Uridine and Phosphatidylcholine, Perfect Together

article4-cellsWhether the human body contains ten trillion or a hundred trillion cells makes little difference. It would take several lifetimes to count them. What does matter is how those cells communicate with each other, how they share messages about function, repair and reproduction. The basic unit of structure and function of living things, the cell is the building block of life. The word “cell” means “small room,” a fitting term for a structure that houses an assembly of bodies that direct life processes. Environment, genetics and lifestyle exert a greater influence on a cell’s viability than many people can imagine. To remain healthy, the cell must overcome insults every day. Air and water degradation, tobacco and alcohol use and abuse, and wretched eating habits are major participants in the unremitting assault on cellular equilibrium.

Of the several compounds vital to the cell’s structure and function, phosphatidylcholine, at 50% or more the major constituent of the cell membrane, is deemed paramount. As a circus would be useless without a tent, so would be the cell without its membrane. Phosphatidylcholine, abbreviated as PC, is a ubiquitous, naturally occurring phospholipid composed of a phosphate group, two fatty acids, and choline. Often confused with lecithin, PC verifiably stands alone, while lecithin is a mix of several second-team players that make a perfect emulsifier for mayonnaise but an inferior contributor to cellular integrity and health. PC is responsible for the surfactants critical to lung function and gastrointestinal stability, and is the precursor to the neurotransmitter, acetylcholine, responsible for arousal, learning, memory and motor activity.

PC is one of four phospholipids that comprise the membrane. The others are phosphatidylethanolamine (PE), phosphatidylserine (PS), and phosphatidylinositol (PI). Without its membrane, the cell would cease to function altogether—the Krebs cycle would be interrupted and there would be no energy and thus no life. It has been postulated that almost one third of all the genetic output of the human DNA cache is rooted in the membrane (Mouritsen, 2005).

The fluid character of the membrane is provided by essential fatty acids (EFA), both the omega-6 and omega-3 that the body must get from dietary sources. It’s not enough that we supply the proper amount of EFA’s; the ratio is perhaps more important. The proportion of n-6 to n-3 fats has been established as 4:1, as discovered in studies that have examined improvement in quality of life for both the well and the infirm (Yehuda, 1993, 1996) (Simopoulos, 2002, 2004, 2008).

All biological processes—every single one— rely on PC for their unimpeded activity. Information flowing from DNA to RNA to proteins needs PC; the manufacture of cellular energy and intracellular communication or signal transduction demands it. EFA-rich PC fluidizes the cell membrane to allow the smooth passage of vital substances into the cytoplasm and the movement of detritus out. It is well-accepted that some diseases, such as certain cancers, liver disease, neurological disorders and cell death, are related to a decrease in cell membrane fluidization resulting from a deficit of PC (PDR, 2001).

article4-bluegraphicThe shape of the PC molecule is ideal to serve as the basic structural unit of the biological membrane. The kink in the polyunsaturated fatty acid (PUFA) chain affords fluidity that acts to balance the lipids—and cholesterol—that are not members of the bilayer family. Lined up, shoulder-to-shoulder, PC molecules organize themselves into a protective phalanx that guards every cell and every organelle within. PC’s two tails are hydrophobic, face the inside of the cell and directly oppose others of their kind, thus forming an inner and an outer leaf. The hydrophilic head group faces the watery environs of which the body is largely made. The channels, gates and receptors that occupy the membrane help to run the machinery of life. Having both hydrophobic and hydrophilic properties, PC is an amphiphilic molecule. Its arrangement in the cell membrane parallels the structure, activity and function of a liposome.

A liposome is a tiny bubble (a vesicle) made from the same material as the cell membrane. But a liposome can be filled with medications and be used to deliver drugs in the treatment of some diseases, such as cancers. The core of a liposome is almost always aqueous and the circumference always a hydrophobic bilayer.

article4-liposomeHydrophobic substances, including pharmacologically active non-drugs, may be encapsulated by a liposome to increase their water solubility, thereby improving bioavailability and absorption. Liposomal delivery protects the contents from degradation in blood, thus increasing efficacy and reducing the possibility of a toxic event. By manipulating the lipid bilayer, scientists can create a time-released product that targets delivery of the material. A liposome can be made when a legitimate phospholipid, such as phosphatidylcholine (not lecithin) is placed in water and agitated or sonicated to form a bilayer. Low shear rates will form multilamellar liposomes, which resemble the layers of an onion. Sonication is the application of ultra sound to disrupt the stable condition of matter, allowing the lipid perimeter to re-amalgamate around the chosen material. (It works especially well to deactivate bacteria and to clean things, like jewelry, by breaking intermolecular interactions.) Vitamins, antigens, and even monoclonal antibodies may constitute a liposomal core.

One bioactive candidate substance that has garnered attention recently is uridine, a nucleoside component of RNA made from one molecule of uracil and one molecule of D-ribose. Uracil is a pyrimidine that replaces the thymine in DNA to make RNA. Together, pyrimidines and purines make both DNA and RNA. Ribose, or rather D-ribose as found naturally, is a simple sugar (monosaccharide) that forms the backbone of RNA. It’s related to the deoxyribose found in DNA.

article4-dna-strandsWhat’s the difference between DNA and RNA? That’s a good question. Both are nucleic acids, but they differ in that RNA is single-stranded while DNA is double-stranded. In RNA, uracil is an unmethylated form of thymine. It might be easier to view RNA as a carrier of messages and DNA as the owner’s manual for cell replication. There’s more, but that can be saved for another time.

Uridine is the active ingredient of its compounds, some of which may be phosphorylated or acetylated. It’s made by the liver from some foods, notably tomatoes, sugarcane, brewer’s yeast, broccoli and organ meats. Eating foods that are rich in RNA, however, may lead to health concerns because RNA also contains purines, the elements (adenosine and guanosine) responsible for conditions such as gout. But on the bright side—the very bright side—uridine as a supplement, combined with the essential n-3 fatty acids EPA and DHA, has been found to be as effective an antidepressant as commonly prescribed medications, such as Prozac® and other SSRI’s (Carlezon, 2005). Not only is uridine associated with positive mental health outcomes, but also with the resolution of mitochondrial disorders, some of which may be induced by certain medications, particularly those related to treatment of HIV and orotic aciduria, the latter a genetic disorder characterized by retarded growth, macrocytic anemia, and leukopenia, accompanied by urinary excretion of large amounts of orotic acid. (Weinberg, 2011).

