Part 4  Fats role in CVD  http://healthfully.org/rh/id4.html   (8/23 /15)

Background: Building on Part 1 the cause of cardiovascular disease (CVD) was not dyslipidemia, but rather reactive chemicals damaging LDL within the muscular part of the artery wall and the subsequent immune response which resulted in atherosclerosis (AS).   Part 1 went to list the vital roles of cholesterol and that lowering cholesterol levels does not prevent CVD since it doesn’t prevent atherosclerosis (AS).  Part 2 follows from part 1; it sets out the cholesterol myth (that cholesterol does not cause CVD) and thus using statins to lower cholesterol not only doesn’t prevent CVD or AS, but given the importance of cholesterol and other products of the mevalonate pathway, that disruption by statins of the synthesis of these essential bioactive chemicals is a very bad idea, especially for the elderly.   Part 3 is on the role of carbohydrates through glycation and oxidative products of metabolism that is the leading causal factor for AS and CVD, and an assortment of chronic age-related conditions.  First among the carbohydrates is fructose, which is one half of the disaccharide sucrose.  Fructose in high amounts damages the liver which leads to the development of insulin resistance (IR) and metabolic syndrome (MeS)--how.  We will be exploring the fat myths. 

Saturated Fats are safer than carbohydrates:  in 11 out of 12 studies reviewed in Wikipedia, results did not show a benefit from low fat, or increased ratio of polyunsaturated fats  “A meta-analysis of 21 studies considered the  effects of saturated fat intake and found that Intake of saturated fat was not associated with an increased risk of CHD (coronary heart disease), stroke, or CVD (cardiovascular disease)" Wiki.  Low fat entails more carbs for energy with their negative consequences.  “Indeed, recent prospective cohort studies have not supported any significant association between saturated fat intake and cardiovascular risk.  Instead, saturated fat has been found to be protective. The source of the saturated fat may be important. Dairy foods are exemplary providers of vitamins A and D. As well as a link between vitamin D deficiency and a significantly increased risk of cardiovascular mortality, calcium and phosphorus found commonly in dairy foods may have antihypertensive effects that may contribute to inverse associations with cardiovascular risk.  Meat is another major source of saturated fat. Consumption of processed [luncheon] meats has been associated with coronary heart disease and diabetes mellitus, which may be explained by nitrates and sodium as preservatives “ BMJ 10/22/13.  And it gets worse:  instead endpoint deaths and ischemic events, pharma uses the surrogate endpoint increased serum levels of LDL, Cholesterol, and triglycerides.  However in quality studies the associate is non-existent or nearly so.  “There are no clear health benefits of replacing saturated fats with starchy foods (reducing the total amount of fat we eat). Heart and vascular disease includes heart attacks, angina, strokes, sudden cardiovascular death and the need for heart surgery” the prestigious Cochrane Review.  It get worse, for saturated fats  have been replaced by the unhealthy polyunsaturated fats, and the recommended low-fat diet entails entails more from carbohydrates and thus an increase in sugars, which has produced the health disaster of the Western diet that has cause the obesity, diabetes, and MeS epidemic.  Having said all this, there are important details.  For one, that a high carb diet low on sugar (the traditional diet of Orientals with the high glycemic index white rice and but 14 grams of sugar does not result in an association with CVD; and also for tribes on a high carb paleo-diet.  As pointed out at http://healthfully.org/rc/id23.html the combination of high fructose with glucose (mainly from starches) as a steady diet causes a fatty liver which results in mucking up the metabolic regulatory system.  This and other factors determine risk (see http://healthfully.org/rh/id12.html).  Thus like fats, all carbs are not equal, and lifestyle difference influence risk—click on link.          

