The Fallacy of Fish Oil Part 1 Posted on July 19, 2014, 0 Comments

Why Fish Oil Fails: A Comprehensive 21st Century Lipids-Based Physiologic Analysis by B. S. Peskin

Original Article Found Here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3914521/#sec18title

 

Abstract
The medical community suffered three significant fish oil failures/setbacks in 2013. Claims that fish oil's EPA/DHA would stop the progression of heart disease were crushed when The Risk and Prevention Study Collaborative Group (Italy) released a conclusive negative finding regarding fish oil for those patients with high risk factors but no previous myocardial infarction. Fish oil failed in all measures of CVD prevention—both primary and secondary. Another major 2013 setback occurred when fish oil's DHA was shown to significantly increase prostate cancer in men, in particular, high-grade prostate cancer, in the Selenium and Vitamin E Cancer Prevention Trial (SELECT) analysis by Brasky et al. Another monumental failure occurred in 2013 whereby fish oil's EPA/DHA failed to improve macular degeneration. In 2010, fish oil's EPA/DHA failed to help Alzheimer's victims, even those with low DHA levels. These are by no means isolated failures. The promise of fish oil and its so-called active ingredients EPA / DHA fails time and time again in clinical trials. This lipids-based physiologic review will explain precisely why there should have never been expectation for success. This review will focus on underpublicized lipid science with a focus on physiology.

1. Introduction
The object of this review is to show how there could be no possible expectation of general patient benefit with prophylactic fish oil use. It will be shown that the amount of EPA/DHA from routine fish oil recommendations is 20Xs–500Xs more than the body would naturally produce on its own from alpha-linolenic acid (ALA)—Parent omega-3.

Advances in quantitative analysis have been made in the 21st century which are not yet disseminated in the medical community; that is, the delta-6/-5 enzymes are not impaired in the general patient population, and the amount of EPA/DHA required on a daily basis by the brain is now known to be less than 7.2 mg/day. Neither extremely important fact was known in the 20th century.

Lipid physiology makes the following clear: (a) Marine oil's EPA/DHA spontaneously oxidizes at room temperature and more rapidly at normal body temperature—no level of antioxidants can stop this deleterious effect. (b) Fish oil blunts the insulin response and raises resting blood glucose levels. (c) Fish oil decreases critical prostacyclin (PGI2) in patients with atherosclerosis—a very bad outcome. (d) Fish oil rapidly decreases arterial compliance—increasing “hardening of the arteries.” (e) In contrast to researcher's expectations, fish oil accelerates metastases in animals. (g) Fish oil's EPA/DHA do nothing to increase cellular and tissue oxygenation; to the contrary, marine oils increase inflammation. (h) Marine oil consumption impairs mitochondrial functionality, making it an anti-antiaging substance.

The medical profession is unaware of or is not acknowledging the lipid science unequivocally showing the great harm that marine/fish oil's supraphysiologic amounts of EPA/DHA cause. As will be shown, the claim that prophylactic use of marine oil produces positive patient results is completely counter to 21st century lipid science.

2. Fish Oil Fails Extensively in Clinical Trials, but These Failures Are Often Underpublicized: Three Significant 2013 Fish Oil Failures
Since many medical professionals are under the wrong impression that fish oil incontrovertibly works, it is instructive to make clear there are numerous recent and not so recent marine oil/fish oil failures occurring across all clinical areas. There are more (underpublicized) failures than (supposed) successes. These failures should cause great pause.

