Food fortification for bone health in adulthood: a scoping review.

Food fortification can deliver essential micronutrients to large population segments without modifications in consumption pattern, suggesting that fortified foods may be formulated for populations at risk for fragility fractures. This scoping review determined the extent to which randomized controlled studies have been carried out to test the impact of fortified foods on bone outcomes, searching PubMed for all studies using the terms 'fortified AND bone', and 'fortification AND bone'. Studies were restricted to English language, published between 1996 and June 2015. From 360 articles, 24 studies met the following criteria: human study in adults ⩾18 years (excluding pregnancy or lactation); original study of a fortified food over time, with specific bone outcomes measured pre- and post intervention. Six studies involved adults <50 years; 18 involved adults ⩾50 years. Singly or in combination, 17 studies included calcium and 16 included vitamin D. There were 1 or 2 studies involving either vitamin K, magnesium, iron, zinc, B-vitamins, inulin or isoflavones. For adults <50 years, the four studies involving calcium or vitamin D showed a beneficial effect on bone remodeling. For adults ⩾50 years, n=14 provided calcium and/or vitamin D, and there was a significant bone turnover reduction. No consistent effects were reported in studies in which addition of vitamin K, folic acid or isoflavone was assessed. Results from this scoping review indicate that up to now most studies of fortification with bone health have evaluated calcium and/or vitamin D and that these nutrients show beneficial effects on bone remodeling.

Vitamin D metabolism, functions and needs: from science to health claims.

BACKGROUND: Vitamin D is a nutrient long considered as essential for skeletal health but is now attracting interest from medical and nutritional communities as knowledge emerges of its biological function and its association with decreased risk of many chronic diseases. RESULTS: A question emerges: How much more vitamin D do we need for these new functions of vitamin D? This review discusses vitamin D physiology and hypovitaminosis D and presents two vitamin D dietary policies: that according to regulatory authorities and that of nutrition scientists. Scientific evidence suggests that 25(OH)D serum levels should be over 75 nmol/L; otherwise, there is no beneficial effect of vitamin D on long-latency diseases. Current regulatory authority recommendations are insufficient to reach this level of adequacy. Observational and some prospective data show that vitamin D has a role in the prevention of cancer as well as immunity, diabetes and cardiovascular and muscle disorders, which supports the actions of 1α,25(OH)2D at cellular and molecular levels. The recent assessments done by the European Food Safety Authority should lead to new health claims. CONCLUSIONS: Vitamin D, through food fortification and supplementation, is a promising new health strategy and thus provides opportunities for food industry and nutrition researchers to work together towards determining how to achieve this potential health benefit.

Pharmacokinetics of acetyl-L-carnitine given in single or multiple doses to HIV-1 Infected patients with toxic peripheral polyneuropathy.

The use of nucleoside reverse transcriptase inhibitors in the treatment of HIV infection is associated with antiretroviral toxic polyneuropathy (ATN). Previous studies suggest that long term treatment with Acetyl-L-carnitine (ALCAR) 1.5 gram twice daily improves symptoms and promotes nerve regeneration. It is unknown whether the drug's pharmacokinetic profile would allow for a once daily administration. Twenty three HIV-1 infected subjects taking ALCAR for ATN were enrolled in a cross over trial and switched from twice to once daily dosing. Their regimen was changed from 1.5 g twice daily to 1g (4 patients), 2g (7), and 3g (12) once daily, respectively. Twelve healthy volunteers served as control. Plasma levels of ALCAR and its metabolite L-carnitine were measured. Patients receiving ALCAR had higher pre-dose levels than control subjects. Post dose levels were not significantly higher than pre dose levels in any treatment group. The pre / post dose ALCAR concentrations were 7.6 / 7.7, 7.1 / 6.8, 7.7 / 6.8, and 7.1 / 7.5 micromol/l for 1.5 g twice daily, 1g once daily, 2g once daily, and 3g once daily, respectively. All values were significantly higher than the mean concentration in the control group (4.3 micromol/l). For ALCAR and L-carnitine, measurements for once daily regimens did not differ from the twice daily regimen. Once daily dosing of ALCAR can achieve similar plasma levels as twice daily dosing but intra-mitochondrial levels remain unknown. The pharmacokinetic profile of orally administered ALCAR is complex and likely to be highly affected by endogenous concentrations.

