Incomprehensive/ble Notes On Choline

Discussion in 'Vitamins' started by Amazoniac, Apr 7, 2018.

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  1. Terma

    Terma Member

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    If it worked as expected, it could allow to increase phospholipid synthesis a little-to-moderately while blunting the acetylcholine effects, to a limited extent where another substrate/cofactor notably CDP/uridine become rate-limiting fairly quickly. Past that (ignoring acetylcholine synthesis) it goes to methylation. 275mg isn't terrible.

    I would be very careful when stopping the drug because the "anticholinergic" properties (usually implied to be at the receptor level - you have to read the cyproheptadine mechanism more closely, I do not know it) effects may not guarantee anything about the acetylcholine synthesis and levels, only the receptors, so in the worst case you could get a very bad surprise if you stop cold turkey (a minority of people have had serious effects from too high choline (and uridine)).

    A better bet would be to use an acetylcholine synthesis/release inhibitor than an anticholinergic that works on the receptors. Wikipedia suggests methylmercury or botulinum.
    Acetylcholine - Wikipedia
     
  2. Makrosky

    Makrosky Member

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    I think that is why good b-complex products have choline added???

    I second your opinion than in 12 months energin will be a whole b-complex even including PABA.

    Sometimes I think we are reinventing the wheel from scratch just to end up with what everyone else is already doing. Something like a philosophical deconstruction that after decades of it you end up with the same reality as everyone else just that you wasted many years making it a 3000 pieces puzzle. Or am I being fatalistic here.
     
  3. OP
    Amazoniac

    Amazoniac Member

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    I now doubt it because it will eventually become unmanageable unless he switches to dry powders (which is something that I keep suggesting him):
     
  4. Makrosky

    Makrosky Member

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    Maybe it is possible to find a choline molecule that is compatible? Just as he is using a magnesium molecule that is soluble in the oil and good for transdermal application. I don't know much about biochemistry anyway.

    But THANKS again for these kind of posts you create. Puts things back in a wider less-deconstructed perspective.
     
  5. Jackrabbit

    Jackrabbit Member

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    Wow thank you!
     
  6. Terma

    Terma Member

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    @Amazoniac Tripped over this on my way home, unfortunately the one true god (sci-hub) is 502 at the moment

    Methionine and choline supply alter transmethylation, transsulfuration, and cytidine 5'-diphosphocholine pathways to different extents in isolated ... - PubMed - NCBI
    it's back:

     
  7. Terma

    Terma Member

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    @Amazoniac Got almost no time but found this:

    Plasma Homocysteine Is Regulated by Phospholipid Methylation

    PEMT was responsible for 50% of the homocysteine levels in the mice. PEMT produces notably unsaturated phospholipids. Therefore, other variables aside, a high homocysteine level (besides its own immediate effects; it has them, but they had control linking them to cardiac issues) as they try to associate with cardiac issues might actually be a possible indicator of high PUFA delivered to cells.

    Therefore, a way to reduce homocysteine is to replace PEMT production of phospholipids with Kennedy. And if you rely on PEMT you screw yourself over on several levels.
     
  8. OP
    Amazoniac

    Amazoniac Member

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    This is really interesting. Have you considered creating a thread to do the consolidation of your ideas? They're scattered throughout the foro.
    Right now I'm trying to choose between you or Elephanto as titular guru. "Got almost no time" is a point against, but I can pretend it was never written.
     
  9. Terma

    Terma Member

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    If you want, you can choose my next username. I can give pre-consent to the change; you tell the admin to change my name to whatever you fancy, and link them this post as proof of my consent. I was gonna go with "Fox Mulder" but it's a little narcissistic. Just let me know what it is so I can login again. You can also choose my avatar, or alternatively, delegate that decision - I also consent for you to delegate my avatar selection and I authorize whomever that may be to choose my avatar. I will upload anything you or they say, unconditionally. However, you personally must choose the username.
     
