Catherine Anderson Spearie

Cross-sectional Study of Vitamin D and Calcium Supplementation Effects on Chronic Periodontitis

BACKGROUND A low dietary intake of vitamin D and calcium hastens bone loss and osteoporosis. Because vitamin D metabolites may also alter the inflammatory response and have antimicrobial effects, we studied whether the use of vitamin D and calcium supplements affects periodontal disease status. METHODS A cohort of 51 subjects receiving periodontal maintenance therapy was recruited from two dental clinics; 23 were taking vitamin D (>or=400 IU/day) and calcium (>or=1,000 mg/day) supplementation, and 28 were not taking such supplementation. All subjects had at least two interproximal sites with >or=3 mm clinical attachment loss. Daily calcium and vitamin D intake (from food and supplements) were estimated by nutritional analysis. The following clinical parameters of periodontal disease were recorded for the mandibular posterior teeth: gingival index, probing depth, cemento-enamel junction-gingival margin distance (attachment loss), bleeding on probing, and furcation involvement. Posterior photostimulable-phosphor bitewing radiographs were taken to determine cemento-enamel junction-alveolar crest distances (alveolar crest height loss). Data were analyzed with a repeated-measures multivariate analysis of variance. RESULTS Compared to subjects who did not take vitamin D and calcium supplementation, supplement takers had shallower probing depths, fewer bleeding sites, lower gingival index values, fewer furcation involvements, less attachment loss, and less alveolar crest height loss. The repeated-measures analysis indicated that collectively these differences were borderline significant (P = 0.08). CONCLUSIONS In these subjects receiving periodontal maintenance therapy, there was a trend for better periodontal health with vitamin D and calcium supplementation. More expanded longitudinal studies are required to determine the potential of this relationship.

Dose effects of dietary phytosterols on cholesterol metabolism: a controlled feeding study

BACKGROUND Phytosterol supplementation of 2 g/d is recommended by the National Cholesterol Education Program to reduce LDL cholesterol. However, the effects of different intakes of phytosterol on cholesterol metabolism are uncertain. OBJECTIVE We evaluated the effects of 3 phytosterol intakes on whole-body cholesterol metabolism. DESIGN In this placebo-controlled, crossover feeding trial, 18 adults received a phytosterol-deficient diet (50 mg phytosterols/2000 kcal) plus beverages supplemented with 0, 400, or 2000 mg phytosterols/d for 4 wk each, in random order. All meals were prepared in a metabolic kitchen; breakfast and dinner on weekdays were eaten on site. Primary outcomes were fecal cholesterol excretion and intestinal cholesterol absorption measured with stable-isotope tracers and serum lipoprotein concentrations. RESULTS Phytosterol intakes (diet plus supplements) averaged 59, 459, and 2059 mg/d during the 3 diet periods. Relative to the 59-mg diet, the 459- and 2059-mg phytosterol intakes significantly (P < 0.01) increased total fecal cholesterol excretion (36 +/- 6% and 74 +/- 10%, respectively) and biliary cholesterol excretion (38 +/- 7% and 77 +/- 12%, respectively) and reduced percentage intestinal cholesterol absorption (-10 +/- 1% and -25 +/- 3%, respectively). Serum LDL cholesterol declined significantly only with the highest phytosterol dose (-8.9 +/- 2.3%); a trend was observed with the 459-mg/d dose (-5.0 +/- 2.1%; P = 0.077). CONCLUSIONS Dietary phytosterols in moderate and high doses favorably alter whole-body cholesterol metabolism in a dose-dependent manner. A moderate phytosterol intake (459 mg/d) can be obtained in a healthy diet without supplementation. This trial was registered at clinicaltrials.gov as NCT00860054.

