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.
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.
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.
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.
> 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... :)
[+] [-] magic5227|11 years ago|reply
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.
[+] [-] barik|11 years ago|reply
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 article can be read for free here: http://jama.jamanetwork.com/article.aspx?articleid=1357266
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."
[1] http://stat.ethz.ch/R-manual/R-patched/library/stats/html/p....
[2] http://www.omegaquant.com/. He also seems to have a pre-canned response, which he pastes as comments to various sites. The pre-canned response is here: http://www.omega-3centre.com/images/stories/pdfs/harris_jama...
[+] [-] jimrandomh|11 years ago|reply
[+] [-] unknown|11 years ago|reply
[deleted]
[+] [-] raverbashing|11 years ago|reply
[+] [-] bobcostas55|11 years ago|reply
[+] [-] aresant|11 years ago|reply
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)
(1) http://en.wikipedia.org/wiki/Shoe-fitting_fluoroscope
(2) http://jnci.oxfordjournals.org/content/early/2013/07/09/jnci...
(3) http://www.health.harvard.edu/blog/fish-oil-friend-or-foe-20...
[+] [-] magic5227|11 years ago|reply
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.
There are even studies that show fish oil could reduce the chances of prostate cancer: http://www.ncbi.nlm.nih.gov/pubmed/12540506
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.
[+] [-] fr0sty|11 years ago|reply
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.
[+] [-] rudolf0|11 years ago|reply
Has there been any alleged mechanism of action for how ALA and EPA may cause harm?
[+] [-] aaxe|11 years ago|reply
You mean http://examine.com/blog/fish-oil-and-your-prostate/ ?
[+] [-] pbreit|11 years ago|reply
It's a shame how little we can depend on all these studies.
[+] [-] mrfusion|11 years ago|reply
[+] [-] therealdrag0|11 years ago|reply
[+] [-] palidanx|11 years ago|reply
[+] [-] wellpast|11 years ago|reply
[+] [-] mqsoh|11 years ago|reply
https://en.wikipedia.org/wiki/Myelin
[+] [-] moveroovee|11 years ago|reply
[+] [-] tghw|11 years ago|reply
[+] [-] evo_9|11 years ago|reply
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.
[+] [-] ggchappell|11 years ago|reply
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?
[+] [-] Zancarius|11 years ago|reply
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.
[+] [-] unknown|11 years ago|reply
[deleted]
[+] [-] jheriko|11 years ago|reply
slightly disappointed that the headline was not fish oil is actually snake oil? or something suitably witty... :)
[+] [-] pbreit|11 years ago|reply
[+] [-] cbd1984|11 years ago|reply
[+] [-] cbd1984|11 years ago|reply
[+] [-] seattlegal|11 years ago|reply
[+] [-] salibhai|11 years ago|reply
[deleted]