95% CI = 0.25 to 0.84), respectively (P(trend) =.043). The inverse association was stronger in postmenopausal women (P(trend) =.006). CONCLUSION: In a population-based, prospective cohort study in Japan, frequent miso soup and isoflavone consumption was associated with a reduced risk of breast cancer.

Adult↗

Proliferative activities of tumor stromal cells play important roles in tumor thickness and progression of T3 ulcerative-type colorectal cancer.

The central depressed area thickness (tumor thickness) of colorectal cancers is an important prognostic parameter for colorectal cancer patients. We examined whether the proliferative activities of tumor and stromal components play important roles in the increase of tumor thickness and the progression of colorectal cancers. Colorectal cancers were classified into thin and thick groups according to tumor thickness. The proliferative activities of fibroblasts and endothelial cells were immunohistochemically evaluated in 157 T3 ulcerative-type colorectal cancers by CD31/MIB-1 (anti-Ki-67 antigen) double staining. The MIB-1 labeling index was estimated as the percentage of fibroblasts with positive nuclei. The CD31-positive microvessels lined by MIB-1-positive endothelial cells were assessed. The proliferative microvessel index was defined as the percentage of proliferative microvessels relative to all microvessels. The fibroblast MIB-1 labeling index was the only parameter significantly associated with tumor thickness ( P=0.049). High fibroblast MIB-1 labeling indices showed significant correlation with tumor recurrence in the thin group ( P=0.020). High proliferative microvessel index was a significant parameter of tumor recurrence in the thick group ( P=0.003) in multivariate analyses. This study strongly suggests that proliferative activities of stromal components are useful parameters of tumor biology and of prognosis for T3 ulcerative-type colorectal cancer patients.

Adenocarcinoma↗

PDE5 inhibitor sildenafil citrate augments endothelium-dependent vasodilation in smokers.

Smoking is associated with endothelial dysfunction. The purpose of this study was to determine the effect of sildenafil, an inhibitor of phosphodiesterase type 5 (PDE5), on endothelial function in smokers. We evaluated the forearm blood flow (FBF) responses to acetylcholine (ACh), an endothelium-dependent vasodilator, and to sodium nitroprusside (SNP), an endothelium-independent vasodilator, before and after oral sildenafil administration (100 mg) with a strain-gauge plethysmograph in 10 young healthy male smokers and 10 young healthy male nonsmokers. FBF response to ACh was lower in smokers than in nonsmokers. The vasodilatory effects of SNP were similar in both groups. Sildenafil increased the FBF response to ACh from 9.3+/-2.0 to 12.5+/-3.5 mL/min per 100 mL tissue in smokers and from 12.6+/-5.6 to 19.6+/-8.4 mL/min per 100 mL tissue in nonsmokers, and it increased the response to SNP from 13.3+/-3.9 to 15.1+/-4.3 mL/min per 100 mL tissue in smokers and from 14.8+/-5.2 to 18.4+/-6.0 mL/min/100 mL tissue in nonsmokers (P<0.05 for all). The ratio of maximal ACh-stimulated FBF expressed as a ratio of maximal SNP-stimulated FBF significantly increased after administration of sildenafil in both groups. Infusion of NG-monomethyl-L-arginine, a nitric oxide synthase inhibitor, abolished sildenafil-induced augmentation of the FBF response to ACh in both groups. The findings suggest that endothelial function is impaired in smokers compared with that in nonsmokers, that inhibition of PDE5 by sildenafil significantly increases nitric oxide-mediated vasodilation, and that the activities of PDE5 in smokers and nonsmokers may be similar.

3',5'-Cyclic-GMP Phosphodiesterases↗

In bafilomycin A1-resistant cells, bafilomycin A1 raised lysosomal pH and both prodigiosins and concanamycin A inhibited growth through apoptosis.

