Chapter 6:  Rancid UFAs membranes MTDD & CAWD:  1, Introduction   2. Science exposing 6 simple, profitable fallacies   3. The value of the omega 3 fatty acids    4. Furan fatty acids and the need for omega 3 and 6 fatty acids   5 Cell membranes    6. Why UFAs become rancid in cell walls    7. Mitochondrial membranes, the assault on UFAs   8.  Mitochondrial repair and prevention systems:  membranes     9.  Linoleic acid, is it essential?    10. Health consequences of rancid fats.    11.  Oxidized cholesterol and lipoproteins as the cause for atheromas?    12. Neurons and oxidized UFAs   13. About the rancid compounds?

UFAs are the second major CC for CAWD.  While it probably won’t cause like fructose, IR, it will both increase the risk factors for CAWD and through MTDD promote IR.  UFAs have  double bonds between carbon on the chain permits reactive electrophilic chemicals to bond there.  This has been known for over a hundred and fifty years.  “Rancidification is the process of complete or incomplete oxidation or hydrolysis of fats and oils when exposed to air, light, or moisture, or by bacterial action, resulting in unpleasant taste and odor…. Animal studies show evidence of organ damage, inflammation, carcinogenesis, and advanced atherosclerosis,’ [6]  Rancid fats are the second most significant cause of MTDD and CAWD (though possible drugs, recreational and pharmaceutical, holds second place.  For those who take more than 4 or more drugs (polypharmacy) [7] would place it in second place, and some of the drugs such as statins and the sedative, taken in sufficient does would place that person in higher risk than a diet high in PUFAs.  Unlike fructose which in sufficient excess causes MTDD, rancid UFAs, merely lower the bar, a lesser CC.  Since rancid UFAs are in mitochondrial membranes, UFAs contribute to the risk for CAWD.  Both UFA and fructose increase the release of ROS from MTD, thereby increasing the rate of damage to MTD.  The words of the surgeon captain UK Thomas Cleave (1906 to 1983) known as Peter among friends. 

I don’t hold the cholesterol view for a moment.  Mankind has been eating saturated fats for hundreds of thousand of years.  For a modern disease to be related to an old-fashioned food is the most ludicrous things I have every heard in my life.  If anybody tells me that eating fat was the cause of coronary disease, I should look at them in amazement.  But when it comes to the dreadful sweet things that are served up… that is a very difference proposition.[8]

 Cleave was a recognized expert on nutrition with books and journal articles.  He called conditions of affluence, the saccharine disease.  Cleave pointed out that the paleo peoples on a high fat diet did experience CVD.  Examples include the Maasai of Kenya and Tanzania whose diet consisted of meat, milk, and blood form cattle, a diet 66% saturated fat.  The Eskimos of Artic whose diet consisted--75% of saturated fat.  The Rendille of the Kaisut Desert of NE Kenya, a diet of camel milk, meat and Banjo which consists of a mixture of camel milk and blood—63% saturated fat.  The Tokelau of three atoll islands off of New Zealand, a diet of fish and coconut—60% saturated fat.  The lesson is that claiming nature functions contrary to evolutionary survival for the village.is tobacco science.  Over and over again, I find tobacco science violating evolution.  

Two reasons for villages, one that most of our primate evolution occurred in the paleo group including villages and they ate saturated fats.  Retain this since I will repeatedly use the evolutionary argument.  Second the village benefits by culling the elderly to make room for younger villagers.  Retain the culling of elderly, for when nature removes a substance from an elderly, such as sex hormones and melatonin it is to cull the elderly (I have yet to find a counter example).  I take those supplements and a high saturated fat diet. 

The content of human milk is for 4.2 gram per 100 of milk, with 3.8 SFA and just 0.6 g PUFAs, and cow’s milk is 69% SFA, 28% MUFA, and 4% PUFA, similar percentages for goat and sheep milk.[9]  Are these mammals making the worse of fats and the least of the best?  When someone tells me that cow’s milk and its extract budder cause coronary disease and type two diabetes, I look at them in amazement.  But when it comes to the dreadful sweet things that make up 20% of calories in the US, that is a different thing. 

          John Yudkin, the leading UK nutritionist (2:1) appeared before the Commission.  “Yudkin blamed heart disease exclusively on sugar, and he was equally adamant that neither saturated fat nor cholesterol played a role.  He explained how carbohydrates and specifically sugar in the diet could induce both diabetes and heart disease, through their effect on insulin secretion…. [He said to McGovern], I believe that high blood cholesterol in itself has nothing whatsoever to do with heart disease. [10] 

This is exactly what I will present in this book, and in this chapter why fructated and oxidized UFAs is a second major CC for CAWD.  Government politics and the Sugar Research Institutes have shortened the lives of every human on the western diet, a reasonable estimate is 8 years and enduring on an average increase in infirmity of 16 years.  A devilish example of how profits come first, tobacco ethics. 