  10. OP
    Amazoniac

    Amazoniac Member

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    Hi, Terma. Here's one username for you:
    I-will-be-sourcing-saturated-phosphatidylcholine-for-everyone-that-is-interested-in-group-buying-it-in-bulk-with-me-and-I-am-committed-to-find-the-cleanest-product-available-because-this-is-how-I-roll
     
  11. OP
    Amazoniac

    Amazoniac Member

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    - Choline Supplementation in Cystic Fibrosis—The Metabolic and Clinical Impact

    "Choline metabolism is characterized by rapid plasma turnover, high turnover of liver PC via the enterohepatic cycle of bile, and by pulmonary PC secretion into the circulation via transfer to apolipoprotein A1 [19,21,22,23,24,34]. In choline deficiency, choline is drained from the lungs to meet the requirements of the liver [25]. These physiological conditions impact on CF patients: exocrine pancreatic insufficiency and low duodenal pH result in decreased pPLaseA2 activity, impairing the cleavage of bile PC to lyso-PC and, therefore, the reabsorption and salvage of its choline moiety. The resulting choline deficiency may impact on the liver, and pulmonary PC/choline drainage to feed the liver may compromise epithelial integrity, repair and homeostasis of the chronically inflamed CF lung [4,12,13]."​
     
  12. khan

    khan Member

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    What is considered a low dose for uridine?
     
  13. OP
    Amazoniac

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    - USDA Database for the Choline Content of Common Foods - Release Two (improved)

    upload_2019-6-5_16-24-12.png
    All cook'd and weighing 100 g, unless indicated.
    In case you discard egg whites, their choline content is negligible, and the yolk represents about 40% of the whole egg weight.
     
  14. OP
    Amazoniac

    Amazoniac Member

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    - Choline: The Underconsumed and Underappreciated Essential Nutrient (by Steve Zeisel and friends)

    "The Adequate Intake (AI) for choline was established by the Food and Nutrition Board of the National Academy of Medicine (NAM) (formerly the Institute of Medicine) in 1998, at a time when dietary intakes across the population were unknown for the nutrient. Traditionally, the AI reflects an observed or experimentally determined approximation or estimate of intake by a group (or groups) of healthy individuals.[1,5] Adequate Intakes have been used when data to calculate an estimated average requirement (EAR) and recommended dietary allowance (RDA) are not available. Unlike this typical NAM approach, the development of the AI for choline was informed by the previously mentioned depletion-repletion study in adult men, in which deficiency resulted in liver damage.[1,5] The AI for adults was calculated as 7 mg/kg times the reference weight of a man (76 kg) or woman (61 kg), with rounding based on prevention of liver damage."

    "The most common forms of choline in foods are fat-soluble phosphatidylcholine and sphingomyelin, as well as water-soluble phosphocholine, glycerophosphocholine, and free choline[11] (Figure 1). Animal-derived products typically contain higher amounts of choline than certain plant foods do."

    "Only about 10% of Americans and 8% of pregnant women currently meet their gender- and life-stage-specific AI for choline[8,13,14]; again, those cutoffs are based on prevention of liver damage (ie, it is not based on the typical mean intake of the healthy population like the AI for other nutrients)."

    "Vegetarians have the lowest intakes among the US population, estimated at 192 ± 7 mg/d.[15] Choline intakes have been shown to be driven by egg intake and, secondarily, protein foods (ie, meat, poultry, and seafood) intake.[14]"

    "Dietary supplements provide less than 5% of dietary choline in relation to recommended intakes because choline salts are bulky and vastly increase the size of the supplemental product.[14] Current intakes cannot be deemed inadequate based upon the AI value alone. Although AIs may be useful in guiding individual dietary plans, by definition, they are established when the evidence is insufficient to calculate an EAR. Therefore, it is not possible to conclusively assess the risk of inadequacy in a population.[16]"

    "Choline production is enhanced by increased estrogen production."

    "The most compelling short-duration challenge study showed supplementation with choline bitartrate to decrease pupil size, a widely accepted biomarker of cholinergic function, within 70 minutes."

    "With only an estimated 10% of the US population achieving the AIs and no indication of excessive intakes above theULs that were set in 1998, coupled with compelling evidence of negative health outcomes associated with lower choline intakes and the absence of harm, the summit participants agreed that there is a need to increase public and health professional awareness of choline by providing education on foods rich in choline. Among health professionals, including registered dietitians and physicians, awareness and knowledge of the importance of choline remain low. Choline has been shown to be ranked last among common nutrients as a nutrient to recommend for a healthy diet, and only about 10% of health professionals indicate moderate familiarity with choline. Among obstetricians and gynecologists, only 6%report they are likely to recommend choline-rich foods to pregnant women.[62]"

    "Current research suggests that failing to achieve the AI is likely detrimental to health, particularly in regard to liver and muscle function in healthy adults, as well as cognitive function in the developing fetus and infant."