In its monophosphate form, uridine is synthesized de novo from glycine, the smallest of the twenty amino acids found in proteins. Glycine is non-essential and can be manufactured by the body from another amino acid, serine. In the central nervous system, glycine acts as an inhibitory neurotransmitter, with primary activity in the brainstem, spinal cord, and retina. Alone, it’s been used to enhance sleep quality (Yamadera, 2007). Uridine monophosphate is successfully converted to its di- and triphosphate forms, eventuating to a factor crucial in the formation of dendritic spines, which are bodies that protrude from the dendrites of a neuron in order to receive messages across the synapse. They act as a storage unit, a kind of capacitor, to assist the transmission of electrical signals to the neuron’s cell body.

article4-blue-orange-strandsDendritic spines are essential for intellectual ability, where their plasticity is associated with motivation, learning and memory. Long-term memory is mediated by the growth of new spines or the enlargement of existing ones. This helps to reinforce specific neural pathways. Because their lifespan is heavily influenced by (sensory) input activity, spine dynamics play a role in the maintenance of memory over a lifetime. In youngsters, the rate of spine turnover is relatively high, producing a net loss because the rate of elimination surpasses the rate of formation. Spines remain persistent in adulthood (Alvarez, 2007) (Zuo, 2005).

A form of uridine known as triacetyluridine is classified as a pro-drug because it serves as a precursor to an endogenous compound—cytidine triphosphate (CTP)—that has the capability to address the progressive degeneration of dopaminergic neurons that characterize Parkinson’s disease (Cansev, 2008). In its several forms, uridine promotes neurite outgrowth and stimulates downstream messengers that modulate neurotransmitter release (Krügel, 2001) (Shoji-Kasai, 2002) and helps to increase the number of dendritic spines in the brain (Sakamoto, 2007).

Living in an impoverished sensory environment retards memory development and impairs its function in adulthood. Brain phosphatidylcholine synthesis uses uridine as an element of its totality and, in combination with polyunsaturated fatty acids, has been found to improve cognitions in young and aged laboratory animals and humans, much the same as would be expected from living in an enriched sensory environment from birth (Holguin, Aug. 2008). In later study by Holguin, phosphatidylcholine constituents, PUFA omega-3’s, and uridine combined to make a cocktail shown to increase total brain phospholipids and to enhance cognitive function by increasing synaptic membrane content (Holguin, Nov., 2008).

When cerebral function is disrupted and presents with periodic convulsive seizures, a diagnosis of epilepsy may be anticipated. Here, a sudden discharge of excess electrical activity may affect many areas of the brain or focus on only a few, resulting in either grand mal or petite mal episodes, the former being characterized by loss of consciousness and the latter by clouded consciousness. More than one condition may elicit seizures, making etiology difficult to pinpoint, although genes, head trauma, dementia, or developmental disorders, among others, may be implicated. Anti-epileptic drugs, because of their limited efficacy and unwelcome side effects, have spurred an interest in new, perhaps even alternative, treatments. The Neuroscience Center at Dartmouth investigated uridine as a possible endogenous anti-epileptic modulator in specific patterns of epilepsy. It was learned that administration of uridine effected a reduction in EEG spike frequency and improved visual spatial memory in laboratory animals exposed to lithium-pilocarpine-induced status epilepticus, which may entail hippocampus damage (Müller, 2009) (Zhao, 2006).

Of greater concern to the general public is Alzheimer’s disease (AD), whether addressing prevention or the presence of inchoate dementia. Often beginning with slight memory loss and culminating with the inability to exercise judgment and to communicate effectively, Alzheimer’s has been the target of a number of pharmaceutical approaches. Decades-old research from the U. of California identified synapse degradation as a major factor in the onset of cognitive impairment (Terry, 1991). Years later, a medical food containing phosphatide precursors (PC) and associated cofactors, including uridine and PUFA’s, was found to improve memory in mild AD patients (Scheltens, 2010). Subjects suffering mild cognitive decline in the absence of dementia also found significant benefit from this medical food. In both mild AD and incipient cognitive impairment, total phospholipid and fatty acid levels were deficient (Conquer, 2000). Herein lies but one rationale for marrying uridine to PC. Because the typical American diet lacks the nutritive wholeness of the past, based on the shared rogueries of perfunctory agricultural practices and food handling, and on the dubious ways of too many home and commercial kitchens, supplementation of uridine and PC might a prudent habit to cultivate.

The information contained in this web site is for educational purposes only and is not intended or implied to be a substitute for professional medical advice. Inclusion here does not imply any endorsement or recommendation.  Always seek the advice of your physician or other qualified medical provider for all medical problems prior to starting any new regiment.

These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

PC (Phosphatidylcholine) – Fountain of Health (Longevity & Vitality)

article3-moleculemodelPhosphatidylcholine is a wunderbar nutrient – yet, it remains an enigma. At 6 syllables it’s a bit of a tongue twister, easier to say PC. In Europe, it’s even longer, Polyenylphosphatidylcholine, 10 syllables, which abbreviates to PPC. Both mean exactly the same. Both refer to the same wonder nutrient. While most all supplements such as anti-oxidants, B- vitamins, minerals, pro-biotics, CoQ-10, electrolytes, digestive enzymes, etc., have excellent nutritional value and contribute to better health, few rank on a level with PC – in fact – none do.

So – why is it that PC is still a relatively modest player in the world of nutrients and natural medicine, while the research literature on PC is awash with positive studies? Why, in the normal evolutionary process of recognition, has PC failed to obtain its rightful role? There’s a story underlying it that needs to be told. Somehow, a glitch on this side of the Atlantic essentially sabotaged its climb up the ladder. About the mid 90’s, our illustrious North American edible oil producers made a decision which muddied the waters and threw a wrench into our wonder nutrient, however, that decision was a profitable one, for them. The history begins with the pressing of the oil from the seeds, such as sunflower, canola, corn, flax, etc., but mainly soybeans, the largest seed oil produced in the world. After pressing, hydrating and harvesting the oil and the seed protein, one of the products left over is a gummy substance called lecithin, found in all cells.

That sticky substance became an important ingredient in foods such as spreads, margarines, chocolates, cosmetics, etc. Nutritionally, it contained PC, so there was also an effort to introduce it as a supplement. The concentrated lecithin was combined with oil, encapsulated in bulk and sold to the vitamin companies who repacked it under their own label. Somehow, in the ensuing effort, someone in charge had the bright idea to call it – Phosphatidylcholine, instead of Lecithin, which is what it really was. The ruling established was this: if the PC content in the lecithin was at least 30% – it could be called Phosphatidylcholine. That turned out to be the ultimate monkey wrench for our wonder nutrient. Soybean lecithin is a complex mix containing ~65-75% phospholipids together with triglycerides and smaller amounts of sterols and carbohydrates. The major phospholipid is phosphatidylcholine, including phosphatidylethanolamine and inositol-containing phosphatides. That singular decision, to name lecithin PC, was clearly a gross biochemical error. It’s just not done in the realms of science because it’s not scientifically accurate. The confusion that followed has been with us to this day with products being marketed and sold as PC regardless of the fact that they are not PC.

