Browsing by Person "Frank, Jan"

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Anemia among Syrian refugee children aged 6 to 23 months living in Greater Beirut, Lebanon, including the Voices of Mothers’ and Local Healthcare Staff: A mixed-methods study
(2023) Jeremias, Theresa; Abou-Rizk, Joana; Burgard, Leonie; Entenmann, Isa; Nasreddine, Lara; Jomaa, Lamis; Hwalla, Nahla; Frank, Jan; Scherbaum, Veronika
Globally, the prevalence of anemia among children during the period of complementary feeding is high. A cross-sectional, mixed-methods study was conducted to examine the main determinants of anemia among Syrian refugee children aged 6 to 23 months (n = 215) and to illuminate the knowledge, attitudes and perceptions of their mothers and Lebanese healthcare staff on its causes and available treatment options. 42% of the children and 20% of their mothers were anemic. Determinants of child anemia were the mother having anemia or not knowing that fish/seafood is a source of iron; the child having been acutely ill the last two weeks or receiving cow’s milk, but not consuming iron-rich infant formula, added fats/oils, or fruits in the previous 24 hours. Several Syrian mothers knew some causes of anemia and named dizziness as a leading symptom but did not mention flesh foods as a key source of heme iron. They reported financial constraints in accessing iron-rich foods and supplements. Lebanese doctors largely gave appropriate dietary advice and prescribed iron supplements as treatment. Multisectoral interventions are needed that combine medical and financial support with nutrition counseling for mothers to reduce the high burden of anemia among young children living in a multiple crises situation.
Anthropometrics, hemoglobin status and dietary micronutrient intake among Tanzanian and Mozambican pigeon pea farmers
(2022) Eleraky, Laila; Issa, Ramula; Maciel, Sónia; Mbwana, Hadijah; Rybak, Constance; Frank, Jan; Stuetz, Wolfgang
Inadequate consumption of micronutrient-dense and protein-rich foods such as vegetables, legumes and meat is an important contributing cause for anemia and deficiencies of vitamin A and iron in rural communities of Tanzania and Mozambique. A cross-sectional study was conducted to assess the nutritional status (anthropometrics and hemoglobin) and diets in particular micronutrient intake of female and male pigeon pea farmers from Lindi, Tanzania, and Gurué, the Zambézia province of Mozambique. A total of 1526 farmers (669 from Tanzania, 857 from Mozambique) were studied, of whom 16% were overweight and 35% were anemic. The highest prevalence of overweight and anemia, at 35% and 48%, was observed in Tanzanian and Mozambican women, respectively. Overall, only a small proportion of women and men reached the recommended daily dietary intake of vitamin A (10%), iron (51%) and zinc (44%). Multiple regression models revealed that dark green leafy vegetables (DGLVs) highly predicted vitamin A intake, whereas legumes in Tanzania and starchy plants in Mozambique were actually the dominant sources of vitamin A. Cereals covered over half of the iron and the zinc intake in both countries. An increased consumption of micronutrient-rich DGLVs and legumes, while reducing the high amounts of refined maize or polished rice, is suggested to counteract the high prevalence of anemia and overweight among smallholder farmers in East and South Eastern Africa.
Antioxidants Attenuate Heat Shock Induced Premature Senescence of Bovine Mesenchymal Stem Cells
(2022) Nir, Dana; Ribarski-Chorev, Ivana; Shimoni, Chen; Strauss, Carmit; Frank, Jan; Schlesinger, Sharon
Mesenchymal stem cells (MSC) have many roles that are important for the body’s proper functioning. When the MSC pool is damaged, it is often correlated with impaired development or health of the organism. MSC are known for their anti-inflammatory, immunomodulatory and trophic characteristics that play an important role in the physiological homeostasis of many tissues. Heat shock impairs MSC capacity by inducing the generation of reactive oxygen species and mitochondrial dysfunction, which, in turn, send the cells into a state of premature senescence. Here, we pre-exposed MSC to melatonin, resveratrol, or curcumin, which are natural antioxidative compounds, and tested the protective effects of these substances from oxidative stress and aging. Our data showed that pre-exposure of MSC to antioxidants decreased reactive oxygen species while mitochondrial damage remained high. Additionally, although the proliferation of the cells was slow, antioxidants protected the cells from premature senescence, and subsequent cytokine release was prevented. We conclude that while elevated temperatures directly cause mitochondrial damage, senescence is induced by elevated ROS levels. We suggest that heat shock alters cell and tissue homeostasis by several independent mechanisms; however, reducing tissue senescence will reduce damage and provide a pathway to overcome physiological challenges in animals.
Demethoxycurcumin and Bisdemethoxycurcumin are more bioavailable than Curcumin: A meta-analysis of randomized cross-over trials in healthy umans and an In Vitro mechanistic exploration
(2023) Desmarchelier, Charles; Sus, Nadine; Marconot, Grégory; Gillet, Guillian; Resseguier, Noémie; Frank, Jan
Background: Curcuminoids are secondary plant metabolites found in turmeric and many dietary supplements. They usually consist of a mixture of curcumin (CUR), demethoxycurcumin (dCUR) and bisdemethoxycurcumin (bdCUR). CUR, the main curcuminoid, has been intensely investigated for its putative effects against, e.g., inflammation, oxidative stress and cancer. However, CUR displays very poor bioavailability. We have previously shown that, when brought by turmeric, dCUR and bdCUR, which can also exert health effects, display greater in vitro bioaccessibility than CUR (PMID: 37073511). However, their bioavailability relative to that of CUR has not been thoroughly investigated. Objective: We aimed to compare the bioavailability of dCUR and bdCUR to that of CUR in a meta-analysis of clinical trials in healthy humans and to compare their in vitro bioaccessibility and enterocyte uptake efficiency. Methods and Results: Studies published until 2022 were searched for using Medline and Scopus. The included studies were randomized trials that measured the bioavailability of CUR, dCUR and bdCUR in healthy participants. Estimates were calculated using a random-effects model. Fifteen trials were included in the study, representing a total of 50 interventions, i.e., each trial investigated several curcuminoid formulations, in 762 participants. The relative bioavailabilities were calculated using the inverse variance method. dCUR was 2.32 (95% CI:1.70, 3.13) times more bioavailable than CUR, while bdCUR was 2.57 (95% CI: 1.58, 4.16) times more bioavailable than CUR, with some heterogeneity across the formulations used. Using an in vitro gastro-intestinal digestion model with pure curcuminoids, we showed that dCUR solubilization efficiency was 4.8 and 5.3 times higher than that of CUR and bdCUR, respectively (p < 0.001), while its micellization efficiency was 10.3 and 5.1 times higher than that of CUR and bdCUR, respectively (p < 0.001). Conclusions: bdCUR and dCUR display greater bioavailability in humans compared to CUR. A subgroup analysis by formulation is undergoing investigation and will be presented. For dCUR, this difference is partly explained by higher in vitro bioaccessibility. Uptake efficiency measurements of pure curcuminoids and of curcuminoids from in vitro digestion fluids are undergoing investigation and will be presented. bdCUR and dCUR might therefore represent relevant alternatives to CUR for the systematic delivery of curcuminoids.
