American Journal of Clinical Nutrition

Extensive cross-sectional studies demonstrate a diminution of total body water in elderly and very old subjects. These findings are supported by less extensive longitudinal studies. Cross-sectional studies indicate that the decrease in total body water is mainly due to decreased intracellular water, but this is not supported by the findings of longitudinal studies. Despite the observed changes in total body water, both animal and human studies indicate little or no change in the relationship between total body water and fat-free mass with aging.

Thirty-one undergraduate men and women who weighed more (overweight) or who weighed less (underweight) than the normal weight limits for their height wore actometers on all four limbs 24 h each day for 14 consecutive days. All groups were found to be equally active. This result fails to replicate previously reported results that overweight men and women are hypoactive. This discrepancy is explained in terms of differences in percent overweight between the present and previous samples. The possibility of a catastrophic decline in activity as a function of percent overweight is discussed.

Difficulties associated with outcome assessment of operations performed for treatment of morbid obesity include lack of uniform standards for reporting results, failure to account for the response of related medical problems to weight loss, and lack of actuarial data for patients greater than or equal to 45 kg overweight. The purpose of this report is to critically analyze various methods of outcome assessment including the 5-y postoperative weight loss results of vertical banded gastroplasty and Roux-en-Y gastric bypass. Weight loss after these procedures usually reaches a nadir between 18 and 24 mo postoperatively. Mean percent excess weight loss at greater than or equal to 5 y ranged from 48% to 74% after gastric bypass and from 50% to 60% after vertical banded gastroplasty. Medical problems are almost invariably improved with satisfactory weight loss. Surgery remains the mainstay in treatment of morbid obesity because of the nearly 100% failure rate of nonoperative treatment in these patients.

Five groups of six (three male, three female) baboons (Papio ursinus) were maintained for 17 months on a semipurified diet containing 40% carbohydrate, 25% casein, 13.9% coconut oil, 0.1% cholesterol, 15% cellulose, 5% salt mix (USP XIV) and 1% vitamin mix. The carbohydrates fed were: fructose, sucrose, starch, glucose, and lactose. A fifth group was used as control and was fed bread, fruit, and vegetables. Serum, liver, and tissue lipids were analyzed at the end of the feeding period as were cholesterol absorption (as 3H-cholesterol) and synthesis (from 14C-mevalonic acid). Serum cholesterol and beta-lipoprotein levels were elevated in all the test groups compared to final control levels or to starting levels for all the baboons. Average serum cholesterol levels of the test groups were not significantly different. Liver lipids were elevated in all test groups except that fed glucose. Baboons on the test diets absorbed more exogenous cholesterol (3H) but biosynthesis of this sterol was not inhibited. The ratio of biliary primary/secondary bile acids was below normal levels only in the animals fed fructose and sucrose. Cholesteryl ester fatty acid spectra of serum and liver reflected the dietary fat. Fecal weight was 69% higher in lactose fed animals and 31% lower in sucrose fed animals than in the controls. The ratio of endogenous or exogenous neutral/acid steroids was considerably lower in the fructose-fed baboons than in the other animals. On this diet average aortic sudanophilia (percentage of surface) was: fructose, 11.3; sucrose, 10.4; starch, 21.3; glucose, 17.2 lactose, 65.8; and control, 1.4. Gross atheromatous lesions were seen in five of six baboons fed lactose; three of six baboons fed fructose; two of six baboons fed sucrose, and one of six baboons fed starch. In a second experiment three groups of baboons were fed the control diet, the semipurified diet in which the carbohydrate was lactose, and the semipurified diet containing lactose plus 0.1% cholesterol for 8.5 months. Serum lipids were elevated in the two test groups but liver lipids were not significantly different from control levels. Average aortic sudanophilia (percentage of area) was: lactose, 2.2; lactose-cholesterol, 20.8; and control, 0.3%. One of the six baboons in the lactose-cholesterol group had visible atherosclerotic lesions. These experiments represent the first successful attempt to produce severe atherosclerosis in baboons by dietary means alone.

Background: Few large studies in China have investigated total physical activity and sedentary leisure time and their associations with adiposity. Objective: We investigated determinants of physical activity and sedentary leisure time and their associations with adiposity in China. Design: A total of 466,605 generally healthy participants (age: 30-79 y, 60% female) in the China Kadoorie Biobank were included in this cross-sectional analysis. Self-reported information on a range of activities was collected by interviewer-administered questionnaire. Physical activity was calculated as metabolic equivalent task hours per day (MET-h/d) spent on work, transportation, housework, and nonsedentary recreation. Sedentary leisure time was quantified as hours per day. Adiposity measures included BMI, waist circumference, and percentage body fat (by bioimpedance analysis). Associations were estimated by linear and logistic regression. Results: The mean physical activity was 22 MET-h/d, and the mean sedentary leisure time was 3.0 h/d. For each sex, physical activity was about one-third lower among professionals/administrators than among factory workers, with intermediate levels for other occupational categories. A 1-SD (14 MET-h/d) greater physical activity was associated with a 0.15-unit (95% CI: 0.14, 0.16) lower BMI (in kg/m(2)), a 0.58-cm (95% CI: 0.55, 0.61) smaller waist circumference, and 0.48 (95% CI: 0.45, 0.50) percentage points less body fat. In contrast, a 1-SD (1.5 h/d) greater sedentary leisure time was associated with a 0.19-unit higher BMI (95% CI: 0.18, 0.20), a 0.57-cm larger waist circumference (95% CI: 0.54, 0.59), and 0.44 (95% CI: 0.42, 0.46) percentage points more body fat. For any given physical activity level, greater sedentary leisure time was associated with a greater prevalence of increased BMI, as was lower physical activity for any given sedentary leisure time. Conclusions: In adult Chinese, physical activity varies substantially by occupation, and lack of physical activity and excess sedentary leisure time are independently and jointly associated with greater adiposity.

