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Biomedical subjects

Robert P Heaney

Publications and source records attributed to Robert P Heaney.

At least 19 recordsLinked to original sources

The case for improving vitamin D status.

Evidence from both physiological experiments and randomized trials demonstrates that elevating vitamin D status above levels prevailing in the North American and European adult populations improves calcium absorption and reduces fall risk and osteoporotic fractures. Additionally observational data suggest that raising vitamin D status protects against various cancers and autoimmune disorders as well. Hence a strong case can be made for immediate improvement in vitamin D status of the general population.

Diet↗

Bone health.

Much evidence indicates that both calcium and vitamin D are efficacious in protecting the skeleton, particularly when these 2 nutrients are used in combination. Each nutrient is necessary for the full expression of the effect of the other, and where their actions are independent, their effects on skeletal health are complementary. Nutrient status for both tends to be deficient in the adult population of the industrialized nations. Hence, supplementation or food fortification with both nutrients is appropriate and, given contemporary diets and sun exposure, probably necessary. Various meta-analyses, systematic evidence reviews, and controlled trials evaluating these 2 nutrients will be defective if they fail 1) to take into consideration the nearly universal need to augment the status of both nutrients in the populations studied rather than just one or the other, 2) to consider the threshold characteristics of both nutrients, and 3) to use the achieved serum 25-hydroxyvitamin D concentration as the independent variable for vitamin D effects (instead of oral vitamin D intake). Problems with adherence to a regimen of taking supplements daily make an appropriate fortification strategy the preferred option for improving the status of both nutrients.

Bone Density↗

Vitamin D status in a rural postmenopausal female population.

BACKGROUND: Inadequate vitamin D nutritional status is increasingly recognized as common in North American and European populations, but the extent of the shortfall and the parameters of the distribution for populations of interest remain uncertain. PURPOSE: To report the distribution of values for serum 25-hydroxyvitamin D [25(OH)D] in a population of rural postmenopausal women, together with quantification of factors related to vitamin D status. SETTING: Nine largely agrarian counties in eastern Nebraska (approximately 41 degrees N). PARTICIPANTS: A population-based sample of 1,179 women 55 years of age and older recruited into a four-year trial of calcium and vitamin D supplementation. METHODS: Baseline biochemical, dietary, and anthropometric measurements obtained on entry into trial. RESULTS: Serum 25(OH)D concentration at baseline varied cyclically with season, with the solar cycle explaining 2.9% of the total variance (P < 0.001). Mean seasonally adjusted 25(OH)D concentration was 71.1 nmol/L. Serum 25(OH)D also exhibited the expected inverse curvilinear relationship with serum parathyroid hormone (PTH), with the inflection point of the curve located at approximately 80 nmol/L. Supplements containing vitamin D were regularly taken by 59% of the cohort (median dose: 200 IU/d). Nevertheless, approximately 4% of all women had values below the laboratory reference range and more than two-thirds fell below 80 nmol/L. Seasonally adjusted serum 25(OH)D concentration was positively correlated with the size of daily vitamin D supplement dose, and negatively with age, weight, and body mass index (P < 0.01 for all). In stepwise multiple linear regression models, weight, age, and supplement dose were independently correlated with seasonally adjusted serum 25(OH)D, and together explained 19% of the total variance of adjusted 25(OH)D concentration. Women taking supplements had only one-sixth the chance of having a 25(OH)D value below the reference limit of the assay, compared to women who did not use supplements. CONCLUSIONS: Approximately two-thirds of this rural population fell below 80 nmol/L, a value considered to be the lower end of the optimal range. Based on the slope of 25(OH)D on supplement dose observed in these women, it would require an additional vitamin D input of nearly 2000 IU/d to reach the goal of an RDA for vitamin D, i.e., to bring 97.5% of the cohort to levels of 80 nmol/L or higher.

Aged↗

Role of dietary sodium in osteoporosis.