Vitamin D status and its association with parathyroid hormone concentrations in women of child-bearing age living in Jakarta and Kuala Lumpur.

OBJECTIVE: To describe the vitamin D status of women living in two Asian cities,--Jakarta (6 degrees S) and Kuala-Lumpur (2 degrees N), to examine the association between plasma 25-hydroxyvitamin D and parathyroid hormone (PTH) concentrations, and to determine a threshold for plasma 25-hydroxyvitamin D above which there is no further suppression of PTH. Also, to determine whether dietary calcium intake influences the relationship between PTH and 25-hydroxyvitamin D. DESIGN: Cross-sectional. SETTING: Jakarta, Indonesia and Kuala Lumpur, Malaysia. PARTICIPANTS: A convenience sample of 504 non-pregnant women 18-40 years. MAIN MEASURES: Plasma 25-hydroxyvitamin D and PTH. RESULTS: The mean 25-hydroxyvitamin D concentration was 48 nmol/l. Less than 1% of women had a 25-hydroxyvitamin D concentration indicative of vitamin D deficiency (<17.5 nmol/l); whereas, over 60% of women had a 25-hydroxyvitamin D concentration indicative of insufficiency (<50 nmol/l). We estimate that 52 nmol/l was the threshold concentration for plasma 25-hydroxyvitamin D above which no further suppression of PTH occurred. Below and above this concentration the slopes of the regression lines were -0.18 (different from 0; P=0.003) and -0.01 (P=0.775), respectively. The relation between vitamin D status and parathyroid hormone concentration did not differ between women with low, medium or high calcium intakes (P=0.611); however, even in the highest tertile of calcium intake, mean calcium intake was only 657 mg/d. CONCLUSION: On the basis of maximal suppression of PTH we estimate an optimal 25-hydroxyvitamin D concentration of approximately 50 nmol/l. Many women had a 25-hydroxyvitamin D below this concentration and may benefit from improved vitamin D status.

Total calcium intake is associated with cortical bone mineral density in a cohort of postmenopausal women not taking estrogen.

BACKGROUND: The optimal intake of calcium and vitamin D for postmenopausal women not taking estrogen is not known. Further, there are indications that excess vitamin A as retinol might be detrimental to bone. OBJECTIVE: We determined whether dietary intakes of calcium and vitamin D were important for maintaining cortical and trabecular bone mineral density (BMD). We also determined whether nutrient supplements increased retinol intake to a level that would reduce BMD. DESIGN: This was a cross-sectional study of 58 women, age 45-75 years. Dietary intakes and lifestyle factors were assessed by retrospective questionnaires. BMD at the whole body, lumbar spine, and proximal femur (including neck, trochanter, and Wards) was measured using dual energy x-ray absorptiometry (DXA) bone densitometry. RESULTS: There were significant (p < 0.05) positive correlations between total calcium intake and BMD at all sites except spine. At the trochanter, the correlation between total vitamin D and BMD was significant while that between total retinol and BMD showed a trend (p < 0.10). In a stepwise multiple regression, a significant proportion of variance of BMD was accounted for by years since menopause (8.0 to 36.2 %) and body weight (14.5 to 27.1%) at most bone sites. Adding total calcium intake (food + supplements) into the model further accounted for a significant proportion of variance of BMD at cortical bone sites such as hip, femoral neck, Wards, and total body ( 5.2 - 8.4 %). There was no dietary calcium effect on BMD at the spine. CONCLUSION: The positive effect of total calcium intake on cortical BMD of postmenopausal women not taking estrogen suggests that supplemental calcium use is critical for maintaining bone mass. Increased retinol intake from nutrient supplements had no adverse effect on BMD.

