Armin Zittermann

Vitamin D in preventive medicine: are we ignoring the evidence?

Vitamin D is metabolised by a hepatic 25-hydroxylase into 25-hydroxyvitamin D (25(OH)D) and by a renal 1alpha-hydroxylase into the vitamin D hormone calcitriol. Calcitriol receptors are present in more than thirty different tissues. Apart from the kidney, several tissues also possess the enzyme 1alpha-hydroxylase, which is able to use circulating 25(OH)D as a substrate. Serum levels of 25(OH)D are the best indicator to assess vitamin D deficiency, insufficiency, hypovitaminosis, adequacy, and toxicity. European children and young adults often have circulating 25(OH)D levels in the insufficiency range during wintertime. Elderly subjects have mean 25(OH)D levels in the insufficiency range throughout the year. In institutionalized subjects 25(OH)D levels are often in the deficiency range. There is now general agreement that a low vitamin D status is involved in the pathogenesis of osteoporosis. Moreover, vitamin D insufficiency can lead to a disturbed muscle function. Epidemiological data also indicate a low vitamin D status in tuberculosis, rheumatoid arthritis, multiple sclerosis, inflammatory bowel diseases, hypertension, and specific types of cancer. Some intervention trials have demonstrated that supplementation with vitamin D or its metabolites is able: (i) to reduce blood pressure in hypertensive patients; (ii) to improve blood glucose levels in diabetics; (iii) to improve symptoms of rheumatoid arthritis and multiple sclerosis. The oral dose necessary to achieve adequate serum 25(OH)D levels is probably much higher than the current recommendations of 5-15 microg/d.

Low vitamin D status: A contributing factor in the pathogenesis of congestive heart failure?

OBJECTIVES This study was designed to evaluate the association between vitamin D status and congestive heart failure (CHF). BACKGROUND Impaired intracellular calcium metabolism is an important factor in the pathogenesis of CHF. The etiology of CHF, however, is not well understood. METHODS Twenty patients age <50 years and 34 patients age >/=50 years with New York Heart Association classes >/=2 and 34 control subjects age >/=50 years were recruited. N-terminal pro-atrial natriuretic peptide (NT-proANP), a predictor of CHF severity; vitamin D metabolites; and parameters of calcium metabolism were measured in fasting blood samples collected between November 2000 and March 2001. RESULTS Both groups of CHF patients had markedly increased serum levels of NT-proANP (p < 0.001), increased serum phosphorus levels (p < 0.001), and reduced circulating levels of both 25-hydroxyvitamin D (p < 0.001) and calcitriol (p < 0.001). Albumin-corrected calcium levels were reduced and parathyroid hormone levels were increased in the younger CHF patients compared with the controls (both p values <0.001). Moreover, parathyroid hormone levels tended to be higher in the elderly CHF patients than in the controls (p = 0.074). In a nonlinear regression analysis 25-hydroxyvitamin D and calcitriol were inversely correlated with NT-proANP (r(2) = 0.16; p < 0.001 and r(2) = 0.12; p < 0.01, respectively). The vitamin D genotype at the BmsI restriction site did not differ between the study groups. CONCLUSIONS The low vitamin D status can explain alterations in mineral metabolism as well as myocardial dysfunction in the CHF patients, and it may therefore be a contributing factor in the pathogenesis of CHF.

Low vitamin D status is associated with low cord blood levels of the immunosuppressive cytokine interleukin‐10

