Fish Oil Is Good! No, Bad! No, Good! No, Wait

Discussion in 'Health and Fitness' started by Frederick Foresight, Aug 6, 2022.

  1. A fascinating read:

    https://www.theatlantic.com/health/archive/2022/08/vascepa-fish-oil-omega-3/671064/

    [​IMG]

    Americans love it. But the science is getting even weirder.

    At first, it was all very exciting. In 1971, a team of Danish researchers stationed on Greenland’s northwest coast found that a local Inuit community had remarkably low levels of diabetes and heart disease. The reason, the researchers surmised, was their high-marine-fat diet—in other words, fish oil. Incidence of heart disease, which once afflicted relatively few Americans, had shot up since the turn of the century, and here, seemingly, was a simple solution. “I remember how exciting those studies were when they first came out,” Marion Nestle, a professor emerita of nutrition and food studies at NYU, told me. “The idea that there were populations of people who were eating fish and were protected against heart disease looked fabulous.”

    The hype didn’t stop with heart disease. Soon, fish oil was being hailed as a panacea. It could help prevent dementia! Depression! Obesity! Cancer! News stories and books parroted these claims. And supplement makers capitalized. By 2014, fish-oil supplements were a billion-dollar industry. Today, the market continues to grow at an astronomical rate. The growth of the science supporting fish oil’s curative properties, meanwhile, has been, shall we say, less astronomical. The early papers that sparked the initial enthusiasm were merely observational, meaning that they could establish only correlation, not causation. When the randomized control trials eventually began to trickle in, the results were mixed at best.

    Tens of thousands of studies later, things haven’t gotten all that much clearer: We still don’t have anything close to a firm grasp of what fish oil can do and what it cannot. And lately, things have only gotten weirder.

    Most experts acknowledge that fish oil does have some modest benefits in certain circumstances. Omega-3, its star nutrient, has been shown to lower levels of a fat associated with heart failure, help prevent premature births, and improve infant formulas. But these are a far cry from the game-changing promise of the early studies. That promise, over the years, has gotten lost in a tangle of theoretical possibilities, Nestle told me. Fish oil contains two distinct types of omega-3, DHA and EPA; maybe only the former is providing the benefit. Or maybe only the latter. Maybe the benefit comes only from pairing the two. Maybe neither does anything unless it’s consumed with other parts of the actual fish.

    And that’s just the beginning. Maybe the benefits have less to do with fish itself and more to do with the fact that if you’re eating fish, you’re probably not also eating a hamburger or a pork chop. Maybe they have to do with your overall diet. Maybe they don’t have to do with your diet at all. Maybe it’s just that fish eaters tend to be wealthier and, not unrelatedly, healthier in the first place. Maybe it’s something else entirely.

    Through much of the 2010s, one fish-oil study after another came up empty, Richard Bazinet, a nutrition researcher at the University of Toronto, told me—“null, null, null, null, null.” And then came REDUCE-IT, a trial funded by the pharmaceutical company Amarin to test its fish-oil-based heart drug, called Vascepa. The results, presented in 2018, found that, among high-risk adults already receiving another type of cholesterol-lowering treatment, the drug decreased the risk of heart failure and other serious cardiovascular events by an eye-popping 25 percent. Fish oil, it seemed, was back in business. When the study’s lead author, the Harvard cardiologist Deepak Bhatt, presented his findings at the American Heart Association’s annual meeting in Chicago, the crowd gave a standing ovation. The following year, the FDA approved the drug for the use studied in REDUCE-IT. (The agency had already approved the drug for a different use back in 2013.)

    With triumph, though, came controversy. Even at the time of Bhatt’s presentation, some cardiologists noted that the study’s mineral-oil-based placebo—a pill selected because its color and consistency mimic those of fish oil, but whose use in fish-oil studies has been debated—seemed not to be entirely neutral. In fact, the placebo seemed to be harming people. Initially, nothing much came of these concerns. Then, last month, a new analysis published in the journal Circulation substantiated them and then some. It showed, based on elevated levels of several biomarkers in blood-test results, that the placebo may have increased volunteers’ risk of heart attack and stroke. Many researchers found these results to be compelling evidence that Vascepa’s eye-popping success could be due to a bad placebo, not a great drug.