The effect of strength training combined with bisphosphonate (etidronate) therapy on bone mineral, lean tissue, and fat mass in postmenopausal women.

The combined and separate effects of exercise training and bisphosphonate (etidronate) therapy on bone mineral in postmenopausal women were compared. Forty-eight postmenopausal women were randomly assigned (double blind) to groups that took intermittent cyclical etidronate; performed strength training (3 d/week) and received matched placebo; combined strength training with etidronate; or took placebo and served as nonexercising controls. Bone mineral, lean tissue, and fat mass were assessed by dual-energy X-ray absorptiometry before and after 12 months of intervention. After removal of outlier results, changes in bone mineral density (BMD) of the lumbar spine and bone mineral content (BMC) of the whole body were greater in the subjects given etidronate (+2.5 and +1.4%, respectively) compared with placebo (-0.32 and 0%, respectively) (p < 0.05), while exercise had no effect. There was no effect of etidronate or exercise on the proximal femur and there was no interaction between exercise and etidronate at any bone site. Exercise training resulted in significantly greater increases in muscular strength and lean tissue mass and greater loss of fat mass compared with controls. We conclude that etidronate significantly increases lumbar spine BMD and whole-body BMC and that strength training has no additional effect. Strength training favourably affects body composition and muscular strength, which may be important for prevention of falls.

Self-reported calcium intake and bone mineral content in children and adolescents.

OBJECTIVE: We examined the relationship between self-reported calcium (Ca) intake and bone mineral content (BMC) in children and adolescents. We hypothesized that an expression of Ca adjusted for energy intake (EI), i.e., Ca density, would be a better predictor of BMC than unadjusted Ca because of underreporting of EI. METHODS: Data were obtained on dietary intakes (repeated 24-hour recalls) and BMC (by DEXA) in a cross-section of 227 children aged 8 to 17 years. Bivariate and multivariate analyses were used to examine the relationship between Ca. Ca density, and the dependent variables total body BMC and lumbar spine BMC. Covariates included were height, weight, bone area. maturity age, activity score and EI. RESULTS: Reported EI compared to estimated basal metabolic rate suggested underreporting of EI. Total body and lumbar spine BMC were significantly associated with EI, but not Ca or Ca density, in bivariate analyses. After controlling for size and maturity, multiple linear regression analysis revealed unadjusted Ca to be a predictor of BMC in males in the total body (p = 0.08) and lumbar spine (p = 0.01)). Unadjusted Ca was not a predictor of BMC at either site in females. Ca density was not a better predictor of BMC at either site in males or females. CONCLUSIONS: The relationship observed in male adolescents in this study between Ca intake and BMC is similar to that seen in clinical trials. Ca density did not enable us to see a relationship between Ca intake and BMC in females, which may reflect systematic reporting errors or that diet is not a limiting factor in this group of healthy adolescents.

Public attitudes towards badger culling to control bovine tuberculosis in cattle.

In 1999, a questionnaire survey was conducted to evaluate public preferences towards badger culling to control bovine tuberculosis in cattle. Three alternative treatments were considered: (1) widespread culling, (2) the current experimental trials, and (3) no culling. One hundred residents from Glastonbury and York were interviewed in person and asked to give preference ratings to each of the three treatments. The single most preferred treatment was no culling, and the least preferred was the widespread cull. Respondents who favoured either the widespread cull or the experimental trials tended to be more knowledgeable about the problem and cited the level of tuberculosis in cattle as the primary factor guiding their preferences. Respondents who favoured the no culling option tended to be less knowledgeable, and cited the conservation and welfare impacts on badger populations as the most important factors. Analysis of the distribution of preference scores suggested that although it was not necessarily the most preferred treatment the experimental trial may be a relatively acceptable alternative.

Low nutrient intake contributes to adverse clinical outcomes in hospitalized elderly patients.

A prospective cohort study on hospitalized elderly patients revealed that inadequate nutrient intake during hospitalization was associated with adverse clinical outcomes and increased morbidity. Because this occurred in patients who were initially assessed as being in good health, it emphasizes the need for continuous nutritional surveillance of hospitalized elderly patients.