Three highly significant fish oil failures occurred in 2013. In May 2013, The Risk and Prevention Study Collaborative Group (Italy) released a conclusive negative finding regarding fish oil for those patients with high risk factors but no previous myocardial infarction. Fish oil failed in all measures of cardiovascular disease (CVD) prevention—both primary and secondary [1]. This study was so conclusive that Eric Topol, MD, Editor-in-Chief of Medscape and Medscape's Heartwire for cardiologists, issued a new directive to patients to stop taking fish oil, that is, long-chain EFA metabolites of EPA/DHA [2]. The July 2013 landmark article published in the Journal of the National Cancer Institute entitled “Plasma Phospholipid Fatty Acids and Prostate Cancer Risk in the SELECT Trial” [3] confirmed prior post-2007 findings of increased prostate cancer risk among men with high blood concentrations of long-chain metabolites of ω-3 fatty acids from fish oil studies [4, 5]. The authors warned, “The consistency of these findings suggests that these fatty acids are involved in prostate tumorigenesis. Recommendations to increase LCω-3PUFA (marine oil's EPA/DHA) intake should consider its potential risks.” The May 2013 trial [6] showed that macular degeneration victims were not helped by fish oil's significant DHA content. The year 2013 was very bad for fish oil findings. Why the failures?

3. Pre-2007 Studies Were Poorly Conducted and Inconsistent with the Science
In a 2012 meta-analysis regarding cardiovascular disease, reviewing 1,007 articles, only 14 studies met the criteria of randomization, double blindness, and placebo control [7]. Clearly, an enormous number of poorly conducted studies in the journals have conclusions that cannot be relied on and are misleading physicians and researchers worldwide. Studies should be used to confirm the physiologic, lipid science, not to be counter to it as many pre-2007 studies were.

In researchers' haste to offer patients a new, effective treatment, fish oil “successes” were highlighted and its failures downplayed. However, post-2007 “studies” of fish oil show significant accumulated failure [8]. When well-controlled studies and experiments are performed, as was done in Harvard Medical School's 1995 experiment giving one group of patients fish oil and a control group olive oil, CVD progression did not lessen with fish oil [9]. Fish oil fails; it has to as the science below confirms.

4. EFAs: Parent Essential Oils (PEOs) and Derivatives
There are only two true 18-chain carbon essential fatty acids (EFAs): linoleic acid (LA) with two double bonds and alpha-linolenic acid (ALA) with three double bonds. Neither can be manufactured in the body; both must come from food.

Longer-chain metabolites are synthesized from LA and ALA. These long-chain metabolites—not essential and often incorrectly termed “EFAs”—are correctly termed “derivatives.” For example, common derivatives of the omega-3 series are EPA (eicosapentaenoic acid) with five double bonds and DHA (docosahexaenoic acid) with six double bonds. To clarify the issue, I term LA and ALA “Parent Essential Oils” (PEOs) or “Parents.” I properly term all of their long-chain metabolites “derivatives.” The body makes these important derivatives from Parents “as needed” in naturally minute amounts. The literature often fails to clearly distinguish these two vastly different substances.

4.1. Most Parents Stay as Parents

A major mistake was made in the 20th century, which misdirected researchers. It was wrongly assumed that the vast majority of “Parents” would be converted into “derivatives.” This did not occur, causing the medical research community to proclaim that there were ubiquitous metabolic deficiencies impacting the delta-6 and delta-5 desaturase enzymes in the general population. This has been shown to be categorically false by advanced 21st century quantitative methods (described later). In humans, no more than one percent (1%) of Parents are naturally converted into derivatives. Fish oil mania wrongly (and hazardously) assumes the converse.

5. Fish Oil Impairs Normal Cellular Physiology: Pathophysiologic Disorders Are Expected
Theoretically (and in clinical experiments) fish oil supplements, in their “normal” although supraphysiologic amounts (calculated below), cause changes in membrane properties that impair oxygen transmission into and through the cell [10]. Physicians and other health professionals often prescribe these supraphysiologic amounts, deleteriously altering phospholipids of cell and mitochondrial membranes.

