Patsy M. Brannon

The 2011 Report on Dietary Reference Intakes for Calcium and Vitamin D from the Institute of Medicine: What Clinicians Need to Know

This article summarizes the new 2011 report on dietary requirements for calcium and vitamin D from the Institute of Medicine (IOM). An IOM Committee charged with determining the population needs for these nutrients in North America conducted a comprehensive review of the evidence for both skeletal and extraskeletal outcomes. The Committee concluded that available scientific evidence supports a key role of calcium and vitamin D in skeletal health, consistent with a cause-and-effect relationship and providing a sound basis for determination of intake requirements. For extraskeletal outcomes, including cancer, cardiovascular disease, diabetes, and autoimmune disorders, the evidence was inconsistent, inconclusive as to causality, and insufficient to inform nutritional requirements. Randomized clinical trial evidence for extraskeletal outcomes was limited and generally uninformative. Based on bone health, Recommended Dietary Allowances (RDAs; covering requirements of ≥97.5% of the population) for calcium range from 700 to 1300 mg/d for life-stage groups at least 1 yr of age. For vitamin D, RDAs of 600 IU/d for ages 1–70 yr and 800 IU/d for ages 71 yr and older, corresponding to a serum 25-hydroxyvitamin D level of at least 20 ng/ml (50 nmol/liter), meet the requirements of at least 97.5% of the population. RDAs for vitamin D were derived based on conditions of minimal sun exposure due to wide variability in vitamin D synthesis from ultraviolet light and the risks of skin cancer. Higher values were not consistently associated with greater benefit, and for some outcomes U-shaped associations were observed, with risks at both low and high levels. The Committee concluded that the prevalence of vitamin D inadequacy in North America has been overestimated. Urgent research and clinical priorities were identified, including reassessment of laboratory ranges for 25-hydroxyvitamin D, to avoid problems of both undertreatment and overtreatment.

IOM Committee Members Respond to Endocrine Society Vitamin D Guideline

In early 2011, a committee convened by the Institute of Medicine issued a report on the Dietary Reference Intakes for calcium and vitamin D. The Endocrine Society Task Force in July 2011 published a guideline for the evaluation, treatment, and prevention of vitamin D deficiency. Although these reports are intended for different purposes, the disagreements concerning the nature of the available data and the resulting conclusions have caused confusion for clinicians, researchers, and the public. In this commentary, members of the Institute of Medicine committee respond to aspects of The Endocrine Society guideline that are not well supported and in need of reconsideration. These concerns focus on target serum 25-hydroxyvitamin D levels, the definition of vitamin D deficiency, and the question of who constitutes a population at risk vs. the general population.

The 2011 Dietary Reference Intakes for Calcium and Vitamin D: What Dietetics Practitioners Need to Know

The Institute of Medicine Committee to Review Dietary Reference Intakes for Calcium and Vitamin D comprehensively reviewed the evidence for both skeletal and nonskeletal health outcomes and concluded that a causal role of calcium and vitamin D in skeletal health provided the necessary basis for the 2011 Estimated Average Requirement (EAR) and Recommended Dietary Allowance (RDA) for ages older than 1 year. For nonskeletal outcomes, including cancer, cardiovascular disease, diabetes, infections, and autoimmune disorders, randomized clinical trials were sparse, and evidence was inconsistent, inconclusive as to causality, and insufficient for Dietary Reference Intake (DRI) development. The EAR and RDA for calcium range from 500 to 1,100 and 700 to 1,300 mg daily, respectively, for ages 1 year and older. For vitamin D (assuming minimal sun exposure), the EAR is 400 IU/day for ages older than 1 year and the RDA is 600 IU/day for ages 1 to 70 years and 800 IU/day for 71 years and older, corresponding to serum 25-hydroxyvitamin D (25OHD) levels of 16 ng/mL (40 nmol/L) for EARs and 20 ng/mL (50 nmol/L) or more for RDAs. Prevalence of vitamin D inadequacy in North America has been overestimated based on serum 25OHD levels corresponding to the EAR and RDA. Higher serum 25OHD levels were not consistently associated with greater benefit, and for some outcomes U-shaped associations with risks at both low and high levels were observed. The Tolerable Upper Intake Level for calcium ranges from 1,000 to 3,000 mg daily, based on calcium excretion or kidney stone formation, and from 1,000 to 4,000 IU daily for vitamin D, based on hypercalcemia adjusted for uncertainty resulting from emerging risk relationships. Urgently needed are evidence-based guidelines to interpret serum 25OHD levels relative to vitamin D status and intervention.

