Bill Harris Sioux Falls, SD 56 minutes ago
As a long-time researcher in omega-3s, I've watched the fish oil rollercoaster since the mid 1980s. This most recent posting by O'Connor continues the trend. The best meta-analysis (grand summary of many studies) published to date was from Rizos et al. in JAMA 2012;308:1024-1033). They concluded that fish oil capsules offer “no benefit” for heart patients. Unfortunately, Rizos used a highly controversial statistical maneuver. In their actual data (Fig 2) there was a highly statistically significant reduction in cardiac death associated with fish oil use (p<0.01 for the stat-saavy). So fish oils DID reduce risk for cardiac death. Why the "no effect" conclusion? Rizos et al. decided to set the statistical bar higher than I’ve ever seen it in meta-analyses. They defined a significant p-value as <0.006, instead of the universally accepted p<0.05. This trick changed a positive finding into a negative one and generated a media storm of "fish oils don't work." More recent meta-analyses (Chowdhury et al. Ann Intern Med 2014;160:398-406) reported that higher dietary intakes AND higher blood levels of omega-3 fatty acids were both significantly linked to reduced risk for heart disease. The problems with the recent fish oil studies are legion, and include using a low dose for a short period of time in older, already-ill patients who are also being treated with up to 5 heart medicines. In this setting it’s nearly impossible to show a benefit. With 0 risk, I still recommend fish oil.
Just a couple of notes. The "Rizos et al. in JAMA 2012;308:1024-1033" refers to the article:
Rizos E. C., Ntzani E. E., Bika E., Kostapanos M. S., Elisaf M. S. (2012). Association between omega-3 fatty acid supplementation and risk of major cardiovascular disease events. JAMA 308, 1024–1033 10.1001/2012.jama.11374
The reason for using .006 is stated in the article:
"Within each assessed outcome, we adopted a level of statistical significance adjusted for multiple comparisons testing by a factor of 8 equaling the number of overall and subgroup analyses performed using the 2 measures of effect (RR and RD); thus, statistical significance was assumed at a P value threshold of .0063."
P-value adjustments are fairly common [1], but I'm not smart enough to say if it was applicable in this case.
Also, in the interest of full disclosure, it might be worth mentioning that Bill Harris is the President of OmegaQuant Analytics [2], whose stated purpose is to "advanc[e] the science and use of omega-3 fatty acids to improve health."
I checked the Rizos et al study (http://jama.jamanetwork.com/article.aspx?articleid=1357266) and the statistical issue is a bit subtle. They applied a multiple-hypothesis correction, to account for the fact that they were looking at multiple subgroups and endpoints. The problem is that in their data, most of the subgroups and endpoints show an effect, and these aren't being combined together. So in that paper, no one subgroup alone contains enough evidence to show an effect, but the groups put together, do.
The effects seen in the various sub-groups and endpoints are all non-significant at the p = 0.05 level. The lowest I can see is p = 0.07 (cardiac death prevention, as reported in their Table 3).
The multiple-hypothesis correction they apply is reasonably appropriate in the case of simply looking at all results, which is what they do.
Furthermore, because the outcomes are disjoint (cardiac survival vs stroke vs sudden death vs all-cause mortality, etc) there is no simple way to combine the results.
To take a silly example, studying the effect of seatbelts on cancer and cardiac death might well show a bit of an effect on both (because people who wear seatbelts are generally healthier, say) but it would be illegitimate to combine those two studies because the endpoints are (so far as we know) unrelated to each other. Without some kind of causal account the issues become very deep and difficult to say anything very definitive about.
So I'd say their statistical treatment is fair and appropriate. If fish-oil is supposed to have such a large effect as to be worth taking the risk that it increases the risk of prostate cancer, its effect should be unequivocally measureable in population studies. That is not the case.