Excessive intake of dietary fat contributes to the development and maintenance of both obesity and hyperlipidemia. Inhibition of gastrointestinal lipases could decrease the amount of ingested fat that is absorbed systemically by preventing the hydrolysis of triglycerides. Ro 18-0647, a chemically synthesized derivative of the natural product lipstatin, inhibits the action of gastrointestinal lipases. Initial studies in humans have shown that Ro 18-0647 can reliably increase fecal fat excretion. Ro 18-0647 has also been shown to be well tolerated in the majority of normal volunteers and obese patients studied. Further research must be conducted to determine whether clinical endpoints of weight loss or cholesterol lowering can be produced by using this new pharmacologic principle.

Although preconception 1,1,1-trichloro-2,2,bis(p-chlorophenyl)ethane (DDT) exposure and B-vitamin deficiencies have each been shown to negatively affect human reproductive outcomes, little is known about their joint effect. We sought to examine whether B-vitamin sufficiency protects against adverse effects of DDT on clinical pregnancy (CP) and subclinical early pregnancy loss (EPL). We measured preconception concentrations of plasma B vitamins (vitamin B-6, vitamin B-12, and folate) and serum total DDT [sum of p,p' and o,p' isomers of DDT and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene] in 291 nulligravid women from Anhui, China, who were studied in 1996-1998. The women were followed prospectively from the time they stopped contraception until CP (gestational age ≥42 d) or 12 mo (whichever occurred first). EPL was identified by using daily urinary human chorionic gonadotropin. The women were categorized according to B-vitamin status (deficiency compared with sufficiency) and DDT concentration (high compared with low). Of 291 study women, a total of 385 conceptions (31% of which ended in EPL) and 265 CPs occurred. Compared with women with adequate B-vitamins and low DDT, incidence rates of CP were reduced in women with B-vitamin deficiency and a high DDT concentration (P < 0.05 for all). Most notably, in women with sufficient vitamin B-12, DDT was not associated with the incidence of CP; in contrast, in women with vitamin B-12 deficiency, high DDT was associated with a lower incidence of CP (HR: 0.44; 95% CI: 0.23, 0.84); and the test for interaction was significant (P < 0.05). The odds of EPL decreased by 45% (95% CI: 21%, 62%) for each interquartile distance increase in folate in women with high DDT concentrations, and the test for interaction was significant (P = 0.006). Our results provide suggestive evidence that vitamin B-12 and folate sufficiency may help protect against adverse reproductive effects of DDT exposure. Additional studies are needed to confirm our findings. © 2014 American Society for Nutrition.

Ascorbic acid has a pronounced enhancing effect on the absorption of dietary nonheme iron when assessed by feeding single meals to fasting subjects. This contrasts with the negligible effect on iron balance of long-term supplementation with vitamin C. Our goal was to examine the effect of vitamin C on nonheme-iron absorption from a complete diet rather than from single meals. Iron absorption from a complete diet was measured during 3 separate dietary periods in 12 subjects by having the subjects ingest a labeled wheat roll with every meal for 5 d. The diet was freely chosen for the first dietary period and was then altered to maximally decrease or increase the dietary intake of vitamin C during the second and third periods. There was no significant difference in mean iron absorption among the 3 dietary periods despite a range of mean daily intakes of dietary vitamin C of 51-247 mg/d. When absorption values were adjusted for differences in iron status and the 3 absorption periods were pooled, multiple regression analysis indicated that iron absorption correlated negatively with dietary phosphate (P = 0.0005) and positively with ascorbic acid (P = 0.0069) and animal tissue (P = 0.0285). The facilitating effect of vitamin C on iron absorption from a complete diet is far less pronounced than that from single meals. These findings may explain why several prior studies did not show a significant effect on iron status of prolonged supplementation with vitamin C.

The dietary guidelines established under the auspices of public health policy are intended to promote healthy diets in the general public. The current recommendations for sodium intake stem from studies and publications that are older than much of the public they are designed to benefit. The past 2 decades have seen a dramatic increase in our knowledge of nutritional science, particularly our understanding of the role of sodium in blood pressure regulation. With a myriad of data from observational studies and randomized, controlled trials, we have the information to finally put sodium into its correct context in terms of its role in the regulation of blood pressure and hypertension. Not the sole and pervasive dietary villain it was once believed to be, sodium is but one factor in the complex interplay of multiple, inextricably related regulatory systems of which hypertension is the end result. With the data now available concerning dietary sodium, including the minimal and specific blood pressure effects of sodium in normotensive adults and both the benefits and risks of sodium reduction, future public health recommendations can be based on carefully acquired, consistent, and rational science.

Human beings evolved consuming a diet that contained about equal amounts of n-3 and n-6 essential fatty acids. Over the past 100-150 y there has been an enormous increase in the consumption of n-6 fatty acids due to the increased intake of vegetable oils from corn, sunflower seeds, safflower seeds, cottonseed, and soybeans. Today, in Western diets, the ratio of n-6 to n-3 fatty acids ranges from approximately 20-30:1 instead of the traditional range of 1-2:1. Studies indicate that a high intake of n-6 fatty acids shifts the physiologic state to one that is prothrombotic and proaggregatory, characterized by increases in blood viscosity, vasospasm, and vasoconstriction and decreases in bleeding time. n-3 Fatty acids, however, have antiinflammatory, antithrombotic, antiarrhythmic, hypolipidemic, and vasodilatory properties. These beneficial effects of n-3 fatty acids have been shown in the secondary prevention of coronary heart disease, hypertension, type 2 diabetes, and, in some patients with renal disease, rheumatoid arthritis, ulcerative colitis, Crohn disease, and chronic obstructive pulmonary disease. Most of the studies were carried out with fish oils [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)]. However, alpha-linolenic acid, found in green leafy vegetables, flaxseed, rapeseed, and walnuts, desaturates and elongates in the human body to EPA and DHA and by itself may have beneficial effects in health and in the control of chronic diseases.

