[Vitamin K2 influences several diseases]. / K2-vitamin har betydning ved en række sygdomme

In this paper we discuss the evidence of vitamin K2 deficiency which is a factor in several chronic diseases like diabetes, osteoporosis, cancer, inflammatory and cardiovascular diseases. This deficiency is very common in the mentioned diseases although it is rarely treated by clinicians. Randomized clinical trials have shown that patients with osteoporosis, cardiovascular diseases and cancer can benefit from vitamin K2 supplement. Further studies are needed to ascertain the effect of vitamin K2 supplement in patients with diabetes and inflammatory bowel diseases.

[Unsuccessful vitamin D treatment]. / Manglende respons på behandling med D-vitamin.

Vitamin D3 (25-OHD3) analyses have increased exponentially and vitamin D deficiency (< 25 nmol/l) is common (15% of patients). The aim of the paper is to discuss reasons for unsuccessful treatment and to question the use of ergocalciferol (vitamin D2). Lack of effect of treatment can be due to: 1) too low dose, 2) incorrect analytical methods when injection treatment (vitamin D2) is used, 3) obesity, 4) seasonal variations, and 5) poor compliance. Treatment is mandatory in order to prevent osteopenia and osteoporosis. Vitamin D3 is more potent than vitamin D2. Injections with vitamin D2 should be replaced by vitamin D3.

[Effect of healthy school meal on selection of blood parameters]. / Effekten af sund skolekost på udvalgte blodparametre.

INTRODUCTION: It was tested if a healthy school meal would result in significant changes in selected blood parameters and if such parameters would lie within generally accepted optimal values. MATERIAL AND METHODS: The study was a block-randomized, controlled trial in which 145 pupils delivered blood before (week 39) and after the intervention (week 49). The intervention group received a healthy meal for two months (25-30% of the daily intake of calories). Blood samples were analyzed for 17 parameters related to carbohydrate, fat and protein metabolism as well as vitamins and minerals. RESULTS: During the intervention period, the intervention group showed a significant change in mean values for thyroid-stimulating hormone (TSH), calcium (CA) haemoglobin (HB), cobalamin (COBA) and creatinine (CREA) compared with the control group (p < 0.025). The optimal value for vitamin D in serum is about 80 nmol/l. In week 49, more than 94% of the pupils were lower than 80 nmol/l, and they generally had low calcium values. CONCLUSION: The intervention group showed significant alterations in TSH, CA, HB, COBA and CREA values from the start to the end of the intervention period compared with the control group. The results should be confirmed in a study with more participants over a longer period of time. The teenagers in the study did not have sufficient vitamin D. Treating adolescents with a daily dose of vitamin D should be considered .

[Vitamin D deficiency]. / Vitamin D-mangel.

The importance of vitamin D for osteoporosis and fractures has been known for more than 40 years. Vitamin D deficiency is diagnosed by measuring 25-hydroxyvitamin D (25-OHD), which should be > 50 nmol/l year round. Recent research suggests that a number of severe diseases could be prevented by increasing 25-OHD to 80 nmol/l. Despite a strong focus on such increase, recommendations for intake of Vitamin D have not been changed and the present recommendations are too low even to ensure > 50 nmol/l. To achieve optimal concentrations > 80 nmol/l, we estimate that 50-70 microgram of vitamin D per day for everyone from the age of 10 years is necessary. Until the safety of this dose has been further documented, we recommend 35-38 micrograms/day.

Effects of five different alcoholic drinks on patients with Crohn's disease.

OBJECTIVE: Many patients with Crohn's disease (CD) complain of abdominal discomfort after alcohol intake. The aim of the present study was to investigate the effect of ethanol and sugar content in five different alcoholic drinks on abdominal discomfort in patients with CD. MATERIAL AND METHODS: In a crossover study, two weeks apart, 12 healthy individuals and 20 patients with CD in remission consumed randomly red wine, white wine, Smirnoff Ice, Elephant Beer and pure ethanol. Blood samples were obtained for determination of serum ethanol and plasma glucose at 0, 30, 60, 90, 120 and 180 min. A self-reported pain symptom score was used. RESULTS: There was no difference between CD patients and healthy individuals in the area under the curve (AUC) for the ethanol concentration after intake of the five different drinks. The plasma AUC for glucose in the CD patients after intake of Smirnoff Ice and Elephant beer was significantly increased (p<0.05) in comparison with that in the remaining three alcoholic drinks. Abdominal pain manifestations were significantly more pronounced in CD patients following intake of Smirnoff Ice and Elephant beer, with their higher sugar concentration, compared with intake of the remaining three drinks (p<0.05). CONCLUSIONS: The present study shows no difference in alcohol absorption between CD patients and controls. The alcoholic drinks Smirnoff Ice and Elephant beer have an increased effect on self-reported abdominal pain in CD patients, probably due to the high sugar content in these drinks.

