Longitudinal follow-up of nutritional status and its influencing factors in adults undergoing allogeneic hematopoietic cell transplantation.

There are few longitudinal data on nutritional status and body composition of patients undergoing allogeneic hematopoietic cell transplantation (alloHCT). We assessed nutritional status of 105 patients before alloHCT and its course during the early post-transplant period to day +30 and day +100 via weight history, body mass index (BMI) normalized for gender and age, Subjective Global Assessment, phase angle normalized for gender, age, and BMI, and fat-free and body fat masses. Furthermore, we present a multivariate regression model investigating the impact of factors on body weight. At admission, 23.8% reported significant weight losses (>5%) in the previous 6 months, and we noted 31.5% with abnormal age- and sex-adjusted BMI values (10th, 90th percentiles). BMI decreased significantly (P<0.0001) in both periods by 11% in total, meaning a weight loss of 8.6±5.7 kg. Simultaneously, the patients experienced significant losses (P<0.0001) of both fat-free and body fat masses. Multivariate regression model revealed clinically relevant acute GVHD (parameter estimate 1.43; P=0.02) and moderate/severe anorexia (parameter estimate 1.07; P=0.058) as independent factors influencing early weight loss. In conclusion, our results show a significant deterioration in nutritional status during the early post-transplant period. Predominant alloHCT-associated complications such as anorexia and acute GVHD became evident as significant factors influencing nutritional status.

Bioavailability of vitamin D2 from UV-B-irradiated button mushrooms in healthy adults deficient in serum 25-hydroxyvitamin D: a randomized controlled trial.

BACKGROUND/OBJECTIVES: Mushrooms contain very little or any vitamin D(2) but are abundant in ergosterol, which can be converted into vitamin D(2) by ultraviolet (UV) irradiation. Our objective was to investigate the bioavailability of vitamin D(2) from vitamin D(2)-enhanced mushrooms by UV-B in humans, and comparing it with a vitamin D(2) supplement. SUBJECTS/METHODS: Fresh mushrooms were irradiated with an UV-B dose of 1.5 J/cm(2), increasing vitamin D(2) content from <1 to 491 µg/100 g and made to an experimental soup. In this 5-week, single-blinded, randomized, placebo-controlled trial, 26 young subjects with serum 25-hydroxyvitamin D (25OHD) ≤ 50 nmol/l were randomly assigned into three groups ((a) mushroom, (b) supplement and (c) placebo). They received during winter (a) 28,000 IU (700 µg) vitamin D(2) via the experimental soup, or (b) 28,000 IU vitamin D(2) via a supplement or (c) placebo, respectively. RESULTS: After 2 weeks, serum 25OHD was significantly higher in the mushroom than in the placebo group (P=0.001). The serum 25OHD concentrations in the mushroom and supplement groups rose significantly and similarly over the study period by 3.9 nmol/l (95% confidence interval (95% CI): 2.9, 4.8) and by 4.7 nmol/l per week (95% CI: 3.8, 5.7), respectively. CONCLUSIONS: We are the first to demonstrate in humans that the bioavailability of vitamin D(2) from vitamin D(2)-enhanced button mushrooms via UV-B irradiation was effective in improving vitamin D status and not different to a vitamin D(2) supplement. This trial was registered at http://germanctr.de as DRKS00000195.

[Antioxidants--helpful or harmful?]. / Antioxidanzien--hilfreich oder schädlich?

Fortified food claiming to exert a special function are increasingly offered on the market. Antioxidants (vitamin C, E and beta-carotene) are the major compounds in fortified foods. Due to the fact that the fortified vitamins do not exceed the recommended daily allowances within a food there is no risk for the consumer. Even in speculative cases of accumulation of antioxidants from different fortfied food sources there is no real risk. However, fortified food should not be taken to compensate an unbalanced and unhealthy diet. This risk is far more real because fortified food contains only a few antioxidants whereas a balanced diet contains hundreds. Whether the consumer may have a benefit from fortified food has not yet been evaluated with respect to antioxidant vitamins.

'Mealthy' food: meat as a healthy and valuable source of micronutrients.