As will be detailed later, nonfunctional LA-based trans fats, oxidized LA entities, and inappropriate omega-6/omega-3 ratios (caused in part from normally recommended, yet supraphysiologic, marine oil supplementation) are all potential sources of unsaturated fatty acids—in particular, LA (Parent omega-6)—that can disrupt the normal membrane structure, significantly increasing the potential for cancer [11]. All of the supraphysiologic, excess EPA/DHA cannot be beta-oxidized away. Thus a significant amount of the excess will be physiologically incorporated into all cell membranes, detrimentally.

6. Arterial Intima: Endothelial Tissue Comprised of Epithelial Cells—CVD Explained
The innermost lining of arterial intima is endothelial tissue, comprised of epithelial cells containing significant LA, but no alpha-linolenic acid (ALA) [12, 13]. A significant biologic effect of oxidized LDL is its cytotoxic effect on cultured endothelial cells directly lining the arterial wall [14]. Dietary LA becomes adulterated (peroxidized) from food processing (described later) and deposited in arterial intimal cell membranes and leads to abnormal oxidation at the vascular injury site, thus causing injurious inflammation.

In this case, abnormal oxidation, caused by ex vivo radical induced lipid peroxidation (adulteration) of LA, involves formation of a hydroperoxide from LA by abstraction of a hydrogen atom as a radical from the doubly allylic methylene group between the two double bonds, followed by the addition of oxygen, a diradical, to make a hydroperoxide radical, which can then pick up another reactive hydrogen atom, perhaps from another LA molecule, to form the hydroperoxide. This, in turn, may break the O–O bond to form an alkoxide and a hydroxyl radical, which can continue to make more undesirable oxidized products [15]. Therefore, atherosclerosis can be prevented/arrested if endothelial cells remain fully functional [16].

Although lipid peroxidation can be caused by injury to tissue or aging, it does not have to be initiated in this fashion. Furthermore, a bivalent metal ion can cleave the O–O bond; nonfunctionality can occur from the commercial processing of the linoleic oil (LA).

7. Bis-Allylic Bonds: Fish Oil's Spontaneous Oxidation (Rancidity) at Room Temperature and In Vivo
Polyunsaturated fatty acids including LA contain the system HC=CH–CH2–CH=CH. Long-chain fatty acids contain bis-allylic hydrogens whereby the –C=C– units are separated by a single-bonded –C– (carbon) atom. The hydrogen atoms attached to each of these intermediate –C– atoms are called bis-allylic hydrogens and have the lowest C–H (weakest) bond-energies of the fatty acid chain. The weak bond makes them enormously susceptible to attack by reactive oxygen species (ROS) generated elsewhere in the body [17]. Because of the five double bonds in EPA and six double bonds in DPA, these metabolites are highly sensitive to temperature.

In particular, DHA, with its 6 double bonds, contains 5 bis-allylic bonds and is therefore 320 times more susceptible to oxidative attack, that is, becoming rancid, than monounsaturated oleic acid (18 : 1), which has no bis-allylic hydrogens in its chain. A saturated fat membrane containing just 5% DHA (fish oil) is 16 times more susceptible to peroxidative damage [18]. Fish oil's DHA is 7 times more susceptible to peroxidative damage than LA (Parent omega-6), the most significant fatty acid by both weight and functionality in the cell's bilipid membrane. The shifting of the body's antioxidants required to combat this physiologic insult causes a shortage elsewhere. This fact should cause the medical community great concern. Keeping tissue fluid in frigid waters is not a physiologic concern of humans.

7.1. Marine Oils Keep Membranes of Fish Fluid in Frigid Waters

The following underpublicized medical fact goes a long way toward explaining marine oil's tremendous cancer- causing potential in humans. Fatty, cold-water fish (the type we are told is best) live in temperatures as low as 32°F, but warm-water fish may live in 70°F waters and have 14Xs less EPA/DHA content than their cold-water relatives [19]. At normal human physiologic temperatures, fish oil spontaneously becomes rancid (as the above section detailed).