Excess retinol intake may explain the high incidence of osteoporosis in northern Europe.

An epidemiologic study of postmenopausal women in Sweden revealed that a chronic excess of retinol intake (> 1.5 mg/day) decreased bone mineral density and increased hip fracture risk. These data provide one explanation for the higher incidence of osteoporosis in Sweden and Norway compared with other European countries. Retinol in fortified milk could explain also the association of high calcium intake and hip fracture incidence in northern Europe because milk is an important source of both nutrients.

Assessing the changing diet of indigenous peoples.

Because a dietary transition is occurring among indigenous populations from traditional foods to more market (store-bought) foods, there are concerns about a rise in diet-related chronic disease. More research into dietary intakes of indigenous peoples is needed. When the use of longitudinal studies is not possible, the use of cross-sectional data to characterize the process of dietary change appears to be an appropriate way to assess change during rapid transition.

Underreporting of energy intake, socioeconomic status, and expression of nutrient intake.

The relationship between socioeconomic status and nutrient intake was examined in a recent study. The investigators used three different expressions of nutrient intake in an attempt to overcome the confounding effect of underreporting on interpretation of dietary intake data. Biologic validation attempts were inconclusive as to which expression yielded the most accurate results.

Calciuric effects of short-term dietary loading of protein, sodium chloride and potassium citrate in prepubescent girls.

OBJECTIVE: Studies using adult human subjects indicate that dietary protein and sodium chloride have negative effects on the retention of calcium by increasing urinary calcium excretion, while alkaline potassium improves calcium retention along with decreasing urinary calcium losses. This study investigated the effect of these dietary factors on acute urinary calcium excretion in 14 prepubescent girls age 6.7 to 10.0 years. METHODS: Subjects provided a fasting urine sample then consumed a meal containing one of five treatments: moderate protein (MP) providing 11.8 g protein, moderate protein plus 26 mmol sodium chloride (MP+Na), high protein (HP) providing 28.8 g protein, high protein plus 26 mmol sodium chloride (HP+Na), or high protein plus 32 mmol potassium as tripotassium citrate (HP+K). Urine was collected at 1.5 and 3.0 hours after the meal. Supplemental protein was given as 80:20 casein:lactalbumin. Test meals were isocaloric, and unless intentionally altered, components of interest except phosphate were equal between treatments. Each subject completed all five treatments. RESULTS: Urinary calcium excretion rose after the meal, peaking at 1.5 hours. There were no significant differences in calcium excretion between treatments at any time point. The high protein treatments did not result in a significant increase in either net acid or sulfate excretion at 1.5 hours compared to moderate protein. Dietary sodium chloride had no effect on urinary sodium or calcium excretion over the 3 hours. After the potassium treatment, sodium excretion increased (p< or =0.002) and net acid excretion decreased (p<0.001) compared to other treatments at 1.5 hours. CONCLUSIONS: In children, a simultaneous increase in protein and phosphorus due to increased milk protein intake did not increase acute urinary calcium excretion. An effect of dietary sodium chloride on acute urinary calcium excretion was not observed. Both these findings were similar to those of adult studies previously conducted in the same laboratory using similar format and treatments. Potassium citrate was not hypocalciuric in children, a response differing from that for adults, who have shown a decrease in acute urinary calcium excretion in response to alkaline potassium treatment. Further characterization of calciuric responses to dietary factors is required for children, who may differ from adults in many respects.

Effect of calcium supplementation is greater in prepubertal girls with low calcium intake.

In a recent calcium supplementation trial, prepubertal girls with spontaneous calcium intake below 900 mg/day, when given additional calcium, had greater increases in bone mineral density than other girls. This lends support to the recently recommended Adequate Intake (AI) of 1300 mg/day calcium for American and Canadian children, although more studies on long-term effects of this intake level are still needed.

Calciuric effects of protein and potassium bicarbonate but not of sodium chloride or phosphate can be detected acutely in adult women and men.