    “What’s somewhat shocking about that paper is that it looks like everything got worse in the placebo group and the treatment group stayed the same,” Bazinet told me. “You could have given the subjects a glass of water. Anything would have been better against that placebo.” Steven Nissen, a cardiologist at the Cleveland Clinic who was involved in a different omega-3 trial, called the Circulation study’s findings “extraordinarily disturbing.” Two members of the expert panel that in 2019 recommended that the FDA green-light Vascepa even told Stat’s Matthew Herper that, if they’d had access to the new data at the time, they might not have voted to approve.

    To make matters more confusing, the Circulation study—as in, the very study that ignited this controversy—was also funded by Amarin, and one of the study’s 13 authors was Bhatt, the lead author on REDUCE-IT. In a statement, Amarin told me it “continues to stand by the results of REDUCE-IT” and is “very surprised” that the panel members would make such comments based on the Circulation paper. The company stressed that REDUCE-IT’s positive results “could not be explained” by the placebo, and that the effects found in the Circulation study were too minor to “correlate to any meaningful changes in outcomes.” Bhatt agreed, telling me he sees the new paper not as undermining REDUCE-IT but simply as clarifying Vascepa’s biological mechanisms. He defended the use of mineral oil as a placebo, arguing that it alone could not explain the significant risk reductions observed in the trial.

    The lead author of the Circulation study, Paul Ridker, declined to comment on the controversial results. But other experts I spoke with were considerably less sanguine than Bhatt. Several would say only that, at this point, the REDUCE-IT results are basically uninterpretable. Nissen, who has in the past called REDUCE-IT “almost certainly a false-positive study,” went so far as to say that he thinks the benefits it found can be “entirely explained by the harms of the placebo” and that Amarin should have known not to use mineral oil. JoAnn Manson, the chief of preventive medicine at Brigham and Women’s Hospital in Boston and the leader of the largest-ever study of vitamin D and omega-3 pills in healthy adults, was more sympathetic to the idea that the Circulation study’s findings likely don’t account for the full 25 percent risk reduction. But she also raised the possibility that the Vascepa, if ineffective, could be dangerous: Some studies have shown that a high daily dosage of fish oil can heighten one’s risk of developing a type of irregular heartbeat. (Amarin called the suggestion that Vascepa could be ineffective and dangerous “a gross distortion of fact,” saying that “the findings of independent, thorough, and impartial scientific and statistical reviews” had determined that the drug’s benefits to the at-risk patients for whom it is designed more than make up for its risks.)

    The upshot of all this is that an already murky situation has become a good deal murkier, and there’s no end to the murk in sight. Which is a shame because, in one sense at least, the stakes are higher now than they’ve been in some time: REDUCE-IT suggested that Vascepa could legitimately save lives. If it can’t, that’s more than a scientific scandal; it’s a real, human loss. “I’ve never seen anything like this,” Bazinet told me. “In a way, it’s not surprising. The field’s been controversial all the time, and now we probably have the biggest controversy.”

    The only way out of this mess, experts said, is to run a whole new trial comparing Vascepa (or its generic equivalent, icosapent ethyl) with something everyone agrees is a true placebo—one that we can be confident doesn’t harm people. Manson is leading a team applying for NIH funding to run such a study. (She said that Amarin told her it was not open to a replication trial and that the company declined to fund three related studies. When I asked Amarin about this, the company told me it would not replicate REDUCE-IT, because the outcomes “read out robustly,” and that it does not publicly discuss research proposals from third parties.) The study would also investigate a pair of promising leads turned up by her own major study, an ongoing project that has found that although omega-3 did very little for the population as a whole, it might have considerable benefits for Black people and people who don’t eat much fish.