Dietary intake of fructooligosaccharides protects against metabolic derangements evoked by chronic exposure to fructose or galactose in rats
(2023) Almasri, Fidèle; Collotta, Debora; Aimaretti, Eleonora; Sus, Nadine; Aragno, Manuela; Dal Bello, Federica; Eva, Carola; Mastrocola, Raffaella; Landberg, Rikard; Frank, Jan; Collino, Massimo
Scope: Diets rich in fat and sugars evoke chronic low-grade inflammation, leading to metabolic derangements. This study investigates the impact of fructose and galactose, two commonly consumed simple sugars, on exacerbation of the harmful effects caused by high fat intake. Additionally, the potential efficacy of fructooligosaccharides (FOS), a fermentable dietary fiber, in counteracting these effects is examined. Methods and results: Male Sprague-Dawley rats (six/group) are fed 8 weeks as follows: control 5% fat diet (CNT), 20% fat diet (FAT), FAT+10% FOS diet (FAT+FOS), FAT+25% galactose diet (FAT+GAL), FAT+GAL+10% FOS diet (FAT+GAL+FOS), FAT+25% fructose diet (FAT+FRU), FAT+FRU+10% FOS diet (FAT+FRU+FOS). The dietary manipulations tested do not affect body weight gain, blood glucose, or markers of systemic inflammation whereas significant increases in plasma concentrations of triacylglycerols, cholesterol, aspartate aminotransferase, and alanine aminotrasferase are detected in both FAT+FRU and FAT+GAL compared to CNT. In the liver and skeletal muscle, both sugars induce significant accumulation of lipids and advanced glycation end-products (AGEs). FOS supplementation prevents these impairments. Conclusion: This study extends the understanding of the deleterious effects of a chronic intake of simple sugars and demonstrates the beneficial role of the prebiotic FOS in dampening the sugar-induced metabolic impairments by prevention of lipid and AGEs accumulation.
Dietary intake, nutritional status of lactating women and their 6-23-months-old children in Genta Afeshum District, Rural Ethiopia : adaptation and validation of calculator for inadequate micronutrient intake (CIMI)
(2020) Desalegn, Beruk; Frank, Jan
Religious fasting is one of the categories of dietary or food taboos, which may affect the dietary intake and nutritional status of individuals. In Ethiopia, about half of the population are followers of Ethiopian Orthodox Tewahedo religion, and approximately 250 days per annum are fasting days. In these fasting days, lactating and pregnant women and children are exempted from fasting. However, lactating and pregnant women fast and are not also happy to prepare non-fasting foods for their children during the fasting days due to fear of contamination of family food. Early identification of micronutrient deficiencies in Ethiopia are flouted, as most often the quantitative dietary data are not available. As a result, the hidden hunger might have not been addressed properly, where it remains high and persistent. Therefore, easy to use, less costly and applicable assessment tool which can estimate the quantitative dietary intake of an individual or a community is urgently needed to achieve the national and international goals set for eradicating malnutrition. The Calculator for Inadequate Micronutrient Intake (CIM) is a simple, easy-to-use, informative, web-based application of quantitative dietary assessment method, which was first developed in Indonesia for Indonesian population. It estimates energy and nutrient intake correctly, and identifies nutrient inadequacy according to FAO/WHO recommended nutrient intake (RNI) regarding age, sex and physiological stage. Thus, the present study was conducted with the aim of assessing and comparing the nutritional status and dietary intake of lactating women and their 6-23-months-old children in fasting and non-fasting periods, and to adapt and validate the CIMI program for Ethiopian population. This study was conducted in rural Genta Afeshum district, in Tigray, Ethiopia, where almost all people in the woreda are followers of Ethiopian Orthodox Christianity. A longitudinal study was conducted using575 and 522 lactating women and their 6-23-months-old children in the lent fasting and non-fasting. In the present study it was found out that the prevalence of underweight (BMI < 18.5 kg/m2) in fasting lactating women was high (50.6%) which is associated with maternal age, maternal illness within four weeks preceding the fasting survey, fasting status during their pregnancy and lactation period of their children included in this study. Additional predictor variables for maternal underweight were grandfathers‘ as household decision maker, use of non-improved water source, household aid experience and the absence of chicken in the household. The average number of meals, diet diversity, and animal source foods consumption scores were significantly higher in non-fasting compared to fasting periods, regardless of the fasting status (p < 0.001, p < 0.05 and p < 0.001, respectively). Whereas, 31.6–33.7%, 11.7–15.7% and 4.4–4.8% of the 6-23-months-old children in the study population were stunted, underweight and wasted, respectively. In the fasting period, the weight-for-length (WLZ) and length-for-age (LAZ) values for the 6-23-months-old children of non-fasting mothers were significantly higher (p < 0.05) than the children of the fasting mothers‘ group. Similarly, the median weight-for-age (WAZ) and diet diversity score (DDS) of children of fasting mothers were also significantly lower in fasting compared to non-fasting period. The proportion of the 6-23-months-old children who met the minimum acceptable diet (MAD) was small (2.3-6.7%) in the study population; however, this proportion was significantly (p < 0.001) higher in the non-fasting than fasting period in the children of fasting mothers. Age of the child, maternal fasting status during pregnancy and lactation periods, maternal education and occupation were associated with child underweight. Likewise, age of the child, colostrum intake status, maternal fasting status during pregnancy and lactation period and toilet presence in the household were associated with child stunting. But, maternal fasting status during lactation period and maternal education predicted wasting in the children precisely. The average energy, protein and almost all micronutrients intakes of children and women were lower in fasting compared to non-fasting period. At the same time, the prevalence of inadequate intakes of energy, protein and most micronutrients were higher in both the children and lactating women during fasting than non-fasting period. The result of this study revealed that the correlation coefficients for the average dietary nutrient intake calculated by CIMI and the reference software NutriSurvey (NS) were between 0.741-0.956 for the children and between 0.779-0.920 for the lactating women groups. As a conclusion, the dietary pattern and nutritional status of lactating women and their breastfed children are affected during the fasting period. Therefore, the existing multi-sectoral nutrition intervention strategies in Ethiopia should include religious institutions in a sustainable manner. CIMI adapted for the rural Ethiopian setting estimates the average nutrient intake accurately; and identifies inadequate micronutrient intake of individuals enabling enumerators to provide feedback and suggest improvements. Thus, CIMI can be used in Ethiopia, as a simple dietary assessment tool by nutrition and related researchers, policy makers, implementers and evaluators.
