Vitamin D Supplementation and Muscle Power, Strength and Physical Performance in Older Adults: A Randomized Controlled Trial.

BACKGROUND: Low 25-hydroxyvitamin D (25[OH]D) concentrations (<30 ng/mL [<50 nmol/L]) have been associated with muscle weakness and impaired physical performance in observational studies. However, the effect of vitamin D supplementation on changes in muscle strength and physical performance in randomized controlled trials has been mixed. OBJECTIVES: To determine the effect of daily vitamin D supplementation on leg power, strength, and physical performance in low-functioning older adults with 25(OH)D concentrations of 18 to <30 ng/mL. METHODS: In this double-blind, randomized controlled trial, 136 low-functioning [Short Physical Performance Battery (SPPB) scores ≤10] adults aged 65-89 y with 25(OH)D concentrations of 18 to <30 ng/mL were randomly assigned to 2000 IU/d vitamin D3 or placebo for 12 mo. Lower-extremity leg power (primary outcome), leg and grip strength, SPPB, timed up and go (TUG), postural sway, and gait velocity and spatiotemporal parameters (secondary outcomes) were assessed at baseline, 4 and 12 mo. A subset (n = 37) also underwent a muscle biopsy at baseline and 4 mo and muscle fiber composition and contractile properties were assessed. RESULTS: Participants' mean ± SD age and SPPB scores at baseline were 73.4 ± 6.3 y and 7.8 ± 1.8, respectively. Mean ± SD 25(OH)D concentrations at baseline and 12 mo were 19.4 ± 4.2 ng/mL and 28.6 ± 6.7 ng/mL in the vitamin D group and 19.9 ± 4.9 ng/mL and 20.2 ± 5.0 ng/mL in the placebo group for a mean ± SE difference of 9.1 ± 1.1 ng/mL (P < 0.0001). However, there were no differences in change in leg power, leg or grip strength, SPPB score, TUG, postural sway, or gait velocity and spatiotemporal parameters by intervention group over 12 mo or muscle fiber composition and contractile properties over 4 mo. CONCLUSIONS: In low-functioning older adults with 25(OH)D concentrations of 18 to <30 ng/mL, randomization to 2000 IU/d vitamin D3 did not result in improvements in leg power, strength, or physical performance or muscle fiber composition and contractile properties. This trial was registered at clinicaltrials.gov as NCT02015611.

Association of Fish Oil and Physical Activity on Mobility Disability in Older Adults.

PURPOSE: This study aimed to examine whether long-term fish oil (FO) supplementation is associated with a lower risk of mobility disability and enhances benefits of physical activity (PA). METHODS: A total of 1635 sedentary adults age 70 to 89 yr from the Lifestyle Interventions and Independence for Elders single-blinded randomized, multicenter clinical trial, which compared a structured PA program to a health education program. Primary outcome was incident major mobility disability (MMD), defined by loss of ability to walk 400 m, measured every 6 months for an average of 2.6 yr. Secondary outcomes included persistent mobility disability, Short Physical Performance Battery, 400-m walk speed, and grip strength. RESULTS: A third of participants reported using FO at baseline (456 (28%); mean age, 78.5 yr; 70.5% women). MMD was experienced by 131 participants (28.7%) in the FO group and 405 (34.4%) participants in the nonuser group. After adjusting for confounders, FO supplementation was associated with a lower risk (HR, 0.78; 95% confidence interval (CI), 0.64-0.96) of incident MMD. However, there was no interaction (P = 0.19) between FO supplementation and PA intervention for MMD. For the secondary outcome of persistent mobility disability, the intervention association differed by supplementation (P = 0.002) with PA intervention associations of (HR, 1.36; 95% CI, 0.83-2.23) for users and (HR, 0.61; 95% CI, 0.46-0.81) for nonusers. Changes in physical performance outcomes were not modified by baseline FO supplementation or combination with PA. CONCLUSIONS: FO supplementation was associated with a lower risk of MMD in low to moderate functioning older adults. However, supplementation did not enhance the benefit of PA on risk of mobility disability. These results are hypothesis generating and need to be confirmed in randomized trials.

Effect of Losartan and Fish Oil on Plasma IL-6 and Mobility in Older Persons. The ENRGISE Pilot Randomized Clinical Trial.