Calling in those holding the opposite views is a common move of blue-ribbon panels; gives the claim of objectivity, but the results were decided before the process began.  The list of critic causes the gullible to believe that the panel came to the table, evaluated both sides, and fairly chose the one supported best by the evidence.  The back door evidence supports that the US government prior decision to support major corporate farms and food manufacturers, and at the same time give cigarettes a free pass on all cancers and CVD.  Excess deaths for those who smoking long-term a pack a day or more is greater for CVD than excess deaths from cancer, including those not exposed such as the pancreas, which is 2.5 times greater than the rate for nonsmokers.[11]  For these smokers every tissues has excess cancers. 

2.      Science exposing 6 simple, profitable fallacies:  One way to win the battle over which fat to eat the KOLs produce tobacco science:  1) PUFAs are better than SFA for cell walls, 2) needed for the essential anti-inflammatory Omega 3, 3) UFA oils are heart healthy.  4) SFAs are toxic:  5) SFAs cause fatty liver, 6) SFAs cause CVD including MI, and 7) SFAs cause diabetes.  The American Heart Association (AHA) recommends under 6% of calories from SFAs, 24% UFAs, and a total 30% of calories from fats, as too most governmental health agencies and all the well-funded organizations similar to the AHA.

For a 1-hour summation of the evidence on good and bad fats, I recommend Dr. Millers lecture:  Enjoy Eating SFAs:  They’re Good for You 53 min.  Donald Miller is Professor of Surgery, Division of cardiothoracic Surgery, University of Washington.  He gave a lecture to audience of physicians, https://www.youtube.com/watch?v=vRe9z32NZHY.  By now you too should be saddened by our system.  There is also a BMJ meta-analysis 21 of 22 articles failed to find an increase-risk in MI with a diet high in SFAs.[21] 

Thanks food manufacturers for protecting us with a low-fat high-sugar diet.  I think of my brother-in-law Ginter with t2d.  He is 13 years my junior and died in 2005 at the age of 49, after 6-years of disability with broken ankle that wouldn’t heal.  He died in the hospital while treating his lower limb, likely of arrythmia; found dead in his room.  His photo at the age of 18 with my wife is on the wall.  He was visiting us in Escondido, CA. 

We all know of dear ones who have suffered with diabetes a progressive condition (not a disease like TB) because the drugs increase insulin resistance and celebrates who suffered, Elea Fitzgerald and Jerry Garcia come to mind.  I still listen to them.

3.    The value of the omega 3 fatty acids: 

                     Furan                              Furan fatty acid 

Roll out the essential healthful PUFAs, omega 3 & 6; however, they aren’t.  It is part of the pitch for PUFAs, another magic supplement.  Over and over again, I find industry generated healthful advice isn’t healthful.  Given the belief in healthful, the size of the sales of omega 3 supplements, and that innocently physician recommend omega 3, it merits a few paragraphs.  Another less in tobacco science. 

I have failed to find strong evidence for biological process producing salubrious intermediates from omega 3.  The claims of a bad ratio of omega 6 to omega 3 is strong on claims, but weak on science.  The lower of inflammation by eicosapentaenoic acid (EPA)[22] is not a vital function and a bad thing for the paleo peoples and us.  Lowering inflammation is like lowering fever, it doesn’t treat the underlying cause, and both inflammation and temperature rise are part of natures way of fight infection. 

Evidence in the population generally does not support a beneficial role for omega−3 fatty acid supplementation in preventing cardiovascular disease (including myocardial infarction and sudden cardiac death) or stroke.  However, omega−3 fatty acid supplementation greater than one gram daily for at least a year may be protective against cardiac death, sudden death, and myocardial infarction in people who have a history of cardiovascular disease.  With the possible exception of breast cancer,^[4][14][15] there is insufficient evidence that supplementation with omega−3 fatty acids has an effect on different cancers. Multiple studies^[14][15] have shown a relationship between α-linolenic acid and an increased risk of prostate cancer.  There is a decreased risk with higher blood levels of DPA, but an increased risk of more aggressive prostate cancer was shown with higher blood levels of combined EPA and DHA.   ALA does not confer the cardiovascular health benefits of EPA and DHAs.[23]

At first, I was a believer the ration of omega 3 to 6 PUFAs is a CC our health disaster (I wasn’t at that time searching for the cause of CAWD, which came 6 years later).  I studied for several days a seminal long article by a researcher for USDA. But with further research several years later as part of my looking into the issues of good and bad fats and business’ pattern promoting cognitive dissonance, this caused me to reverse my acceptance.  The evidence for modus operandi of the omega 3 & 6 proposed by KOLs is far from convincing.  Just because Americans average 16 times as much omega 6 as 3, while some paleo peoples average between 1:1 and 1:4 does not prove that American have a pathogenic imbalance.   “We found no convincing evidence for the efficacy of omega‐3 PUFA supplements in the treatment of mild to moderate AD.” [25]  “α-Linolenic acid is relatively more susceptible to oxidation and will become rancid more quickly than many other oils.” [26]    Slowly since 2009 I had come to realize that claims of healthful substance coming from the highest levels and promoted in the media were nearly always grossly inflated or worse. The fish oil omega-3 acceptance fits that pattern.  This skepticism was confirmed in a 2007 seminal article which found excess omega 3s are toxic:

The furans extinguish the chain reaction that occurs when ROS bond to PUFAs.  The importance of this seminal article by Spiteller calls for more space (and it has some valuable insights concerning lipid peroxidation--see #4 the reactions under heading: 

Now I feel compelled to gripe about the amount of time wasted on industry influence crapolla, and my time wasted in this area on.  Overall, I spend more time on bad science, bad medicine, than on the sound science and net healthful drugs.  It is devilish when profits trumps science and those at the highest place are enablers. 

