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    <head><title>The Great Fish Oil Experiment</title></head>
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        <h1>
            The Great Fish Oil Experiment
        </h1>

        Reading medical journals and following the mass media, it's easy to get the idea that fish oil is something any
        sensible person should use. It's rare to see anything suggesting that it could be dangerous. During the recent
        years in which the U.S. government has gone from warning against the consumption of too much of these omega-3
        oils
        <em>("to assure that the combined daily intake of two fatty acids that are components" "(i.e., eicosapentaenoic
            acid (EPA) and docosahexaenoic acid (DHA)) would not exceed 3 grams per person per day (g/p/d)")</em> to
        sponsoring biased industry claims, there has been considerable accumulation of information about the dangers of
        fish oils and omega-3 fatty acids. But there has been an even greater increase in the industry's promotional
        activities. The US government and the mass media selectively promote research that is favorable to the fish oil
        industry. The editorial boards of oil research journals often include industry representatives, and their
        editorial decisions favor research conclusions that promote the industry, in the way that editorial decisions in
        previous decades favored articles that denied the dangers of radiation and reported that estrogen cures almost
        everything. Marcia Angell, former editor of the NEJM, has observed that the "significant results" reported in
        published studies can be properly interpreted only by knowing how many studies reporting opposite results were
        rejected by the editors. One way to evaluate published studies is to see whether they tell you everything you
        would need to know to replicate the experiment, and whether the information they provide is adequate for drawing
        the conclusions they draw, for example whether they compared the experimental subjects to proper control
        subjects. With just a few minimal critical principles of this sort, most "scientific" publications on nutrition,
        endocrinology, cancer and other degenerative diseases are seen to be unscientific. In nutritional experiments
        with fish oil, controls must receive similar amounts of vitamins A, D, E, and K, and should include fat free or
        "EFA" deficient diets for comparison. In declaring EPA and DHA to be safe, the FDA neglected to evaluate their
        antithyroid, immunosuppressive, lipid peroxidative (Song et al., 2000), light sensitizing, and antimitochondrial
        effects, their depression of glucose oxidation (Delarue et al., 2003), and their contribution to metastatic
        cancer (Klieveri, et al., 2000), lipofuscinosis and liver damage, among other problems. <hr />
        <hr />
        <hr />

        "Houston-based Omega Protein Inc.'s bottom line may get a little fatter. The publicly traded company, which
        produces an Omega-3 fatty acid product called OmegaPure, has signed an agreement to provide its fish oil in
        school lunches in 38 school districts in South Texas beginning this month. The 500-person company, which has
        ties to former President George Bush's Zapata Corp., will distribute the product through an agreement with
        Mercedes-based H&amp;H Foods. Although the dollar amount of the contract between Omega Protein and H&amp;H Foods
        hinges on future sales, the company is poised to cash in as school administrators and parents refocus their
        attention on the nutritional content of student diets. Omega Protein President and CEO Joseph von Rosenberg says
        the company's recent investment of $16.5 million for a fish oil refinery in Reedville, Va., scheduled for
        completion in May, and an increased awareness of the benefits of Omega-3 in human food, positions Omega to
        capitalize on predicted demand." Jenna Colley Houston Business Journal

        <hr />
        <hr />
        <hr />

        Andrew Weil was on the radio recently recommending DHA (usually found in fish oil*) to treat depression, and I
        think that means that a lot of people are buying it and eating it. A few years ago the government declared that
        it was "generally regarded as safe" and approved its use in baby formula, and a few months ago Texas school
        districts contracted with Omega Protein (which grew out of the Bush family's Zapata Corporation) to provide
        menhaden fish oil for school lunches. Between the 1950s and the 1970s, people were assured that eating
        polyunsaturated seed oils would protect them against heart disease. There's no evidence that the bad outcome of
        that campaign decreased the gullibility of the public. They are happily joining in the latest public health
        experiment.<p></p>

        <p>
            <em>*Weil recommends eating "oily fish"--"wild Alaskan salmon, mackerel, sardines, or herring"--. "If you do
                take supplements, fish oil is a better source of DHA than algae"
            </em>
            When a group of people in government and industry decide on a policy, they can use carrots (good jobs,
            grants, and prestige) and sticks (loss of jobs and grants, organized slander, and worse) to make their
            guidelines clear, and most people will choose to follow those cues, even if they know that the policy is
            wrong. Historically, policy makers have told the public that "radiation is good for you," "estrogen will
            make you fertile (or safely infertile) and feminine and strong and intelligent," "starchy foods will prevent
            diabetes and obesity," "using diuretics and avoiding salt will make pregnancy safer," and that the
            polyunsaturated fatty acids are "nutritionally essential, and will prevent heart disease."