In bafilomycin A(1)-resistant cells (Vero-317 and MC-3T3-E1), bafilomycin A(1) neither inhibited cell growth, induced cell death, nor activated caspase-3. However, 100 nM bafilomycin A(1) did raise the lysosomal pH similar to 10 mM NH(4)Cl. Prodigiosins, H(+)/Cl(-) symporters that raise the lysosomal pH, inhibited cell growth through apoptosis and caused the activation of caspase-3. Concanamycin A also inhibited the growth of these cells through apoptosis. 10 mM NH(4)Cl inhibited the growth of these cells as well, but cytostatically. These results suggest that plecomacrolides inhibited cell growth apoptotically through specific site(s), in contrast to the cytostatic effect of 10 mM NH(4)Cl, besides raising the lysosomal pH.

3T3 Cells↗

Discovery of a thieno[2,3-d]pyrimidine-2,4-dione bearing a p-methoxyureidophenyl moiety at the 6-position: a highly potent and orally bioavailable non-peptide antagonist for the human luteinizing hormone-releasing hormone receptor.

We have previously disclosed the first potent and orally effective non-peptide antagonist for the human luteinizing hormone-releasing hormone (LHRH) receptor, a thieno[2,3-b]pyridin-4-one derivative, T-98475 (1). Extensive research on developing non-peptide LHRH antagonists has been carried out by employing a strategy of replacing the thienopyridin-4-one nucleus with other heterocyclic surrogates. We describe herein the design and synthesis of a series of thieno[2,3-d]pyrimidine-2,4-dione derivatives containing a biaryl moiety, which led to the discovery of a highly potent and orally active non-peptide LHRH antagonist, 5-(N-benzyl-N-methylaminomethyl)-1-(2,6-difluorobenzyl)-6-[4-(3-methoxyureido)phenyl]-3-phenylthieno[2,3-d]pyrimidine-2,4(1H,3H)-dione (9k: TAK-013). Compound 9k showed high binding affinity and potent in vitro antagonistic activity for the human receptor with half-maximal inhibition concentration (IC(50)) values of 0.1 and 0.06 nM, respectively. Oral administration of 9k caused almost complete suppression of the plasma LH levels in castrated male cynomolgus monkeys at a 30 mg/kg dose with sufficient duration of action (more than 24 h). The results demonstrated that the thienopyrimidine-2,4-dione core is an excellent surrogate for the thienopyridin-4-one and that thienopyrimidine-2,4-diones and thienopyridin-4-ones constitute a new class of potent and orally bioavailable LHRH receptor antagonists. Furthermore, molecular modeling studies indicate that the unique methoxyurea side chain of 9k preferentially forms an intramolecular hydrogen bond between the aniline NH and the methoxy oxygen atom. The hydrogen bond will shield the hydrogen bonding moieties from the solvent and reduce the desolvation energy cost. It is therefore speculated that the intramolecular hydrogen bond resulting from judicious incorporation of an oxygen atom into the terminal alkyl group of the urea may increase the apparent lipophilicity to allow increased membrane permeability and consequently to improve the oral absorption of 9k in monkeys. On the basis of its profile, compound 9k has been selected as a candidate for clinical trials and it is expected that it will provide a new class of potential therapeutic agents for the clinical treatment of a variety of sex-hormone-dependent diseases.

Administration, Oral↗

A population-based dietary intervention trial in a high-risk area for stomach cancer and stroke: changes in intakes and related biomarkers.

BACKGROUND: Dietary intervention is one of the important fields in cancer and cardiovascular disease prevention. The Hiraka Dietary Intervention Study is a community-based randomized cross-over trial designed to develop an effective dietary modification tool and system in an area with high mortality of stomach cancer and stroke. METHODS: The subjects were 550 healthy volunteers and were randomized into two groups with tailored dietary education to decrease sodium intake and to increase vitamin C and carotene intakes either in the first year (intervention group) or in the second year (control group). Dietary changes were assessed using a validated self-administered diet history questionnaire, fasting blood samples, and 48-hour urine samples, which were obtained before and after the one year period. RESULTS: During the first year, changes differed significantly between the intervention and control group for both dietary sodium intake (-384 and +255 mg/day, intervention and control respectively, p < 0.001) and urinary sodium excretion (-1003 and -84 mg/day, p < 0.001). Although favorable net changes were also observed in dietary carotene (+418 and +220 mug/day, p < 0.05) and vitamin C (+13 and +2 mg/day, p < 0.05), the serum level differences were modest (+13 and -25 mg/L, p = 0.09 for carotene, +0.1 and -0.5 mg/L, p = 0.07 for ascorbic acid). CONCLUSION: The present dietary intervention strategy effectively decreased sodium and increased carotene and vitamin C intakes, although the former was more distinct.