Effect of a diet rich in galactose or fructose, with or without fructooligosaccharides, on gut microbiota composition in rats
(2022) Mhd Omar, Nor Adila; Dicksved, Johan; Kruger, Johanita; Zamaratskaia, Galia; Michaëlsson, Karl; Wolk, Alicja; Frank, Jan; Landberg, Rikard
Recent studies suggest that a diet rich in sugars significantly affects the gut microbiota. Adverse metabolic effects of sugars may partly be mediated by alterations of gut microbiota and gut health parameters, but experimental evidence is lacking. Therefore, we investigated the effects of high intake of fructose or galactose, with/without fructooligosaccharides (FOS), on gut microbiota composition in rats and explored the association between gut microbiota and low-grade systemic inflammation. Sprague–Dawley rats (n = 6/group) were fed the following isocaloric diets for 12 weeks (% of the dry weight of the sugars or FOS): (1) starch (control), (2) fructose (50%), (3) galactose (50%), (4) starch+FOS (15%) (FOS control), (5) fructose (50%)+FOS (15%), (6) galactose (50%)+FOS (15%), and (7) starch+olive (negative control). Microbiota composition in the large intestinal content was determined by sequencing amplicons from the 16S rRNA gene; 341F and 805R primers were used to generate amplicons from the V3 and V4 regions. Actinobacteria, Verrucomicrobia, Tenericutes, and Cyanobacteria composition differed between diets. Bifidobacterium was significantly higher in all diet groups where FOS was included. Modest associations between gut microbiota and metabolic factors as well as with gut permeability markers were observed, but no associations between gut microbiota and inflammation markers were observed. We found no coherent effect of galactose or fructose on gut microbiota composition. Added FOS increased Bifidobacterium but did not mitigate potential adverse metabolic effects induced by the sugars. However, gut microbiota composition was associated with several metabolic factors and gut permeability markers which warrant further investigations.
Identification and quantification of tocomonoenol isomers in plants and microalgae and investigation of their metabolism in liver cells
(2022) Montoya Arroyo, Alexander; Frank, Jan
Tocopherols (T), tocomonoenols (T1), and tocotrienols (T3) are tocochromanols, a group of bioactive compounds composed of a chromanol ring and a 16-carbon sidechain with biological functions, such as the protection of lipid membranes from oxidation and the modulation of cellular signaling. T have saturated sidechains, while T1 and T3 have a single or three double bonds in theirs, respectively. The prefixes alpha-, beta-, gamma-, and delta- are assigned based on the number and positions of methyl groups on the chromanol ring. alpha-, beta-, gamma-, and delta-congeners of T1 have been reported, with alpha-T1 being the predominantly identified congener. Two different alpha-T1 isomers are known, 11-alpha-T1, which has been mainly found in land plants, and 12-alpha-T1, which has been mostly detected in marine organisms. However, little is known regarding the occurrence of T1 in photosynthetic organisms and their metabolism in the liver, a strong determinant of bioavailability and bioactivity. The aim of this thesis was to evaluate underutilized plant-based food sources, cyanobacteria, and microalgae as potential sources of T1 and to characterize the uptake and conversion into metabolites of T1 in cultured liver cells in comparison to T and T3. Acrocomia aculeata fruits were analyzed for alpha-T1 due to its phylogenetic relationship with Elaeis spp, the most common source of this congener. No alpha-T1 was detected in oils from endosperm and mesocarp of wild fruits of Acrocomia aculeata from Costa Rica. Aerial parts of the local underutilized leafy vegetable Urtica leptophylla were evaluated as source of T1 due to its agronomical potential and previous reports of T1 in leaves of plants. LC-MS analyses indicated that leaves and flowers of Costa Rican Urtica leptophylla contain minor amounts of alpha-T1 and gamma-T1. Cyanobacteria and microalgae from different species and origins were analyzed as source of alpha-T1 due to their role as primary producers in aquatic ecosystems and the reported presence of 12-alpha-T1 in marine phytoplankton. alpha-T1 in cyanobacteria and microalgae ranged from traces up to 17% of the total tocochromanol content. alpha-T1 concentrations alone were higher than the sum of all four T3. 11-alpha-T1 was the major alpha-T1 isomer in cyanobacteria and microalgae, as determined by GC-MS. Hence, 11-alpha-T1 is a product of biosynthetic pathways even in aquatic organisms. The effect of nitrogen depletion during the cultivation of microalgae on their alpha-T1 content was investigated. Nitrogen depletion did neither significantly affect the relative or absolute content of alpha-T1, despite an increase in tocochromanol content, nor the proportion of 11-alpha-T1/12-alpha-T1 in microalgae. The uptake and conversion into metabolites of 11-alpha-T1 in HepG2 liver cells was compared to those of alpha-T3 and alpha-T. Cellular uptake of alpha-T1 in liver cells was higher than that of alpha-T. 11-alpha-T1, similar to alpha-T, was converted mostly to alpha-carboxymethylhydroxychroman in a time dependent manner, but to lower extend than alpha-T3. The effect of both ring methylation and sidechain saturation on the uptake and metabolism of the alpha- and gamma-congeners of T1, T and T3 was studied in HepG2 cells. gamma-Congeners were metabolized at higher extent than alpha-congeners and metabolite production increased with increasing number of double bonds in the sidechain independently of chromanol ring methylation. In conclusion, alpha-T1 is present with up to 17% of total tocochromanols in cultured microalgae, which thus are an important new source of this congener. gamma-T1 is only a minor tocochromanol in U. leptophylla flowers. 11-alpha-T1, and not 12-alpha-T1, is the major alpha-T1 isomer in cyanobacteria and microalgae and nitrogen depletion of microalgae does not significantly affect alpha-T1 concentration. The metabolic conversion of alpha-T1 into alpha-carboxymethylhydroxychroman in HepG2 cells is similar to that of alpha-T and significantly lower than that of alpha-T3, suggesting that it may be handled by the organism similar to alpha-T. In conclusion, novel potential food sources of alpha-T1 have been identified and, because of similarities with alpha-T, its pharmacokinetics and biological activities warrant further investigation.