Acetate and propionate, produced during colonic fermentation of unabsorbed carbohydrate, may influence systemic lipid metabolism. As a preliminary study to see whether colonic acetate is incorporated into plasma lipids and whether propionate inhibits this process, 5 healthy males were studied after fasting overnight. They were given, in random order, 12.5 mmol (1.05 g) [1,2-13C]sodium acetate by intravenous or rectal infusion, and the rectal infusion was given with or without 6 mmol (0.58 g) sodium propionate. Two hours after rectal acetate, 13C recoveries in plasma cholesterol (0.59 +/- 0.22%) and triglycerides (1.24 +/- 0.69%) were significantly greater than after intravenous acetate (0.09 +/- 0.12% and 0.29 +/- 0.18%, respectively). Addition of propionate reduced 13C recovery in triglycerides (0.19 +/- 0.06%, P = 0.024) compared with rectal acetate alone, but the effect on cholesterol (0.26 +/- 0.05%) was not significant. These data suggest that incorporation of colonic acetate into plasma triglycerides is inhibited by propionate. Further studies are required to quantify the effects of colonic acetate and propionate on lipid synthesis.

Dietary supplementation with nutrients rich in antioxidants is associated with inhibition of atherogenic modifications to LDL, macrophage foam cell formation, and atherosclerosis. Pomegranates are a source of polyphenols and other antioxidants. We analyzed, in healthy male volunteers and in atherosclerotic apolipoprotein E-deficient (E(0)) mice, the effect of pomegranate juice consumption on lipoprotein oxidation, aggregation, and retention; macrophage atherogenicity; platelet aggregation; and atherosclerosis. Potent antioxidative effects of pomegranate juice against lipid peroxidation in whole plasma and in isolated lipoproteins (HDL and LDL) were assessed in humans and in E(0) mice after pomegranate juice consumption for </=2 and 14 wk, respectively. In humans, pomegranate juice consumption decreased LDL susceptibility to aggregation and retention and increased the activity of serum paraoxonase (an HDL-associated esterase that can protect against lipid peroxidation) by 20%. In E(0) mice, oxidation of LDL by peritoneal macrophages was reduced by up to 90% after pomegranate juice consumption and this effect was associated with reduced cellular lipid peroxidation and superoxide release. The uptake of oxidized LDL and native LDL by mouse peritoneal macrophages obtained after pomegranate juice administration was reduced by 20%. Finally, pomegranate juice supplementation of E(0) mice reduced the size of their atherosclerotic lesions by 44% and also the number of foam cells compared with control E(0) mice supplemented with water. Pomegranate juice had potent antiatherogenic effects in healthy humans and in atherosclerotic mice that may be attributable to its antioxidative properties.

To investigate the effects of the difference in the geometry of dietary fatty acids on colon tumorigenesis, male rats were fed semipurified diets containing either partially hydrogenated corn oil (trans-monoene fat) or olive oil (cis-monoene fat) at the 10% level and received a single oral dosage of 1,2-dimethylhydrazine (DMH). The difference in the fatty acid composition of dietary fats was confined essentially to the geometrical isomerism of octadecenoate, and the linoleic acid content was made equivalent (2% of total energy). After about 15 mo of feeding, colon tumor incidence in DMH treated rats was nearly the same in both fat groups. Fecal neutral steroid excretion was higher, while the transformation of cholesterol to coprostanol was lower in rats given the trans-fat. There were no marked differences in the excretion and composition of fecal bile acids between two fat groups. Serum cholesterol and tocopherol levels of rats given trans-fat diets tended to be low. The results suggested that the trans-monoene behaves much like the cis-monoene in the incidence of DMH-induced colon tumors, although there were characteristic differences in metabolic events in the intestine.

Free radicals and other reactive species are constantly generated in vivo and cause oxidative damage to DNA at a rate that is probably a significant contributor to the age-related development of cancer. Agents that decrease oxidative DNA damage should thus decrease the risk of cancer development. That is, oxidative DNA damage is a "biomarker" for identifying persons at risk (for dietary or genetic reasons, or both) of developing cancer and for suggesting how the diets of these persons could be modified to decrease that risk. This biomarker concept presupposes that we can measure oxidative damage accurately in DNA from relevant tissues. Little information is available on whether oxidative DNA damage in blood cells mirrors such damage in tissues at risk of cancer development. Measurement of 8-hydroxylated guanine (eg, as 8-hydroxy-2'-deoxyguanosine; 8OHdG) is the commonest method of assessing DNA damage, but there is no consensus on what the true levels are in human DNA. If the lowest levels reported are correct, 8OHdG may be only a minor product of oxidative DNA damage. Indeed, 8OHdG may be difficult to measure because of the ease with which it is formed artifactually during isolation, hydrolysis, and analysis of DNA. Mass spectrometry can accurately measure a wide spectrum of DNA base damage products, but the development of liquid chromatography-mass spectrometry techniques and improved DNA hydrolysis procedures is urgently required. The available evidence suggests that in Western populations, intake of certain fruit and vegetables can decrease oxidative DNA damage, whereas ascorbate, vitamin E, and beta-carotene cannot.

The nutritional value and safety of various commercial FPC for human consumption was studied with rats. Although we found evidence that certain factor(s) depressed the nutritional quality of DCE-FPC, the presence of specific toxicants as causative agents of depressed growth could not be demonstrated. It appears that the method of fish processing and solvent extraction can have profound effects on the nutritional quality of FPC. Isopropanol extraction of fish resulted in a more nutritious FPC than DCE extraction. Further processing of DCE-FPC did not negate this nutritional inferiority. Species differences of fish are not the main reason for nutritional differences between IP- and DCE-extracted FPC (8, 17). These studies suggest that the more desirable FPC for human use would be that extracted with isopropanol.

To investigate whether low calcium absorption in osteoporosis improves by increasing 1,25-dihydroxyvitamin D both systemically in plasma and locally in gut, the effects of oral 25-hydroxycholecalciferol and oral 1,25-dihydroxycholecalciferol on plasma 1,25-dihydroxy-vitamin D (1,25-(OH)2D) and calcium absorption were studied in 20 postmenopausal patients with vertebral osteoporosis. In 10 patients taking oral 0.25 micrograms 1,25-dihydroxycholecalciferol twice daily for 7 d, calcium absorption increased more than in 10 patients taking oral 40 micrograms 25-hydroxycholecalciferol once daily for 7 d (p less than 0.02) despite both groups having a similar increase in plasma 1,25-(OH)2D. These results support the view that the major effects of oral 1,25-dihydroxycholecalciferol on absorption is due to a local action on the gut and that it is possible to increase calcium absorption in osteoporosis with oral 1,25-dihydroxycholecalciferol without increasing its undesirable action on bone resorption.