.    cis-2-butene

Saturated fats are best, polyunsaturated fats worse:  The truth lies in the details:  one, health science has been kicked under the bus by corporate influence which produces tobacco science and uses its influence in the process and among politicians to promote financial gains.  In particular the agriculture and manufactured food lobbies have shaped government regulations around the world, starting with the US in 1977 and UK in 1983 to recommend cutting the intake of fats by 25% and reducing saturated fats as much as possible on the bogus claim that they cause dyslipidemia (high serum fatty acids and triglycerides) and coronary heart disease (CHD).  For an excellent historical thorough recount of how this happened plus a summation of the benefits of saturated fats, click on the link to Prof. Miller’s lecture (notes are in supplement below).  However saturated fats don’t go rancid:  they are not subject to oxidation on the shelf or in your body.  All the carbon bonds are taken—unlike monounsaturated fats such as the cis and trans-oleic acid shown above and polyunsaturated fats are subject to a much higher rate of oxidation and glycation[2].  This oxidation and glycation is called rancidification.  Rancid fats cannot be safely disposed of because of lack of enzyme for that purpose.  They accumulate in your body and mess up various systems.  Moreover they also in the process of their product give rise to reactive oxygen species (ROS), which cause more damage.  It is to prevent ROS and rancidification that milk fat is very low in polyunsaturated fats (under 5%) and so too for beef fat (<10%).  Evolution has set it up so that milk is low in the unhealthful polyunsaturated fats.  And it gets worse.  Polyunsaturated fats are high in omega-6 fatty acids and they block the healthful  omega-3.  Omega-3 fats (EPA and DHA—not plant ALA)[3] have important immune system functions.  This unhealthful low omega-3 has many chronic conditions relating to the immune system.  Vegetable oils are high in omega-6 and high in polyunsaturated fats.  Nut oils are low in polyunsaturated fats as too are animal sources of fats.  The highly processed vegetable oils are high in polyunsaturated fats.  Moreover to improve their flavor when used with starches, food manufactures buy the partially hydrogenated plant fats.  Like with rancid fats, they too lack enzymes for their disposal, and thus contribute to cardiovascular disease.  These are the best kind. Eat more of them and less carbs.  At the end of this paper this topic is further developed as to diet.     

Basics on fatty acids (fats) and triglycerides:  the dietary significant fats consist of a chain of 4 to 28 carbon molecules with an organic carboxylic acid group on the last carbon.  Fatty acids are derived from triglycerides  or phospholipids.  Each carbon can have 4 single bonds because there are just 4 valance electrons.  If the carbon has a double bond with another carbon it is ”unsaturated”, and “polyunsaturated” with 2 or more double bonds.  Having a double bond entails that there is only a single hydrogen (see stick drawing above) on each of the carbons in the double bond; and if they are on the same side it is called “cis” and if on opposite sides “trans”.  Natural trans-fats occur only in trace amounts.  A few polyunsaturated fatty acids are termed “essential” because they are used to synthesize a number of important bioactive compounds and they come only from food sources.  They are grouped into omega-3 (N-3) and omega-6 (N-6) fatty acids.[4]  Compared to carbohydrates and protein, fatty acids yield the most ATP on an energy per gram basis—9 calories of energy per gram, digestible sugars and starches 4.  Free fatty acids can be converted to triglycerides and stored in adipose tissue.  “They are consumed in the mitochondria to produce ATP through beta oxidation, whereby they generate acetyl-coA, which enters the citric acid cycle, and NADH andFADH2, which are used by the electron transport chain” Wiki.  Fatty-acid catabolism involves three stages. The first stage is beta-oxidation. The second stage is acetyl CoA oxidation to carbon dioxide. The third stage is electron transfer from electron carriers to the electron transfer chain.  α-Oxidation is used for branched fatty acids that cannot directly undergo β-oxidation such as phytanic acid. Fatty acids with very long chains (20 or more carbons) are first broken down to a manageable size in peroxisomes.  Nearly every type of cell can produce its own ATP from fatty acids.  “Muscle cells also contain globules of fat, which are used for energy during aerobic exercise. The aerobic energy systems take longer to produce the ATP and reach peak efficiency, and requires many more biochemical steps, but produces significantly more ATP than anaerobic glycolysis, which produces 2 lactic acid molecules” Wiki.   Because of the lack of glycation type reaction, fats are a preferred ATP source.

Role of dietary fats:  “Knowledge of the nutritional importance of dietary fats has greatly expanded since the time when fats were considered only a source of calories.  We now know that dietary fats supply the essential fatty acids (linoleic and linolenic acid) that are precursors for prostaglandins and they are important components of membrane structures.  Fats also influence cell functions, serve as carriers for fat-soluble vitamins, affect immunological function, and are associated or involved with a number of diseases and disorders” Am Rev Nut, 1984 pgs.339-364.     Though we have heard much about the importance of the omega-3 fatty acid, saturated also have important bodily functions.