Increasing post-digestive solubility of curcumin is the most successful strategy to improve its oral bioavailability: A randomized cross-over trial in healthy adults and in vitro bioaccessibility experiments
(2021) Flory, Sandra; Sus, Nadine; Haas, Kathrin; Jehle, Sina; Kienhöfer, Eva; Waehler, Reinhard; Adler, Günther; Venturelli, Sascha; Frank, Jan
Scope: Different mechanistic approaches to improve the low oral bioavailability of curcumin have been developed, but not yet directly compared in humans. Methods and Results: In a randomized, double-blind, cross-over trial with 12 healthy adults, the 24 h pharmacokinetics of a single dose of 207 mg curcumin is compared from the following formulations: native, liposomes, with turmeric oils, with adjuvants (including piperine), submicron-particles, phytosomes, γ-cyclodextrin complexes, and micelles. No free, but only conjugated curcumin is detected in all subjects. Compared to native curcumin, a significant increase in the area under the plasma concentration–time curve is observed for micellar curcumin (57-fold) and the curcumin-γ-cyclodextrin complex (30-fold) only. In vitro digestive stability, solubility, and micellization efficiency of micellar curcumin (100%, 80%, and 55%) and curcumin-γ-cyclodextrin complex (73%, 33%, and 23%) are higher compared to all other formulations (<72%, <8%, and <4%). The transport efficiencies through Caco-2 cell monolayers of curcumin from the digested mixed-micellar fractions did not differ significantly. Conclusion: The improved oral bioavailability of micellar curcumin, and to a lesser extent of γ-cyclodextrin curcumin complexes, appears to be facilitated by increased post-digestive stability and solubility, whereas strategies targeting post-absorptive processes, including inhibition of biotransformation, appear ineffective.
Infant feeding practices, nutrition, and associated health factors during the first six months of life among Syrian refugees in Greater Beirut, Lebanon: A mixed methods study
(2022) Abou-Rizk, Joana; Jeremias, Theresa; Nasreddine, Lara; Jomaa, Lamis; Hwalla, Nahla; Frank, Jan; Scherbaum, Veronika
The objective was to describe infant feeding practices, nutrition and related health aspects of infants under six months among Syrian refugees in Greater Beirut, Lebanon. A cross-sectional study was conducted among Syrian refugee mothers with infants under six months in July–October 2018 (N = 114). Additionally, eleven focus group discussions were conducted to explore supportive factors and barriers associated with early breastfeeding practices. The prevalence of pre-lacteal feeding was high (62.5%), whereas early initiation of breastfeeding was low (31%), and exclusive breastfeeding very low (24.6%). One-fifth of the infants were anemic (20.5%) and 9.6% were wasted. A significantly higher proportion of non-exclusively breastfed infants had a fever and took medicines than those who were exclusively breastfed. Supporting factors of adequate infant feeding practices comprised knowledge on maternal nutrition and exclusive breastfeeding, along with receiving support from healthcare professionals and family members. Identified barriers included preterm delivery, pre-lacteal feeding, an at-risk waist circumference and moderate to severe depression among mothers, bottle feeding, early introduction of food, maternal health reasons, breastmilk substitutes’ distribution, and misinformation offered by mothers-in-law. To address sub-optimal feeding practices documented among Syrian refugees, awareness on proper breastfeeding practices, maternal nutrition, and psychosocial support should be provided to mothers and family members alike.
