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Clinical Uses of Membrane Lipid Replacement Supplements

DISCOVERIES (ISSN 2359-7232), 2016, January-March issue


Nicolson GL, Rosenblatt S, Ferreira de Mattos G, Settineri R, Breeding PC, Ellithorpe RR, Ash MEClinical Uses of Membrane Lipid Replacement Supplements in Restoring Membrane Function and Reducing Fatigue  in Chronic Diseases and Cancer. Discoveries 2016, Jan-Mar; 4(1): e54. DOI: 10.15190/d.2016.1

Submitted: February 4th, 2016Revised: February 10th, 2016Accepted: February 15th, 2016Published: February 18th, 2016;

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Clinical Uses of Membrane Lipid Replacement Supplements in Restoring Membrane Function and Reducing Fatigue  in Chronic Diseases and Cancer

Garth L. Nicolson (1,*), Steven Rosenblatt (2), Gonzalo Ferreira de Mattos (3), Robert Settineri (4), Paul C. Breeding (5), Rita R. Ellithorpe (6), Michael E. Ash (7)

(1) The Institute for Molecular Medicine, Huntington Beach, California 92647, USA;

(2) Saint John’s Health Center, Santa Monica, CA, USA;

(3) Laboratory of Ion Channels, School of Medicine, Universidad de la República, Montevideo, Uruguay,

(4) Sierra Productions Research, Irvine, CA, USA;

(5) Blue Hole Wellness, Wimberley, TX, USA;

(6) Tustin Longevity Center, Tustin, CA, USA;  

(7) Clinical Education, Newton Abbot, Devon, UK.

*Correspondence to: Prof. Emeritus Garth L. Nicolson, PhD, MD (H), Department of Molecular Pathology, The Institute for Molecular Medicine, P.O. Box 9355, S. Laguna Beach, CA 92652; Email: gnicolson@immed.org; Website: www.immed.org


Membrane Lipid Replacement is the use of functional oral supplements containing cell membrane glycerolphospholipids and antioxidants to safely replace damaged membrane lipids that accumulate during aging and in various chronic and acute diseases.  Most if not all clinical conditions and aging are characterized by membrane phospholipid oxidative damage, resulting in loss of membrane and cellular function.  Clinical trials have shown the benefits of Membrane Lipid Replacement supplements 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 observations have indicated that Membrane Lipid Replacement can be a useful natural supplement strategy in a variety of conditions: chronic fatigue, such as found in many diseases and disorders; fatiguing illnesses (fibromyalgia and chronic fatigue syndrome); chronic infections (Lyme disease and mycoplasmal infections); cardiovascular diseases; obesity, metabolic syndrome and diabetes; neurodegenerative diseases (Alzheimer’s disease); neurobehavioral diseases (autism spectrum disorders); fertility diseases; chemical contamination (Gulf War illnesses); and cancers (breast, colorectal and other cancers).  Membrane Lipid Replacement provides general membrane nutritional support during aging and illness to improve membrane function and overall health without risk of adverse effects.

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1. Nicolson GL. Lipid replacement as an adjunct therapy in chronic fatigue, anti-aging and restoration of mitochondrial function. J. Am. Nutraceut. Assoc. 2003; 6(3): 22-28.

2. Nicolson GL, Ash ME. Lipid Replacement Therapy: a natural medicine approach to replacing damaged lipids in cellular membranes and organelles and restoring function.  Biochim, Biophys. Acta 2014; 1838: 1657-1679.

3. Nicolson GL. Lipid replacement therapy: a nutraceutical approach for reducing cancer-associated fatigue and the adverse effects of cancer therapy while restoring mitochondrial function.  Cancer Metastasis Rev. 2010; 29(3), 543-552.

4. Nicolson GL.  Membrane Lipid Replacement: clinical studies using a natural medicine approach to restoring membrane function and improving health. Intern. J. Clin. Med. 2016; 7: in press.

5. Küllenberg D, Taylor LA, Schneider M, Massing  U. Health effects of dietary phospholipids. Lipids Health Dis. 2012; 11: e3.

6. van Meer G, Voelker DB, Feigenson GW.  Membrane lipids: where they are and how they behave. Nat. Rev. Mol. Cell Biol. 2008; 9: 112-124.

7. Escribá PV.  Membrane-lipid therapy: a new approach in molecular medicine. Trends Mol. Med. 2006; 12, 34-43.

8. Ibarguren M, López DJ, Escriba PV.  The effect of natural and synthetic fatty acids on membrane structure, microdomain organization, cellular functions and human health. Biochim.  Biophys. Acta 2014; 1838: 1518-1528.

9. Dobbins WO III. Morphologic aspects of lipid absorption. Am. J. Clin. Nutr. 1969; 22: 257-265.

10. Zierenberg O, Grundy SM. Intestinal absorption of polyenephosphatidylcholine in man. J. Lipid Res. 1982; 23: 1136-1142.