Even though it is a component in the lecithin mix, PC and its membrane partner phospholipids, P-ethanolamine, P-inositoI, and Phosphatidic Acid, because of digestion, cannot make it through the gut intact. The lipase enzymes in the gut disassemble all oils which include phospholipids and triglycerides. Gut enzymes, such as proteases and amylases digest proteins and carbohydrates in the same manner as lipases do to the oils, they cut them apart. Only the basic components are allowed through, not the whole PC molecule.

article1-PC-moleculeTo obtain PC along with the other PLs, which every cell membrane needs, those parts must be created from scratch or reconstituted from the digested components, which young and healthy cells can easily do. For aging or diseased cells, it’s another story. For PC, and the other PLs in lecithin to become valuable nutrients, they must first be separated from the raw lecithin, an expensive complex process, which only a small group of nutrition companies have succeeded in doing. Once separated, PC and its associate phospholipids become miscible in water – repeat – they dissolve in water, enabling them to make the trip through the gut – intact. Only then can PC perform its membrane enhancing wonders as we will see in the following Israeli studies.

Presently, as far as we know, the only companies that have succeeded to separate the phosphatides from lecithin are BodyBio, American Lecithin, and Essentiale Forte®, sold in pharmacies in Europe. All other vitamin companies continue to market the misnamed capsules under their own label, which, will not succeed in providing any PC, and which recently, has been shown to be a possible cause of atherosclerosis (Wang 2011). Imagine – how many people have heard about the wonder nutrient PC, searched on Google, and bought the misnamed lecithin capsules in shops, or on line? How many of those funny capsules with zero value have been consumed worldwide in over a half a century as a result of that labeling loophole? And it’s still going on, unfortunately, to the detriment of all those who, as yet, don’t know the difference. Talk about selling snake oil…

article3-supplementsSo, why is PC such a wonder nutrient and why is it important in maintaining health and longevity? Are we destined to succumb to illness as we age and lose PC? Our cell membranes naturally contain PC and SM (sphingomyelin), both are phospholipids and both have a choline head group. However, there is a shift that occurs in the composition of the membrane with the growth of SM and a fall in PC levels. SM is a combination of ceramide and PC, wherein ceramide combines with PC and absconds with PC’s choline head, enabling the formation of SM. The relationship between those two choline phospholipids in mammalian plasma membranes is critical and directly affects cell function. This was demonstrated most clearly by Professor Yechezkel Barenholz and his colleagues in 1985.

article3-barenholzIn a dramatic study, Dr. Barenholz, head of biochemistry at Hebrew University in Jerusalem, reported on the changes of PC and SM in the lipid composition of rat myocytes (heart cells). They were able to extract rat hearts and separate the myocytes, the heart cells, and keep the cells alive in Petri dishes in their lab with a nourishing culture. After a day or two, by themselves, the myocytes would congregate together and begin to beat in unison. They did what heart cells are designed to do. They beat – and they did it at ~160 beats/minute. The scientists measured the beats as well as the PC and SM content in the cells and watched the decline of the PC/ SM ratio in the first three days from 20% SM to ~33% SM — then, over the next 14 days, from 33% to about 50% SM. What occurred in the culture was a steady loss of PC, replaced by Sphingomyelin, from 20% to 50% in 14 days, accompanied by a steady decrease in heart beats. Between days 7 and 12 in culture, the beats/minute fell from a vibrant 160, down to a near lifeless 20 beats/minute. On day 16, they added PC into their Petri dishes, and in one day, the myocytes reverted back to their healthy rate of 160 beats per/minute. In just 24 hours, they went from near death back to vibrant heart cells. This was also accompanied by a normalization of seven vital enzymes (Yechiel 1985a, 1985b). Simply changing their diet by adding PC into their cultures, reversed the rise in SM and brought life back to the near dead myocytes, a dramatic example of the wonders of PC.

However, Professor Barenholz delved even deeper. In 1989, he was awarded a US patent #4,812,314, on the use of PC for increasing male longevity and fertility. Dr. Barenholz, a recognized world leader in lipid technology, together with colleagues, focused on the changes that occur with cell aging, principally on the loss of PC as with the myocyte example, which showed a rise in the levels of SM, and a concomitant rise in cholesterol (CH) (Barenholz 1982, 1984). The scenario of lowered PC and raised SM is especially pronounced in senescent or diseased tissues. For example, plasma membranes associated with the aorta and arterial wall show a 6-fold decrease in PC/SM ratio with aging. SM is also increased in several diseases, such as the hereditary Niemann-Pick Disease, and in toxic exposures. In atherosclerosis, the leading cause of death and morbidity worldwide, the SM content can be as high as 70-80% of the total phospholipids in advanced aortic lesion (Barenholz 1982, 1984). To put this in context, Kummerow et al, article3-labratUniversity of Illinois, Urbana, analyzed the SM content in umbilical cord, and discovered that it was ~10% (Kummerow 2001). In essence, we start life with ~10% SM and 90% PC, and thereafter SM increases, and as recorded, with disturbing cellular outcomes. Kummerow further has shown that arteriole obstructions are directly related to the change of PC and SM reaching above 45-48% SM, resulting in a rise of arteriole sclerosis and death, similar to the findings of Barenholz fifteen years prior. Type in ‘sphingomyelin atherosclerosis’ on Medline, and you will get 228 studies from around the world, corroborating Barenholz and Kummerow on SM and cardiac disease. Clearly, a loss of PC is an unhealthy event. Thus, maintaining the level of PC in the cell membrane as we age is vital to cellular health and longevity. It may even be the sought after fountain of youth we are looking for.

The 1989 invention involves administering PC liposomes as an intravenous injection (parenterally, not orally as used earlier), to an individual (animal or human) to reverse age-related changes in the lipid composition of organs and tissues, such as heart muscle cells and red blood cells, by an infusion of egg PC as a lipid exchange (egg PC is molecularly similar to soy PC, the fatty acids may alter, but not the molecule). Since the aging process in heart muscle is characterized by a decrease in PC, with a coinciding increase in SM and cholesterol, the PC liposomes have the ability to promote an exchange of PC for SM and CH within the membrane. Adding PC liposomes into the blood induces an exchange of PC within the heart cell membranes and reverses the membrane concentration of SM and CH. This would also occur in membranes throughout the body, including the brain.

article3-petridishAn important therapeutic application of the invention is increasing an individual’s ability to withstand cardiac stress. The utility of the treatment was shown in laboratory animals following congestive heart failure or serious damage to the heart, the red cells showed about a two-fold decline in PC/SM between ages 3 and 18 months. This was reversed by three PC liposome treatments within nine days with PC SUVs administered to 18 month aged rats, whereby there was an increase in the ratio nearly sevenfold. The treated 18 month old male rats were able to maintain blood pressure under stress about 50% longer than untreated rats. There were several additional studies, however, the most impressive were the next two on longevity and sex.