An acute load test was used to test the influence of dietary factors on urinary calcium excretion. In study 1, 10 fasting premenopausal women consumed test meals providing a moderate amount of protein (MP; 23 g), MP plus 23 mmol KHCO3 (MP+K), MP plus 23 mmol NaCl (MP+Na), and a high amount of protein (HP; 53 g), HP plus 70 mmol KHCO3 (HP+K), and HP plus 70 mmol NaCl (HP+Na). Protein was casein:lactalbumin (80:20), except for the treatments with added sodium chloride, to which only casein was added. In study 2, the effects of HP and HP plus 50 mmol KHCO3 (HP+K) were compared with those of MP or MP plus 7.5 mmol phosphate (MP+Pi), equaling the additional phosphate of HP, in 10 adult men. Subjects completed all treatments in random order. In study 1, the peak of calcium excretion was at 3 h for all treatments, except for HP+K, which indicated an acute hypocalciuric effect of potassium. Unexpectedly, there was no hypercalciuric effect of adding sodium chloride, nor was urine sodium increased. In study 2, calcium excretion was significantly higher with HP than with MP+Pi but not with MP at 3 h, indicating an acute hypercalciuric effect of protein alone. A hypocalciuric effect of potassium (HP+K compared with HP) but not of phosphate (MP compared with MP+Pi) was seen. An acute load test measuring changes 3 h postload was appropriate for examining the calciuric effects of protein and potassium bicarbonate, but not those of sodium chloride or phosphate in adults.

Calcium supplementation.

Calcium is necessary for the prevention and treatment of diseases such as osteoporosis, hypertension, and, possibly, colon cancer. Supplementation is useful when dietary calcium intake is low, as is the current situation in North America. There are many factors to consider before recommending any one form of supplement. A consideration for calcium carbonate tablets is whether the tablet disintegrates and whether or not a lack of food or acid in the stomach will hinder utilization. Other forms of calcium, particularly the chelated calcium salts, are better absorbed in fasting achlorhydric subjects but have less calcium per gram of supplement. Interaction of calcium with other mineral nutrients and the presence of contaminating metals has focused attention on safety. Based on present evidence, chelated calcium and refined calcium carbonate tablets (including those labeled as antacids) may be safely and effectively ingested by most people at doses generally recommended for treatment or prevention of osteoporosis. One should not exceed 2,000 mg of calcium, except at the advice of their health care provider, as inadvertent mineral deficiencies may arise. Persons at risk for developing milk-alkali syndrome, such as thiazide users and persons with renal failure, should be identified and monitored for alkalosis and hypercalcemia when using calcium supplements.

Adverse effects of high-calcium diets in humans.

While the National Institutes of Health Consensus Conference on Calcium has recommended that all elderly persons need calcium intakes of 1500 mg/day, it also recognizes that adverse effects of high-calcium diets may occur at intakes greater than 2000 mg/day. The purpose of this paper is to highlight adverse effects of high-calcium diets that could have a negative impact on health.

Dietary salt, urinary calcium, and kidney stone risk.

Both salt-loading studies and reports of free-living populations find that urinary calcium excretion increases approximately 1 mmol (40 mg) for each 100 mmol (2300 mg) increase in dietary sodium in normal adults. Renal calcium stone-formers with hypercalciuria appear to have greater proportional increases in urinary calcium (approximately 2 mmol) per 100 mmol increase in salt intake. Thus, reduction of dietary NaCl may be a useful strategy to decrease the risk of forming calcium-containing kidney stones.

The inhibitory effect of dietary calcium on iron bioavailability: a cause for concern?

Increased intake of calcium has been recently recommended by a National Institutes of Health (NIH) Consensus Development Panel on Optimal Calcium Intake. However, high intakes of dietary calcium can inhibit iron absorption if both are present in the same meal. The mechanism for the calcium-iron interaction is not known. A recent study has demonstrated that separating foods high in calcium from meals high in iron can prevent some of the calcium-induced inhibition of iron absorption. The feasibility of changing the nature of meals or the timing of calcium supplementation to adjust for this phenomenon is untested.