For what it's worth, I think the prostate cancer studies are at least as flawed, at least the one I've seen, which is a case-control study that shows an extremely modest increase in relative risk of the kind it is very easy to produce from statistically identical populations: http://www.tjradcliffe.com/?p=1745
The vast majority of medical researchers don't have a deep understanding of statistics. The ones that do understand statistics comply with the "universal expectations" of their editors and reviewers.
Short term, ranged, and non-clinical studies always remind me of the story of the "Shoe-fitting fluoroscopes" (1)
AKA - x-ray machines placed in shoe stores so you could stick your foot in, dial up the radiation, and see your wiggling toes in the shoe.
Invented in the 1920s. Debates raged for decades. Outlawed finally in most states in the 1970s.
So for 50 years people thought taking your kid to the shoe store and blasting their feet with radiation was a good idea.
Largely because they had limited data and ability to measure the outcome, as the data became available it became crystal clear that these had the potential to be dramatically harmful.
Even with this lesson in mind I took fish oil for years, despite a lack of clear data.
The study a couple of years ago that linked fish-oil (natural and supplemental) to a 41% increase in prostate cancer / 71% increase in aggressive prostate cancer, reminded me of the flouroscope story. (2)
This Harvard health article, a couple of years old, puts it best:
"How food, and its component molecules, affect the body is largely a mystery. That makes the use of supplements for anything other than treating a deficiency questionable." (3)
Not sure that comparing x-rays to fish oil is a good comparison of risk/reward.
People (like myself) take fish oil for a variety of reasons, in my case to lower the risks of serious heart disease over the risks it might contribute to prostate cancer.
Ultimately each person has to judge the benefits/risks for themselves until better data is available. It's also worth noting that prostate cancer is increasingly a risk for all men as they age, fish oil or not.
Indeed. Not to be too snarky, but if fish oil increases your longevity it may also increase your risk for cancer, simply because you'll live long enough to get one.
Simpson's paradox paradox comes into play here a little bit. Your risk of dying of prostate cancer is in the ballpark of 1 in 40 but your risk of dying of heart disease is 1 in 4.
If trading a higher risk of prostate cancer for a lower risk of heart-disease (which others have mentioned) might be the better choice here.
Caveats abound here, of course, but just because something 'increases your risk of' something doesn't mean it's an aggregate loss.
> The study a couple of years ago that linked fish-oil (natural and supplemental) to a 41% increase in prostate cancer / 71% increase in aggressive prostate cancer
What I'm really curious about is the research for fish oil and dry eyes. After I had lasik, I was told to take fish oil 4 times a day for a long time. My dry eyes seem to have gotten better, but I don't know whether that is due to the fish oil or from just a general recovery.
I started taking fish oil (algae oil actually, but the active ingredients are identical) a month before my LASIK surgery and continue to take it today, and I've still never had any problems with dry eyes, including immediately after the surgery.
So, can't say whether it helped or not, but it certainly hasn't hurt.
The title is a little misleading. Claims about fish oil and its potential decrease of cardiovascular events in high-risk populations is not supported by research. The article does not address other potentially beneficial effects, such as decreased inflammation.
My wife takes fish-oil daily as a mood stabilizer. When she skips a day or two all hell breaks lose in our house. Hell I take a smaller dose myself and it's amazing how much better I am at keeping my mood in check; I've never had much trouble but I have always gotten little edgy when hungry. That doesn't happen anymore.
It is nearly impossible to be objective about your own brain. If you suspect X makes you happier, then it probably will. After it works once, you will probably believe X makes you happier, and if definitely will.
In other words, even if fish-oil does work as a mood stabilizer, there would be no way for you, as a consumer of fish oil, to be even slightly certain it works.
I used to play a trick on myself where I'd hold a particular hand position and meditate on a state of mind, one intended to clear my mind and get centered, the other to get me amped up to go do some work. (I worked in construction at the time) It worked amazingly well, and I spent several weeks / months feeling no other emotions. I'd feel the state slipping, and just hold the hand position and the state would come back. Only reason I stopped was that the emotional monotony got old after awhile.
I have no trouble believing that fish oil as a mood stabilizer can work fantastically, and yet have no physiological effect whatsoever.