Effect of Treatment on Longevity with PC SUVs
(SUVs are small spherical membrane enclosures, cellular look-a-likes)

This study examines the effect of PC treatment on animal longevity. The rats tested were 30 month old male Sprague-Dawley rats. Since Sprague-Dawley rats normally die between the ages of about 24-30 months, the rats tested showed a dramatic increase in longevity. A test group of six rats were each given PC-SUVs, prepared as an IV, at a dose of between 0.5 and 1 g PC liposome lipid through the tail vein, and similarly dosed after one week, and then every two months thereafter. A second control group of same-age male rats was similarly injected with saline water on the same dose schedule, 2 doses a week apart, then one dose every 2 months, until the animal died of natural causes. The 6 animals in the control group had an average age at death of ~34 months. Of the PC treated animals, 2 were sacrificed at 44 months, 1 at 45 months, and 3 at 48 months, giving an average age at death of about 46 months, however all of the treated animals were sacrificed (killed), so, the actual length of survival remains unknown. Even so, this equates to a substantial life extension, approximately 33% in the animals treated.

article3-cellEffect of PC-SUV Treatment on Sexual Competence/ Virility
It is known that sexual function in male rats declines with age. If males 30 months of age or older are housed with younger, fertile females, many have fewer litters, and the actual litter count is lower than would be born if the same females had been with young males. To test the effect of PC liposome treatment on sexual function, a group of 10 rats, each 34-36 months old (close to or near death), were treated with egg PC-SUVs every three days for six days (a total of three doses) with 0.5 to 1 gm lipid per animal through the tail vein with the untreated animals received just sterile saline over the same period. Nine days after the first injection, the animals were each placed in a cage with 3 female Sprague-Dawley rats 5 to 6 months old. The single male and 3 females stayed together for l to 3 weeks, or even more, ~7 weeks, after which the males were removed. Only 1 of the 3 females in contact with untreated males for the single week produced litters, and this increased to about 2 of the 3 females that were able to stay together for 7 weeks. In all cases, litter sizes were less than 10. With treated males, about 2 of the 3 females produced litters with 1 week of contact, and virtually all of the females littered with 3 weeks of contact. Litter sizes were the normal 10-14 animals. Thus, sexual performance and virility was substantially greater in the animals who received PC. Something to consider if conception has been difficult – PC.

Earlier, I indicated the three oral PC products with acceptable quality, which requires additional explanation. PC from BodyBio, American Lecithin and Essentiale are all miscible (water dissolving) and efficacious. However, there is recent research on mitochondria energy that is noteworthy. In 2012-13 there were a number of studies on mitochondria and ETC (electron transport chain). Production of ATP, which initiates on the inner membrane of mitochondria, is newly recognized to be dependent on PE (phosphatidylethanolamine) – not on PC (Böttinger, Joshi, 2012, Tasseva 2013). PE is generally ~half the concentration of PC in cell membranes; however, the dynamics responsible for the separation of protons that drive the production of ATP, sit on the inner membrane of the mitochondria, and are enshrouded with a predominance of PE for the ETC chemistry to play out. BodyBio PC contains both PC and PE, whereas Phos Chol® (and/or Nutrasal®) from American Lecithin, and Forte® contain
only PC.

The results of Professor Barenholz and his colleagues in demonstrating the overwhelming, and mostly hidden results of PC, were performed over a quarter of a century ago, and are nothing short of ‘remarkable’. Dr. Barenholz used IV egg PC, which, to our knowledge, has not been commercially duplicated. However, he used oral PC liposomes as a food in the myocyte petri dishes and witnessed the myocytes recovery, which was admirable, even shocking. If PC is produced correctly, which BodyBio PC is, there is every reason to expect it to be the Super Star nutritional supplement. Maintaining sexual activity and disease-free life as we age has been a universal dream. Having experienced the life-saving, life-promoting qualities of PC with thousands of doctors and their patients has been a fascinating healing journey for all of us at BodyBio. We invite you to join us at and begin your BodyBio PC journey towards better health. Also, take a look at the video on PC and cancer – “An Amazing Story”.

The information contained in this web site is for educational purposes only and is not intended or implied to be a substitute for professional medical advice. Inclusion here does not imply any endorsement or recommendation.  Always seek the advice of your physician or other qualified medical provider for all medical problems prior to starting any new regiment.

These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

Phosphatidylcholine: Life’s Designer Molecule

article1-LipidMembraneOf the tens of thousands of molecules that make up the life of a cell, Phosphatidylcholine (PC) stands apart. PC is a phospholipid, one of four that link together to form the membrane. The largest is Choline (PC), 2nd, Ethanolamine (PE), 3rd, Serine (PS), and 4th, Inositol (PI), with each having the same prefix “phosphatidyl”. However, Phosphatidylcholine at ~50% is the largest concentration in the membrane and reigns supreme of all cell components. If there is the possibility of such an exalted position, PC deserves that titled role as the pinnacle of the marvelous membrane and all metabolism.

The membrane is the structural skin that surrounds the cell as well as the tiny organelles within it. But it is far more than an outside protective layer — it is literally the essence of life. You may damage other parts of the cell, even remove the center of the nucleus, the DNA (enucleate), and the cell will still carry on for several months. But damage the membrane and the cell is no more (Lipton 2005). “By spontaneously closing off to form an underwater bubble, the lipid bilayer membrane acts as Nature’s Test Tube, which packs the other biochemical families into a confined interior, so that biochemical evolution can proceed. In brief, lipids provide biological packaging and, in this capacity, they are the molecules which actually create the biological cell (Rudin 1985).