Impact of enteral supplements enriched with omega-3 fatty acids and/or omega-6 fatty acids, arginine and ribonucleic acid compounds on leptin levels and nutritional status in active Crohn's disease treated with prednisolone.

BACKGROUND: Patients with Crohn's disease (CD) often develop malnutrition due to disease activity. We aimed to assess the effect of two different enteral supplements of Impact(R) Powder (IP; Novartis, Switzerland) on leptin levels and nutritional status in active CD patients during prednisolone treatment and tapering. METHODS: Thirty-one CD patients were randomized to IP Extra (group 1) or IP Standard (group 2). Leptin levels, nutritional, clinical and biochemical markers were studied at inclusion, after 5 and after 9 weeks of the study. RESULTS: Leptin levels, body mass index (BMI) and total cholesterol increased significantly within both groups at week 5 compared to inclusion. Leptin levels correlated with BMI in both groups at inclusion and in group 2 at week 9. In group 1, triglyceride levels remained unchanged, while levels in group 2 increased significantly at week 5 compared to inclusion. Clinical and biochemical markers improved during the study compared to inclusion. CONCLUSIONS: Increased leptin levels during the study progress were transient, decreasing due to prednisolone withdrawal at the end of the study. Both formulas used as adjuvant therapy to prednisolone treatment were able to improve nutritional status in CD patients.

Serum trefoil factors in patients with inflammatory bowel disease.

BACKGROUND: Trefoil factors (TFF1-3) play a critical role in mucosal protection and repair in the gastrointestinal tract. The aims of the present study were to examine associations between serum TFF1-3 and clinical and biochemical markers reflecting disease activity and to examine changes in TFF1-3 in patients with inflammatory bowel disease (IBD) before and during high-dose prednisolone treatment and tapering. METHODS: Serum concentrations of TFF1-3 were quantified in 48 ulcerative colitis (UC) and 50 Crohn's disease (CD) patients with little or moderate activity. Additionally, serum TFF concentrations were determined in patients with severe activity in colon IBD (4 UC and 6 CD) before and during prednisolone treatment with 7 healthy subjects as controls. RESULTS: Median concentrations of TFF1, TFF2, and TFF3 were significantly increased in IBD patients compared with healthy controls (p < 0.01). TFF3 concentrations correlated with clinical and biochemical parameters of disease activity in UC patients. In addition, a trend towards reduction in TFF concentrations during treatment with prednisolone and concomitant clinical and biochemical remission was observed. CONCLUSIONS: The present data support the concept that trefoil peptides are upregulated and may play a role in IBD mucosal protection and repair. In UC patients, TFF3 levels were increased in active disease levels correlated with disease activity indices. Due to a large variation, serum TFFs are not a potential marker for disease activity.

[The influence of six alcoholic beverages on ethanol concentration in the blood and breath]. / Seks alkoholiske drikkes indflydelse på alkoholpromille i blod og udåndingsluft.

INTRODUCTION: We investigated the area under the curve (AUC) as a measure of the bioavailability of ethanol in healthy volunteers drinking six alcoholic beverages of different types. Furthermore, we investigated the correlation between the ethanol concentration in the blood and the breath test. MATERIALS AND METHODS: Twelve healthy volunteers (seven females, five males) consumed six drinks of different types in a crossover design after a six-hour fast. The men ingested 36 g of ethanol and the women 24 g. Venous blood was obtained for determination of serum ethanol and glucose concentration at 0, 30, 60, 90, 120 and 180 minutes postdosing, and at the same time a breath alcohol test was done using an alcoholometer. RESULTS: The AUC of ethanol differed significantly between pure ethanol and the three beverages red wine, sparkling wine and Smirnoff Ice (p < 0.01). The glucose and insulin concentrations increased by factors of 2 and 4, respectively, 60 minutes after drinking beer or Smirnoff Ice, respectively (p < 0.05). We found a high correlation between the ethanol concentration in the blood and the breath test, r 2 = 0.77, r = 0.87 (p < 0.005). Using the blood alcohol concentration as a "gold standard", we found that the risk of obtaining a false- positive breath test was 1% at the legal limit for driving in Denmark (0.5%). Conversely, 59% of the participants with a blood alcohol level > or = 0.5% showed a negative (false negative). DISCUSSION: This investigation shows that the type of alcoholic beverage consumed determines the amount of alcohol absorbed. Furthermore, the different drinks caused different changes in the glucose and insulin concentrations, which might be important in connection with alcohol-induced disturbances in carbohydrate metabolism (e.g., hypo- and hyperglycaemia). Our data indicate that the alcoholometer breath test was an acceptable screening method to estimate the blood alcohol level and to measure the amount of ethanol ingested. However, for evidental purposes during prosecution of drunk drivers, more sophisticated breath test instruments are desirable.

