Membrosia Complex

The circle of life of cells is as complex as it is simple. The cell links molecular energy and matter into a type of intelligence that drives the tissues and organs. The cell membrane is comprised of two layers of fats and phospholipids. This duality allows the cell to maintain and balance both internal and external water levels allowing cells and molecules to move more efficiently.

Membrosia Complex contains a unique blend of the cellular-supporting nutrients lecithin, uridine and trehalose.

Lecithin (from Soy).  Lecithin is a naturally occurring combination of phosphatidylcholine with other phospholipids—a group of phosphorus-containing, fatty substances found in the membrane of all cells that includes phosphatidylethanolamine and phosphatidylinositol—along with glycolipids and triglycerides. Hundreds of different phospholipid molecules have been identified, but the major types are the phosphatidyl- phospholipids. They consist of two fatty acids groups that are connected through a glycerol backbone to a phosphate ester group. (2)

Phosphatidylcholine is the most abundant phospholipid component in all cells. Phosphatidylcholine levels in brain cell membranes decline with age, contributing to memory loss. A recent study showed that administration of phosphatidylcholine in the murine model of dementia increases brain acetylcholine concentration and improves memory. (3) Most people normally ingest 3 to 6 grams of lecithin a day via eggs, soy, or meats; while vegetables, fruits, and grains contain very little lecithin. There are approximately 230mg of phosphatidylcholine per gram of lecithin. (2)

Trehalose.  Trehalose, also known as mycose or tremalose, is a natural alpha-linked disaccharide formed by a 1,1-glycosidic bond between two a-glucose units. Trehalose is found naturally in many animals, plants, and microorganisms. In animals, Trehalose is found in high amounts in shrimp and also in insects, including locusts, butterflies, grasshoppers, and bees, in which blood sugar is Trehalose. (9)

Trehalose is the molecule that gives many of these organisms the ability to withstand dry spells and prolonged droughts, also known as anhydrobiosis. It has high water retention capabilities and is used in food and cosmetics for that property. The carbohydrate is thought to form a gel phase as cells dehydrate that prevents disruption of internal cell organelles by effectively splinting them in position. Rehydration then allows normal cellular activity to resume without the major, lethal damage that would normally follow a dehydration/rehydration cycle. (10) Taking full advantage of Trehalose’s properties to preserve tissue and protein, it is already being used medically in organ protection solutions for organ transplants. Trehalose has the added advantage of being an antioxidant, and it is being used as a protein-stabilizing agent in emerging research. (11) It is that protein-stabilizing effect that has been shown to have such benefit in preserving the healthy function of nerves.

Trehalose promotes autophagy via TFEB (transcription factor EB), ameliorating disease phenotype in multiple neurodegenerative disease models. Trehalose regulates autophagy by inducing rapid and transient lysosomal enlargement and membrane permeabilization (LMP). This effect correlates with the calcium-dependent phosphatase PPP3/calcineurin activation, TFEB dephosphorylation and nuclear translocation. Trehalose upregulates genes for the TFEB target and regulator Ppargc1a, lysosomal hydrolases and membrane proteins (Ctsb, Gla, Lamp2a, Mcoln1, Tpp1) and several autophagy-related components (Becn1, Atg10, Atg12, Sqstm1/p62, Map1lc3b, Hspb8 and Bag3) mostly in a PPP3- and TFEB-dependent manner. Thus, limited lysosomal damage might induce autophagy, perhaps as a compensatory mechanism, a process that is beneficial to counteract neurodegeneration. (68)

Ribose.  Ribose (or D-Ribose) is a simple, 5-carbon monosaccharide, or pentose sugar. It is used by all the cells of the body and is an essential compound in energy metabolism. Ribose also provides the structural backbone of our genetic material, DNA and RNA, certain vitamins and other important cellular compounds. (22)

Ribose is an essential component in stimulating natural energy production. (23) Research has shown that Ribose reduces the effects of stress on the body associated with arduous activity and helps improve athletic performance. Ribose also helps heart and skeletal muscles maintain healthy energy levels, and it accelerates energy recovery when tissues are stressed by exhausting exercise or overwork. (24)

Ribose is made in the body from glucose through a metabolic pathway called the Pentose Phosphate Pathway. Unfortunately, in heart and muscle cells, important enzymes that regulate the activity of this Pathway are lacking. (25) As such, forming Ribose in heart and muscle cells is a slow process. This delay in Ribose synthesis in heart and muscle tissues also delays energy recovery when energy pools have been depleted by disease or exercise.

