Morbus Fabry ist eine multisystemische Erkrankung, die zahlreiche Komplikationen mit sich bringt. Eine verminderte Aktivität des Enzyms α-Galactosidase führt zu einer Anreicherung von Globotriaosylceramiden in verschiedenen Organen und Geweben. Betroffene Patienten entwickeln häufig eine linksventrikuläre Hypertrophie und eine renale Fibrose. Wegen Hitzeintoleranz und Hypohidrosis vermeiden Patienten häufig eine Sonnenexposition. Wir stellten die Hypothese auf, dass ein Vitamin D-Mangel an der Ausprägung einer Fabry-kardiomyopathie beteiligt ist. In dieser Querschnittstudie wurde der Einfluss des Vitamin D-Status auf die typischerweise auftretenden Komplikationen der Erkrankung an 111 Patienten mit gesichertem Morbus Fabry vor Beginn einer Enzymersatztherapie untersucht. Dafür bestimmten wir das 25(OH)D und teilten die Patienten anhand dieser Werte in drei Gruppen ein: Vitamin D-defizient (25(OH)D<15 ng/ml), Vitamin D-insuffizient (25(OH)D 15-30 ng/ml und Vitamin Dsuffizient (25(OH)D >30 ng/ml). Es erfolgten Magnetresonanztomographie- und echokardiographische Untersuchungen zur Bestimmung der linksventrikulären Masse und einer möglichen Kardiomyopathie. In Querschnittsanalysen wurden Assoziationen zwischen auftretenden klinischen Symptomen und dem Vitamin D-Status durch lineare bzw. binäre logistische Regressionsanalysen bestimmt und nach Alter, Geschlecht, BMI und Jahreszeit der Messung adjustiert. Die Patienten waren im Durchschnitt 40,1±12,5 Jahre alt (42% männlich) und hatten einen durchschnittlichen 25(OH)D-Wert von 23,5±11,4 ng/ml. Patienten der defizienten 25(OH)D-Gruppe hatten ein adjustiertes 6-fach erhöhtes Risiko für eine hypertrophe Kardiomyopathie verglichen mit der suffizienten Kontrollgruppe (p=0,04). Die durchschnittliche linksventrikuläre Masse unterschied sich signifikant: 170±75 g in der defizienten, 154±60 g in der insuffizienten und 128±58 g in der suffizienten Gruppe (p=0,01). Mit dem Schweregrad der Vitamin D-Defizienz stieg der Median einer vorhandenen Proteinurie sowie die Prävalenz von Hitzeintoleranz, Ödemen, Cornea verticillata, Diarrhoen und dem Bedarf einer Schmerzmedikation. Unsere Studie hat gezeigt, dass Patienten mit niedrigen Vitamin D-Werten gehäuft an Komplikationen leiden.75 Dazu gehören die progressive Fabry-Nephropathie, hypertrophe Kardiomyopathie und die Krankheit typischerweise begleitende klinische Symptome. Zum jetzigen Zeitpunkt können wir allerdings eine Vitamin D-Therapie, basierend auf unseren Daten noch nicht grundsätzlich empfehlen obwohl eine Vitamin D-Supplementierung über Vitamin D angereicherte Nahrungsmittel im Allgemeinen empfohlen wird. Unsere Ergebnisse sind bisher nur Beobachtungen und können einen kausalen Zusammenhang nicht beweisen. / Patients with Fabry disease frequently develop left ventricular (LV) hypertrophy and renal fibrosis. Due to heat intolerance and an inability to sweat, patients tend to avoid exposure to sunlight. We hypothesized that subsequent vitamin D deficiency may contribute to Fabry cardiomyopathy. This study investigated the vitamin D status and its association with LV mass and adverse clinical symptoms in patients with Fabry disease. 25-hydroxyvitamin D (25[OH]D) was measured in 111 patients who were genetically proven to have Fabry disease. LV mass and cardiomyopathy were assessed by magnetic resonance imaging and echocardiography. In cross-sectional analyses, associations with adverse clinical outcomes were determined by linear and binary logistic regression analyses, respectively, and were adjusted for age, sex, BMI and season. Patients had a mean age of 40 ± 13 years (42 % males), and a mean 25(OH)D of 23.5 ± 11.4 ng/ml. Those with overt vitamin D deficiency (25[OH]D ≤ 15 ng/ml) had an adjusted six fold higher risk of cardiomyopathy, compared to those with sufficient 25(OH)D levels >30 ng/ml (p = 0.04). The mean LV mass was distinctively different with 170 ± 75 g in deficient, 154 ± 60 g in moderately deficient and 128 ± 58 g in vitamin D sufficient patients (p = 0.01). With increasing severity of vitamin D deficiency, the median levels of proteinuria increased, as well as the prevalences of depression, edema, cornea verticillata and the need for medical pain therapy. In conclusion, vitamin D deficiency was strongly associated with cardiomyopathy and adverse clinical symptoms in patients with Fabry disease. Whether vitamin D supplementation improves complications of Fabry disease, requires a randomized controlled trial.

