Membrane Lipid Replacement: Clinical Studies Using a Natural Medicine Approach to Restoring Membrane Function and Improving Health — Oak Academic Publishing
Research ArticleOpen AccessGoogle Scholar indexed
Membrane Lipid Replacement: Clinical Studies Using a Natural Medicine Approach to Restoring Membrane Function and Improving Health
Department of Molecular Pathology, The Institute for Molecular Medicine, Huntington Beach, CA, USA
1 Department of Molecular Pathology, The Institute for Molecular Medicine, Huntington Beach, CA, USA
Functional oral supplements containing cell membrane glycerolphospholipids and antioxidants have been used to safely replace damaged membrane lipids that accumulate during aging and in various clinical conditions. This approach differs from other dietary and intravenous interventions in the composition of phospholipids and the presence of fructooligosaccharides that protect the phospholipids against oxidation and bile and enzymatic damage. Various chronic clinical conditions are characterized by membrane phospholipid oxidative damage, resulting in loss of cellular function. Recent clinical trials have shown the benefits of Membrane Lipid Replacement in replenishing damaged membrane lipids and restoring mitochondrial function, resulting in reductions in fatigue in aged subjects and patients with a variety of clinical diagnoses. Recent in vitro experiments with nonphysiological concentrations of phospholipids did not result in enhancement of mitochondrial electron transport enzyme activities. This can be explained by the use of the wrong phospholipid fatty acids, over-dilution of membrane constituents and mitochondrial swelling. A similar phenomenon was seen when human sperm were incubated in vitro with high concentrations of glycerolphospholipids and their motility was assessed. Only lower, more physiological concentrations of glycerolphospholipids stimulated sperm motility. Additional studies are needed to determine the functional effects of Membrane Lipid Replacement on other cellular membranes, such as the plasma membrane and other intracellular membranes of various cells and tissues.
Nicolson, G.L. (2003) Lipid Replacement as an Adjunct Therapy in Chronic Fatigue, Anti-Aging and Restoration of Mitochondrial Function. Journal of the American Nutraceutical Association, 6, 22-28. http://www.immed.org/treatment%20considerations/GNicolsonJANAvol6_3_.pdf
Küllenberg, D., Taylor, L.A., Schneider, M. and Massing, U. (2012) Health Effects of Dietary Phospholipids. Lipids in Health and Disease, 11, e3. http://dx.doi.org/10.1186/1476-511X-11-3
Nicolson, G.L. and Ash, M.E. (2014) Lipid Replacement Therapy: A Natural Medicine Approach to Replacing Damaged Lipids in Cellular Membranes and Organelles and Restoring Function. Biochimica et Biophysica Acta (BBA)— Biomembranes, 1838, 1657-1679. http://dx.doi.org/10.1016/j.bbamem.2013.11.010
van Meer, G., Voelker, D.B. and Feigenson, G.W. (2008) Membrane Lipids: Where They Are and How They Behave. Nature Reviews Molecular and Cell Biology, 9, 112-124. http://dx.doi.org/10.1038/nrm2330
Escribá, P.V. (2006) Membrane-Lipid Therapy: A New Approach in Molecular Medicine. Trends in Molecular Medicine, 12, 34-43. http://dx.doi.org/10.1016/j.molmed.2005.11.004
Gundermann, K.J., Kuenker, A., Kuntz, E. and Drozdzik, M. (2011) Activity of Essential Phospholipids (EPL) from Soybean in Liver Diseases. Pharmacology Reports, 63, 643-659. http://dx.doi.org/10.1016/S1734-1140(11)70576-X
Le Kim, D. and Betzing, H. (1976) Intestinal Absorption of Polyunsaturated Phosphatidylcholine in the Rat. Hoppe Seylers Zeitschriftfür Physiologische Chemie, 357, 1321-1331. http://dx.doi.org/10.1515/bchm2.1976.357.2.1321
Zierenberg, O. and Grundy, S.M. (1982) Intestinal Absorption of Polyenephosphatidylcholine in Man. Journal of Lipid Research, 23, 1136-1142.