Cell membrane also known as plasma membrane is a biological membrane that separates the interior of cells from the outside environment or the organelle from the cytosol (the intracellular fluids).  The cytosol is the liquid matrix around the organelles.  Membranes within cells separate and control the movement of substances within an organelle and substances outside the organelle.  Cell membranes are involved in a number of cellular processes, including ion conductivity, storage of molecules, transport of chemicals in and out of cells and organelles either active requiring energy or passive, rigidity of organelle, chemical signaling, cell adhesion, cell potential, o name some key functions. 

Example of major membrane phospholipids and glycolipids;

Phosphyatidylcholine (PtdCho), phosphatidylethanolamine (PtdEtn)

Phosphatidylinositol (Ptdins) phosphatidylserine (PtdSer)

Sphingosine the simplest of sphingolipids

Another family besides phospholipids is that of sphingolipids “a class of lipids containing a backbone of sphingoid bases, a set of aliphatic amino alcohols that includes sphingosine.”[6] There are over a dozen different types, each with a molecule attached to a of saturated carbon but for a double bond on the 1:2 carbs.  They have a number of functions including mechanical stability, chemical resistance on the outer leaf of the membrane, and other functions such as “cell recognition, cascades involving apoptosis, proliferation, restress responses, necrosis, inflammation, autophagy, senescence, and differentiation.” [7]  There are other classes of compounds in cell walls: glycolipids and glycerophospholipids.   

Because of this bonding there are system that restore the walls and reduces the damage caused by ROS, by glycation, by oxidized UFAs, and by the products that they form.  Like everything, it is complex:  membranes are fine tuned for their functions.  Look at the 2^nd illustration above, this transport channel through the membrane, look at the careful folding of the amino acids in the protein.  The folding is controlled by genes, and it is conserved across species:  sequence of amino acids of different species often differ under 5% in their amino acid sequences.  The sequence of amino acids determines the folds.

Plasma membranes are composed of a double layer of lipids (phospholipids, cholesterol, etc.).  They serve as an internal and external barrier.  Membranes in general have a polar hydrophobic head consisting of a phospholipid.   “The phospholipid allows the liquid portion of a biological membrane to be self-assembling and to reseal (repair itself quickly when torn)...  The lipid layer contains about 10% of the externally facing lipid molecules with an attached sugar group (glycolipid). . . integral proteins are firmly inserted in the lipid bilayer . . . of which most are transmembrane and protrude on both sides. ” [8]  For entry into a cell and organelles, there is active transport, simple diffusion, and selective permeability in an aqueous solution.  Macromolecules such as LDL are transported through plasma membranes by bulk transport energized by ATP.  With exocytosis the product from within the cell is encapsulated, fuses with the membrane, and ruptures spilling the sac contents outside the cells.  With endocytosis macromolecules enter the cell contained in a membrane where its contents are digested and/or dispersed.  

There are many variations of functions and specialty molecules to promote functions.  The variations for functions could fill a book and has.  There are over 14 major types of organelles and many more specialty organelles for the 200 tissue types.  The immediate concern here is the deleterious role oxidized UFAs play and the system to mitigate the consequences of oxidation.  The illustrations above speak louder than words. 

This is not a new finding, just ignored:

Lipid peroxidation is the oxidative degradation of lipids. It is the process in which free radicals "steal" electrons from the lipids in cell membranes, resulting in cell damage. This process proceeds by a free radical chain reaction mechanism. It most often affects polyunsaturated fatty acids, because they contain multiple double bonds in between which lie methylene bridges (-CH₂-) that possess especially reactive hydrogen atoms. . .  The toxicity of lipid hydroperoxides to animals is best illustrated by the lethal phenotype of glutathione peroxidase 4 (GPX4) knockout mice. These animals do not survive past embryonic day 8, indicating that the removal of lipid hydroperoxides is essential for mammalian life. Antioxidants such as vitamin C and vitamin E may inhibit lipid peroxidation.[4]

The Via a free radical process, the double bonds of an unsaturated fatty acid can undergo cleavage, releasing the volatile aldehydes and ketones.  Oxidation primarily occurs with PUFAs. For example, even though meat is held under refrigeration or in a frozen state, the poly-unsaturated fat will continue to oxidize and slowly become rancid…. Rancidification can produce potentially toxic compounds associated with long-term harmful health effects concerning advanced aging, neurological disorders, heart disease, and cancer.” [6]  

Lipid peroxidation (LPO) product accumulation in human tissues is a major cause of tissular and cellular dysfunction that plays a major role in ageing and most age-related and oxidative stress-related diseases. The current evidence for the implication of LPO in pathological processes is discussed in this review. New data and literature review are provided evaluating the role of LPO in the pathophysiology of ageing and classically oxidative stress-linked diseases, such as neurodegenerative diseases, diabetes and atherosclerosis (the main cause of cardiovascular complications). Striking evidences implicating LPO in foetal vascular dysfunction occurring in pre-eclampsia, in renal and liver diseases, as well as their role as cause and consequence to cancer development are addressed.[7]

