Dr. Mercola's Comments: Dr. Patricia Kane is an expert in the fatty acid field. If you are interested in fatty acid metabolism, brain architecture, detoxification, neurochemistry and the cell membrane and beyond I encourage you to check out The Fatty Acid BioMedical Symposium with Dr. Kane being held this October in Atlantic City, New Jersey. By Patricia Kane, Ph.D. The study of lipids is the most striking area of research today that can improve patient outcomes. Understanding the critical balance of omega-6 and omega-3 fatty acids through supplementation is vital to restoring vibrant life into the lipid membrane and rejuvenating the patient. Assessing the stability of the cell membrane through the examination of red cell lipids leads the clinician into a wide realm of metabolic strategies to influence the health of the patient. Lipids evolve into hormones called prostaglandins, immune components, and myelin as well as the bilipid membrane of every cell in the body. There is virtually no system of the body that does not require attenuation of specific fatty acid substrates and coenzymes to maintain health and repair of bodily tissues. The human cell membrane cannot be created nor its function controlled without respect to lipid substrate, yet fatty acid metabolism has been poorly delineated and often simply ignored in treatment protocols. Exploration of lipid metabolism brings a striking new tool that unlocks some of the complexities of disease, as lipid imbalance and deficiency have an intimate link to the endocrine, hepatic, renal, CNS/Blood-Brain Barrier/Brain, gastrointestinal, pulmonary, musculoskeletal and cardiovascular systems as well as exquisite capacity to impact health. The membrane of every cell and organelle is a lipid envelope that encases and protects the internal working cellular components. The bilipid layer is far more than isolation and protection, for linked and interlocked within the membrane are literally thousands of proteins (peptides) large and small that form the windows and doors of the cell. These mucopolypeptides form the gates for ingress and egress but also provide the multitudinous array of receptors that trigger not only access but create the vast intercellular communication and information system through their prostaglandin regulatory activity. Prostaglandins may have evolved to be the basic control mechanism that permitted metazoa agglomeration (which is principally what we are, a vast agglomeration of cells) since emerging from the primordial sea millions of years ago. Thus the mere thought of multicellular activity, and especially the evolution of humankind is, at our present level of knowledge, not possible without essential fatty acids, which are the precursors to the regulatory prostaglandins, which provide the communication and control absolutely necessary for a group of cells to stay together. Before one can advance beyond unizoa or single cell organisms into multi-cell metazoa there must be both communication and eventually a means of regulation. This is the marvelous, magical world of the prostaglandins (PGs), the "local hormones" that control all cell-to-cell interactions without which there is no complex life form. The explosion of fatty acid studies appearing in medical research have led us into a new era in our approach to resolving disease, however, the focus of medical lipid manipulation has led to a great deal of confusion as pharmaceutical companies often dictate individual fatty acids as drugs rather than essential nutrients. As we begin to unfold the incredible complexity of lipid metabolism in the human body we are forced to acknowledge that lipid individuality must be respected if we are to achieve positive medical outcomes as we approach illness. To begin we must first understand the importance of maintaining a balance between omega-6 and omega-3 fatty acids, which has only recently been brought into clearer focus. Shlomo Yehuda reported in 1986 that the optimum ratio of base lipids linoleic-omega-6 to alphalinolenic-omega-3 fatty acids was 4:1. [NOTE: Dr. Mercola recommends a 1:1 ratio] Arachidonic (AA), the lead eicosanoid, must be stabilized first along with the other w6 EFAs before w3 fatty acids are introduced and balanced in the patient’s supplementation regime. There exists a crucial balance between omega-6 and omega-3 fatty acids in human lipid metabolism, which has only recently been brought into clearer focus as Yehuda’s SR-3 (specific ratio of omega-6-LA to omega-3-ALA as 4:1). This ratio of base lipids has been successfully utilized by clinicians for the past three years in the United States, Canada, South America, Europe and Australia in patients with a myriad of health problems. Most profound is the stabilization