    In the meantime, doctors are unlikely to ditch Vascepa, Clifford Rosen, a professor at Tufts University School of Medicine, told me. In the first quarter of 2022, Amarin sold nearly $100 million worth of the drug, which is its only product. “There’s such momentum to use this agent that until the next study comes around, I think there’s still going to be widespread use,” Rosen said. To his point: In 2019, the American Diabetes Association recommended icosapent ethyl for certain patients as part of its official standards of care, based explicitly on the REDUCE-IT results. Since the publication of the Circulation paper, the ADA has made no move to withdraw that recommendation. (When I asked whether the group is considering doing so, its chief scientific and medical officer said only that it had “followed the evidence based on what was available at the time.”)

    Not that this state of affairs is particularly novel. We’ve known for years that fish-oil supplements have virtually no benefits for your average, healthy person, Pieter Cohen, a professor at Harvard Medical School, told me. That hasn’t stopped tens of millions of Americans from popping the pills every day. “People just love to take supplements,” Rosen said. “It’s religiosity … It’s magical thinking.” Vascepa is an FDA-approved drug, not merely a supplement, but in some ways the line isn’t all that clear. The dosage is certainly higher, the packaging is certainly better, and the regulations are certainly stricter. But if you don’t understand the biological mechanism behind either the drug or the supplement—and scientists do not—that makes it tough to assert with any confidence that they’re fundamentally distinct.

    “If you don’t know how something works—like you have no idea how it works—it’s hard to say that they’re different!” Bazinet told me. “Because it could just be a little bit more of the same mechanism. It’s not clear.” When it comes to fish oil, very little is.
     
    Bugenhagen likes this.
  2. notagain

    notagain

    Carlson fish oil provides omega 3 to balance against too much omega 6 in your diet.
    Eating fish along with enough exercise is good for health.
    You have to exercise to increase circulation, sedentary lifestyle is the real problem.
     
    murray t turtle likes this.
  3. Bugenhagen

    Bugenhagen

    I always consider what happens to the suppliment when its put in hydrochloric acid. So many in theory beautiful molecules completely wrecked.
     
    Last edited: Aug 6, 2022
  4. %%
    Exactly.......................................................
    Folk Medicine book by Dr Jarvas MD, observed fish benefits some groups s of people more than others.
     
  5. The saga continues...

    A New Shot at Using Fish Oil

    https://www.wsj.com/articles/a-new-shot-at-using-fish-oil-11662385576

    Injecting forms of omega-3 fatty acids directly into the bloodstream shows promise in treating stroke and other conditions

    In a new push to figure out whether fish oil can help with conditions from heart disease to depression, scientists are digging deeper into its key nutrient: omega-3 fatty acids.

    They are exploring higher doses and specific fish-oil components that may be more effective for targeted use, developing new delivery mechanisms, and studying ways to use omega-3s to treat acute events such as stroke, in addition to chronic diseases.

    Eating fish with omega-3 fatty acids is beneficial for heart health, research suggests. But the findings of studies on the potential health benefits of fish-oil dietary supplements, which millions of people take daily, have been mixed.


    Fish oil “is not a panacea,” said JoAnn Manson, chief of the division of preventive medicine at Brigham and Women’s Hospital in Boston, who led a large randomized trial of omega-3s. But, she added, “The research to date would suggest there may be some benefits with targeted use.”

    Studies suggest omega-3s may benefit patients with autoimmune diseases or reduce damage after strokes, she said. Other studies show that the fatty acids, which have anti-inflammatory properties, help certain critically ill patients recover after surgery.

    One team at Columbia University has developed a therapeutic made with a high dose of omega-3s to protect and repair cells damaged when they are cut off from oxygen, such as in a stroke or in newborns during a complicated labor. The therapy, if proven to work, potentially could be used for other conditions as well, including heart attacks or sickle-cell disease, said Richard Deckelbaum, a professor of pediatrics, nutrition and epidemiology at Columbia who is leading the research.

