Liposomes as building blocks

Phospholipids: vital molecules

Our bioactives are encapsulated in lipid bilayers that consist of two components: phospholipids and cholesterol. Phospholipids have a polar, hydrophilic head group and two hydrophobic tails, which are usually fatty acids. When phospholipids are dispersed in water, they will spontaneously form bilayers: the hydrophobic tails cluster together whilst the hydrophilic heads are exposed to the water.In our bodies, phospholipids are components of the cellular membranes and are crucial for shape as well as cellular signaling [1,2]. 

The most abundant phospholipid type in mammalian membranes is phosphatidylcholine (PC), followed by phosphatidylethanolamine (PE). Both molecules are essential in metabolic processes and healthy organ function. For example, they are required for the assembly and secretion of lipoproteins that transport lipids and cholesterol through the bloodstream. Furthermore, maintaining proper levels and ratios of phospholipid types is vital for healthy organ function [3]. Phospholipids like PC and PE naturally occur in several dietary sources such as egg, soybeans and milk [4].

Health benefits of phospholipids

Various studies have shown that intake of phospholipids can have beneficial effects for both healthy and diseased people. The most well-established effects are discussed below.

Inflammation

Firstly, cholines seem to have anti-inflammatory properties [5], which may be helpful in the treatment of inflammatory diseases. Levels of PC are reduced in the colon of patients with ulcerative colitis (UC), a type of inflammatory bowel disease [6,7]. Human trials have shown improvements in clinical and endoscopic symptoms of UC after daily intake of PC [8-11]. This beneficial effect may be due to the ability of PC to create a hydrophobic surface in the colon, which prevents bacterial penetrance [12]. 

Liver health

Furthermore, maintaining the proper balance between PCs and PEs is crucial for liver health. The ratio of PC to PE is lowered in patients with non-alcoholic fatty liver disease and non-alcoholic steatohepatitis [13,14]. Administration of PCs increases hepatic PC levels [15] and is widely known to benefit the treatment of several liver diseases, including chronic hepatitis and toxic liver damage. Specifically PCs from soybean show many positive effects (e.g. antioxidant, membrane-protective) and help improve clinical and pathological symptoms [16-18]. 

Fatigue

Finally, supplementation with phospholipid mixtures is used to replace damaged membrane phospholipids and restore cellular and organ function. This therapy is called Membrane Lipid Replacement and has been shown to reduce fatigue in aged and chronically ill people [25]. Daily oral intake of soy lecithin, a mixture of phospholipids, is the most common, efficient and safe variant of the therapy and was recently shown to increase vigor and lower blood pressure in middle-aged women [26]. 

Brain function

PCs have also been connected to brain function. Memory and learning was better in people with high intake of choline, a precursor for PC [19]. Diminished levels of PCs were found in the blood of patients with Alzheimer’s Disease and are associated with lower hippocampal volume [20,21]. Oral administration of PC and PE improved learning ability and memory and diminished cognitive decline in animal models [22-24]. Concentrations of PC in the brain were elevated after supplementation, demonstrating that oral intake leads to local phospholipid increases despite physiological and metabolic challenges. 

Sources

[1] Alberts B, Johnson A, Lewis J, et al. Molecular Biology of the Cell. 4th edition. New York: Garland Science; 2002. The Lipid Bilayer. Available from: https://www.ncbi.nlm.nih.gov/books/NBK26871/

[2] Sunshine, H., Iruela-Arispe, M.L. (2017). Membrane lipids and cell signaling. Current Opinion in Lipidology 28(5), 408-413. doi: 10.1097/MOL.0000000000000443.

[3] Van der Veen, J.N., Kennelly, J.P., Wan, S., Vance, J.E., Vance, D.E., Jacobs, R.L. (2017). The critical role of phosphatidylcholine and phosphatidylethanolamine metabolism in health and disease. Biochimica et Biophysica Acta Biomembranes 1859(9 Pt B), 1558-1572. doi: 10.1016/j.bbamem.2017.04.006

[4] Küllenberg, D., Taylor, L.A., Schneider, M., Massing, U. (2012). Health effects of dietary phospholipids. Lipids in Health and Disease 11, 3. doi: 10.1186/1476-511X-11-3.

