26 replies to this topic

[xsiv1]

Ruh Roh

http://www.medscape....58684PR&spon=17

[ta5]

It was 1g of fish oil. That's not much. What kind of fish oil? How much epa and dha?
It was in Italy, near the Mediterranean. How many in both groups were eating fish regularly anyway?



N Engl J Med. 2013 May 9

n-3 fatty acids in patients with multiple cardiovascular risk factors.

BACKGROUND:
Trials have shown a beneficial effect of n-3 polyunsaturated fatty acids in patients with a previous myocardial infarction or heart failure. We evaluated the potential benefit of such therapy in patients with multiple cardiovascular risk factors or atherosclerotic vascular disease who had not had a myocardial infarction.
METHODS:
In this double-blind, placebo-controlled clinical trial, we enrolled a cohort of patients who were followed by a network of 860 general practitioners in Italy. Eligible patients were men and women with multiple cardiovascular risk factors or atherosclerotic vascular disease but not myocardial infarction. Patients were randomly assigned to n-3 fatty acids (1 g daily) or placebo (olive oil). The initially specified primary end point was the cumulative rate of death, nonfatal myocardial infarction, and nonfatal stroke. At 1 year, after the event rate was found to be lower than anticipated, the primary end point was revised as time to death from cardiovascular causes or admission to the hospital for cardiovascular causes.
RESULTS:
Of the 12,513 patients enrolled, 6244 were randomly assigned to n-3 fatty acids and 6269 to placebo. With a median of 5 years of follow-up, the primary end point occurred in 1478 of 12,505 patients included in the analysis (11.8%), of whom 733 of 6239 (11.7%) had received n-3 fatty acids and 745 of 6266 (11.9%) had received placebo (adjusted hazard ratio with n-3 fatty acids, 0.97; 95% confidence interval, 0.88 to 1.08; P=0.58). The same null results were observed for all the secondary end points.
CONCLUSIONS:
In a large general-practice cohort of patients with multiple cardiovascular risk factors, daily treatment with n-3 fatty acids did not reduce cardiovascular mortality and morbidity. (Funded by Società Prodotti Antibiotici and others; ClinicalTrials.gov number, NCT00317707.).
PMID: 23656645

[joelcairo]

The "placebo" was olive oil? Really?

[niner]

I'm not sure I buy Topol's logic regarding the trial population. They were in pretty bad shape- hypercholesterolemic, diabetic, and atherosclerotic. He says if fish oil doesn't help them, it won't help anyone. Maybe if they'd used fish oil before they were such a mess, they'd be healthier. The trial showed that fish oil isn't a miracle cure for people on the verge of a cardiovascular event. To try to extend it to healthy people seems like a stretch.

[xsiv1]

I find it a stretch to make this proclamation:


What Does This Say About Fish Oil?

I don't know about you, but I have an awful lot of patients who come to me on fish oil and I try to implore them to stop taking it. This trial arms us [with proof against fish oils] for our patients who have not had an MI, who have not had heart failure, where the worry is not suppression of ventricular arrhythmia (and even that is a little suspect). Fish oil does nothing and we cannot continue to argue about either "the right dose" or "the right preparation." It's a "nada effect."

I think this is a really important trial in cardiovascular medicine. It's also interesting that 70% of the patients [in the trial] had hypercholesterolemia and only 40% were taking statins. This group [of patients] was even more "loaded," if you will, to derive some benefit.

Fish oil is a "no-go." If it doesn't work in this group, it's hard to imagine in lesser-risk groups that it's going to have any salutary impact.

[majkinetor]

>I find it a stretch to make this proclamation:

Indeed. Fish oil benefits are not limited to cardiovascular system. It also has indirect effect, i.e. it help somewhat with obesity and it has direct role as COX inihibitor and antiplatelete agent. If fish oil doesn't work, why do CD patientes take aspirin...

[xsiv1]

It's funny that my own cardiologist whom I visited after experiencing subtle and intermittent chest pain told me that fish oils have a direct impact on heart health at 6grams per day which I said is a lot! He said, well, some, is better than none. Every test I conducted came back clear including the stress test where they had me running on a full incline at 8mph. Never sweat so much in my life and I work out 5 days a week...and end up sweaty as hell. That's at 45-1hr. The stress test took 11 minutes just to get my heart rate to 162 at age 40. I'll continue to take them as I believe they have an affect on mood and cognition.

[mikeinnaples]

Why in the name of science would they use Olive Oil as a placebo? Were those conducting the study completely ignorant of the studies involving olive oil itself?