    The therapeutic, an emulsion of omega-3s—microdroplets of oil dispersed in a watery liquid—is injected directly into the bloodstream, unlike fish-oil pills which have to go through the digestive system. It hasn’t yet been tested in humans, but studies in mice and rats show that within an hour the omega-3s in the emulsion start preventing cells in the brain and other organs from dying when deprived of oxygen, such as in a stroke, reducing cell death by between 65% and 90%, he said.

    “The whole omega-3 field has been based on oral intakes—supplements, eating fish,” Dr. Deckelbaum said. “We’re coming up with a new paradigm.”

    Finding potent uses for omega-3s would mark a rare breakthrough in a field that has tried for decades to find major benefits from fish oil. In the 1970s, researchers discovered that Inuit people, whose diet consisted mostly of fish they caught, had low rates of cardiovascular disease. That led to reams of studies of omega-3s to try to unlock their suspected superpowers.

    Omega-3s are essential fats the body needs to function, but can’t make on its own. Dietary sources of omega-3s include salmon, tuna and other cold-water fatty fish, as well as certain plant oils, nuts and seeds. An important part of human cell membranes, they help to give the body energy and are important to regulate functions in the blood vessels, the endocrine system and other parts of the body. They help reduce inflammation, a factor in many diseases.

    The American Heart Association recommends eating fish at least twice a week for heart health. But researchers say the jury is still out on the health benefits of fish-oil supplements. Omega-3s taken at a dosage found in many over-the-counter supplements didn’t reduce the incidence of invasive cancer or a composite of major cardiovascular events in the Vitamin D and Omega-3 Trial, a study known as VITAL that Dr. Manson led and whose results were published in 2018.

    In addition, high doses of omega-3 fatty acids have been linked to an increased risk of atrial fibrillation, an irregular heart rhythm, Dr. Manson said.

    Some researchers had thought that omega-3s could help combat depression, because the brain requires those fatty acids to function properly and they help lower inflammation, a factor in depression. But recent studies of VITAL data and a review of several studies found no benefit for preventing depression, or improving mood.

    Olivia Okereke, director of geriatric psychiatry at Massachusetts General Hospital and lead author of the VITAL depression study, said she and her colleagues are looking more closely at the findings and also plan to study the effects of higher doses of omega-3s. More research should be done to identify the mechanisms by which omega-3s might work against depression, said Katherine Appleton, a professor of psychology at Bournemouth University in Poole, England, who led the review of depression studies.

    There are some other signals that omega-3s have potential benefits and should be studied further, Dr. Manson said. For example, she would like to see a randomized controlled trial in which young adults with a family history of autoimmune diseases are given a high dose of omega-3s to see if that reduces the risk of developing them.

    A study of VITAL data that was published last year, which Dr. Manson was an author on, found signs that omega-3s may help reduce the risk of functional limitations or physical disabilities after strokes, she said. Dr. Deckelbaum’s research into an omega-3 emulsion to treat stroke damage “seems plausible but needs much more study,” she said.

    Omega-3s given intravenously can help some critically ill patients recover more quickly after surgery by decreasing the inflammatory response, said Martin Rosenthal, a trauma and critical care surgeon at University of Florida Health in Gainesville, Fla., who has studied the fatty acids and their effects on patients.

    A 2020 analysis of the results of previous studies published in the medical journal Critical Care, in which he participated as an author, found that patients in intensive-care units who were given intravenous omega-3 emulsions had shorter ICU and hospital stays and fewer infections after their procedures, he said.

    “There are different nutrients we can use and exploit to help augment our immune system and portend to having better surgical outcomes,” he said.

    Questions have emerged about the effectiveness of a fish oil-derived prescription drug called Vascepa. The drug is made of a high dose of a purified form of the omega-3 fatty acid eicosapentaenoic acid, or EPA. In 2019, the U.S. Food and Drug Administration approved it to reduce the risk of heart attacks, strokes and other serious cardiovascular-disease events in patients with elevated triglyceride levels who are at high risk and on cholesterol-lowering drugs.