Reversal on saturated fats, history of dogma and its decline:  The confusion comes from using the surrogate marker cholesterol level instead of CVD, though it isn’t a causal factor.  This is compounded by the association of the artificially high dietary omega-6 fats (see below section) causes of CVD. Without a mechanism for the association of CVD with saturated fats and the failure to find evidence in a meta-analysis of 21 studies,[5] the current government position on dietary fats (recommending reduction) is in error.  “A hundred years ago 1 in 100 obesity and cardiac heart disease was unknown.  The primary causes of death were enteritis [intestinal infection], TB, pneumonia, and diarrhea.   Heart disease and cancer today account for 75% of death.  There were 500 cardiologists practicing in 1950; there are 39,000 now.  In 1911 Procter and Gambled stared marketing manufactured Crisco, which they marketed it as more healthful than animal fat.  It was hydrogenated vegetable fat.  In 1913 Nikolaj Anitschkow (Russian) fed rabbits cholesterol and showed that it caused atherosclerosis. In 1948 Framingham Study a comprehensive study of a town in Massachusetts funded by the government; it showed that those with elevated cholesterol were more likely to die of heart disease.   Six years later the American Heart Association 6 years later promoted with the prudent diet.  Ancel Keyes Six Country study found the highest percentage of carbohydrates and the lowest of fats in their diet have the lowest incidence of heart disease.  This study was flawed:  Keyes had the data on 22 countries and picked out 6 to support his hypothesis.[6] Moreover, those who have the highest saturated fat in their diet have the lowest rate of coronary disease:  Maasi of Kenya 66% saturated fats; Inuit of Canada, 75%; Rendille tribe of Kenya, 63%; Tokelau of New Zealand, 63%.  Most hunter gatherers groups eat high amounts of saturated fats, up to 93% of their calories.  The Framingham Study[7] reversed its position:  “(1) over the age of 50 there is no increased overall mortality form either high or low serum cholesterol levels, and (2) in people with a falling cholesterol level (over the first 14 years of the study, before statins) for each 1% mg/dl drop in cholesterol there was an 11 percent increase in all-cause mortality (over the next 18 years).  Dr. William Castelli, the third director of the Study, states: “In Framingham, Mass., the more saturated fat one ate, the more cholesterol one ate, the more calories one ate, the lower the person’s serum cholesterol… We found that the people who ate the most cholesterol, ate the most saturated fat, ate the most calories, weighed the least, and were the most physically active” quoted from the lecture to a professional audience by Dr. Donald Miller, professor of Surgery at the Cardiothoracic Division of the University of Washington, July 17,2011, at http://www.youtube.com/watch?v=vRe9z32NZHY.  These statements by Dr. Miller are supported in the journal literature.  Dr. Miller also listed on a slide the importance of saturated fats:

“Cell membranes:  Require (50%) saturated fatty acids to be waterproof and function properly.

Heart:  Prefers saturated long-chain 16-carbon palmitic and 18-C stearic (over carbohydrates) for energy

Bone: needs saturated fats to assimilate calcium effectively

Liver:  Protects from adverse effects of alcohol and medications like acetaminophen

Lung: Lung surfactant, which prevent asthma and other breathing disorders, is composed entirely of 16-C palmitic acid

Hormones:  Function as signaling messengers for hormone production

Immune system:  Saturated fats play an important role here.  They prime white-blood cells to destroy invading bacteria, viruses and fungi, and to fight tumors.  Medium Chain 12-C lauric acid and 14-C mystic acid (in butter) kill bacteria and candida in the gut

Signal satiety:  Promotes satiation through slowing digestion

General health:  Eating saturated fats lowers the consumption of health when compared to polyunsaturated fats which due to high content of omega-6 fat acids reduce the positive immune system effect of omega-3 fatty acids.

Reduces age related chronic conditions which are a result of the monosaccharides obtained through digestion of carbohydrates which damage proteins through the process of glycation. Eating less fats entails replacing them with carbohydrates as a source of energy.  The high carbohydrate Western diet has brought about the sharp rise in obesity, metabolic syndrome, insulin resistance, and type-2 diabetes all of which are strongly statistically associated with an assortment of chronic and fatal conditions.   