11. Gundermann KJ, Kuenker A, Kuntz E, Drozdzik M.  Activity of essential phospholipids (EPL) from soybean in liver diseases.  Pharmacol. Rep. 2011; 63: 643-659.

12. Le Kim D, Betzing H.  Intestinal absorption of polyunsaturated phosphatidylcholine in the rat.  Hoppe Seylers Zeit. Physiol. Chem. 1976; 357: 1321-1331.

13. Liao TH, Hamosh P, Hamosh M. Fat digestion by lingual lipase: mechanism of lipolysis in the stomach and upper small intestine. Pediatric Res. 1984; 18: 402-409.

14. Adibhatla RM, Hatcher JF.  Lipid oxidation and peroxidation in CNS health and disease: from molecular mechanisms to therapeutic opportunities. Antioxid. Redox Signal. 2010; 12: 125-169.

15. Catalá A.  Lipid peroxidation modifies the picture of membranes from the “Fluid Mosaic Model” to the “Lipid Whisker Model.” Biochimie 2012; 94: 101-109.

16. Wagener HH, Fontaine R, Neumann B.  Pharmakologie “essentiele” phospholipide (EPL). Drug Res. 1976; 26: 1733-1743.

17. Gundermann KJ.  The “essential” phospholipids as membrane therapeutic. European Society of Biochemical Pharmacology, 1993, Szczecin, Poland.

18. Pandey NR, Sparks DL.  Phospholipids as cardiovascular therapeutics. Curr. Opin. Invest. Drugs 2008; 9(3), 281-285.

19. Ellithorpe RR, Settineri R, Ellithorpe T,  Nicolson GL. Blood homocysteine and fasting insulin levels are reduced and erythrocyte sedimentation rates are increased with a glycophospholipid-vitamin formulation: a retrospective study in older subjects. Funct. Foods Health Dis. 2015; 5(4): 126-135.

20. Cohn JS, Wat E, Kamili A, Tandy S.  Dietary phospholipids, hepatic metabolism and cardiovascular disease. Curr. Opin. Lipidol. 2008; 19: 257-262.

21. U. S. Federal Drug Administration.  Scientific literature reviews on generally recognized as safe (GRAS) food ingredients: Lecithins.  GRAS Report, 1970; PB-241 970.

22. Hendry GAF.  Evolutionary origins and natural functions of fructans—a climatological, biogeographic and mechanistic appraisal. New Phytol. 1993; 123: 3-14.

23. Nicolson GL, Settineri R, Ellithorpe R.  Lipid Replacement Therapy with a glycophospholipid formulation with NADH and CoQ10 significantly reduces fatigue in intractable chronic fatiguing illnesses and chronic Lyme disease. Intern. J. Clin. Med. 2012; 3: 163-170.

24. Nicolson GL.  Mitochondrial dysfunction and chronic disease: treatment with natural supplements. Altern. Ther. Health Med. 2014; 20(Suppl 1): 18-25.

25. Jorissen BL, Brouns F, van Boxtel MP, Ponds RW, Verhey FR, Jolles J, Riedel WJ.  The influence of soy-derived phosphatidylserine on cognition in age-associated memory impairment.  Nutr. Neurosci. 2001; 4: 121-134.

26. Morrison JD.  Fatigue as a presenting complaint in family practice. J. Family Pract. 1980; 10: 795-801.

27. Kroenke K, Wood DR, Mangelsdorff AD, Meier NJ, Powell JB.  Chronic fatigue in primary care.  Prevalence, patient characteristics, and outcome. JAMA 1988; 260: 929-934.

28. Filler K, Lyon D, Bennett J, McCain N, Elswick R, Lukkahatai N, Saligan LN. Association of mitochondrial dysfunction and fatigue: a review of the literature. BBA Clin. 2014; 1: 12-23.

29. Krupp LB, Pollina DA.  Mechanisms and management of fatigue in progressive neurological disorders. Curr. Opin. Neurol. 1996; 9: 456-460.

30. Myhill S, Booth NE,  McLaren-Howard J.  Chronic fatigue syndrome and mitochondrial dysfunction. Intern. J. Clin. Expl. Med. 2009; 2: 1-16.

31. Brown LF, Kroenke K.  Cancer-associated fatigue and its association with depression and anxiety: a systematic review.  Psychosomat. 2009; 50: 440-447.

32. Manuel y Keenoy B, Moorkens G, Vertommen J, De Leeuw I.  Antioxidant status and lipoprotein peroxidation in chronic fatigue syndrome. Life Sci. 2001; 68: 2037-2049.

33. Fulle S, Mecocci P, Fano G, Vecchiet I, Racciotti D, Cherubini A, Pizzigallo E, Vecchiet L, Senin U, Beal MF.  Specific oxidative alterations in vastus lateralis muscle of patients with the diagnosis of chronic fatigue syndrome. Free Rad. Biol. Med. 2000; 29: 1252-1259.

34. Pall ML.  Elevated, sustained peroxynitrite levels as the cause of chronic fatigue syndrome. Med. Hypoth. 2000; 54: 115-125.

