Fat soluble vitamins

Vitamin A

Cassava enrichend with carotenoids
Photo: F. J. Schweigert
Yellow cassava contains many carotenoids

Background

The term vitamin A describes a group of chemical compounds, which show similar structural characteristics (ß-ionone ring and isopropyl side chain) and directly or indirectly reveal vitamin A functions. The transport form and the central metabolite of the vitamin A family is retinol, which can be metabolized to the active metabolites retinal aldehyde (retinal) and retinoic acid by oxidation. Retinal is a chromophore and an integral component  of the visual purple (rhodopsin) in the retina and therefore of crucial significance for the visual process. Retinoic acid in contrast functions as transcription factor that regulates gene expression and is thus significantly involved in numerous central processes like the immune function, cell differentiation, reproduction and embryonal development1,2.

 

Vitamin A has to be supplied with the diet and will, after the uptake via the gastrointestinal tract, be stored in the liver in form of retinyl esters (predominantly retinyl palmitate). These storage sites can be mobilized by hydrolyzation and the released retinol will be secreted into the circulation. For this purpose prior to the hepatic secretion retinol binds the retinol binding protein 4 (RBP4), which facilitates the transport of the lipophilic ligand in the watery environment of the blood and protects it at the same time from oxidative damage. To prevent the loss of this low-molecular weight complex of retinol and RBP4 (holo-RBP4, ca. 21. kDa) due to renal filtration, it will furthermore bind to the protein transthyretin (TTR). The resulting trimolar structure with a molecular weight of approximately 75 kDa will then facilitate the transport of vitamin A (retinol) to the target tissues, where it will be taken up via the membrane receptor STRA6 (Stimulated by Retinoic Acid 6). The remaining complex of apo-RBP4 and TTR falls apart and will be catabolized renally1-4.

Research

Due to the complexity of the vitamin A metabolism physiological or pathophysiological events on a systemic level or in isolated organ systems can cause an imbalance of the vitamin A metabolism and consequently represent an are of focus of the department.

  • Association of kidney maturation of normally born and premature infants and the vitamin A metabolism as well as changes occurring during pregnancy5-8
  • Changes in the vitamin A metabolism due to chronic kidney disease and associated morbidities9-14
  • Significance of the vitamin A status for inflammatory processes15,16
  • Association of the vitamin A metabolism and the metabolic syndrome, insulin resistence and diabetes mellitus, respectively17-19
Cassava enrichend with carotenoids
Photo: F. J. Schweigert
Yellow cassava contains many carotenoids

Literature

  1. Blaner and Olson: The retinoids - Biology, chemistry, and medicine. S. 229-255 (Raven Press, New York, 1994)
  2. Blomhoff and Blomhoff: Overview of retinoid metabolism and function. J Neurobiol. 2006 Jun;66(7):606-30.
  3. Blaner: STRA6, a cell-surface receptor for retinol-binding protein: the plot thickens. Cell Metab. 2007 Mar;5(3):164-6.
  4. Harrison: Mechanisms involved in the intestinal absorption of dietary vitamin A and provitamin A carotenoids. Biochim Biophys Acta. 2012 Jan;1821(1):70-7.
  5. Longardt et al: Characterization of the vitamin A transport in preterm infants after repeated high-dose vitamin A injections. Eur J Clin Nutr. 2014 Dec;68(12):1300-4.
  6. Schmiedchen et al: The relative dose response test based on retinol-binding protein 4 is not suitable to assess vitamin A status in very low birth weight infants. Neonatology. 2014;105(2):155-60.
  7. Raila et al: Excretion of vitamin A in urine of women during normal pregnancy and pregnancy complications. Ann Nutr Metab. 2004 Sep-Oct;48(5):357-64.
  8. Nagl et al: Urinary vitamin A excretion in very low birth weight infants. Pediatr Nephrol. 2009 Jan;24(1):61-6.
  9. Raila et al: Microalbuminuria is a major determinant of elevated plasma retinol-binding protein 4 in type 2 diabetic patients. Kidney Int. 2007 Aug;72(4):505-11.
  10. Henze et al: Alterations of retinol-binding protein 4 species in patients with different stages of chronic kidney disease and their relation to lipid parameters. Biochem Biophys Res Commun. 2010 Feb 26;393(1):79-83.
  11. Frey et al: Effect of renal replacement therapy on retinol-binding protein 4 isoforms. Clin Chim Acta. 2009 Mar;401(1-2):46-50.
  12. Frey et al: Isoforms of retinol binding protein 4 (RBP4) are increased in chronic diseases of the kidney but not of the liver. Lipids Health Dis. 2008 Aug;7:29.
  13. Espe et al: Impact of vitamin A on clinical outcomes in haemodialysis patients. Nephrol Dial Transplant. 2011 Dec;26(12):4054-61.
  14. Danquah et al: Vitamin A: potential misclassification of vitamin A status among patients with type 2 diabetes and hypertension in urban Ghana. Am J Clin Nutr. 2015 Jul;102(1):207-14.
  15. Bobbert et al: Increased plasma retinol binding protein 4 levels in patients with inflammatory cardiomyopathy. Eur J Heart Fail. 2009 Dec;11(12):1163-8.
  16. Schweigert: Inflammation-induced changes in the nutritional biomarkers serum retinol and carotenoids. Curr Opin Clin Nutr Metab Care. 2001 Nov;4(6):477-81.
  17. Henze et al: Evidence that kidney function but not type 2 diabetes determines retinol-binding protein 4 serum levels. Diabetes. 2008 Dec;57(12):3323-6.
  18. Espe et al: High-normal C-reactive protein levels do not affect the vitamin A transport complex in serum of children and adolescents with type 1 diabetes. Pediatr Res. 2007 Dec;62(6):741-5.
  19. Thawnashom, K. et al. Association between retinol-binding protein and renal function among Asian subjects with type 2 diabetes mellitus: A cross-sectional study. Southeast Asian J Trop Med Public Health. 2011 Jul;42(4):936-45.