One-Year Effects of Vitamin D and Calcium Supplementation on Chronic Periodontitis

BACKGROUND A previous study reported by this group found that patients in periodontal maintenance programs taking vitamin D and calcium supplementation had a trend for better periodontal health compared to patients not taking supplementation. The objective of the present study is to determine, for the same cohort of subjects, whether such differences persist over a 1-year period. METHODS Fifty-one patients enrolled in maintenance programs from two dental clinics were recruited. Of these, 23 were taking vitamin D (≥400 IU/day) and calcium (≥1,000 mg/day) supplementation, and 28 were not. All subjects had at least two interproximal sites with ≥3 mm clinical attachment loss. For mandibular-posterior teeth, gingival index, plaque index, probing depth, attachment loss, bleeding on probing, calculus index, and furcation involvement were evaluated. Photostimulable-phosphor, posterior bitewing radiographs were taken to assess alveolar bone. Daily vitamin D and calcium intakes were estimated by nutritional analysis. Data were collected at baseline, 6 months, and 12 months. RESULTS Total daily calcium and vitamin D intakes were 1,769 mg (95% confidence interval, 1,606 to 1,933) and 1,049 IU (781 to 1,317) in the taker group, and 642 mg (505 to 779) and 156 IU (117 to 195) in the non-taker group, respectively (P <0.001 for both). Clinical parameters of periodontal health improved with time in both groups (P <0.001). When clinical measures were considered collectively, the differences between supplement takers and non-takers had the following P values: baseline (P = 0.061); 6 months (P = 0.049); and 12 months (P = 0.114). After adjusting for covariates, the P values for the effect of supplementation were as follows: baseline (P = 0.028); 6 months (P = 0.034); and 12 months (P = 0.058). CONCLUSIONS Calcium and vitamin D supplementation (≤1,000 IU/day) had a modest positive effect on periodontal health, and consistent dental care improved clinical parameters of periodontal disease regardless of such supplements. Our findings support the possibility that vitamin D may positively impact periodontal health and confirm the need for randomized clinical trials on the effects of vitamin D on periodontitis.

Phytosterol glycosides reduce cholesterol absorption in humans.

Dietary phytosterols inhibit intestinal cholesterol absorption and regulate whole body cholesterol excretion and balance. However, they are biochemically heterogeneous and a portion is glycosylated in some foods with unknown effects on biological activity. We tested the hypothesis that phytosterol glycosides reduce cholesterol absorption in humans. Phytosterol glycosides were extracted and purified from soy lecithin in a novel two-step process. Cholesterol absorption was measured in a series of three single-meal tests given at intervals of 2 wk to each of 11 healthy subjects. In a randomized crossover design, participants received approximately 300 mg of added phytosterols in the form of phytosterol glycosides or phytosterol esters, or placebo in a test breakfast also containing 30 mg cholesterol-d7. Cholesterol absorption was estimated by mass spectrometry of plasma cholesterol-d7 enrichment 4-5 days after each test. Compared with the placebo test, phytosterol glycosides reduced cholesterol absorption by 37.6+/-4.8% (P<0.0001) and phytosterol esters 30.6+/-3.9% (P=0.0001). These results suggest that natural phytosterol glycosides purified from lecithin are bioactive in humans and should be included in methods of phytosterol analysis and tables of food phytosterol content.

Combined Effects of Ezetimibe and Phytosterols on Cholesterol Metabolism A Randomized, Controlled Feeding Study in Humans

