73 replies to this topic

[FunkOdyssey]

Mech Ageing Dev. 2006 Apr 16; [Epub ahead of print]
 
    Extended longevity of wild-derived mice is associated with peroxidation-resistant membranes.

    Hulbert AJ, Faulks SC, Harper JM, Miller RA, Buffenstein R.

    Metabolic Research Centre, University of Wollongong, Wollongong, NSW 2522, Australia; School of Biological Sciences, University of Wollongong, Wollongong, NSW 2522, Australia.

    Two lines of mice, Idaho (Id) and Majuro (Ma), both derived from wild-trapped progenitors, have previously been shown to have extended lifespans in captivity when compared to a genetically heterogenous laboratory line of mice (DC). We have examined whether membrane fatty composition varies with lifespan within the species Mus musculus in a similar manner to that previously demonstrated between mammal species. Muscle and liver phospholipids from these long-living mice lines have a reduced amount of the highly polyunsaturated omega-3 docosahexaenoic acid compared to the DC mice, and consequently their membranes are less likely to peroxidative damage. The relationship between maximum longevity and membrane peroxidation index is similar for these mice lines as previously observed for mammals in general. It is suggested that peroxidation-resistant membranes may be an important component of extended longevity.

    PMID: 16620917 [PubMed - as supplied by publisher]

[jaydfox]

Heh, I always did like MR's reasoning about this on the CR mailing list. His hypothesis had quite a few detractors, IIRC, but the logic seemed pretty good to me.

It's funny, because in a way, this would play right into the saturated fat advocates' point of view.

[zoolander]

Funk, could you possible post a summary of MR's anti-DHA stand?

Some recent info...

Last year a workshop was held at the Institute of Human Nutrition, Columbia University, New York, NY (22 may 2005). The topic of the workshop "n-3 fatty acids: Recommendations for Therapeutics and Prevention". The quote function is not working so I'm going straight into this

Here is a summary of their discussion:

PREGNANCY

Current knowledge for which a general consensus exists

1.High fish oil consumption is associated with an increase in gestational length and may reduce the rates of postpartum depression.
2.Women should have 100–300 mg DHA/d.

Gaps and recommendations for research and policy

1.More work should be done to assess whether these doses are associated with any increased bleeding.
2. More extensive dose-response studies should be conducted.
3. Further assessment of specific effects of DHA and EPA should be conducted on neuropsychological function, immune response, and rates of infection in the infant.

INFANTS

Current knowledge for which a general consensus exists
1.High intake ratios of EPA to DHA can lead to a decreased growth rate.
2.Current levels of DHA:AA (1.4:1 to 2:1) are beneficial for the visual and cognitive development of low-birth-weight infants and likely also normal-birth-weight infants.

Gaps and recommendations for research and policy
1.The role of ALA is poorly understood and should be further examined, but ALA likely cannot substitute for DHA.
2.Dose responses of AA and DHA need to be more fully characterized.
3. Whether DHA is beneficial for immune and allergic response in older infants should be examined.

CARDIOVASCULAR DISEASE

Current knowledge for which a general consensus on EPA and DHA exists
1. Reduced overall mortality after onset of cardiovascular disease.
2. Reduced sudden death and arrhythmias, primarily in secondary prevention trials.
3. Reduced blood triacylglycerol concentrations with higher doses.
4. May slightly increase LDL, but the increase is not clinically significant.
5. Limited effect associated with increased ALA.

Gaps and recommendations for research and policy
1. Dose-response data for EPA and DHA are limited and should be studied.
2. Some data from small clinical trials suggest that DHA alone is similar to or better than a combination of EPA plus DHA; these studies should be replicated in larger trials.
3.A large trial on the effects of n–3 fatty acids in the primary prevention of cardiovascular disease should be conducted.

MENTAL HEALTH

Current knowledge for which a general consensus exists
1.EPA plus DHA appear to have better efficacy than either alone.
2. DHA alone has not been effective.
3. n–3 Fatty acids are likely to improve psychotic, depressive, and aggressive symptoms in severe patients.

Gaps and recommendations for research and policy
1. A clear body of treatment data on effects of EPA, DHA, or both has not yet been developed for either schizophrenia, depressive, or aggressive disorders; thus, recommendations should be cautious.
2. Dose-response data and primary prevention trials are lacking.