I am not even sure what to say about this.....

[zorba990]

Why in the name of science would they use Olive Oil as a placebo? Were those conducting the study completely ignorant of the studies involving olive oil itself?

I am not even sure what to say about this.....

And how does something like that pass peer review?

[joelcairo]

Why in the name of science would they use Olive Oil as a placebo? Were those conducting the study completely ignorant of the studies involving olive oil itself?

I am not even sure what to say about this.....

Exactly. Why is it they couldn't use plain water instead? I can see that then critics could point out that test subjects were getting an extra tablespoon or so of oil in their diets, but that would be a far better proxy for testing fish oil supplementation vs. non-supplementation.

BTW, the study was looking at dosing with 1g of omega-3 fatty acids, not 1g of fish oil. Based on the EPA/DHA content of fish oil works out to about a tablespoon of fish oil, maybe a bit less. Please correct me if I'm wrong.

[niner]

One gram of olive oil isn't going to do much of anything. In the Spanish cohort from the EPIC trial, where they looked at the health effects of olive oil consumption, the top quartile where the biggest health benefit was noted had an olive oil consumption of 30g/day. I don't think the argument that the placebo was "active" holds much water.

[nameless]

BTW, the study was looking at dosing with 1g of omega-3 fatty acids, not 1g of fish oil. Based on the EPA/DHA content of fish oil works out to about a tablespoon of fish oil, maybe a bit less. Please correct me if I'm wrong.

If 1g of EPA/DHA, and let's say 30% concentration, that would be around 3g of olive oil. That's probably too little still to have much of any effect. And if it was 1g of fish oil (not omega content), then it would seem to be too dinky amount to make any difference on the fish oil side of things.

But yeah, I agree, ideally they wouldn't use olive oil as a placebo. The argument against using water would be that perhaps the participants would notice the difference, as the consistency is different.... I guess. But unless the olive oil had a fishy taste, I'd think they could tell the difference regardless.

What I would find interesting, (and I assume they didn't do it, as I didn't read the full study) is if they measured Omega 3 serum levels amongst all participants. That way they could perhaps see if those who didn't eat fish regularly received some benefit. If the entire group ate fish several times weekly, it may simply mean extra omega 3s won't matter at that point.

Edited by nameless, 15 May 2013 - 10:57 PM.

[nowayout]

The guy who does the large mouse screenings, someone remind me what his name was (they have been discussed in more than one recent thread) said at a rcent conference that fish oil not only didn't extend lifespan, but actually had a negative effect.

Of course mice are not people, but just thought it worth mentioning.

[joelcairo]

One gram of olive oil isn't going to do much of anything. In the Spanish cohort from the EPIC trial, where they looked at the health effects of olive oil consumption, the top quartile where the biggest health benefit was noted had an olive oil consumption of 30g/day. I don't think the argument that the placebo was "active" holds much water.

I believe it would be 3 to 4 grams, but given that the study was conducted in Italy then you could have a valid point. In the UK or North America, I would think the majority of the population gets little or no olive oil on a daily basis. I don't even know how you go about getting 30g in your diet every day.

But let's think this through... If for argument's sake, the typical intake of olive oil in Italy is such that the addition of another tbsp isn't going to have much effect, then maybe this group is getting its cardio benefits from olive oil, i.e.the "Mediterranean Diet". After all, nobody's saying there's nothing magic about fish oil. It's primary benefit is probably to put balance out the overconsumption of omega-6 oils, which is similar to what olive oil does.

[Hebbeh]

Why in the name of science would they use Olive Oil as a placebo? Were those conducting the study completely ignorant of the studies involving olive oil itself?

I am not even sure what to say about this.....

Exactly. Why is it they couldn't use plain water instead? I can see that then critics could point out that test subjects were getting an extra tablespoon or so of oil in their diets, but that would be a far better proxy for testing fish oil supplementation vs. non-supplementation.

BTW, the study was looking at dosing with 1g of omega-3 fatty acids, not 1g of fish oil. Based on the EPA/DHA content of fish oil works out to about a tablespoon of fish oil, maybe a bit less. Please correct me if I'm wrong.

I didn't read the study but standard fish oil usually has 180mg of EPA + 120mg of DHA = 300mg per 1gram of fish oil. There are other omega-3 components in addition to EPA/DHA in the fish but just counting the EPA/DHA it would take 3.3 grams of fish oil to yield 1 gram of EPA/DHA. A tablespoon of oil contains 15 grams oil or 4.55 grams of EPA/DHA. So if in fact they were getting 1 gram EPA/DHA, that would equate to 3.3 grams standard fish oil....less than 3 grams if high concentration EPA/DHA oil.

edit....looks like nameless beat me to it and I was late to the party..