The cytokine interleukin‐10 (IL‐10) plays a pivotal regulatory role in tolerizing exogenous antigens. Experimental data indicate that low cellular availability of the vitamin D hormone 1,25‐dihydroxyvitamin D [1,25(OH)2D] results in a down‐regulation of IL‐10 concentrations. The tissue production of an adequate amount of 1,25(OH)2D depends on a high circulating 25‐hydroxyvitamin D (25‐OHD) level. The present study was thus aimed at evaluating the associations between season of birth, vitamin D status, and the allergy risk markers IL‐10 and total immunoglobulin (IgE) in newborns. Cord blood was obtained from 49 infants born during the summer half year (mid‐April to mid‐October, geographic latitude 51°N) and from 47 infants born during the winter half year (mid‐October to mid‐April, geographic latitude of 51°N). Serum levels of 25‐OHD were 99% higher, and IL‐10 levels were 43% higher in the summer half year compared with the winter half year (p < 0.001 and p = 0.018). Moreover, the ratio of IL‐10 to total IgE was 124% higher in the summer half year compared with the winter half year (p = 0.039). Serum levels of 25‐OHD were correlated with IL‐10 levels (r = +0.22; p < 0.05). Mothers’ age, gestational ages, birth weights and serum 1,25(OH)2D levels did not differ between study groups. We conclude that the low vitamin D status of infants born in winter may at least in part adversely affect biomarkers of allergy risk.

Effects of vitamin K on calcium and bone metabolism.

The K vitamins, a group of napthoquinones, are required for the carboxylation of a limited number of proteins including the bone matrix protein osteocalcin. Vitamin K1 (phylloquinone) and vitamin K2 (menaquinones), differ regarding food source (green vegetables and fermented products, respectively), bioavailabilty and intermediate metabolism. Epidemiological studies provide evidence for an association between a low vitamin K intake and an enhanced osteoporotic fracture risk. Doses of vitamin K1 up to 15 times the current recommended dietary allowance have successfully been used to reduce the percentage of undercarboxylated osteocalcin in the circulation. Studies demonstrating clear beneficial effects on bone health, however, are still lacking. In contrast, therapy with very high pharmacological doses of the vitamin K2 menatetrenone has impressively been used to prevent further bone mineral loss and fracture risk in osteoporotic patients.

Low serum levels of intact osteocalcin in patients with congestive heart failure.

Abstract Impaired bone metabolism is a frequent complication following heart transplantation. Little is known, however, about possible alterations in bone turnover of pretransplant patients with congestive heart failure (CHF). We therefore studied biomarkers of bone turnover in 21 male patients with CHF (New York Heart Association [NYHA] classification > II) compared with 21 controls (NYHA classification < II). Biomarkers of bone formation (intact osteocalcin and carboxy-terminal propeptide of type I collagen), markers of bone resorption (N-telopeptide and C-telopeptide of type I collagen), undercarboxylated osteocalcin (an indicator of fracture risk), and concentrations of calcium, parathyroid hormone, and vitamin D metabolites (25-hydroxyvitamin D and calcitriol) were measured in fasting blood samples. Serum levels of intact osteocalcin were 44.5% lower (P < 0.01), and the ratio of undercarboxylated-to-intact osteocalcin was 113% higher (P < 0.01) in the patients in comparison with the controls. Moreover, patients had 34% lower 25-hydroxyvitamin D levels (P < 0.01) and 22% lower calcitriol levels (P < 0.05) than the controls. The bone resorption markers, N-telopeptide and C-telopeptide; the bone formation marker, carboxy-terminal propeptide of type I collagen; parathyroid hormone levels; and albumin-adjusted serum calcium concentrations did not differ between patients and controls (all P values > 0.05). In summary, there were no biochemical signs of enhanced bone collagen resorption in pretransplant CHF patients. However, the low serum levels of intact osteocalcin and the high ratio of undercarboxylated-to-intact osteocalcin deserve further consideration.

Carbamazepine Does Not Alter Biochemical Parameters of Bone Turnover in Healthy Male Adults

It is still not completely clear whether or not carbamazepine (CBZ) causes alterations in vitamin D status and in bone metabolism. The objective of this study was therefore to investigate prospectively in healthy adults the effects of CBZ on serum levels of 25-hydroxyvitamin D (25OHD) and on biomarkers of bone formation and resorption. Twenty-one free-living male adults were taking 800 mg/day CBZ for 10 weeks. The study was performed from December 1997 until September 1998 at a geographic latitude of 51°N. Blood samples were collected before treatment (t1), 33 days (SE 2.5) after starting treatment (t2), and 70 days (SE 3.6) after starting treatment (t3). In 13 out of the 21 subjects blood samples were also drawn 64 days (SE 9.0) after treatment had been terminated (t4). Serum 25OHD levels remained constant during study periods t1–t3. 25OHD levels were, however, significantly higher at t4 compared to t1–t3. Serum concentrations of intact osteocalcin, a bone formation marker, and C-telopeptide, a bone resorption marker, were similar during all examinations. Moreover, serum levels of parathyroid hormone, calcium, and inorganic phosphate did not change. Data indicate that CBZ per se does not alter bone metabolism and does not lead to decreased circulating 25OHD levels in young males without epilepsy. Variations in 25OHD levels are in line with the seasonal fluctuations in vitamin D status.