Vitamin D in Pregnancy and Lactation in Humans

Concerns exist about the adequacy of vitamin D in pregnant and lactating women. This review assesses the evidence that maternal vitamin D status influences maternal, fetal, and breast-fed infant bone health; maternal adverse outcomes (preeclampsia, gestational diabetes, obstructed labor, and infectious disease); fetal adverse outcomes (growth, gestational age, and developmental programming); and infant adverse outcomes. The evidence for all of these outcomes is contradictory (except for maternal infectious disease) and lacking causality; thus, it is inconclusive. The 2011 Dietary Reference Intakes for vitamin D and their implications for assessing vitamin D status are discussed. An estimated 5% to 29% of American pregnant women may have inadequate vitamin D status, with the higher prevalence in African Americans. Little is known about the prevalence of inadequacy in American lactating women. Research needs are also identified, especially the need for rigorous and well-designed randomized clinical trials to determine the role of vitamin D in nonbone health outcomes in pregnancy and lactation.

National Institutes of Health Consensus Development Conference: Lactose Intolerance and Health

National Institutes of Health (NIH) consensus and stateof-the-science statements are prepared by independent panels of health professionals and public representatives on the basis of 1) the results of a systematic literature review prepared under contract with the Agency for Healthcare Research and Quality; 2) presentations by investigators working in areas relevant to the conference questions during a 2-day public session; 3) questions and statements from conference attendees during open discussion periods that are part of the public session; and 4) closed deliberations by the panel during the remainder of the second day and morning of the third. This statement is an independent report of the panel and is not a policy statement of the National Institutes of Health or the U.S. government. The following statement is an abridged version of the panel’s report, which is available in full at http: //consensus.nih.gov/2010/lactosestatement.htm. Lactose intolerance is the syndrome of diarrhea, abdominal pain, flatulence, or bloating occurring after lactose ingestion. These symptoms, which are produced by malabsorption of lactose, a sugar found in milk and other dairy products, often cause afflicted individuals to avoid dairy products in their diets. Lactose malabsorption is caused by a decreased ability to digest lactose that is due to a deficiency in the levels of the enzyme lactase. Lactase breaks lactose down into 2 simpler sugars, glucose and galactose, which are readily absorbed into the bloodstream. This enzyme is produced by expression of the lactase‐phlorizin hydrolase gene in the cells lining the small intestine. All infants produce lactase and successfully digest lactose provided by human milk or by infant formulas. However, sometime after weaning, a genetically programmed decrease in lactase (lactase nonpersistence) occurs in most children worldwide. The symptoms of lactose intolerance result from bacterial fermentation of undigested lactose in the colon. Lactose malabsorption can be diagnosed by having individuals ingest a standard dose of lactose after fasting and measuring breath hydrogen; elevated breath hydrogen levels are caused by bacterial fermentation of undigested lactose in the colon. Other diagnostic tools include measuring lactase activity in an intestinal biopsy sample or genetic testing for the common polymorphism that is linked to lactase nonpersistence. The demonstration of lactose malabsorption does not necessarily indicate that an individual will have symptoms. Many variables determine whether a person who malabsorbs lactose develops symptoms, including the dose of lactose ingested, the residual intestinal lactase activity, the ingestion of food along with lactose, the ability of the colonic flora to ferment lactose, and individual sensitivity to the products of lactose fermentation.

Primary cultures of rat pancreatic acinar cells in serum-free medium

SummaryRat pancreatic acinar cells were isolated and cultured in Hams F12 medium with 15% bovine calf serum. Caerulein, insulin, somatostatin, and dexamethasone (DEX) had no effect on intracellular or secreted amylase in these cultured cells. A serum-free medium, using Waymouths MB 752/1 supplemented with albumin, epidermal growth factor (EGF), DEX, and HEPES, was then developed to avoid serum factors that might mask hormonal effects. In this SF medium, pancreatic acinar, cells maintained the morphological and ultrastructural characteristics of freshly isolated cells and secreted amylase in response to the secretagogue, carbamyl choline. Insulin, at a concentration of 1 μg/ml, significantly increased intracellular and secreted amylase activity after 3 d. This model cell system can be used to study the regulation of the synthesis of amylase and other pancreatic enzymes in vitro.

Vitamin D and adverse pregnancy outcomes: beyond bone health and growth.

Concerns exist about adequacy of vitamin D in pregnant women relative to both maternal and fetal adverse health outcomes. Further contributing to these concerns is the prevalence of inadequate and deficient vitamin D status in pregnant women, which ranges from 5 to 84% globally. Although maternal vitamin D metabolism changes during pregnancy, the mechanisms underlying these changes and the role of vitamin D during development are not well understood. Observational evidence links low maternal vitamin D status with an increased risk of non-bone health outcome in the mother (pre-eclampsia, gestational diabetes, obstructed labour and infectious disease), the fetus (gestational duration) and the older offspring (developmental programming of type 1 diabetes, inflammatory and atopic disorders and schizophrenia); but the totality of the evidence is contradictory (except for maternal infectious disease and offspring inflammatory and atopic disorders), lacking causality and, thus, inconclusive. In addition, recent evidence links not only low but also high maternal vitamin D status with increased risk of small-for-gestational age and schizophrenia in the offspring. Rigorous and well-designed randomised clinical trials need to determine whether vitamin D has a causal role in non-bone health outcomes in pregnancy.