AGING: DEMENTIA AND MACULAR DEGENERATION

Current knowledge for which a general consensus exists
1. Increased fish and DHA intake are protective against cognitive decline.
2. Fish consumption and DHA are associated with a reduced risk of developing Alzheimer disease.
3. DHA may improve mental function and reduce aggression in patients with dementia.
4. Consuming fish and low linoleic acid is associated with reduced risk of age-related macular degeneration.

Gaps and recommendations for research and policy
1. Dose-response and primary prevention studies for both dementia and age-related macular degeneration are needed.

METABOLIC SYNDROME

Current knowledge for which a general consensus exists
1. To improve insulin sensitivity, n–3 fatty acids are more useful in prevention than in treatment.
2. EPA plus DHA effectively lowers blood triacylglycerol concentrations.
3. High doses tend to decrease small, dense LDL concentrations and may improve insulin sensitivity.
4. Inclusion of n–3 fatty acids should be considered along with other lifestyle interventions such as exercise, diet, and medication.

Gaps and recommendations for research and policy
1. Dose-response studies should be examined, especially because different individuals seem to be affected differently by n–3 fatty acids. 2. An upper level of intake for benefit needs to be established.
3. A primary intervention or prevention trial should be conducted.

INFLAMMATORY AND IMMUNE RESPONSE

Current knowledge for which a general consensus exists
1. For rheumatoid arthritis, there is a proven therapeutic benefit of EPA plus DHA. All studies that monitored use of nonsteroidal antiinflammatory agents reported a significant reduction in use, and n–3 fatty acids reduce requirements for corticosteroids.
2. Although evidence is weaker for treatment of Crohn disease and psoriasis, n–3 fatty acids prolong remission in Crohn disease and reduce the requirement for corticosteroids in both conditions.
-Linolenic acid is not antiinflammatory at intakes <10 g/d.

Gaps and recommendations for research and policy
1. Dose-response and primary prevention studies are needed in all areas of inflammatory and immune response.
2. Some evidence exists that n–3 fatty acids are therapeutic for childhood asthma; more studies are needed.
3. There is contradictory or no evidence that n–3 fatty acids are therapeutic in the treatment of ulcerative colitis, systemic lupus erythematosus, or adult asthma; more studies are needed.

GENERAL CONCLUSIONS RELEVANT TO ALL AREAS

Current knowledge for which a general consensus exists
1. Preformed long-chain n–3 fatty acids, derived from marine or algal sources, are more efficient biologically than are plant-derived n–3 ALA.
2. The efficiency of conversion of plant-derived ALA to EPA and DHA, where it has been shown to be beneficial, is dependent in large part on the n–6 fatty acid content of the diet.

Gaps and recommendations for research advancing policy
1. In almost every area, data are insufficient to make recommendations for intake of specific n–3 fatty acids, eg, EPA versus DHA versus EPA + DHA combined.
2. To develop more specific recommendations, more data will be needed that compare dose-response relations for both EPA and DHA.
3. Biological effects of n–3 fatty acids will be better elucidated when tissue concentrations of each n–3 fatty acid are measured. Wherever possible, tissue concentrations should be used to develop dose-response curves. Determining the appropriate tissue still requires more research, but at this time, plasma concentrations can be used as a reliable surrogate when the specific tissue level of interest cannot be obtained.
4. The intake of n–6 fatty acids may markedly affect the n–3 fatty acid intake required to achieve a desirable tissue n–3 fatty acid level. Future studies should consider that higher n–6 fatty acid intakes may lead to higher n–3 fatty acid requirements to achieve desired biological effects.
5. Intervention trials at a given dosage or form of an n–3 fatty acid are not necessarily going to have the same effect as more prolonged or lifelong intakes of n–3 fatty acids. Therefore, intakes required to prevent a specific disease may be different from intakes required to treat a disease, and research data should be interpreted with this in mind.
6. Data are lacking for primary prevention in almost every health area, and secondary prevention trials do not necessarily predict the usefulness of n–3 fatty acids for primary prevention.
7. National public health initiatives to increase n–3 fatty acid consumption are needed; the working group believes that data are currently sufficient to indicate that intake of n–3 fatty acids is suboptimal, and a national and international initiative should be launched to shift n–3 fatty acid intake upward.
8. Cross-disciplinary initiatives should be encouraged when studying the effects of n–3 fatty acids (eg, if a mental health study is being performed, include endpoints relevant to cardiovascular disease).