Ibarguren, M., López, D.J. and Escribá, P.V. (2014) The Effect of Natural and Synthetic Fatty Acids on Membrane Structure, Microdomain Organization, Cellular Functions and Human Health. Biochimica et Biophysica Acta (BBA)— Biomembranes, 1838, 1518-1528. http://dx.doi.org/10.1016/j.bbamem.2013.12.021
Adibhatla, R.M. and Hatcher, J.F. (2010) Lipid Oxidation and Peroxidation in CNS Health and Disease: From Molecular Mechanisms to Therapeutic Opportunities. Antioxidants and Redox Signaling, 12, 125-169. http://dx.doi.org/10.1089/ars.2009.2668
Catalá, A. (2012) Lipid Peroxidation Modifies the Picture of Membranes from the “Fluid Mosaic Model” to the “Lipid Whisker Model”. Biochimie, 94, 101-109. http://dx.doi.org/10.1016/j.biochi.2011.09.025
Wagener, H.H., Fontaine, R. and Neumann, B. (1976) Pharmakologie “Essentiele” Phospholipide (EPL). Drug Research, 26, 1733-1743.
Pandey, N.R. and Sparks, D.L. (2008) Phospholipids as Cardiovascular Therapeutics. Current Opinion in Investigative Drugs, 9, 281-285.
Ellithorpe, R.R., Settineri, R., Ellithorpe, T. and Nicolson, G.L. (2015) Blood Homocysteine and Fasting Insulin Levels Are Reduced and Erythrocyte Sedimentation Rates Increased with a Glycophospholipid-Vitamin Formulation: A Retrospective Study in Older Subjects. Functional Foods in Health and Disease, 5, 126-135. http://functionalfoodscenter.net/files/102987419.pdf
Cohn, J.S., Wat, E., Kamili, A. and Tandy, S. (2008) Dietary Phospholipids, Hepatic Metabolism and Cardiovascular Disease. Current Opinion in Lipidology, 19, 257-262. http://dx.doi.org/10.1097/MOL.0b013e3282ffaf96
US Federal Drug Administration (1970) Scientific Literature Reviews on Generally Recognized as Safe (GRAS) Food Ingredients: Lecithins. GRAS Report, PB-241 970.
Hendry, G.A.F. (1993) Evolutionary Origins and Natural Functions of Fructans—A Climatological, Biogeographic and Mechanistic Appraisal. New Phytology, 123, 3-14. http://dx.doi.org/10.1111/j.1469-8137.1993.tb04525.x
Nicolson, G.L., Settineri, R. and Ellithorpe, R. (2012) Lipid Replacement Therapy with a Glycophospholipid Formulation with NADH and CoQ10 Significantly Reduces Fatigue in Intractable Chronic Fatiguing Illnesses and Chronic Lyme Disease. International Journal of Clinical Medicine, 3, 163-170. http://dx.doi.org/10.4236/ijcm.2012.33034
Jorissen, B.L., Brouns, F., van Boxtel, M.P., Ponds, R.W., Verhey, F.R., Jolles, J. and Riedel, W.J. (2001) The Influence of Soy-Derived Phosphatidylserine on Cognition in Age-Associated Memory Impairment. Nutrition and Neuroscience, 4, 121-134.
Nicolson, G.L. (2014) Mitochondrial Dysfunction and Chronic Disease: Treatment with Natural Supplements. Alternative Therapies in Health and Medicine, 20, 18-25. http://www.immed.org/treatmentconsiderations/05.23.14.TreatmentConsiderations/Mito_Dysfunct_ Treatm-NicolsonATHD2014.pdf
Kroenke, K., Wood, D.R., Mangelsdorff, A.D., Meier, N.J. and Powell, J.B. (1988) Chronic Fatigue in Primary Care. Prevalence, Patient Characteristics, and Outcome. Journal of the American Medical Association, 260, 929-934. http://dx.doi.org/10.1001/jama.1988.03410070057028
Morrison, J.D. (1980) Fatigue as a Presenting Complaint in Family Practice. Journal of Family Practice, 10, 795-801.
Filler, K., Lyon, D., Bennett, J., McCain, N., Elswick, R., Lukkahatai, N. and Saligan, L.N. (2014) Association of Mitochondrial Dysfunction and Fatigue: A Review of the Literature. BBA Clinical, 1, 12-23. http://dx.doi.org/10.1016/j.bbacli.2014.04.001
Myhill, S., Booth, N.E. and McLaren-Howard, J. (2009) Chronic Fatigue Syndrome and Mitochondrial Dysfunction. International Journal of Clinical and Experimental Medicine, 2, 1-16.