A human placed in ice-cold, frigid waters would suffer hypothermia, freeze, and likely die. Fish do not freeze because they have significantly higher levels of the EFA derivatives EPA and DHA than those in humans.

Our ambient and physiologic conditions are not similar to that of fish. Marine/fish oil researchers did not consider this important fact. EPA/DHA acts as “biological antifreeze” to fish living in frigid waters. Humans do not require such copious amounts because we have an internal temperature of 98.6°F. The deleterious effects when humans consume supraphysiologic amounts of marine oil's EPA/DHA are described next.

8. Primary and Secondary Lipid Oxidation and Hydroperoxides
There is much to know regarding specific lipid oxidation markers. Oxidative rancidity occurs in 3 distinct stages/phases: initiation, propagation, and ultimately termination. During the initiation stage, molecular oxygen combines with unsaturated fatty acids to produce hydroperoxides and free radicals, both of which are very reactive. Heat and light increase the rate of all phases. Then, the products of this stage react with additional lipids to form other reactive chemical species—often termed “autooxidation.” In the final termination (secondary) phase, relatively unreactive compounds are formed, including hydrocarbons, aldehydes, and ketones. Quantitative measure of all phases is required for a complete picture.

8.1. Malondialdehyde (MDA)/p-Anisidine Increases with Fish Oil/Marine Oil

Supplementation with polyunsaturated fatty acids in particular, EPA/DHA, as opposed to saturated fatty acids, results in a statistically significant increase in lipid peroxidation in the plasma and liver. Fish oil ingestion raises levels of extremely harmful malondialdehyde (MDA) [20]: “Ingestion of CLO [cod liver oil] was associated with an increase in MDA excretion in all six subjects. The mean increase of 37.5%, from 24.5 ± 3.5 μg to 34.7 ± 2.5 μg MDA (mean + SEM), was [statistically] significant and CLO ingestion again was associated with an increase in MDA excretion in all subjects. The mean increase of 54.3%, from 31.7 μg to 49.1 μg MDA/sample was highly significant.” Parent omega-6 (LA) undergoes—like all PUFAs—lipid peroxidation, but the amount of MDA produced is much, much lower than that by oxidation of EPA or DHA because MDA production requires at least 3 or more double bonds in a molecule.

The p-anisidine test measures the aldehyde content generated during decomposition of hydroperoxides. It correlates well with volatile substances. Volatile aldehydes and other later-stage aldehydes leave behind a nonvolatile product that the p-anisidine test measures well (via correlation). “Pristine” fish oil can have an allowable p-anisidine value of 19, clearly showing significant secondary stage oxidation [21], whereas a PEO formulation without fish oil is closer to a p-anisidine value of 4—confirming fish oil's substantial inherent propensity to become rancid at room temperature.

8.2. Thiobarbituric Acid Reactive Substances (TBARS) Increase with Fish Oil/Marine Oil

A 2000 study reported in the American Journal of Clinical Nutrition found that plasma TBARS (substances which react to the organic compound thiobarbituric acid and which are a result of lipid peroxidation) were >21% higher after fish-oil supplementation than after sunflower-oil supplementation (containing Parent LA, not derivatives) and 23% higher than after safflower-oil supplementation (containing Parent LA, not derivatives). The article explored the limitations of the various assays available for the measurement of lipid peroxidation in vivo, including the F2-isoprostane assay's inability to provide direct information about the peroxidation of 20:5n-3 (EPA) and 22:6n-3 (DHA) [22]. Fish oil oxidizes in plasma, producing numerous deleterious products. This long-term damaging effect is cumulative.