Saturated fats:  Saturated fats were linked to CVD by failing to control for the transfats, high N-6 to N-3 ratio and transfats produced through hydrogenation of unsaturated oils.   Though these flaws have been pushed by business, surprising, 22 metastudies found no association of saturated fats with CVD.  If you have any doubt over the venal nature of governments, read about the disjunction between government holdings around the world, read this footnote. [8]  In general, a more reliable way to solve biological question is in the laboratory where analysis reveals the disease causing process, and this is confirmed in animal experiments.  At Scholar.Goolge.com, a search of “rats + saturated fats + cardiovascular disease” had zero studies. Wikipedia also under saturated fats doesn’t have a section show the bio-pathway for causing CVD. The proposed association with elevated LDL is without sound, consistent evidence; moreover, elevated LDL does not promote CVD, though pharma promotes that myth for to sell cholesterol lowering drugs—see cholesterol myth.  The lack of modus operandi based on laboratory experiments is a major reason to question the putative causal connection to CVD.  A high saturated fats diet lowers the consumption of sugars and is low in vegetable oils (lower trans-fats and high levels of n-6), and thus lowers risk for CVD and obesity.  The recommendations of the national health agencies around the world are another example of marketing before science and the politicalization of the guideline process.  It stands in contrast to science:  A meta-analysis of 21 studies considered the effects of saturated fat intake and found that "Intake of saturated fat was not associated with an increased risk of CHD (coronary heart disease), stroke, or CVD (cardiovascular disease)” Wiki. Moreover the main saturated fatty acid from tropical trees (coconut and palm kernel oil), lauric acid is cardiovascular protective because it increases HDL.[9]  Finally “the energy yield from a gram of fatty acids is approximately 9 kcal (37 kJ), compared to 4 k cal/g (17 kJ/g) for carbohydrate, and compared to carbohydrates fatty acids can hold more than six times the amount of energy per unit of storage space.  Put another way, if the human body relied on carbohydrates to store energy, then a person would need to carry 31 kg (67.5 lb) of hydrated glycogen to have the energy equivalent to 4.5 kg (10 lb) of fat” Wiki.  Fats don’t cause glycation.  For these reasons a diet low in (a) fructose, (b) those starches that are quickly absorbed (have high insulin index) and (c) omega-6 and trans-fats, and are high in saturated fats and most starches is the best source for ATP (energy).  Pharma, food industry, and government have done it again:  turned good into bad, and the bad into good, and we the consumers pay with the length and quality of our lives.

Essential fatty acids (EFAs) “are fatty acids that humans and other animals must ingest because the body requires them for good health but cannot synthesize them.  Only two fatty acids are known to be essential for humans: alpha-linolenic acid (an omega-3 fatty acid, N-3) and linoleic acid (LA, an omega-6 fatty acid, N-6).  They are modified to make.  Omega-6 fatty acids are a family of unsaturated fatty acids that have in common a final carbon-carbon double bond in the n-6 position, that is, the sixth bond, counting from the methyl end.  Functions  (The biological effects of the ω-3 and ω-6 fatty acids are mediated by their mutual interactions):

• the classic eicosanoids (affecting inflammation and many other cellular functions)

• the endocannabinoids (affecting mood, behavior and inflammation)

• the lipoxins which are a group of eicosanoid derivatives formed via the lipoxygenase pathway from N-6 EFAs and resolvins from N-3 (in the presence of acetylsalicylic acid, down regulating inflammation)

• the isofurans, neurofurans, isoprostanes, hepoxilins, epoxyeicosatrienoic acids (EETs) and Neuroprotectin D

• They form lipid rafts (affecting cellular signaling)^[4]

• They act on DNA (activating or inhibiting transcription factors such as NF-κB, which is linked to pro-inflammatory cytokine production)” Wiki. 

  “Arachidonic acid is derived from the N-6 linoleic acid and is the precursor in the production of eicosanoids:   

• The enzymes cyclooxygenase and peroxidase lead to prostaglandin H2, which in turn is used to produce the prostaglandins, prostacyclin, and thromboxanes.

• The enzyme 5-lipoxygenase leads to 5-HPETE, which in turn is used to produce the leukotrienes.

