Impact of supplementation with bicarbonate on lower-extremity muscle performance in older men and women.

UNLABELLED: This study describes the impact of bicarbonate treatment for 3 months on net acid excretion (NAE), nitrogen excretion, and muscle performance in older men and women. Bicarbonate reduced NAE, and the decrement was associated with a decrease in nitrogen excretion. Treatment also improved muscle power and endurance in the women. INTRODUCTION: Bicarbonate enhances muscle performance during strenuous exercise, but its effect on performance during normal activity in older subjects is unknown. METHODS: In this trial, healthy subjects age 50 and older were randomized to 67.5 mmol of bicarbonate or to no bicarbonate daily for 3 months. Changes in lower-extremity muscle power, endurance, urinary nitrogen, and NAE were compared across treatment groups in the 162 participants included in the analyses. RESULTS: In the men and the women, bicarbonate was well tolerated, and as expected, it significantly decreased NAE. The change in NAE correlated with change in nitrogen excretion in women (r = 0.32, P = 0.002) with a similar trend in men (r = 0.23, P = 0.052). In the women, bicarbonate increased double leg press power at 70% one repetition maximum by 13% (P = 0.003) compared with no bicarbonate and improved other performance measures. Treatment with bicarbonate had no significant effect on muscle performance in the men. CONCLUSIONS: Ingestion of bicarbonate decreased nitrogen excretion and improved muscle performance in healthy postmenopausal women. The bicarbonate-induced decline in NAE was associated with reduced nitrogen excretion in both men and women. These findings suggest that bicarbonate merits further evaluation as a safe, low-cost intervention that may attenuate age-related loss of muscle performance and mass in the elderly.

The prevalence of cardiovascular risk factors among elderly Chinese Americans.

In 1981 to 1983, the nutrition and health status of 346 Chinese immigrants in Boston, Mass, aged 60 to 96 years was surveyed and analyzed for cardiovascular risk factors. These elderly Chinese were physically active and seldom obese and consumed a high-carbohydrate (57% of total energy intake), low-fat (24% of total energy intake), low-ascorbic acid (0.62 mmol/d) diet. Current cigarette smoking was common (39%) only in men, while alcoholism was rare in both sexes. Compared with elderly whites, they had lower mean blood pressure and blood levels of total, low-density lipoprotein, and high-density lipoprotein cholesterol, apolipoproteins A-I and B, and ascorbic acid. These characteristics resemble those of the urban population in mainland China, where hemorrhagic stroke is the major cause of cardiovascular mortality.

The role of eating frequency on relative weight in urban school-age children.

BACKGROUND: The role of eating frequency on relative weight in childhood is not well understood. OBJECTIVE: To clarify this relationship by assessing the cross-sectional and prospective relationships of weekday eating frequency with BMI z-score (BMIz) and change in BMIz in a sample of schoolchildren. METHODS: Eating frequency, the average number of reported daily eating occasions, was assessed using two weekday 24-h diet recalls. BMIz was measured at baseline, 6 months and 1 year in 155 urban schoolchildren, ages 9-15 years. Multiple linear regression models were used. RESULTS: Cross-sectional analyses at baseline suggest that BMIz was 0.23 units lower for each additional reported eating occasion (regression coefficient = -0.23; 95% confidence interval [CI]: -0.44, -0.07). From baseline to 6 months, BMIz increased by 0.03 units for each additional reported eating occasion (regression coefficient = 0.03; 95% CI: 0.01, 0.05). This relationship was no longer statistically significant at 1 year (regression coefficient = 0.01; 95% CI: -0.01, 0.03). CONCLUSIONS: The findings suggest that the relationship of eating frequency with BMIz differs from that of change in BMIz. This difference may be due to methodological deficiencies of cross-sectional studies, challenges of dietary assessment or differences in eating patterns among normal and overweight youth. Controlled trials are needed to further clarify this relationship.

Serum ionized calcium, as well as phosphorus and parathyroid hormone, is associated with the plasma 1,25-dihydroxyvitamin D3 concentration in normal postmenopausal women.