Krupp, L.B. and Pollina, D.A. (1996) Mechanisms and Management of Fatigue in Progressive Neurological Disorders. Current Opinion in Neurology, 9, 456-460. http://dx.doi.org/10.1097/00019052-199612000-00011
Manuel y Keenoy, B., Moorkens, G., Vertommen, J. and De Leeuw, I. (2001) Antioxidant Status and Lipoprotein Peroxidation in Chronic Fatigue Syndrome. Life Sciences, 68, 2037-2049. http://dx.doi.org/10.1016/S0024-3205(01)01001-3
Fulle, S., Mecocci, P., Fano, G., Vecchiet, I., Racciotti, D., Cherubini, A., Pizzigallo, E., Vecchiet, L., Senin, U. and Beal, M.F. (2000) Specific Oxidative Alterations in Vastus Lateralis Muscle of Patients with the Diagnosis of Chronic Fatigue Syndrome. Free Radical Biology and Medicine, 29, 1252-1259. http://dx.doi.org/10.1016/S0891-5849(00)00419-6
Richards, R.S., Roberts, T.K., McGregor, N.R., Dunstan, R.H. and Butt, H.L. (2000) Blood Parameters Indicative of Oxidative Stress Are Associated with Symptom Expression in Chronic Fatigue Syndrome. Redox Reports, 5, 35-41. http://dx.doi.org/10.1179/rer.2000.5.1.35
Pall, M.L. (2000) Elevated, Sustained Peroxynitrite Levels as the Cause of Chronic Fatigue Syndrome. Medical Hypotheses, 54, 115-125. http://dx.doi.org/10.1054/mehy.1998.0825
Ellithorpe, R.R., Settineri, R. and Nicolson, G.L. (2003) Reduction of Fatigue by Use of a Dietary Supplement Containing Glycophospholipids. Journal of the American Nutraceutical Association, 6, 23-28.
Agadjanyan, M., Vasilevko, V., Ghochikyan, A., Berns, P., Kesslak, P., Settineri, R. and Nicolson, G.L. (2003) Nutritional Supplement (NTFactor) Restores Mitochondrial Function and Reduces Moderately Severe Fatigue in Aged Subjects. Journal of Chronic Fatigue Syndrome, 11, 23-36. http://dx.doi.org/10.1300/J092v11n03_03 http://www.immed.org/treatment%20considerations/06.16.12/AgadjanyanNicolsonJCFS.pdf
Nicolson, G.L. and Ellithorpe, R. (2006) Lipid Replacement and Antioxidant Nutritional Therapy for Restoring Mitochondrial Function and Reducing Fatigue in Chronic Fatigue Syndrome and Other Fatiguing Illnesses. Journal of Chronic Fatigue Syndrome, 13, 57-68. http://dx.doi.org/10.1300/J092v13n01_06 http://www.immed.org/publications/Nicolson_ElllithorpeJCFS_copy.pdf
Ellithorpe, R.A., Settineri, R., Jacques, B. and Nicolson, G.L. (2012) Lipid Replacement Therapy Functional Food with NTFactor for Reducing Weight, Girth, Body Mass, Appetite, Cravings for Foods and Fatigue While Improving Blood Lipid Profiles. Functional Foods in Health and Disease, 2, 11-24. http://ffhdj.com/index.php/ffhd/article/view/102/212
Nicolson, G.L., Ellithorpe, R.R., Ayson-Mitchell, C., Jacques, B. and Settineri, R. (2010) Lipid Replacement Therapy with a Glycophospholipid-Antioxidant-Vitamin Formulation Significantly Reduces Fatigue within One Week. Journal of the American Nutraceutical Association, 13, 11-15. http://www.ana-jana.org/reprints/JANA13-1Reprint-GarthNicolson.pdf
Nicolson, G.L. (2010) Lipid Replacement Therapy: A Nutraceutical Approach for Reducing Cancer-Associated Fatigue and the Adverse Effects of Cancer Therapy While Restoring Mitochondrial Function. Cancer Metastasis Reviews, 29, 543-552. http://dx.doi.org/10.1007/s10555-010-9245-0
Nicolson, G.L., Settineri, R. and Ellithorpe, R.R. (2012) Lipid Replacement Therapy with a Glycophospholipid Formulation with NADH and CoQ10 Significantly Reduces Fatigue in Intractable Chronic Fatiguing Illnesses and Chronic Lyme Disease. International Journal of Clinical Medicine, 3, 163-170. http://dx.doi.org/10.4236/ijcm.2012.33034
Nicolson, G.L., Settineri, R. and Ellithorpe, R.R. (2012) Glycophospholipid Formulation with NADH and CoQ10 Significantly Reduces Intractable Fatigue in Western Blot-Positive Chronic Lyme Disease Patients: Preliminary Report. Functional Foods in Health and Disease, 2, 35-47. http://ffhdj.com/index.php/ffhd/article/view/100/208
Piper, B.F., Linsey, A.M. and Dodd, M.J. (1987) Fatigue Mechanism in Cancer. Oncology Nursing Forum, 14, 17-23.