Over the last two or three decades meat and especially liver have been looked upon as unhealthy food with high fat content and carcinogenic potential. In addition, its content of highly valuable micronutrients has mostly been ignored. As a result, the mean uptake and serum levels of several micronutrients in the population are below the recommended levels. In the meantime, the contamination of liver with heavy metals and other contaminants has fallen far below the allowed thresholds and sometimes even below the detection limit while its content of micronutrients like iron, folate, selenium or zinc are still high. As a further advantage, the bioavailability of many micronutrients often is better from meat and liver then from plant sources. Considering these advantages and the low content of contaminants in meat and liver leads us to propose that meat - including liver - should be a regular part of a mixed and balanced healthy diet along with vegetables and fruits as the major components to ensure an optimal supply of micronutrients.

Studies of phosphodiesterase effects on adipose tissue metabolism in obese subjects by the microdialysis technique.

The effect of non-selective (theophylline) inhibition of cyclic AMP breakdown on norepinephrine stimulated lipolysis rate was investigated in subcutaneous adipose tissue of obese subjects. In addition, changes in interstitial glucose and lactate concentration were assessed by means of the microdialysis technique. The interaction of endogenous released insulin and theophylline on adipocyte metabolism was determined. Theophylline and norepinephrine alone increased glycerol outflow significantly. When both agents were perfused in combination, interstitial glycerol concentration increased further. The enhanced glycerol level due to theophylline application was slightly decreased by insulin. In the presence of theophylline, extracellular glucose concentration increased, in contrast to the catecholamine. Norepinephrine decreased interstitial glucose level. When both drugs were added in combination, the level of interstitial glucose increased to about 1 mM, greater than with theophylline alone. With each intervention, lactate was synthesized. Local adipose tissue blood flow was increased by theophylline and theophylline plus norepinephrine. In conclusion, post-receptor mechanisms increased norepinephrine maximal stimulated lipolysis rate in subcutaneous adipose tissue. Glucose uptake was inhibited by the non-specific inhibitor of phosphodiesterase. The effect of insulin on inhibition of lipolysis was modest but sustained in the presence of high theophylline (10(-4) M) concentration. Phosphodiesterase activity may be relatively low in obese subjects in comparison with lean subjects. In lean subjects theophylline caused a transient reversal of the antilipolytic effect of insulin.

Monitoring of hematological, inflammatory and oxidative reactions to acute oral iron exposure in human volunteers: preliminary screening for selection of potentially-responsive biomarkers.

BACKGROUND: Iron is an essential micronutrient but also a major catalyst of oxidative and inflammatory reactions. OBJECTIVE: To evaluate the potential utility of selected biomarkers in blood or urine to indicate in vivo oxidative or inflammatory response to oral iron intake at pharmacological doses. METHODS: Three healthy volunteers provided morning, fasting samples of blood and urine on up to 13 study days--3 before, 7 during and 3 following a 7-consecutive-day period of receiving 120 mg of iron per day as ferrous sulfate in commercially available syrup. A series of 23 biomarkers were measured on each collection of biological fluids to monitor iron-responsive changes in biomarkers related to hematological or iron status, inflammation and in vivo oxidation. RESULTS: Among the inflammatory biomarkers measured, white blood cells, serum CRP and urinary neopterin showed no response to iron dosing. Only circulating interleukin-4 (IL-4) and TNF-alpha had abnormal responses with a time association to the oral iron intake. Among the oxidative biomarkers, expression of blood superoxide dismutase (SOD), hemoxygenase-1, catalase as well as circulating thiobarbituric acid reactive substances (TBARS), total oxidative capacity and carbonyl proteins were stable in response to iron exposure. Only urinary TBARS, 8-hydroxy-2-desoxyguanosine and isoprostanes evidenced consistent or suggestive responses to ingestion of the iron challenge. Serum hepcidin concentration increased dramatically in all three subjects after only the first 120 mg dose of iron, and remained elevated even 9 days after cessation of the iron intervention. CONCLUSIONS: Most of the candidate biomarkers show very limited promise as response-indicators to oral iron dosing at the 120 mg dosages or lower, but circulating IL-4, TNF-alpha as well as urinary TBARS, 8-hydroxy-2-desoxyguanosine and isoprostanes showed potential utility as reliable indicators of oxidative and inflammatory response to oral ferrous sulfate.

Meat as a component of a healthy diet - are there any risks or benefits if meat is avoided in the diet?