Uridine.  Uridine is a type of molecule known as a nucleoside that is formed when uracil (one of the four nucleobases in the nucleic acid of RNA) is attached to a ribose ring (the 5-carbon sugar used in DNA & RNA structures). Uridine has been shown to increase the utilization of choline to stimulate brain phosphatide synthesis, and it is considered a membrane phosphatide precursor. (37) Unlike dementia medications that decrease the synthesis of phosphatidylcholine, uridine stimulates brain phosphatide synthesis without diminishing synthesis or release of acetylcholine—the excitatory neurotransmitter that is often at reduced levels in Alzheimer’s Disease. (38)

L-Glutamine.  L-glutamine is the most prevalent amino acid in the blood. Human cells readily manufacture it; and under normal circumstances, dietary intake and production is sufficient. (49) However, a growing body of evidence suggests that during certain stressful times or increased energy output (intense exercise and certain disease states), the body’s tissues need more than usual, and the body may require more glutamine than it can produce. For people in a catabolic (muscle breakdown) state, it may be considered a “conditionally essential” amino acid. Glutamine is involved in maintaining a positive nitrogen balance (an anabolic state) and aids rapidly growing cells (immune system lymphocytes and intestinal cell enterocytes). It is also a regulator of acid-base balance and a nitrogen transporter. (50)

Lecithin:  In cerebral infarctions or “strokes,” diminished blood flow to the brain (ischemia) typically results in a decrease of brain phospholipids. Treatment of victims with lecithin within 48 hours of their stroke has been shown to limit the damage caused by a stroke by replenishing phospholipids in the brain—thereby preventing the usual brain atrophy. (4)

In another double-blind, placebo-controlled, randomized trial involving patients over age 55 with mild cognitive disorders, daily lecithin supplementation for 3 months resulted in statistically relevant improvement in the main target measure, the overall Sandoz Clinical Assessment Geriatric (SCAG) score, which was achieved with lecithin 37% more often than placebo with a high degree of statistical significance. Furthermore, lecithin demonstrated significant superiority over placebo in its ability to improve cognitive skills and a number of the other target measures. (5)

A six-month trial of lecithin in Alzheimer’s senile dementia resulted in the greatest improvement in the subgroup of older patients who had intermediate levels of plasma choline, which indicates that the older the patient, the more likely they are to see a direct benefit from taking lecithin. (6) As well as its direct effects, the addition of lecithin into formulations with other Alzheimer’s-fighting, memory enhancing drugs has been shown to increase their efficacy. (7, 8)

Trehalose.  Amyloidogenic proteins undergo an alternative-folding pathway under stressful conditions leading to formation of fibrils having cross beta-sheet structure, which is the hallmark of many neurodegenerative diseases. In initial studies, Trehalose was shown to prevent this abnormal protein folding and to contribute to protein stability, which hinted at its efficacy against the amyloid formation associated with neurodegenerative disorders. (12)

A key event in Alzheimer’s disease pathogenesis is the conversion of the peptide beta-amyloid (A-beta) from its soluble monomeric form into various aggregated morphologies (“plaques”) in the brain. Preventing aggregation of A-beta is being pursued actively as a primary therapeutic strategy for treating Alzheimer’s. In a 2005 study, researchers showed that Trehalose is effective in inhibiting aggregation of A-beta and reducing its cytotoxicity. They concluded that the use of Trehalose could be recommended as part of a therapeutic cocktail to control A-beta peptide aggregation and toxicity. (13) Additional studies have confirmed this inhibitory effect and elucidated the precise molecular mechanism by which Trehalose inhibits A-beta oligomeric aggregation. (14-17)

In a 2008 follow-up study, researchers used two amyloid-forming proteins, W7FW14F apomyoglobin and insulin, as model systems to determine the molecular mechanism by which Trehalose affects the amyloid aggregation process. They found that it acted at different stages of the fibrillization process depending on the protein model used. Trehalose dose-dependently inhibited fibril formation in the W7FW14F apomyoglobin model and increased the lag phase in the insulin model. The results suggested that Trehalose might inhibit the formation of “on-pathway” or “off-pathway” oligomeric intermediates depending on the nature of the aggregating protein. (18)