Selected Nutrients and Their Implications for Health and Disease across the Lifespan: A Roadmap

Worldwide approximately two billion people have a diet insufficient in micronutrients. Even in the developed world, an increasing number of people consume nutrient-poor food on a regular basis. Recent surveys in Western countries consistently indicate inadequate intake of nutrients such as vitamins and minerals, compared to recommendations. The International Osteoporosis Foundation’s (IOF) latest figures show that globally about 88% of the population does not have an optimal vitamin D status. The Lancet’s “Global Burden of Disease Study 2010” demonstrates a continued growth in life expectancy for populations around the world; however, the last decade of life is often disabled by the burden of partly preventable health issues. Compelling evidence suggests that improving nutrition protects health, prevents disability, boosts economic productivity and saves lives. Investments to improve nutrition make a positive contribution to long-term national and global health, economic productivity and stability, and societal resilience.

Wheat bran supplementation does not affect biochemical markers of bone turnover in young adult women with recommended calcium intake

We investigated the effect of wheat bran on biochemical indicators of Ca and bone metabolism in nineteen healthy women, aged 25.5 (SE 0.9) years. Subjects received six wheat bran biscuits or six white flour biscuits per day for a period of 4 weeks (crossover). Wheat bran consumption increased fibre intake from 17.7 (SE 1.3) to 29.6 (SE 1.3) g/d (7 d food record) and enhanced P intake from 1225 (SE 59) mg/d to 1663 (SE 65) mg/d; P < 0.001. Mean daily Ca intake during wheat bran consumption (1110 (SE 82) mg/d) significantly (P = 0.008) exceeded Ca ingestion during the white flour period (955 (SE 67) mg/d). Wheat bran increased the number of defecations per week from 7.9 (SE 0.8) to 12.2 (SE 1.4) (P = 0.0018). Urinary Ca excretion over 24 h significantly (P = 0.021) decreased from 473 (SE 53) mumol/mmol creatinine (control period) to 339 (SE 37) mumol/mmol creatinine (wheat bran period). Serum 25-hydroxyvitamin D, 2 h fasting urinary Ca/creatinine excretions and 24 h urinary P excretion remained constant. No differences in serum levels of carboxy-terminal propeptide of type I procollagen (biomarker of bone formation) or in 2 h fasting urinary hydroxyproline/creatinine excretions (biomarker of bone resorption) were observed at the end of the two cycles of dietary supplementation. We conclude that a high fibre intake of approximately 30 g/d has no significant adverse effects on bone turnover in subjects with Ca intakes above 1000 mg/d and that the reduction in 24 h urinary Ca excretion is most probably the result of an adaptation process, induced by a decrease in net absorbed Ca.

Role of nutrition during long-term spaceflight

The authors discuss changes in macro- and micro-nutrients which occur in weightlessness and consider factors which help maintain appropriate nutrition during extended space flight. Basic energy requirements and metabolism are reviewed. The discussion of handling of foodstuffs includes protein, fats, carbohydrates, vitamins, folic acid, iron, and selenium. The discussion of fluids and minerals includes fluid intake, sodium, potassium, and calcium. Changes in gastrointestinal function are examined.