Carotenoids

Background

Carotenoids are yellow and orange, organic pigments, which can exclusively be synthesized by plants and microalgae, in which they mainly assist photosynthesis. More than 800 carotenoids are known that are classified as carotenes and  xanthophylls. For humans especially the carotenes α-carotene, β-carotene, β-cryptoxanthene and lycopene as well as the xanthophylls lutein and zeaxanthin are of significant importance and therefore in the focus of the department`s research. α- and β-carotene as well as β-cryptoxanthene serve as provitamin A carotenoids in the supply with vitamin A for humans. Whereas lutein and zeaxanthin are important for the protection of the retina against damages by UV light and radicals and therefore for the prevention of age-related macular degeneration (AMD). Furthermore all carotenoids are natural antioxidants and therefore valuable food compounds1-3.

Research

The significance of carotenoids for the human organism is researched in the department of Physiology and Pathophysiology of Nutrition under several aspects:

  • Carotenoids as a source of provitamin A and for the evaluation of the vitamin A status4-8
  • Importance of carotenoids for inflammatory processes9,10
  • Importance of carotenoids as antioxidants and for the prevention of chronic diseases (e.g. AMD)11-13

Literature

  1. Hinds et al: Carotenoids and retinoids: a review of research, clinical, and public health applications. J Clin Pharmacol. 1997 Jul;37(7):551-8.
  2. Li and Tso: Vitamin A uptake from foods. Curr Opin Lipidol. 2003 Jun;14(3):241-7.
  3. Schweigert: in Carotenoids. S. 249-284 (Birkhäuser Verlag, Basel, 1998).
  4. Andert et al: Nutritional status of pregnant women in Northeast Thailand. Asia Pac J Clin Nutr. 2006;15(3):329-34.
  5. Gouado et al: Systemic levels of carotenoids from mangoes and papaya consumed in three forms (juice, fresh and dry slice). Eur J Clin Nutr. 2007 Oct;61(10):1180-8.
  6. Schweigert et al: Effect of the stage of lactation in humans on carotenoid levels in milk, blood plasma and plasma lipoprotein fractions. Eur J Nutr. 2004 Feb;43(1):39-44.
  7. Schweigert et al: Vitamin A, carotenoid and vitamin E plasma concentrations in children from Laos in relation to sex and growth failure. Nutr J. 2003 Nov;2:17.
  8. Macias and Schweigert: Changes in the concentration of carotenoids, vitamin A, alpha-tocopherol and total lipids in human milk throughout early lactation. Ann Nutr Metab. 2001;45(2):82-5.
  9. Schweigert: Inflammation-induced changes in the nutritional biomarkers serum retinol and carotenoids. Curr Opin Clin Nutr Metab Care. 2001 Nov;4(6):477-81.
  10. Schweigert and Raila: Entzündungen führen infolge der Akute-Phase-Reaktionen zu einem funktionellen Mangel an Retinol, alpha-Tocopherol und Carotinoiden. Ernährung & Medizin 21, 77-81 (2006).
  11. Carlsohn et al: Exercise increases the plasma antioxidant capacity of adolescent athletes. Ann Nutr Metab. 2008;53(2):96-103.
  12. Carlsohn et al: Physical activity, antioxidant status, and protein modification in adolescent athletes. Med Sci Sports Exerc. 2010 Jun;42(6):1131-9.
  13. Schweigert and Reimann: [Micronutrients and their relevance for the eye--function of lutein, zeaxanthin and omega-3 fatty acids]. Klin Monbl Augenheilkd. 2011 Jun;228(6):537-43.