of health status in patients with MS, ALS, Autism, Epilepsy, Bipolar, Schizophrenia, Alzheimer’s Disease, Parkinson’s, Pervasive Developmental Delay, Fibromyalgia and CFIDS. Conversely, clinicians are often met with poor patient outcomes when merely administering omega-3 lipids without first introducing omega-6 fatty acids, balancing the lower order of essential fatty acids (linoleic and alpha linolenic acid in a 4:1 ratio), stabilizing the structural lipids, increasing the fat content of the diet, stimulating the ß-oxidation of renegade fatty acids, flushing of the gall bladder/biliary tree, and supporting digestion of fats with bile salts/lipase. To view the brain beyond its architecture as a biological orchestration of the physical and chemical constituents necessary for performance, we cannot begin to conceptualize without considering the importance of fatty acids, as the human brain is 60 percent lipid. Dendrites and synapses are up to 80 percent in lipid content. Although AA has been given a negative association, it is the most prominent essential fatty acid in the red cell and comprises 12 percent of the total brain and 15.5 percent of the body lipid content. If AA is depleted by overdosing with marine or flax oil, establishing the balance of the essential fatty acids (EFAs) is profoundly impaired. Often both prostaglandin one and two series relating to omega-6 metabolism are compromised when flax and marine oils are overdosed or lipid intake is insufficient. When AA is suppressed due to overdosing of marine oil the control circuitry of the body is impaired as is clearly viewed in the patient's presentation. Increases in Phospholipase A2 (PLA2) activity result in premature uncoupling of the EFAs from phospholipids in the cell membrane. Accelerated loss of EFA places the patient in a severely compromised position of inflammation, which results from the promiscuous release of AA in the presence of an over-expression of PLA2. Carbohydrate consumption must be restricted to control the insulin response and the subsequent loss of EFAs. The phospholipids and their essential fatty acid components provide second messengers and signal mediators. In essence, phospholipids and their essential fatty acid components play a vital role in the cell signaling systems in the neuron. The functional behavior of neuronal membranes largely depends upon the ways in which individual phospholipids are aligned, interspersed with cholesterol, and associated with proteins. All neurotransmitters are wrapped up in phospholipid vesicles. The release and uptake of the neurotransmitters depends upon the realignment of the phospholipid molecules. The nature of the phospholipid is a factor in determining how much neurotransmitter or metal ion will pass out of a vesicle or be taken back in. Phospholipid remodeling may be accomplished by supplying generous amounts of balanced lipids and catalysts via nutritional intervention and the use of intravenous Phospholipid Exchange. Research focused on individual fatty acids, as the current interest in Docosahexaenoic Acid (DHA), erupted due to the availability of an algae-based (non-fishy) DHA available for infant formula. However, not revealed to the public were studies (Susan Carlson) of premature infants given algae-based DHA who developed necrotizing enterocolitis. Infant formula is now augmented with DHA and AA, however, other essential higher-order supplements are still missing as omega-6 gamma linolenic acid (GLA from primrose oil) and EPA (omega-3). Supplementing one fatty acid, DHA, has failed even in its application to children with ADHD/ ADD, often negatively affecting their immune response and overstimulating the CNS. Children with hyperactivity are deficient in all essential fats, not exclusively DHA, and the administration of one fatty acid without a balance of EFAs is inappropriate for any medical disorder. We have a new understanding of cellular organelle and microtubule function in regard to the role of fatty acids. Tremendous attention has been directed to the mitochondria with its bilipid cell layer membrane (energy-producing organelles), yet the most important organelle in regard to lipid synthesis is the peroxisome, a monolipid layer organelle. Peroxisomes, present in virtually all cells, but most prevalent in the liver and kidney, play a critical role in cellular lipid metabolism in the biosynthesis of fatty acids via ß-oxidation involving physiologically important substrates for VLCFAs, dicarboxylic fatty acids, prostaglandins, thromboxanes, leukotrienes, pristanic acid, DHCA, THCA, and xenobiotics. Individuals with aging difficulties and immune, CNS and endocrine disorders often present with complex xenobiotics involving disturbances in