It has long been known that vitamin D is important for calcium absorption and bone health. More recently, vitamin D has been found to modulate breast cancer cell growth and increasingly epidemiologic studies suggest vitamin D may be associated with reduced breast cancer risk. The primary objective of this thesis was to evaluate the associations between vitamin D from all sources (food, supplements and sunlight exposure) and breast cancer. Secondary objectives were focused on methodological issues including the development of a solar vitamin D score and adapting the measurement of vitamin D from foods for use among Canadians. The data source for this study was the “Ontario Women’s Diet and Health Study”, a population-based case-control study of women in Ontario. Cases (n = 3,101) diagnosed between 2002 and 2003 were identified through the Ontario Cancer Registry and controls (n = 3,471) were identified through random digit dialing of Ontario households. Study participants completed mailed risk factor and food frequency questionnaires. Vitamin D intake from supplements (>400 IU/day compared to none) was found to be associated with reduced breast cancer risk (OR = 0.76; 95% CI: 0.59, 0.98). However, total vitamin D intake (from food and supplements) and intake from food alone were not associated with breast cancer risk. Time spent outdoors during 4 periods of life (including adolescence) was associated with reduced breast cancer (e.g., highest versus lowest categories of exposure at age 40 to 59: OR = 0.74; 95% CI: 0.61, 0.88). The novel solar vitamin D score, derived from time spent outdoors, skin color, sun protection practices, and ultraviolet radiation of residence, was also associated with reduced breast cancer risk. In summary, there is some evidence to suggest that vitamin D intake from supplements and determinants of cutaneous vitamin D production are associated with reduced breast cancer risk.

Current vitamin D intakes in Canada are inadequate. The extension of vitamin D fortification to additional foods may be an effective and appropriate strategy for increasing vitamin D intakes in the general population. Cheese is potentially an ideal candidate for vitamin D fortification. We introduce the potential use of casein proteins as a vehicle for vitamin D3 fortification in industrially made cheeses where we found that over 90% of vitamin D3 added to milk was retained in both Cheddar and Mozzarella cheeses. Use of casein proteins for vitamin D3 fortification did not fully prevent vitamin D3 loss into whey. However the loss was minimized to approximately 8%. We then show that vitamin D3 is bioavailable from fortified Mozzarella cheese baked with pizza suggesting that the high temperature baking process does not significantly breakdown vitamin D3. Our findings could have important implications in increasing fortified food options for Canadians.

All populations risk vitamin D inadequacy. We conducted a randomized double- blind trial of vitamin D3 fortified cheddar cheese to study bioavailability based on serum 25-hydroxyvitamin D [25(OH)D] concentrations, and its effects on mental health scores in older adults. Once a week, 28 subjects received 200 IU or 28000 IU of vitamin D3 per fortified cheese serving. The mean increases in 25(OH)D over 8 weeks were: 4.2±11.4 and 29.4±16.2 for the 200 IU/week and 28,000 IU/ week dose groups, respectively (groups differ, P<0.001). Subjects who consumed 28,000 IU/week cheese improved their Mental Component Summary (MCS) scores, based upon the SF-36v2 questionnaire conducted at baseline and at 8 weeks (P<0.05). There was also a positive correlation between the change in MCS score and the change in 25(OH)D (1 tail; P<0.05). These data demonstrate the suitability of fortified cheddar cheese, and provide evidence of neurocognitive benefits with higher 25(OH)D levels.

Current vitamin D intakes in Canada are inadequate. The extension of vitamin D fortification to additional foods may be an effective and appropriate strategy for increasing vitamin D intakes in the general population. Cheese is potentially an ideal candidate for vitamin D fortification. We introduce the potential use of casein proteins as a vehicle for vitamin D3 fortification in industrially made cheeses where we found that over 90% of vitamin D3 added to milk was retained in both Cheddar and Mozzarella cheeses. Use of casein proteins for vitamin D3 fortification did not fully prevent vitamin D3 loss into whey. However the loss was minimized to approximately 8%. We then show that vitamin D3 is bioavailable from fortified Mozzarella cheese baked with pizza suggesting that the high temperature baking process does not significantly breakdown vitamin D3. Our findings could have important implications in increasing fortified food options for Canadians.

All populations risk vitamin D inadequacy. We conducted a randomized double- blind trial of vitamin D3 fortified cheddar cheese to study bioavailability based on serum 25-hydroxyvitamin D [25(OH)D] concentrations, and its effects on mental health scores in older adults. Once a week, 28 subjects received 200 IU or 28000 IU of vitamin D3 per fortified cheese serving. The mean increases in 25(OH)D over 8 weeks were: 4.2±11.4 and 29.4±16.2 for the 200 IU/week and 28,000 IU/ week dose groups, respectively (groups differ, P<0.001). Subjects who consumed 28,000 IU/week cheese improved their Mental Component Summary (MCS) scores, based upon the SF-36v2 questionnaire conducted at baseline and at 8 weeks (P<0.05). There was also a positive correlation between the change in MCS score and the change in 25(OH)D (1 tail; P<0.05). These data demonstrate the suitability of fortified cheddar cheese, and provide evidence of neurocognitive benefits with higher 25(OH)D levels.

