Karl-Heinz Wagner

Gamma-Tocopherol – An Underestimated Vitamin?

The main research activities of the last decades on tocopherols were mainly focused on α-tocopherol, in particular when considering the biological activities. However, recent studies have increased the knowledge on γ-tocopherol, which is the major form of vitamin E in the diet in the USA, but not in Europe. γ-Tocopherol provides different antioxidant activities in food and in-vitro studies and showed higher activity in trapping lipophilic electrophiles and reactive nitrogen and oxygen species. The lower plasma levels of γ- compared to α-tocopherol might be discussed in the light of different bioavailability, but also in a potential transformation from γ- into α-tocopherol. From the metabolism end product, only that of γ-tocopherol (2,7,8-trimethyl-2-(β-carboxyethyl)-6-hydroxychroman), but not that of α-tocopherol, was identified to provide natriuretic activity. Studies also indicate that only the γ-tocopherol plasma level served as biomarker for cancer and cardiovascular risk. Therefore, this paper provides a comprehensive review on γ-tocopherol with emphasis on its chemistry, biosynthesis, occurrence in food, different intake linking to different plasma levels in USA and Europe, absorption and metabolism, biological activities, and possible role in human health.

Biological Relevance of Terpenoids

The role of fruit and vegetables in human nutrition and public health are taken into account in most nutritional recommendations. Fruit and vegetables contain an abundance of phenolic substances, terpenoids and other natural antioxidants that have been associated with protection from and treatment of chronic diseases such as heart disease or cancer. Terpenoids are a group of substances which occur in nearly every natural food. Their main subclasses discussed as beneficial to maintain and improve health are monoterpenes (like limonene, carvone or carveol), diterpenes (including the retinoids), and tetraterpenes (which include all different carotenoids like α- and β-carotene, lutein, lycopene, zeaxanthine and cryptoxanthine). To be discussed as health promoting or biofunctional, the significant impact of a substance either on human metabolism or on well-defined and appropriate biomarkers must be shown. Based on the latter point, this paper reviews the literature on mono-, di- and tetraterpenes, with special focus on their impact on human health to answer the question of their biofunctionality. Special emphasis will be placed on their different mode of action, e.g. to affect oxidative stress, carcinogenesis and cardiovascular diseases.

A global view on the development of non communicable diseases.

For a long time non communicable diseases (NCDs) were discussed as burden of the developed world. Recent alarming data show a reverse trend and a dramatic increase of NCDs in the developing world, in particular in highly populated transition countries. This is true for the main mortality triggering diseases such as CVD, cancer or diabetes. Almost 4 out of 5 NCD based deaths happen in low- and middle income countries. This development is multi-factorial and is based on some main trends such as globalization, supermarket growth, rapid urbanization and increasingly sedentary lifestyles. The latter leads to overweight or obesity, which again promotes NCDs similar as high blood pressure, high cholesterol and elevated blood glucose. A high quality diet including functional food or functional ingredients, accompanied by physical activity and a non-smoking policy, is one of the most promising factors in primary and secondary prevention of NCDs.

Curcumin, resveratrol and flavonoids as anti-inflammatory, cyto- and DNA-protective dietary compounds

Numerous dietary compounds, ubiquitous in fruits, vegetables and spices have been isolated and evaluated during recent years for their therapeutic potential. These compounds include flavonoid and non-flavonoid polyphenols, which describe beneficial effects against a variety of ailments. The notion that these plant products have health promoting effects emerged because their intake was related to a reduced incidence of cancer, cardiovascular, neurological, respiratory, and age-related diseases. Exposure of the body to a stressful environment challenges cell survival and increases the risk of chronic disease developing. The polyphenols afford protection against various stress-induced toxicities through modulating intercellular cascades which inhibit inflammatory molecule synthesis, the formation of free radicals, nuclear damage and induce antioxidant enzyme expression. These responses have the potential to increase life expectancy. The present review article focuses on curcumin, resveratrol, and flavonoids and seeks to summarize their anti-inflammatory, cytoprotective and DNA-protective properties.