Nutritional and hemoglobin status in relation to dietary micronutrient intake: studies in female and male small-scale farmers from Lindi region, Tanzania, and Gurué district, Mozambique
(2024) Eleraky, Laila; Frank, Jan
Inadequate consumption of micronutrient-dense and protein-rich foods, such as vegetables, legumes and meat, are important contributing causes for malnutrition, anemia and micronutrient deficiencies in rural communities of Tanzania and Mozambique. The increasing public health concern of the malnutrition form of overweight has repeatedly been reported in urban as well as rural areas of Sub-Sahara Africa and may have already reached farmers in Tanzania and Mozambique. Nutritional status is assessed by anthropometry, dietary intake and hemoglobin. Compared to the often-used body mass index (BMI) and traditional 24-hour recall, the mid-upper-arm-circumference (MUAC), as well as a food group-based algorithm (CIMI) can be suitable additional assessment tools, especially in resource poor environments. Cross-sectional studies within the framework of the Vegi-Leg project were conducted to assess the nutritional status (anthropometrics and hemoglobin measurements), and the dietary behaviours (Household Dietary Diversity Scores (HDDS), Food Frequency Questionnaires (FFQ) and 24-hour recalls) of female and male farmers from rural areas of Tanzania and Mozambique. Data were analysed by region, sex, age, partly season (Tanzania)and correlates. Additional data from similar projects, namely Scale-N and Trans-SEC in rural villages of Tanzania were included in MUAC and CIMI analysis. MUAC as an additional and easy-to-handle anthropometric marker for underweight, as well as overweight was evaluated using data from Vegi-Leg and Scale-N surveys. MUAC cut-offs, calculated via BMI cut-offs and multiple linear regression (MLR), compared to those selected by highest Youden’s index (YI) value, were assessed. The CIMI algorithm included 23 food groups and was tested in comparison to NutriSurvey (detailed quantitative 24 hour recalls) with data from Scale-N and Trans-SEC.A total of 1526 farmers from the Vegi-Leg project (669 from Tanzania, 857 from Mozambique) were studied, of whom 19% were overweight and 35% were anemic. The study showed an overall higher prevalence of overweight (19%) than underweight (10%), mainly due to the high prevalence of overweight female farmers (up to 35%) in southern Tanzania. The highest prevalence of overweight and anemia, at 35% and 48%, was observed in Tanzanian and Mozambican women, respectively. Regarding HDDS and FFQ data, pigeon pea farmers in Lindi and Gurué reported high consumption frequencies of cereals, legumes, vegetables and oil, while meat, fish and eggs were only consumed rarely. Overall, only a small proportion of enrolled women and men reached the recommended daily dietary intake of vitamin A (10%), iron (51%) and zinc (44%) according to the 24-hour recalls. Multiple regression models revealed that dark green leafy vegetables (DGLVs) highly predicted vitamin A intake, whereas legumes in Tanzania and starchy plants in Mozambique were the dominant sources of vitamin A. Cereals contributed to over half of the iron and the zinc intake in both countries. Seasonal analysis revealed high fluctuations for the consumption frequency of food items from the food groups ‘legumes and pulses’, ‘green leafy vegetables’, ‘other vegetables’ and ‘fruits’, including tomatoes, pigeon peas, mangoes and oranges. The results from Lindi Tanzania revealed, that in seasons, when the availability of food groups like fruits, legumes or vegetables was low, the consumption frequency decreased significantly. BMI, which correlated positively and strongly with MUAC, was higher in Tanzania than in Mozambique and higher among female than male farmers, and decreased significantly from the age of 65 years. MUAC cut-offs of <24 cm and ≥30.5 cm, calculated by multiple linear regression, detected 55% of farmers being underweight and 74% being overweight, with a specificity of 96%; the higher cut-off <25 cm and lower cut-off ≥29 cm, each selected according to Youden’s Index, consequently detected more underweight (80%) and overweight farmers (91%), but on the basis of a lower specificity (87–88%). The results of the algorithm CIMI and NutriSurvey were similar with regard to the average intake and range of data distribution. The correlation coefficients of NutriSurvey and CIMI with regards to energy (0.931), protein (0.898), iron (0.775) and zinc (0.838) intake, supported the matching of both calculations. An increased consumption of micronutrient rich DGLVs and legumes, while reducing the high amounts of refined sugar, maize and polished rice, is suggested to counteract the high prevalence of anemia and overweight among smallholder farmers in rural Tanzania and Mozambique. MUAC cut-offs to detect malnutrition whether defined via linear regression or Youden’s Index, proved to be easy-to-use tools for large-scale rural screenings of both underweight and overweight. The food group based CIMI algorithm is a valid instrument that calculates energy and nutrient intake in agreement with the preferred nutrition software NutriSurvey.
Optimization of supercritical carbon dioxide extraction of polyphenols from black rosehip and their bioaccessibility using an In Vitro digestion/Caco-2 cell model
(2023) Kasapoğlu, Kadriye Nur; Kruger, Johanita; Barla-Demirkoz, Aslı; Gültekin-Özgüven, Mine; Frank, Jan; Özçelik, Beraat
The fruits of Rosa pimpinellifolia are rich sources of (poly)phenols, however they are underutilized due to the limited information available. The influence of the pressure, temperature, and co-solvent concentration (aqueous ethanol) of the supercritical carbon dioxide extraction (SCO2-aqEtOH) on the extraction yield, total phenolic-, total anthocyanin-, catechin-, cyanidin-3-O-glucoside contents, and total antioxidant activity of black rosehip was investigated simultaneously. The maximum obtained total phenolic and total anthocyanin contents under the optimized extraction conditions (280 bar, 60 °C and 25% ethanol, v/v) were 76.58 ± 4.25 mg gallic acid equivalent and 10.89 ± 1.56 mg cyanidin-3-O-glucoside equivalent per g of the dry fruits, respectively. The optimal extract obtained by SCO2-aqEtOH was compared to two other extraction procedures: ultrasonication using ethanol as solvent (UA-EtOH) and pressurized hot water extraction (PH-H2O). The bioaccessibility and cellular metabolism of the phenolic compounds in the different black rosehip extracts were assessed using an in vitro digestion coupled with a human intestinal Caco-2 cell model. The in vitro digestive stability and cellular uptake of the phenolic compounds had no significant difference among the different extraction methods. The results of this study confirm the efficiency of SCO2-aqEtOH extraction for phenolic compounds and, in particular, for anthocyanins, and could be used to produce new functional food ingredients from black rosehip with high antioxidant power containing both hydrophilic and lipophilic compounds.