One recent study showed that in addition to delaying A-beta aggregation, Trehalose is able to reduce the increased cell membrane permeability that is induced by accelerated conversion of high order oligomers to fibrils such as A-beta. The researchers postulated that the observed effects on A-beta membrane interaction may be due to a more general phenomena associated with Trehalose’s capacity to enhance A-beta oligomer stability and/or direct interaction of Trehalose with the membrane surface. (19)

In late 2009, researchers at the University of Wisconsin undertook molecular simulations to examine the specific effects of Trehalose on the conformational stability of A-beta and its effect on the interaction between A-beta and the phospholipid bilayer membrane. In aqueous solution, Abeta exhibited a random coil conformation, but in the presence of Trehalose, it adopted an alpha helical conformation. The researchers then showed that the insertion of A-beta into a cell membrane is more favorable when the peptide is folded into an alpha helix than in a random coil conformation. These findings suggest that at least some of the observed actions of Trehalose may be a result of its ability to promote the insertion of this favorable alpha-helical A-beta into nerve cell membranes. (20)

In the murine model of Alzheimer’s disease with Parkinsonism, 1% Trehalose in the drinking water was shown to revert the disease phenotype while being increasingly neuroprotective the earlier it was begun. The researchers found a new mechanism for the action of Trehalose as well, showing that it increases the removal of abnormal proteins through enhancement of autophagy— the process by which the body rids itself of damaged or disordered cellular components. The study authors noted the excellent safety profile of Trehalose even at high concentrations and recommended further clinical studies of the effects of Trehalose in human neurodegenerative diseases. (21)

Ribose.  The physiologically functional form of Ribose, called 5-phosphoribosyl-1-pyrophosphate (PRPP), regulates the metabolic pathway that synthesizes energy transfer compounds (Krebs cycle intermediates) in all living tissue. This pathway is called the Purine Nucleotide Pathway. If PRPP is not available in sufficient quantity, synthesis of these energy transfer molecules slows, and tissue recovery is delayed. (26)

If the cellular pool of energy transfer molecules is depleted by disease, overwork, or exercise it must be replenished. PRPP is required to stimulate the metabolic pathway used by the body to restore this cellular energy pool. Supplemental Ribose bypasses the slow rate-limiting step of the Pentose Phosphate Pathway, forms PRPP very quickly, and accelerates the process of energy transfer molecule synthesis. (27)

Multiple studies have shown that energy levels in the heart can be dramatically lowered by exercise or changes in normal cellular energy metabolism. (28,29) Depleted cardiac energy reserves may be associated with increased cardiac stress, reduced blood flow to the periphery of the body, fatigue, and decreased exercise tolerance. Ribose is the key nutrient for quickly restoring cardiac energy. (30)

Three or four workouts per week may not allow enough rest time between sessions for the pools of heart and muscle energy transfer molecules to return to normal levels. Taking Ribose supplementally shortens the time needed by heart and muscle tissue to replace these transfer molecules that are lost through vigorous exercise. (31) Maintaining optimal levels of these energy transfer molecules in the cells helps to keep heart and skeletal muscles in good physiological condition, increase power and endurance, and reduce fatigue. Recent research has also shown that Ribose supplementation during exercise reduces free radical formation. (32)

One of the most important energy transfer molecules for which Ribose forms the substrate is adenosine diphosphate ribose (ADP-Ribose). ADP-Ribose is an ester formed between Ribose and the terminal phosphate of ADP. It is produced by the hydrolysis of nicotinamide-adenine dinucleotide (NAD), which is itself a coenzyme composed of ribosylnicotinamide 5’-diphosphate coupled to adenosine 5’-phosphate by a pyrophosphate linkage. Ribosylnicotinamide is an enzymatic product of nicotinamide riboside kinase, which utilizes nicotinamide (the amide of niacin or vitamin B3) and phosphorylated D-Ribose as its substrates. (33)