8.3. Clinical Proof and Verification of Fish Oil's Harmful Oxidation

Regardless of antioxidant level added to the fish oil supplement, rancidity/peroxidation upon ingestion (in vivo) becomes a very significant and problematic issue. Oxidation of EPA leads to generation of a mixture of aldehydes, peroxides, and other oxidation products. Highly polyunsaturated, long-chained EPA and more so with DHA, due to its additional double bond, is readily oxidized at room temperature even in the absence of exogenous oxidizing reagents. Importantly, in vivo, a large increase in tissue and plasma accumulation of fatty acid oxidation products is noted in subjects consuming fish oil even after addition of antioxidant supplements to the diet—this effect strongly suggests extensive oxidation of omega-3 fatty acids such as EPA in vivo. This deleterious effect is true as evidenced by the trial in which a 14% decrease in life expectancy occurred in those animals fed fish oil [23].

In humans and primates such as the monkey, no quantity of in vivo antioxidants will stop EPA/DHA damage as measured by lipofuscin, the peroxidized “age spots.” Lipofuscin was three-fold (3Xs) greater in the livers of monkeys fed fish oil. Furthermore, another measure of oxidative damage, the levels of basal thiobarbituric acid reactive substances (TBARS), was four-fold (4Xs) greater than that of the monkeys fed corn oil with no EPA/DHA. The researchers found that even a ten-fold (10Xs) increase in alpha-tocopherol, a potent antioxidant, was not fully able to prevent the peroxidative damage from fish oil [24].

9. Inflammation and the Cancer Connection
As per the above details, oxidation of marine oil's EPA/DHA is inherently inflammatory. Inflammation is now seen as causal to cancer as it is to CVD: “The connection between inflammation and cancer has moved to center stage in the research arena” [25]. This rewriting of the textbooks comes from one of the world's most renowned cancer researchers, Robert Weinberg of MIT (originator of the term “oncogene”), causing him to revise his leading textbook, The Biology of Cancer (Garland Science, 2006), to reflect this new understanding.

Prior sections detailed how fish oil causes inflammation in vivo because EPA/DHA spontaneously oxidize at room temperature and much more quickly at body temperature. Their harmful hydroperoxide products become incorporated in esterified cholesterol and it is well known in cardiology that oxidized cholesterol causes the inflammation leading to CVD. Increased cancer is expected with increased consumption of marine oils.

The inflammation/cancer connection is supported with the finding that asbestos causes inflammation, reported in 2010 in Medical News Today. “For the past 40 years researchers have tried to understand why asbestos causes cancer. This research emphasizes the role of inflammation in causing different types of cancer” [26, 27].

Inflammation alone, regardless of initiating conditions, accelerates cancer proliferation. Since 2007, cancer researchers understand and acknowledge that the fundamental, prime cause of cancer is inflammation, not genetics [28–30]. A further inflammation/cancer connection was reported in Cancer Epidemiology, Biomarkers & Prevention in 2005, with the statement that “There is a growing body of evidence supporting the role of chronic inflammation with prostate carcinogenesis and thus the associations of transfatty acids with increased inflammatory response may explain their associations with prostate cancer risk” [31]. The SELECT [3] showed that marine oil's DHA was more inflammatory than trans fats.

10. Parent-to-Derivative Amounts and Metabolism
What percentage of PEOs does become converted (naturally) to long-chain metabolites such as EPA and DHA? This important question must be addressed and answered before their correct supplemental dosage (if any) can be determined. This fundamental research was neglected concerning marine oils, which tragically led to recommendations of haphazard supraphysiologic overdoses of marine oil's EPA/DHA.

New, twenty-first century quantitative research from both NIH and USDA shows considerably lesser amounts of natural DHA conversion/usage from ALA than the medical community has been led to believe. These findings will be upsetting to those health professionals recommending fish oil prophylactically. The conversion amount is much less than the medical field assumes: it is less than 5%—often less than 1%—with at least 95% of PEOs staying in Parent form. This singular mistake of assuming very high conversion amounts, whereas in actuality their conversion amounts are extremely low, led to the irrational fish oil mania.