            <strong><em> </em></strong>The original "essential fatty acids" were linoleic, linolenic, and arachidonic
            acids. Now that the toxic effects of those are coming to be recognized, new "essential fatty acids," the
            omega-3 fatty acids, including those with long chains, found in fish oils, are said to make babies more
            intelligent, to be necessary for good vision, and to prevent cancer, heart disease, obesity, arthritis,
            depression, epilepsy, psychosis, dementia, ulcers, eczema and dry skin. With just a normal amount of vitamin
            E in the diet, cod liver oil is certain to be highly oxidized in the tissues of a mammal that eats a lot of
            it, and an experiment with dogs showed that it could increase their cancer mortality from the normal 5% to
            100%. Although fish oils rapidly destroy vitamin E in the body, some of them, especially the liver oils, can
            provide useful vitamins, A and D. In studies comparing fish oil diets with standard diets, these nutrients,
            as well as any toxins besides fatty acids (Huang, et al., 1997; Miyazaki, et al., 1998) in either type of
            oil, should be taken into account, but they seldom are.
        </p>
        <p>
            Despite the nutritional value of those vitamins, fish oils are generally much more immunosuppressive than
            the seed oils, and the early effects of fish oil on the "immune system" include the suppression of
            prostaglandin synthesis, because the more highly unsaturated long chain fats interfere with the conversion
            of linoleic acid into arachidonic acid and prostaglandins. The prostaglandins are so problematic that their
            suppression is helpful, whether the inhibition is caused by aspirin or vitamin E, or by fish oil.
        </p>

        <p>
            Some of the important antiinflammatory effects of fish oil result from the oxidized oils, rather than the
            unchanged oils (Sethi, 2002; Chaudhary, et al., 2004). These oils are so unstable that they begin to
            spontaneously oxidize even before they reach the bloodstream.
        </p>
        <p>
            In experiments that last just a few weeks or months, there may not be time for cancers to develop, and on
            that time scale, the immunosuppressive and antiinflammatory effects of oxidized fish oil might seem
            beneficial. For a few decades, x-ray treatments were used to relieve inflammatory conditions, and most of
            the doctors who promoted the treatment were able to retire before their patients began suffering the fatal
            effects of atrophy, fibrosis, and cancer. (But a few people are still advocating x-ray therapy for
            inflammatory diseases, e.g., Hildebrandt, et al., 2003.) The fish oil fad is now just as old as the x-ray
            fad was at its peak of popularity, and if its antiinflammatory actions involve the same mechanisms as the
            antiinflammatory immunosuppressive x-ray treatments, then we can expect to see another epidemic of fibrotic
            conditions and cancer in about 15 to 20 years. Around 1970 researchers reported that animals given fish oil
            in their food lived longer than animals on the standard diet. Alex Comfort, who was familiar with the
            research showing that simple reduction of food intake increased longevity, observed that the animals were
            very reluctant to eat the food containing smelly fish oil, and were eating so little food that their
            longevity could be accounted for by their reduced caloric intake. Even when "fresh" deodorized fish oil is
            added to the diet, its spontaneous oxidation before it reaches the animal's tissues reduces its caloric
            value. Without antioxidants, fish oil is massively degraded within 48 hours, and even with a huge amount of
            antioxidant there is still considerable degradation (Gonzalez, 1988; Klein, et al., 1990). Fish oil has been
            used for hundreds of years as varnish or for fuel in lamps, and the fatty fish have been used as fertilizer
            and animal feed, and later the hydrogenated solid form of the oil, which is more stable, has been used in
            Europe as a food substitute for people. When whale hunting was reduced around 1950, fish oil was substituted
            for whale oil in margarine production. Like the seed oils, such as linseed oil, the fish oils were mostly
            replaced by petroleum derivatives in the paint industry after the 1960s.
        </p>
        <p>
            Although by 1980 many animal diseases were known to be caused by eating oily fish, and the unsaturated oils
            were known to accelerate the formation of the "age pigment," lipofuscin, many "beneficial effects" of
            dietary fish oil started appearing in research journals around that time, and the mass media, responding to
            the industry's public relations campaign, began ignoring studies that showed harmful effects from eating
            fish oil.
        </p>
        <p>
            When reviewers in professional journals begin to ignore valid research whose conclusions are harmful to the
            fish oil industry, we can see that the policy guidelines set by the industry and its agents in government
            have become clear. Around the end of the century, we begin to see a strange literary device appearing, in
            which research reports on the toxic effects of omega-3 oils are prefaced by remarks to the effect that "we
            all know how great these oils are for good health." I think I detect groveling and shuffling of the feet by
            authors who want to get their work published. If you are willing to say that your work probably doesn't mean
            what it seems to mean, maybe they will publish it.
        </p>