Die Bestimmung der intestinalen Strontiumabsorption — Etablierung und Validierung eines routinemäßig anwendbaren Testverfahrens

ZusammenfassungDie Erfassung der Strontiumabsorption wird heute als indirektes Verfahren zur Beurteilung der intestinalen Calciumabsorption diskutiert. Voraussetzung für die klinische Anwendung ist ein vertrauenswürdiges Testverfahren inclusive kontrollierter Strontiumgabe, Probenaufarbeitung und -analyse sowie die Erfassung von Normalwerten.Für unsere Studien wurde ein Kollektiv junger Frauen (n=33, 24,0 ± 2,7 Jahre; BMI 21,5 ± 1,9) herangezogen. Die Probandinnen erhielten eine Bolusgabe von 2,27 mmol Strontium zusammen mit einem Standardfrühstück (ca. 0,625 mmol Calcium). Vor und 220 min nach der Bolusgabe erfolgte die Bestimmung des Serum-Strontiumgehaltes mittels Atomabsorptionsspektrometrie. Der Variationskoeffizient der Methode lag innerhalb eines Tages bei 4,8 % (n=10) und von Tag zu Tag 9,5 % (n=8). Der Fehler der Methode betrug 2,7 %.Die Berechnung der fraktionellen Strontiumabsorptionsrate erfolgte unter Berücksichtigung des entsprechenden Verteilungsraumes (Extrazellulärflüssigkeit; Schätzverfahren über Körpergewicht bzw. Bioimpedanz-Analyse [BIA]). Die Strontiumabsorptionsrate lag im Mittel bei 13,3 ± 3,1 %, unter Berücksichtigung der BIA-Werte bei 13,6 ± 2,6 %. Rauchen, sportliche Aktivität bzw. Einnahme oraler Kontrazeptiva zeigten keinen Einfluß.Das hier vorgestellte Testverfahren ist aufgrund seiner hohen Vertrauenswürdigkeit und relativ einfacher Handhabung für Routine-untersuchungen geeignet.SummaryIntestinal strontium absorption has been discussed recently as an indirect measure for calcium uptake. Prerequisite for the clinical use of an oral strontium test is the availability of a reliable procedure including controlled strontium supply, sample pretreatment and analysis as well as the assessment of normal values.In the present study, a group of young females (n=33; 24.0 ± 2.7 y; BMI 21.5 ± 1.9) received an oral dose of 2.27 mmol strontium in a standardized breakfast that contained 0.625 mmol calcium. Before and 220 min after the bolus serum strontium concentrations were determined by means of atomic absorption spectrophotometry (coefficient of variation: within day 4.8 %, n=10; day-to-day 9.5 %, n=8). The error of the method was 2.7 %.Calculation of the fractional strontium absorption rate considered the respective distribution volume (extracellular fluid; either estimated using body weight or determined by means of bioimpedance analysis [BIA]). Average absorption rates were 13.3 ± 3.1 % and, considering BIA measurement 13.6 ± 2.6 %, respectively. Smoking, exercise and, use of oral contraceptives showed no effects.Our oral strontium test is characterized by excellent reliability, easy handling and low costs and, thus, is suitable for routine use.Intestinal strontium absorption has been discussed recently as an indirect measure for calcium uptake. Prerequisite for the clinical use of an oral strontium test is the availability of a reliable procedure including controlled strontium supply, sample pretreatment and analysis as well as the assessment of normal values. In the present study, a group of young females (n = 33; 24.0 +/- 2.7 y; BMI 21.5 +/- 1.9) received an oral dose of 2.27 mmol strontium in a standardized breakfast that contained 0.625 mmol calcium. Before and 220 min after the bolus serum strontium concentrations were determined by means of atomic absorption spectrophotometry (coefficient of variation: within day 4.8%, n = 10; day-to-day 9.5%, n = 8). The error of the method was 2.7%. Calculation of the fractional strontium absorption rate considered the respective distribution volume (extracellular fluid; either estimated using body weight or determined by means of bioimpedance analysis [BIA]). Average absorption rates were 13.3 +/- 3.1% and, considering BIA measurement 13.6 +/- 2.6%, respectively. Smoking, exercise and, use of oral contraceptives showed no effects. Our oral strontium test is characterized by excellent reliability, easy handling and low costs and, thus, is suitable for routine use.