BACKGROUND: Low-grade chronic inflammation, characterized by elevations in plasma Interleukin-6 (IL-6), is an independent risk factor of impaired mobility in older persons. Angiotensin receptor blockers and omega-3 polyunsaturated fatty acids (ω-3) may reduce IL-6 and may potentially improve physical function. To assess the main effects of the angiotensin receptor blocker losartan and ω-3 as fish oil on IL-6 and 400 m walking speed, we conducted the ENRGISE Pilot multicenter randomized clinical trial. METHODS: The ENRGISE Pilot enrolled participants between April 2016 and June 2017, who participated for 12 months. Participants were aged ≥70 years with mobility impairment, had IL-6 between 2.5 and 30 pg/mL, and were able to walk 400 m at baseline. Participants were randomized in three strata 2 × 2 factorial to: (i) losartan 50-100 mg/d or placebo (n = 43), (ii) fish oil 1,400-2,800 mg/d or placebo (n = 180), and (iii) with both (n = 66). RESULTS: Two hundred eighty-nine participants were randomized (mean age 78.3 years, 47.4% women, 17.0% black). There was no effect of losartan (difference of means = -0.065 ± 0.116 [SE], 95% confidence interval [CI]: -0.293-0.163, p = .58) or fish oil (-0.020 ± 0.077, 95% CI: -0.171-0.132, p = .80) on the log of IL-6. Similarly, there was no effect of losartan (-0.025 ± 0.026, 95% CI: -0.076-0.026, p = .34) or fish oil (0.010 ± 0.017, 95% CI: -0.025-0.044, p = .58) on walking speed (m/s). CONCLUSIONS: These results do not support the use of these interventions to prevent mobility loss in older adults at risk of disability with low-grade chronic inflammation. REGISTRATION: Clinicaltrials.gov NCT02676466.

The Enabling Reduction of Low-Grade Inflammation in Seniors (ENRGISE) Pilot Study: Screening Methods and Recruitment Results.

BACKGROUND: The Enabling Reduction of Low-grade Inflammation in Seniors (ENRGISE) Pilot Study is a multicenter randomized clinical trial examining the feasibility of testing whether omega-3 fish oil (ω-3) and the angiotensin receptor blocker losartan alone or in combination can reduce inflammation and improve walking speed in older adults with mobility impairment. We describe recruitment methods and results. METHODS: Eligible participants were 70 years and older, had elevated interleukin-6 levels (2.5-30 pg/mL) and mobility impairment. RESULTS: Of those who responded to recruitment, 83% responded to mailings. A total of 5,424 telephone screens were completed; of these, 2,011 (37.1%) were eligible for further screening. The most common reasons for ineligibility at the telephone screens were lack of mobility impairment or use of angiotensin receptor blockers or angiotensin-converting enzyme inhibitors (n=1.789). Of the 1,305 initial screening visits, 1,087 participants had slow gait speed (<1 m/s). Of these, 701 (64%) had elevated interleukin-6 and were eligible for second screening visits. Of the 582 second screening visits, 335 (57.6%) were eligible to be randomized. A total of 289 participants (96% of goal) were randomized: 180 in the ω-3 stratum (240% of goal); 43 in the losartan (57% of goal), and 66 in the combination (44% of goal). The telephone screen and first screening visit to randomization ratio was 19 to 1 and 4.5 to 1, respectively. The estimated cost of recruitment per randomized participant was $1,782. CONCLUSION: Recruitment for ω-3 exceeded goals, but goals for the losartan and combination strata were not met due to the high proportion of participants taking angiotensin receptor blockers or angiotensin-converting enzyme inhibitors.

Association of Vitamin K Status Combined With Vitamin D Status and Lower-Extremity Function: A Prospective Analysis of Two Knee Osteoarthritis Cohorts.