Relative bioavailability of curcumin as affected by formulation strategies : from in vitro digestion and cell culture experiments to human clinical trials
(2022) Flory, Sandra; Frank, Jan
Curcumin, the bioactive component of turmeric (Curcuma longa L.), has been used for thousands of years in traditional medicine for the prevention or treatment of several diseases and symptoms. Nowadays, curcumin is investigated worldwide as a nutritional supplement. To overcome the central limitation of its naturally low oral bioavailability, several formulation strategies have been developed, such as its co-administration with turmeric oils or piperine to inhibit its metabolism and efflux or its incorporation into micelles, cyclodextrin complexes or phospholipid bilayers to improve its stability and solubility. So far, the different formulations have not been compared directly, in one cohort of participants and at equal doses. The present doctoral thesis aimed, for the first time, at a direct comparison of the bioavailability of curcumin in form of a native curcuma extract or seven formulations, namely polysorbate 80 micelles, g-cyclodextrin complexes, liposomes, phytosomes, submicron-particle curcumin or curcumin administered with turmeric oils or piperine, in healthy adults. The project further aimed to investigate several critical factors for curcumin bioavailability in vitro and to explain thereby the observations made in vivo. In a randomized, double-blind crossover trial with 12 healthy participants (6 females, 6 males), curcumin pharmacokinetics, namely AUC (area under the plasma concentration-time curve), Cmax (maximum plasma concentration) and tmax (time to reach Cmax) were compared after administration of a single oral dose of 207 mg curcumin in form of a native curcuma extract or one of the seven formulations. Curcumin incorporated into polysorbate 80 micelles or g-cyclodextrin complexes showed 57-fold and 30-fold improved bioavailability compared to the native extract, whereas all other formulations showed no or minor effects. tmax of the better bioavailable formulations was smaller (1 to 2 hours) compared to all others (up to 7 hours). To compare the formulations regarding their digestion characteristics and transepithelial transport, in vitro digestion experiments followed by Caco-2 cell transport assays were conducted with the formulations normalized to their curcumin content. In parallel to the effects in vivo, curcumin showed higher stability, solubility and micellization efficiency when it was incorporated into polysorbate 80 micelles (100%, 80%, 55%) or g-cyclodextrin complexes (73%, 33%, 23%), whereas curcumin permeability through Caco-2 cell monolayers was not affected by its formulation. In the next study, curcumin efflux, partially mediated by P-glycoprotein (P-gp), was investigated, because the inhibition of curcumin efflux from the intestinal cells back to the intestinal lumen is targeted by the co-administration of curcumin with turmeric oils or piperine. In LS180 (colon adenocarcinoma) cells, native curcuma extract and the seven formulations were studied regarding cellular curcumin uptake within 1 hour and efflux within further 8 hours, as well as their effects on P-gp activity. Independently from its formulation, curcumin inhibited the activity of P-gp. Cellular curcumin uptake and efflux showed significant variability between formulations but no consistent effects. Cellular uptake and efflux may thus not be important for curcumin bioavailability in vivo. Another potential factor influencing bioavailability, that was investigated for native and micellar curcumin, was the time-dependent intracellular distribution in intestinal cells. Uptake and intracellular distribution in Caco-2 cells mainly did not differ between native and micellar curcumin. After 30 minutes, both were localized in lysosomes and mitochondria, after 180 minutes in peroxisomes and native curcumin also in mitochondria. The temporary localization in lysosomes is in line with the involvement of endocytosis in cellular uptake of curcumin. Nevertheless, the intracellular localization of curcumin was not affected by its incorporation into polysorbate 80 micelles. The data generated in this doctoral project thus demonstrate that the incorporation of curcumin into polysorbate 80 micelles or g-cyclodextrin complexes successfully improve its bioavailability. The improved bioavailability of both formulations can be explained by enhanced digestive stability, solubility and micellization efficiency and appears to be independent from post-digestive processes, such as intestinal permeability, cellular uptake, cellular efflux or intracellular distribution. Consequently, the present doctoral thesis delivers relevant information for the therapeutical application of curcumin, for the development of highly bioavailable formulations, as well as the basis for further clinical research on the health beneficial effects of curcumin.
Synthesis of human phase I and phase II metabolites of hop (Humulus lupulus) prenylated flavonoids
(2022) Buckett, Lance; Schönberger, Sabrina; Spindler, Veronika; Sus, Nadine; Schoergenhofer, Christian; Frank, Jan; Frank, Oliver; Rychlik, Michael
Hop prenylated flavonoids have been investigated for their in vivo activities due to their broad spectrum of positive health effects. Previous studies on the metabolism of xanthohumol using untargeted methods have found that it is first degraded into 8-prenylnaringenin and 6-prenylnaringenin, by spontaneous cyclisation into isoxanthohumol, and subsequently demethylated by gut bacteria. Further combinations of metabolism by hydroxylation, sulfation, and glucuronidation result in an unknown number of isomers. Most investigations involving the analysis of prenylated flavonoids used surrogate or untargeted approaches in metabolite identification, which is prone to errors in absolute identification. Here, we present a synthetic approach to obtaining reference standards for the identification of human xanthohumol metabolites. The synthesised metabolites were subsequently analysed by qTOF LC-MS/MS, and some were matched to a human blood sample obtained after the consumption of 43 mg of micellarised xanthohumol. Additionally, isomers of the reference standards were identified due to their having the same mass fragmentation pattern and different retention times. Overall, the methods unequivocally identified the metabolites of xanthohumol that are present in the blood circulatory system. Lastly, in vitro bioactive testing should be applied using metabolites and not original compounds, as free compounds are scarcely found in human blood.
The influence of phosphate-availability and phytic acid on the profiles of fatty acids, (poly)phenols, carotenoids, and tocochromanols in maize (Zea mays L.) grains – from field experiments to human in vitro digestion studies
(2022) Lux, Peter Erwin; Frank, Jan
Phosphorus (P) is an essential element for living organisms and involved in phosphorylation reactions, including the biosynthesis of several organic micronutrients. Since P is taken up by plants from soil as phosphates, phosphate fertilizers are applied on fields to support the P-supply for crops. Today, shrinking global P-resources demand a reduction in the application of P-containing fertilizers, but knowledge about possible effects of a reduced phosphate-availability in soils on the quality of maize grains is lacking. Thus, it was hypothesized that a reduced phosphate-availability in soil influences the concentrations of dietary organic compounds (phenolics, fatty acids, carotenoids, and tocochromanols) in grains of maize during cultivation. Moreover, concentration differences in the P-storage form phytic acid in maize grains may impact the oxidative stability of these organic compounds during processing and digestion. Fertilizer experiments with maize hybrids were conducted at study sites with low to high phosphate concentrations in soil (1.6 to 20.6 mg CAL-P/100 g soil) in Germany. GC-MS or HPLC-(MS) analyses of the ground maize grains revealed the identity of fatty acids, insoluble (mostly diferulic and triferulic acids) and soluble (poly)phenols, carotenoids, and tocochromanols. The concentrations of these (poly)phenols, carotenoids, and tocochromanols as well as the fatty acid composition in the grains of the maize plants grown with or without phosphate fertilizer were not significantly (p < 0.05) different. Interaction effects between phosphate application and the locations on the fatty acid composition as well as on carotenoids and tocochromanols were considered as insignificant, concluding that a reduction in phosphate fertilization could be implemented on most fields in Germany when only considering these dietary compounds. Lastly, the influence of phytic acid on oxidation processes in maize during processing of porridge and in vitro digestion was examined. Porridges were prepared from maize flour containing either high phytic acid concentration or low phytic acid concentration supplemented with or without phytate. The porridges were digested using a human in vitro digestion model, resulting in a decrease in tocochromanols, carotenoids and unsaturated fatty acids. Oxidation products (alpha-tocopherylquinone, malondialdehyde) were formed in all samples, implying that phytic acid addition did not show the expected protective effect. The addition of phytate evoked a significant reduction in the micellarization efficiency of most carotenoids. Thus, the knowledge about phytic acid as antinutrient was extended.