Meat is frequently associated with a "negative" health image due to its "high" fat content and in the case of red meat is seen as a cancer-promoting food. Therefore, a low meat intake, especially red meat is recommended to avoid the risk of cancer, obesity and metabolic syndrome. However, this discussion overlooks the fact, that meat is an important source for some of micronutrients such as iron, selenium, vitamins A, B12 and folic acid. These micronutrients are either not present in plant derived food or have poor bioavailability. In addition, meat as a protein rich and carbohydrate "low" product contributes to a low glycemic index which is assumed to be "beneficial" with respect to overweight, the development of diabetes and cancer (insulin resistance hypothesis). Taken together meat is an important nutrient for human health and development. As an essential part of a mixed diet, meat ensures adequate delivery of essential micronutrients and amino acids and is involved in regulatory processes of energy metabolism.

Pilot study on the effect of parenteral vitamin E on ischemia and reperfusion induced liver injury: a double blind, randomized, placebo-controlled trial.

BACKGROUND AND AIMS: Liver surgery usually involves ischemia and reperfusion (I/R) which results in oxidative stress and cell damage. The administration of antioxidants should diminish or prevent this damage. The purpose of this study was to investigate the effect of the antioxidant vitamin E on I/R injury. METHODS: We carried out a placebo-controlled double-blind study on 68 patients undergoing elective, tumor-related, partial liver resection. 47 patients were qualified for the per protocol population based evaluation. The patients were randomly assigned to two groups. The day before surgery one group received three infusions containing vitamin E (600 IU=540 mg vitamin E emulsion). The other group received three infusions of placebo. RESULTS: Length of stay in the intensive care unit (ICU) was significantly shorter in the verum group than in the placebo group (P<0.05). There were signs of improvement for AUC AST (P<0.05), ALT and GLDH in the verum group after surgery. Serum vitamin E concentration increased after administration of vitamin E infusion and declined in both treatment groups after surgery (P<0.01). In the verum group vitamin E deficiency was prevented while vitamin E concentration remained low in the placebo group (P<0.01). CONCLUSIONS: The findings from this study indicate that preoperative administration of vitamin E is safe and that this treatment may have beneficial effects by reducing the impact of I/R injury in liver surgery.

Uptake of vitamin A in buccal mucosal cells after topical application of retinyl palmitate: a randomised, placebo-controlled and double-blind trial.

Retinoids have been reported to produce regressions in metaplastic changes of the mucosal epithelium. In order to define the role of these micronutrients in the prevention of squamous metaplasia of the oral cavity, it is necessary to measure their uptake in target tissues such as the buccal mucosal epithelium. We demonstrated in a trial that retinyl palmitate applied topically via a toothpaste is taken up by buccal mucosal cells in young healthy volunteers. In the randomised, parallel-designed, placebo-controlled and double-blind trial, forty volunteers divided in two groups cleaned their teeth either with a placebo toothpaste or a retinyl palmitate-containing toothpaste (1 mg/g) for 56 d. Buccal mucosal cells samples were taken from the healthy volunteers during the retinyl palmitate application and the following wash-out phase to determine the concentration of retinyl palmitate and retinol by HPLC. Supplementary blood samples were taken from the volunteers on days 0 and 56 to investigate changes in plasma retinyl palmitate and retinol concentrations. Results from only thirty participants (sixteen placebo and fourteen treated subjects) were used in the statistical evaluation as the remaining sample results were spoiled by a technical defect during the HPLC analysis. A significant (P<0.05) uptake of retinyl palmitate in buccal mucosal cells after 7 d and a significant (P<0.05) increase of plasma retinol after 17 d was demonstrated in our present study. The uptake of retinyl palmitate and the following hydrolysis to retinol led to an enrichment of vitamin A in buccal mucosal cells.

Carotenoids are decreased in biopsies from colorectal adenomas.