OBJECTIVE: Vitamins K and D are important for the function of vitamin K-dependent proteins in joint tissues. It is unclear whether these nutrients are mutually important to functional outcomes related to knee osteoarthritis (OA). We evaluated the association of vitamin K and D sufficiency with lower-extremity function in the Health, Aging and Body Composition knee OA substudy (Health ABC) and conducted a replication analysis in an independent cohort, the Osteoarthritis Initiative (OAI). METHODS: In Health ABC (60% female, mean ± SD age 75 ± 3 years) baseline nutrient status was measured using circulating vitamin K and 25-hydroxyvitamin D (25[OH]D). Lower-extremity function was assessed using the Short Physical Performance Battery (SPPB) and usual 20-meter gait speed. In the OAI (58% female, mean ± SD age 61 ± 9 years), baseline nutrient intake was estimated by food frequency questionnaire. Lower-extremity function was assessed using usual 20-meter gait speed and chair stand completion time. Multivariate mixed models were used to evaluate the association of vitamin K and D status and intake with lower-extremity function over 4-5 years. RESULTS: Health ABC participants with sufficient plasma vitamin K (≥1.0 nmoles/liter) and serum 25(OH)D (≥50 nmoles/liter) generally had better SPPB scores and faster usual gait speed over followup (P ≤ 0.002). In the OAI, sufficient vitamin K and vitamin D intake combined was associated with overall faster usual gait speed and chair stand completion time over followup (P ≤ 0.029). CONCLUSION: Sufficient vitamin K status combined with sufficient vitamin D status was associated with better lower-extremity function in 2 knee OA cohorts. These findings merit confirmation in vitamin K and D co-supplementation trials.

Modeling the shape and composition of the human body using dual energy X-ray absorptiometry images.

There is growing evidence that body shape and regional body composition are strong indicators of metabolic health. The purpose of this study was to develop statistical models that accurately describe holistic body shape, thickness, and leanness. We hypothesized that there are unique body shape features that are predictive of mortality beyond standard clinical measures. We developed algorithms to process whole-body dual-energy X-ray absorptiometry (DXA) scans into body thickness and leanness images. We performed statistical appearance modeling (SAM) and principal component analysis (PCA) to efficiently encode the variance of body shape, leanness, and thickness across sample of 400 older Americans from the Health ABC study. The sample included 200 cases and 200 controls based on 6-year mortality status, matched on sex, race and BMI. The final model contained 52 points outlining the torso, upper arms, thighs, and bony landmarks. Correlation analyses were performed on the PCA parameters to identify body shape features that vary across groups and with metabolic risk. Stepwise logistic regression was performed to identify sex and race, and predict mortality risk as a function of body shape parameters. These parameters are novel body composition features that uniquely identify body phenotypes of different groups and predict mortality risk. Three parameters from a SAM of body leanness and thickness accurately identified sex (training AUC = 0.99) and six accurately identified race (training AUC = 0.91) in the sample dataset. Three parameters from a SAM of only body thickness predicted mortality (training AUC = 0.66, validation AUC = 0.62). Further study is warranted to identify specific shape/composition features that predict other health outcomes.

Vitamin K Status and Lower Extremity Function in Older Adults: The Health Aging and Body Composition Study.

BACKGROUND: While low vitamin K status has been associated with several chronic diseases that can lead to lower extremity disability, it is not known if low vitamin K status is associated with worse lower extremity function. METHODS: Vitamin K status was measured according to plasma phylloquinone (vitamin K1) and dephosphorylated-uncarboxylated MGP (dp-ucMGP) in 1,089 community-dwelling older adults (mean ± SD age =74±3 years; 67% female). Lower extremity function was assessed using the short physical performance battery (SPPB), gait speed, and isokinetic leg strength. Linear regression and mixed models were used to determine the cross-sectional and longitudinal associations between vitamin K status and functional outcome measures. RESULTS: Cross-sectionally, higher plasma phylloquinone was associated with better SPPB scores and 20-m gait speed (p ≤ .05). After 4-5 years, those with ≥1.0nM plasma phylloquinone (the concentration achieved when recommended intakes are met) had better SPPB scores (p = .03) and 20-m gait speed (p < .05). Lower plasma dp-ucMGP (reflective of better vitamin K status) was associated with better SPPB scores and leg strength cross-sectionally (p ≤ .04), but not longitudinally. Neither measure of vitamin K status was associated with walking endurance or with the rate of decline in function. CONCLUSION: Older adults with higher vitamin K status had better physical performance scores at baseline, but data are less consistent longitudinally. Since lower extremity disability is a common consequence of multiple chronic diseases for which a role of vitamin K has been suggested, future studies are needed to determine if vitamin K supplementation could improve function in those with vitamin K insufficiency and clarify underlying mechanism(s).

Delivery of a Vitamin D Intervention in Homebound Older Adults Using a Meals-on-Wheels Program: A Pilot Study.