Vitamin D

Photo: Thomas Roese

Background

No other vitamin is currently being researched as intensely as vitamin D. This research interest can mainly be attributed to new effects of vitamin D on the organism, which have been discovered in the recent years in addition to the known effects on the bone health.

Especially during the winter months in the northern hemisphere a great part of the population shows a reduced vitamin D status1,2. The recently investigated and discussed diseases as a result of reduced vitamin D status and vitamin D deficiency, respectively, are attributed to the non-calcaemic effects of vitamin D. This includes for example diabetes mellitus, cancer, cardiovascular disease and diseases of the immune system3. The underlying, responsible mechanisms in this context are so far not completely understood4 and therefore object of many research activities.

Research

One main area of research at the department of Physiology and Pathophysiology of Nutrition is the investigation regarding the association of vitamin D and kidney diseases. The quantification of different vitamin D metabolites is one approach of the department to solve this question.
Further research activities pursue the analysis of the connection between the vitamin D status, kidney diseases and cardiovascular diseases by using in vitro models systems to analyze the integrity of vessels depending on the vitamin D supply and simulating conditions of kidney disease.

Photo: Thomas Roese

Literature

  1. Ovesen et al: Geographical differences in vitamin D status, with particular reference to European countries. Proc Nutr Soc, 2003 Nov; 62(4):813-21
  2. Mithal et al: Global vitamin D status and determinants of hypovitaminosis D.
    Osteoporos Int. 2009 Nov; 20(11):1807-1820
  3. Jones: Extrarenal Vitamin D Activation and Interactions Between Vitamin D2, Vitamin D3, and Vitamin D Analogs. Annu Rev Nutr. 2013; 33:23-44
  4. Bikle: Nonclassic actions of vitamin D. J Clin Endocrinol Metab. 2009 Jan; 94(1):26-34

Vitamin E

Background

The term vitamin E includes all natural and synthetic tocopherol and tocotrienol derivatives, which show qualitatively the biological activity of α-tocopherol. In animal cells α-tocopherol is a compound of biological membranes, where it serves as fat soluble antioxidant. The important biological antioxidant function of vitamin E is to protect membrane lipids, lipoproteins and depot fats from lipid peroxidation.

Vitamin E is an essential nutrient and therefore has to be supplied with the food. The absorption of vitamin E occurs in the small intestine together with other food lipids. The transport in the blood occurs, in contrast to the vitamins A and D, unspecifically by binding to the lipoprotein fractions (VLDL/LDL, HDL). The uptake of vitamin E into the cells is therefore strongly related to the lipoprotein metabolism.  

Research

Due to the central position of vitamin E as lipophilic antioxidant, analyses regarding the influence of different physiological and pathophysiological conditions on the vitamin E metabolism are a focus area of our department. The basis is formed by the quantification of tocopherol and tocotrienol derivatives in blood and tissue of humans and pets using HPLC. In this context we were able to demonstrate in a prospective study that patients that suffer from type 2 diabetes mellitus requiring dialysis and that reveal a reduced α-tocopherol concentration in blood have an increased risk for strokes1. Further studies focused on the transfer of α-tocopherol from blood into the ovarian follicle in women2 as well as the measurement of α-tocopherol losses via the ascites liquid of women with progressing ovarian carcinoma3. If a supplementation of vitamin E has an influence on the progress of the disease continues to be a research focus.

The adequate supply of vitamin E with the food is also of significant importance for pet animals to maintain their health. In this context our department demonstrated that dogs are able to absorb different tocopherol and tocotrienol derivatives in the gut and that the associated increase in the blood is accompanied by an increase of antioxidant capacity4. If a dietetic supplementation with tocotrienols has a positive effect on the progression of diseases with increased oxidative stress, will be analyzed in further studies.

Literature

  1. Espe et al: Low Plasma α-Tocopherol Concentrations and Adverse Clinical Outcomes in Diabetic Hemodialysis Patients. Clin J Am Soc Nephrol. 2013 Mar;8(3):452-8
  2. Schweigert et al: Carotenoids and α-tocopherol in plasma and follicular fluid of women undergoing in-vitro fertilisation. Hum Reprod. 2003 Jun;18(6):1259-64.
  3. Schweigert et al: Accumulation of selected carotenoids, α-tocopherol and retinol in human ovarian carcinoma ascitic fluid. Ann Nutr Metab. 2004;48(4):241-5.
  4. Raila et al: Increased antioxidant capacity in plasma of dogs after a single oral dosage of tocotrienols. Br J Nutr. 2011 Oct;106 Suppl 1:S116-9.