        <p>
            For more than 50 years, the great majority of the medical publications on estrogen were part of the drug
            industry's campaign to fraudulently gain billions of dollars, and anyone who cared to analyze them could see
            that the authors and editors were part of a cult, rather than seekers of useful knowledge. Likewise, the
            doctrine of the harmlessness of x-rays and radioactive fallout was kept alive for several decades by
            demonizing all who challenged it. It now looks as though we are in danger of entering another period of
            medical-industrial-governmental cultism, this time to promote the universal use of polyunsaturated fats as
            both drugs and foods. In 2004, a study of 29,133 men reported that the use of omega-3 oil or consumption of
            fish didn't decrease depression or suicide, and in 2001, a study of 42,612 men and women reported that after
            more than 9 years the use of cod liver oil showed no protective effect against coronary heart disease
            (Hakkarainen, et al., 2004; Egeland, et al., 2001).
        </p>
        <p>
            The most popular way of arguing that fish oil will prevent heart disease is to show that it lowers blood
            lipids, continuing the old approach of the American Heart Association's "heart protective diet."
            Unfortunately for that argument, it's now known that the triglycerides in the blood are decreased because of
            the fish oil's toxic effects on the liver (Hagve and Christophersen, 1988; Ritskes-Hoitinga, et al., 1998).
            In experiments with rats, EPA and DHA lowered blood lipids only when given to rats that had been fed, in
            which case the fats were incorporated into tissues, and suppressed mitochondrial respiration (Osmundsen, et
            al., 1998).
        </p>

        <p>
            The belief that eating cholesterol causes heart disease was based mainly on old experiments with rabbits,
            and subsequent experiments have made it clear that it is <strong><em>oxidized</em></strong> cholesterol that
            damages the arteries (Stapran, et al., 1997). Since both fish oil and oxidized cholesterol damage rabbits'
            arteries, and since the lipid peroxides associated with fish oil attack a great variety of biological
            materials, including the LDL lipoproteins carrying cholesterol, the implications<strong> </strong>of the
            rabbit experiments now seem very different.
        </p>
        <p>
            Another way of arguing for the use of fish oil or other omega-3 fats is to show a correlation between
            disease and a decreased amount of EPA, DHA, or arachidonic acid in the tissues, and to say "these oils are
            deficient, the disease is caused by a deficiency of essential fatty acids." Those oils are extremely
            susceptible to oxidation, so they tend to spontaneously disappear in response to tissue injury, cellular
            excitation, the increased energy demands of stress, exposure to toxins or ionizing radiation, or even
            exposure to light. That spontaneous oxidation is what made them useful as varnish or paint medium. But it is
            what makes them sensitize the tissues to injury. Their "deficiency" in the tissues frequently corresponds to
            the intensity of oxidative stress and lipid peroxidation; it is usually their presence, rather than their
            deficiency, that created the disposition for the disease.
        </p>
        <p>
            One of the earliest harmful effects of polyunsaturated fatty acids, PUFA, to be observed was their
            acceleration of the formation of lipofuscin or ceroid, the "age pigment," during oxidative stress or vitamin
            E deficiency. Associated with the formation of lipofuscin, the PUFA were discovered to cause degeneration of
            the gonads and brain, and the fact that vitamin E could prevent some of their toxic effects led to the idea
            that vitamin E was essentially an antioxidant. Unfortunately, the protective effect of vitamin E against the
            PUFA is only partial (Allard, et al., 1997).
        </p>
        <p>
            The degenerative diseases are all associated with disturbances involving fat metabolism and lipid
            peroxidation. Alzheimer's disease, alcoholic and nonalcoholic liver disease, retinal degeneration, epilepsy,
            AIDS, diabetes, and a variety of circulatory problems involve breakdown products of the PUFA. The products
            of PUFA decomposition include acrolein, malondialdehyde, hydroxynonenal, crotonaldehyde, ethane, pentane,
            and the neuroprostanes, which are prostaglandin-like molecules formed from DHA by free radical lipid
            peroxidation products, especially in the brain and at a higher level in Alzheimer's disease.
        </p>
        <p>
            The reactions of three types of cell--vascular endothelium, nerve cells, and thymus cells--to the PUFA will
            illustrate some of the important processes involved in their toxicity.
        </p>
        <p>
            When the body doesn't have enough glucose, free fatty acids are released from the tissues, and their
            oxidation blocks the oxidation of glucose even when it becomes available from the breakdown of protein
            caused by cortisol, which is released during glucose deprivation. Cells of the thymus are sensitive to
            glucose deprivation, and even in the presence of glucose, cortisol prevents them from using glucose, causing
            them to take up fatty acids. The thymic cells die easily when exposed either to excess cortisol, or
            deficient glucose. The polyunsaturated fatty acids<strong> </strong>linoleate, arachidonate, and
            eicosapentaenoic, are especially toxic to thymic cells by preventing their inactivation of cortisol,
            increasing its action. (Klein, et al., 1987, 1989, 1990). Lymphocytes from people with AIDS and leukemia are
            less able to metabolize cortisol. An extract of serum from AIDS patients caused lymphocytes exposed to
            cortisol to die 7 times faster than cells from healthy people. AIDS patients have high levels of both
            cortisol and free polyunsaturated fatty acids (Christeff, et al., 1988). The cytotoxicity caused by EPA and
            its metabolites (15 mg. of EPA per liter killed over 90% of a certain type of macrophage) isn't inhibited by
            vitamin E (Fyfe and Abbey, 2000). Immunological activation tends to kill T cells that contain PUFA (Switzer,
            et al., 2003).
        </p>
        <p>
            When animals are fed fish oil and then exposed to bacteria, their immunosuppressed thymic (T) cells cause
            them to succumb to the infection more easily than animals fed coconut oil or a fat free diet. Natural killer
            cells, which eliminate cancer cells and virus infected cells, are decreased after eating fish oil, and T
            suppressor cells are often increased. More subtle interference with immunity is produced by the actions of
            PUFA on the "immune synapse," a contact between cells that permits the transmission of immunological
            information. The immunosuppressive effect of fish oil is recognized as a useful aid in preventing the
            rejection of transplanted organs, but some studies are showing that survival a year after transplantation
            isn't improved.
        </p>