The membrane is a lipid envelope that encases and protects the internal working of cell. It’s the beginning of life itself, for without the benefits of an enclosure there is only momentary bits of chemistry that form in the primordial sea and as quickly swoosh away. There are ~100 trillion cells in the body, all with the same basic membrane structure, even for the neurons of our brain. The chemistry of neurons is only partially understood, however, the membrane is responsible for the propagation (carries) of all our messages, both sending and receiving. The dry weight of the brain is 60% fat, with the balance protein. Since the membrane manages all our thoughts and is basically fat, the term fathead should be deemed a compliment. The membrane manages the production of energy in the mitochondria, for without the double membrane structure there is no storage space for the separation of electrical charge — no Krebs cycle, and subsequently no energy. The sheer volume of membrane in the body is mind-bending. The liver alone has ~300,000 square feet of membrane. That’s more than 4 football fields; 4.63 to be exact.

article1-PC-moleculeIt manages all of our senses, and particularly the miracle of sight. The retina of the eye contains 100 million photo-receptor cells, rods and cones. Within each one of those cells are 140 million receivers (peptides) called rhodopsin, sitting in a stack of membrane flattened sacks in each photo-receptor cell waiting patiently for a portion of light, a photon which, after capturing one or two, sends a signal back to the brain, again on the membrane of the optic nerve, giving us the ability to see (Rodieck 1998). This and much more assemble miraculously together to make up the mental and physical structure of each of us, with the lipid membrane literally the center of it all.

article1-polypeptide-subunitThe membrane is composed of phospholipids (PLs) lined up soldier fashion in a double layer of opposing PLs, with the head groups looking out into the surrounding water on either side of the membrane. The membrane is an extremely tiny spark of life’s chemistry. Even “tiny” pales in being able to convey the smallness. The membrane is only 5 nanometers thick (Owen 1981, Lee 1983, Shinitsky 1984) If you were to stack sheets of them one upon the other — it would take 10,000 membranes to make up the thickness of a piece of paper. It’s physically not possible to envision a world that small. They automatically organize themselves into a bilipid sphere to provide the protecting outer garment of every cell and every organelle within the cell. The phospholipid structure is a marvel. Its two lipid tails (the oil) are hydrophobic, hate water, while the head groups, PC, PE etc, are hydrophilic and love water. The term is amphipathic, meaning that the molecule (the PL) has both hydrophobic and hydrophilic ends, one end comfortable in water, and one that is not. That combination provides an automatic ability to self-assemble with both oily tails protected in the middle of the membrane. All life on the planet is water based. The cellular trick is to have a protective outer skin that shields and acts as an insulator since the chemistry inside must be able to maintain a different composition from the watery world it is now floating in.

PLs perform their self-organization with aplomb. They jump together, or flee together, for self protection since oil and water do not mix. You could say that the lipids are hiding–actually, they are. Each layer of the bilipid arrangement is completely independent of the other; there is no connection between the inner leaflet of the membrane and the outer leaflet. The two float separately but stay together because they must. The water on either side sets the rules. However, this importance of PL self-organization and the relation to our watery environment is not readily apparent.

With the head groups looking out on either side of the cell, comfortably sticking their heads into water, the cell has an ingeniously designed protective outer garment. That, however, is only the beginning, for within the membrane sits a huge selection of ion channels and receptors from our genetic library that literally run the entire cellular system, all from the comfort and protection of that oily center. It is proposed that ~30% of all the genetic output of our DNA library is embedded in the membrane as peptides, ion channels or receptors, with another ~30% attached to the membrane (60% total) (Mouritsen 2005).

Phospholipids (PL) are composed of a glycerol backbone, a head group, and 2 fatty acid lipid tails,16 to 24 carbons long. The tails are like a flexible goose neck lamp. They comprise ~70 % of the total PL molecule ~800 Daltons (Fox 1972) and are critical to its function. A large percentage of those lipid tails are Essential Fatty Acids (EFAs), meaning that they must be part of our diet, we cannot make them. Each of the four parts of the phospholipid membrane is critical, but it is the makeup of those lipid tails, part saturated and part unsaturated, that gives the cell the essence of life.

article1-PC-capsLecithin: Lecithin is a residue from soybean oil production and contains a relatively high concentration of PC, along with PE, PI and other phosphatides. Most vitamin manufacturers market a lecithin product and call it phosphatidylcholine. The majority of lecithin is used in the food and cosmetic industries. However, a portion is pre-encapsulated by the oil producers, ADM, Central Soya, etc., and sold to supplement packers, who market it as PC. Somehow, over the years, the terms lecithin and PC have been used interchangeably, even by medical researchers. However, they are not one and the same, nor should they be. PC, PE, PI etc, are just chemical components of lecithin.

The PC in Lecithin is oil based. The PC molecule is a phospholipid, which is ~70% oil because of its two lipid tails. It is partially hydrophobic (the oily tails), amphipathic, while its head group is hydrophilic. In brief, it’s two-faced. To become a structural PL, It must be exposed or introduced along with many other PLs into a watery environment to form a membrane. Oil does not run away from oil, there’s no need. The oily tails automatically run away from water (hydrophobic), which becomes the driving force for the formation of the membrane. Take that hydrophobic force away, which oily lecithin does, and the molecule cannot perform as intended. It will not become an important cellular structural component. Once lecithin is ingested, the lipases of the digestive tract cleave apart the PLs, removing the lipid tails and the head groups such as choline, and are recycled as cellular raw material. That’s basic fatty acid digestion. Taking lecithin as a food or supplement can raise choline levels. Adding additional choline has recently been shown to be potentially harmful. (see below.)

Yehuda: Each of our cells can produce non-essential FAs, such as the saturated palmitic and stearic acids and the monounsaturated oleic and nervonic acids, but not the essential FAs (EFAs), the omega 6 or the omega 3s. Those two lipid families are the EFAs. However, it is the ratio of those vital n6s and n3s that is critical. For that we are indebted to the research of Yehuda, Mostofsky, Rabinowitz and Carrasso from Bar Ilan University, Haifa, Israel (1993,94,95,962,972,983,992,20002,02,03,04,052,07,08). They have unlocked the most important missing piece of dietary science — the balance of the essential fatty acids. It is difficult to describe the value this discovery represents. We are only in the infancy of understanding fatty acid biochemistry. EFAs provide the highly fluid character of the membrane, which is the essence of life in both plants and animals. The studies of Yehuda et al solved a long debated question — what fats should we be eating? What is the optimum dietary ratio of n6 to n3. Yehuda et al have unequivocally shown this to be 4:1, 80% n6 to 20% n3*, and from our brief dozen years of employing the 4:1 ratio, our clinical success has been extremely positive.

Finding a research basis for dietary EFAs was a milestone. We could now, with reasonable confidence, adjust the diet to elevate the base EFAs* using sunflower oil for linoleic (LA), and flaxseed oil for linolenic (ALA). Raising the EFA levels in the body using the 4:1 ratio has not only provided positive clinical results but has unlocked a hidden secret for nutritional health. As FA researchers, we had strongly felt that raising fluidity alone was the underlying need, but without Yehuda we were just guessing. Adding in excessive amounts of fish oil was rapidly proving unhealthy, as was the excess of omega 6 oils that were part of our newly-processed food world. Balancing the EFAs was the answer, and not only was it a relief clinically for our patients, but also it’s inexpensive as well – a clearly elegant solution. The value of Yehuda’s research to the future health of society is so significant it warrants a Nobel Award.