Serum parathyroid hormone (PTH) and low-normal serum phosphorus (P) concentrations have well-known trophic effects on renal 1-hydroxylase. A role for serum ionized calcium (Ca2+) in the day-to-day regulation of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] has not been identified in normal humans. The associations between serum Ca2+, PTH, P, and plasma 1,25-(OH)2D3 were evaluated in a cross-sectional study of 275 healthy postmenopausal women. Partial correlations of Ca2+, PTH, and P (each controlled for the other two) with 1,25-(OH)2D3 were sought within quintiles of Ca2+. At low-normal concentrations (less than 1.26 mmol/liter, quintile 1) Ca2+ was inversely correlated with 1,25-(OH)2D3 (rp = -0.30, p = 0.028). At mid-normal concentrations Ca2+ was not significantly correlated with 1,25-(OH)2D3. At high-normal concentrations (greater than 1.32 mmol/liter, quintile 5) Ca2+ attenuated the positive associations of both PTH and low-normal P with 1,25-(OH)2D3. In quintile 5 Ca2+, PTH, and P together accounted for none of the variability in 1,25-(OH)2D3 (R2 = 0.03, p = 0.671). Women with Ca2+ below 1.32 mmol/liter were next examined by quintile of P. As expected, at low-normal concentrations (less than 1.03 mmol/liter, quintile 1) P was significantly correlated with 1,25-(OH)2D3 (rp = -0.32, p = 0.047). The association between PTH and 1,25-(OH)2D3 was statistically significant only at mid-normal concentrations of P (rp = 0.52, p = 0.001, quintile 3). We conclude that Ca2+, along with PTH and P, is associated with the plasma concentration of 1,25-(OH)2D3 in normal postmenopausal women.

Calcium retention and hormone levels in black and white women on high- and low-calcium diets.

Black-white differences in calcium metabolism are sought because they may reveal why blacks have higher bone mass than whites. Comparative studies of calcium absorption in blacks and whites are not available. In this study, we compare fractional calcium retention, an index of calcium absorption, and calcium regulating hormone levels in black and white women on a high-calcium diet and after adaptation to a low-calcium diet. A total of 30 healthy women (15 black and 15 white) had measurements of fractional 47Ca retention and calcium regulating hormone levels after 8 weeks on a 2000 mg calcium diet and, subsequently, after 1, 2, 4, and 8 weeks on a 300 mg calcium diet. By 2 weeks after the diet change, fractional 47Ca retention, parathyroid hormone (PTH), and 1,25-dihydroxyvitamin D [1,25-(OH)2D] had reached a plateau at higher levels, urine calcium at a low level, and serum calcium at the same level (repeated-measures ANOVA). Fractional 47Ca retention, serum calcium, and PTH were similar on both diets in blacks and whites. Blacks had higher levels of 1,25-(OH)2D on both diets (e.g., 125.1 +/- 53.5 SD versus 73.4 +/- 19.0 pmol/liter, P = 0.003 on low-calcium diet) and a greater increase in 1,25-(OH)2D after the diet change (33.9 +/- 30.1 SD versus 11.8 +/- 17.9 pmol/liter, P = 0.021). Serum phosphorus was lower in blacks throughout. For hormone levels and fractional calcium retention to stabilize after a diet change, 2 weeks was needed.(ABSTRACT TRUNCATED AT 250 WORDS)

A multicenter comparison of dual-energy X-ray absorptiometers: in vivo and in vitro measurements of bone mineral content and density.

As part of a multicenter research project, we compared dual-energy X-ray absorptiometry (DXA) instruments at three research centers (sites 1, 2 and 3) to determine both intra- and intersite variability of bone mineral content (BMC), bone mineral density (BMD), and bone area (BA). Scans of the total body and lumbar spine were performed in duplicate on five humans (in vivo), and scans of the total body were performed on two whole body phantoms with artificial skeletons and thickness overlays (in vitro) at all sites over 15 days. The average intrasite variability in two consecutive total body BMD measurements, expressed as a percent difference, was significantly higher in vitro, 1.74 +/- 1.97%, than in vivo, 0.71 +/- 0.38% (p < 0.05). Average intrasite variability of the in vivo lumbar spine BMD was 1.08 +/- 1.12%. The intersite coefficients of variation for all BMD, BMC, and BA measurements were < 2.0%. The total body BMD from site 2 was systematically lower than at sites 1 and 3 both in vivo and in vitro (p < 0.05) with no differences in BMC and BA. Although significant, the total body BMD differences between sites were small (< 1.2%) in vivo compared with in vitro (< 2.6%) and are encouraging for the comparison and pooling of human data from multicenter trials, provided that appropriate standardized cross-calibration and analysis procedures are applied.