        <p>
            Polyunsaturated fatty acids, especially those that can be turned into prostaglandins, are widely involved in
            causing inflammation and vascular leakiness. EPA and DHA don't form ordinary prostaglandins, though the
            isoprostanes and neuroprostanes they produce during lipid peroxidation behave in many ways like the more
            common prostaglandins, and their enzymically formed eicosanoids have some functions similar to those of the
            common prostaglandins. The brain contains a very high concentration of these unstable fatty acids, and they
            are released in synapses by ordinary excitatory process.
        </p>
        <p>
            Chan, et al., 1983, found that polyunsaturated fats caused brain swelling and increased blood vessel
            permeability. In 1988, Chan's group found that DHA and other polyunsaturated fatty acids added to cultured
            cells from the cerebral cortex produced free radicals and stimulated production of malondialdehyde and
            lactate, and inhibited the uptake of glutamic acid, which suggests that they would contribute to prolonged
            excitation of the nerves (Yu, et al., 1986). In brain slices, the polyunsaturated fatty acids caused the
            production of free radicals and swelling of the tissue, and the saturated fatty acids didn't (Chan and
            Fishman, 1980). The PUFA inhibited the respiration of mitochondria in brain cells (Hillered and Chan, 1988),
            and at a higher concentration, caused them to swell (Hillered and Chan, 1989), but saturated fatty acids
            didn't produce edema. Free radical activity was shown to cause the liberation of free fatty acids from the
            cellular structure (Chan, et al., 1982, 1984). The activation of lipases by free radicals and lipid
            peroxides, with the loss of potassium from the cells, suggests that excitation can become a self-stimulating
            process, leading to cellular destruction.
        </p>
        <p>
            DHA itself, rather than its decomposition products, facilitates excitatory (glutamate) nerve transmission
            (Nishikawa, et al., 1994), and that excitatory action causes the release of arachidonic acid (Pellerin and
            Wolfe, 1991).
        </p>
        <p>
            Considering just one of the products of fish oil peroxidation, acrolein, and a few of its effects in cells,
            we can get an idea of the types of damage that could result from increasing the amount of omega-3 fats in
            our tissues. The "barrier" between the brain and blood stream is one of the most effective vascular barriers
            in the body, but it is very permeable to oils, and lipid peroxidation disrupts it, damaging the ATPase that
            regulates sodium and potassium (Stanimirovic, et al., 1995). Apparently, anything that depletes the cell's
            energy, lowering ATP, allows an excess of calcium to enter cells, contributing to their death (Ray, et al.,
            1994). Increasing intracellular calcium activates phospholipases, releasing more polyunsaturated fats
            (Sweetman, et al., 1995) The acrolein which is released during lipid peroxidation inhibits mitochondrial
            function by poisoning the crucial respiratory enzyme, cytochrome oxidase, resulting in a decreased ability
            to produce energy (Picklo and Montine, 2001). (In the retina, the PUFA contribute to light-induced damage of
            the energy producing ability of the cells [King, 2004], by damaging the same crucial enzyme.) Besides
            inhibiting the ability of nerve cells to produce energy from the oxidation of glucose, acrolein inhibits the
            ability of cells to regulate the excitatory amino acid glutamate (Lovell, et al., 2000), contributing to the
            excitatory process. High levels of acrolein (and other products of PUFA degradation) are found in the brain
            in Alzheimer's disease (Lovell, et al., 2001).
        </p>
        <p>
            The "prion" diseases, CJD and TSE/BSE (mad cow disease) have many features in common with Alzheimer's
            disease, and several studies have shown that the "prion" protein produces its damage by activating the
            lipases that release polyunsaturated fatty acids and produce lipid peroxides (Bate, et al., 2004, Stewart,
            et al., 2001). Acrolein reacts with DNA, causing "genetic" damage, and also reacts with the lysine in
            proteins, for example contributing to the toxicity of oxidized low density lipoproteins (LDL), the proteins
            that carry cholesterol and that became famous because of their involvement in the development of
            atherosclerosis that was supposedly caused by eating saturated fats.
        </p>
        <p>
            My newsletter on mad cow disease discussed the evidence incriminating the use of fish meal in animal feed,
            as a cause of the degenerative brain diseases, and earlier newsletters (glycemia, and glycation) discussed
            the reasons for thinking that inappropriate glycation of lysine groups in proteins, as a result of a lack of
            protective carbon dioxide/carbamino groups, produces the amyloid (or "prion") proteins that characterize the
            dementias. Acrolein, produced from the decomposing "fish oils" in the brain, is probably the most reactive
            product of lipid peroxidation in the brain, and so would be likely to cause the glycation of lysine in the
            plaque-forming proteins. These toxic effects of acrolein in the brain are analogous to the multitude of
            toxic effects of the omega-3 fatty acids and their breakdown products in all of the other organs and tissues
            of the body. Cancer cells are unusual in their degree of resistance to the lethal actions of the lipid
            peroxides, but the inflammatory effects of the highly unsaturated fatty acids are now widely recognized to
            be essentially involved in the process of cancerization (my newsletters on cancer and leakiness discuss some
            of the ways the fats are involved in tumor development). The fats that we synthesize from sugar, or coconut
            oil, or oleic acid, the omega-9 series, are protective against the inflammatory PUFA, in some cases more
            effective even than vitamin E.
        </p>