        Autophagy, the orderly dismantling of damage parts is a costly process, so nature supplies us with a large battery of antioxidants as a preventative.  “One important antioxidant is vitamin E. Another important antioxidant is vitamin C. Other anti-oxidants made within the body include the enzymes superoxide dismutase, catalase, and peroxidase.” [8]  I would add to the list glutathione and CoQ10.   So why are not pharma, media, and physicians telling us that antioxidants are important?[9] 

          There are other types of reactions such as with reducing sugars.  When the reducing sugar reacts with an amino acid it is known as the Maillard reaction.[10]  The reactive compounds produce can then react with lipids.  Methylglyoxal is 50,000 more reactive than glucose.  “During the metabolism of carbohydrates, otherwise known as glycolysis methylglyoxal is formed, which is a major precursor to the formation of AGEs.  It is the dicarbonyl compound that can inhibit mitochondrial respiration and other physiological pathways.” [11] Among the reactive chemicals to bond to PUFAs are the reactive nitrogen species.  “Reactive nitrogen species derived from nitric oxide are potent oxidants formed during inflammation that can oxidize membrane and lipoprotein lipids in vivo. . .  several of these species react with unsaturated fatty acids to yield nitrated oxidation products.” [12]  And there are other types of reactive chemicals such as hypochlorous acid.[13] 

The process by which an ROS attaches to a PUFAs in membranes is explained using the anti-Markovnikov’s rule.  This is why PUFAs are pathogenic in cell walls.

Quite simplified, the plasma membrane is bio-molecular leaflet of phospholipids, with hydro-phobic, hydrophilic, and amphipathic substances interdigitated into and interacting with the leaflet by hydrophobic and ionic forces. As shown in figure 3 the plasma membrane lipid bilayer has a hydrophobic mid-zone area. This is the nonpolar medium in which O2 is so soluble. It is also the location of the polyunsaturated fatty acids with their allylic carbon-hydrogen bonds which are so susceptible to free-radical attack (fig. 2). Thus, the normal membrane has the highest concentration of O2 (with its diradical potential) in the hydrophobic mid-zone area, where it has the potential for doing the most damage to the membrane's polyunsaturated fatty acids, i.e., the membrane is poised for disruption.... In the absence of sufficient cholesterol and in the presence of iron and copper complexes, catalysis of free radical reactions would proceed unchecked, disrupting membrane integrity.  And anything that disrupts the normal integrity of the plasma membrane (such as lipid peroxidation) must, as a consequence, also disrupt that membrane's functions, e.g., permeability, transport, barrier capacity, bioenergetics. The ultimate result would be cellular damage, necrosis, cerebral edema, and all the complications thereof.[14]

The article goes on to describe how compromised membranes cause ischemic events.    

Another source of PUFAs is cooking:

The oxidative deterioration of polyunsaturated fatty acids (PUFAs) in culinary oils and fats during episodes of heating associated with normal usage (80-300 degrees C, 20-40 min).  . . . the thermal oxidation of PUFAs is a free radical chain reaction, in which hydroperoxides are generally recognized as the primary major products. Hydroperoxides of PUFAs are easily decomposed into a very complex mixture of secondary products with the decrease in unsaturation.... The results show there is a decrease in unsaturation starting at 150 degrees C and becoming more pronounced at temperatures around 250 degrees C [deep frying temperature is 176 degrees C].[15]  [16]

As Prof. Lustig warns about fructose applies not just to proteins (the Maillard reaction), and the browning process, but fructose and ROS can bond non-enzymatically to UFAs.  “You can brown your meat at 375 degrees for one hour, or you can brown your meat at 98.6 degrees for 75 years.”[17]  “The most apparent feature of the oxidative breakdown of lipids is rancidity, a problem that was recognized centuries and half ago during the storage of seed oils. Rancidity persists as a widespread problem in today's society because of the common use of polyunsaturated fats and seed oils.” [18] Any electron rich molecule will do for an unbound electrophilic chemical.  Sounds like the fructation scenario again.

7.  Mitochondrial membranes, the assault on UFAs:    

The cardiolipin are the darker molecules in the membrane surrounding complexes 1-1V

This brings us full circle, back to the ways in which mainly fructose among the sugars and the compounds made from them that damages the MTD, now we have UFAs and their compounds made from them doing causing MTDD by basically different procedure.  The sugar when effecting the ATP production bonds to the amino acids in complex 1 through 5 and ATP synthase (above illustration, blue is proteins) affecting efficiency and thereby slowing up the metabolism through a feedback system which causes IR.  With the rancid UFAs, they affect the integrity of the membrane which allows the leakage of the protons.  This reduces the production of ATP. The leaked protons also start the chain reaction producing more rancid UFAs both inside and outside the membrane.  The reduction in the rate of ATP like with fructose causing MTDD, this too promotes IR in the liver.  

   Reactive oxygen species (ROS) are chemically reactive chemical species containing oxygen. Examples include peroxides, superoxide, hydroxyl radical, singlet oxygen,^[3] and alpha-oxygen.

          There are a number of ways the MTD reduces the damage done by ROS and other reactive compounds.