Effects of age on energy balance.

The effects of aging on energy requirements and energy balance have been studied by several research groups using the doubly labeled water method. The weight of evidence from these investigations suggests that current recommended dietary allowances underestimate the usual energy needs of adults of all ages, including older adults. In addition, doubly labeled water studies have found a significant negative association between body fatness and energy expenditure for physical activity, and a significant positive association between energy expenditure for physical activity and fat-free mass. Further studies are needed to refine estimates of energy requirements for different population groups and to address the role of physical activity in the prevention and treatment of obesity.

Effect of high-fat and low-fat diets on voluntary energy intake and substrate oxidation: studies in identical twins consuming diets matched for energy density, fiber, and palatability.

There remains controversy over the effects of dietary fat content on voluntary energy intake. Additionally, the question of whether there is a genetic susceptibility to overeating high-fat diets has not been resolved. To address these issues, we designed two diets: a low-fat diet providing approximately 20% of energy as fat and a high-fat diet with approximately 40% of energy as fat. The diets were matched for energy density, fiber, and palatability. In a two-phase, 18-d intervention study, voluntary energy intakes and macronutrient oxidation rates during the fasting and fed states were determined in seven pairs of identical male twins. In contrast with results of previous intervention studies, in which low-fat and high-fat diets were not matched for energy density and other associated variables, we observed no significant difference in voluntary energy intake between the low-fat and high-fat phases, and mean daily intakes were similar (10.3 and 10.7 MJ/d, respectively). Postprandial rates of fat oxidation tended to reflect fat intakes in the two dietary phases, thus helping to explain the lack of a difference in mean energy intakes. There was also a significant twin-pair similarity in differences in energy intakes between dietary phases (P = 0.013). These results suggest that dietary fat content does not have a major influence on voluntary energy intake when dietary variables usually associated with fat are controlled for and that there may be a familial influence on the effects of dietary fat content on energy intake.

Reference data for obesity: 85th and 95th percentiles of body mass index (wt/ht2) and triceps skinfold thickness.

Body mass index (BMI) and triceps skinfold thickness (TSF) are commonly used measures of adiposity in clinical and epidemiologic studies. The 85th and 95th percentiles of BMI and TSF are often used operationally to define obesity and superobesity, respectively. Race-specific and population-based 85th and 95th percentiles of BMI and TSF for people aged 6-74 y were generated from anthropometric data gathered in the National Health and Nutrition Examination Survey 1 (NHANES I). The complex sample design of the survey is reflected in the reference values presented. Racial differences in these extremes of the distribution do not emerge until adulthood. Researchers may choose population-based, race-specific, or age-specific criteria for obesity on the basis of assumptions underlying their specific research questions.

Plasma calcidiol, season, and serum parathyroid hormone concentrations in healthy elderly men and women.

Wintertime declines in vitamin D lead to increased concentrations of parathyroid hormone (PTH) and accelerated bone loss in postmenopausal women. We conducted this study to compare calcidiol (25-hydroxyvitamin D) concentrations of men and women, to examine the influence of season, travel, vitamin D intake, and other variables on these concentrations, and to compare associations between calcidiol and PTH concentrations in elderly men and women. In this cross-sectional study of 182 men and 209 women aged > 65 y, mean calcidiol concentrations were higher in men than in women overall (mean +/- SD: 82.4 +/- 35.8 compared with 68.9 +/- 32.1 nmol/L, P < 0.001). In the subset measured in winter (February-May), plasma calcidiol concentrations were lower and not significantly different in men (59.4 +/- 21.8, n = 52) and women (57.7 +/- 23.4 nmol/L, n = 83). In a multiple-regression model, calcidiol concentrations were positively influenced by wintertime travel (P = 0.012), vitamin D intake (P = 0.002), and time spent outdoors (P = 0.096) and negatively influenced by weight (P < 0.001) and age (P = 0.039). Plasma calcidiol and serum PTH concentrations were inversely related, with PTH rising slowly as calcidiol concentrations declined below 110 nmol/L (95 CI: 60, 168 nmol/L). More than 90% of the men and women had calcidiol concentrations below this value in the wintertime. The high prevalence of lower wintertime calcidiol values may increase risk of bone loss in elderly men and women.