Saliva Interleukin-6 in patients with inflammatory bowel disease.

OBJECTIVE: The inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory conditions that affect the gastrointestinal tract. In regulation of this inflammatory process, Interleukin-6 (IL-6) has a major role. Overproduction of IL-6 by immunocompetent cells contributes to development of the inflammatory condition. Elevated levels of IL-6 in saliva could be expected, because the saliva-producing cells are part of the digestive system. MATERIAL AND METHODS: IL-6 concentrations in saliva and plasma were studied in patients with CD (n=15), UC (n=7) and reference persons (RP) (n=19) by use of an ELISA method. RESULTS: A significant difference in saliva IL-6 concentration between CD patients (median 16.9 ng/L; p<0.05) and RP (median 6.3 ng/L) was found. A significant difference in plasma IL-6 concentration between CD (median 10.3 ng/L; p<0.001) or UC (median 7.8 ng/L; p<0.001) and RP (median 0.8 ng/L) was observed. In patients with CD, plasma IL-6 correlated significantly with C-reactive protein (CRP) as well as albumin. In patients with UC, saliva IL-6 and plasma IL-6 correlated significantly with AI (activity index) scores as well as albumin. In patients with UC, a significant correlation between the saliva and plasma IL-6 concentrations was found. CONCLUSIONS: IL-6 was found in saliva in patients with IBD, documenting the general involvement of the gastrointestinal tract extending to the mouth cavity, and measuring IL-6 may be an additional method for evaluating and monitoring the disease activity.

Insulin-like growth factors (IGFs) and IGF binding proteins in active Crohn's disease treated with omega-3 or omega-6 fatty acids and corticosteroids.

OBJECTIVE: Catabolism and growth impairment are well-known complications of inflammatory bowel disease (IBD). This may be caused by the disease activity itself and/or the medical treatment, and both may lead to changes in the growth hormone (GH)/insulin-like growth factor I (IGF-I) axis. The aim of the present study was to examine the effects of enteral nutrition, Impact Powder, as adjuvant therapy to corticosteroid treatment on changes in the GH/IGF-I axis in patients with Crohn's disease (CD). MATERIAL AND METHODS: The patients were randomized to 3-IP (omega-3-fatty acid (FA), 3 g/day) or 6-IP (omega-6-FA, 9 g/day). Changes in total IGF-I (tIGF-I) and total IGF-II (tIGF-II), free IGF-I (fIGF-I), IGF binding proteins (IGFBP-1 and IGFBP-3), IGFBP-3 protease activity and insulin levels were examined in 31 patients with active CD (CDAI: 186-603) during treatment with prednisolone (40 mg for 1 week) and tapering the dose by 5 mg/week. Clinical and biochemical markers of inflammation were studied at day 0, and after 5 and 9 weeks. RESULTS: There were no differences at baseline between the two groups. During the treatment period, tIGF-I, fIGF-I and IGFBP-3 increased significantly in both groups compared to baseline (p<0.05) without differences between the groups. Insulin and IGFBP-1 showed no significant changes throughout the treatment period. CONCLUSIONS: There was no difference between 3-IP and 6-IP as adjuvant enteral nutrition on the GH/IGF-I axis. The changes observed in the GH/IGF-I axis are in line with previously published studies and may be explained by corticosteroid treatment; however, we cannot exclude an additional effect of omega3-/omega6 FA as adjuvant enteral nutrition.

How accurate are clinical activity indices for scoring of disease activity in inflammatory bowel disease (IBD)?