8.  Mitochondrial repair and prevention systems:  membranes:  To cope with these reactive chenical  tissues and mitochoindria store vitamin C and beta carotene, CoQ10, superoxided demutase, glutothionene, and other anti-oxidant enzymes.   One major system to nuetralize the chain reaction of UFAs is the incorportion of cardiolipin in MTD inner membrane—see illustration above, which shows the inner membrane, but is lacking the label for the 20% of cardiolipin in inner membrane.  The cardiolipin are the darker molecules in #6 above and in the illustration below. 

Cardioliptin  (CL)

The number of double bonds in the carbon chain is two, some that have 3.

Cardiolipin, CL, (IUPAC name 1,3-bis(sn-3’-phosphatidyl)-sn-glycerol, also known as Calcutta antigen) is an important component of the inner mitochondrial membrane, where it constitutes about 20% of the total lipid composition. It can also be found in the membranes of most bacteria. The name "cardiolipin" is derived from the fact that it was first found in animal hearts. It was first isolated from beef heart in the early 1940s.^[1] In mammalian cells, but also in plant cells, cardiolipin (CL) is found almost exclusively in the inner mitochondrial membrane, where it is essential for the optimal function of numerous enzymes that are involved in mitochondrial energy metabolism…. In eukaryotes such as yeasts, plants and animals, the synthesis processes are believed to happen in mitochondria...  Complex IV has been shown to require two associated CL molecules in order to maintain its full enzymatic function. 

This why variety of functions and the consequences when compromised explain why cardiolipin is widely preserved, including plants, bacteria, fungus, and vertebrates.

Showing CL’s function in the outer membrane; it can trigger apoptosis

CL also functions as a proton trap in oxidative phosphorylation mainly in complex IV & V. It is essential for MTD proper functions and is part of the system for prolonging the duration of optimal functions of the MTD. While the antioxidants play a vital role in reducing the damage from reactive chemicals, CL has many other functions. One other is the Furan fatty acids.  

9.  Linoleic acid, is it essential?:  It is an omega 6 fatty acids with 2 double bonds at the 9-10 and 11-12 carbons.  It is the most common fat in seed oils, 75% in safflower oil, 66% in sunflower, 59% in corn oil, 54% in cottonseed oil, 51% in soybean oil, 21% canola oi, 10% in olive and palm oil[21], and 2% in butter and coconut oil.

What is the evidence for essential? and how essential?  Is this another part of the healthful UFAs and harmful saturated claims.  “The consumption of linoleic acid is vital to proper health, as it is an essential fatty acid.^[15] In rats, a diet deficient in linoleate (the salt form of the acid) has been shown to cause mild skin scaling, hair loss,^[16] and poor wound healing.”  ^[22]  This is because oleic acid is converted to omega 3, and the shortage is only created in laboratory experiments, not in the real world.    

Replacing SFAs with linoleic acid ((18:2 cis 9, 12) increases death rate from CVD.

Objective:  To evaluate the effectiveness of replacing dietary saturated fat with omega 6 linoleic acid, for the secondary prevention of coronary heart disease and death Results:  The intervention group (n=221) had higher rates of death than controls (n=237) (all cause 17.6%v11.8%, hazard ratio 1.62 (95%confidence interval 1.00 to 2.64), P=0.05; cardiovascular disease 17.2%v11.0%, 1.70 (1.03 to 2.80), P=0.04; coronary heart disease 16.3%v10.1%, 1.74 (1.04 to 2.92), P=0.04). Clinical benefits of the most abundant polyunsaturated fatty acid, omega 6 linoleic acid, have not been established. In this cohort, substituting dietary linoleic acid in place of saturated fats increased the rates of death from all causes, coronary heart disease, and cardiovascular disease[23]

I hear the linoleic acid lubricating the cash register. 

9.  Neurons:  Because of the reactive chemical leaked in the MTD their membranes are a target, and because of the high level of lipids in axons of neuron, they too are above the norm vulnerable to reactive chemicals:

The outer limiting membrane of cells and membranes of subcellular organelles, e.g., mitochondria, liposomes, peroxisomes, etc., are generally rich in PUFA and their protection from oxidation is essential for the optimal function and survival of the cell. In addition to lipids, cell membranes also contain proteins in varying amounts depending on the unique physiology of the membrane. Thus, the inner mitochondrial membrane, because of its high density of respiratory complex proteins, contains only 20% lipids; this is also the case with chloroplast thylakoid membranes. In contrast, the myelin sheath surrounding axons are up to 80% lipid. Due to the differences in the percentage of lipids in membranes, they are subjected to different degrees of peroxidation.[1]

          This brings us back to other CCs for MTDD and the downstream contributions of diminished heal processes as a result of RATP and RRAP which will be covered Section 3, 4, and 6.  It is not just melatonin but general poor maintenance schedule and others system stressing the neurons.   What occurs to neuron, the types of assaults, they occur to every cell in the body, with the greatest stress placed upon those that are the most metabolically active and least replaced.  Many of the neurons are never replaced.   Most of those essential tissues types, depending on their functions and their system affording protection, are at increased risks.  The following 3 sections add details and consequences.   