Contributions of vitamin D intake and seasonal sunlight exposure to plasma 25-hydroxyvitamin D concentration in elderly women.

We investigated the contributions (1.00-8.03 micrograms/d, or 40-321 IU/d) of vitamin D intake and seasonal sunlight exposure to plasma 25(OH)D in 59 healthy women aged 70-97 y with a mean total vitamin D intake of 8.58 micrograms/d (343 IU/d). In the summer and winter, each subject had a fasting blood measurement and assessments of vitamin D intake and sunlight exposure. Vitamin D intake was significantly correlated with plasma 25(OH)D in the summer (r = 0.52, P < 0.01) and winter (r = 0.63, P < 0.01). The influence of sunlight exposure measured in the summer on the 25(OH)D concentration was dependent on the vitamin D intake. In subjects with lower vitamin D intakes (1.00-8.03 micrograms/d, or 40-321 IU/d), the wintertime 25(OH)D concentrations of those with low and high sunlight exposure were comparable. In subjects with higher vitamin D intakes (11.15-28.68 micrograms/d, or 446-1147 IU/d), however, the wintertime 25(OH)D concentrations of those with high sunlight exposure were lower than those with lower exposure [63.8 +/- 3.9 and 80.6 +/- 6.7 nmol/L, respectively, P = 0.066; P (intake by exposure interaction) < 0.05]. This suggests that the contribution of vitamin D intake to plasma 25(OH)D concentration may be influenced by sunlight exposure.

Effects of different calcium sources on iron absorption in postmenopausal women.

We measured the effect of calcium from food and supplement sources on whole-body retention of 59Fe in 19 normal postmenopausal women. Each woman received a placebo and 500 mg calcium from a mixed calcium citrate-malate salt (CCM), from orange juice plus CCM, and from milk after a test breakfast meal to which 59Fe had been added. The test meal contained 238 mg calcium. Whole-body countings of 59Fe were performed before and 30 min and 2 wk after each test meal. Retention of 59Fe was 8.3 +/- 1.1% (means +/- SEM) with placebo, 3.4 +/- 0.78% with milk, 6.0 +/- 0.97% with CCM, and 7.4 +/- 1.7% with CCM plus orange juice. When compared with placebo, milk and CCM significantly lowered iron retention (p less than 0.05) whereas CCM plus orange juice did not. The reduction with milk was greater than that with CCM (p less than 0.05) or CCM plus orange juice (p less than 0.05). The differences in the effects of these calcium sources on 59Fe retention may result from their varied contents of citric and ascorbic acids, known enhancers of iron absorption.

A 1-y walking program and increased dietary calcium in postmenopausal women: effects on bone.

The effects of a supervised 1-y walking program and increased dietary calcium (milk supplement, 831 mg/d, vs placebo drink, 41 mg/d) on bones were examined in 36 postmenopausal women (60.2 +/- 6.5 y). Trabecular bone-mineral density (BMD) of the lumbar spine (L1-L3), measured by computed tomography, increased by 0.5% in exercising women (n = 18) and decreased by 7.0% in sedentary women (n = 18; P = 0.02). Femoral-neck BMD measured by dual-photon absorptiometry (DPA) increased by 2.0% in women consuming high dietary calcium (n = 18) and decreased by 1.1% in those on moderate calcium intake (n = 18; P = 0.001). Neither exercise nor dietary calcium had an effect on lumbar spine (L2-L4) measured by DPA, distal radius measured by single-photon absorptiometry, or total body calcium measured by in vivo neutron activation. The varying proportions and rates of turnover of trabecular and cortical bone from one site to another suggest that exercise and high dietary calcium may preferentially alter bone density at different skeletal sites.

A randomized trial of Lactobacillus acidophilus BG2FO4 to treat lactose intolerance.