OBJECTIVES: To assess the feasibility of a vitamin D intervention delivered through a Meals-on-Wheels (MOW) program to improve 25-hydroxyvitamin D (25(OH)D) concentrations and reduce falls in homebound older adults. DESIGN: Single-blind, cluster randomized trial. SETTING: MOW, Forsyth County, North Carolina. PARTICIPANTS: Community-dwelling homebound adults aged 65 to 102 (N = 68). INTERVENTION: MOW clients were randomized to vitamin D3 (100,000 IU/month; n = 38) or active placebo (400 IU vitamin E/month; n = 30) according to MOW delivery route. MEASUREMENTS: Serum 25(OH)D was assessed at baseline and 5-month follow-up; proportions of participants in 25(OH)D categories were compared using Fisher exact test. Falls were assessed using monthly fall calendars, and rate of falls was estimated using negative binomial generalized estimating equation models. RESULTS: Mean ± standard deviation 25(OH)D concentrations were 20.9 ± 11.5 ng/mL at baseline, with 57% having 25(OH)D concentrations less than 20 ng/mL. Retention and adherence were high (>90%). After the 5-month intervention, only one of 34 participants randomized to vitamin D3 had 25(OH)D concentrations less than 20 ng/mL, compared with 18 of 25 participants randomized to placebo (P < .001). In unadjusted analyses, the rate of falls over 5 months was not significantly different according to intervention group (risk ratio (RR) = 0.48, 95% confidence interval (CI) = 0.19-1.19), but after adjustment for sex, race, season of year, baseline 25(OH)D status, and history of falls, participants randomized to vitamin D3 had a lower rate of falling than those randomized to placebo (RR = 0.42, 95% CI = 0.21-0.87). CONCLUSION: A vitamin D intervention delivered through MOW was feasible, resulting in improvements in 25(OH)D concentrations and a lower rate of falls in adjusted analyses. Further research is needed to validate the reduction in falls from this type of intervention.

Genetic and environmental factors are associated with serum 25-hydroxyvitamin D concentrations in older African Americans.

BACKGROUND: Low circulating 25-hydroxyvitamin D [25(OH)D] is prevalent in African Americans, but predictors of vitamin D status are understudied compared to Caucasian populations. OBJECTIVE: We investigated whether certain environmental and genetic factors are predictors of circulating 25(OH)D in 989 elderly African Americans participating in the Health, Aging, and Body Composition (Health ABC) Study. METHODS: Regression analysis estimated the cross-sectional association of nongenetic (environmental) factors with 25(OH)D. Single nucleotide polymorphisms (SNPs) associated with 25(OH)D in Caucasian genome-wide association studies (GWASs) were analyzed for association with serum 25(OH)D, including analyses of all imputed SNPs in identified genomic regions. Genome-wide complex trait analysis (GCTA) evaluated the association of all (genome-wide) genotyped SNPs with serum 25(OH)D in the Health ABC Study with replication in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort. RESULTS: Gender, study site, season of blood draw, body mass index, dietary supplement use, dairy and cereal consumption, Healthy Eating Index score, and walking >180 min/wk were associated with 25(OH)D (P < 0.05), jointly explaining 25% of the variation in circulating 25(OH)D. Multivitamin supplement use was the strongest predictor of circulating 25(OH)D, and supplement users had a 6.3-µg/L higher serum 25(OH)D concentration compared with nonusers. Previous GWAS-identified gene regions were not replicated in African Americans, but the nonsynonymous rs7041 SNP in group-specific component (vitamin D binding protein) was close to significance thresholds (P = 0.08), and there was evidence for an interaction between this SNP and use of multivitamin supplements in relation to serum 25(OH)D concentration (P = 0.04). Twenty-three percent (95% CI: 0%, 52%) of the variation in serum 25(OH)D was explained by total genetic variation in a pooled GCTA of 2087 Health ABC Study and MESA African-American participants, but population substructure effects could not be separated from other genetic influences. CONCLUSIONS: Modifiable dietary and lifestyle predictors of serum 25(OH)D were identified in African Americans. GCTA confirms that a proportion of 25(OH)D variability is attributable to genetic variation, but genomic regions associated with the 25(OH)D phenotype identified in prior GWASs of European Americans were not replicated in the Health ABC Study in African Americans.

Strength and function response to clinical interventions of older women categorized by weakness and low lean mass using classifications from the Foundation for the National Institute of Health sarcopenia project.