    Check out their menu sugarbabies (Tables 2-5)!​

    - Dietary Choline Intake: Current State of Knowledge Across the Life Cycle

    "Different forms of choline vary in how absorption and metabolism occur. After absorption, water-soluble forms of choline reach the liver through portal circulation while lipid soluble forms are packaged into chylomicrons, which are absorbed and transported through lymphatic circulation [10]. Interestingly, the different dietary choline forms consumed during infancy differ from those in adulthood. This can be explained by the primary food source, where the majority of choline present in human milk is in the water-soluble form [you can confirm above, but not for humanoids], versus lipid-soluble forms for foods consumed later on. Hence, it has been suggested that the form in which dietary choline is consumed should be considered [11]. Evidence from animal studies have shown that different forms of choline present in milk will be utilized differently, as evidenced by the fact that maternal and offspring immune systems respond differently to various forms of choline consumed [12,13,14,15]."

    "[..]choline is a precursor for the synthesis of phosphatidylcholine, the most abundant form of phospholipid in the body. Phosphatidylcholine is synthesized through the cytidine diphosphate (CDP)-choline pathway, which occurs in all nucleated cells [35]. It has been estimated that 70% of total phosphatidylcholine in the liver is synthesized by this pathway [36,37,38]. Alternatively, phosphatidylcholine can be generated by the de novo synthesis pathway by the sequential methylation of phosphatidylethanolamine by phosphatidylethanolamine N-methyltransferase (PEMT) [39,40,41]. This reaction consumes three molecules of SAM, which in turn generate three molecules of S-adenosyl homocysteine (SAH), a precursor of homocysteine [1,42]. It has been estimated that up to 50% of homocysteine production [as posted before] may originate from PEMT activity, with the highest activity being detected in the liver (although activity is also observed in other tissues, such as the mammary gland) [1,37,39,43,44,45,46]. In humans, this is the only known endogenous de novo pathway for choline synthesis. Recently, it has been reported that phosphatidylcholine produced by the PEMT pathway differs from that originating from the CDP-choline pathway, particularly in the fatty acid composition, with the first characterized by having a higher composition of long-chain fatty acids, such as docosahexaenoic acid [47,48]." ← Terma's work.

    "In humans, liver damage (e.g., elevated serum alanine aminotransferase concentration) occurred in healthy men after only three weeks of dietary choline restriction (n = 7, 0.42 to 0.62 µkat/L), which was not observed in the control group (n = 8, 0.40 to 0.32 µkat/L) [7]. [..also post'd.] In the same study, a 30% decrease in plasma free choline concentration was observed in the choline-deficient group. Similarly, muscular damage (e.g., elevated serum creatine phosphokinase concentration) was reported after three weeks of dietary choline restriction [83]. These examples of tissue damage were attributed to altered structural integrity and increased cellular membrane permeability that arises due to a decreased phosphatidylcholine to phosphatidylethanolamine ratio [84,85,86,87]."

    "It has [] been reported that only a low proportion of choline intake derived from eggs is converted to TMAO [107], which is then excreted and does not accumulate in the blood [108]. In addition to choline intake and gut microbiota, TMAO levels are also controlled by renal excretion [109]. To date, the mechanisms by which TMAO increases CVD risk and the identification of the type of bacteria involved in TMA synthesis are now becoming understood [21,110]. However, it is important to recognize that TMAO content is high in seafood [111], and only a small variation of TMAO concentrations can be explained by dietary intake [112]."

    "It has been previously reported that total choline content in human milk increases from colostrum to two weeks after birth, and then stays stable beyond six months [115,116,117,118]. Studies have reported a total choline content in mature human milk ranging from 125 to 166 mg/L (1198 to 1600 µmol/L) (Table 1) [118,119]. In mature human milk, phosphocholine is the predominant form of choline, followed by glycerophosphocholine; thus, the water-soluble forms of choline account for approximately 84% of the total choline [115,116,120,121]. In contrast, the lipid-soluble forms of choline (phosphatidylcholine and sphingomyelin) are mainly present as a minor component of the milk fat globule membrane, and thus make up a relatively small fraction of the total choline in human milk [122,123]."