Serum levels of 1,25-dihydroxycholecalciferol (1,25-CC), the form of vitamin D active in stimulating intestinal absorption of calcium, phosphorus, and lead, were determined in 177 human subjects ages 1 to 16 yr. Significant negative association (r = -0.88) was observed between serum 1.25-CC levels and blood lead concentrations over the entire range of blood lead levels, 12 to 120 micrograms/dl. Adolescents ages 11 to 16 yr had serum 1,25-CC levels higher than those observed among children 10 yr old or younger. No effect of sex or season on serum 1,25-CC level was observed. When the 1,25-CC values for children with blood lead concentrations greater than 30 micrograms/dl were excluded from the analysis, no significant effect of geographic location on 1,25-CC levels was observed.

Vitamin D metabolism in elderly individuals can be compromised by several mechanisms. We previously described reduced concentrations of 1,25-dihydroxyvitamin D [1,25(OH)2D] in 30% of elderly nursing home residents. The present study assesses the effect of vitamin D supplementation on 25-hydroxyvitamin D [25(OH)D] and 1,25(OH)2D. We performed a double-blind study in which 30 elderly nursing home residents were randomly given either 50 micrograms vitamin D or a placebo daily for 6 wk. Vitamin D metabolites, immunometrically assayed parathyroid hormone (IRMA-PTH), ionized calcium, and bone Gla hormone (BGP) were measured in serum at baseline and biweekly for 6 wk. Serum 25(OH)D concentrations increased significantly (P less than 0.0001) over the 6 wk in the treatment group but were unchanged in the placebo group. Serum 1,25(OH)2D, ionized calcium, BGP, and PTH were not significantly altered by the supplement. We conclude that vitamin D supplementation results in an increase in circulating 25(OH)D but not 1,25(OH)2D; however, the long-term effect on bone mineral metabolism remains unclear.

During lactation maternal losses of calcium and phosphorus through human milk average 220 to 340 and 110 to 170 mg/day, respectively. The present study reports maternal serum concentrations of vitamin D metabolites, parathyroid hormone, calcitonin, calcium, magnesium, and phosphorus during the first 6 months of lactation. Serum calcium and magnesium concentrations increased during the first 6 months of lactation. Serum 1,25-(OH)2 vitamin D was increased at 6 months of lactation compared to values in nonpregnant nonlactating controls. During this same period, serum parathyroid hormone decreased slightly and serum calcitonin remained unchanged. Our data do not support the observation that lactation represents a state of physiological hyperparathyroidism. On the contrary, our results suggest that lactating women are able to adequately compensate for the losses of calcium and phosphorus during the early months of lactation, although increased serum 1,25-(OH)2 vitamin D concentrations may be necessary to maintain calcium homeostasis with lactation beyond 6 months.

The roles of vitamin D, calcitonin, and parathyroid hormone in calcium metabolism during lactation may be more evident in women secreting very large amounts of milk for a number of months, as in mothers nursing twins. We report significant increases in serum concentrations of parathyroid hormone, calcitonin, and 1,25(OH)2 vitamin D in mothers nursing twins compared to mothers nursing single infants. Serum concentrations of calcium actually increased in both groups during lactation. Maternal intakes of calories, calcium, and phosphorus were significantly higher in mothers nursing twins. Thus, mothers nursing twins were able to compensate for higher calcium losses in breast milk by increased dietary intakes of calcium as well as increased serum concentrations of parathyroid hormone, calcitonin, and 1,25(OH)2 vitamin D.

We evaluated the relationship between plasma concentrations of the renal hormone 1,25-(OH)2-vitamin D and net intestinal absorption of Ca, PO4, and Mg in vitamin D-replete patients eating similar diets, who had undetectable, normal or elevated plasma 1,25-(OH)2-D levels, Net intestinal Ca absorption was positively correlated to plasma 1,25-(OH)2-D concentrations: percentage dietary Ca absorbed = 10 + 0.17 x plasma total 1,25-(OH)2-3, pmole/liter, r = + 0.58; P less than 0.001. By contrast, there was no significant correlation between PO4 or Mg absorption and plasma 1,25-(OH)2-D concentrations. Moreover, significant quantities of PO4 and Mg were absorbed in the absence of detectable plasma 1,25-(OH)2-D. We conclude that net intestinal Ca absorption is critically dependent upon the availability of the renal hormone 1,25-(OH)2-D in vitamin D-replete humans when dietary Ca intake is normal. By contrast, other factors must play a dominant role in regulating net intestinal PO4 and Mg absorption.

The seasonal variation of 25-hydroxycholecalciferol and 1,25-dihydroxycholecalciferol was analyzed in 240 elderly subjects (mean age: 78 yr) in Belgium. Serum 25-hydroxycholecalciferol was lowest from February until May (mean levels less than 25 nmol/L). Summer peak levels were, however, not higher than nadir levels in younger control subjects. A seasonal variation in total and free 1,25-dihydroxycholecalciferol concentrations was also observed in the geriatric population with a nadir in February and March (50 +/- 24 pmol/L). The peak values in summer (110 +/- 33 pmol/L) were not different from those of the younger controls. Serum calcium and phosphate were decreased whereas alkaline phosphatase and parathyroid hormone were increased throughout the year in the geriatric patients. Oral 25-hydroxycholecalciferol treatment rapidly normalized serum 1,25-dihydroxycholecalciferol concentrations in vitamin D-deficient subjects. Deficiency of both the vitamin D substrate and hormone is frequent in the elderly population in Belgium.

It has been conclusively shown that vitamin D3(cholecalciferol) must first be metabolized prior to its mediating intestinal calcium transport. The first transformation is conversion of vitamin D3by the liver to 25-hydroxyvitamin D3. This compound is then subsequently metabolized by the kidney to 1,25-dihydroxyvitamin D3. 1,25-Dihydroxyvitamin D3is over four times as effective as vitamin D3and more than twice as effective as 25-OH-vitamin D3in stimulating intestinal calcium transport. Additionally, 1,25-dihydroxyvitamin D3is highly active in stimulating bone calcium resorption. As such, 1,25-dihydroxyvitamin D3likely represents the biologically active form of the vitamin in the intestine and bone. The secretion of this steroid by the kidney and its selective accumulation by the target organs supports the concept that this compound should be regarded as a hormonal regulator of calcium metabolism.