UNLABELLED: A lower intake of carotenoids is associated with an increased risk of colorectal cancer. In order to take advantage of the chemopreventive properties of carotenoids, it is necessary to determine carotenoid concentration at the target tissue. As early stages in the adenoma-carcinoma sequence of colorectal cancer might be susceptible to chemoprevention, we sought to determine carotenoid concentrations in biopsies from colorectal adenomas. METHODS: Biopsies from colorectal adenomas and non-involved mucosa were taken from seven patients. For controls, biopsies were obtained from the ascending and descending colon of patients without polyps (n = 5). Concentration of carotenoids (alpha-, beta-carotene, lutein, lycopene, zeaxanthin, beta-cryptoxanthin) were determined by optimizing gradient HPLC-analysis. Results are expressed as pmol/microg DNA. RESULTS: Except for alpha-carotene, all carotenoids could reliably be detected in all specimens. In control patients carotenoid concentrations were highest in the ascending colon, being followed by the descending colon and non-involved mucosa from polyp-carriers. In colorectal adenomas all carotenoids were significantly reduced as compared to-non-involved mucosa (beta-carotene: 0.37 vs 0.19, P<0.03; lycopene: 0.34 vs 0.21, P<0.06, beta-cryptoxanthin: 0.14 vs 0.09, P<0.03, zeaxanthin: 0.18 vs 0.09, P<0.02; lutein: 0.18 vs 0.13,P <0.02). CONCLUSION: All carotenoids investigated are reduced in colorectal adenomas, suggesting that mucosal carotenoids could serve as biomarkers for predisposition to colorectal cancer. Moreover, anti-tumor activity exerted by carotenoids is limited due to mucosal depletion. We speculate that supplementation of a larger array of carotenoids might be beneficial for patients with colorectal adenoma.

2-Methoxyestradiol enhances reactive oxygen species formation and increases the efficacy of oxygen radical generating tumor treatment.

In an investigation of the antitumor effects of 2-methoxyestradiol (2-ME) in combination with other reactive oxygen generating treatments, 2-ME (0.5 microM) was found to completely inhibit cell proliferation of rat DS-sarcoma cells in vitro, with 71% of cells dying after exposure to 5 microM 2-ME. Concentration-dependent increases in ROS-formation, lipid peroxidation and mitochondrial changes were also observed, and an elevation in caspase-3 activity resulted in DNA fragmentation and apoptosis. Combination of 2-ME with hypoxanthine and xanthine oxidase enhanced in vitro cytotoxicity. In vivo, 2-ME caused a slight inhibition of tumor growth, with no tumors cured. Combination of 2-ME treatment with localized 44 degrees C hyperthermia, respiratory hyperoxia and xanthine oxidase caused a tumor growth delay with 51% of tumors cured. These results suggest that amplifying the levels of reactive oxygen species within tumor tissue with substances such as 2-ME may prove to be a promising strategy for adjuvant treatment of solid tumors.

Meat and cancer: meat as a component of a healthy diet.

Based on epidemiological studies it is assumed that meat, especially red meat, enhances risk for cancer, particularly of the colon, breast and prostate. Meat and meat products are important sources of protein, some micronutrients and fat. High fat intake has been blamed for correlation with different diseases, including cancer. Meat protein is reported to contribute to cancer formation. However, meat, including liver, is not only composed of fat and protein, it contains essential nutrients which appear exclusively in meat (vitamin A, vitamin B12) and micronutrients for which meat is the major source because of either high concentrations or better bioavailability (folate, selenium, zinc). In particular, vitamin A, folate and selenium are reported to be cancer-preventive, with respect to colon, breast and prostate cancer. Taken together, meat consists of a few, not clearly defined cancer-promoting and a lot of cancer-protecting factors. The latter can be optimized by a diet containing fruit and vegetables, which contain hundreds of more or less proven bioactive constituents, many of them showing antioxidative and anticarcinogenic effects in vitro.

Inhalation of aerosolized vitamin a: reversibility of metaplasia and dysplasia of human respiratory epithelia -- a prospective pilot study.

The objective of this preliminary uncontrolled study was twofold: First, to assess the feasibility of retinyl palmitate inhalation and second, to analyze the changes of metaplastic lesions of the respiratory epithelium (metaplasia or dysplasia) following retinyl palmitate inhalation. The response to a daily dose of 18.000 I.U. retinyl palmitate by inhalation over a period of 3 month was assessed in 11 subjects (9 smokers, 2 ex-smokers). Using white-light bronchoscopy combined with autofluorescence bronchoscopy, bronchial biopsies were taken before and after a 3 month-period. The biopsy samples were evaluated blind by a referee lung pathologist. The overall response rate (remission or partial remission) was 56% (95% CI 0.30 0.79; p<0.05). These data suggest that inhalation of retinyl esters could be a promising therapeutical approach for chemoprevention of lung cancer. Vitamin A; chemoprevention; lung cancer; squamous metaplasia; dysplasia; retinoids

The effect of beta-carotene on the expression of interleukin-6 and heme oxygenase-1 in UV-irradiated human skin fibroblasts in vitro.