the cytochrome P450 superfamily (hepatic detoxification), which parallels disturbances in peroxisomal function. The cytochrome P450s are responsible for the biotransformation of endogenous compounds including fatty acids, steroids, prostaglandins, leukotrienes and vitamins as well as the detoxification of exogenous compounds resulting in substantial alterations of P450s, as xenobiotics may turn off or greatly reduce the expression of constitutive isoenzymes. Inappropriate use of antioxidants such as mega-dosing with Vitamin E (> 800 IU) will inhibit tumor shrinkage as beta oxidation is suppressed, thus potent antioxidants would be contraindicated in the buildup of very long chain fatty acids (VLCFAs) and therefore reduced cellular metabolism as in states of aging and toxicity. The administration of DHEA, pregnenolone, or thyroid hormones stimulates the ß-oxidation of VLCFAs, as would nutrients (riboflavin, pyruvate, manganese) as well as oxidative therapies that stimulate oxidation, prostaglandin synthesis and detoxification. Patients presenting with low serum cholesterol often do not have a positive response with the administration of DHEA or growth hormone as their metabolism is diminished due to catabolism and/or dietary regimes that have failed to meet their basic nutritional requirements. The arbitrary use of DHEA or growth hormone will beta oxidize or burn not just VLCFAs but all the essential fatty acids as well. Antioxidants slow cellular metabolism and must remain in the proper balance with all the essential nutrients and substrates (lipids, protein) to maintain metabolic equilibrium. Renegade fats such as VLCFAs that are over expressed, disrupt the membrane structure. There is a beautiful geometry to the membrane that is highly sensitive to the size of the lipid chains. The overall width of the fatty acid portion of the membrane is ~3 ½ nm, which must be maintained for stability. Saturated or monounsaturated fatty acids with a length of 16 or 18 carbons are preferred to permit the structure to maintain optimal horizontal fluidity. VLCFAs that range from 20 to 26 carbons force the parallel dimensions vertically. There simply is not enough room. The distortion weakens the phosphate bonds that derive their strong attraction only as long as the phospholipids are parallel to each other on both sides of the membrane. The cell weakness is then expressed in leaky attraction to ion channels and receptors, which marginalize cell cytosol fluids and electrolytes with the only option as early cell death. Genetic expression is the preferential individual propensity to code and produce certain proteins enzymes, hormones and peptides. How this expression degrades over time is in part individually determined, but also strongly influenced by lifestyle of which diet plays a crucial role. An optimum balance of fatty acids make up the dynamic membrane. The membrane of every living cell and organelle, including the nucleus that holds the DNA, is composed of two fatty acid tails facing each other. This bilipid layer is so minute (3 nanometers) that it would take 10,000 membranes layered on top of each other to make up the thickness of a piece of paper. Yet the dynamics that occur within this tiny envelope with organelles prancing up and down the cytoskeleton microtubules is a microcosm that is a challenge for the human mind to envision. All cells must synthesize molecules and expel waste. All cells must create, through gene expression, the proteins needed for cellular gates embedded in the membrane as ion channels and receptors. The ultimate control of how those peptides behave rests with the character of the membrane while the integrity of the membrane rests with the structural (oleic, stearic, palmitic) and essential lipids. In essence, the life of the cell is intimately tied to membrane health and the health of the entire organism. The membrane is everything. Newly documented research delineates that targeted lipid manipulation can dramatically influence the human body. Medicine has been slow to acknowledge the crucial lipid requirements to address neurological degeneration often accompanying states of disease, yet now that data is emerging from the medical literature it is difficult to extrapolate and organize the data into meaningful therapeutic applications for use in a clinical setting. Our database holds 10,000 red cell lipid analyses from 1997 to the present from Johns Hopkins Peroxisomal Diseases Laboratory, the gold standard laboratory in the United States. By organizing the research data and isolating individual fatty acids in red cells we can now examine the cellular integrity/structure, fluidity, the formation of renegade fats that impair membrane function, myelination status, and