Budwig and Rudin: Joanna Budwig, a brilliant German scientist with PhDs in both chemistry and physics, and Donald Rudin, an equally brilliant MD and Harvard professor, both recognized that the n3s, linolenic (ALA), were missing from our diet, due in no small part from the meteoric rise of the large food producers in the last century. Both Budwig and Rudin struggled with flax oil for their patients, since flax contained 55% ALA. They each had success with patients in relieving various symptoms, such as cold sensitivities, dry skin, tanning, eye pressure, diabetes, headache, tinnitus, palpitations, hand eczema, rheumatoid pain, racing thoughts, and even allergies. However, the relief was a brief 3-6 months duration, after which Rudin would stop the flax oil. After ~3-4 months he would try it again, reporting that there was a relief of symptoms each time he repeated the flax oil treatment if he spaced it a few months between. Neither he nor Budwig knew the problem was the ratio. Flax is 2 parts of n6 to 5.5 parts of n3 (2:5.5), which is almost the exact opposite of Yehuda’s 4:1. Imagine how much further we could have progressed if they had known of the correct ratio then.

Yechiel and Barenholtz: In 1985 Yechiel and Barenholtz, from Hebrew University, authored a significant paper highlighting phosphatidylcholine and its relationship to aging and disease (Yechiel 1985a.b, 1986, Muscona-Amir 1986). Using rat myocytes (heart cells) in a 20 day in-vitro study, they demonstrated the ability of PC to completely rejuvenate cells that were all but expired. Myocytes can be separated in a petri dish, and with proper feeding, survive. After ~two days, they congregate together in each dish and begin to beat in unison at a rate of ~160 beats per minute.

article1-beats-chartTo demonstrate the power of PC, the researchers fed group (A) egg yolk PC for the life of the experiment (20 days), but not so to groups B and C. However, they received it in their feed later. Group A is represented with a straight line (Green) at the top of the chart. They were given egg PC after day 6 and for the entire 20 days they maintained a constant beating rate of ~160 beats/ min. Group B cultures (Red) were not as fortunate and were denied PC. After 6 days the Group B cells started to weaken; after day 8 began a precipitous decline in the beating rate, reaching a low point by day 12 with some of Group Bs beating at ~20 beats/min,and some not beating at all. Group C (Blue) was given PC like Group A, after day 6, but only up to day 11, after which PC was removed from their feed. As you can see on the chart, almost immediately the Group C started a similar decline in their beating rate, which mirrored the decline of group B with a 5 day drop to ~20 beats/min. In addition, both B and C groups suffered a variety of cellular distortions in cell size and in production of protein, specifically an elevated Creatinine PhosphoKinase.

On day 16 all cultures were given PC, and within 24 hours, the Bs and Cs recovered their beating rate to ~160 beats/min and continued until the study was concluded at day 20. In addition, they also recovered most of their distorted chemistry, even lowering CPK. This was one of the most remarkable demonstration of the cellular power of phosphatidylcholine, or to put it in more precisely, the absolute necessity of PC and life.

article1-pink-moleculeA Medline search on ‘Phosphatidylcholine’ will reward you, or inundate you, with ~50,000 citations. To review them would easily take a year or two, but it speaks volumes of the importance of PC. In all of our studies, we have yet to uncover a report as powerful as that of Yechiel and Barenholtz. However, there are two that are noteworthy. The review by Cui and Howeling, PC and Cell Death, 2002, that focuses on the ability of PC to reverse a number of biochemical distortions and prevent cellular necrosis and/ or apoptosis. Apoptosis is a controlled, regulated death, while necrosis is a rupture of the membrane with the release of vital components into the surrounding blood stream. Cui et al presented their prior biochemical studies and many others, demonstrating that perturbation of PC leads to cell death, and the replacement of PC re-establishes homeostasis.

The work of K.J. Gundermann, PhD, MD, is also highly noteworthy. In his book (“The Essential Phospholipids as a Membrane Therapeutic” 1993), he thoroughly covers the use of PC in the studies of toxicology and hemorrheology, and in the treatment of lipid peroxidation, alocholic & diabteic fatty liver, malnutrition, kidney, cirrhosis, gastrointestinal, neurological, lung, psoriasis, MS, cerebral circulation, elevated lipids, atherosclerosis and even drug enhancement.

The book is a review of 776 research papers published from 1959 to 1993 on the therapeutic value of Essential Phospholipids (EPL), and is the European reference for a concentrated phosphatidylcholine (also made from soy, but water based). This product was developed by Nattermann, a German producer of lecithin products for food and cosmetics. EPL became recognized in general medicine under the names of Essentiale and Lipostabil. Nattermann developed them in both an oral supplement called Forte (not in oil), and an ampoule for intravenous infusions, a PC water/bile mixture similar to the body’s natural bile-oil carrying system.

article1-micelleEPL was accepted throughout Europe as a natural medical i.v. treatment. However it was in Eastern Europe that it achieved a higher degree of popularity. Russia and her satellites were not as close to Big Pharma as we in the West. A natural product like PC (EPL) was a less expensive alternative to Western drug therapy, and is efficacious for a wide variety of disorders. The result was an almost total acceptance of PC by doctors throughout the Communist World. Their experience with PC provided a rich history of therapeutic use, both orally and as an IV for ~50-60 years, with many of these studies detailed in Gundermann’s review.

During the 70’s Nattermann AG was absorbed by Aventis and Rhone Poulanc (later sold off). However, in spite of rave reviews in a wide range of treatments, PC received little attention in the West. Natural products like PC are un-patentable and, even with an excellent medical record, have little sex appeal in the pharmaceutical world. IV-PC is not approved in France–and Rhone Poulanc is a French company. They certainly could have organized its approval if healing had a higher priority.

Aventis marketed their IV-PC under the brand name of Essentiale, which was yellow in color. B-Vitamins were included, with riboflavin (B2) providing the color. Rhone Poulanc marketed their IV-PC as Lipostabil, which was clear, no vitamins added. Both products were produced in the same factory on the same production line. In 2005 Aventis abruptly took Essentiale off the European market and in 2011 Lipostabil ceased production. However, Essentiale is still available in the US, coming from Switzerland.

Lecithin and The Marketplace: The majority of PC currently sold today is lecithin, or triple lecithin. The membrane of a cell is a liposome, and oil based lecithin cannot form a liposome. As noted earlier, even though lecithin or triple lecithin contains PC and PE, when taken orally they are assaulted by lipases, phospho-lipases etc, which remove the fatty acid chains and the head groups. By the time fat absorption occurs in the gut, the components of the phospholipids are indistinguishable from the components of other lipids, such as triglycerides. However, while the job of re-assembling PC from the individual components is questionable, it is possible, but only if you’re young and healthy. But if you’re young and healthy you don’t need a supplement. Simply eat an egg or two.