Tocotrienols, tocopherols and tocomonoenols : characterization in Costa Rican palm oils, and intracellular and tissue distribution as a function of the hepatic alpha-tocopherol transfer protein
(2018) Irías-Mata, Andrea Paola; Frank, Jan
Vitamin E is a generic term for a group of micronutrients exhibiting the biological activity of alpha-tocopherol. Initially, four tocopherols (T) and four tocotrienols (T3) were recognized as the naturally occurring vitamin E compounds. The main difference among T and T3 is the 3-fold unsaturated 16-carbon side chain of the T3 compared to the saturated 16-carbon side chain of the T. Recently, a group of four vitamin E compounds with a single double bond at carbon 11 were discovered, namely tocomonoenols (T1). Edible oils are the major source of T, T3, and of T1. As a fat-soluble vitamin, the vitamin E is absorbed after oral intake and transported in the circulation to the liver, where vitamin E undergoes sorting by the action of the alpha-hepatic-tocopherol transfer protein (TTP) and the cytochrome P450 (CYP) enzymes. alpha-T is preferentially secreted into the bloodstream, while the non-alpha-T congeners are metabolized by CYP to the carboxyethylhydroxychromanols (CEHC), which are excreted via urine and feces. The TTP has been recognized as necessary for the maintenance of normal alpha-T concentrations in plasma and extrahepatic tissues. Interestingly, TTP might also protect the non-alpha-T congeners from side-chain degradation, and therefore prevent their metabolic degradation. The present thesis aimed at increasing our knowledge of the non-αT congeners of vitamin E with respect to their occurrence in food, their intracellular localization upon uptake into liver cells, and their tissue distribution in mammals. A potential role of the TTP in the intracellular and intra-organismic trafficking of the non-alpha-T congeners was a second focus of the current investigations. To this purpose, the vitamin E profiles and contents in oils of three Elaeis Guineensis, two Elaeis Oleifera, and one hybrid OxG palm fruit genotypes from Costa Rica were determined after mechanical extraction with a screw press and chemical extraction with hexane. Vitamin E profiles in the palm oils were similar, irrespective of the genotype and extraction procedure, and alpha- and gamma-T3 were the most abundant congeners. alpha-T1 was found in oils from five of the six varieties. Hexane extraction yielded up to 2.5-fold higher total vitamin E compared to screw press extraction. The two most abundant tocotrienols in the oils were selected for further studies with respect to their cellular uptake and intracellular distribution in cultured liver cells with and without stable expression of TTP and compared to their respective tocopherol counterparts. After uptake, all four congeners were primarily associated with the lysosomes, endoplasmic reticulum and plasma membrane. Overall, the results conclude that neither the structural differences between the four congeners, nor the TTP-expression are important factors behind the intracellular trafficking (uptake and distribution) of the congeners in cultured liver cells. Finally, an animal study was performed to examine the tissue distribution of alpha-T1 in mice in comparison to alpha-T. Besides was investigated the influence of TTP. Wild-type and TTP knockout mice were fed a standard diet with either alpha-T or alpha-T1 for 2 weeks. Concentrations were measured in blood and several tissues. alpha-T1 was only found in blood, not in tissues. Loss of TTP function in knockout mice resulted in almost complete depletion of alpha-T in all tissues. Interestingly, alpha-T1 was still present in blood. In conclusion, alpha-T1 reached the blood in mice with and without TTP function, suggesting that TTP may not, or only to a limited extent, be required for the secretion of alpha-T1 into the systemic circulation. Since more is known about alpha-T than the non-alpha-T congeners, new opportunities for further research on the biological activities and consequent health benefits of the non-alpha-T congeners have arisen based on the contributions of the present thesis.
Uptake and time‐dependent subcellular localization of native and micellar curcumin in intestinal cells
(2022) Flory, Sandra; Benz, Ann‐Kathrin; Frank, Jan
Uptake into intestinal cells and intracellular distribution into metabolically competent organelles, such as the endoplasmic reticulum, are important processes potentially limiting the bioavailability of xenobiotics. The incorporation of curcumin into polysorbate 80 micelles improves its naturally low oral bioavailability in humans. Here, we investigated uptake and time‐dependent localization of curcumin in intestinal cells when administered as native or micellar formulation. Differentiated Caco‐2 cells were incubated with 200 μmol/L native or micellar curcumin for up to 180 min and cellular uptake was quantified. Intracellular curcumin was detected already after 30 min and did not differ significantly between formulations or over time. Subcellular localization of native and micellar curcumin in Caco‐2 cells was studied by density gradient centrifugation. After 30 min, curcumin from both formulations was mainly associated with mitochondria and lysosomes, after 180 min native curcumin was associated with mitochondria and peroxisomes, micellar curcumin with peroxisomes only. Uptake and localization of native and micellar curcumin in intestinal cells do not differ significantly and consequently do not explain differences in bioavailability in humans. The temporary co‐localization with lysosomes is in agreement with the previously proposed role of endocytosis in cellular uptake of curcumin and warrants further investigation.