the intricate circuitry of the prostaglandins and for the first time lipid treatment protocols may be established due to a clearer view into red cell membrane dynamics. Our clinical protocol at the Haverford Wellness Center in Havertown, PA and the Center for Wellness in Charlotte, NC is to initiate treatment with changing the patient’s overall diet, addressing the lipid balance and especially the outer lipid leaflet of the cell membrane through fatty acid therapy and the addition of supplementation targeted toward healing the cell membrane. By stabilizing lipid status with intravenous Phospholipid Exchange and oral EFA supplementation we have remarkable tools toward healing a myriad of disorders in both pediatric and adult populations, without side effects. Through isolating individual fatty acids and dimethyl acetyls in red cells we can now examine the cellular integrity/structure, fluidity, the formation of renegade fats that impair membrane function, myelination status, and the intricate circuitry of the prostaglandins. The systemic health of the individual patient may be reached and targeted nourishment utilized through evidence based intervention, which may yield positive patient outcome. Healing the membrane is virtually healing the body, and healing the brain. References Aoyama T, Souri M, Kamijo T, Ushikubo S, Hashimoto T Peroxisomal Acyl-Coenzyme A Oxidase is a Rate-Limiting Enzyme in a Very-Long-Chain Faty Acid ß-Oxidation System Biochemical and Biophysical Res Com 201:3:1541-1547 June 30, 1994 Attwell D, Miller B, Saantis M Arachidonic Acid as a Messenger in the Central Nervous System Seminars in the Neurosciences 5: 159-169, 1993 Bazan NG, Murphy MG, Toffano G Neurobiology of Essential Fatty Acids Advances in Experimental Medicine and Biology Vol 318 from the proceedings July 10-12,1991 in Palm Cove, Far North Queensland, Australia, Plenum Publishing, NYC,1992 Baumgart E, Volkl A, Pill J, Fahimi HD Profileration of Peroxisomes without Simultaneous Induction of the Peroxisomal Fatty Acid ß-oxidation Federation of European Biochemical Societies Letters 264:5-9,1990 Beier K, Volkl A Fahimi HD Suppression of Peroxisomal Lipid ß-oxidation enzymes by TNF-alpha FEBS Lett 310:273-278,1992 Bentley P, Calder I, Elcombe C, Grasso P, Stringer D, Wiegand HS Hepatic Peroxisome Proliferation in rodents and its significance for Humans Food Chem Toxic 31:857-907,1993 Brown FR, Voight R, Singh AK, Singh I Peroxisomal Disorders AJDC 147, June 1993 Claassen N, Coetzer H, Steinmann CM, Kruger MC The effect of different n-6/n-3 essential fatty acid ratios on calcium balance and bone in rats Prostaglandins Leukot Essent Fatty Acids. 1995 Jul;53(1):13-9, Jul 1995 Clandinin MT, Jumpsen J, Suh M Relationship between Fatty Acid Accretion, Membrane Composition and Biological Functions J of Pediatrics 125:5:S25-S32 Nov 1994 Carlson SE, Montalto, MB, Ponder DL, Werkman SH, Korones SB Lower Incidence of Necrotizing Enterocolitis in Infants fed a preterm formula Egg phospholipids Pediatric Research 44:4:491-498 , 1998 Collier GR, Sinclair AJ Role of N-6 and N-3 Fatty Acids in the Dietary Treatment of Metabolic Disorders Annals NY Acad Sci 322-329, 1993 Crawford MA A Biochemical Theory on the Evolution of the Human Brain After-Dinner Speech at the Proceedings From the Scientific Conference on Omega-3 Fatty Acids Nutrition, Vascular Biology, and Medicine Houston, TX April 17-19, 1994 Delion S, Chalon S, Guilloteau D, Besnard JC, Durand G Alpha Linolenic Acid Dietary Deficiency Alters Age-Related Changes of Dopaminergic and Serotoninergic Neurotransmision in the Rat Frontal Cortex J of Neurochem 66:1582-1591, 1996 Dias VC, Parsons HG Modulation in delta 9, delta 6, and delta 5 fatty acid desaturase Activity in the Human Intestinal CaCo-2 Cell Line J of Lipid Research 36:552-563, 1995 Diczfalusy U ß-Oxidation of Eicosanoids Prog Lipid Res 33:4:403-428, 1994 Flood JF, Morley JE, Roberts E Memory enhancing effects in male mice of Pregnenolone and Steroids Metabolically Derived from it. Proc Natl Acad Sci USA 89:1567-1571,1992 George MS, Guidotti, Rubinow D, Pan B, Mikalauskas K, Post RM CSF Neuroactive Steroids in Affective Disorders: Pregnenolone, Progesterone, and DBI Biol Psychiatry 35:775-780,1994 Gibson GG, Milton MN, Elcombe CR Induction of Cytochrome P450 IVA 1-Mediated Fatty Acid Hydroxylation: Relevance to Peroxisome Proliferation Biochemical Society Transactions 18:97-99, 1990 Gibson GG, Lake B Peroxisomes: Biology and Importance in Toxicology and Medicine Taylor and Francis: London, 1993 Gordon JA, Heller SK, Rhead WJ, Watkins PA, Spector AA Formation of a Novel Arachidonic Acid Metabolite in Peroxisomes Prostaglandins Leukotriences and Essential Fatty Acids 52:77-81, 1995 Guengerich FP