    Some researchers say that the placebo used in a large clinical trial of Vascepa may have raised the heart-disease risk for people who took it, making the benefit from Vascepa look larger than it would otherwise have been. Data from a recent analysis appeared to suggest that.

    Amarin Corp., maker of the drug, said it stands by the results of the trial and doesn’t plan to replicate it. The placebo’s effects were small, in absolute terms, and didn’t exaggerate Vascepa’s benefits, the company said.

    Dr. Deckelbaum and other scientists hope that the benefits of omega-3s will become clearer when it is delivered in new forms and for more diseases and conditions. The omega-3 emulsion that Dr. Deckelbaum and his colleagues developed is made up of omega-3 fatty acids in a diglyceride form–two fatty acids–that is substantially smaller than the triglyceride form normally contained in fish-oil supplements, he said.

    “These particles have a better chance of getting across the blood-brain barrier much faster,” Dr. Deckelbaum said. “We also have other evidence that they’re incorporated into cell membranes more efficiently than triglycerides.” In addition to his academic posts, Dr. Deckelbaum is a founder of DeckTherapeutics Inc. and chair of its scientific-advisory board. The company was formed in 2019 to further develop the therapeutic for unmet medical needs, initially in children and later in adults.

    It will take about three years to complete studies of the therapy in animals and then humans, said Soren Weis Dahl, chief executive officer of DeckTherapeutics.

    If those studies are successful, the company plans to apply for regulatory approval initially to use the therapy to treat hypoxic-ischemic encephalopathy, or HIE, Dr. Dahl said. The condition occurs when an infant’s brain is deprived of oxygen before, during or after delivery due to complications such as separation of the placenta from the uterine wall. HIE is a leading cause of cerebral palsy, cognitive impairment and other disabilities. DeckTherapeutics received a small grant recently from the Bill & Melinda Gates Foundation, which is looking for therapeutics to treat HIE in the developing world.
     
  6. Baron

    Baron ET Founder

    This is another example of traditional science screwing everything up because they keep putting "normal people" into these studies.

    Trust me, take a guy who's on TRT and who's working out 4 - 5 days per week and eating tons of chicken and beef, and then measure his bio-markers. Then add some fish oil into the mix and measure those markers again. Cholesterol goes down, blood pressure goes down, inflammatory markers go down, etc.

    So yeah, maybe fish oil doesn't have as much benefit for the average person as a supplement.

    Bodybuilding science has always been 15 - 20 years ahead of traditional medicine, and it will always be like that. 20 years ago Testosterone was demonized by traditional medicine but these days, TRT clinics are everywhere handing out prescriptions daily because we've now learned that the health benefits of maintaining your hormone levels as you get older far outweigh the risks associated with it.
     
    Buy1Sell2 and murray t turtle like this.
  7. Yes, but this study is a bit different. It's about mainlining the stuff for the critically ill.

    So is that something like having a pizza and a statin? :D

    I don't think it's a foregone conclusion yet for borderline cases:

    https://www.health.harvard.edu/mens...safe-take-a-breath-before-you-take-the-plunge
     
  8. Baron

    Baron ET Founder

  9. Damn.

    A cardiologist says she's seeing a rise in 20-somethings with heart arrhythmias caused by herbal supplements

    • Fish oil, taken at a dose of one gram a day or more, might increase the risk for a type of irregular heart rhythm called atrial fibrillation, according to several clinical studies. Gulati said fish oil can also interact with blood thinners to cause dangerous bleeding.
    https://www.insider.com/cardiologist-supplements-causing-heart-arrhythmias-in-young-people-2022-9

    https://www.cedars-sinai.org/newsroom/omega-3-supplements-could-elevate-risk-of-atrial-fibrillation/
     
    Last edited: Sep 8, 2022
  10. Pekelo

    Pekelo


    Is this a realistic price?:

    "yearly program fees will be due which can range from $1200 to $1750 for the first year,"
     
    #10     Sep 8, 2022