Factors affecting bone calcium deposition across pregnancy and lactation are not well characterized. The impact of maternal age, calcium intake, race-ethnicity, and vitamin D status on the rate of bone calcium deposition (VO+) was assessed across pregnancy and lactation. Stable calcium isotopes were given to 46 women at pre- or early pregnancy (trimester 1), late pregnancy (trimester 3), and 3-10 wk postpartum. Three cohorts were included: 23 adolescents from Baltimore (MD), aged 16.5 ± 1.4 y (mean ± SD; Baltimore cohort); 13 adults from California, aged 29.5 ± 2.6 y (California cohort); and 10 adults from Brazil, aged 30.4 ± 4.0 y (Brazil cohort). The total exchangeable calcium pool, VO+, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D [1,25(OH)₂D], parathyroid hormone, and calcium intake were evaluated. At trimester 3, inverse associations between 1,25(OH)₂D and VO+ were evident in the Baltimore (P = 0.059) and Brazil (P = 0.008) cohorts and in the whole group (P = 0.029); calcium intake was not a significant determinant of VO+ in any group during pregnancy. At postpartum, a significant positive association was evident between VO+ and calcium intake (P ≤ 0.002) and between VO+ and African ethnicity (P ≤ 0.004) in the whole group and within the Baltimore and Brazil cohorts. Elevated 1,25(OH)₂D was associated with decreased rates of bone calcium deposition during late pregnancy, a finding that was particularly evident in pregnant adolescents and adult women with low calcium intakes. Higher dietary calcium intakes and African ethnicity were associated with elevated rates of bone calcium deposition in the postpartum period.

Vitamin D is an important immune system regulator. The active form of vitamin D, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], has been shown to inhibit the development of autoimmune diseases, including inflammatory bowel disease (IBD). Paradoxically, other immune system-mediated diseases (experimental asthma) and immunity to infectious organisms were unaffected by 1,25(OH)2D3 treatment. There are similar paradoxical effects of vitamin D deficiency on various immune system functions. Vitamin D and vitamin D receptor (VDR) deficiency resulted in accelerated IBD. Experimental asthma was unaffected by 1,25(OH)2D3 treatment and was less severe among VDR-deficient mice. Vitamin D is a selective regulator of the immune system, and the outcome of 1,25(OH)2D3 treatment, vitamin D deficiency, or VDR deficiency depends on the nature of the immune response (eg, infectious disease, asthma, or autoimmune disease). An additional factor that determines the effect of vitamin D status on immune function is dietary calcium. Dietary calcium has independent effects on IBD severity. Vitamin D-deficient mice on low-calcium diets developed the most severe IBD, and 1,25(OH)2D3 treatment of mice on low-calcium diets improved IBD symptoms. However, the best results for IBD were observed when the calcium concentration was high and 1,25(OH)2D3 was administered. Both the type of immune response and the calcium status of the host determine the effects of vitamin D status and 1,25(OH)2D3 on immunity.

The present studies were designed to investigate phosphate transport across the brush border and basolateral membranes of enterocytes and to determine the effect of 1,25-dihydroxycholecalciferol [1,25(OH)2D3] on these processes in suckling and adolescent rats. Vitamin D deficiency was induced in suckling rats by feeding pregnant dams a vitamin D-deficient diet 48 h after insemination; they were then kept in the dark. Vitamin D deficiency in the adolescent rats was induced by feeding the vitamin D-deficient diet to weanling rats for 4 wk. V max values for Na(+)-dependent phosphate uptake in the brush border membranes of vitamin D-deficient and 1,25(OH)2D3-injected suckling rats was 0.7 +/- 0.1 and 1.5 +/- 0.2 nmol.mg protein-1.10 s-1 (P less than 0.01), respectively; V max values in adolescent rats were 0.2 +/- 0.05 and 0.36 +/- 0.04 nmol.mg protein-1.10 s-1 (P less than 0.05), respectively. Vmax values for Na(+)-dependent phosphate uptake in basolateral membranes of vitamin D-deficient and 1,25(OH)2D3-treated suckling rats were 0.006 +/- 0.001 and 0.047 +/- 0.006 nmol.mg protein-1.10 s-1 (P less than 0.01).

Low serum 25-hydroxyvitamin D ¿25(OH)D concentrations are commonly found in the elderly and are associated with hip fracture. Treatment with vitamin D and calcium can reduce the risk of fracture. The relation between the rise in parathyroid hormone (PTH) with age and the decrease in 25(OH)D is not clear. Neither is there any consensus on the serum concentration of 25(OH)D required for bone health. Our objective was to study the relations between serum PTH, serum vitamin D metabolites, and other calcium-related variables in postmenopausal women. This was a cross-sectional study of 496 postmenopausal women without vertebral fractures attending our menopausal osteoporosis clinics. PTH was significantly positively related to age and serum 1, 25-dihydroxyvitamin D ¿1,25(OH)(2)D and inversely related to 25(OH)D and plasma ionized calcium. There was a step-like increase in PTH as serum 25(OH)D fell below 40 nmol/L. In women with 25(OH)D concentrations >40 nmol/L, 1,25(OH)(2)D was positively related to 25(OH)D; in women with 25(OH)D concentrations </=40 nmol/L, the relation was the inverse. In women with 25(OH)D concentrations </=40 nmol/L, 1,25(OH)(2)D was most closely related to PTH; in women with 25(OH)D concentrations >40 nmol/L, 1,25(OH)(2)D was most closely (inversely) related to plasma creatinine. Therefore, with serum 25(OH)D concentrations increasingly <40 nmol/L, serum 1,25(OH)(2)D becomes critically dependent on rising concentrations of PTH. The data suggest that aging women should maintain 25(OH)D concentrations >40 nmol/L (which is the lower limit of our normal range for healthy young subjects) for optimal bone health.