Reactions and Significance of Cytochrome P450 Enzymes Journal of Biological Chemistry 266:10019-10023, 1991 Hayashi H, Takahata S Role of Peroxisomal Fatty Acyl-CoA Beta-Oxidation in Phospholipid Biosynthesis Archives of Biochemistry and Biophysics 284:326-331, 1991 Horrobin DF Fatty Acid Metabolism in Health and Disease: The Role of delta-6-Desaturase Am J Clin Nutr 57(suppl):732S-7S, 1993 Horrobin DF Nutritional and Medical Importance of Gamma-Linolenic Acid Prog Lipid Res 31:2:163-194, 1992 Horrobin DF DNA-Protein and Membrane-Lipid: Competing Paradigms in Biomedical Research Med Hypotheses 44:4:229-232, Apr 1995 Horrobin DF, Glen AIM Hudson CJ Possible Relevance of Phospholipid Abnormalities and Genetic Interactions in Psychiatric Disorders: The Relationship Between Dyslexia and Schizophrenia Medical Hypotheses 45:605-613, 1995 Horrobin, DF Schizophrenia: The Illness that Made Us Human Medical Hypothesis 50:269-288, 1998 Horrobin, DF A new category of psychotropic drugs: neuroactive lipids as exemplified by ethyl eicosapentaenoate (E-E) Prog Drug Res. 2002;59:171-99 Horrobin, DF, Jenkins K, Bennett CN, Christie WW Eicosapentaenoic Acid and arachidonic acid: collaboration and not antagonism is the key to biological understanding Prostaglandins, Leukotrienes and Essential Fatty Acids 66: 1: 83-90, Jan 2002 Huang YS, Wainwright PE, Redden PR, Mills DE, Bulman-Fleming B, Horrobin DF Effect of Maternal Dietary Fats with Variable N3/n-6 Ratios on Tissue Fatty Acid Composition in Sucking Mice Lipids 27:2:104-110, 1992 Jaeschke H, Werner C, Wendel A Disposition and Hepatoprotection by Phosphatidyl Choline liposomes in mouse liver Chem Biol Interact 64:1-2:127-137, 1987 Jorisse 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 4:2:121-34, 2001 Kane PC, Kane E Peroxisomal Disturbances in Autistic Spectrum Disorder J. 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Membrane lipid composition and cellular function J Lipid Res 26:1015-1035, 1985 Thompson GA The Regulation of Membrane Lipid Metabolism CRC Press: Boca Raton, FL, 1992 Vamecq J, Vallee L, Lechene de la Porte P el al Effect of Various n-3/n-6 Fatty Acid Ratio contents of High Fat diets on rat liver and Heart Peroxisomal and Mitochondrial ß-oxidation Biochim Biophys Acta 1170:151-157, 1993 Van den Bosch H, Schutgens RBH, Wanders RJA, Tager J Biochemistry of the Peroxisomes Annu Rev Biochem 61:157-197,1992 Xu L, Ash M, Abdel-Aleem S, Lowe JE, Badr M Hyperinsulinemia Inhibits Hepatic Peroxisomal ß-Oxidation in Rats Hormone Metabolism Research 27:76-78, 1995 Yehuda S, Leprohom-Greenwood CE, Dixon LM Coscina DV Effects of dietary fat on pain threshold, thermoregulation and motor activity in rats Pharmacol Biochem Behav 24:1775-1777, 1986 Yehuda S, Carasso RL Modulation of learning pain thresholds, and thermoregulation in the rat by preparations of free -purified alpha linolenic and linoleic acids: determination of the optimal w3-to-w6 ratio Proc Natl Acad Sci USA 90:10345-10349, 1993 Yehuda S, Carasso RL, Motofsky DI Essential fatty acid preparation (SR-3) raises the seizure threshold in rats Eur J Pharmacol 254:193-198, 1994 Yehuda S, Carasso RL, Motofsky DI Essential fatty acid preparation (SR-3) rehabilitates learning deficits induced by AF64A and 5,7-DHT NeuroReport 6:511-515, 1995 Yehuda S, Rabinovitz S, Mostofsky DI Effects of essential fatty acid preparation (SR-3) on brain lipids, biochemistry and behavioraland cognitive functions. In: Yehuda A, Mostofsky DI Eds. Handbook of essential fatty acid biology, biochemistry physiology, and behavioral neurobiology New York: Humana Press 427-452, 1997 Yehuda S, Mostofsky DI Handbook of Fatty Acid Biology Humana Press: Totowa, NJ, 1997 Yehuda S, Rabinovitz S, Mostofsky DI Modulation of learning and neuronal membrane composition in the rat by essential fatty acid preparation: time-course analysis Neurochem Res 23:5:627-34, May 1998 Yehuda S, Rabinovitz S, Mostofsky DI Essential fatty acids and sleep: mini review and hypothesis Med Hypothesis 50:2:139-45, Feb 1998 Yehuda S, Rabinovitz S, Carasso RL, Mostofsky DI Fatty acids and Brain Peptides Peptide 19:2:407-419, 1998 Yehuda S, Rabinovitz S, Carasso RL, Mostofsky DI Fatty acid mixture counters stress changes in cortisol, cholesterol, and impair learning Int J Neurosci 101:1-4:73-87, 2000 Yehuda S Possible anti-Parkinson roperties of N-(alpha-linolenoyl) tyrosine. 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Dr. Patricia Kane is an expert in the fatty acid field. If you are interested in fatty acid metabolism, brain architecture, detoxification, neurochemistry and the cell membrane and beyond I encourage you to check out The Fatty Acid BioMedical Symposium with Dr. Kane being held this October in Atlantic City, New Jersey.