Aged↗

Seasonal misclassification error and magnitude of true between-person variation in dietary nutrient intake: a random coefficients analysis and implications for the Japan Public Health Center (JPHC) Cohort Study.

OBJECTIVE: We examine (1) the extent to which seasonal diet assessments correctly classify individuals with respect to their usual nutrient intake, and (2) whether the magnitude of true variation in intake between individuals is seasonal. These effects could lead, respectively, to bias in estimates of relative risk for associations between usual nutrient exposure and disease, and to an increase in required sample size. SUBJECTS AND SETTING: One hundred and twenty-seven families in four regions of the Japan Public Health Center (JPHC) Cohort Study. DESIGN: On average, 48 weighed daily food records were collected per family over six seasons of 1994 and 1995. RESULTS: A random slopes regression model was used to predict the correlation between seasonal and annual average intakes, and to estimate true between-person variation in intakes by season. Mean vitamin C intake was greatest in summer and autumn, and seasonal variation was attributable to the consumption of fruit and vegetables. Predicted correlations between seasonal and annual average vitamin C intake ranged from 0.62 to 0.87, with greatest correlations in summer and autumn. True between-person variation in vitamin C intake was also strongly seasonal, ranging from 45 to 78% of total variance, and was again greatest in summer and autumn. These effects were less seasonal among energy and 13 other nutrients. CONCLUSIONS: It may be possible substantially to reduce both seasonal misclassification of individuals with respect to their usual vitamin C intake, and required sample size, by asking subjects to report high-season intake of fruit and vegetables in the JPHC Study.

Aged↗

Effect of five-year supplementation of vitamin C on serum vitamin C concentration and consumption of vegetables and fruits in middle-aged Japanese: a randomized controlled trial.

OBJECTIVE: This study was aimed at evaluating the effect of long-term vitamin C supplementation on serum and dietary vitamin C and identifying the factors associated with change in serum concentration. METHODS: A total of 439 subjects with atrophic gastritis initially participated in a randomized clinical trial using vitamin C and beta-carotene to prevent gastric cancer. We originally randomized the participants into four treatment groups using a 2x2 factorial design, whereby 0 or 15 mg/day beta-carotene and 50 or 500 mg/day vitamin C were administered in a double-blind manner. The beta-carotene component was terminated early after a mean treatment duration of four months. Before and upon early termination of beta-carotene supplementation, 134 subjects dropped out this trial, while 120 and 124 subjects took the vitamin C supplement at either 50 mg or 500 mg daily for five years. RESULTS: Changes in serum vitamin C were significantly higher in the high-dose group (38.5% increase, 95% CI = 27.0-49.9) than in the low-dose group (13.0% increase, 5.1-20.9) or in the dropout group (3.3% increase, -2.1-8.6) after five-year supplementation. The serum vitamin C at baseline was negatively associated with changes in serum vitamin C (p < 0.0001), while high-dose (p < 0.0001) and low-dose (p < 0.05) supplementation and female gender (p < 0.001) were positively associated. Dietary intake of vitamin C in the supplementation group was almost identical before and after five-year supplementation of vitamin C (2.31 mg/day decrease, 95% CI = -15.3-10.7), while a 17.7 mg/day decrease (95% CI = -44.2-8.86) was observed in the drop-out group. CONCLUSION: Five-year vitamin C supplementation induces a remarkable increase in serum vitamin C concentration, and our intervention program appears to have no effect on dietary vitamin C intake.

Adult↗