Edited by Hebbeh, 16 May 2013 - 12:26 AM.

[joelcairo]

Thanks. I guess even 30 grams of olive oil is not really that much to get into your diet.

Edited by joelcairo, 16 May 2013 - 12:40 AM.

[niner]

Fish oil might also be useless in secondary prevention:

Arch Intern Med. 2012 May 14;172(9):686-94. doi: 10.1001/archinternmed.2012.262.
Efficacy of omega-3 fatty acid supplements (eicosapentaenoic acid and docosahexaenoic acid) in the secondary prevention of cardiovascular disease: a meta-analysis of randomized, double-blind, placebo-controlled trials.
Kwak SM, Myung SK, Lee YJ, Seo HG; Korean Meta-analysis Study Group.

Center for Cancer Prevention and Detection, Ilsan, Republic of Korea.
BACKGROUND:

Although previous randomized, double-blind, placebo-controlled trials reported the efficacy of omega-3 fatty acid supplements in the secondary prevention of cardiovascular disease (CVD), the evidence remains inconclusive. Using a meta-analysis, we investigated the efficacy of eicosapentaenoic acid and docosahexaenoic acid in the secondary prevention of CVD.
METHODS:

We searched PubMed, EMBASE, and the Cochrane Library in April 2011. Two of us independently reviewed and selected eligible randomized controlled trials.
RESULTS:

Of 1007 articles retrieved, 14 randomized, double-blind, placebo-controlled trials (involving 20 485 patients with a history of CVD) were included in the final analyses. Supplementation with omega-3 fatty acids did not reduce the risk of overall cardiovascular events (relative risk, 0.99; 95% CI, 0.89-1.09), all-cause mortality, sudden cardiac death, myocardial infarction, congestive heart failure, or transient ischemic attack and stroke. There was a small reduction in cardiovascular death (relative risk, 0.91; 95% CI, 0.84-0.99), which disappeared when we excluded a study with major methodological problems. Furthermore, no significant preventive effect was observed in subgroup analyses by the following: country location, inland or coastal geographic area, history of CVD, concomitant medication use, type of placebo material in the trial, methodological quality of the trial, duration of treatment, dosage of eicosapentaenoic acid or docosahexaenoic acid, or use of fish oil supplementation only as treatment.
CONCLUSION:

Our meta-analysis showed insufficient evidence of a secondary preventive effect of omega-3 fatty acid supplements against overall cardiovascular events among patients with a history of cardiovascular disease.
Comment in

ACP Journal Club: review: omega-3 fatty acid supplements provide no protective benefit in cardiovascular disease. [Ann Intern Med. 2012]
The big ones that got away: omega-3 meta-analysis flawed by excluding the biggest fish oil trials. [Arch Intern Med. 2012]
Omega-3 fatty acids and secondary prevention of cardiovascular disease-is it just a fish tale?: comment on “Efficacy of omega-3 fatty acid supplements (eicosapentaenoic acid and docosahexaenoic acid) in the secondary prevention of cardiovascular disease”. [Arch Intern Med. 2012]

PMID: 22493407

Bear in mind that EPA and DHA, being highly oxidation prone, are harmful in large quantities. "large", in this context, isn't all that much. It would be really interesting to see all the fish oil results stratified by ApoE genotype. The response to fish oil varies according to ApoE type.

[joelcairo]

Here's a published response to the preceding study. I don't have a strong opinion on this subject either way, BTW. I do take fish oil but not for cardio protection. What I do have strong feelings about is doctors like EricTopol prematurely trumpeting that we have "proof" that fish oil "does nothing". Certainty is the enemy of wisdom.

The Big Ones That Got Away: Omega-3 Meta-analysis Flawed by Excluding the Biggest Fish Oil Trials
http://archinte.jama...ticleid=1377495

[xsiv1]

Here's a published response to the preceding study. I don't have a strong opinion on this subject either way, BTW. I do take fish oil but not for cardio protection. What I do have strong feelings about is doctors like EricTopol prematurely trumpeting that we have "proof" that fish oil "does nothing". Certainty is the enemy of wisdom.