    "[..]free choline represents only a small fraction of the total choline in human milk[.]"

    "The first database on the total choline and its individual forms, in foods that are common in North American diets, was made available in 2004 by the US Department of Agriculture (USDA). The data set listed 434 food items [148], which was updated and expanded in 2008 [2]." "It is relevant to note that the first released version of the database for choline content in foods contained erroneously high betaine values, which were rectified in the second edition."

    "Foods that contain the highest content of choline include liver, eggs, beef, fish, pork, and chicken [2]. In these foods, the majority of choline is present as phosphatidylcholine, a lipid-soluble form, as part of the cell membrane. Milk is also a good food source for total choline, as it is usually consumed on a daily basis."

    "It should be noted that the small depletion-repletion study used to derive [AI] values was conducted only in men and did not provide information on whether less choline would be effective, as researchers only studied one dose [7]."

    "The Panel on Dietetics Products, Nutrition, and Allergies from the European Food Safety Authority (EFSA) published the Dietary Reference Values for Choline in 2016 [9]. Similar to IOM, EFSA considered that requirements for choline cannot be estimated, and therefore set AIs for total choline (Table 2)."

    "Dietary choline intake information is currently available mainly from North American and European countries (Table 4)."

    "Given that the AIs established by the IOM were set based on a single study conducted in men where only one choline dose was used, it is interesting to note that a common finding is that mean intakes are below the corresponding dietary choline recommendation. The evaluation of choline intake must be done with caution, as intake levels above the AI imply a low probability of inadequate intake, but intake below the AI does not necessarily indicate inadequacy [198]. Therefore, given the definition of AI, no conclusion on the prevalence of choline intake deficiency can be made."

    "Only a small number of studies have reported on the individual choline forms in addition to total choline intake. In adults, lipid-soluble choline forms contribute between 45 to 60% of total choline intake, with phosphatidylcholine being the major form [199,201,202,203,204,205]. Intakes of water-soluble choline forms (free choline and glycerophosphocholine) contribute approximately 25% and 15% of total choline, respectively [167,185]. The richest food groups identified contributing to dietary choline intake in the US are animal-food sources: meat, poultry, and fish [192]. Major food sources of dietary choline vary by country. For example, eggs, meat, and dairy are the major sources of total dietary choline in New Zealand [200]. In contrast, eggs, seafood, meats, and soy products are the predominant sources in Japan and China [56,199]."​

    - Mito Right? Treating Fatty Liver (choline chloride)
     
  15. OP
    Amazoniac

    Amazoniac Member

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    - Food Components to Enhance Performance: An Evaluation of Potential Performance-Enhancing Food Components for Operational Rations
    Choline: Human Requirements and Effects on Human Performance

    "In the adult human, serum choline concentrations fluctuate modestly (increase 1.5-fold) when common choline-containing foods are ingested (Zeisel et al., 1980). Total body stores of choline in humans can be estimated on the basis of measurements of choline pool concentrations in animal tissues; it is estimated that a 70-kg human contains more than 5 mmol of free choline (500 mg) and more than 300 mmol of choline (30 g) in esterified form (Zeisel et al., 1991)."

    "The demand for choline as a methyl donor is probably the major factor that determines how rapidly a diet deficient in choline induces pathology."

    "A disturbance in folate or methionine metabolism results in changes in choline metabolism and vice versa. During choline deficiency, the hepatic choline concentration decreases rapidly (Zeisel et al., 1989)."

    "Choline deficiency is [] associated with inhibition of hepatic glycine-N-methyltransferase activity, which is believed to be important for the removal of excess S-adenosylmethionine from the liver (Cook et al., 1989)."

    "Folate metabolism is also altered in choline-deficient rats (Horne et al., 1989; Selhub et al., 1991), which is reflected by the greater residence time of folate molecules within liver."