ADP-ribose is formed into chains by the important regulator of gene expression, Poly (ADP-Ribose) polymerase (PARP), which is used by the body in a number of cellular processes involving DNA repair, post-translational modification of other proteins of epigenetic significance, and apoptosis (programmed cell death). (34) Mild activation of the PARP1 enzyme has been shown to facilitate DNA repair in nerve cells, while excessive activation can lead to a significant decrease in NAD, ATP depletion, and apoptosis. (35)

The D-Ribose in Membrosia helps gently upregulate the activity of the PARP enzymes by providing increased levels of an otherwise rate-limited substrate for its activity. Increased DNA damage repair via mild activation of the PARP family of enzymes with relatively moderate dosing of Ribose follows the hormetic biphasic dose response curve by initiating only the brain’s cellular DNA repair mechanisms at this concentration. PARP’s mild activation is modulated by the relatively high dose of Trehalose in the formula, which subsequently acts to prevent further A-beta misfolding and aggregation. (36)

Uridine.  Because phosphatidylcholine can provide choline for acetylcholine synthesis, a recent study investigated whether administration of uridine can significantly increase levels of acetylcholine levels in the murine brain and its extracellular fluid. The researchers found that giving a uridine source enhances some cholinergic functions, probably by increasing acetylcholine levels and release in the brain. (39)

MIT brain researchers are working on a combination of nutraceuticals that may be supportive in mind enhancement or in the treatment of age-related mental decline. The MIT research suggests that a cocktail treatment of omega-3 fatty acids, uridine, and choline from lecithin—all of which are present in the 2-Step Membrosia Drink—are all needed by brain neurons to make the phospholipids that make up the majority of those cells’ membranes. After adding those nutrients to the diets of their test subjects, the researchers observed a dramatic increase in membrane phospholipids and the protein levels in brain cell synapses, where messages between cells are relayed. (40)

Damage in brain synapses is believed to cause the dementia that characterizes Alzheimer’s disease. Alzheimer’s disease brains contain fewer and smaller synapses and reduced levels of synaptic proteins, membrane phospholipids, choline, and DHA. The three phospholipid precursors—omega-3 fatty acids, lecithin, and uridine—may thus be useful in treating Alzheimer’s disease. (41)

Uridine has also been shown to have anticonvulsant effects in some models of epilepsy. In a study at the Neuroscience Center at Dartmouth Medical School, researchers examined the possible neuroprotective effects of uridine by administering the agent following drug-induced epileptic seizures. In the subjects receiving uridine, there was a trend toward more normal brainwave patterns, improved memory of their surroundings, and healthier brain tissue. (42)

The epilepsy-preventive and anticonvulsant effects of uridine were later studied by administering uridine to subjects undergoing rapid electric stimulation to induce seizures. In these electricity-induced seizure models, uridine had a moderate preventive effect on the onset of seizures as well as an acute anticonvulsant effect. These results suggest uridine has potential as an intervention in the prevention and treatment of epilepsy. (43)

Researchers at the Department of Neurosciences at the University of California at San Diego in La Jolla investigated a group of young patients who suffered from developmental delay, seizures, ataxia, recurrent infections, severe language deficit, hyperactivity, short attention span, and/or poor social interaction. Their metabolic testing was normal except for persistent low urinary uric acid. Further investigation showed that all of the patients had a 6- to 10-fold elevation in the activity of an enzyme that is responsible for the breakdown of uridine nucleotides. (44)

Based on the possibility that the observed increased breakdown might be causing a uridine deficiency, the patients were treated with oral uridine at a dose of 1.000 mg/kg daily in divided doses every 6 hours. All patients showed remarkable improvements in speech and behavior as well as decreased seizure activity and frequency of infections, which were later confirmed by a double-blind, placebo-controlled trial. These researchers observations suggest that genetic polymorphisms that result in increased uridine breakdown may be related to these symptoms, and that the effects of this increased breakdown are reversed by administration of uridine. (45)

A recent double-blind, placebo-controlled study into the application of uridine in the treatment of bipolar depression demonstrated for the first time a direct effect of uridine on membrane phospholipid precursors in healthy adult humans using magnetic resonance spectroscopy (MRS). Subjects underwent a MRS scan at baseline and then again after seven days of either 2 g of uridine or placebo administration. The uridine group had significantly increased total phosphocholine and phosphoethanolamine levels over the one- week period. (46)