Serum concentrations of 25-hydroxyvitamin D (25-OHD) and 1,25-dihydroxyvitamin D [1,25-(OH)2D] of vitamin D2 and D3 origin were determined separately in 10 women before vitamin intake in early pregnancy, and repeated in maternal and cord serum obtained at delivery after 20 to 30 wk of vitamin D2 supplementation in a dose of 400 IU/day. Before supplementation 25-OHD2 and 1,25-(OH)D2D2 were present in just traceable or nondetectable concentrations, but the levels increased in all to a mean +/- 1 SD of 7.3 +/- 3.7 ng/ml and 37.2 +/- 18.1 pg/ml, respectively (p less than 0.0025), by the time of delivery. At delivery the total 25-OHD and 1,25-(OH)2D levels were always lower in the cord than in the maternal serum (30.7 +/- 14.2 versus 20.1 +/- 9.1 ng/ml, and 90.1 +/- 31.2 versus 37.3 +/- 11.6 pg/ml, p less than 0.0025). The paired concentrations of 25-OHD were closely related (r = 0.89, p less than 0.0005), while the association for 1,25-(OH)2D was not statistically significant (r = 0.53, p less than .01). The 25-OHD of D2 and D3 origin accounted for a similar proportion of the total 25-OHD in the maternal and cord serum (ratio of 25-OHD2 to 25-OHD3: 0.40 +/- 0.28 versus 0.45 +/- 0.29, p = NS), as did the respective 1,25-(OH)2D metabolites [ratio of 1,25-(OH)2D2 to 1,25-(OH)2D3: 0.73 +/- 0.35 versus 0.90 +/- 0.50, p = NS].(ABSTRACT TRUNCATED AT 250 WORDS)

This report describes the effects of treatment with 1,25 dihydroxyvitamin D3 (1,25(0H)2D3) or 1α hydroxyvitamin D3 (1α(OH)D3) on net absorption of phosphorus in patients with advanced renal failure and in normal volunteers. The results indicate that these 2 analogs of vitamin D3 can augment intestinal absorption of phosphorus in man.

In a cross-sectional, population-based study we measured casual, seated blood pressure with a random-zero sphygmomanometer and 1,25-dihydroxyvitamin D (1,25-[OH]2D) with a protein-binding assay in 373 women aged 20-80 y. 1,25-(OH)2D, an active metabolite that regulates serum calcium, was associated significantly and positively with systolic blood pressure (p = 0.020) and diastolic blood pressure (p = 0.003) after adjustment for age, Quetelet's index (a measure of obesity), and current thiazide use. A model including age, Quetelet's index, current thiazide use, and 1,25-(OH)2D explained 37% of the variability in systolic blood pressure observations, of which 7% of variability was explained by 1,25-(OH)2D. In this geographically defined population of women, the variability of blood-pressure measurements attributable to 1,25-(OH)2D was of the same order of magnitude as that attributable to Quetelet's index.

In rat with massive resection of mid-small intestine, calcium transport per segment, measured by in vivo perfusion 10 days after surgery, is decreased in duodenum and ileum but is the same in cecum and colon as compared with controls with transection and reanastomosis of mid-small intestine. To extend these findings, we measured balances of calcium, phosphorus, and fat from the 5th to 10th day after surgery and serum concentration of 1,25-dihydroxycholecalciferol on the 10th day after surgery in this experimental model. We found steatorrhea in the resected group, but balances of calcium and phosphorus and serum levels of 1,25-dihydroxycholecalciferol were the same in resected and control groups. We conclude that decreased transport defined by direct examination of membrane function may be undetectable when net transport is measured by balance. Calcium balance during early post-resection period provides no evidence for future calcium deficiency in this experimental model.

S-Adenosyl-L-methionine (SAMe), a natural compound, is the most important methyl donor in the central nervous system. In several clinical trials, SAMe showed antidepressant activity. Two multicenter studies were conducted in patients with a diagnosis of major depressive episode [baseline score on the 21-item Hamilton Depression Rating Scale (HAM-D) >or=18] to confirm the efficacy and safety of SAMe in the treatment of major depression. In the first study (MC3), 1600 mg SAMe/d was given orally; whereas, in the second study (MC4), 400 mg SAMe/d was given intramuscularly. In both studies, the effects of SAMe were compared with those of 150 mg imipramine/d given orally in a double-blind design. In MC3, 143 patients received oral SAMe and 138 patients received imipramine for 6 wk. In MC4, 147 patients received SAMe intramuscularly and 148 patients received imipramine for 4 wk. In both studies the 2 main efficacy measures were the final HAM-D score and the percentage of responders to Clinical Global Impression at the endpoint. Secondary efficacy measures were the endpoint Montgomery-Asberg Depression Rating Scale scores and the percentage of responders, responders being those patients showing a decrease in HAM-D score of >or=50% from baseline. In both studies, the results of SAMe and imipramine treatment did not differ significantly for any efficacy measure. However, significantly fewer adverse events were observed in the patients treated with SAMe. The antidepressive efficacy of 1600 mg SAMe/d orally and 400 mg SAMe/d intramuscularly is comparable with that of 150 mg imipramine/d orally, but SAMe is significantly better tolerated.

Synthetic folic acid (0.4-1.0 mg) consumed during the periconceptional period has been shown to reduce the risk of neural tube defects. Women with poor supplement adherence or a previous pregnancy affected by a neural tube defect may need to take higher doses of folic acid (4-5 mg). However, there are limited data on the pharmacokinetics of higher folic acid doses. Our aim was to compare steady state folate concentrations in women of childbearing age who took 5 or 1.1 mg folic acid daily for 30 wk. Forty nonpregnant women aged between 18 and 45 y, who did not take folic acid supplements, were enrolled in the study. Subjects were randomly assigned to take either 5 or 1.1 mg folic acid daily for 30 wk. Plasma and red blood cell (RBC) folate concentrations were measured at baseline and at weeks 2, 4, 6, 12, and 30. There was no significant difference in baseline RBC folate concentrations between the 2 groups (1121 +/- 410 and 1035 +/- 273 nmol/L for the 5- and 1.1-mg folic acid groups, respectively). Significant differences in RBC folate were detected between groups at weeks 4, 6, 12, and 30. RBC folate concentrations by week 30 were 2339 +/- 782 and 1625 +/- 339 nmol/L for the 5- and 1.1-mg folic acid groups, respectively. The use of 5 mg folic acid among women of childbearing age produced higher blood folate concentrations, with a faster rate of folate accumulation, compared with 1.1 mg folic acid.