BACKGROUND: The Foundation for the National Institutes of Health Sarcopenia Project developed data-driven cut-points for clinically meaningful weakness and low lean body mass. This analysis describes strength and function response to interventions based on these classifications. METHODS: In data from four intervention studies, 378 postmenopausal women with baseline and 6-month data were evaluated for change in grip strength, appendicular lean mass corrected for body mass index, leg strength and power, and short physical performance battery (SPPB). Clinical interventions included hormones, exercise, and nutritional supplementation. Differences in outcomes were evaluated between (i) those with and without weakness and (ii) those with weakness and low lean mass or with one but not the other. We stratified analyses by slowness (walking speed ≤ 0.8 m/s) and by treatment assignment. RESULTS: The women (72±7 years; body mass index of 26±5kg/m(2)) were weak (33%), had low lean mass (14%), or both (6%). Those with weakness increased grip strength, lost less leg power, and gained SPPB score (p < .05) compared with nonweak participants. Stratified analyses were similar for grip strength and SPPB. With lean mass in the analysis, individuals with weakness had larger gains in grip strength and SPPB scores regardless of low lean mass (p < .01). CONCLUSIONS: Older women with clinically meaningful muscle weakness increased grip strength and SPPB, regardless of the presence of low lean mass following treatment with interventions for frailty. Thus, results suggest that muscle weakness, as defined by the Foundation for the National Institutes of Health Sarcopenia Project, appears to be a treatable symptom.

Calcium/vitamin D supplementation, serum 25-hydroxyvitamin D concentrations, and cholesterol profiles in the Women's Health Initiative calcium/vitamin D randomized trial.

OBJECTIVE: The objective of this study was to evaluate whether increased serum 25-hydroxyvitamin D3 (25OHD3) concentrations, in response to calcium/vitamin D (CaD) supplementation, are associated with improved lipids in postmenopausal women. METHODS: The parent trial was a double-blind, randomized, placebo-controlled, parallel-group trial designed to test the effects of CaD supplementation (1,000 mg of elemental calcium + 400 IU of vitamin D3 daily) versus placebo in postmenopausal women. Women from the general community, including multiple sites in the United States, were enrolled between 1993 and 1998. This cohort included 300 white, 200 African-American, and 100 Hispanic participants who were randomly selected from the Women's Health Initiative CaD trial. Serum 25OHD3 and lipid (fasting plasma triglycerides [TG], high-density lipoprotein cholesterol [HDL-C], and calculated low-density lipoprotein cholesterol [LDL-C]) levels were assessed before and after CaD randomization. RESULTS: There was a 38% increase in mean serum 25OHD3 concentrations after 2 years (95% CI, 1.29-1.47, P < 0.001) for women randomized to CaD (24.3 ng/mL postrandomization mean) compared with placebo (18.2 ng/mL). Women randomized to CaD had a 4.46-mg/dL mean decrease in LDL-C (P = 0.03). Higher concentrations of 25OHD3 were associated with higher HDL-C levels (P = 0.003), along with lower LDL-C and TG levels (P = 0.02 and P < 0.001, respectively). CONCLUSIONS: Supplemental CaD significantly increases 25OHD3 concentrations and decreases LDL-C. Women with higher 25OHD3 concentrations have more favorable lipid profiles, including increased HDL-C, lower LDL-C, and lower TG. These results support the hypothesis that higher concentrations of 25OHD3, in response to CaD supplementation, are associated with improved LDL-C.

Relationship between 25-hydroxyvitamin D and cognitive function in older adults: the Health, Aging and Body Composition Study.