    "Choline deficiency may be of clinical importance in several groups of individuals. Humans running a marathon have lower blood choline concentrations after the run than before the run (Conlay et al., 1986). Supplementation with choline before and during a 32-km (20-mile) run prevented this drop in plasma choline and improved the subjects’ run times by 5 min (Sandage et al., 1992). The reasons for this drop in choline are undefined and might not reflect the utilization of choline but the redistribution of choline as fluid pools shift during exertion."

    "The demand for choline in normal adults is likely to be smaller than the demand for choline in infants, because large amounts of choline must be used to make phospholipids in growing organs (Zeisel, 1990). The observed changes that occurred in choline-deficient adult humans might have been greater if growing children were studied. Malnourished humans, in whom stores of choline, methionine, and folate have been depleted (Chawla et al., 1989; Sheard et al., 1986), are also more likely than healthy adult subjects to need dietary choline."

    "Only a small fraction of dietary choline is acetylated, catalyzed by the activity of choline acetyltransferase (Haubrich et al., 1975b; White and Cavallito, 1970). Choline acetyltransferase is highly concentrated in the terminals of cholinergic neurons (Malthe and Fonnum, 1972), but it is also present in such non-nervous system tissues as the placenta (Rama Sastry and Henderson, 1972). The availability of choline and acetyl-coenzyme A (acetyl-CoA) influence choline acetyltransferase activity (Cohen and Wurtman, 1975, 1976; Haubrich et al., 1974, 1975a). In the brain it is unlikely that choline acetyltransferase is saturated with either of its substrates, so that choline (and possibly acetyl-CoA) availability determines the rate of acetylcholine synthesis (White and Wu, 1973)."

    "Some investigators report that administration of choline or phosphatidylcholine results in the accumulation of acetylcholine within brain neurons (Haubrich et al., 1974, 1975a; Cohen and Wurtman, 1975, 1976), whereas others observe that such acceleration of acetylcholine synthesis by choline administration can be detected only after pretreatments with agents that cause cholinergic neurons to fire rapidly (Miller et al., 1989; Trommer et al., 1982; Wecker, 1986, 1988; Wecker and Dettbarn, 1979; Wecker et al., 1989). Increased brain acetylcholine synthesis is associated with an augmented release into the synapse of this neurotransmitter. A temporal dissociation between choline administration and effects on brain acetylcholine synthesis and release has been observed (Trommer et al., 1982). The choline taken up by the brain may first enter a storage pool (perhaps the phosphatidylcholine in membranes) before being converted to acetylcholine."​
     
  16. OP
    Amazoniac

    Amazoniac Member

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    "With respect to choline, it is a poor source of labile methyl groups in humans owing to the fact that human hepatic choline oxidase activity is very low compared to that found in rodents (39) (in which choline is an effective lipotrope). Thus, while supplemental choline may aid phosphatidylcholine synthesis by the salvage pathway, it could not be expected to correct a deficit of SAM."​

    [39] Liver Choline Oxidase Activity in Man and in Several Species of Animals

    "Hepatic choline oxidase activity varies considerably from one species to another, and Handler (1, 2) suggested that the activity of this enzyme is correlated with the ease with which choline deficiency fatty liver is induced."

    "The results of the present study agree in general with the few previous reports available in showing large species differences in hepatic choline oxidase activity (4,10-13). The level in man is the lowest of all the species examined."

    upload_2019-7-28_15-12-28.png
    18 animals? How rude!?​

    "Choline deficiency has been implicated in the pathogenesis of some forms of fatty liver in the rat, (14-16), mouse (17-19), dog (17,20), rabbit (21), hamster (3), guinea pig (22,23), monkey (24), calf (25), pig (26, 27), duckling (28), and chicken (29). However, in the few instances where comparative studies have been made, it is apparent that the rate of development and the degree of fatty change in the liver varies considerably among different species. For example, the rat and mouse on a choline-deficient diet develop an obvious fatty liver within a few days, while in the guinea pig only slight fatty changes appear after 4-6 weeks on the deficient diet."

    "Since choline oxidase provides the only known mechanism for irreversible biological degrada.tion of choline in higher animals, an abundance of choline oxidase in the liver might easily be important in determining the dietary choline requirements of each species. A very low level of the enzyme might help to conserve the body's store of choline and could make it much more difficult to induce a choline deficiency."