Contrary to wrong dogma, the enzymes that produce PEO derivatives (the delta-6 and delta-5 desaturase enzymes) are not impaired in the vast majority of patients [32]. Conversion of ALA (Parent omega-3) to DHA is unlikely to ever normally exceed 1% in humans [33].

Research at the United States Department of Agriculture's USDA Food Composition Laboratory (2001) reported a natural net conversion rate of a mere 0.046% of ALA to DHA and 0.2% to EPA—not the highly misleading 15% conversion rate that is often quoted [34]. This is a mistake of nearly 2 orders of magnitude (100-fold). In 2009 NIH researchers determined the amount of DHA utilized in human brain tissue to be a mere 3.8 mg ± 1.7 mg/day. Therefore, based on the variance, brain tissue in 95% of all subjects, allowing for variation in brain size, would consume no more than 0.4 mg–7.2 mg of DHA per day [32].

10.1. No Delta-6/-5 Desaturase Widespread Impairment in (Average) Patients

Highly accurate, quantitative experiments were performed showing that both animals and the average healthy person are quite capable of metabolizing adequate amounts of DHA from Parent omega-3 (ALA).

As will be clearly demonstrated, there is no widespread impairment in the typical patient whatsoever; the normal conversion amounts are simply very low. These conversion amounts are extremely small and naturally limited. This mistake often leads to suprapharmacologic recommendations and can potentially overdose patients by factors of 20-fold to 500-fold, depending on specific supplement and amounts prescribed.

Because the body cannot oxidize away these tremendous overdoses of EPA/DHA, they become incorporated into tissue and organs with deleterious effects as confirmed by the skyrocketing increase in all epithelial-based cancers (described later). Supraphysiologic amounts are forced into tissue, causing gross physiologic imbalance and great potential for harm.

An important experiment measuring plasma fatty acids in 62 fire fighters concluded that the consumption of ALA-enriched (Parent omega-3) supplements over a 12-week period elevated levels of long-chain metabolites EPA and DHA. This experiment unequivocally showed the unimpaired effectiveness of ALA conversion from Parent omega-3. The researchers further stated that the general population could achieve the amounts of ALA required to obtain these effects by modifying their diet, ensuring adequate ALA (Parent omega-3) [35].

10.2. Vegans—Consuming No Fish—Produce Sufficient DHA

Even vegetarians consuming little or no fish had acceptable EPA/DHA levels [36]. This is a group that absolutely would be expected to manifest gross neurological abnormalities, including both visual impairment and cognitive impairment, yet there is no clinical evidence of such neurologic and cognitive abnormalities in vegetarians [36, 37].

Confirmation in 2010 showed that vegetarians with an intake of 0.3% DHA compared to fish eaters produced 85% of the EPA levels and 83% of the DHA levels that consumers of fish did. These amounts are within the “normal” ranges [37].

10.3. Rodents Have a 50-Fold Safety Margin: Would Not Humans?

Rats fed a DHA-free but α-LNA (n-3 PUFA) (Parent omega-3) adequate diet naturally produced from Parent omega-3 (ALA) fifty times (50Xs) more DHA than their brains required [38]—an enormous “safety factor.” Certainly, nature would ensure humans the same margin of safety shown to a rodent. This result in an animal species clearly supports highly quantitative 21st century research from the National Institutes of Health (NIH) finding extremely low—yet adequate—natural conversion rates in humans [32].

11. Amounts of EPA/DHA in Fish Oil Supplements: Pharmacological Plasma Overdoses
Given the above analyses, how much EPA/DHA does the typical marine oil/fish oil supplement provide? An average 1,000 mg health-food-grade fish oil capsule contains approximately 180 mg EPA and 120 mg DHA. Pharmaceutical-grade versions contain higher doses. Furthermore EPA [left and right double arrow ] DHA. This is not the case with PEOs. They are unidirectional. The American Heart Association states that those with documented CHD are advised to consume about 1 gm (1,000 mg) of EPA + DHA per day. Is this advice rational? No.