Background— Both ezetimibe and phytosterols inhibit cholesterol absorption. We tested the hypothesis that the combination of ezetimibe and phytosterols is more effective than ezetimibe alone in altering cholesterol metabolism. Methods and Results— Twenty-one mildly hypercholesterolemic subjects completed a randomized, double-blind, placebo-controlled, triple-crossover study. Each subject received a phytosterol-controlled diet plus (1) ezetimibe placebo+phytosterol placebo, (2) 10 mg/d ezetimibe+phytosterol placebo, and (3) 10 mg/d ezetimibe+2.5 g phytosterols for 3 weeks each. All meals were prepared in a metabolic kitchen. Primary outcomes were intestinal cholesterol absorption, fecal cholesterol excretion, and low-density lipoprotein cholesterol levels. The combined treatment resulted in significantly lower intestinal cholesterol absorption (598 mg/d; 95% confidence interval [CI], 368 to 828) relative to control (2161 mg/d; 95% CI, 1112 to 3209) and ezetimibe alone (1054 mg/d; 95% CI, 546 to 1561; both P <0.0001). Fecal cholesterol excretion was significantly greater ( P <0.0001) with combined treatment (962 mg/d; 95% CI, 757 to 1168) relative to control (505 mg/d; 95% CI, 386 to 625) and ezetimibe alone (794 mg/d; 95% CI, 615 to 973). Plasma low-density lipoprotein cholesterol values during treatment with control, ezetimibe alone, and ezetimibe+phytosterols averaged 129 mg/dL (95% CI, 116 to 142), 108 mg/dL (95% CI, 97 to 119), and 101 mg/dL (95% CI, 90 to 112; ( P <0.0001 relative to control). Conclusion— The addition of phytosterols to ezetimibe significantly enhanced the effects of ezetimibe on whole-body cholesterol metabolism and plasma low-density lipoprotein cholesterol. The large cumulative action of combined dietary and pharmacological treatment on cholesterol metabolism emphasizes the potential importance of dietary phytosterols as adjunctive therapy for the treatment of hypercholesterolemia. Clinical Trial Registration— URL: . Unique identifier: [NCT00863265][1]. # Clinical Perspective {#article-title-27} [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00863265&atom=%2Fcirculationaha%2F124%2F5%2F596.atomBACKGROUND Both ezetimibe and phytosterols inhibit cholesterol absorption. We tested the hypothesis that the combination of ezetimibe and phytosterols is more effective than ezetimibe alone in altering cholesterol metabolism. METHODS AND RESULTS Twenty-one mildly hypercholesterolemic subjects completed a randomized, double-blind, placebo-controlled, triple-crossover study. Each subject received a phytosterol-controlled diet plus (1) ezetimibe placebo+phytosterol placebo, (2) 10 mg/d ezetimibe+phytosterol placebo, and (3) 10 mg/d ezetimibe+2.5 g phytosterols for 3 weeks each. All meals were prepared in a metabolic kitchen. Primary outcomes were intestinal cholesterol absorption, fecal cholesterol excretion, and low-density lipoprotein cholesterol levels. The combined treatment resulted in significantly lower intestinal cholesterol absorption (598 mg/d; 95% confidence interval [CI], 368 to 828) relative to control (2161 mg/d; 95% CI, 1112 to 3209) and ezetimibe alone (1054 mg/d; 95% CI, 546 to 1561; both P<0.0001). Fecal cholesterol excretion was significantly greater (P<0.0001) with combined treatment (962 mg/d; 95% CI, 757 to 1168) relative to control (505 mg/d; 95% CI, 386 to 625) and ezetimibe alone (794 mg/d; 95% CI, 615 to 973). Plasma low-density lipoprotein cholesterol values during treatment with control, ezetimibe alone, and ezetimibe+phytosterols averaged 129 mg/dL (95% CI, 116 to 142), 108 mg/dL (95% CI, 97 to 119), and 101 mg/dL (95% CI, 90 to 112; (P<0.0001 relative to control). CONCLUSION The addition of phytosterols to ezetimibe significantly enhanced the effects of ezetimibe on whole-body cholesterol metabolism and plasma low-density lipoprotein cholesterol. The large cumulative action of combined dietary and pharmacological treatment on cholesterol metabolism emphasizes the potential importance of dietary phytosterols as adjunctive therapy for the treatment of hypercholesterolemia. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00863265.

Effect of acute dietary nitrate intake on maximal knee extensor speed and power in healthy men and women.