OBJECTIVES: To examine the relationship between 25-hydroxyvitamin D (25(OH)D) levels and cognitive performance over time in older adults in the Health, Aging and Body Composition (Health ABC) Study. DESIGN: Prospective cohort study. SETTING: Community-dwelling participants in Pittsburgh, Pennsylvania, and Memphis, Tennessee. PARTICIPANTS: Well-functioning adults aged 70 to 79 at baseline with serum 25(OH)D measured at the 12-month follow-up visit and cognitive function measured at baseline and 4-year follow-up visit (N = 2,777). MEASUREMENTS: Vitamin D status was categorized as 25(OH)D levels of less than 20.0 ng/mL, 20.0 to 29.9 ng/mL, or 30.0 ng/mL or greater. Cognition was measured using the modified Mini-Mental State Examination (3MS) and Digit Symbol Substitution Test (DSST). Linear regression models adjusting for multiple covariates, including age, education, sex, race, site, season, physical activity, and comorbidities, were used in the analysis. RESULTS: Sixty-eight percent of participants had 25(OH)D levels of less than 30.0 ng/mL. Lower 25(OH)D levels were associated with lower baseline cognitive scores on the 3MS (adjusted mean 89.9, 95% confidence interval (CI) = 89.4-90.4 for <20.0 ng/mL; adjusted mean 90.8, 95% CI = 90.4-91.3 for 20.0-29.9 ng/mL; adjusted mean 90.6, 95% CI = 90.2-91.1 for ≥ 30.0 ng/mL; P trend = .02) and the DSST (adjusted mean 35.2, 95% CI = 34.5-36.0 for <20.0 ng/mL; adjusted mean 35.9, 95% CI = 35.2-36.6 for 20.0-29.9 ng/mL; adjusted mean 37.0, 95% CI = 36.3-37.8 for ≥ 30.0 ng/mL; P trend = .01). Participants with low 25(OH)D levels had greater declines in 3MS scores over 4 years than those with higher levels (least square mean change -1.0, 95% CI = -1.5 to -0.6 for <20.0 ng/mL; least square mean change -0.8, 95% CI = -1.2 to -0.3 for 20.0-29.9 ng/mL; least square mean change -0.2, 95% CI = -0.7 to 0.2 for ≥30.0 ng/mL; P = .05). There was no significant difference in DSST decline according to 25(OH)D level. CONCLUSION: Low 25(OH)D levels were associated with worse global cognitive function and greater decline over time according to the 3MS. Intervention trials are needed to determine whether vitamin D supplementation can reduce cognitive decline.

Association between circulating vitamin K1 and coronary calcium progression in community-dwelling adults: the Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Animal studies have shown that vitamin K treatment reduced vascular calcification, but human data are limited. OBJECTIVE: We determined the association between vitamin K status and coronary artery calcium (CAC) progression in the Multi-Ethnic Study of Atherosclerosis by using a case-cohort design. DESIGN: Serum phylloquinone (vitamin K1) was measured in 296 participants with extreme CAC progression and 561 randomly selected participants without extreme CAC progression; all subjects had baseline and follow-up CAC measures (mean follow-up: 2.5 y). A serum vitamin K1 concentration was considered low at <1.0 nmol/L (the distribution median). Outcomes were replicated by using post hoc per-protocol analyses of a vitamin K1 supplementation trial. RESULTS: The OR (95% CI) for extreme CAC progression for subjects with low serum vitamin K1 compared with subjects without extreme CAC progression was 1.34 (0.94, 1.90; NS) when adjusted for demographics and confounders. A significant interaction between low vitamin K1 and antihypertension medication use was detected (P = 0.016). Hypertension medication users with low serum vitamin K1 were more likely to have extreme CAC progression than were medication users without extreme CAC progression [OR (95% CI): 2.37 (1.38, 4.09)]. In replication, baseline antihypertensive medication users in the supplementation group had less CAC progression than did those in the control group [adjusted mean ± SEM of the 3-y CAC change was +5 ± 20 Agatston units (AU) in the vitamin K1 group (n = 40) and +44 ± 13 AU in the placebo group (n = 49); P < 0.01]. CONCLUSIONS: Although the point estimate of our primary analysis suggests low serum vitamin K1 is associated with greater CAC progression, the difference was NS. Low serum vitamin K1 was significantly associated with CAC progression in antihypertension medication users, which, to our knowledge, is a novel finding conditionally replicated by using an independent sample. Intervention trials are needed to determine whether improving serum vitamin K1 reduces CAC progression, especially in hypertensive individuals. This trial was registered at clinicaltrials.gov as NCT00183001.

Total zinc intake may modify the glucose-raising effect of a zinc transporter (SLC30A8) variant: a 14-cohort meta-analysis.