As an example, using the USDA food composition research formulas covered earlier, if patients consumed a supplement of 600 mg of Parent ALA, they would naturally convert it to EPA by no more than the (generous) factor of 0.25% = 1.5 mg EPA and 1.5 mg × 0.63 × 0.37 = 0.35 mg to DHA in patient plasma. Therefore, just one capsule provides the amounts shown in the analysis below, and many people are overdosing even more by taking 2 to 4 fish oil capsules each day, likely in part because the cardiology and heart recommendations are often “EPA + DHA ranging from 0.5 to 1.8 grams per day.” What overdose does this translate to?

11.1. Potential EPA/DHA Overdoses Are Frequent

Potential Overdose equates to the following plasma overdoses: EPA = 180 mg/1.5 mg = 120 times overdose and DHA = 120 mg/0.35 mg = 340 times overdose. These facts should cause great pause and concern. (Technically, a bit more is required for additional metabolic pathways aside from direct tissue incorporation like prostaglandin production, but it is not a significant amount by weight on a daily basis.) The medical community and most physicians and other health professionals may unknowingly be overdosing patients prophylactically with supraphysiologic supplemental amounts of omega-3 derivatives.

12. The Significant Problem: Radical Induced Lipid Peroxidation—Food Processors Require Long Shelf Life
Radical induced lipid peroxidation (adulteration) of omega-6 fats—in particular, LA—is created by food processors' need for long oil life during frying and baking, especially because their use of saturated fats is avoided. Omega-3 fats are never used in cooking; they are far too reactive.

Abnormal peroxidation of the Parent omega-6 oil (LA), therefore, is the core of the EFA-based deficiency. It has nothing to do with marine oils and everything to do with the adulteration of the plant-based Parent essential oil, LA. For example, trans fats—to some extent—are found in all commercial restaurants, supermarkets' prepared food and frozen food sections, and even in fine-dining restaurants' frying oils. The substrate for trans fats is Parent omega-6 (LA). Just 0.5 grams of a 1% trans fat containing adulterated oil (a conservative amount) is very harmful to humans. Even with the FDA's 2014 ban on trans fats, the FDA allows <0.5 grams/serving to be labeled as zero (0). Yet, this apparently negligible amount contains enough trans fats to overpower each cell in the body by a factor of approximately 3,600 [39].

12.1. Cellular Oxygenation Maximized with Unadulterated LA—Parent Omega-6

Marine/fish oils do nothing to promote cellular oxygenation in the mitochondria—this is a key role exclusive to Parent omega-6 (LA) [10, 40]. Marine oils, due to their inherent inflammatory property in vivo, cause the opposite of the desired effect and are therefore deleterious.

12.2. Pathophysiology Effects from Damaged Cell Membranes Caused by Radical Induced Lipid Peroxidation

With functional LA deficiency there is an enormous increase in permeability of epithelial tissue and an increase in capillary fragility, further explaining the pathophysiology of CVD and how it may be prevented [41]. Oxidation of LDL-C causes significant depletion of LA (Parent omega-6) [14]. Because LDL cholesterol is the transport vehicle for PEO delivery into the cell (described below), LDL cholesterol will transport LA into cells, whether the LA is defective or not (such as oxidized or trans entities).

Of great importance is the fact that with ingestion of marine/fish oil (EPA/DHA) there was a corresponding decrease in tissue's LA, causing pathophysiologic deficiency [42].

13. Tissue Incorporation of Dietary Fats is Proportional to Consumption
The concentration in adipose tissue triacylglycerols is roughly proportional to dietary concentration and is now frequently used as a measure of relative dietary intake. It has been long known that the fatty acid composition of the diet can influence membrane fatty acid composition [43, 44].

Fortunately, tissue alteration caused by supraphysiologic amounts of marine oil consumption can be remedied. Once removed, it takes 18 weeks to fully rid patients of the negative effects of fish oil [45].