EFFECT OF ADDED DIETARY CALCIUM ON ESOPHAGEAL EPITHELIAL-CELL PROLIFERATION IN SUBJECTS AT HIGH RISK FOR ESOPHAGEAL CANCER: A DOUBLE-BLIND INTER-VENTION STUDY

A randomized double-blind intervention trial was carried determine whether oral calcium supplementation could lower the proliferation of epithelial cells of the esophagus. 41 subjects identified with precancerous lesions by histopathology were randomized to receive oral supplementation of their conventional diets with 0.6 g of calcium as calcium carbonate or placebo. Both at the entry to the study and at the end of the treatment, seven months later, the subjects were examined, with an emphasis on the frequency and distribution of proliferating epithelial cells of the esophagus. Patterns of cell proliferation was defined by dividing the esophageal epithelium into cell columns oriented perpendicularly to the basal cell layer and by comparing the numbers and fractions of tritiated thymidine-labeled epithelial cells in the various cell columns and cell compartments.Before dietary supplementation with calcium, the profile of proliferating epithelial cells in the esophageal compartments in calcium group is similar to that in the placebo group, which is comparable to that previously observed in subjects with high risk for esophageal cancer. Seven months after supplementation having been started, in calcium group, proliferation was significantly reduced and the profile of the esophageal columns approached to that previously observed in subjects at low risk for esophageal cancer, however, in the placebo group, the proliferation and profile maintain at the same level as that before supplementation. Our findings indicate that oral calcium supplementation induces a more quiescent equilibrium in epithelial-cell proliferation in the esophageal mucosa of the subjects at high-risk for esophageal cancer, similar to that observed in subjects at low risk.

Metabolomic changes in fatty liver can be modified by dietary protein and calcium during energy restriction

AIM： To characterise the effect of energy restriction （ER） on liver lipid and primary metabolite profile by using metabolomic approach. We also investigated whether the effect of energy restriction can be further enhanced by modification of dietary protein source and calcium. METHODS： Liver metabolomic profile of lean and obese C57BI/6J mice （n = 10/group） were compared with two groups of weight-reduced mice. ER was performed on control diet and whey protein-based high-calcium diet （whey ＋ Ca）. The metabolomic analyses were performed using the UPLC/MS based lipidomic platform and the HPLC/MS/MS based primary metabolite platform.RESULTS： ER on both diets significantly reduced hepatic lipid accumulation and lipid droplet size, while only whey ＋ Ca diet significantly decreased blood glucose （P 〈 0.001） and serum insulin （P 〈 0.01）. In hepatic lipid species the biggest reduction was in the level of triacylglycerols and cerarnides while the level of cholesterol esters was significantly increased during ER. Interestingly, diacylglycerol to phospholipid ratio, an indicator of relative amount of diabetogenic diglyceride species, was increased in the control ER group, but decreased in the whey ＋ Ca ER group （P 〈 0.001, vs obese）. ER on whey ＋ Ca diet also totally reversed the obesity induced increase in the relative level of lipotoxic cerarnides （P 〈 0.001, vs obese; P 〉 0.05, vs lean）. These changes were accompanied with up-regulated TCA cycle and pentose phosphate pathway rnetabolites. CONCLUSION： ER-induced changes on hepatic rnetabolornic profile can be significantly affected by dietary protein source. The therapeutic potential of whey protein and calcium should be further studied.

Change of BMD after Weaning or Resumption of Menstruation in Chinese Women with Different FokI VDR-genotypes:A Randomized,Placebo-controlled,Calcium Supplementation Trial

Objective To investigate the effect of calcium supplementation on bone mineral density （BMD） in Chinese women with different Fokl vitamin D receptor （VDR） genotypes （FF, Ff, and ff） after weaning or resumption of menstruation during lactation. Methods A total of 40 subjects with the same Fokl VDR genotype were randomly divided into two groups： one received calcium tablet （600 mg once daily as CaCO3） and the other placebo tablet once daily for 1 year. At baseline, BMD was measured by dual-energy X-ray absorptiometry at lumbar spine （L2-L4） and at left hip whereas serum PICP, serum OC, and urinary CTX, serum 25（OH）VitD3, and serum estradiol were measured at weaning and I year thereafter. Results After the intervention, BMD at lumbar spine and at left hip increased significantly in all these women with a trend among different Fokl VDR genotypes such as FF 〉 Ff 〉 ff （P〈O.05, 〈0.01, and 〈0.001, respectively）. BMD at lumbar spine in women with FF VDR genotype increased much more rapidly than in those with ff VDR genotype （P〈0.05）. Compared with the control group women with the FF genotype regained more BMD after calcium supplementation （P〈0.05）. Conclusion Daily calcium 600 mg supplementation has beneficial effect on the bone health of women with FF VDR genotype.

Intestinal Ca2+ absorption revisited: A molecular and clinical approach

Ca2+has an important role in the maintenance of the skeleton and is involved in the main physiological processes.Its homeostasis is controlled by the intestine,kidney,bone and parathyroid glands.The intestinal Ca2+absorption occurs mainly via the paracellular and the transcellular pathways.The proteins involved in both ways are regulated by calcitriol and other hormones as well as dietary factors.Fibroblast growth factor 23(FGF-23)is a strong antagonist of vitamin D action.Part of the intestinal Ca2+movement seems to be vitamin D independent.Intestinal Ca2+absorption changes according to different physiological conditions.It is promoted under high Ca2+demands such as growth,pregnancy,lactation,dietary Ca2+deficiency and high physical activity.In contrast,the intestinal Ca2+transport decreases with aging.Oxidative stress inhibits the intestinal Ca2+absorption whereas the antioxidants counteract the effects of prooxidants leading to the normalization of this physiological process.Several pathologies such as celiac disease,inflammatory bowel diseases,Turner syndrome and others occur with inhibition of intestinal Ca2+absorption,some hypercalciurias show Ca2+hyperabsorption,most of these alterations are related to the vitamin D endocrine system.Further research work should be accomplished in order not only to know more molecular details but also to detect possible therapeutic targets to ameliorate or avoid the consequences of altered intestinal Ca2+absorption.