Nitric oxide (NO) has been demonstrated to enhance the maximal shortening velocity and maximal power of rodent muscle. Dietary nitrate (NO3(-)) intake has been demonstrated to increase NO bioavailability in humans. We therefore hypothesized that acute dietary NO3(-) intake (in the form of a concentrated beetroot juice (BRJ) supplement) would improve muscle speed and power in humans. To test this hypothesis, healthy men and women (n = 12; age = 22-50 y) were studied using a randomized, double-blind, placebo-controlled crossover design. After an overnight fast, subjects ingested 140 mL of BRJ either containing or devoid of 11.2 mmol of NO3(-). After 2 h, knee extensor contractile function was assessed using a Biodex 4 isokinetic dynamometer. Breath NO levels were also measured periodically using a Niox Mino analyzer as a biomarker of whole-body NO production. No significant changes in breath NO were observed in the placebo trial, whereas breath NO rose by 61% (P < 0.001; effect size = 1.19) after dietary NO3(-) intake. This was accompanied by a 4% (P < 0.01; effect size = 0.74) increase in peak knee extensor power at the highest angular velocity tested (i.e., 6.28 rad/s). Calculated maximal knee extensor power was therefore greater (i.e., 7.90 ± 0.59 vs. 7.44 ± 0.53 W/kg; P < 0.05; effect size = 0.63) after dietary NO3(-) intake, as was the calculated maximal velocity (i.e., 14.5 ± 0.9 vs. 13.1 ± 0.8 rad/s; P < 0.05; effect size = 0.67). No differences in muscle function were observed during 50 consecutive knee extensions performed at 3.14 rad/s. We conclude that acute dietary NO3(-) intake increases whole-body NO production and muscle speed and power in healthy men and women.

The effects of phytosterols present in natural food matrices on cholesterol metabolism and LDL-cholesterol: a controlled feeding trial

Background/Objectives:Extrinsic phytosterols supplemented to the diet reduce intestinal cholesterol absorption and plasma low-density lipoprotein (LDL)-cholesterol. However, little is known about their effects on cholesterol metabolism when given in native, unpurified form and in amounts achievable in the diet. The objective of this investigation was to test the hypothesis that intrinsic phytosterols present in unmodified foods alter whole-body cholesterol metabolism.Subjects/Methods:In all, 20 out of 24 subjects completed a randomized, crossover feeding trial wherein all meals were provided by a metabolic kitchen. Each subject consumed two diets for 4 weeks each. The diets differed in phytosterol content (phytosterol-poor diet, 126 mg phytosterols/2000 kcal; phytosterol-abundant diet, 449 mg phytosterols/2000 kcal), but were otherwise matched for nutrient content. Cholesterol absorption and excretion were determined by gas chromatography/mass spectrometry after oral administration of stable isotopic tracers.Results:The phytosterol-abundant diet resulted in lower cholesterol absorption (54.2±2.2% (95% confidence interval 50.5%, 57.9%) vs 73.2±1.3% (69.5%, 76.9%), P<0.0001) and 79% higher fecal cholesterol excretion (1322±112 (1083.2, 1483.3) vs 739±97 mg/day (530.1, 930.2), P<0.0001) relative to the phytosterol-poor diet. Plasma lathosterol/cholesterol ratio rose by 82% (from 0.71±0.11 (0.41, 0.96) to 1.29±0.14 μg/mg (0.98, 1.53), P<0.0001). LDL-cholesterol was similar between diets.Conclusions:Intrinsic phytosterols at levels present in a healthy diet are biologically active and have large effects on whole-body cholesterol metabolism not reflected in circulating LDL. More work is needed to assess the effects of phytosterol-mediated fecal cholesterol excretion on coronary heart disease risk in humans.

Acute Dietary Nitrate Intake Improves Muscle Contractile Function in Patients With Heart Failure A Double-Blind, Placebo-Controlled, Randomized Trial

Background—Skeletal muscle strength, velocity, and power are markedly reduced in patients with heart failure, which contributes to their impaired exercise capacity and lower quality of life. This muscle dysfunction may be partially because of decreased nitric oxide (NO) bioavailability. We therefore sought to determine whether ingestion of inorganic nitrate (NO3−) would increase NO production and improve muscle function in patients with heart failure because of systolic dysfunction. Methods and Results—Using a double-blind, placebo-controlled, randomized crossover design, we determined the effects of dietary NO3− in 9 patients with heart failure. After fasting overnight, subjects drank beetroot juice containing or devoid of 11.2 mmol of NO3−. Two hours later, muscle function was assessed using isokinetic dynamometry. Dietary NO3− increased (P<0.05–0.001) breath NO by 35% to 50%. This was accompanied by 9% (P=0.07) and 11% (P<0.05) increases in peak knee extensor power at the 2 highest movement velocities tested (ie, 4.71 and 6.28 rad/s). Maximal power (calculated by fitting peak power data with a parabola) was therefore greater (ie, 4.74±0.41 versus 4.20±0.33 W/kg; P<0.05) after dietary NO3− intake. Calculated maximal velocity of knee extension was also higher after NO3− ingestion (ie, 12.48±0.95 versus 11.11±0.53 rad/s; P<0.05). Blood pressure was unchanged, and no adverse clinical events occurred. Conclusions—In this pilot study, acute dietary NO3− intake was well tolerated and enhanced NO bioavailability and muscle power in patients with systolic heart failure. Larger-scale studies should be conducted to determine whether the latter translates into an improved quality of life in this population. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01682356.