Some head groups, like choline and inositol, are hard for the body to make, so absorption of these components from food can be important to a healthy diet (Onken 1996). However, as the recent 2011 Nature study showed, the value of raising choline levels is now questionable (Wang Z et al, Nature, 2011, Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease). The details of the danger of raising choline are important to learn since there are many people taking supplements under the guise of Phosphatidylcholine (Triple Lecithin). That may very possibly be putting themselves at risk.

Lecithin itself was not the answer; it needed a much higher phospholipid concentration, which Nattermann was developing. The 1940’s German method extracted a “Pure Phospholipid” (EPL), which only recently has been duplicated by BodyBio. While the process is more expensive, the exercise of discarding undesired components from lecithin (basically the oil) leaves a water based product (BodyBio PC) that encourages formation into a Liposome. A micelle/liposome, when exposed to a watery environment, forms exactly like a cell, with a spherical shape, only a thousand times smaller.

The PLs of micelles and liposomes are identical to cellular PLs, however, a liposome is a bilipid layer and appears (looks like) a cell membrane. That tiny sphere can then traverse the gut without being dismembered, and not only deliver itself but also deliver a tiny cargo, such as a drug (Big Pharma employs Liposome technology for a wide range of drugs) or even another supplement. Today, most pharmaceutical companies are engaged in liposome technology. In the manufacturing process, the drug is trapped inside the sphere and, as the cell-like liposome reaches a normal cell, it is absorbed by endocytosis; the tiny sphere becomes one with the cell membrane and delivers the drug or nutrient inside the cell, an efficient method of absorption for either a drug or a vitamin.

The fallacy of using lecithin has been difficult to see. For years there have been conflicting medical reports about the benefits of Lecithin-PC (Wood 1982), which now becomes understandable through liposome research and the Nature study.

BodyBio PC will blend in plain water. It does not dissolve. Rather, it is miscible; it mixes in the watery environment, and naturally forms a liposome, or more precisely, tens of thousands of PLs will. Lecithin or triple lecithin will not blend with water no matter how vigorously it is mixed. We are well aware that oil and water do not mix. This is easily seen in a laboratory or in the kitchen with lecithin or BodyBio PC.

PC Products That Work: BodyBio PC, PhosphaLine®, PhosChol®, Liposome Lab products, Lipoflow Forte, Essentiale Forte N (Europe), PC Injectable by prescription only in 5 ml ampoule for IV therapy as Essentiale from Paracelsus Apotheke.

Wood et al, 1982 comments, because high intakes of lecithin or choline produce acute gastrointestinal distress, sweating, salivation, and anorexia, it is improbable that individuals will incur lasting health benefits from self-administration.

PE acts as a reservoir for PC, since, by the addition of three methyl groups it is converted to PC. Thirty percent of PC is endogenously derived from methylation (Cui 2002). To encourage this conversion of PE to PC, it is advisable to add into the diet folinic acid (an advanced form of folate) and a methylated form of B-12, methylcobalamin. Both nutrients increase methylation and tend to lower homosysteine levels.

The information contained in this web site is for educational purposes only and is not intended or implied to be a substitute for professional medical advice. Inclusion here does not imply any endorsement or recommendation. Always seek the advice of your physician or other qualified medical provider for all medical problems prior to starting any new regiment.

These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

Cardiovascular Disease: What’s Choline Got to Do With It?

article2-nature-mastheadOur Answer to the 2011 Study in Nature ‘Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease’

Phosphatidyl Choline (PC) is the largest of the phospholipids that comprise the membrane of our cells. PC is also prominent in egg and soy lecithin. While PC may be the largest of the phosphatides in lecithin there are other principle phospholipids, phosphatidyl-ethanolamine (PE), phosphatidyl-inositol (PI), phosphatidyl-serine and phosphatidic acid that together, constitute a higher concentration in lecithin than does PC. Soybeans are the principle source of commercial lecithin, and lecithin is the most important by-product of the soy oil processing industry because of its many applications in foods, cosmetics and industrial products. Lecithin is also available as a dietary supplement in two forms: as granular lecithin which contains ~12% PC (calcium phosphate as a flow agent), and in a concentrated form called triple lecithin at ~35% PC in capsules fluidized with soy oil (Wood and Allison 1981). While lecithin has been on the health food scene for over a half century, somehow, it picked up the perception of being called phosphatidylcholine. Many researchers used the two interchangeably as if they were the same. They are not. Lecithin is not PC, and while PC is the largest phosphatide in lecithin, technically, it is only a chemical component of lecithin. Oddly, no one reverses it by saying PC when referring to lecithin.

In April, 2011 in an article in Nature, Gut flora of phosphatidylcholine promotes cardiovascular disease, Wang et al wrote that “Foods rich in the lipid phosphatidylcholine (PC, also called lecithin)* which predominantly include eggs, milk, liver, red meat, poultry, shell fish and fish, are believed to be the major dietary sources for choline”. Note the age-old error again. However, confusing PC and lecithin pales in comparison to the egregious characterization in the title saying that “phosphatidylcholine promotes cardiovascular disease”. We must presume the authors to be knowledgeable of the long and voluminous history of PC as the largest phospholipid component of our cellular membranes and especially as a nutrient with its quite exceptional history in alleviating heart health disorders specifically cardiovascular disease. The title ‘Gut flora of phosphatidylcholine promotes cardiovascular disease’ completely disregards the scientific history of PC and casts a disturbing and untrue image of a highly valuable nutrient with a long history of lowering cholesterol and successful treatment of atherosclerosis, (Cho BH 2011, Navab M 2003, Chung BH 2005, Hajj Hassan H 2005, Koizumi J 1988, Ke Y 1996, Ovesen L 1985). The title could be correct if lecithin was used, which if intended, should have been so stated.

article2-calloutThe disturbing title further calls in question the veracity of what appears to be significant scientific information. The implication of PC as potentially dangerous is simply wrong; however, if lecithin was used, the study becomes of significant value for shedding light on the difficulty of using lecithin as a nutrient. While there have been a large number of studies over the last 50 years using lecithin as a source for PC, the effort to achieve medical benefits have been plagued with mixed results, while the reverse of using phosphatidylcholine has consistently maintained positive medical results particularly in international studies. Research and clinical experience has revealed that PC is possibly the most prestigious nutrient of all (Yechiel and Barenholtz 1985, Cui and Howling 2002).

* The authors again make the mistake of referring to PC as Lecithin.

article2-cholinesupplementsRhone Poulanc, in its brochure for Lipostabil, lists 197 references for oral and i.v. administration of PC for hyperlipoproteinemia and atherosclerosis. Gundermann KJ, PhD, MD, in “The Essential Phospholipids as a Membrane Therapeutic” 1993, has 776 referenced studies in his technical manual which covers the use of PC in toxicology, hemorrheology, lipid peroxidation, alcohol and diabetic fatty liver, malnutrition, kidney, cirrhosis, gastrointestinal, neurological, lung, psoriasis, MS, cerebral circulation, elevated lipids, atherosclerosis, even drug enhancement. It is a thorough review of PC research published from 1959 to 1993, which portrays a positive image of PC quite the opposite as in the Nature study.