Sodium, in the form of sodium chloride, elevates urinary calcium excretion and, at prevailing calcium intakes, evokes compensatory responses that may lead to increased bone remodeling and bone loss. The calciuria is partly due to salt-induced volume expansion, with an increase in GFR, and partly to competition between sodium and calcium ions in the renal tubule. Potassium intakes in the range of current recommendations actually reduce or prevent sodium chloride-induced calciuria. At calcium intakes at or above currently recommended levels, there appear to be no deleterious effects of prevailing salt intakes on bone or the calcium economy, mainly because adaptive increases in calcium absorption offset the increased urinary loss. Such compensation is likely to be incomplete at low calcium intakes. Limited evidence suggests equivalent bone-sparing effects of either salt restriction or augmented calcium intakes. Given the relative difficulty of the former, and the ancillary benefits of the latter, it would seem that the optimal strategy to protect the skeleton is to ensure adequate calcium and potassium intakes.

Animals↗

Absorbability and utility of calcium in mineral waters.

BACKGROUND: Calcium intake in North America remains substantially below recommended amounts. Bottled waters high in calcium could help close that gap. OBJECTIVES: The objectives were to summarize and integrate published absorbability and biodynamic data concerning high-calcium mineral waters and to combine these data with hitherto unpublished analyses from my laboratory. DESIGN: The usual library database was searched. The absorbability of calcium from a high-mineral water labeled with tracer quantities of (45)Ca was measured in human volunteers as a part of an otherwise low-calcium test meal. Published reports that used differing load sizes and meal conditions were harmonized by making corrections based on published calcium absorbability data. RESULTS: All the high-calcium mineral waters had absorbabilities equal to milk calcium or slightly better. When tested, all produced biodynamic responses indicative of absorption of appreciable quantities of calcium (ie, increased urinary calcium, decreased serum parathyroid hormone, decreased bone resorption biomarkers, and protection of bone mass). CONCLUSION: High-calcium mineral waters could provide useful quantities of bioavailable calcium.

Biological Availability↗

Low calcium intake among African Americans: effects on bones and body weight.

This review was performed to summarize and integrate the evidence relating calcium intake to health status in African Americans, with special attention to bone and fat. Despite lower average calcium intakes, African Americans typically have skeletons more massive than those of whites. This is the result of a relative resistance of the bony resorptive apparatus to parathyroid hormone, which forces better urinary conservation of calcium and, at some life stages, more efficient intestinal calcium absorption as well. This adaptation, however, has other costs and appears to contribute to a greater risk in African Americans for several chronic diseases, including cardiovascular disease and stroke, obesity, and the insulin resistance syndrome. Higher calcium intakes not only support the skeleton in African Americans, just as they do in whites, but reduce the disease burden for other chronic diseases as well.

Adaptation, Physiological↗

Barriers to optimizing vitamin D3 intake for the elderly.

Available data on metabolic utilization of vitamin D3 indicate a total daily requirement of approximately 4000 international units (iu) (100 microg) or twice the current tolerable upper intake level (UL). In young individuals, most of this comes from the skin. However, cutaneous vitamin D3 synthesis declines with age, creating a need for increasing oral intake to maintain optimal serum 25-hydroxyvitamin D [25(OH)D] concentrations. Estimates of the population distribution of serum 25(OH)D values, coupled with available dose-response data, indicate that it would require input of an additional 2600 iu/d (65 microg/d) of oral vitamin D3 to ensure that 97.5% of older women have 25(OH)D values at or above desirable levels. The age-related decline in cutaneous input, taken together with the UL, creates a substantial barrier to the deployment of public health strategies to optimize vitamin D status in the elderly.

Adult↗

Calcium intake and disease prevention.

While the fundamental metabolic function of calcium is to serve as a second messenger, coupling intracellular responses to extracellular signals, nutritional deficiency of calcium is manifested at a higher level of organization: 1) depletion of the calcium nutrient reserve; 2) inadequate complexation of digestive byproducts; and 3) collateral effects of hormones produced primarily to compensate for low calcium intake. The first mechanism contributes to the osteoporosis problem, the second to kidney stones and colon cancer, and the third to hypertension, preeclampsia, obesity, and insulin resistance, among others. Adequate calcium intakes (1000-1500 mg/d) in adults have been shown in controlled trials to lower the risk of osteoporotic fractures, kidney stones, obesity, and hypertension. The best source of calcium is dairy foods, largely because the disorders concerned depend upon multiple nutrients, not just calcium, and dairy provides a broad array of essential nutrients in addition to calcium, and at low cost.