BACKGROUND: Lactose intolerance is the most common disorder of intestinal carbohydrate digestion. Lactobacillus acidophilus BG2FO4 is a strain of lactobacilli with properties of marked intestinal adherence and high beta-galactosidase activity. OBJECTIVE: This study was designed to determine whether oral feeding of Lactobacillus acidophilus BG2FO4 leads to a lactose-tolerant state. DESIGN: We studied 42 subjects with self-reported lactose intolerance and performed breath-hydrogen tests to determine whether they were lactose maldigesters. Subjects with established lactose maldigestion (n = 24) were invited to be randomly assigned to an omeprazole-treated (hypochlorhydric) group or a non-omeprazole-treated group, but 6 subjects chose not to participate. All randomly assigned subjects (n = 18) ingested Lactobacillus acidophilus BG2FO4 twice per day for 7 d and stool samples were collected. Breath-hydrogen tests were performed and symptom scores were recorded at baseline and after lactobacilli ingestion. RESULTS: Lactose maldigestion was established in 24 of 42 subjects (57%) with self-reported lactose intolerance. In 18 lactose-maldigesting subjects, overall hydrogen production and symptom scores after ingestion of Lactobacillus acidophilus BG2FO4 were not significantly different from baseline values. Live Lactobacillus acidophilus BG2FO4 was recovered in stool samples from 7 subjects. CONCLUSIONS: Lactose intolerance is overreported in subjects with gastrointestinal symptoms after lactose ingestion. Treatment of lactose-maldigesting subjects with and without hypochlorhydria with Lactobacillus acidophilus BG2FO4 for 7 d failed to change breath-hydrogen excretion significantly after lactose ingestion.

Phylloquinone in plasma from elderly and young adults: factors influencing its concentration.

Fasting plasma phylloquinone concentrations were determined by reverse-phase high-performance liquid chromatography in a population of young (n = 131) and elderly (n = 195) human subjects. The distribution of values was non-Gaussian but was converted to Gaussian form after a logarithmic transformation of the data. The normal range derived from the lognormal distribution was 0.29-2.64 nmol/L (geometric means = 0.87 nmol/L, median = 0.86 nmol/L). Young females had significantly decreased plasma phylloquinone concentrations when compared with the elderly females whereas concentrations in young males were slightly higher than those in elderly males. A regression model was constructed and revealed that plasma phylloquinone concentrations were positively correlated with plasma triglycerides and alpha-tocopherol. Although the elderly subjects (means = 1.05 nmol/L) had higher levels of phylloquinone than the young subjects (0.94 nmol/L), when the concentration of phylloquinone in plasma is expressed as nanomoles phylloquinone per millimole of triglyceride, the elderly subjects (0.62 x 10(-6) showed decreased levels for phylloquinone compared with the young subjects (0.82 x 10(-6) (p less than 0.001).

Increased protein requirements in elderly people: new data and retrospective reassessments.

Dietary protein requirements of elderly people were determined by short-term nitrogen-balance techniques and using calculations recommended by the 1985 Joint FAO/WHO/UNU Expert Consultation. Twelve men and women aged 56-80 y were randomly assigned to groups that consumed either 0.80 +/- 0.01 or 1.62 +/- 0.02 g protein.kg-1.d-1 (mean +/- SEM). Net nitrogen balance was negative for the lower-protein group (-4.6 +/- 3.4 mg N.kg-1.d-1) and positive for the higher-protein group (13.6 +/- 1.0 mg N.kg-1.d-1); the intake required for nitrogen equilibrium was estimated to be 1.00 g.kg-1.d-1. Nitrogen-balance data from three previous protein requirement studies in elderly people were recalculated by using the same balance formula and combined with the current study data to provide an overall weighted mean protein requirement estimate of 0.91 +/- 0.043 g.kg-1.d-1. Together, the current and retrospective nitrogen-balance data suggest that the mean protein requirement in elderly adults is considerably greater than the 0.60 g.kg-1.d-1 established by the 1985 Joint FAO/WHO/UNU Expert Consultation. A safe protein intake for elderly adults would be 1.0-1.25 g.kg-1.d-1 of high-quality protein.

Protein turnover and energy metabolism of elderly women fed a low-protein diet.

The metabolic mechanisms of accommodation to a low-protein diet in elderly women were studied. Diets containing 1.47 (low) or 2.94 (adequate) g protein.kg body cell mass-1.d-1 (0.45 or 0.92 g.kg body weight-1.d-1, respectively) were fed for 10 wk. Fed state leucine kinetics, fasted and fed metabolic rate, and acute-phase responses to a bout of exercise were measured. Leucine uptake into protein, breakdown, and acute-phase responses were not significantly different within or between diet groups. In the low-protein group, leucine flux and oxidation were lower after 3 wk and oxidation continued to decrease throughout the 10-wk study. When expressed per body cell mass, metabolic rate increased over time in the low-protein group only. Leucine oxidation was a more sensitive index of the adequacy of protein intake than synthesis, flux, metabolic rate, or acute-phase response.

Effect of withdrawal of calcium and vitamin D supplements on bone mass in elderly men and women.

BACKGROUND: Supplementation with calcium and vitamin D reduces bone loss and prevents fractures in elderly people, but it is not known whether any lasting benefit remains if the supplements are discontinued. OBJECTIVE: The objective was to determine whether gains in bone mineral density (BMD) induced by calcium and vitamin D supplementation persist after supplement withdrawal. DESIGN: Two-hundred ninety-five healthy, elderly men and women (aged >/=68 y) who had completed a 3-y randomized, placebo-controlled trial of calcium and vitamin D supplementation were followed for an additional 2 y during which no study supplements were given. BMD was measured by dual-energy X-ray absorptiometry, and biochemical variables related to calcium metabolism and bone turnover were measured. RESULTS: In the 128 men, supplement-induced increases in spinal and femoral neck BMD were lost within 2 y of supplement discontinuation, but small benefits in total-body BMD remained. In the 167 women, there were no lasting benefits in total-body BMD or at any bone site. Consistent with the observations on BMD, the bone turnover rates in both men and women (as measured by serum osteocalcin concentrations) returned to their original higher concentrations within the same 2-y period. CONCLUSION: Discontinued calcium and vitamin D supplementation has limited cumulative effect on bone mass in men and women aged >/=68 y.

Dietary fat and serum lipids: an evaluation of the experimental data.

Regression analysis of the combined published data on the effects of dietary fatty acids and cholesterol on serum cholesterol and lipoprotein cholesterol evaluated with groups of human subjects shows that 1) saturated fatty acids increase and are the primary determinants of serum cholesterol, 2) polyunsaturated fatty acids actively lower serum cholesterol, 3) monounsaturated fatty acids have no independent effect on serum cholesterol and, 4) dietary cholesterol increases serum cholesterol and must be considered when the effects of fatty acids are evaluated. More limited data on low-density-lipoprotein cholesterol (LDL-C) show that changes in LDL-C roughly parallel the changes in serum cholesterol but that changes in high-density-lipoprotein cholesterol cannot be satisfactorily predicted from available data.

Plasma vitamin B-12 concentrations relate to intake source in the Framingham Offspring study.

BACKGROUND: Low vitamin B-12 status is prevalent among the elderly, but few studies have examined the association between vitamin B-12 status and intake. OBJECTIVE: We hypothesized that vitamin B-12 concentrations vary according to intake source. DESIGN: Plasma concentrations and dietary intakes were assessed cross-sectionally for 2999 subjects in the Framingham Offspring Study. The prevalence of vitamin B-12 concentrations <148, 185, and 258 pmol/L was examined by age group (26-49, 50-64, and 65-83 y), supplement use, and the following food intake sources: fortified breakfast cereal, dairy products, and meat. RESULTS: Thirty-nine percent of subjects had plasma vitamin B-12 concentrations <258 pmol/L, 17% had concentrations <185 pmol/L, and 9% had concentrations <148 pmol/L, with little difference between age groups. Supplement users were significantly less likely than non-supplement-users to have concentrations <185 pmol/L (8% compared with 20%, respectively). Among non-supplement-users, there were significant differences between those who consumed fortified cereal >4 times/wk (12%) and those who consumed no fortified cereal (23%) and between those in the highest and those in the lowest tertile of dairy intake (13% compared with 24%, respectively), but no significant differences by meat tertile. Regression of plasma vitamin B-12 on log of intake, by source, yielded significant slopes for each contributor adjusted for the others. For the total group, b = 40.6 for vitamin B-12 from vitamin supplements. Among non-supplement-users, b = 56.4 for dairy products, 35.2 for cereal, and 16.7 for meat. Only the meat slope differed significantly from the others. CONCLUSIONS: In contrast with previous reports, plasma vitamin B-12 concentrations were associated with vitamin B-12 intake. Use of supplements, fortified cereal, and milk appears to protect against lower concentrations. Further research is needed to investigate possible differences in bioavailability.