It has long been known that vitamin D is important for calcium absorption and bone health. More recently, vitamin D has been found to modulate breast cancer cell growth and increasingly epidemiologic studies suggest vitamin D may be associated with reduced breast cancer risk. The primary objective of this thesis was to evaluate the associations between vitamin D from all sources (food, supplements and sunlight exposure) and breast cancer. Secondary objectives were focused on methodological issues including the development of a solar vitamin D score and adapting the measurement of vitamin D from foods for use among Canadians. The data source for this study was the “Ontario Women’s Diet and Health Study”, a population-based case-control study of women in Ontario. Cases (n = 3,101) diagnosed between 2002 and 2003 were identified through the Ontario Cancer Registry and controls (n = 3,471) were identified through random digit dialing of Ontario households. Study participants completed mailed risk factor and food frequency questionnaires. Vitamin D intake from supplements (>400 IU/day compared to none) was found to be associated with reduced breast cancer risk (OR = 0.76; 95% CI: 0.59, 0.98). However, total vitamin D intake (from food and supplements) and intake from food alone were not associated with breast cancer risk. Time spent outdoors during 4 periods of life (including adolescence) was associated with reduced breast cancer (e.g., highest versus lowest categories of exposure at age 40 to 59: OR = 0.74; 95% CI: 0.61, 0.88). The novel solar vitamin D score, derived from time spent outdoors, skin color, sun protection practices, and ultraviolet radiation of residence, was also associated with reduced breast cancer risk. In summary, there is some evidence to suggest that vitamin D intake from supplements and determinants of cutaneous vitamin D production are associated with reduced breast cancer risk.

Purpose: National prevalence of childhood overweight and obesity has plateaued in recent years, but rates remain high, with approximately 10% among children“high weight.” The relationship between adiposity and serum 25-hydroxyvitamin D [25(OH)D] status has been well-explored in older individuals, with inconsistent results. Furthermore, previous studies have suggested a relationship between adequate consumption of calcium and vitamin D and healthy weight status in older children and adults. However, in the infant population, there are few studies detailing the interaction between body composition and serum 25(OH)D or intake of calcium and vitamin D. Our study aims were to assess the association between serum 25(OH)D and body composition and to examine the association between adiposity and dietary intake of calcium and vitamin D in a sample of infants and toddlers. Methods: Our population included healthy male and female infants and toddlers from Pittsburgh, PA who participated in the “Practices Affecting Vitamin D Status in Pittsburgh Infants and Toddlers” study. Parents completed a Vitamin D and Sunlight Exposure Questionnaire, which assessed dietary intake of foods high in calcium and vitamin D as well as daily sunlight exposure (≥2 hours vs. >2 hours). Anthropometric measures and bloodwork for serum 25(OH)D were obtained during at the time of the study visit. Weight-for-length (WFL) percentile status was determined using WHO growth standards (low weight97.7 %ile) and WFL z-scores were calculated. ANOVA was used to compare mean serum 25(OH)D and calcium and vitamin D intake by WFL status. Chi square analysis was used to evaluate the relationship between serum 25(OH) D status (deficient =/mL, insufficient = 12-20 ng/mL, sufficient >20 ng/mL), calcium intake status (sufficient = >700 mg), vitamin D intake status (sufficient = >400 IU) and WFL percentile status. Pearson’s correlation coefficient was used to assess the strength and significance of associations between serum 25(OH)D, calcium and vitamin D intake and WFL z-score. The analysis was repeated after subdivision by race and sun exposure. Results: 125 infants and toddlers (9 to 24 months of age, 68% African American) participated in the study. Approximately 11% of the population had a high weight. Mean vitamin D intake (~600 IU/d) and median calcium intake (~1550 mg/d) exceeded recommendations. Prevalence of high weight was higher among children with adequate intake compared to those who consumed less than the recommendations (calcium: 41% vs. 36%, respectively; vitamin D: 45% vs. 29%, respectively). However, this difference was not statistically significant. Mean serum 25(OH)D level (37 ng/mL) was sufficient. When compared across WFL status, neither mean serum 25(OH)D nor mean intake of calcium and vitamin D varied significantly. No significant correlation was found between WFL and serum 25(OH)D for the cohort or any of the subgroups examined. Conclusions: Rates of infant overweight and obesity in our sample are similar in comparison with the national average. Our results do not support a relationship between calcium and vitamin D intake on weight status or an association between serum vitamin D and body composition in children of this age. Future studies are needed to re-examine these relationships in a larger group of children of more evenly distributed weight status.

Thesis (Ph. D.)--Rutgers University, 2008. / "Graduate Program in Food Science." Includes bibliographical references (p. 78-97).

Thesis (Ph. D.)--University of Hong Kong, 1984.