Malnutrition and depression in the institutionalised elderly

Malnutrition and depression are highly prevalent in the institutionalised elderly and can lead to unfavourable outcomes. The aim of the present study was to assess associations between nutritional status and depressive symptoms and to explore their impact on self-caring capacity and quality of life (QoL) in elderly nursing-home residents (NHR). We conducted a cross-sectional study with 114 NHR (eighty-six female) with a mean age of 84.6 (sd 9.1) years. Nutritional status was assessed with the Mini Nutritional Assessment (MNA). Depressive symptoms were rated with the Geriatric Depression Scale (GDS). Self-caring capacity was measured with the Barthel index (BI) and QoL was assessed with the short-form thirty-six-item (SF-36) questionnaire. Of the NHR, twenty-six (22.8 %) were malnourished according to the MNA and sixty-six (57.9 %) were at nutritional risk. Of the residents, seventy-five could be assessed with the GDS, whereof sixteen (21.3 %) had major and twenty-six (34.7 %) had minor depressive symptoms. GDS scores tended to be higher in patients with impaired nutritional status (5.4 (sd 3.6) in well-nourished subjects and 6.9 (sd 3.2) in residents with malnutrition or at risk of malnutrition). The MNA correlated significantly with the GDS (r - 0.313; P = 0.006) and the GDS emerged as the only independent risk factor for malnutrition in a multiple regression analysis, whereas age, sex, care level, number of prescriptions and self-caring capacity had no influence. The BI was not reduced in patients with a high GDS. QoL was affected in malnourished residents as well as in study participants with depressive symptoms. The results of the present study point towards an association between malnutrition and depressive symptoms. However, the relationship is complex and it remains unclear whether depression in NHR is the cause or consequence of impaired nutritional status. Further studies are needed to identify the direction of this relationship and to assess the effect of depression treatment on nutritional and functional status as well as on QoL.

Antioxidative potential of melanoidins isolated from a roasted glucose-glycine model

Abstract The antioxidative activity of the total water soluble fraction (sol A), high molecular weight (HMW; MW>12,400 Dalton), low molecular weight (LMW) and the insoluble fraction (IS) of a glucose–glycine model system roasted at 120°C was studied in hydrophilic solutions (PBS buffer, fruit juices; addition: 0.01–0.1%) at ambient temperature and lipophilic (coconut fat, triolein and corn oil; addition: 0.01–0.5%) matrices at 60°C and frying conditions at 200°C. The hydrophilic reducing power in the water-soluble fractions was evaluated with the ABTS [2,2′-azino-bis(3-ethylbenz-thiazoline-6-sulfonic acid)] method. Fat stability was determined by observing the development of the peroxide value and conjugated dienes. All fractions increased the hydrophilic reducing power in the water-soluble fractions as a matter of concentration with highest effects for the 0.1% enrichment. In PBS buffer the HMW was most effective, in fruit juices the IS. A slight antioxidative effect in fats was observed only for 0.5% IS and 0.5% sol A in corn oil. Neither in coconut fat at 200°C nor in triolein at 60°C Maillard reaction products (MRPs) were able to extend shelf life. The results performed describe MRPs as highly antioxidative in water-soluble but less effective in water-insoluble fractions.

Use of conventional and -omics based methods for health claims of dietary antioxidants: a critical overview.

This article describes the principles and limitations of methods used to investigate reactive oxygen species (ROS) protective properties of dietary constituents and is aimed at providing a better understanding of the requirements for science based health claims of antioxidant (AO) effects of foods. A number of currently used biochemical measurements aimed of determining the total antioxidant capacity and oxidised lipids and proteins are carried out under unphysiological conditions and are prone to artefact formation. Probably the most reliable approaches are measurements of isoprostanes as a parameter of lipid peroxidation and determination of oxidative DNA damage. Also the design of the experimental models has a strong impact on the reliability of AO studies: the common strategy is the identification of AO by in vitro screening with cell lines. This approach is based on the assumption that protection towards ROS is due to scavenging, but recent findings indicate that activation of transcription factors which regulate genes involved in antioxidant defence plays a key role in the mode of action of AO. These processes are not adequately represented in cell lines. Another shortcoming of in vitro experiments is that AO are metabolised in vivo and that most cell lines are lacking enzymes which catalyse these reactions. Compounds with large molecular configurations (chlorophylls, anthocyans and polyphenolics) are potent AO in vitro, but weak or no effects were observed in animal/human studies with realistic doses as they are poorly absorbed. The development of -omics approaches will improve the scientific basis for health claims. The evaluation of results from microarray and proteomics studies shows that it is not possible to establish a general signature of alterations of transcription and protein patterns by AO. However, it was shown that alterations of gene expression and protein levels caused by experimentally induced oxidative stress and ROS related diseases can be normalised by dietary AO.