Using lecithin as a source of PC is a poor scientific approach because the phospholipids within lecithin are oil based. The PC used in the European studies was either egg PC, or, if soy lecithin based, the oil had been purged and the phospholipids were isolated. In the 1940s, Nattermann GMBH, successfully produced a high concentrated PC from lecithin in an oil free form called Phospholipon which was the source for the PC used in all the medical studies previously mentioned. The formation of the membrane occurs in water and cannot occur if the lipid tails of the phospholipids are immersed in oil. Oil and water do not mix, but oil and oil mix very well. All life on the planet is water based and depends on the “hydrophobic effect” to drive the formation of the membrane of all cells. There is little excuse for the continued PC / lecithin confusion or the implication of PC as a troublesome nutrient.

Under normal digestion, PC and all lipids ingested are degraded by lipases in the gut. The phospholipids and the triglycerides are reduced by enzymes PLC or PLD which attack the head groups (choline, ethanolamine, etc) with PLA1 or PLA2 doing the same for the lipid tails. The PC research reports referenced above did not use raw lecithin as a source of PC. The majority of the PC was either i.v. Essentiale (Aventis) or Lipostabil (Rhone Poulanc) or, as a PC capsule “Forte” under both labels. Forte is currently available in most European and Eastern European pharmacies, i.v. Essentiale is available in Eastern Europe and the US, all of which used phosphatidylcholine that originated from Nattermann, which, as already indicated, is no longer lecithin.

In the 2011 Nature paper by Wang et al, there are 18 listed authors from the Cleveland Clinic, UCLA, Cleveland State, and USC. It is appalling that such a prestigious journal, Nature, would permit such gross error in basic biochemistry. The article does indeed help to resolve the age-old problem of why lecithin has consistently failed to provide positive results as a phosphatidylcholine nutritional supplement, because it isn’t phosphatidyl choline. The implication of Choline and TMAO in CVD was also corroborated in a number of studies prior to the Nature study such as recent publications from Italy in 2005, UNC in 2007, Emory and Aventis in 2009 and from Germany in 2007 – 2010, to name a few. However, none of these publications mentioned lecithin or even PC as a critical choline source or of PC in promoting cardiovascular disease. In light of the abundant positive research for phosphatidyl choline for over half a century, the choice of the title in the April 2011 Nature paper borders on scientific ignorance and demands a retraction.

In the Nature study it is prudent to bear in mind that the laboratory animals were inbred strains, predisposed to CVD.

article2-tmao-moleculeThere is clear evidence that choline released from the cell membrane by ischemia-related cytolysis may be used as a predictor of cardiac events in the presence of chest pain, despite low levels of troponin. (Danne, 2007) In this regard, choline elevation is a result of tissue damage (vulnerable plaque), and is not a causative agent.

Specific gut bacteria will degrade choline to trimethylamine, which is then oxidized by the liver to TMAO. The liver enzyme, Hepatic Flavin Monooxygenase 3 (FMO3) is responsible for the conversion. (It may be important to note that this is a “flavin” enzyme, dependent upon riboflavin for its activity. Without further attention, it is unseemly to indict this B vitamin as part of the etiology of CVD.) TMAO—and its companion choline metabolite, betaine—promote upregulation of multiple macrophage scavenger receptors as part of the inflammatory cascade, following platelet activation and monocyte adhesion, but preceding the formation of macrophage foam cells from the endocytosis of oxidized LDL and the subsequent smooth muscle cell migration from vascular epithelium that forms protective fibrous caps. Foam cells that accrue from this phagocytosis comprise the fatty streaks of the plaques of atheroma in the vascular intima. Foam cells necrotize and cause the fibrous cap to rupture and form a thrombus which can lead to emboli capable of occluding smaller blood vessels.

Knowing that gut flora may generate a pro-atherosclerotic metabolite has aroused interest in probiotic research. Lactobacillus rhamnosus appears to potentiate the colonic manufacture of TMAO, while L. paracasei has inhibitory properties on the formation of TMAO. Both strains are dose-dependent. If the inflammation induced by TMAO can be eliminated, or at least curtailed, the number of related cardiac events can be limited. Disrupting the inflammatory cascade that provokes foam cell induction may be as simple as preventing the oxidation of LDL in the first place. Several dietary components have demonstrated the capability to prevent LDL oxidation, including capsaicin, curcumin, and several bioflavonoids.

In 1998, Crawford et al noted that “…natural dietary antioxidants inhibit both LDL oxidation and atherogenesis in animals with elevated LDL…”

Arterioscler Thromb Vasc Biol. 1998 Sep;18(9):1506-13. Dietary antioxidants inhibit development of fatty streak lesions in the LDL receptor-deficient mouse. Crawford RS, Kirk EA, Rosenfeld ME, LeBoeuf RC, Chait A.

In 2005, Indian researchers identified the pepper constituent as cardiac friendly, when they announced, “Dietary capsaicin was found to be protective to the LDL oxidation…as indicated by reduction in TBARS by more than 40%.”

Mol Cell Biochem. 2005 Jul;275(1-2):7-13. Protective effect of dietary capsaicin on induced oxidation of low-density lipoprotein in rats. Kempaiah RK, Manjunatha H, Srinivasan K.

Quercitin (a constituent of apples and onions) and curcumin (the active ingredient of turmeric) demonstrated the greatest effects in the prevention of LDL oxidation. Both are available as supplements.

Molecular and Cellular Biochemistry. Jan 2002; Vol 229, Num 1-2: pp. 19-23 Inhibition of human low density lipoprotein oxidation by active principles from spices K. Akhilender Naidu and N.B. Thippeswamy

Future treatment of CVD symptoms may include testing for TMAO, as well as for the traditional cardiac markers. Preventive measures, especially for individuals with a family history of heart disease, may address limiting choline intake, reducing gut bacterial load via broad spectrum antibiotics, and/or using probiotics designed to modulate intestinal ecology.

The highest sources of Choline are in liver, egg yolk, red meat, fish, milk, chicken, and peanuts while the highest source of Betaine is in dark bread, white bread, spinach, cold breakfast cereals, and pasta. So becoming a vegetarian or avoiding meat will not solve the problem of avoiding the formation of plaque if a gut infection is brewing.

The information contained in this web site is for educational purposes only and is not intended or implied to be a substitute for professional medical advice. Inclusion here does not imply any endorsement or recommendation. Always seek the advice of your physician or other qualified medical provider for all medical problems prior to starting any new regiment.

These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.