You can look at double blind trials of the effects of fish oil as a mood stabilizer. Its possible that the GP's wife has an idiosyncratic lack of reaction and is just fooling herself but that would be pretty improbably so I'd say her beliefs are well justified. The observed effects aren't small, we're talking about things like reducing assaults in prison by 1/3.
This is interesting, but 1) it does not test the effects of fish oil as a mood stabilizer and 2) there is something sketchy about the way the data are reported.
1) It is a study of vitamin, mineral and essential oil supplements. There is no basis for ascribing any measured effect to essential oils as such.
2) In a number-rich report, it's odd that they don't report either the number or distribution of incidents in any detail, and I can't make their averages work out.
For example, they have 172 people in the study for an average of 142 days, and they talk about numbers like 11 and 16 incidents per thousand person-days, which would lead one to predict around 170x140x(11 to 16)/1000 ~ 250 - 300 incidents, but they then go on to talk about studying 754 Governor and minor reports, or 338 Governor reports and 416 minor reports (in all cases the reports appear to cover the full study population, which is the majority of the prison population).
One can conclude from this that most of the incidents in the prison are due to the people who weren't in the study, maybe? I don't know, but there's something odd going on.
Furthermore, they don't given any idea of individual variation within the population. The conclusion you'd draw if most of the incidents are associated with a few individuals vs spread out across the population might not be the same. Were all individuals pretty much similar in their response, or was the effect localized to some? The results as reported are consistent with a few problematic individuals becoming peaceful and everyone else getting slightly worse.
When making an argument that an intervention is good for a population, you really have to dig into the support for the claim across the population, not report averages as if they could only arise one way.
So while this is intriguing an interesting, it isn't as strongly convincing as one would like.
What I'd like to see (and would have insisted on as a reviewer) is a table showing the raw numbers of minor and Governor's reports issued on each population over the study period, and at least histograms showing the number of individuals in each populations with N Governor's and M minor reports against them, which would allow one to judge the distribution of incidents in the population.
>It is nearly impossible to be objective about your own brain.
People can't trust their own perceptions? Isn't that what gaslighting is about? Why do we accept eye-witness testimony in court cases if people should not trust their own perceptions?
If a person saw another person strike another person, should we trust their testimony? No! We should have a double-blind placebo controlled experiment where we go back in time and have a large sample size of identical people watching the same person getting struck and not struck in alternate universes and ask them if the person was struck to determine if their perceptions can be trusted.
Eye-witness testimony is mostly bunk and is often not trusted in court. It's been shown over and over that eye-witnesses can be manipulated (even without their knowledge) and are not reliable.
No, you can't trust your own perceptions. You can only really trust that you are having a perception at this moment in time.
At some point I had to take medication where one of the known side effects where higher blood pressure.
I also noticed a significantly increased blood pressure every time I took this medicine.
This continued until one day someone knocked the door just before I took my pills, and I still got the same symptoms while the pills where safely on the kitchen.
I then realised my brain had played games with me and since then the side effects disappeared.
>My wife takes fish-oil daily as a mood stabilizer.
This is why I take it as well. Its incredible how well it works. I hate to engage in conspiratorial thinking, but some of these overly critical analysis really seem to be coming from a big pharma "tell them the shit doesn't work" perspective. In a country with for-profit medicine, non-patented or low-profit treatments often get demonized. Especially by "useful idiots" who follow this ultra skeptical mindset where only what they hear from an authority like the government or academia, has any real value. They refuse to believe these institutions can have institutional fraud, incompetence, groupthink, or unfair motivators to getting published. As someone who works in a healthcare related field, its pretty obvious that industry controls the narrative, at least to me.
Or can be gamed by private industry and other benefactors who have a bias or agenda.
Indeed. To close the loop, for those who don't see it: the companies that make "dietary supplements" have all the same incentives that Big Pharma does.
> The article does not address other potentially beneficial effects, such as decreased inflammation.