10.   What about rancid fats?

          Like so much what is of relevant for health isn’t a concern for researchers:  I entered into “google.scholar.com “Rancid fat metabolism, and out of the first 50 articles listed, just one; it was as though I entered Greek in the search engine. What happens to for example the dicarbonyl bonding to lipids?  However, there are extensive article under dicarbonyl, lipids because over 50 years ago they were being investigated mainly as products deep frying with vegetable oils.  But I haven’t found articles on how the body handles the many different dicarbonyls once formed and bonded to proteins and lipids.  I was familiar with that issue in 1969 of them forming from heating UFAs.    

There are two area in which FFAs can be prepared for metabolism in the Krebs cycle, the outer area of the MTD and also in the ER.  The process starts for both areas with the TG converted to FFA in the cytosol or in the ER.  Next acyl-CoA attaches to the FFA. 

When transported into the mitochondria outer area, a series of reactions occur which lop off 2 carbons from the chain, and to which are attached to an acyl-CoA and carnitine.  The carnitine is essential for transport into the inner membrane area (crystae) of the MTD.  In the process of passing through the inner membrane the carnitine is removed.  In the crystae the 2-carbon chain attached to the acyl-CoA enters the Krebs cycle. 

The same series of reactions can occur in the ER resulting in 2 carbon chain attached to an acyl-CoA for transport into the MTD.  There inside the MTD carnitine attaches for transport of the acyl-CoA into the inner membrane area.  In that transport process the carnitine is removed.  The acyl-CoA with 2 carbons is metabolism in the Krebs cycle.   

The UFA can be modified by reactive chemicals.  This may occur in 4 ways:  hydrolytic, oxidative, microbial, and by an assortment of reactive chemicals that haven’t been quenched.[4]  

  Dicarbonyl                                                Methylglyoxal

Dicarbonyl is a molecule containing two carbonyl group (C=O). “The 1,2‐dicarbonyl compounds glyoxal, methyl glyoxal and diacetyl which are known to be mutagens without metabolic activation in the Salmonella typhimurium TA100 system, were detected in autoxidised edible oils (sesame, safflower and sardine oil).” [5] “Advanced glycation end products (AGEs) are proteins or lipids that become glycated after exposure to sugars. AGEs are prevalent in the diabetic vasculature and contribute to the development of atherosclerosis.” [6] 

“During the metabolism of carbohydrates, otherwise known as glycolysis, methylgloyoxal (MG) is formed.  MG is a major precursor to the formation of AGEs. . . . MG is more reactive than glucose, fructose, and even the highly reacative ribose in creating AGEs.[7]  Given what has gone before it isn’t just proteins, but also UFA that are targets.  

Proteins that function of mitigate the damage of UFAs outside the membrane I haven’t found.  This  is one of the reasons given that there are several proteins which function as receptors for advanced glycation endproducts, called “RAGE”.  “RAGE exists in the body in two forms: a membrane-bound form known as mRAGE, and a soluble form, known as sRAGE. mRAGE has three domains, and sRAGE has only the extracellular domain. sRAGE is either the product of alternative splicing or the product of proteolytic cleavage of mRAGE.” [8]  “Dicarbonyls, which are formed during glycolysis, lipid oxidation, or protein degradation, include glyoxal, methylglyoxal, and 3‐deoxyglucosone and are regarded as major precursors of AGEs. . . . These dicarbonyls not only fuel the AGE pool in living organisms but also evoke carbonyl stress, which may contribute to the carbonylative damage of carbohydrates, lipids, proteins, or DNA.” [9] 

This is a continuation of the topic in 2:4, 4, 5, and 6 as caused by fructose and focused upon bonding to proteins, here it is on UFAs. The net result is that fats are a significant CC for MTDD and thus CAWD.

9.  Linoleic acid, is it essential?:  It is an omega 6 fatty acids with 2 double bonds at the 9-10 and 11-12 carbons.  It is the most common fat in seed oils, 75% in safflower oil, 66% in sunflower, 59% in corn oil, 54% in cottonseed oil, 51% in soybean oil, 21% canola oi, 10% in olive and palm oil[1], and 2% in butter and coconut oil.

What is the evidence for essential? and how essential?  Is this another part of the healthful UFAs and harmful saturated claims.  “The consumption of linoleic acid is vital to proper health, as it is an essential fatty acid.^[15] In rats, a diet deficient in linoleate (the salt form of the acid) has been shown to cause mild skin scaling, hair loss,^[16] and poor wound healing.”  ^[2]  This is because oleic acid is converted to omega 3, and the shortage is only created in laboratory experiments, not in the real world.    

Replacing SFAs with linoleic acid ((18:2 cis 9, 12) increases death rate from CVD.

Objective:  To evaluate the effectiveness of replacing dietary saturated fat with omega 6 linoleic acid, for the secondary prevention of coronary heart disease and death Results:  The intervention group (n=221) had higher rates of death than controls (n=237) (all cause 17.6%v11.8%, hazard ratio 1.62 (95%confidence interval 1.00 to 2.64), P=0.05; cardiovascular disease 17.2%v11.0%, 1.70 (1.03 to 2.80), P=0.04; coronary heart disease 16.3%v10.1%, 1.74 (1.04 to 2.92), P=0.04). Clinical benefits of the most abundant polyunsaturated fatty acid, omega 6 linoleic acid, have not been established. In this cohort, substituting dietary linoleic acid in place of saturated fats increased the rates of death from all causes, coronary heart disease, and cardiovascular disease[3]

I hear the linoleic acid lubricating the cash register. 