[5] Detopoulou, P., Panagiotakos, D. B., Antonopoulou, S., Pitsavos, C., & Stefanadis, C. (2008). Dietary choline and betaine intakes in relation to concentrations of inflammatory markers in healthy adults: the ATTICA study. The American journal of clinical nutrition, 87(2), 424-430. 

[6] Ehehalt, R., Wagenblast, J., Erben, G., Lehmann, W.D., Hinz, U., Merle, U., Stremmel, W. (2004). Phosphatidylcholine and lysophosphatidylcholine in intestinal mucus of ulcerative colitis patients. A quantitative approach by nanoElectrospray-tandem mass spectrometry. Scandinavian Journal of Gastroenterology 39, 737-742.

[7] Braun, A., Treede, I., Gotthardt, D., Tietje, A., Zahn, A., Ruhwald, R., Schoenfeld, U., Welsch, T., Kienle, P., Erben, G., Lehmann, W.D., Fuellekrug, J., Stremmel, W., Ehehalt, R. (2009). Alterations of phospholipid concentration and species composition of the intestinal mucus barrier in ulcerative colitis: a clue to pathogenesis. Inflammatory Bowel Diseases 15, 1705-1720.

[8] Stremmel, W., Merle, U., Zahn, A., Autschbach, F., Hinz, U., Ehehalt, R. (2005). Retarded release phosphatidylcholine benefits patients with chronic active ulcerative colitis. Gut 54, 966-971.

[9] Stremmel, W., Ehehalt, R., Autschbach, F., Karner, M. (2007). Phosphatidylcholine for steroid-refractory chronic ulcerative colitis: a randomized trial. Annals of Internal Medicine 147(9), 603-10.

[10] Stremmel, W., Braun, A., Hanemann, A., Ehehalt, R., Autschbach, F., Karner, M. (2010). Delayed release phosphatidylcholine in chronic-active ulcerative colitis: a randomized, double-blinded, dose finding study. Journal of Clinical Gastroenterology 44, e101-e107.

[11] Karner, M., Kocjan, A., Stein, J., Schreiber, S., von Boyen, G., Uebel, P., Schmidt, C., Kupcinskas, L., Dina, I., Zuelch, F., Keilhauer, G., Stremmel, W. (2014). First multicenter study of modified release phosphatidylcholine “LT-02” in ulcerative colitis: a randomized, placebo-controlled trial in mesalazine-refractory courses. American Journal of Gastroenterology 109, 1041-1051.

[12] Parian, A.M., Mullin, G.E., Langhorst, J., Brown, A.C. (2018). Integrative Medicine. Chapter 50 – Inflammatory Bowel Disease. p501-516.

Pollard, T.D., Earnshaw, W.C., Lippincott-Schwartz, J., Johnson, G.T. (2017). Cell Biology (Third Edition). Chapter 26 – Second Messengers. p443-462.

[13] Li, Z., Agellon, L.B., Allen, T.M., Umeda, M., Jewell, L., Mason, A., Vance, D.E. (2006). The ratio of phosphatidylcholine to phosphatidylethanolamine influences membrane integrity and steatohepatitis. Cell Metabolism 3(5), 321-31.

[14] Puri, P., Baillie, R.A., Wiest, M.M., Mirshahi, F., Choudhury, J., Cheung, O., Sargeant, C., Contos, M.J., Sanyal, A.J. (2007). A lipidomic analysis of nonalcoholic fatty liver disease. Hepatology 46(4), 1081-90.

[15] Lieber, C.S., Robins, S.J., Li, J., DeCarli, L.M., Mak, K.M., Fasulo, J.M., Leo, M.A. (1994). Phosphatidylcholine protects against fibrosis and cirrhosis in the baboon. Gastroenterology 106(1), 152-9.

[16] Gundermann, K.J., Kuenker, A., Kuntz, E., Droździk, M. (2011). Activity of essential phospholipids (EPL) from soybean in liver diseases. Pharmacological Reports 63(3), 643-59.

[17] Gundermann, K.J., Gundermann, S., Drozdzik, M., Mohan Prasad, V.G. (2016). Essential phospholipids in fatty liver: a scientific update. Clinical and Experimental Gastroenterology 9, 105-17. doi: 10.2147/CEG.S96362. eCollection 2016.