    "If the suggested correlation (1, 2) between the level of hepatic choline oxidase and the ease of induction of choline-deficiency fatty liver proves to be valid, then one would expect human beings to be less susceptible to choline-deficiency fatty liver than any of the common laboratory animals. Conversely, it would appear likely that choline deficiency is not as important in the pathogenesis of dietary fatty liver in human beings as it often is in rats."​


    Terma, thank you for tagging me elsewhere. Your posts are great. :salute
     
  17. Terma

    Terma Member

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    Than you for this bit, I can't remember if I read that or not but it's the kind of finding that clarifies your choices.
     
  18. Terma

    Terma Member

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    This means that choline chloride - at least for these animal cells - was the key to driving the methylation cycle around the "long" path - using B9/B12 instead of TMG. That's remarkable.

    The lowering of MAT1A is very interesting (of course critical since it consumes ATP):
    What is clear is that choline and methionine are geared toward VLDL export. Maybe in this case MAT1A is regulated by them as a program to throttle an increase in methylation because it consumes ATP, while GNMT is variable based on other factors so they implement different strategiese.
     
  19. OP
    Amazoniac

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    - Lecithin as a Therapeutic Agent in Ulcerative Colitis (there are various similar articles)

    "The outer surface of our body is covered by the skin, which is a strong corneal layer whose function is to protect the inner organs from mechanical injury and irradiation. The inner surface consists of the mucosa, which protects – among others – against the invasion of microbes. The essential component of the mucosal surface is the mucus, which is composed of a scaffold of mucins, a family of highly glycosylated proteins [1, 2]. They are negatively charged and attract the phospholipid phosphatidylcholine (PC), which is another essential component of the mucus [3–5] and synonymously called lecithin."

    "In areas of oxygen exposure, i.e. the lung, the fatty acid side chains of PC have to be saturated (mostly palmitic acid). In contrast, in mucus of the urogenital and gastrointestinal tract, the majority of PC molecules contain a saturated as well as an unsaturated fatty acid residue (palmitoyl, oleyl PC)."

    "In the intestine, the PC-containing structures are referred to as ‘surfactant- like particles’ and prevent invasion of the commensal flora of the colon [9]. In a healthy gut, there are 1 trillion bacteria per gram of stool which live in harmony with the organism. No inflammation or ulceration occurs under normal conditions, due in part to the hydrophobic barrier created by the mucus PC layer."

    "It was shown that the mucus PC content in ulcerative colitis (UC) is significantly reduced as compared to controls. In fact, in rectal mucus specimens from UC patients, PC was by ca. 70% lower compared to healthy controls and even patients with Crohn’s disease [10] . Moreover, in terminal ileum and transverse colon, similarly low PC concentrations were detected [11]. As a result of PC subspecies analysis, it became apparent that mucus samples from UC patients contained higher proportions of saturated fatty acid side chains than samples from controls, even though absolute amounts were still low [11]."

    "Of special interest was that the low PC content of mucus in UC was also observed when the patients were in remission, as defined by the endoscopic appearance of ‘mucosal healing’ [10, 11]. This indicates that a lack of mucus PC in UC patients might be an intrinsic feature of UC. It was indeed shown that the surface hydrophobicity of the mucus gel was significantly reduced in UC compared to control and Crohn’s disease samples [12]. It can be hypothesized that in most cases of UC, the reduced mucus PC concentrations are for a long time sufficient to maintain an – albeit labile – barrier. However, when yet undefined additional factors further suppress the PC contents, the remaining PC concentration may fall below a critical threshold, and the commensal microbiota can attack. These factors may be hormonal changes, environmental influences, or, particularly, alterations to the composition of the colonic flora towards colonies with higher phospholipase activities [13]."

    "It was indeed shown that PC is predominantly secreted by the ileal mucosa [14]. It is suggested that the mucus moves along the mucosal wall, from the ileum in an aboral direction, via the colon to the rectum. Accordingly, the mucus PC contents decrease continually in the aboral direction. This phenomenon is suggested to be aggravated by the exposure of PC molecules to bacterial phospholipases, which degrade PC to lysoPC (LPC) [13]."

    "The reduction of mucus PC towards the distal colon could support the fact that UC always starts in the rectum and spreads to more oral parts of the colon – the lower the PC content of mucus, the farther the extension of colitis."