  10.  Health consequences of rancid fats:  The experimental literature on rats as to health consequences is thin.[4]  Rats fed rancid oil 15 to 20%, they all died within 3 weeks  Found was diarrhea, “the occurrence of large livers, kidneys, and adrenals, and small spleens and thymuses.” [5]  The long list of products formed by aerated heating to create rancid fats includes reactive aldehydes and the polymerization of fats.

11  Oxidized cholesterol and lipoproteins as the cause for atheromas?  The autopsy

evidence for bacteria in the intima media causing atheroma goes back over 100 years[6]  Most telling is that fats and cholesterol amount to between 7 and 22% of the contents of an atheroma.  The 1974 summation article on atherosclerosis confirmed the content of fat and cholesterol as being minor.  These are prima facia reasons, along with the failure of statins and other cholesterol lowering drugs to reduce ischemic events (subtract FRUB).  The B5 and S5 explain ischemic events through the diminished functioning of the immune system and autophagy and the down-stream other major CCs in Section 4.  Why aren’t the LSPs having their cholesterol and lipoproteins oxidized?  Or could it be that the oxidized theory is wrong?  The quality Framingham Study of over 50 years found that , those with the highest 20% of cholesterol live the longest. 

Oxysterol are enzyme directed derivatives of cholesterol which “play important roles in various biological processes such as cholesterol homeostasis, lipid metabolism, apoptosis, autophagy and prenylation of proteins.” [7]

Cholesterol

Oxysterols are oxygenated derivatives of cholesterol that are intermediates or even end products in cholesterol excretion pathways. Because of their ability to pass cell membranes and the blood-brain barrier at a faster rate than cholesterol itself, they are also important as transport forms of cholesterol. In addition, oxysterols have been ascribed a number of important roles in connection with cholesterol turnover, atherosclerosis, apoptosis, necrosis, inflammation, immunosuppression, and the development of gallstones. According to current concepts, oxysterols are physiological mediators in connection with a number of cholesterol-induced metabolic effects. However, most of the evidence for this is still indirect, and there is a discrepancy between the documented potent effects of oxysterols under in vitro conditions and the studies demonstrating that they are of physiological importance in vivo.[8]

This article indicates that the fireman has a function.  Oxysterols have a long history, and evolution has developed receptors for their functions.[9]  So far there has been identified 11 oxysterol receptors.  Could the oxidized cholesterol have a function by design, like the immune system’s use of hydrogen peroxide to destroy bacteria? 

Other articles show oxidation of LDL isn’t a demon, it has an immune function. 

Sixty years ago, researchers discovered that the lipoproteins participate in our immune system by binding and inactivating bacteria, viruses, and their toxic products.  The lipoprotein immune system may be particularly important work immediately and with great efficiency.  There are many ways to demonstrate it.... In the laboratory it has been shown that human LDL is able to inactivate more than 90% of the most toxic bacterial products.[10]

This function of LDL ties in well with the finding of bacteria in atheroma, which first made the literature over 100 years ago based on autopsy studies of ruptured plaque (autopsy study).  This function of LDL explains in part why endothelial cells actively transport through their receptor’s LDL into the artery walls: to mop up toxins from bacteria and to promote cell building follow apoptosis brought on by bacteria in the artery walls. 

          I suspect that the oxidized theory is an attempt to deflect the fact that the level of serum cholesterol is NOT associated with atherosclerosis but for by FRUB (See Uffe Ravnskov, Atherosclerosis caused by high cholesterol? at http://healthfully.org/rl/id5.html).  Since there is no convenient lab test for oxidized sterols,[13] the testing for serum cholesterol is a profitable surrogate. 

There is strong evidence that the bacteria within the artery wall are responsible for both the formation of plaque and modified LDL.  For those who wish to get started on this topic, I recommend looking at the articles pasted at http://healthfully.org/rl/id8.html and related article at the /rl2, ‘rl5, /rl9, /rl1 and /rl10.  The topics of pathogens, atherosclerosis, lipid hypothesis, and drugs to lower cholesterol is fit for books, and there are over a dozen quality ones in print.  It is too off course for me to continue here. Ravnskov,s and Calpo’s[14] are the best I have read on the lipid myth, see appendix.   

          Again, we have an example of industry Harpies snatching medical science from the table and depositing crapolla.  I have saved the scape-goat, trans-fats for the next chapter (2:7).  A scape-goat for UFAs, and the US regulation is Swiss cheese.  The sum total of the prima facie evidence entails that I move on to neuron. 