We developed a method for calculating adipose-tissue areas from transverse body scans by magnetic-resonance imaging (MRI). The method is based on an inversion recovery experiment (repetition time 820 ms, inversion delay time 300 ms, and echo time 20 ms). Total-fat areas and subcutaneous-fat areas were calculated by this method and by computed tomography (CT) from abdominal scans taken in seven male volunteers. The SEE ranged from 4.4 cm2 (CV 4.4%) for subcutaneous-fat areas to 8.3 cm2 (CV 12.8%) for visceral-fat areas. The reproducibility of measuring fat areas with MRI was assessed in seven other volunteers (four males, three females). The average errors of the method for different fat areas were 5.4%, 10.6%, and 10.1% for total-, visceral-, and subcutaneous-fat areas, respectively. We conclude that CT and MRI may yield different absolute values of fat areas (especially visceral fat) but that the ranking of individuals on the basis of their fat areas will be similar by both methods.

Breastfeeding is considered an optimal nutritional source of n-6 (omega-6) and n-3 (omega-3) fatty acids (FAs) for the proper visual and cognitive development of newborn children. In addition to maternal nutrition as an important regulator of FA concentrations, first results exist on an association of breast-milk FAs with single nucleotide polymorphisms (SNPs) in the FADS gene cluster, which encodes the rate-limiting enzymes in the elongation-desaturation pathway of long-chain polyunsaturated fatty acids (LC-PUFAs). We analyzed the influence of FADS SNPs on breast-milk FA concentrations and their time course during lactation in the Ulm Birth Cohort study, which comprised 772 nursing mothers at 1.5 mo after giving birth, and in a subset of 463 mothers who were still breastfeeding at 6 mo postpartum. We conducted linear regression analysis of 8 FADS SNPs with FA concentrations at both time points separately and assessed the genotype effect over time in a longitudinal analysis by using a generalized estimating equation regression model. We observed significant associations of FADS genotypes with arachidonic acid (AA) concentrations and the 20:4n-6/20:3n-6 ratio at both time points but no association of FADS SNPs with the time course of AA concentrations. A longitudinal analysis of FAs other than LC-PUFAs by genotype over time showed associations for dodecanoic acid, cis-15-tetracosenoic acid, and trans-9-octadecenoic acid. Maternal FADS genotypes are associated with breast-milk AA concentrations and might therefore influence the supply of this FA for children. Furthermore, our data indicate an interrelation between the LC-PUFA pathway and saturated and monounsaturated FAs.

The prevalence of childhood overweight and obesity has increased recently, but the mechanisms involved are incompletely known. Previous research has shown a correlation between the percentage of total body fat (TBF) and physical activity level (PAL). However, the PAL values used may involve a risk of spurious correlations because they are often based on predicted rather than measured estimates of resting energy metabolism. We studied the development of body composition during early childhood and the relation between the percentage of TBF and PAL on the basis of the measured resting energy metabolism. Body composition was previously measured in 108 children when they were 1 and 12 wk old. When 44 of these children (21 girls and 23 boys) were 1.5 y old, their total energy expenditure and TBF were assessed by using the doubly labeled water method. Resting energy metabolism, which was assessed by using indirect calorimetry, was used to calculate PAL. Significant correlations were shown for TBF (r = 0.32, P = 0.035) and fat-free mass (r = 0.34, P = 0.025) between values (kg) assessed at 12 wk and 1.5 y of age. For TBF (kg) a significant interaction (P = 0.035) indicated a possible sex difference. PAL at 1.5 y was negatively correlated with the percentage of TBF (r = -0.40, P = 0.0076) and the increase in the percentage of TBF between 12 wk and 1.5 y (r = -0.38, P = 0.0105). The results indicate that body fatness and physical activity interact during early childhood and thereby influence obesity risk. Our results are based on a small sample, but nevertheless, they motivate additional studies in boys compared with girls regarding the development of body composition during early life.

Eleven obese subjects (body mass index, 41.3 kg/m2) were examined to determine their metabolic and acid-base responses during two hypoenergetic diets, and the diets' influence on subsequent responses to prolonged total fasting. Subjects were first treated for 2 wk with 400-kcal/d (1.67-MJ/d) diets of either protein (13.2 g nitrogen, 23 mmol potassium) or glucose with 16 mmol potassium chloride and a multivitamin supplement. Mild acidosis developed during the protein diet as well as greater excretions of urinary ammonium and urea N, a greater degree of ketosis, and significantly better N balance (-42.7 vs -80.4 g, p less than 0.05) than during the glucose diet. The subsequent fast was associated with greater negative N balance after protein (-129 vs 83 g), mainly as urea N, but despite similar ketosis there was a greater acidosis after glucose and greater ammonium N excretion and cumulative K losses. These data support the concept of a labile N pool, depleted during a glucose diet and resulting in a decreased loss with the subsequent fast. We suggest a role for K depletion in augmenting fasting ammonium excretion.

Birth weight is an early correlate of disease later in life, and animal studies suggest that low birth weight is associated with reduced activity and increased sedentary time. Whether birth weight predicts later sedentary time in humans is uncertain. We examined the relation between birth weight and sedentary time in youth and examined whether this association was mediated by central adiposity. We used pooled cross-sectional data from 8 observational studies conducted between 1997 and 2007 that consisted of 10,793 youth (boys: 47%) aged 6-18 y from the International Children's Accelerometry Database. Birth weight was measured in hospitals or maternally reported, sedentary time was assessed by using accelerometry (<100 counts/min), and abdominal adiposity (waist circumference) was measured according to WHO procedures. A mediation analysis with bootstrapping was used to analyze data. The mean (±SD) time spent sedentary was 370 ± 91 min/d. Birth weight was positively associated with sedentary time (B = 4.04, P = 0.006) and waist circumference (B = 1.59, P < 0.001), whereas waist circumference was positively associated with sedentary time (B = 0.82, P < 0.001). Results of the mediation analysis showed a significant indirect effect of birth weight on sedentary time through waist circumference (B: 1.30; 95% bias-corrected CI: 0.94, 1.72), and when waist circumference was controlled for, the effect of birth weight on sedentary time was attenuated by 32% (B = 2.74, P = 0.06). The association between birth weight and sedentary time appears partially mediated by central adiposity, suggesting that both birth weight and abdominal adiposity may be correlates of sedentary time in youth.