Clinical activity indices are essential instruments in monitoring inflammatory bowel diseases such as Crohn's disease (CD) and ulcerative colitis (UC). To subclassify components of disease indices in CD and UC, investigate technical noise in estimation of the indices, establish a signal-to-noise ratio (SNR), evaluate correlation between indices and calculate the reference change value (RCV) for selected biochemical variables in individual cases, 50 patients with CD and 49 patients with UC were included in the study. Qualitative index variables were assessed for scoring errors. The standard deviation (SD) was estimated according to a rectangular model, while SD in biochemical variable scoring was estimated according to a Gaussian model; a combined SD was also calculated. These values were investigated for their individual contribution to variation. The 95% CI of an index value was based on +/- 1.96 x SD(combined) and a change in separate biochemical variables was calculated as RCV 1.96 x radical2 x SD(combined). Correlation between different disease activity indices was assessed for unexplained variation. The Crohn's disease activity index (CDAI) had the highest variation compared to the van Hees (Hees) and the Harvey-Bradshaw index (HBI) in CD, but it also had the best SNR, whereas HBI had the lowest. In UC the clinical activity index (CAI) showed the highest variance, but the best SNR compared to Seo's activity index (AI). The 95% CI of the CDAI discriminatory activity sum of 150 in individual cases was 105-195, whereas the 95% interval for a change was +/-62.4. Self-reported wellness contributed 40% to total variance in the CDAI. Factors of clinical importance increased errors in estimates and variance of the indices. Poor correlation was obtained between activity indices, with up to 70% unexplained variance. The SD(combined) for estimated errors was as high as 23 points, with the best SNR being approximately 20. Index factors increase the sensitivity of SNRs to errors and lower the disease specificity. Sensitivity optimisation may be achieved by standardisation of the variables and their use.

Low S-adenosylmethionine concentrations found in patients with severe inflammatory bowel disease.

BACKGROUND: S-adenosylmethionine is a methyl donor in many cellular reactions including detoxification of constantly produced hydrogen sulphide in the colon. A reduced capacity to detoxify hydrogen sulphide may be implicated in the pathogenesis of inflammatory bowel disease. S-adenosylmethionine could be low if this assumption is correct. We compared S-adenosylmethionine concentrations in whole blood in patients with severe and moderate inflammatory bowel disease with healthy reference persons. METHODS: S-adenosylmethionine concentrations in whole blood were measured using high-pressure liquid chromatography. Patients with Crohn's disease (n=21), ulcerative colitis (n=7) and healthy age-matched reference persons (or controls) (n=17) were studied. RESULTS: S-adenosylmethionine concentrations were significantly decreased in patients with severe inflammatory bowel disease (mean 1.10 mg/l) as compared to patients with moderate Crohn's disease and ulcerative colitis (mean 1.83 mg/l) and reference persons (mean 1.84 mg/l). Statistically significant inverse correlations were found between S-adenosylmethionine concentration and activity index (p<0.01 and R2=0.86) as well as Crohn's disease activity index (p<0.01 and R2=0.50) scores. CONCLUSIONS: Low concentrations of S-adenosylmethionine were found in patients with severe inflammatory bowel disease. Future studies will show whether S-adenosylmethionine is a marker for disease activity and a possible tool for investigation of sulphur toxicity as a causative mechanism in inflammatory bowel disease.

Platelets and anticoagulant capacity in patients with inflammatory bowel disease.

Patients with inflammatory bowel disease (IBD) are susceptible to thromboembolic complications. Several mechanisms can be responsible, including abnormal regulation of coagulation activity, disturbances of fibrinolysis, inflammatory reactions and thrombocytosis. The aim of this study was to assess hemostatic alterations in these parameters during exacerbation of disease. We studied disease activity in 99 IBD patients receiving anti-inflammatory therapy, in relation to: procoagulant markers, i.e. prothrombin fragment F1 + 2 (F1 + 2), D-dimer and platelet count, anticoagulant markers, i.e. protein C, protein S and antithrombin, and a mediator of inflammation (IL-6). Coagulation activity and platelet count were increased during active disease in IBD patients compared with those in a state of remission. The IL-6 concentrations were positively correlated with disease activity and thrombocytosis in patients with ulcerative colitis, but no association with the anticoagulant capacity could be demonstrated except for a decrease in protein C during high disease activity.