        <p>
            In Woody Allen's 1973 movie, <strong><em>Sleeper,</em></strong> the protagonist woke up after being frozen
            for 200 years, to find that saturated fats were health foods. At the time the movie was made, that had
            already been established (e.g., Hartroft and Porta, 1968 edition of<em>
                Present Knowledge in Nutrition</em>, who showed that adequate saturated fat in the diet helped to
            protect against the formation of lipofuscin). PS: Royal Society for the Protection of Birds says 2004 has
            been the most catastrophic breeding season on record for seabirds along UK coasts. It says industrial
            fishing to supply fish meal and oil is barely sustainable and imperils the whole marine food web. "The UK
            has suffered serious seabird disasters this year already. In Shetland and Orkney, entire colonies of birds
            failed to produce any young because of severe food shortages. "On top of that, hundreds of seabirds have
            been washing ashore having perished at sea. Again, lack of food is thought to be one of the reasons." The
            report, Assessment Of The Sustainability Of Industrial Fisheries Producing Fish Meal And Fish Oil, was
            compiled for the RSPB by Poseidon Aquatic Resource Management Ltd and the University of Newcastle-upon-Tyne.
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            Chan PH, Chen SF, Yu AC. Clin Exp Immunol. 2002 Oct;130(1):12-8.<strong>
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            Hagve TA, Christophersen BO. Am J Psychiatry. 2004 Mar;161(3):567-9.<strong>
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        </p>

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