    "The reason for the low mucus PC content in UC is yet unexplained; it might be linked, though, to the pathogenesis of the disease. Most likely it has something to do with a postulated active mucosal translocation mechanism for PC, as PC and LPC species account for >90% of surfactant- like particles in mucus [3]."

    "It is conceivable that the bile acids serve as detergents which attract secreted PC, thus creating a luminal sink. This could point to another biological function of bile acids which are primarily used in the jejunum for fatty acid solubilization to facilitate their most efficient absorption. However, after fatty acid absorption is completed, bile acids travel all the way down to the terminal ileum where re-absorption occurs. During their passage through the ileum, they could assist in PC secretion. Indeed, the cholestatic disease primary sclerosing cholangitis, with reduced bile acid secretion, is often associated with UC."

    "Due to the reduced mucus PC content, the commensal microbiota can attack. Therefore, it would be helpful to reduce the concentration of bacteria in stool, and, in particular, to decrease bacteria expressing membrane phospholipases. The reduction of the bacterial density can be achieved by topical acting antibiotics, e.g. neomycin or rifaximin. It has indeed been shown that rifaximin is therapeutically active in Crohn’s disease [17]. Antibiotics which can selectively attack phospholipase-carrying bacteria have not been developed."

    "Another aim is to increase the mucus PC content for re-establishment of an intact mucosal barrier. This concept has recently been followed by the development of an oral delayed-release PC preparation, which prohibits its absorption and enables substitution of missing PC in colonic mucus [18].
    In a monocentric randomized controlled trial, it was shown that delayed-release PC leads to a more than 50% improvement in 90% of active UC, and in most patients even to clinical remission as well as endoscopic healing [18]."

    "Even in the most difficult-to-treat population of steroid-refractory UC, 80% of the patients could be withdrawn from steroids, and 50% achieved overall clinical remission [19]. A dose of 3 g was shown in a phase IIB study to be most effective, and, most importantly, significant adverse events were not recorded [20]."​
     
  20. OP
    Amazoniac

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    - Health effects of dietary phospholipids

    "GPLs extracted from food products (e.g. soybeans, egg yolk, milk, or marine organisms like fish, roe or krill) are defined as "dietary GPLs". They can be ingested either with normal diet or as supplements. Naturally occurring GPLs, either from plant or animal origin, predominantly contain an unsaturated FA in the sn-2 position1, such as oleic, linoleic or linolenic acid, or the proinflammatory arachidonic acid (usually from animal origin) or the anti-inflammatory eicosapentaenoic acid (usually from marine origin), while the sn-1 position predominantly carries a saturated FA, such as stearic acid or palmitic acid.

    The mean dietary intake of GPLs is not exactly known. In a normal diet, the daily intake of PC is approximately 2-8 grams [1]. Foods with a high PC content are e.g. egg yolk, pig or chicken liver, soybeans and beef.

    In the intestine, GPLs are almost completely absorbed (> 90%). In the lumen most of them are hydrolysed at the sn-2 position by the pancreatic phospholipase A2 (pPLA2) and then taken up by the enterocytes as free fatty acids (FFAs) and lysoPL. Both can be reesterified to GPLs and enter the bloodstream incorporated in chylomicrons and, in a small proportion, in very low density lipoproteins (VLDL). However, it has been assumed that almost 20% of intestinal PLs are absorbed passively and without hydrolysation [2], and preferentially incorporated directly into high density lipoproteins (HDL). From HDL, GPLs can be transferred into the plasma membranes of numerous cells (e.g. liver, muscle, kidneys, lung, tumor cells, etc.) as their corresponding lyso-form after enzymatic activity of the lecithin-cholesterol-acyl-tranferase (LCAT) [3]. This mechanism is complex and has not yet been completely elucidated, but it has been shown that dietary GPLs are able to deliver their FAs for incorporation into cellular membranes, thus altering the membrane composition of the cells [4]."

    "Since GPLs are the main PL class found in cell membranes, their FA composition has a major impact on membrane characteristics, for example membrane fluidity and therefore formation of lipid rafts."

    "Different types of dietary GPLs vary in their FA-composition and headgroup, and therefore may have different effects. Table 1 provides an overview of the regular composition of dietary GPLs; and table 2 provides a selection of PL products used as supplements in the published papers included in this review."​
     
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