Because of its role in increasing cell membrane phospholipids, uridine has an important role in promoting proper intra- and extracellular water balance. In fact, studies have shown that uridine helps promote the elimination of excess sodium from the body and may reduce blood pressure and decrease excess extracellular fluid retention. In salt-sensitive hypertensive patients, the metabolic clearance rate of uridine is raised and basal plasma uridine diminished, suggesting that increased turnover of uridine is linked to unfavorable increases in extracellular space. (47)

Uridine was also studied in a model of lung disease to evaluate its ability to affect fluid movement in the distal airspaces (the alveoli) of the lungs. Japanese researchers studied the effect of uridine on baseline and stimulated alveolar fluid clearance in the murine model of pulmonary edema. One of the uridine compounds tested showed an increased alveolar fluid clearance by 40% of the baseline values. When combined with isoproterenol (a non-selective beta-adrenergic agonist structurally similar to adrenaline), alveolar fluid clearance was increased by 280% of the basal value. So, in addition to its own effect of stimulating alveolar fluid clearance, uridine has a synergistic effect with the most common medications prescribed to help reduce extracellular fluid retention in the lungs. (48)

Glutamine.  Glutamine-supplemented foods have been shown to prevent deterioration of gut permeability, protect against the development of intestinal mucosal atrophy, and improve nitrogen balance. (51) Glutamine levels in plasma and skeletal muscle are decreased in people with cancer. (52) Glutamine supplementation can decrease the loss of protein in muscles and protect immune and gut-barrier function during radiation and chemotherapy in patients with advanced cancer. (53)

Glutamine and glutamate with proline, histidine, arginine, and ornithine, make up 25% of the dietary amino acid intake and form the “glutamate family” of amino acids, which are disposed of through conversion into glutamate. (54) Although glutamine has been classified as a nonessential amino acid, in major trauma, major surgery, sepsis, bone marrow transplantation, intense chemotherapy, and radiotherapy, when its consumption exceeds its synthesis; it becomes a conditionally essential amino acid. (55) In mammals, glutamine is one of the most important substrate for the creation of ammonia in the gut and in the kidneys due to its important role in the regulation of acid-base homeostasis. (56)

L-glutamine helps speed recovery and reduce healing time after surgery. In cells, glutamine is a key link between carbon metabolism of carbohydrates and proteins and plays an important role in the growth of fibroblasts, lymphocytes, and enterocytes. Providing nutrition regimens containing high amounts of glutamine to patients can reduce hospital-stay times after abdominal surgery. Randomized, double- blind, placebo-controlled trials have revealed that postoperative patients on supplementation regimens containing glutamine have improved nitrogen balances, generation of chemical messengers (cysteinyl- leukotrienes) from specialized white blood cells (polymorphonuclear neutrophil granulocytes), and improved lymphocyte recovery and intestinal permeability in comparison to those that have no glutamine within their dietary regimen without any side effects. (57)

Breakdown of glutamine via the glutaminase enzyme produces glutamate, a precursor of gamma-amino butyric acid (GABA)—an inhibitory neurotransmitter. (58) L-glutamic acid is a ubiquitous amino acid present in many foods either in free form or in peptides and proteins. Animal protein may contain from 11 to 22%, and plant protein may contain as much as 40% glutamate by weight. L-glutamate is the most abundant free amino acid in brain, and it is the major excitatory neurotransmitter of the vertebrate central nervous system. (59)

Most free L-glutamic acid in brain is derived from local synthesis from L-glutamine and Kreb’s cycle intermediates. It clearly plays an important role in neuronal differentiation, migration, and survival in the developing brain via facilitated calcium transport. Glutamate also plays a critical role in synaptic maintenance and plasticity. It contributes to learning and memory through use-dependent changes in synaptic efficacy and plays a role in the formation and function of the cytoskeleton. Glutamine in the form of glutamate is converted to alpha-ketoglutarate, an important component of the citric acid cycle. It is a component of the antioxidant glutathione and of the naturally occurring forms of folic acid. Glutamate also serves as a precursor to proline, an amino acid important for synthesis of collagen and connective tissue. (60)