The Big Ones That Got Away: Omega-3 Meta-analysis Flawed by Excluding the Biggest Fish Oil Trials
http://archinte.jama...ticleid=1377495

My sentiments exactly. Science changes and discoveries are often trumped by another. It's proven all the time when we see certain pharmaceutical drugs that become approved for human use only to be discovered as actually promulgating the opposite desire effects. Statins for example have no evidence whatsoever that they prevent death, MI, and other cardiac events from occurring. In fact, there's evidence suggesting that they actually may increase the risk for diabetes and stroke.

Taking various antioxidants is something anyone should consider regardless of whether or not they take EFA's if they're truly interested in 'longevity'. The problem lies in assessing which ones are the most useful and offer the broadest spectrum of beneficial effects.

Although simplified, and rather old, wasn't it stated that the Eskimo population who consume high amounts of fat and EFA's naturally in their diet had one of the lowest incidents on cardiovascular disease? I realize there's probably a dozen or more intervening variables but I wish I could find that study just to read through it again. I personally take 2 grams of high content EPA/DHA capsule EFA's per day and have noticed positive effects on mood and certain joints that used to be problematic when running or weight training. Otherwise, nothing has changed in my supplement regimen barring a varying cycle(s) of nootropics.

[majkinetor]

Although simplified, and rather old, wasn't it stated that the Eskimo population who consume high amounts of fat and EFA's naturally in their diet had one of the lowest incidents on cardiovascular disease?

Its really optimistic to describe that via EFAs. The eskimos are also on ketogenic diet for instance which lowers Tg by huge. Its probable that combination of those factors are in play, but possibly many others - clean air/environment, absence of industrial food etc. Nick Lane also described beneficial mitochondrial mutation as alternative explanation.

Personally, I think DHA/EPA are great, especially for little kids and especially in those with learning disabilities. I find it strange that supplement would enhance brain function in detriment to overall health.

[Mind]

The guy who does the large mouse screenings, someone remind me what his name was (they have been discussed in more than one recent thread) said at a rcent conference that fish oil not only didn't extend lifespan, but actually had a negative effect.

Of course mice are not people, but just thought it worth mentioning.

Spindler

[Ultravioletbllc]

I'm not sure I buy Topol's logic regarding the trial population. They were in pretty bad shape- hypercholesterolemic, diabetic, and atherosclerotic. He says if fish oil doesn't help them, it won't help anyone. Maybe if they'd used fish oil before they were such a mess, they'd be healthier. The trial showed that fish oil isn't a miracle cure for people on the verge of a cardiovascular event. To try to extend it to healthy people seems like a stretch.

I could not agree more ..... ( in my best self important atypical higher then Internet shrouded longecity voice) " apparently he's not up to date on sears work" (dr william sears and dr James sears .....who's amazing book " the omega3 effect is a must own for those interested in Nootropia or life extension). Saying omega threes do nothing is akin too telling me about the merits of 1,4-butanediol ..,,, please jus stop cause I'm not Trynna hear that shit !

[nowayout]

Most panaceas aren't.

Edited by nowayout, 11 July 2013 - 01:49 PM.

[ironfistx]

All fish oil did for me was make me sleepy.

[lazarian]

I think the hypothesis should be more specific in order to eliminate discussion around its legitimacy.

[ta5]

The full study can be found here.

STUDY PROCEDURES
Study patients were randomly assigned to receive one capsule daily containing 1 g of n−3 fatty acids (polyunsaturated fatty acid ethyl esters with eicosapentaenoic acid and docosahexaenoic acid content not <85%, in a ratio that could range from 0.9:1 to 1.5:1) or placebo (olive oil). Treatment was centrally assigned by means of telephone on the basis of a concealed, computer-generated randomization list, stratified according to general practitioner. Patients, general practitioners, coordination and statistical staff, and outcome assessors were unaware of the study assignments until the final analyses were completed.

They got as little as 850mg of EPA+DHA. In both groups, about 24% never ate fish, 43% ate fish once a week, 27% twice, and 6% three or more times per week.

It's an interesting study. I would like to have seen a dose of 2-3 grams EPA+DHA.

[nameless]

They got as little as 850mg of EPA+DHA. In both groups, about 24% never ate fish, 43% ate fish once a week, 27% twice, and 6% three or more times per week.

It's an interesting study. I would like to have seen a dose of 2-3 grams EPA+DHA.

Did a quick glance, but didn't see if they did any subgroup analysis. Did they mention any results for just those who never ate fish? If there is any benefit at all from 850mg EPA/DHA, it's possible it'd only be in those who consume little to no omega 3s from diet.

Or it's very possible the only benefit is in those prone to arrhythmias, which they mention in the study.