Effects of tocopherols and their mixtures on the oxidative stability of olive oil and linseed oil under heating

The tested tocopherols (γ, δ, α) showed antioxidative activity at all levels of addition to the monounsaturated olive oil, the effects increased as a function of concentrations (maximum: + 287% with 800 mg γ-tocopherol/100 g oil compared to the control oil). In the highly unsaturated linseed oil, which contains 58 mg/100 g initial concentration of γ-tocopherol, γ-tocopherol showed antioxidative behavior up to the addition of 100 mg/ 100 g oil. Additions of more than the 100 mg/100 g affected the oil, resulting in a faster oxidation. Mixtures of γ/δ-tocopherols in olive oil were found to protect more efficiently than both vitamins when added separately α-tocopherol reduced effects of other tocopherols in both plant oils. The stabilizing effect of added tocopherols and their mixtures (100 mg/100 g oil each) in olive oil are γ/δ-T>γ-T > δ-T > γ/α-T > δ/α-T > a-T and in linseed oil γ-T > γ/δ-T > δ-T > γ/α-T > α-T > α/δ-T.

Bilirubin and beyond : A review of lipid status in Gilbert's syndrome and its relevance to cardiovascular disease protection

Gilberts syndrome (GS) is characterized by a benign, mildly elevated bilirubin concentration in the blood. Recent reports show clear protection from cardiovascular disease in this population. Protection of lipids, proteins and other macromolecules from oxidation by bilirubin represents the most commonly accepted mechanism contributing to protection in this group. However, a recent meta-analysis estimated that bilirubin only accounts for ~34% of the cardioprotective effects within analysed studies. To reveal the additional contributing variables we have explored circulating cholesterol and triacylglycerol concentrations, which appear to be decreased in hyperbilirubinemic individuals/animals, and are accompanied by lower body mass index in highly powered studies. These results suggest that bilirubin could be responsible for the development of a lean and hypolipidemic state in GS. Here we also discuss the possible contributing mechanisms that might reduce circulating cholesterol and triacylglycerol concentrations in individuals with syndromes affecting bilirubin metabolism/excretion, which we hope will stimulate future research in the area. In summary, this article is the first review of lipid status in animal and human studies of hyperbilirubinemia and explores possible mechanisms that could contribute to lowering circulating lipid parameters and further explain cardiovascular protection in Gilberts syndrome.

Reduced circulating oxidized LDL is associated with hypocholesterolemia and enhanced thiol status in Gilbert syndrome

A protective association between bilirubin and atherosclerosis/ischemic heart disease clearly exists in vivo. However, the relationship between bilirubin and in vivo oxidative stress parameters in a clinical population remains poorly described. The aim of this study was to assess whether persons expressing Gilbert syndrome (GS; i.e., unconjugated hyperbilirubinemia) are protected from thiol oxidation and to determine if this, in addition to their improved lipoprotein profile, could explain reduced oxidized low-density lipoprotein (oxLDL) status in them. Forty-four matched GS and control subjects were recruited and blood was prepared for the analysis of lipid profile and multiple plasma antioxidants and measures of oxidative stress. GS subjects possessed elevated plasma reduced thiol (8.03±1.09 versus 6.75±1.39 nmol/mg protein; P<0.01) and glutathione concentrations (12.7±2.39 versus 9.44±2.45 μM; P<0.001). Oxidative stress status (reduced:oxidized glutathione; GSH:GSSG) was significantly improved in GS (0.49±0.16 versus 0.32±0.12; P<0.001). Protein carbonyl concentrations were negatively associated with bilirubin concentrations and were significantly lower in persons with >40 μM bilirubin versus controls (<17.1 μmol/L; P<0.05). Furthermore, absolute oxLDL concentrations were significantly lower in GS subjects (P<0.05). Forward stepwise regression analysis revealed that bilirubin was associated with increased GSH:GSSG ratio and reduced thiol concentrations, which, in addition to reduced circulating LDL, probably decreased oxLDL concentrations within the cohort. In addition, a marked reduction in total cholesterol concentrations in hyperbilirubinemic Gunn rats is presented (Gunn 0.57±0.09 versus control 1.69±0.40 mmol/L; P<0.001), arguing for a novel role for bilirubin in modulating lipid status in vivo. These findings implicate the physiological importance of bilirubin in protecting from atherosclerosis by reducing thiol and subsequent lipoprotein oxidation, in addition to reducing circulating LDL concentrations.