Calcium, Dietary↗

Hospitalization-related bone loss and the protective effect of risedronate.

Intercurrent illness and episodes of hospitalization and surgery are common in an aging population, who, at the same time, are experiencing age-related bone loss. The objective was to test the hypotheses (1) that intercurrent illness severe enough to require hospitalization produces clinically important bone loss, and (2) that antiresorptive therapy will reduce that loss. The study was a retrospective analysis of bone mineral density (BMD) change at hip and spine in subjects of the risedronate postmenopausal osteoporosis phase III trials experiencing serious adverse events (SAEs). Subjects were 243 hospitalized for non-skin cancers, pneumonia, myocardial infarction, cerebrovascular accident, gallbladder disease, and pancreatitis, on whom BMD data were available both before and after the SAE; and 286 non-hospitalized control subjects matched to those with SAEs by age, height, weight, prevalent fracture, and visit interval. In hospitalized, placebo-treated participants, the annualized percent change in BMD (mean+/-SEM) across the period of hospitalization was -0.65+/-0.39 at lumbar spine, -1.13+/-0.55 at femoral neck, and -2.66+/-0.58 at femoral trochanter; the corresponding values for the non-hospitalized, placebo controls were +0.46+/-0.28, -0.77+/-0.34, and -0.67+/-0.34. These values were more negative at all three sites for the hospitalized subjects, and significantly so at lumbar spine and femoral trochanter (P=0.019 and 0.002, respectively). By contrast, in the risedronate-treated participants, all sites exhibited bone gain and there was no significant difference between hospitalized and non-hospitalized participants. Intercurrent illness resulting in hospitalization produced a rapid bone loss across the period of illness comparable in magnitude to documented age-related loss. Risedronate in a dose of 5 mg/day effectively abolished this loss.

Aged↗

The Vitamin D requirement in health and disease.

Advances in Vitamin D nutritional physiology since publication of the DRIs in 1997 are briefly summarized. Available data indicate that (1) Vitamin D's canonical function, optimizing intestinal calcium absorption, is fully expressed at serum 25-hydroxyvitamin D (25OHD) concentration of approximately 80nmol/L; (2) elevated parathyroid activity, typical of aging populations, is minimized at the same 25OHD value and (3) osteoporotic fractures are reduced when serum 25OHD is raised to near 80nmol/L. Depending upon starting value, achieving 25OHD concentrations of 80 or higher may require a daily oral intake of 2200IU (55microg) or more in addition to prevailing cutaneous inputs. The tolerable upper intake level (TUIL), currently set at 2000IU (50microg)/day, is too low to permit optimization of Vitamin D status in the general population. Actual toxicity is not seen below serum 25OHD values of 250nmol/L, a value that would be produced only at continuing oral intakes in excess of 10,000IU (250microg)/day.

Disease↗

Calcium absorptive efficiency is positively related to body size.

BACKGROUND: Calcium absorption efficiency is a more important determinant of calcium balance than calcium intake itself. The sources of variability in absorptive performance are only partly elucidated. PURPOSE: The aim of the study was to explore the relationship between body size and calcium absorption efficiency. DESIGN AND SETTING: Metabolic studies were performed on an inpatient metabolic unit in an academic health sciences center. SUBJECTS: One hundred seventy-eight women, with an average age of 50.2 yr, were studied from one to five times and yielded an aggregate data set containing 633 individual studies. METHODS: Calcium absorption fraction was measured by the dual-tracer method. Observed values were expressed as residuals from predicted values for each woman's actual calcium intake, using the previously published relationship between intake and absorption. RESULTS: Absorption residuals were significantly positively correlated with height, weight, and surface area, and after adjusting for estrogen status, these body size variables accounted for approximately 4% of the total variability. CONCLUSION: The magnitude of the effect is such that a woman 1.8 m in height would absorb 30+% more calcium from a given intake than a woman 1.4 m tall.

Absorption↗