12.  Neurons: 

Most neurons are very long lived and some are very long.[15].  Because of the reactive chemical leaked in the MTD, cell membranes are a target, and because of the high level of lipids in axons of neuron, they are above the norm vulnerable to reactive chemicals:

The outer limiting membrane of cells and membranes of subcellular organelles, e.g., mitochondria, liposomes, peroxisomes, etc., are generally rich in PUFA and their protection from oxidation is essential for the optimal function and survival of the cell. In addition to lipids, cell membranes also contain proteins in varying amounts depending on the unique physiology of the membrane. Thus, the inner mitochondrial membrane, because of its high density of respiratory complex proteins, contains only 20% lipids; this is also the case with chloroplast thylakoid membranes. In contrast, the myelin sheath surrounding axons are up to 80% lipid. Due to the differences in the percentage of lipids in membranes, they are subjected to different degrees of peroxidation.[16]

          This brings us back to other CCs for MTDD and the downstream contributions of diminished heal processes as a result of RATP and RRAP which will be covered Section 3, chapters 4, and 6.  It is not just less melatonin but general poor maintenance schedule and others system stressing the neurons.  What occurs to neuron, the types of assaults, they occur to every cell in the body, with the greatest stress placed upon those that are the most metabolically active and least replaced.  Most of the neurons are never replaced.   Fructation and rancidification are the major CCs for CAWD.      

13.   About the rancid compounds:

There are two area in which FFAs can be prepared for metabolism in the Krebs cycle, the cytosol and mostly in its ER regions.  Next acyl-CoA attaches to the FFA.  However, with rancid fats they don’t enter either reaction, they aren’t metabolized.  For example, cottonseed oil made rancid by heating to 225 degrees centigrade produces “nonurea adduct-forming monomers and dimers were formed which were toxic to rats.  Analyses showed that the toxic fractions contained moderate amounts of carbonyl and hydroxyl and that they contained unsaturation difficult to remove by hydrogenation. Cyclic structures appeared to be present in the dimer fraction. The production of nonurea adducting monomers and dimers is associated with polymerization and other reactions of linoleic acid.”[20]  Diminished weight of spleen, and increased of the kidneys, liver, and thymus have been observed.[21] 

When fats are transported into the mitochondria outer area, a series of reactions occur which lop off 2 carbons from the chain, and to which are attached to an acyl-CoA and carnitine.  The carnitine is essential for transport into the inner membrane area (cristae) of the MTD.  In the process of passing through the inner membrane the carnitine is removed.  In the cristae of the MTD, the 2-carbon chain attached to the acyl-CoA enters the Krebs cycle. 

The same series of reactions can occur in the ER resulting in 2 carbon chain attached to an acyl-CoA for transport into the MTD.  There inside the MTD carnitine attaches for transport into the inner membrane area.  In that transport process the carnitine is removed.  The acyl-CoA with 2 carbons is metabolism in the Krebs cycle.  

The UFA can be modified by reactive chemicals (ROS).  This may occur in 4 ways:  hydrolytic, oxidative, microbial, and by an assortment of reactive chemicals that haven’t been quenched.[22] 

  Dicarbonyl                                                Methylglyoxal

Dicarbonyl is a molecule containing two carbonyl group (C=O). “The 1,2‐dicarbonyl compounds glyoxal, methyl glyoxal and diacetyl which are known to be mutagens without metabolic activation in the Salmonella typhimurium TA100 system, were detected in auto-oxidised edible oils (sesame, safflower and sardine oil).” [23] “Advanced glycation end products (AGEs) are proteins or lipids that become glycated after exposure to sugars. AGEs are prevalent in the diabetic vasculature and contribute to the development of atherosclerosis.” [24] 

“During the metabolism of carbohydrates, otherwise known as glycolysis, methylyglyoxal (MG) is formed.  MG is a major precursor to the formation of AGEs.... MG is more reactive than glucose, fructose, and even the highly reactive ribose in creating AGEs.” [25]  Given what has gone before it isn’t just proteins, but also UFA that are targets.   

There are several proteins which function as receptors for advanced glycation endproducts, called “RAGE”.  “RAGE exists in the body in two forms: a membrane-bound form known as mRAGE, and a soluble form, known as sRAGE.  mRAGE has three domains, and sRAGE has only the extracellular domain. sRAGE is either the product of alternative splicing or the product of proteolytic cleavage of mRAGE.” [26]  “Dicarbonyls, which are formed during glycolysis, lipid oxidation, or protein degradation, include glyoxal, methylglyoxal, and 3‐deoxyglucosone and are regarded as major precursors of AGEs.... These dicarbonyls not only fuel the AGE pool in living organisms but also evoke carbonyl stress, which may contribute to the carbonylative damage of carbohydrates, lipids, proteins, or DNA.” [27]   The net result is that UFAs are a significant CC for MTDD and thus CAWD.

Rossell, JB, B King, et al Feb 1985, Composition of oils “Palm kernel and coconut oils both contain about 47% lauric acid.”

Sleiman, Eama, Jeffrey Henry, et al Jun 2016, Exercise promotes the expression of brain derived neurotrophic factor (BDNF) through the action of the ketone body β-hydroxybutyrate

 Most plants use toxic chemicals a defense to promote survival.  They don't have a dinner sign, Eat Here! The exception are some fruits which use animals and insects to spread the seed. 

An example of toxic chemicals is the family of lectins. Cooking and fermentation are two ways humans get around toxicity. Another is eating moderate amount of one type of plant, A steady diet of Rhubarb would prove deadly, as it does to rabbits and insects.  

A common toxin is the family of lectins, found in beans and other plants: