Catherine A. Peterson

Correcting vitamin D insufficiency improves insulin sensitivity in obese adolescents: a randomized controlled trial

BACKGROUND Obese adolescents are at a greater risk of vitamin D deficiency because vitamin D is thought to be sequestered by excess adipose tissue. Poor vitamin D status has been associated with a higher prevalence of the metabolic syndrome, type 2 diabetes, or both in adults and adolescents. OBJECTIVE The objective was to determine in obese adolescents the efficacy and safety of 4000 IU vitamin D3/d and whether subsequent increased circulating concentrations of 25-hydroxyvitamin D [25(OH)D] are associated with improved markers of insulin sensitivity and resistance and reduced inflammation. DESIGN Obese adolescent patients [n = 35; mean ± SD age: 14.1 ± 2.8 y; BMI (in kg/m(2)): 39.8 ± 6.1; 25(OH)D: 19.6 ± 7.1 ng/mL] were recruited from the University of Missouri Adolescent Diabetes and Obesity Clinic and were randomly assigned to receive either vitamin D3 (4000 IU/d) or placebo as part of their standard care. Anthropometric measurements, inflammatory markers (IL-6, TNF-α, C-reactive protein), adipokines (leptin, adiponectin), fasting glucose, fasting insulin, and HOMA-IR values were measured at baseline and at 2 follow-up visits (3 and 6 mo). RESULTS After 6 mo, there were no significant differences in BMI, serum inflammatory markers, or plasma glucose concentrations between groups. Participants supplemented with vitamin D3 had increases in serum 25(OH)D concentrations (19.5 compared with 2.8 ng/mL for placebo; P < 0.001), fasting insulin (-6.5 compared with +1.2 μU/mL for placebo; P = 0.026), HOMA-IR (-1.363 compared with +0.27 for placebo; P = 0.033), and leptin-to-adiponectin ratio (-1.41 compared with +0.10 for placebo; P = 0.045). Inflammatory markers remained unchanged. CONCLUSION The correction of poor vitamin D status through dietary supplementation may be an effective addition to the standard treatment of obesity and its associated insulin resistance. This trial was registered at clinicaltrials.gov as NCT00994396.

Serum tumor necrosis factor-alpha concentrations are negatively correlated with serum 25(OH)D concentrations in healthy women.

BackgroundCirculating 25 hydroxyvitamin D (25 (OH)D), an accurate measure of vitamin D status, is markedly greater in individuals with increased exposure to ultraviolet B (UVB) light via sunlight or the use of artificial UV light. Aside from the known relationship between vitamin D and bone, vitamin D has also been implicated in immune function and inflammation. Furthermore, a mass of evidence is accumulating that vitamin D deficiency could lead to immune malfunction. Our overall objective was to study the relationship between vitamin D status (as determined by serum 25(OH) D concentrations) and inflammatory markers in healthy women.MethodsThis observational study included 69 healthy women, age 25–82 years. Women with high UVB exposure and women with minimal UVB exposure were specifically recruited to obtain a wide-range of serum 25(OH)D concentrations. Health, sun exposure and habitual dietary intake information were obtained from all subjects. Body composition was determined by dual-energy-x-ray absorptiometry. A fasting blood sample was collected in the morning and analyzed for serum 25(OH)D, parathyroid hormone (iPTH), estradiol (E2), cortisol, and inflammatory markers [tumor necrosis factor -alpha (TNF-α), interleukin-6 and -10 (IL-6, IL-10), and C-reactive protein (CRP)].ResultsWomen with regular UVB exposure (Hi-D) had serum 25(OH)D concentrations that were significantly higher (p < 0.0001) and iPTH concentrations that were significantly lower (p < 0.0001) than women without regular UVB exposure (Lo-D). Although IL-6, IL-10, and CRP did not have a statistically significant relationship with 25(OH)D concentrations, linear regression models revealed a significant inverse relationship between serum 25(OH)D and TNF-α concentrations. This relationship remained significant after controlling for potential covariates such as body fat mass, menopausal status, age, or hormonal contraceptive use.ConclusionSerum 25(OH)D status is inversely related to TNF-α concentrations in healthy women, which may in part explain this vitamins role in the prevention and treatment of inflammatory diseases. Results gleaned from this investigation also support the need to re-examine the biological basis for determining optimal vitamin D status.

Lack of multidisciplinary collaboration is a barrier to outcomes research

OBJECTIVES To identify and describe methods of collaboration used by dietitians to conduct outcomes research and to identify perceived barriers to participation in outcomes research. DESIGN A questionnaire was mailed to dietitians to obtain descriptive information about outcomes research involvement. Details of collaborative research experiences were collected in follow-up telephone interviews. SUBJECTS Subjects were a regional sample of 300 dietitians from the Clinical Nutrition Managers practice group of The American Dietetic Association. One hundred fifty-three subjects (51%) responded to the questionnaire and 25 of 42 eligible respondents were interviewed. ANALYSIS Frequency counts on questionnaire and closed-ended interview data were analyzed. Chi2 tests were used to identify significant associations between participation in outcomes research and demographic variables. Content analysis of open-ended interview data was used to detect emergence of recurrent themes. RESULTS Forty-two (27%) respondents had conducted outcomes research. Although all respondents collaborated on at least 1 project, half collaborated only with other dietitians, and 27 of 42 (64%) did not report research findings outside their facility. Interview data suggest that collaboration, especially between disciplines, enhances the entire research process and generates benefits beyond the specific project. The most frequently cited barriers among respondents who had not conducted outcomes research (n=111) were lack of research skills (65%) and lack of time or staff (41%). APPLICATIONS These findings support the assertion that lack of multidisciplinary involvement is a barrier to generating evidence of nutrition therapy effectiveness. Educators, health care professionals, and dietitians must model and encourage multidisciplinary, collaborative outcomes research in diverse practice settings.

Vitamin D insufficiency and insulin resistance in obese adolescents

Obese adolescents represent a particularly vulnerable group for vitamin D deficiency which appears to have negative consequences on insulin resistance and glucose homeostasis. Poor vitamin D status is also associated with future risk of type 2 diabetes and metabolic syndrome in the obese. The biological mechanisms by which vitamin D influences glycemic control in obesity are not well understood, but are thought to involve enhancement of peripheral/hepatic uptake of glucose, attenuation of inflammation and/or regulation of insulin synthesis/secretion by pancreatic β cells. Related to the latter, recent data suggest that the active form of vitamin, 1,25-dihydroxyvitamin D, does not impact insulin release in healthy pancreatic islets; instead they require an environmental stressor such as inflammation or vitamin D deficiency to see an effect. To date, a number of observational studies exploring the relationship between the vitamin D status of obese adolescents and markers of glucose homeostasis have been published. Most, although not all, show significant associations between circulating 25-hydroxyvitamn D concentrations and insulin sensitivity/resistance indices. In interpreting the collective findings of these reports, significant considerations surface including the effects of pubertal status, vitamin D status, influence of parathyroid hormone status and the presence of nonalcoholic fatty liver disease. The few published clinical trials using vitamin D supplementation to improve insulin resistance and impaired glucose tolerance in obese adolescents have yielded beneficial effects. However, there is a need for more randomized controlled trials. Future investigations should involve larger sample sizes of obese adolescents with documented vitamin D deficiency, and careful selection of the dose, dosing regimen and achievement of target 25-hydroxyvitamn D serum concentrations. These trials should also include clamp-derived measures of in vivo sensitivity and β-cell function to more fully characterize the effects of vitamin D replenishment on insulin resistance.

Vitamin D Status Is Not Associated with Outcomes of Experimentally-Induced Muscle Weakness and Pain in Young, Healthy Volunteers

Vitamin D receptors have been identified in skeletal muscle; and symptoms of vitamin D deficiency include muscle weakness and pain. Moreover, increased serum 25-hydroxyvitamin D (25(OH)D) concentrations have been associated with improved muscle function. To further clarify the importance of vitamin D to muscle, we examined the association between vitamin D status and exercise-induced muscle pain and weakness in healthy people. Muscle damage to the elbow flexors was induced with eccentric exercise (EE) in 48 individuals (22.5 ± 3.2 yrs). Muscle pain ratings following unloaded movement and peak isometric force (IF) were collected before EE and for 4 days post-EE. Linear regression was used to determine if serum 25(OH)D was a predictor of any outcome. In males, R 2-values from 0.48 to 1.00. R 2 for IF ranged from 0 to 0.02 and P-values from 0.48 to 1.00. In females, R 2 for pain ratings ranged from 0.01 to 0.11 and P-values from 0.14 to 0.59. R 2 for IF ranged from 0 to 0.04 and P-values from 0.41 to 0.90. In conclusion, vitamin D status did not predict muscle pain or strength after EE-induced muscle damage in young healthy men and women.