Nicolson, G.L. and Conklin, K.A. (2008) Reversing Mitochondrial Dysfunction, Fatigue and the Adverse Effects of Chemotherapy of Metastatic Disease by Molecular Replacement Therapy. Clinical and Experimental Metastasis, 25, 161-169. http://dx.doi.org/10.1007/s10585-007-9129-z
Colodny, L., Lynch, K., Farber, C., Papish, R., Phillips, K., Sanchez, M., Cooper, K., Pickus, O., Palmer, D., Percy, T.B., Faroqui, M. and Block, J.B. (2001) Results of a Study to Evaluate the Use of Propax to Reduce Adverse Effects of Chemotherapy. Journal of the American Nutraceutical Association, 3, 17-25.
Ellithorpe, R.R., Settineri, R., Mitchell, C.A., Jacques, B., Ellithorpe, T. and Nicolson, G.L. (2011) Lipid Replacement Therapy Drink Containing a Glycophospholipid Formulation Rapidly and Significantly Reduces Fatigue While Improving Energy and Mental Clarity. Functional Foods in Health and Disease, 1, 245-254. http://ffhdj.com/index.php/ffhd/article/view/126/259
Richter, Y., Herzog, Y., Lifshitz, Y., Hayun, R. and Zchut, S. (2103) The Effect of Soybean Phosphatidylserine on Cognitive Performance in Elderly with Subjective Memory Complaints: A Pilot Study. Clinical Interventions in Aging, 8, 557-563.
Kato-Kataoka, A., Sukai, M., Ebina, R., Nonaka, C., Asano, T. and Miyamori, T. (2010) Soybean-Derived Phosphatidylserine Improves Memory Function of Elderly Japanese Subjects with Memory Complaints. Journal of Clinical Biochemistry and Nutrition, 47, 246-255. http://dx.doi.org/10.3164/jcbn.10-62
Cernacchi, T., Bertoldin, T., Farina, C., Flori, M.G. and Crepaldi, G. (1993) Cognitive Decline in the Elderly: A Double-Blind, Placebo-Controlled Multicenter Study on the Efficacy of Phosphatidylserine Administration. Aging (Milano), 5, 123-133.
Jorissen, B.L., Brouns, F., Van Baxtel, M.P. and Riedel, W.J. (2002) Safety of Soy-Derived Phosphatidylserine in Elderly People. Nutrition and Neuroscience, 5, 337-343. http://dx.doi.org/10.1080/1028415021000033802
Booth, N.E., Mayhill, S. and McLaren-Howard, J. (2012) Mi-tochondrial Dysfunction and the Pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). In-ternational Journal of Clinical and Experimental Medicine, 5, 208-220.
Gorman, G.S., Elson, J.L., Newman, J., Payne, B., McFarland, R., Newton, J.L. and Turnbull, D.M. (2015) Perceived Fatigue Is Highly Prevalent and Debilitating in Patients with Mitochondrial Disease. Neuromuscular Disorders, 25, 563-566. http://dx.doi.org/10.1016/j.nmd.2015.03.001
Brown, L.F. and Kroenke, K. (2009) Cancer-Associated Fatigue and Its Association with Depression and Anxiety: A Systematic Review. Psychosomatics, 50, 440-447. http://dx.doi.org/10.1016/S0033-3182(09)70835-7
Myhill, S., Booth, N.E. and McLaren-Howard, J. (2013) Targeting Mitochondrial Dysfunction in the Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)—A Clinical Audit. International Journal of Clinical and Experimental Medicine, 6, 1-15.