A higher maternal choline intake among third-trimester pregnant women lowers placental and circulating concentrations of the antiangiogenic factor fms-like tyrosine kinase-1 (sFLT1)

This study investigated the influence of maternal choline intake on the human placental transcriptome, with a special interest in its role in modulating placental vascular function. Healthy pregnant women (n=26, wk 26–29 gestation) were randomized to 480 mg choline/d, an intake level approximating the adequate intake of 450 mg/d, or 930 mg/d for 12 wk. Maternal blood and placental samples were retrieved at delivery. Whole genome expression microarrays were used to identify placental genes and biological processes impacted by maternal choline intake. Maternal choline intake influenced a wide array of genes (n=166) and biological processes (n=197), including those related to vascular function. Of special interest was the 30% down‐regulation (P=0.05) of the antiangiogenic factor and preeclampsia risk marker fms‐like tyrosine kinase‐1 (sFLT1) in the placenta tissues obtained from the 930 vs. 480 mg/d choline intake group. Similar decreases (P=0.04) were detected in maternal blood sFLT1 protein concentrations. The down‐regulation of sFLT1 by choline treatment was confirmed in a human trophoblast cell culture model and may be related to enhanced acetylcholine signaling. These findings indicate that supplementing the maternal diet with extra choline may improve placental angiogenesis and mitigate some of the pathological antecedents of preeclampsia.—Jiang, X., Bar, H. Y., Yan, J., Jones, S., Brannon, P. M., West, A. A., Perry, C. A., Ganti, A., Pressman, E., Devapatla, S., Vermeylen, F., Wells, M. T., and Caudill, M. A. A higher maternal choline intake among third‐trimester pregnant women lowers placental and circulating concentrations of the antiangiogenic factor fms‐like tyrosine kinase‐1 (sFLT1). FASEB J. 27, 1245–1253 (2013). www.fasebj.org

Key questions in vitamin D research.

Abstract Despite interest and expanding research on non-bone health outcomes, the evidence remains inconclusive concerning the causal role of vitamin D in the non-bone health outcomes. To improve our understanding of its role, research needs to address five key areas related to vitamin D: 1) its physiology and molecular pathways. 2) its relationship to health outcomes. 3) its exposure-response relationships, 4) its interactions with genotype and other nutrients and 5) its adverse effects. Its metabolism needs to be elucidated including extra-renal activation and catabolism, distribution and mobilization from body pools, kinetics of this distribution, and their regulation during pregnancy and lactation. Rigorous, well-designed randomized clinical trials need to evaluate the causal role of vitamin D in a diverse array of non-bone health and chronic disease outcomes across the life cycle and reproductive states. Critically needed is the determination of the exposure-response, inflection and threshold of serum 25(OH)D concentrations relative to functional and health outcomes. The dose-response relationships of standardized measures of serum 25(OH)D need to be understood in response to low and high doses of total vitamin D with careful consideration of confounding factors including catabolic rates. How do relevant genetic polymorphisms, dietary calcium and phosphate and potentially dietary cholesterol interact with vitamin D exposure on its bioavailability, transport, distribution in body pools, metabolism and action as well as on bone and non-bone health outcomes? The nature and mechanisms of U-shaped risk relationships with adverse health outcomes at higher exposure to vitamin D needs elucidated across the life cycle and reproductive stages.

Effect of diet on intestinal and pancreatic enzyme activities in the pig.

Intestinal and pancreatic enzyme activities are known to respond to changes in dietary composition. Studies in rats and humans suggest that adaptive mechanisms differ between species in response to altered intakes of carbohydrate and fat. Because of increased use of the pig in the study of human nutrition, we compared the responses of pancreatic enzymes and intestinal disaccharidases in groups of 7- to 10-week-old pigs fed either high-carbohydrate/low-fat (70 cal% starch, 25% protein, 5% fat) or low-carbohydrate/high-fat (5, 25, 70%, respectively) diets for 7 and 30 days. No changes were observed in the activities for lactase, trypsin, or chymotrypsin or in the tissue protein concentrations, regardless of diet duration. High-carbohydrate/low-fat intake resulted in higher specific activities of sucrase, maltase, and amylase for both periods studied. Low-carbohydrate/high-fat intake resulted in higher specific activities of pancreatic lipase for both periods studied. The response of the intestinal disaccharidases differs from that observed previously in rodents but resembles the response reported in humans. Conversely, amylase and lipase responded similarly to the pattern in the rat. These data support the continued use of the pig as a suitable model in the study of adaptation to altered intakes of carbohydrate and fat.