Acute Dietary Nitrate Intake Improves Muscle Contractile Function in Patients With Heart FailureCLINICAL PERSPECTIVE

Background—Skeletal muscle strength, velocity, and power are markedly reduced in patients with heart failure, which contributes to their impaired exercise capacity and lower quality of life. This muscle dysfunction may be partially because of decreased nitric oxide (NO) bioavailability. We therefore sought to determine whether ingestion of inorganic nitrate (NO3−) would increase NO production and improve muscle function in patients with heart failure because of systolic dysfunction. Methods and Results—Using a double-blind, placebo-controlled, randomized crossover design, we determined the effects of dietary NO3− in 9 patients with heart failure. After fasting overnight, subjects drank beetroot juice containing or devoid of 11.2 mmol of NO3−. Two hours later, muscle function was assessed using isokinetic dynamometry. Dietary NO3− increased (P<0.05–0.001) breath NO by 35% to 50%. This was accompanied by 9% (P=0.07) and 11% (P<0.05) increases in peak knee extensor power at the 2 highest movement velocities tested (ie, 4.71 and 6.28 rad/s). Maximal power (calculated by fitting peak power data with a parabola) was therefore greater (ie, 4.74±0.41 versus 4.20±0.33 W/kg; P<0.05) after dietary NO3− intake. Calculated maximal velocity of knee extension was also higher after NO3− ingestion (ie, 12.48±0.95 versus 11.11±0.53 rad/s; P<0.05). Blood pressure was unchanged, and no adverse clinical events occurred. Conclusions—In this pilot study, acute dietary NO3− intake was well tolerated and enhanced NO bioavailability and muscle power in patients with systolic heart failure. Larger-scale studies should be conducted to determine whether the latter translates into an improved quality of life in this population. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01682356.

Plasma Biomarker of Dietary Phytosterol Intake

Background Dietary phytosterols, plant sterols structurally similar to cholesterol, reduce intestinal cholesterol absorption and have many other potentially beneficial biological effects in humans. Due to limited information on phytosterol levels in foods, however, it is difficult to quantify habitual dietary phytosterol intake (DPI). Therefore, we sought to identify a plasma biomarker of DPI. Methods and Findings Data were analyzed from two feeding studies with a total of 38 subjects during 94 dietary periods. DPI was carefully controlled at low, intermediate, and high levels. Plasma levels of phytosterols and cholesterol metabolites were assessed at the end of each diet period. Based on simple ordinary least squares regression analysis, the best biomarker for DPI was the ratio of plasma campesterol to the endogenous cholesterol metabolite 5-α-cholestanol (R2 = 0.785, P < 0.0001). Plasma campesterol and 5-α-cholestanol levels varied greatly among subjects at the same DPI level, but were positively correlated at each DPI level in both studies (r > 0.600; P < 0.01). Conclusion The ratio of plasma campesterol to the coordinately regulated endogenous cholesterol metabolite 5-α-cholestanol is a biomarker of dietary phytosterol intake. Conversely, plasma phytosterol levels alone are not ideal biomarkers of DPI because they are confounded by large inter-individual variation in absorption and turnover of non-cholesterol sterols. Further work is needed to assess the relation between non-cholesterol sterol metabolism and associated cholesterol transport in the genesis of coronary heart disease.