There are statements above that report the current knowledge and general consensus of supplementation with EPA plus DHA to be beneficial for various population groups

[opales]

Funk, could you possible post a summary of MR's anti-DHA stand?

Here is the whole argument pretty much in full (one really long e-mail)

http://health.groups...y/message/12674

[doug123]

He's a hard core scientist. Skeptical, but able to decipher what's important and subtle patterns in the data. I will have to pour through the data in that link. I have great admiration for his attention to detail.

i don't know if he is definitively anti DHA as he is presenting the data that might suggest DHA supplements might have an adverse impact on maximum lifespan and other concerns. Maximum lifespan is in fact the main concern for many...particularly in this group...

Edited by nootropikamil, 14 June 2006 - 08:41 AM.

[opales]

He's a hard core scientist.  Skeptical, but able to decipher what's important in the data.  I will have to pour through the data in that link.

i don't know if he is definitively anti DHA as he is presenting the data that might suggest DHA supplements might have an adverse impact on maximum lifespan.  That's the main concern for many...particularly in this group...

Actually it is just not DHA but long chain PUFAs in general (thus including EPA), however, DHA being the ultimate culprit. I am not sure what you mean by being anti DHA but obviously in his opinion pure EPA/DHA should be (rather strictly) avoided and replaced with ALA, and that's anti DHA in my book.

[doug123]

Yeah, I did not read the whole thing; it's 1:41am. I am off to bed, Opales. Peace out.

[scottl]

Mech Ageing Dev. 2006 Apr 16; [Epub ahead of print]
 
    Extended longevity of wild-derived mice is associated with peroxidation-resistant membranes.

    Hulbert AJ, Faulks SC, Harper JM, Miller RA, Buffenstein R.

    Metabolic Research Centre, University of Wollongong, Wollongong, NSW 2522, Australia; School of Biological Sciences, University of Wollongong, Wollongong, NSW 2522, Australia.

    Two lines of mice, Idaho (Id) and Majuro (Ma), both derived from wild-trapped progenitors, have previously been shown to have extended lifespans in captivity when compared to a genetically heterogenous laboratory line of mice (DC). We have examined whether membrane fatty composition varies with lifespan within the species Mus musculus in a similar manner to that previously demonstrated between mammal species. Muscle and liver phospholipids from these long-living mice lines have a reduced amount of the highly polyunsaturated omega-3 docosahexaenoic acid compared to the DC mice, and consequently their membranes are less likely to peroxidative damage. The relationship between maximum longevity and membrane peroxidation index is similar for these mice lines as previously observed for mammals in general. It is suggested that peroxidation-resistant membranes may be an important component of extended longevity.

    PMID: 16620917 [PubMed - as supplied by publisher]

This is data in mice and mice data does not always carryover into the same results in humans.

OTOH there is data in humans as Zoolander has pointed out on the benefits in humans.

[FunkOdyssey]

This is data in mice and mice data does not always carryover into the same results in humans.

OTOH there is data in humans as Zoolander has pointed out on the benefits in humans.

There are no lifespan studies in humans we can reference here. I do not question the ability of fish oil to improve various parameters of health in the short-term. However, we know that eating more DHA will increase the DHA content of our membranes, and likewise increase their vulnerability to oxidation. Optimal short-term function vs. long-term durability are likely at odds here. If that is the case, then it makes sense to limit DHA, and to a lesser extent EPA, intake as much as possible without compromising function unacceptably.

It is worth noting that healthy populations do exist that include no fish in their diet and still manage to thrive by relying solely on the conversion of ALA to DHA and EPA. They are not essential nutrients.

[FunkOdyssey]

I encourage everyone who wants to participate in this discussion to please familiarize yourself with MR's hypothesis by following the link provided by Opales above.

[scottl]

QUOTE (FunkOdyssey)
Optimal short-term function vs. long-term durability are likely at odds here.
---------------------------------------------------------------------------------------------


Well ya except the data for one is more solid then the data for the other.

