Microalgae-derived sterols do not reduce the bioavailability of oral vitamin D3 in mice
Abstract
Abstract: Microalgae have drawn increasing attention as sustainable food sources, also because of their lipid-lowering phytosterols. As phytosterols are also discussed critically regarding their effect on the availability of fat-soluble vitamins, this study aimed to investigate microalgae-derived phytosterols and their effect on vitamin D status. GC–MS analysis showed large variations in the phytosterol profiles of microalgal species. The most frequent sterols were β-sitosterol and stigmasterol. To investigate their effects on vitamin D status, 40 mice were randomized to four groups and fed a vitamin D3-adequate (25 μg/kg) Western-style diet with 0% phytosterols (control) or 1% ergosterol (a fungal sterol not typical for microalgae), β-sitosterol or stigmasterol for four weeks. Contrary to the hypothesis that phytosterols adversely affect vitamin D uptake, mice fed β-sitosterol had significantly higher concentrations of vitamin D3 in plasma (3.15-fold, p<0.01), liver (3.15-fold, p<0.05), and skin (4.12-fold, p<0.005) than the control group. Small increases in vitamin D3 in plasma and skin were also observed in mice fed stigmasterol. In contrast, vitamin D3 levels in the ergosterol and control groups did not differ. The increased tissue levels of vitamin D3 in mice fed β-sitosterol and stigmasterol were not attributable to the observed reduction in liver triglycerides in these groups. The data rather suggest that changes in bile acid profiles were responsible for the beneficial effect of microalgae sterols on the bioavailability of vitamin D3. In conclusion, consumption of microalgae might not adversely affect vitamin D status.
References
1 . Relationship between the colour and the chemical structure of carotenoid pigments. Food Chem. 2007;101(3):1145–50.
2 . Microalgae for “healthy” foods – possibilities and challenges. Compr Rev Food Sci Food Saf. 2010;9(6):655–75.
3 . Micro-algae as a source of protein. Biotechnol Adv. 2007;25(2):207–10.
4 . Microalgae as sources of carotenoids. Mar Drugs. 2011;9(4):625–44.
5 . Heterotrophic cultivation of microalgae for pigment production: A review. Biotechnol Adv. 2018;36(1):54–67.
6 . Phenylpropanoids inhibit protofilament formation of Escherichia coli cell division protein FtsZ. J Med Microbiol. 2011;60(Pt 9):1317–25.
7 . The effect of light, salinity, and nitrogen availability on lipid production by Nannochloropsis sp. Appl Microbiol Biotechnol. 2011;90(4):1429–41.
8 . Plant sterols: Diversity, biosynthesis, and physiological functions. Biochemistry (Mosc). 2016;81(8):819–34.
9 . Microalgae metabolites: A rich source for food and medicine. Saudi J Biol Sci. 2019;26(4):709–22.
10 Analysis of phytosterol, fatty acid, and carotenoid composition of 19 microalgae and 6 bivalve species. J Aquatic Food Prod Technol. 2020;29(5):461–79.
11 Plant-based sterols and stanols in health & disease: “Consequences of human development in a plant-based environment?”. Prog Lipid Res. 2019;74:87–102.
12 . Phytosterols: physiologic and metabolic aspects related to cholesterol-lowering properties. Nutr Res. 2008;28(4):217–25.
13 . ABCG5/G8: A structural view to pathophysiology of the hepatobiliary cholesterol secretion. Biochem Soc Trans. 2019;47(5):1259–68.
14 . Influence of phytosterol and phytostanol food supplementation on plasma liposoluble vitamins and provitamin A carotenoid levels in humans: An updated review of the evidence. Crit Rev Food Sci Nutr. 2017;57(9):1906–21.
15 . Dietary reference intakes for calcium and vitamin D. Washington, DC: The National Academies Press; 2010.
16 . New reference values for vitamin D. Ann Nutr Metab. 2012;60(4):241–46.