OBJECTIVE: Many genetic variants have been associated with glucose homeostasis and type 2 diabetes in genome-wide association studies. Zinc is an essential micronutrient that is important for ß-cell function and glucose homeostasis. We tested the hypothesis that zinc intake could influence the glucose-raising effect of specific variants. RESEARCH DESIGN AND METHODS: We conducted a 14-cohort meta-analysis to assess the interaction of 20 genetic variants known to be related to glycemic traits and zinc metabolism with dietary zinc intake (food sources) and a 5-cohort meta-analysis to assess the interaction with total zinc intake (food sources and supplements) on fasting glucose levels among individuals of European ancestry without diabetes. RESULTS: We observed a significant association of total zinc intake with lower fasting glucose levels (ß-coefficient ± SE per 1 mg/day of zinc intake: -0.0012 ± 0.0003 mmol/L, summary P value = 0.0003), while the association of dietary zinc intake was not significant. We identified a nominally significant interaction between total zinc intake and the SLC30A8 rs11558471 variant on fasting glucose levels (ß-coefficient ± SE per A allele for 1 mg/day of greater total zinc intake: -0.0017 ± 0.0006 mmol/L, summary interaction P value = 0.005); this result suggests a stronger inverse association between total zinc intake and fasting glucose in individuals carrying the glucose-raising A allele compared with individuals who do not carry it. None of the other interaction tests were statistically significant. CONCLUSIONS: Our results suggest that higher total zinc intake may attenuate the glucose-raising effect of the rs11558471 SLC30A8 (zinc transporter) variant. Our findings also support evidence for the association of higher total zinc intake with lower fasting glucose levels.

Circulating uncarboxylated matrix gla protein is associated with vitamin K nutritional status, but not coronary artery calcium, in older adults.

Matrix Gla protein (MGP) is a calcification inhibitor in vascular tissue that must be carboxylated by vitamin K to function. Evidence suggests circulating uncarboxylated MGP (ucMGP) is elevated in persons with disease characterized by vascular calcification. The primary purpose of this study was to determine cross-sectional and longitudinal associations between plasma ucMGP, vitamin K status, and coronary artery calcium (CAC) in older adults without coronary heart disease. Genetic determinants of ucMGP were also explored. Cross-sectional associations among baseline plasma ucMGP, vitamin K status biomarkers [plasma phylloquinone, uncarboxylated prothrombin (PIVKA-II), serum uncarboxylated osteocalcin (%ucOC)], CAC, and plausible genetic polymorphisms were examined in 438 community-dwelling adults (60-80 y, 59% women). The effect of phylloquinone supplementation (500 µg/d) for 3 y on plasma ucMGP was determined among 374 participants. At baseline, plasma phylloquinone was lower and %ucOC and PIVKA-II were greater across higher plasma ucMGP quartiles (all P < 0.001, age-adjusted). Major allele homozygotes for MGP rs1800801 and rs4236 had higher plasma ucMGP than heterozygotes or minor allele homozygotes. (P ≤ 0.004). The decrease in plasma ucMGP was greater in the 190 participants who received phylloquinone (mean ± SD) (-345 ± 251 pmol/L) than in the 184 who did not (-40 ± 196 pmol/L) (P < 0.0001). CAC did not differ according to ucMGP quartile (P = 0.35, age-adjusted). In the phylloquinone-supplemented group, the 3-y change in ucMGP was not associated with the 3-y change in CAC [unstandard ß (SE) = -0.02 (0.02); P = 0.44]. Plasma ucMGP was associated with vitamin K status biomarkers and was reduced following phylloquinone supplementation, suggesting it may be a useful marker of vitamin K status in vascular tissue. Plasma ucMGP did not reflect CAC in healthy older adults.

Correlates and prevalence of insufficient 25-hydroxyvitamin D status in black and white older adults: the health, aging and body composition study.

OBJECTIVES: To determine the prevalence and correlates of vitamin D insufficiency in black and white older adults. DESIGN: Cross-sectional. SETTING: Health, Aging and Body Composition Study. PARTICIPANTS: Nine hundred seventy-seven black and 1,604 white adults aged 70 to 81. MEASUREMENTS: Logistic regression and classification and regression tree analysis were used to identify correlates of vitamin D insufficiency (25-hydroxyvitamin D (25(OH)D) <30 ng/mL) separately in blacks and whites. RESULTS: The prevalence of 25(OH)D insufficiency was 84% in blacks and 57% in whites. Seventy-six percent of blacks and 56% of whites did not take a multivitamin; those who did not take a multivitamin were more likely to be vitamin D insufficient (odds ratio (OR)=5.17 (95% confidence interval (CI)=3.47-7.70) for blacks; OR=2.56, 95% CI=2.05-3.19 for white). Additional risk factors for vitamin D insufficiency were vitamin D-containing supplement use, female sex, and obesity in blacks; and winter season, low dietary vitamin D intake, obesity, type 2 diabetes mellitus, and female sex in whites. CONCLUSION: Vitamin D insufficiency was more prevalent in blacks than whites. Not consuming a multivitamin increased the odds of vitamin D insufficiency in blacks and whites. Knowledge of additional risk factors such as dietary intake and comorbid conditions may help identify older adults who are likely to be vitamin D insufficient.