By Patricia Kane, Ph.D.
The study of lipids is the most striking area of research today that can improve patient outcomes. Understanding the critical balance of omega-6 and omega-3 fatty acids through supplementation is vital to restoring vibrant life into the lipid membrane and rejuvenating the patient.
Assessing the stability of the cell membrane through the examination of red cell lipids leads the clinician into a wide realm of metabolic strategies to influence the health of the patient. Lipids evolve into hormones called prostaglandins, immune components, and myelin as well as the bilipid membrane of every cell in the body. There is virtually no system of the body that does not require attenuation of specific fatty acid substrates and coenzymes to maintain health and repair of bodily tissues. The human cell membrane cannot be created nor its function controlled without respect to lipid substrate, yet fatty acid metabolism has been poorly delineated and often simply ignored in treatment protocols.
Exploration of lipid metabolism brings a striking new tool that unlocks some of the complexities of disease, as lipid imbalance and deficiency have an intimate link to the endocrine, hepatic, renal, CNS/Blood-Brain Barrier/Brain, gastrointestinal, pulmonary, musculoskeletal and cardiovascular systems as well as exquisite capacity to impact health.
The membrane of every cell and organelle is a lipid envelope that encases and protects the internal working cellular components. The bilipid layer is far more than isolation and protection, for linked and interlocked within the membrane are literally thousands of proteins (peptides) large and small that form the windows and doors of the cell.
These mucopolypeptides form the gates for ingress and egress but also provide the multitudinous array of receptors that trigger not only access but create the vast intercellular communication and information system through their prostaglandin regulatory activity. Prostaglandins may have evolved to be the basic control mechanism that permitted metazoa agglomeration (which is principally what we are, a vast agglomeration of cells) since emerging from the primordial sea millions of years ago.
Thus the mere thought of multicellular activity, and especially the evolution of humankind is, at our present level of knowledge, not possible without essential fatty acids, which are the precursors to the regulatory prostaglandins, which provide the communication and control absolutely necessary for a group of cells to stay together. Before one can advance beyond unizoa or single cell organisms into multi-cell metazoa there must be both communication and eventually a means of regulation. This is the marvelous, magical world of the prostaglandins (PGs), the "local hormones" that control all cell-to-cell interactions without which there is no complex life form.
The explosion of fatty acid studies appearing in medical research have led us into a new era in our approach to resolving disease, however, the focus of medical lipid manipulation has led to a great deal of confusion as pharmaceutical companies often dictate individual fatty acids as drugs rather than essential nutrients. As we begin to unfold the incredible complexity of lipid metabolism in the human body we are forced to acknowledge that lipid individuality must be respected if we are to achieve positive medical outcomes as we approach illness.
To begin we must first understand the importance of maintaining a balance between omega-6 and omega-3 fatty acids, which has only recently been brought into clearer focus. Shlomo Yehuda reported in 1986 that the optimum ratio of base lipids linoleic-omega-6 to alphalinolenic-omega-3 fatty acids was 4:1. [NOTE: Dr. Mercola recommends a 1:1 ratio]
Arachidonic (AA), the lead eicosanoid, must be stabilized first along with the other w6 EFAs before w3 fatty acids are introduced and balanced in the patient’s supplementation regime. There exists a crucial balance between omega-6 and omega-3 fatty acids in human lipid metabolism, which has only recently been brought into clearer focus as Yehuda’s SR-3 (specific ratio of omega-6-LA to omega-3-ALA as 4:1).
This ratio of base lipids has been successfully utilized by clinicians for the past three years in the United States, Canada, South America, Europe and Australia in patients with a myriad of health problems. Most profound is the stabilization of health status in patients with MS, ALS, Autism, Epilepsy, Bipolar, Schizophrenia, Alzheimer’s Disease, Parkinson’s, Pervasive Developmental Delay, Fibromyalgia and CFIDS.