35. Richards RS, Roberts TK, McGregor NR, Dunstan RH, Butt HL.  Blood parameters indicative of oxidative stress are associated with symptom expression in chronic fatigue syndrome. Redox Rep. 2000; 5: 35-41.

36. Ellithorpe RR, Settineri R, Nicolson GL.  Reduction of fatigue by use of a dietary supplement containing glycophospholipids.  J. Am. Nutraceut. Assoc. 2003; 6(1): 23-28.

37. Agadjanyan M, Vasilevko V, Ghochikyan A, Berns P, Kesslak P, Settineri R, Nicolson GL. Nutritional supplement (NTFactor) restores mitochondrial function and reduces moderately severe fatigue in aged subjects.  J. Chronic Fatigue Syndr. 2003; 11(3): 23-36.

38. Nicolson GL, Ellithorpe R.  Lipid replacement and antioxidant nutritional therapy for restoring mitochondrial function and reducing fatigue in chronic fatigue syndrome and other fatiguing illnesses. J. Chronic Fatigue Syndr. 2006; 13(1), 57-68.

39. Ellithorpe RA, Settineri R, Jacques B, Nicolson GL.  Lipid Replacement Therapy functional food with NTFactor for reducing weight, girth, body mass, appetite, cravings for foods and fatigue while improving blood lipid profiles. Funct. Foods Health Dis. 2012; 2(1): 11-24.

40. Nicolson GL, Ellithorpe RR, Ayson-Mitchell C, Jacques B, Settineri R.  Lipid Replacement Therapy with a glycophospholipid-antioxidant-vitamin formulation significantly reduces fatigue within one week. J. Am. Nutraceut. Assoc. 2010; 13(1): 11-15.

41. Nicolson GL, Settineri R, Ellithorpe RR.  Lipid Replacement Therapy with a glycophospholipid formulation containing NADH and CoQ10 significantly reduces fatigue and improves mood and cognition in intractable chronic fatiguing illnesses and chronic Lyme disease.  Townsend Lett. 2012; 347(6): 58-61.

42. Nicolson GL, Settineri R, Ellithorpe RR.  Glycophospholipid formulation with NADH and CoQ10 significantly reduces intractable fatigue in Western blot-positive chronic Lyme disease patients: preliminary report. Funct. Foods Health Dis. 2012; 2(3): 35-47.

43. Piper BF, Linsey AM, Dodd MJ.  Fatigue mechanism in cancer. Oncol. Nurs. Forum 1987; 14:17-23.

44. Nicolson GL, Conklin KA. Reversing mitochondrial dysfunction, fatigue and the adverse effects of chemotherapy of metastatic disease by Molecular Replacement Therapy. Clin. Expl. Metastasis 2008; 25: 161-169.

45. Colodny L, Lynch K, Farber C, Papish R, Phillips K, Sanchez M, Cooper K, Pickus O, Palmer D, Percy TB, Faroqui M, Block JB.  Results of a study to evaluate the use of Propax to reduce adverse effects of chemotherapy.  J. Am. Nutraceut. Assoc. 2001;  3(1): 17-25.

46. Nicolson GL, Settineri R, Ellithorpe RR.  Neurodegenerative and fatiguing illnesses, infections and mitochondrial dysfunction: the use of natural supplements to improve mitochondrial function.  Funct. Foods Health Dis. 2014; 4(1): 23-65.

47. Nicolson GL. Metabolic syndrome and mitochonrial function: molecular replacement and antioxidant supplements to prevent membrane oxidation and restore mitochondrial function. J. Cell. Biochem. 2007; 100: 1352-1369.

48. Nicolson GL, Berns P, Nasralla M, Haier J, Nicolson NL, Nass M. Gulf War Illnesses: chemical, radiological and biological exposures resulting in chronic fatiguing illnesses can be identified and treated. J. Chronic Fatigue Syndr. 2003; 11(1): 135-154.

49. Ellithorpe RR, Settineri R, Mitchell CA, Jacques B, Ellithorpe T, Nicolson  GL.  Lipid replacement therapy drink containing a glycophospholipid formulation rapidly and significantly reduces fatigue while improving energy and mental clarity.  Funct. Foods Health Dis. 2011; 1(8): 245-254.

50. Richter Y, Herzog Y, Lifshitz Y, Hayun R, Zchut S.  The effect of soybean phosphatidylserine on cognitive performance in elderly with subjective memory complaints: a pilot study. Clin. Intervent. Aging 2013; 8: 557-563.

51. Kato-Kataoka A, Sukai M, Ebina R, Nonaka C, Asano T, Miyamori T. Soybean-derived phosphatidylserine improves memory function of elderly Japanese subjects with memory complaints. J. Clin. Biochem. Nutr. 2010; 47: 246-255.

52. Cernacchi T, Bertoldin T, Farina C, Flori MG. Crepaldi G.  Cognitive decline in the elderly: a double-blind, placebo-controlled multicenter study on the efficacy of phosphatidylserine administration. Aging (Milano) 1993; 5: 123-133.

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