Markers of mineral metabolism are not associated with aortic pulse wave velocity in community-living elderly persons: the Health Aging and Body Composition study.

BACKGROUND: Disorders in mineral metabolism are associated with risk for cardiovascular disease (CVD) events in patients with kidney disease as well as in the general population. This risk is thought to be mediated, in part, through the mechanism of stiffening of the arteries. METHODS: The objective of this study was to evaluate the relationships between serum calcium, phosphorus, intact parathyroid hormone (iPTH), and 25-hydroxyvitamin D levels and arterial pulse wave velocity (aPWV) among 2,229 community-dwelling elderly persons participating in the Health Aging and Body Composition (Health ABC) study. RESULTS: The mean age of the participants was 72 years; 52% were woman, 39% were black, and 17% had chronic kidney disease (CKD) (estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2)). In parallel unadjusted analyses, the following associations were observed: 2.86% greater aPWV per 12 ng/ml (s.d.) lower 25-hydroxyvitamin D (95% confidence interval -4.38%, -1.31%), 3.04% greater aPWV per 28 pg/ml (s.d.) higher iPTH (95% confidence interval 1.42-4.68%), and 2.37% lower aPWV per 0.5 mg/dl (s.d.) higher phosphorus (95% confidence interval -3.90% to - 0.81%). Except for phosphorus, these associations were attenuated and rendered no longer statistically significant after adjustment for demographic risk factors, clinical site, season, medications and other CVD risk factors. The results were similar in men and women and were not dependent on the presence of CKD. CONCLUSIONS: Among well-functioning community-dwelling elderly persons, only serum phosphorus was associated with aPWV; and this association was in the opposite direction of the one hypothesized. Factors other than vascular stiffening may mediate the relationship between disordered mineral metabolism and CVD events in community-living elders.

Translating research to promote healthy aging: the complementary role of longitudinal studies and clinical trials.

An important challenge in epidemiology is the difficulty in inferring causality from observational studies. Even the best longitudinal studies have limitations in this regard, and when clinical trials are feasible, they will provide more-definite evidence of causality, but even when clinical trials are feasible, a large amount can be learned about the disease process, assessment techniques, subject selection criteria, and the effect of potential interventions from longitudinal studies. This review covers the theoretical issues supporting the value and limitations of longitudinal studies, the practical utilization in clinical trials of different aspects of knowledge that can be gained from longitudinal studies, critical issues in the translation of longitudinal observational studies into clinical trials, and the value of observational studies in broadening the applicability of specific trials. Relevant issues are illustrated with examples of unsuccessful and successful trials, with a major emphasis on clinical trials of physical activity in older persons.

Common genetic variants associate with serum phosphorus concentration.

Phosphorus is an essential mineral that maintains cellular energy and mineralizes the skeleton. Because complex actions of ion transporters and regulatory hormones regulate serum phosphorus concentrations, genetic variation may determine interindividual variation in phosphorus metabolism. Here, we report a comprehensive genome-wide association study of serum phosphorus concentration. We evaluated 16,264 participants of European ancestry from the Cardiovascular Heath Study, Atherosclerosis Risk in Communities Study, Framingham Offspring Study, and the Rotterdam Study. We excluded participants with an estimated GFR <45 ml/min per 1.73 m(2) to focus on phosphorus metabolism under normal conditions. We imputed genotypes to approximately 2.5 million single-nucleotide polymorphisms in the HapMap and combined study-specific findings using meta-analysis. We tested top polymorphisms from discovery cohorts in a 5444-person replication sample. Polymorphisms in seven loci with minor allele frequencies 0.08 to 0.49 associate with serum phosphorus concentration (P = 3.5 x 10(-16) to 3.6 x 10(-7)). Three loci were near genes encoding the kidney-specific type IIa sodium phosphate co-transporter (SLC34A1), the calcium-sensing receptor (CASR), and fibroblast growth factor 23 (FGF23), proteins that contribute to phosphorus metabolism. We also identified genes encoding phosphatases, kinases, and phosphodiesterases that have yet-undetermined roles in phosphorus homeostasis. In the replication sample, five of seven top polymorphisms associate with serum phosphorous concentrations (P < 0.05 for each). In conclusion, common genetic variants associate with serum phosphorus in the general population. Further study of the loci identified in this study may help elucidate mechanisms of phosphorus regulation.