Vitamin E and carotenoid profiles in leaves, stems, petioles and flowers of stinging nettle (Urtica leptophylla Kunth) from Costa Rica
(2022) Montoya‐Arroyo, Alexander; Toro‐González, Camilo; Sus, Nadine; Warner, Jorge; Esquivel, Patricia; Jiménez, Víctor M; Frank, Jan
BACKGROUND Local leafy vegetables are gaining attention as affordable sources of micronutrients, including vitamins, pro-vitamin carotenoids and other bioactive compounds. Stinging nettles (Urtica spp.) are used as source of fibers, herbal medicine and food. However, despite the relatively wide geographical spread of Urtica leptophylla on the American continent, little is known about its content of vitamin E congeners and carotenoids. We therefore investigated the particular nutritional potential of different plant structures of wild Costa Rican U. leptophylla by focusing on their vitamin E and carotenoid profiles. RESULTS Young, mature and herbivore-damaged leaves, flowers, stems and petioles were collected and freeze-dried. Vitamin E and carotenoids were determined by high-performance liquid chromatography after liquid/liquid extraction with hexane. α-Tocopherol was the major vitamin E congener in all structures. Flowers had a high content of γ-tocopherol. Herbivore-damaged leaves had higher contents of vitamin E than undamaged leaves. Lutein was the major and β-carotene the second most abundant carotenoid in U. leptophylla. No differences in carotenoid profiles were observed between damaged and undamaged leaves. CONCLUSION The leaves of U. leptophylla had the highest nutritional value of all analyzed structures; therefore, they might represent a potential source of α-tocopherol, lutein and β-carotene.
Walnut oil reduces Aβ levels and increases neurite length in a cellular model of early Alzheimer disease
(2022) Esselun, Carsten; Dieter, Fabian; Sus, Nadine; Frank, Jan; Eckert, Gunter P.
Mitochondria are the cells’ main source of energy. Mitochondrial dysfunction represents a key hallmark of aging and is linked to the development of Alzheimer’s disease (AD). Maintaining mitochondrial function might contribute to healthy aging and the prevention of AD. The Mediterranean diet, including walnuts, seems to prevent age-related neurodegeneration. Walnuts are a rich source of α-linolenic acid (ALA), an essential n3-fatty acid and the precursor for n3-long-chain polyunsaturated fatty acids (n3-PUFA), which might potentially improve mitochondrial function. (2) Methods: We tested whether a lipophilic walnut extract (WE) affects mitochondrial function and other parameters in human SH-SY5Y cells transfected with the neuronal amyloid precursor protein (APP695). Walnut lipids were extracted using a Soxhlet Extraction System and analyzed using GC/MS and HPLC/FD. Adenosine triphosphate (ATP) concentrations were quantified under basal conditions in cell culture, as well as after rotenone-induced stress. Neurite outgrowth was investigated, as well as membrane integrity, cellular reactive oxygen species, cellular peroxidase activity, and citrate synthase activity. Beta-amyloid (Aβ) was quantified using homogenous time-resolved fluorescence. (3) Results: The main constituents of WE are linoleic acid, oleic acid, α-linolenic acid, and γ- and δ-tocopherol. Basal ATP levels following rotenone treatment, as well as citrate synthase activity, were increased after WE treatment. WE significantly increased cellular reactive oxygen species but lowered peroxidase activity. Membrane integrity was not affected. Furthermore, WE treatment reduced Aβ1–40 and stimulated neurite growth. (4) Conclusions: WE might increase ATP production after induction of mitochondrial biogenesis. Decreased Aβ1–40 formation and enhanced ATP levels might enhance neurite growth, making WE a potential agent to enhance neuronal function and to prevent the development of AD. In this sense, WE could be a promising agent for the prevention of AD.
What factors are associated with maternal undernutrition in eastern zone of Tigray, Ethiopia? Evidence for nutritional well-being of lactating mothers
(2020) Abera, Semaw Ferede; Kantelhardt, Eva Johanna; Bezabih, Afework Mulugeta; Tsadik, Mache; Lauvai, Judith; Ejeta, Gebisa; Wienke, Andreas; Frank, Jan; Scherbaum, Veronika
Background: Maternal undernutrition is a pervasive health problem among Ethiopian mothers. This study aims at identifying the level of maternal undernutrition and its associated factors in Kilte Awaleo-Health and Demographic Surveillance Site (KA-HDSS), Tigray region, Ethiopia. Methods: Nutritional status of 2260 lactating mothers was evaluated using the mid-upper-arm circumference (MUAC). Data from the vital events and verbal autopsy databases were linked to the survey and baseline recensus data to investigate the association of adult mortality from chronic causes of death (CoD) on maternal undernutrition. We employed a generalized log-binomial model to estimate the independent effects of the fitted covariates. Results: The overall prevalence of maternal undernutrition based on MUAC < 23 cm was 38% (95% CI: 36.1, 40.1%). Recent occurrence of household morbidity (adjusted prevalence ratio (adjPR) = 1.49; 95%CI: 1.22, 1.81) was associated with increased risk of maternal undernutrition. In addition, there was a 28% higher risk (adjPR = 1.28; 95%CI: 0.98, 1.67) of maternal undernutrition for those mothers who lived in households with history of adult mortality from chronic diseases. Especially, its association with severe maternal undernutrition was strong (adjusted OR = 3.27; 95%CI: 1.48, 7.22). In contrast, good maternal health-seeking practice (adjPR = 0.86; 95%CI: 0.77, 0.96) and production of diverse food crops (adjPR = 0.72; 95%CI: 0.64, 0.81) were associated with a lower risk of maternal undernutrition. Relative to mothers with low scores of housing and environmental factors index (HAEFI), those with medium and higher scores of HAEFI had 0.81 (adjPR = 0.81; 95%CI: 0.69, 0.95) and 0.82 (adjPR = 0.82; 95%CI: 0.72, 0.95) times lower risk of maternal undernutrition, respectively. Conclusions: Efforts to ameliorate maternal undernutrition need to consider the influence of the rising epidemiology of adult mortality from chronic diseases. Our data clearly indicate the need for channeling the integrated intervention power of nutrition-sensitive development programs with that of nutrition-specific sectoral services.