Vitamin D deficiency and childhood obesity: interactions, implications, and recommendations

Vitamin D deficiency and childhood obesity have been classified as epidemics throughout the world, and both share some common risk factors including poor diet and inactivity. Observational and clinical studies show that vitamin D status and fat mass are inversely correlated. It is not clear whether vitamin D deficiency contributes to, or is a consequence of obesity, or whether there are regulatory interactions between excess adiposity and vitamin D activity. The effects of this deficiency in childhood obesity appear to have negative influences on overall health, including insulin resistance, inflammation, and impeded bone mineralization, as well as increased future risk of type 2 diabetes, cardiovascular disease, and osteoporosis. The rather ubiquitous distribution of the vitamin D receptor and the 25-hydroxyvitamin D 1α-hydroxylase throughout the body, including evidence for a role of vitamin D in adipogenesis and adipocyte metabolism, may in part explain these widespread effects. Most of the findings to date suggest that the vitamin D needs of obese children are greater than the nonobese. Although ultraviolet B-induced skin synthesis is a main source of vitamin D, its use is neither feasible nor prudent due to limited sun availability for many and concerns for skin cancer. Likewise, obtaining adequate vitamin D from natural food sources alone is generally not achievable, and even in countries that allow fortification, vitamin D intakes are low. Therefore, in obese children, vitamin D supplementation is warranted. Weight loss interventions using energy restriction and physical activity may also improve the poor vitamin D status associated with obesity. More research is needed to define optimal vitamin D status in this vulnerable population, including investigations to determine the efficacy of vitamin D supplementation in attenuating the con - ditions associated with childhood obesity, and to further elucidate the mechanisms by which vitamin D exerts its effects on health.

Lack of Skeletal Effect of Soy Isoflavones in Intact Growing, Female Rats May Be Explained by Constant Serum Estrogenic Activity despite Reduced Serum Estradiol

Background/Aims: Scarce data exist on the effects of soy isoflavones (IF) on bone during peripuberty, a known ‘window of opportunity’ for bone consolidation. Our aim was to determine the skeletal, reproductive, and serum estradiol (E2)/estrogenic activity response of consuming naturally-occurring soy protein-associated IF during peripuberty. Methods: Weanling (∼3 weeks old), female rats were placed on one of four nutritionally-complete dietary regimens in which protein (200 g/kg diet) was provided as casein or soy protein isolates containing either 0.11 (Low IF), 2.16 (Med IF), or 3.95 (High IF) mg total aglycone isoflavones/g protein for 8 weeks, during which body weights and estrus cycling were recorded. Results: Bone growth and density were unaffected by soy intake while the reproductive tissues showed a slight response (greater uterine weights of the Med and High IF groups). Despite suppression of E2 concentrations in the High IF group, total circulating estrogenic activity was unaltered. Moreover, in the High IF group, E2 was significantly depressed compared with bioassayable estrogenic activity, suggesting negative feedback inhibition of E2 by the elevated circulating levels of IF. Conclusions: This suppression in E2 with maintenance of total serum estrogenicity in the High IF group may explain the lack of effect observed in the skeletal tissues.

The Effects of Regular Tanning Bed Use and Increased Vitamin D Status on Serum Markers of Bone Turnover in Healthy Adult Women

Background: Vitamin D is a key nutrient in bone health and the vitamin D status of individuals with regular exposure to solar or artificial ultraviolet B (UVB) radiation is generally superior to those with limited exposure. Objective: By means of a cross-sectional, observational design, explore the association of serum 25-hydroxy vitamin D (25(OH)D) concentrations and biochemical markers of bone turnover across a spectrum of vitamin D status by comparing women who regularly use tanning beds with women of minimal UVB exposure. Methods: A total of 69 healthy women, ages 25–82y, were recruited. Serum concentrations of 25(OH)D, intact parathyroid hormone (iPTH), leptin, bone-specific alkaline phosphatase (BAP), osteocalcin (OC), and C-terminal telopeptides of Type I collagen (CTx) were measured. Results: There were no significant differences in age, height, weight, BMI and dietary intakes between groups. Serum 25(OH)D concentrations were significantly higher in tanners (n = 20) compared with non-tanners (n = 49) (p < 0.0001). Serum iPTH concentrations were lower in tanners than in non-tanners (p < 0.0001) and were negatively correlated with serum 25(OH)D concentrations (r = –4571, p < 0.0001). Of the bone turnover markers, only serum OC concentrations were lower in tanners compared with non-tanners (p = 0.0002). After adjusting for age and menopausal status, osteocalcin was negatively correlated (r = –0.0178; p = 0.04) with 25(OH)D and positively correlated with iPTH (r = 0.035; p = 0.05). Conclusions: Our results show healthy women with regular UVB exposure via tanning beds have significantly greater vitamin D status and lower serum osteocalcin concentrations than those without and that there is a significant inverse relationship between serum serum 25(OH)D and osteocalcin concentrations which appears to be PTH-dependent.