17
Nordic Council of Ministers . Nordic Nutrition Recommendations 2012: Integrating Nutrition and Physical Activity. Nordic Council of Ministers; 2014.18 Phytosterols can impair vitamin D intestinal absorption in vitro and in mice. Mol Nutr Food Res. 2011;55(Suppl. 2):S303–11.
19 . Vitamin D status of mice deficient in scavenger receptor class B type 1, cluster determinant 36 and ATP-binding cassette proteins G5/G8. Nutrients. 2020;12(8):2169.
20 . Cholesterol reduction by different plant stanol mixtures and with variable fat intake. Metabolism. 1999;48(5):575–80.
21 . Retinol, vitamin D, carotenes and alpha-tocopherol in serum of a moderately hypercholesterolemic population consuming sitostanol ester margarine. Atherosclerosis. 1999;145(2):279–85.
22 . The effect of a very high daily plant stanol ester intake on serum lipids, carotenoids, and fat-soluble vitamins. Clin Nutr. 2010;29(1):112–8.
23 . Safety of long-term consumption of plant sterol esters-enriched spread. Eur J Clin Nutr. 2003;57(5):681–92.
24 Safety aspects and cholesterol-lowering efficacy of low fat dairy products containing plant sterols. Eur J Clin Nutr. 2006;60(5):633–42.
25 . Cholesterol-lowering effect of stanol ester in a US population of mildly hypercholesterolemic men and women: a randomized controlled trial. Mayo Clin Proc. 1999;74(12):1198–206.
26 Deutsche Einheitsmethoden zur Untersuchung von Fetten, Fettprodukten, Tensiden und verwandten Stoffen, Wissenschaftliche Verlagsgesellschaft, Stuttgart; 2019.
27 . Guide for the care and use of laboratory animals, 8th ed. National Academy Press, Washington, DC; 2011.
28 Lupin protein isolate versus casein modifies cholesterol excretion and mRNA expression of intestinal sterol transporters in a pig model. Nutr Metab (Lond). 2014;11(1):9.
29 . Inhibition of Niemann-Pick C1-like protein 1 by ezetimibe reduces uptake of deuterium-labeled vitamin D in mice. J Steroid Biochem Mol Biol. 2020;197:105504.
30 . Tissue-specific expression of monocarboxylate transporters during fasting in mice. PLoS One. 2014;9(11):e112118.
31 . A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 2001;29(9):e45.
32 . FXR agonists and FGF15 reduce fecal bile acid excretion in a mouse model of bile acid malabsorption. J Lipid Res. 2007;48(12):2693–700.
33 . Reduction in intestinal cholesterol absorption by various food components: Mechanisms and implications. Atheroscler Suppl. 2010;11(1):45–8.
34 . LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012. Bile Acids. Last update: Sep 25, 2017.
35 Disruption of cholesterol 7alpha-hydroxylase gene in mice. II. Bile acid deficiency is overcome by induction of oxysterol 7alpha-hydroxylase. J Biol Chem. 1996;271(30):18024–31.
36 . Feeding natural hydrophilic bile acids inhibits intestinal cholesterol absorption: studies in the gallstone-susceptible mouse. Am J Physiol Gastrointest Liver Physiol. 2003;285:G494–502.
37 Redundant pathways for negative feedback regulation of bile acid production. Dev Cell. 2002;2(6):721–31.
38 Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis. Cell Metabolism. 2005;2(4):217–25.
39 . Markers indicating body vitamin d stores and responses of liver and adipose tissues to changes in vitamin D intake in male mice. Nutrients. 2020;12(5):1391.
40 . Novel activities of CYP11A1 and their potential physiological significance. J Steroid Biochem Mol Biol. 2015;151:25–37.
41 Aloe vera phytosterols act as ligands for PPAR and improve the expression levels of PPAR target genes in the livers of mice with diet-induced obesity. Obes Res Clin Pract. 2011;5(3):e190–e201.
42 . Animal models to study bile acid metabolism. Biochim Biophys Acta Mol Basis Dis. 2019;1865(5):895–911.
43 . UVB exposure stimulates production of vitamin D3 in selected microalgae. Algal Res. 2021;59:102472.