In one study on the effects of 8 weeks of creatine monohydrate and glutamine supplementation on body composition and performance measures; twenty-nine (17 men, 12 women) collegiate track and field athletes were randomly received 0.3 g creatine per kg of body mass per day for 1 week, followed by 0.03g creatine per kg body mass per day for 7 weeks plus 4g glutamine per day or placebo. Both groups participated in an identical strength and conditioning program. Body composition, vertical jump, and cycle performances were tested before and after the 8-week supplementation period. The researchers found that the creatine-glutamine combination significantly increased body mass, lean body mass, and initial rate of power production compared to the placebo group. They concluded that the combination of glutamine and creatine increases muscle mass and power. (61)

The influence of combined supplementation of glutamine and recombinant human growth hormone on the protein metabolism was studied in China for sixty people who suffered some severe burns. Study participants were randomly divided into control and glutamine with human growth hormone (hGH) groups. The total hospital stay days in the glutamine + hGH group were less than that in the control group. Combined administration of glutamine and hGH elevated plasma glutamine levels in these burn victims, which enhanced systemic protein synthesis, and improved the rate of wound healing. (62)

Glutamine supplementation has increased body weight, body cell mass, and intracellular water when compared with placebo in HIV patients. (63) It is especially helpful in those with HIV who are taking anti-viral medicines and others who may be particularly susceptible to medication-associated diarrhea. In one study on HIV positive people taking the anti-retroviral drug nelfinavir, HIV-infected patients with nelfinavir-associated diarrhea for at least 1 month were randomized to receive L-glutamine or placebo for 10 days in a prospective, double-blind, crossover study. There was a significant difference between the L-glutamine and placebo groups when placebo was administered first; and when L-glutamine was administered first, there was a significant crossover effect. Thus, L-glutamine significantly reduced the severity of drug-associated diarrhea and produced improved quality of life compared with placebo. (64)

The high rate of glutamine utilization and its metabolism in immune cells such as lymphocytes, macrophages, and neutrophils has raised the question of why glutamine is responsible for these functions. The macrophage has access to a variety of metabolic fuels both in vivo and in vitro; so, why does it seem to prefer glutamine? It seems that high levels of glutamine are key in the processes of free radical and cytokine (chemical messenger) production. Our current understanding of the rate of utilization and the pathway of metabolism of glutamine by cells of the immune system raises some intriguing questions regarding the therapeutic application of glutamine supplementation. There seems to be an indication for using glutamine supplementally to enhance its utilization by white blood cells, thereby specifically improve their phagocytic and secretory capacities. This heightened level of cellular functioning seems to result in a supportive effect on the immune system as a whole. (65)

Aging is associated with declining activity of the growth hormone-insulin-like growth factor-I (GH- IGF-I) axis and with a decrease in cognitive function. The stimulatory effect of an orally administered nutritional supplement, mainly containing glutamine, on the GH-IGF-I axis and on mood and cognition was investigated in the Netherlands. Forty-two healthy subjects were enrolled in a randomized, double blind, placebo-controlled trial. They received 5g of a supplement containing glutamine or placebo, twice daily orally for a period of 3 weeks. The nutritional supplement ingestion for 3 weeks was found to increase serum GH levels with 70% relatively to placebo. Increases in IGF-I, the marker of GH levels in the blood, were associated with improved memory and vigor. The researchers concluded that oral supplementation of a mixture containing glutamine can enhance GH secretion and cognitive function in healthy middle-aged and elderly subjects. (66)

In another study designed to determine the effects of orally administered glutamine on the resting energy expenditure (REE) and nutritional status of children and adolescents with sickle cell anemia, twenty-seven children and adolescents received orally administered glutamine for 24 weeks. High REE is associated with catabolism and delays in growth. After 24 weeks, the patients’ median REE (kcal/d) decreased by 6%. Patients with less than 90% ideal body weight had even greater declines in REE after 24 weeks. Improvements in nutritional status and in the levels of two amino acids in the blood were observed. Thus, lowering REE via glutamine supplementation looks to be an effective way to improve the growth of children and adolescents, especially those who are underweight for their age or height. (67)

Take the Membrosia Fluidzer along with the Membrosia Complex amd mixed together with a favorite juice to produce a tasty, satisfying smoothie-like drink.

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