Conversely, clinicians are often met with poor patient outcomes when merely administering omega-3 lipids without first introducing omega-6 fatty acids, balancing the lower order of essential fatty acids (linoleic and alpha linolenic acid in a 4:1 ratio), stabilizing the structural lipids, increasing the fat content of the diet, stimulating the ß-oxidation of renegade fatty acids, flushing of the gall bladder/biliary tree, and supporting digestion of fats with bile salts/lipase.
To view the brain beyond its architecture as a biological orchestration of the physical and chemical constituents necessary for performance, we cannot begin to conceptualize without considering the importance of fatty acids, as the human brain is 60 percent lipid. Dendrites and synapses are up to 80 percent in lipid content. Although AA has been given a negative association, it is the most prominent essential fatty acid in the red cell and comprises 12 percent of the total brain and 15.5 percent of the body lipid content.
If AA is depleted by overdosing with marine or flax oil, establishing the balance of the essential fatty acids (EFAs) is profoundly impaired. Often both prostaglandin one and two series relating to omega-6 metabolism are compromised when flax and marine oils are overdosed or lipid intake is insufficient. When AA is suppressed due to overdosing of marine oil the control circuitry of the body is impaired as is clearly viewed in the patient's presentation.
Increases in Phospholipase A2 (PLA2) activity result in premature uncoupling of the EFAs from phospholipids in the cell membrane. Accelerated loss of EFA places the patient in a severely compromised position of inflammation, which results from the promiscuous release of AA in the presence of an over-expression of PLA2. Carbohydrate consumption must be restricted to control the insulin response and the subsequent loss of EFAs.
The phospholipids and their essential fatty acid components provide second messengers and signal mediators. In essence, phospholipids and their essential fatty acid components play a vital role in the cell signaling systems in the neuron. The functional behavior of neuronal membranes largely depends upon the ways in which individual phospholipids are aligned, interspersed with cholesterol, and associated with proteins. All neurotransmitters are wrapped up in phospholipid vesicles.
The release and uptake of the neurotransmitters depends upon the realignment of the phospholipid molecules. The nature of the phospholipid is a factor in determining how much neurotransmitter or metal ion will pass out of a vesicle or be taken back in. Phospholipid remodeling may be accomplished by supplying generous amounts of balanced lipids and catalysts via nutritional intervention and the use of intravenous Phospholipid Exchange.
Research focused on individual fatty acids, as the current interest in Docosahexaenoic Acid (DHA), erupted due to the availability of an algae-based (non-fishy) DHA available for infant formula. However, not revealed to the public were studies (Susan Carlson) of premature infants given algae-based DHA who developed necrotizing enterocolitis. Infant formula is now augmented with DHA and AA, however, other essential higher-order supplements are still missing as omega-6 gamma linolenic acid (GLA from primrose oil) and EPA (omega-3).
Supplementing one fatty acid, DHA, has failed even in its application to children with ADHD/ ADD, often negatively affecting their immune response and overstimulating the CNS. Children with hyperactivity are deficient in all essential fats, not exclusively DHA, and the administration of one fatty acid without a balance of EFAs is inappropriate for any medical disorder.
We have a new understanding of cellular organelle and microtubule function in regard to the role of fatty acids. Tremendous attention has been directed to the mitochondria with its bilipid cell layer membrane (energy-producing organelles), yet the most important organelle in regard to lipid synthesis is the peroxisome, a monolipid layer organelle. Peroxisomes, present in virtually all cells, but most prevalent in the liver and kidney, play a critical role in cellular lipid metabolism in the biosynthesis of fatty acids via ß-oxidation involving physiologically important substrates for VLCFAs, dicarboxylic fatty acids, prostaglandins, thromboxanes, leukotrienes, pristanic acid, DHCA, THCA, and xenobiotics.
Individuals with aging difficulties and immune, CNS and endocrine disorders often present with complex xenobiotics involving disturbances in the cytochrome P450 superfamily (hepatic detoxification), which parallels disturbances in peroxisomal function. The cytochrome P450s are responsible for the biotransformation of endogenous compounds including fatty acids, steroids, prostaglandins, leukotrienes and vitamins as well as the detoxification of exogenous compounds resulting in substantial alterations of P450s, as xenobiotics may turn off or greatly reduce the expression of constitutive isoenzymes.