The aim of this study was to systematically compare postprandial insulin responses to isoenergetic 1000-kJ (240-kcal) portions of several common foods. Correlations with nutrient content were determined. Thirty-eight foods separated into six food categories (fruit, bakery products, snacks, carbohydrate-rich foods, protein-rich foods, and breakfast cereals) were fed to groups of 11-13 healthy subjects. Finger-prick blood samples were obtained every 15 min over 120 min. An insulin score was calculated from the area under the insulin response curve for each food with use of white bread as the reference food (score = 100%). Significant differences in insulin score were found both within and among the food categories and also among foods containing a similar amount of carbohydrate. Overall, glucose and insulin scores were highly correlated (r = 0.70, P < 0.001, n = 38). However, protein-rich foods and bakery products (rich in fat and refined carbohydrate) elicited insulin responses that were disproportionately higher than their glycemic responses. Total carbohydrate (r = 0.39, P < 0.05, n = 36) and sugar (r = 0.36, P < 0.05, n = 36) contents were positively related to the mean insulin scores, whereas fat (r = -0.27, NS, n = 36) and protein (r = -0.24, NS, n = 38) contents were negatively related. Consideration of insulin scores may be relevant to the dietary management and pathogenesis of non-insulin-dependent diabetes mellitus and hyperlipidemia and may help increase the accuracy of estimating preprandial insulin requirements.

The glycemic index (GI) characterizes foods by using the incremental area under the glycemic response curve relative to a similar amount of oral glucose. Its ability to differentiate between curves of different shapes, the peak response, and other aspects of the glycemic response is debatable. The objective was to explore the association between a food's GI and the shape of the curve in healthy individuals. A large database of 1,126 foods tested by standardized GI methodology in 8-12 healthy subjects was analyzed systematically. Each food's absolute and incremental blood glucose concentrations were compared at individual time points with the GI. The average curve was generated for low-GI (< or = 55), medium-GI (56-69), and high-GI (> or = 70) foods within major food categories. The GI of individual foods was found to correlate strongly with the incremental and actual peak (Spearman's correlations of r = 0.76 and r = 0.73, respectively), incremental and actual glucose concentration at 60 min (r = 0.70 and r = 0.66, respectively), and maximum amplitude of glucose excursion (r = 0.68) (all P < 0.001). In contrast, there was only a weak correlation between the food's GI and the 120-min glucose concentration (incremental r = 0.20, P < 0.001; absolute r = 0.16, P < 0.001). Within food groups, the mean GI, 30- and 60-min glucose concentrations, and maximum amplitude of glucose excursion varied significantly for foods classified as having a low, medium, or high GI (P < 0.001). The GI provides a good summary of postprandial glycemia. It predicts the peak (or near peak) response, the maximum glucose fluctuation, and other attributes of the response curve.

Background: The effects of vitamin D supplementation in healthy prepubertal children on physiologic outcomes have not been investigated. Objective: The objective was to evaluate the effects of supplementation with 1000 IU vitamin D(3)/d on calcium absorption. Design: In a double-blind, placebo-controlled trial, we randomly assigned 64 children to 1000 IU vitamin D(3)/d (n = 32) or placebo (n = 32) for 8 wk. Stable isotopes were used to assess calcium absorption. The main outcome measure was calcium absorption before and after supplementation. Results: All of the data are shown as means ± SDs. At baseline, vitamin D intake was 221 ± 79 IU/d and calcium intake was 830 ± 197 mg/d. Baseline serum 25-hydroxyvitamin D [25(OH)D] was not significantly correlated with fractional or total calcium absorption. After 8 wk, with baseline values used as a covariate, no differences were seen in fractional or total calcium absorption based on supplementation group (P = 0.75 and 0.36, respectively). Supplemented children had a significant increase in 25(OH)D concentrations (from 27.7 ± 7.4 to 36.0 ± 10.3 ng/mL; P < 0.0001) and a decrease in parathyroid hormone (from 21.4 ± 10.4 to 12.9 ± 7.1 pg/mL; P < 0.001); no significant changes in the placebo group were observed. No adverse side effects were noted in either group. Conclusions: Vitamin D(3) supplementation at 1000 IU/d increases 25(OH)D and decreases parathyroid hormone in children with average vitamin D intakes below the dietary recommendations of the Institute of Medicine. However, no significant effects of this change on calcium absorption occurred. This trial was registered at clinicaltrials.gov as NCT 00868738.

The mechanism by which TPGS (alpha-tocopheryl succinate esterified to polyethylene glycol 1000 [PEG 1000]) delivers tocopherol (vitamin E) was studied in human fibroblasts and erythrocytes and a human intestinal cell line, Caco-2. The total cellular tocopherol content of saponified samples of fibroblasts or Caco-2 incubated for 4 h with TPGS (4 mumol/L) increased 10-fold without an increase in the free tocopherol content of nonsaponified samples. A 24-h incubation resulted in a free tocopherol content of approximately 20%, suggesting that intracellular hydrolysis of ester bonds had occurred. The increase in total tocopherol content after a 4-h incubation with TPGS was temperature dependent; no change was measurable at 4 degrees C. Addition of metabolic inhibitors during incubation with TPGS at 37 degrees C did not prevent the increase. [14C]TPGS (synthesized from [14C]PEG 1000) was taken up by Caco-2 cells but [14C]PEG 1000 was not. The intracellular total tocopherol (pmol) equaled the [14C]TPGS (pmol), unequivocally demonstrating uptake of the intact TPGS molecule.