• Arachidonic acid is also used in the biosynthesis of anandamide.

• Some arachidonic acid is converted into hydroxyeicosatetraenoic acids (HETEs) and epoxyeicosatrienoic acids (EETs) by epoxygenase” Wiki.

A few of the polyunsaturated fats in the human diet are EFAs. Essential fatty acids play an important role in the life and death of cardiac cells” Wiki.  “Following WWI large-scale production of vegetable oils and the shift to o grain-fed cattle (from grazing cattle) caused a marked increase in the ratio of the omega 6 to 3 oils from 2:1 to 16:1.  Man evolved in a world for which n-6 to n-3 ratio was around 2:1; the gross 20^th century deviation from this ratio has dire consequences.  Proof of this causality is demonstrated both in laboratory analysis and clinical trials, but only when the ratio of N-6 to N-3 is 4:1 or less” A. P. Simopulos. “The actions of the N-3 (omega-3) and N-6 (omega-6) essential fatty acids (EFAs) are best characterized by their  interactions; they cannot be understood separately” Wiki.  They compete for the same receptors during synthesis, see above.  “Some older clinical studies indicate that the ingested ratio of omega-6 to omega-3 (especially linoleic vs alpha-linolenic) fatty acids is important to maintaining cardiovascular health. However, three studies published in 2005, 2007 and 2008, including a randomized controlled trial, found that, while omega-3 polyunsaturated fatty acids are extremely beneficial in preventing heart disease in humans, the levels of omega-6 polyunsaturated fatty acids (and, therefore, the ratios) did not matter” Wiki. 

Omega-3 fatty acid:  “Out of a total of 11, there are three types of omega-3 fatty acids involved in human physiology are ALA (found in plant oils), EPA, and DHA (both commonly found in marine oils)” Wiki.   “Many experimental studies have provided evidence that incorporation of alternative fatty acids into tissues may modify inflammatory and immune reactions and that omega-3 fatty acids in particular are potent  therapeutic agents for inflammatory diseases [AS, Alzheimer’s, arthritis, etc.]  Supplementing the diet with omega-3 fatty acids (3.2 g EPA and 2.2 g DHA [N-3s]) in normal subjects increased the EPA content in neutrophils and monocytes more than sevenfold without changing the quantities of AA [arachidonic acid] and DHA.  Inflammation plays an important role in both the initiation of atherosclerosis and the development of atherothrombotic events. When humans ingest fish or fish oil, the EPA and DHA from the diet partially replace the omega-6 fatty acids, especially AA, in the membranes of probably all cells, but especially in the membranes of platelets, erythrocytes, neutrophils, monocytes, and liver cells.  Inflammation plays an important role in both the initiation of atherosclerosis and the development of atherothrombotic events” 2002 Biomed.  And again pharma’s devil is in the details of this 2002 Biomed article:   the negative results of some studies arise from the failure to limit dietary N-6, which blocks the positive effects of the N-3 supplement.  The same is confirmed in Am J Clin Nutr, Sept 1999, 560—569 and supported by the reduction in diabetes, arrhythmia, hypertension, and cardiac arrest.  Another detail is related to source, with vegetable oil derived N-3, ALA; it has “only about 1/10^th the active of EPA and DHA” Wiki.[10]  I find the evidence convincing for N-3, but there are critics:  Wikipedia, e.g., states “but the health benefits of supplementation appear to be few if any.”  This is contradicted at Wiki. Those who challenge the claims for N-3 rely on studies with the principle source of N-3 coming from vegetable oil and/or a high ratio of N-6 to N-3; who’s right?    