beta-Carotene is discussed as an anti-oxidant micronutrient and singlet oxygen quencher in human skin, protecting against UV light-induced damage. However, we recently demonstrated that beta-carotene has a pro-oxidant potential in cultured human skin fibroblasts because it enhances the UVA induction of heme oxygenase-1 (HO-1). Herein, we further show that beta-carotene also strongly promotes the UVA induction of pro-inflammatory interleukin-6 (IL-6) in skin fibroblasts in vitro. Singlet oxygen quencher sodium azide abrogated up-regulation of IL-6, and likewise also of HO-1. In UVB-irradiated cells, beta-carotene did not modulate levels of IL-6 and HO-1. The observed effects might be relevant for UV-induced inflammatory processes.

Topical application of vitamin A reverses metaplasia of rat vaginal epithelium: a rapid and efficient approach to improve mucosal barrier function.

Retinyl palmitate and its metabolites retinol and retinoic acid control growth and epithelial differentiation. Systemic or local vitamin A deficiency induced by malnutrition, continuous chemical irritation or locally induced by inflammation causes squamous metaplastic changes in the epithelium of mucous membranes. We demonstrate that in an animal model topically applied retinyl palmitate can be taken up by the mucosal cells independently from the systemic supply. Under in vivo conditions metabolic changes in vaginal epithelium of rats were shown to be reversed by treatment with topical retinyl palmitate. - After only two days treatment squamous metaplastic vaginal epithelium in rats shows a reversal of the epithelium into a normal phenotype which continues after cessation of the treatment for 7 to 11 days. Higher concentrations and longer retention times lead to a statistically significant (p = 0.025) increase in the protection time. These data demonstrate that squamous changes induced by vitamin A deficiency can be totally reversed with topically applied retinyl palmitate.

UV light, beta-carotene and human skin--beneficial and potentially harmful effects.

Solar radiation is one of the most important environmental stress agents for human skin, causing sunburn, premature skin aging, and skin cancer. Beta-carotene is discussed to protect against photooxidative stress and thus prevent skin damage. Though beta-carotene has been successfully used against photosensitivity in patients with erythropoietic protoporphyria, its beneficial potential in normal skin is still uncertain. A number of experimental studies indicate protective effects of beta-carotene against acute and chronic manifestations of skin photodamage. However, most clinical studies have failed to convincingly demonstrate its beneficial effects so far. Nevertheless, intake of oral beta-carotene supplements before sun exposure has been recommended on a population-wide basis. Recent studies on skin cells in culture have revealed that beta-carotene acts not only as an antioxidant but also has unexpected prooxidant properties. At present, there is an ongoing debate on the protective or potentially harmful role of beta-carotene in human skin.

Protective effects of vitamins C and E on the number of micronuclei in lymphocytes in smokers and their role in ascorbate free radical formation in plasma.

Cigarette smoke is widely believed to increase free radical concentrations causing subsequent oxidative processes that lead to DNA damage and hence, to several diseases including lung cancer and atherosclerosis. Vitamin C is a reducing agent that can terminate free-radical-driven oxidation by being converted to a resonance-stabilized free radical. To investigate whether short-term supplementation with the antioxidants vitamin C and E decreases free-radical-driven oxidation and thus decreases DNA damage in smokers, we determined the frequency of micronuclei in lymphocytes in 24 subjects and monitored the electron paramagnetic resonance signal of ascorbate free radical formation in plasma. Further parameters comprised sister-chromatid exchanges and thiobarbituric acid-reactive substances. Twelve smokers and twelve non-smokers took 1000 mg ascorbic acid daily for 7 days and then 1000 mg ascorbic acid and 335.5 mg RRR-alpha-tocopherol daily for the next 7 days. Baseline concentrations of both vitamins C and E were lower and baseline numbers of micronuclei were higher (p < 0.0001) in smokers than in non-smokers. After 7 days of vitamins C and E, DNA damage as monitored by the number of micronulei was decreased in both, smokers and non-smokers, but it was more decreased in smokers as indicated by fewer micronuclei in peripheral lymphocytes (p < 0.05). Concomitantly, the plasma concentrations of vitamin C (p < 0.001) as well as the ascorbate free radical (p < 0.05) were increased. The corresponding values in non-smokers, however, did not change. Our findings show that increased ascorbate free radical formation in plasma after short-term supplementation with vitamins C and E can decrease the number of micronuclei in blood lymphocytes and thus DNA damage in smokers.