[18] Maev, I.V., Samsonov, A.A., Palgova, L.K., Pavlov, C.S., Vovk, E.I., Shirokova, E.N., Starostin, K.M. (2020). Effectiveness of phosphatidylcholine in alleviating steatosis in patients with non-alcoholic fatty liver disease and cardiometabolic comorbidities (MANPOWER study). BMJ Open Gastroenterology 7(1), e000341. doi: 10.1136/bmjgast-2019-000341. eCollection 2020.

[19] Poly, C., Massaro, J.M., Seshadri, S., Wolf, P.A., Cho, E., Krall, E., Jacques, P.F., Au, R. (2011). The relation of dietary choline to cognitive performance and white-matter hyperintensity in the Framingham Offspring Cohort. The American Journal of Clinical Nutrition 94(6), 1584-91. doi: 10.3945/ajcn.110.008938.

[20] Whiley, L., Sen, A., Heaton, J., Proitsi, P., García-Gómez, D., Leung, R., Smith, N., Thambisetty, M., Kloszewska, I., Mecocci, P., Soininen, H., Tsolaki, M., Vellas, B., Lovestone, S., Legido-Quigley, C.; AddNeuroMed Consortium. (2014). Evidence of altered phosphatidylcholine metabolism in Alzheimer’s disease. Neurobiology of Aging 35(2), 271-8. doi: 10.1016/j.neurobiolaging.2013.08.001. Epub 2013 Sep 13.

[21] Kim, M., Nevado-Holgado, A., Whiley, L., Snowden, S.G., Soininen, H., Kloszewska, I., Mecocci, P., Tsolaki, M., Vellas, B., Thambisetty, M., Dobson, R.J.B., Powell, J.F., Lupton, M.K., Simmons, A., Velayudhan, L., Lovestone, S., Proitsi, P., Legido-Quigley, C. (2017). Association between Plasma Ceramides and Phosphatidylcholines and Hippocampal Brain Volume in Late Onset Alzheimer’s Disease. Journal of Alzheimer’s Disease 60(3), 809-817. doi: 10.3233/JAD-160645.

[22] Suzuki, S., Yamatoya, H., Sakai, M., Kataoka, A., Furushiro, M., Kudo, S. (2001). Oral administration of soybean lecithin transphosphatidylated phosphatidylserine improves memory impairment in aged rats. The Journal of Nutrition 131(11), 2951-6.

[23] Lee, B., Sur, B.J., Han, J.J., Shim, I., Her, S., Lee, Y.S., Lee, H.J., Hahm, D.H. (2015). Oral administration of squid lecithin-transphosphatidylated phosphatidylserine improves memory impairment in aged rats. Progress in Neuro-psychopharmacology and Biological Psychiatry 56, 1-10. doi: 10.1016/j.pnpbp.2014.07.004. Epub 2014 Jul 22.

[24] Zhou, M.M., Xue, Y., Sun, S.H., Wen, M., Li, Z.J., Xu, J., Wang, J.F., Yanagita, T., Wang, Y.M., Xue, C.H. (2016). Effects of different fatty acids composition of phosphatidylcholine on brain function of dementia mice induced by scopolamine. Lipids in Health and Disease 15(1), 135. doi: 10.1186/s12944-016-0305-5.

[25] Nicolson, G.L., Ash, M.E. (2017). Membrane Lipid Replacement for chronic illnesses, aging and cancer using oral glycerolphospholipid formulations with fructooligosaccharides to restore phospholipid function in cellular membranes, organelles, cells and tissues. Biochimica et Biophysica Acta. Biomembranes 1859(9 Pt B), 1704-1724. doi: 10.1016/j.bbamem.2017.04.013. 

[26] Hirose, A., Terauchi, M, Osaka, Y., Akiyoshi, M., Kato, K., Miyasaka, N. (2018). Effect of soy lecithin on fatigue and menopausal symptoms in middle-aged women: a randomized, double-blind, placebo-controlled study. Nutrition Journal 17(1), 4. doi: 10.1186/s12937-018-0314-5.]