Omega-6 fatty acid and CVD:  “Excess omega−6 fatty acids from vegetables oils interfere with the health benefits of omega−3 fats, in part because they compete for the same rate-limiting enzymes” Wiki .  The disease promotion effects of N-6 come from its “conversion to omega-6 eiscosanoids that bind to diverse receptors found in every tissue of the body…. The eicosanoids from AA [derived from omega 6 linoleic acid] are biologically active in very small quantities and, if they are formed in large amounts, they contribute to the formation of thrombus and atheromas, to allergic and inflammatory disorders, particularly in susceptible people, and to proliferation of cells [tumors].  Thus a diet rich in omega-6 fatty acids shift the physiological state to one that is pro-thrombotic and pro-aggregatory, with increases in blood viscosity, vasospasm, and vasoconstriction and decreased n bleeding time [promotes ischemic events].  The higher the ratio of omega-6/omega-3 fatty acids in platelet phospholipids … caused the higher the death rate from cardiovascular disease [65,100]. Biomed.  Other disease conditions in this article by A. P. Simopulos for which the evidence from laboratory research, clinical trials, and epidemiological studies link the unhealthful 16:1 ratio of N-6 to N-3 to  CVD asthma, breast and colon cancers, arthritis and Alzheimer’s disease.  In Paleolithic and hunter-gatherer times the ratio was 2:1.  N-6 competes with N-3 for cellular receptors.   This attack on omeg-3 follows the pattern of bad pharma ran by its marketing department which promotes profits first.   

 Essential fatty acids and arachidonic acid (AA):  “Arachidonic acid (AA) is a 20-carbon N-6 conditionally essential fatty acid.^[1] It sits at the head of the "arachidonic acid cascade" – more than 20 different signaling paths that control a wide array of bodily functions, but especially those functions involving inflammation and the central nervous system.  Most AA in the human body derives from dietary linoleic acid (another essential fatty acid, 18:2 N-6), which comes both from vegetable oils and animal fats ….  EPA (20:5 N-3) provides the most important competing cascade…. These two parallel cascades [second fat is GLA (18:3 N-6)] soften the inflammatory effects of AA and its products.  Animal studies show that increased dietary N-3 results in decreased AA in brain and other tissues. The reverse is also true – high dietary linoleic acid decreases the body's conversion of α-linolenic acid to EPA.  Low dietary intake of these less inflammatory essential fatty acids, especially the N-3s, is associated with a variety of inflammation-related diseases…. These changes have been accompanied by increased rates of many diseases – the so-called diseases of civilization – that involve inflammatory processes. There is now very strong evidence that several of these diseases are ameliorated by increasing dietary N-3, and good evidence for many others. There is also more preliminary evidence showing that dietary N-3 can ease symptoms in several psychiatric disorders” Wiki.  The totality of evidence support dietary changes with reduced N-6 and N-3 supplementation. 

So what is driving this high ratio:  Among the changes have been the effects of grain fed livestock and chicken.  For example USDA eggs have a ratio of 20 to 1, while Amplelistra farms in Greece the ratio is 3 to 1.3, 2002 in Biomed.  Other sources rich in N-6 include vegetable oils and nuts.  On these grounds it is a good course to increase intake of fish over meats[11] and limit vegetable oils and nuts.  Based on the totality of evidence, a prudent course is to lower the ratio of N-6 to N-3 both by changes in diet and taking fish oil pills high in N-3, which can be obtain quite economically from Costco.  Thus to maximize benefits limit n-6.

Health benefits of Omega-3:  The American Heart Association in a 2003 on intake of omega-3 made finds and issued recommendations.  “Research to date suggests that they {omega-3] can decrease risk for arrhythmia, thrombosis, triglyceride and lipoprotein levels, rate of growth of growth of the atherosclerotic plaque, improve endothelial function [arteries], (slightly) lower blood pressure, and inflammatory responses.  The AHA recommends that all adults eat fish (particularly fatty fish) at least two times a week.  For patients with documented CHD, the AHA recommends ≈1 g of EPA and DHA (combined) per day. … An EPA+DHA supplement may be useful in patients with hypertriglyceridemia. Two to four grams of EPA+DHA per day can lower triglyceride 20% to 40%. 

100 gm portions in gm, omega 3 & 6 fatty acids, omega-3 listed first (blank when under ½ gm  http://nutritiondata.self.com/tools/nutrient-search   (a user friendly resource)

Plant sources of N-3 are mostly ALA, of which about only 1/10^th is converted to the essential EPA and DHA.   Another source on content of oils is at eat real food site. 

Fishes high in Omega-3 p er 85 gm serving in grams:  herring & sardines 1.3-2, mackerel 1.1-1.7, salmon 1.1-1.9, halibut 0.60-1.12, tuna 0.21-1.1, swordfish 0.97, shark 0.84, flounder 0,48

Fatty Acids in Dietary Fats -- Wiki