Monteiro, J.P., Pereira, C.V., Silva, A.M., Maciel, E., Baldeiras, I., Peixoto, F., Domingues, M.R., Jurado, A.S. and Oliveira, P.J. (2013) Rapeseed Oil-Rich Diet Alters Hepatic Mitochondrial Membrane Lipid Composition and Disrupts Bioenergetics. Archives of Toxicology, 87, 2151-2163. http://dx.doi.org/10.1007/s00204-013-1068-7
Duzdevich, D. and Greene, E.C. (2012) Towards Physiological Complexity with in Vitro Single-Molecule Biophysics. Philosophical Transactions of the Royal Society London B: Biological Sciences, 368, Article ID: 20120271. http://dx.doi.org/10.1098/rstb.2012.0271
Shaikh, S.R., Sullivan, E.M., Alleman, R.J., Brown, D.A. and Zeczycki, T.N. (2014) Increasing Mitochondrial Membrane Phospholipid Content Lowers the Enzymatic Activity of Electron Transport Complexes. Biochemistry, 53, 5589-5591. http://dx.doi.org/10.1021/bi500868g
Ahang, M., Mileykovskaya, E. and Dowhan, W. (2002) Gluing the Respiratory Chains Together. Cardiolipin Is Required for Supercomplex Formation in the Inner Mitochondrial Membrane. Journal of Biological Chemistry, 277, 43533-43556.
Böttinger, L., Horvath, S.E., Kleinschroth, T., Hunte, C., Daum, G., Pfanner, N. and Becker, T. (2012) Phosphatidylethanolamine and Cardiolipin Differentially Affect the Stability of Mitochondrial Respiratory Chain Supercomplexes. Journal of Molecular Biology, 248, 677-686. http://dx.doi.org/10.1016/j.jmb.2012.09.001
Dawaliby, R., Trubbia, C., Delporte, C., Noyon, C., Ruysschaert, J.-M., Van Antwerpen, P. and Guvaerts, C. (2015) Phosphatidylethanolamine Is a Key Regulator of Membrane Fluidity in Eukaryotic Cells. Journal of Biological Chemistry, 291, 3658-3667. http://dx.doi.org/10.1074/jbc.M115.706523
Mileykovskaya, E., Penczek, P.A., Fang, J., Mallampalli, V.K., Sparagna, G.C. and Dowhan, W. (2012) Arrangement of the Respiratory Chain Complexes in Saccharomyces cerevisiae Supercomplex III2IV2 Revealed by Single Particle Cryo-Electron Microscopy. Journal of Biological Chemistry, 287, 23095-23103. http://dx.doi.org/10.1074/jbc.M112.367888
Costa, C., Gonzales, T., Ferreira, G. and Nicolson, G.L. (2015) Lipid Replacement with a Membrane Glycerol Phospholipid Formulation: Enhancement of Spermatoozoa Motility and Viability. In: Martirosyan, D., Welty, F. and Zhou, J.-R., Eds., Functional and Medical Foods for Chronic Diseases: Bioactive Compounds and Biomarkers, Volume 18, Food Science Publisher, Dallas, 202-206.
Plaza Davila, M., Martin Muñoz, P., Tapla, J.A., Ortega Ferrusola, C., Balao da Silva, C.C. and Peña, F.J. (2015) Inhibition of Mitochondrial Complex I Leads to Decreased Motility and Membrane Integrity Related to Increased Hydrogen Peroxide and Reduced ATP Production, While the Inhibition of Glycolysis Has Less Impact on Sperm Motility. PLoS ONE, 10, e0138777. http://dx.doi.org/10.1371/journal.pone.0138777
Nicolson, G.L. (2014) The Fluid—Mosaic Model of Membrane Structure: Still Relevant to Understanding the Structure, Function and Dynamics of Biological Membranes after More Than 40 Years. Biochimica et Biophysica Acta (BBA)—Biomembranes, 1838, 1451-1466. http://dx.doi.org/10.1016/j.bbamem.2013.10.019
Goñi, F.M. (2014) The Basic Structure and Dynamics of Cell Membranes: An Update of the Singer-Nicolson Model. Biochimica et Biophysica Acta, 1838, 1467-1476. http://dx.doi.org/10.1016/j.bbamem.2014.01.006
Nicolson, G.L., Rosenblatt, S., Ferreira de Mattos, G., Settineri, R., Breeding, P.C., Ellithorpe, R.R. and Ash, M.E. (2016) Clinical Uses of Membrane Lipid Replacement Supplements in Restoring Membrane Function and Reducing Fatigue in Chronic Diseases and Cancer. Discoveries, 4, e54.