Inappropriate use of antioxidants such as mega-dosing with Vitamin E (> 800 IU) will inhibit tumor shrinkage as beta oxidation is suppressed, thus potent antioxidants would be contraindicated in the buildup of very long chain fatty acids (VLCFAs) and therefore reduced cellular metabolism as in states of aging and toxicity. The administration of DHEA, pregnenolone, or thyroid hormones stimulates the ß-oxidation of VLCFAs, as would nutrients (riboflavin, pyruvate, manganese) as well as oxidative therapies that stimulate oxidation, prostaglandin synthesis and detoxification.
Patients presenting with low serum cholesterol often do not have a positive response with the administration of DHEA or growth hormone as their metabolism is diminished due to catabolism and/or dietary regimes that have failed to meet their basic nutritional requirements. The arbitrary use of DHEA or growth hormone will beta oxidize or burn not just VLCFAs but all the essential fatty acids as well. Antioxidants slow cellular metabolism and must remain in the proper balance with all the essential nutrients and substrates (lipids, protein) to maintain metabolic equilibrium.
Renegade fats such as VLCFAs that are over expressed, disrupt the membrane structure. There is a beautiful geometry to the membrane that is highly sensitive to the size of the lipid chains. The overall width of the fatty acid portion of the membrane is ~3 ½ nm, which must be maintained for stability. Saturated or monounsaturated fatty acids with a length of 16 or 18 carbons are preferred to permit the structure to maintain optimal horizontal fluidity. VLCFAs that range from 20 to 26 carbons force the parallel dimensions vertically.
There simply is not enough room. The distortion weakens the phosphate bonds that derive their strong attraction only as long as the phospholipids are parallel to each other on both sides of the membrane. The cell weakness is then expressed in leaky attraction to ion channels and receptors, which marginalize cell cytosol fluids and electrolytes with the only option as early cell death.
Genetic expression is the preferential individual propensity to code and produce certain proteins enzymes, hormones and peptides. How this expression degrades over time is in part individually determined, but also strongly influenced by lifestyle of which diet plays a crucial role. An optimum balance of fatty acids make up the dynamic membrane. The membrane of every living cell and organelle, including the nucleus that holds the DNA, is composed of two fatty acid tails facing each other.
This bilipid layer is so minute (3 nanometers) that it would take 10,000 membranes layered on top of each other to make up the thickness of a piece of paper. Yet the dynamics that occur within this tiny envelope with organelles prancing up and down the cytoskeleton microtubules is a microcosm that is a challenge for the human mind to envision. All cells must synthesize molecules and expel waste.
All cells must create, through gene expression, the proteins needed for cellular gates embedded in the membrane as ion channels and receptors. The ultimate control of how those peptides behave rests with the character of the membrane while the integrity of the membrane rests with the structural (oleic, stearic, palmitic) and essential lipids. In essence, the life of the cell is intimately tied to membrane health and the health of the entire organism. The membrane is everything.
Newly documented research delineates that targeted lipid manipulation can dramatically influence the human body. Medicine has been slow to acknowledge the crucial lipid requirements to address neurological degeneration often accompanying states of disease, yet now that data is emerging from the medical literature it is difficult to extrapolate and organize the data into meaningful therapeutic applications for use in a clinical setting.
Our database holds 10,000 red cell lipid analyses from 1997 to the present from Johns Hopkins Peroxisomal Diseases Laboratory, the gold standard laboratory in the United States. By organizing the research data and isolating individual fatty acids in red cells we can now examine the cellular integrity/structure, fluidity, the formation of renegade fats that impair membrane function, myelination status, and the intricate circuitry of the prostaglandins and for the first time lipid treatment protocols may be established due to a clearer view into red cell membrane dynamics.
Our clinical protocol at the Haverford Wellness Center in Havertown, PA and the Center for Wellness in Charlotte, NC is to initiate treatment with changing the patient’s overall diet, addressing the lipid balance and especially the outer lipid leaflet of the cell membrane through fatty acid therapy and the addition of supplementation targeted toward healing the cell membrane.
By stabilizing lipid status with intravenous Phospholipid Exchange and oral EFA supplementation we have remarkable tools toward healing a myriad of disorders in both pediatric and adult populations, without side effects. Through isolating individual fatty acids and dimethyl acetyls in red cells we can now examine the cellular integrity/structure, fluidity, the formation of renegade fats that impair membrane function, myelination status, and the intricate circuitry of the prostaglandins. The systemic health of the individual patient may be reached and targeted nourishment utilized through evidence based intervention, which may yield positive patient outcome.
Healing the membrane is virtually healing the body, and healing the brain.
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