I'm wondering about that. Particularly given the increasing interest in the anti-inflammatory properties of statins & whatnot, an effective, easily obtained anti-inflammatory supplement should be very much worth looking at.
The article does not say any thing about how well tested the claimed anti-inflammatory effects of fish oil supplements are. Does anyone know?
The article does mention reduced inflammation, albeit somewhat indirectly (referring to the omega-3s in fish oil). Otherwise, it's rather dismissive. That seems to be a side effect of headline fads along the lines of "studies show X is bad/has no benefit" or "studies show X is good for you!" The best answer, of course, is "we need more data."
However, I did find this gem buried quite a ways down toward the end of the article:
> Dr. JoAnn Manson, the chief of preventive medicine at Brigham and Women’s Hospital in Boston, said the large clinical trials of fish oil focused only on people who already had heart disease or were at very high risk.
If that's true, then it appears TFA is looking at it from the wrong angle. In other words, fish oils may have no effect on someone who's already suffered from a heart attack (or is at high risk), but someone who is aiming to use it as a preventative treatment might reduce their risk. Should this be the case, studying at risk populations who may have already had heart problems might not be the best starting point. It's a bit like fretting over a nutritious diet and plenty of fluids being of little use for someone who already has the flu, regardless of how poor their diet was prior.
On the other hand, jimrandomh [1] near the top of these comments links to the study and warns there may be something more at work here. This is in the thread where magic5227 points out a comment on the NYT article that the statistical work in the study raises some considerable questions because it may have established too high a burden of proof. jimrandomh's comment suggests otherwise. So, who knows. It's worth reading through that thread as well.
Personally, I think the truth is probably somewhere between these two extremes. It's apparently clear the Inuit's diet has influence on their cardiac health, but is it really just the omega-3s and not the wider range of benefits from eating fish? Or is it possibly tied to a lifetime of omega-3 intake rather than starting supplementation on a whim or only after serious health problems? If that's the case, shouldn't long-term supplementation (on the order of decades) be a focus of study instead? (Note: I have never followed fish oil studies, nor do I take it, so perhaps someone will be kind enough to link to such a study.)
Anyway, I'm no nutritionist, and I'm kind of an idiot, but it seems to me that it's the long-term dietary (or supplementation) choices we make that are most the important, hence why I am increasingly more inclined to approach studies examining short-term effects (or lack of) with caution.
interesting, not entirely surprising given how we love to jump to conclusions over these things, and the history of fish oil as a 'common knowledge' 'good thing'.
slightly disappointed that the headline was not fish oil is actually snake oil? or something suitably witty... :)
Bill Harris Sioux Falls, SD 56 minutes ago As a long-time researcher in omega-3s, I've watched the fish oil rollercoaster since the mid 1980s. This most recent posting by O'Connor continues the trend. The best meta-analysis (grand summary of many studies) published to date was from Rizos et al. in JAMA 2012;308:1024-1033). They concluded that fish oil capsules offer “no benefit” for heart patients. Unfortunately, Rizos used a highly controversial statistical maneuver. In their actual data (Fig 2) there was a highly statistically significant reduction in cardiac death associated with fish oil use (p<0.01 for the stat-saavy). So fish oils DID reduce risk for cardiac death. Why the "no effect" conclusion? Rizos et al. decided to set the statistical bar higher than I’ve ever seen it in meta-analyses. They defined a significant p-value as <0.006, instead of the universally accepted p<0.05. This trick changed a positive finding into a negative one and generated a media storm of "fish oils don't work." More recent meta-analyses (Chowdhury et al. Ann Intern Med 2014;160:398-406) reported that higher dietary intakes AND higher blood levels of omega-3 fatty acids were both significantly linked to reduced risk for heart disease. The problems with the recent fish oil studies are legion, and include using a low dose for a short period of time in older, already-ill patients who are also being treated with up to 5 heart medicines. In this setting it’s nearly impossible to show a benefit. With 0 risk, I still recommend fish oil.