It may be a bad example but this reminds me of the person who questioned my personal use of high dose folic acid given the discussion of (forgive if I botch this wording as it is kinda over my head without more reading) of the problems with increased methylation and aging. The benefits to high dose folic acid (MR would disagree on dose, but that is another discussion) are mroe clear, while the other are more speculative (I believe).

.
QUOTE (FunkOdyssey)

It is worth noting that healthy populations do exist that include no fish in their diet and still manage to thrive by relying solely on the conversion of ALA to DHA and EPA. They are not essential nutrients.
--------------------------------------------------------------------------------------------------


healthy is not necessarily optimal, and barring having one's blood levels of various lipids measured I'll stick with the more certainty of taking preformed DPA/DHA.

Plus no one has mentioned the risk of increased prostate cancer linked with ALA (another discussion but probably needs to be mentioned even if I'm skeptical).


Sorry for the formatting but the board glitch (is a fix in the works??) ate my post.

[scottl]

Since I daren't edit my post:

healthy is not necessarily optimal, and barring having one's blood levels of various lipids measured I'll stick with the more certainty of taking preformed DPA/DHA **since one can't be sure of your conversion factor**.

[jaydfox]

I think I mentioned this in paleo's thread on fish oils, but I go for a hybrid approach. I eat a lot of ALA (ground flaxseed predominately, but I also use canola oil sometimes when I cook; I know I should add another source to dilute any negative effects of flaxseed that we'll discover five or ten years from now...), but I also eat fish from time to time. Not the best sources of fish: packaged tuna, store-bought salmon, restaurant salmon, sashimi and mackerel at a sushi restaurant, etc. But I only eat fish once every week or two, and usually a small serving, so any mercury or other toxins should be diluted, and it's mostly just a failsafe to get extra EPA/DHA in case my ALA conversion is inadequate.

[FunkOdyssey]

But I only eat fish once every week or two, and usually a small serving, so any mercury or other toxins should be diluted, and it's mostly just a failsafe to get extra EPA/DHA in case my ALA conversion is inadequate.

That's very reasonable, considering epidemiological studies suggest the limit of benefits from eating fish are reached at 1-2 servings a week.

http://circ.ahajourn...ull/107/21/2632

Taken together, the evidence from epidemiological studies suggests a possible threshold effect for n-3 PUFA intake. Compared with no (or very low) intake, modest dietary intake of fatty fish and n-3 PUFAs from seafood, the equivalent of 1 fatty fish meal a week, is associated with a marked (40% to 50%) reduction in sudden cardiac death.2–4 Thus, some intake of n-3 PUFAs from seafood appears to be better than none. On the other hand, there is little evidence from epidemiological studies that greater dietary intake of fatty fish is better than modest intake; more does not appear to be better than less. These findings are consistent with a threshold effect at modest dietary n-3 PUFA intake from seafood, rather than a dose-response effect. Additionally, we recently reported that in contrast to fatty fish, consumption of fried fish, typically low in n-3 PUFAs and not associated with n-3 plasma phospholipid levels, was not associated with a lower risk of fatal CHD or arrhythmic death among older adults.15 The available evidence, therefore, supports the clinical and public health recommendation for dietary intake of at least 1 fatty fish meal (high in n-3 PUFAs) per week.

[stellar]

I'll take my chances with fish oil. [thumb]

It improves my mood. However I do recall reading a study on Avant that basically stated , DHA's anti inflammatory action reduces the number of NK cells. So there is an upper limit, to how much you should take.

[rhakshasa]

I wish I could understand everything posted in here, so it's better to have higher EPA and lower DHA in fish oils?

[FunkOdyssey]

Yes, that is one of the take-home messages (another would be limiting fish oil intake all together).

[scottl]

That's very reasonable, considering epidemiological studies suggest the limit of benefits from eating fish are reached at 1-2 servings a week.

http://circ.ahajourn...ull/107/21/2632



"Taken together, the evidence from epidemiological studies suggests a possible threshold effect for n-3 PUFA intake. Compared with no (or very low) intake, modest dietary intake of fatty fish and n-3 PUFAs from seafood, the equivalent of 1 fatty fish meal a week, is associated with a marked (40% to 50%) reduction in sudden cardiac death.2–4 Thus, some intake of n-3 PUFAs from seafood appears to be better than none. On the other hand, there is little evidence from epidemiological studies that greater dietary intake of fatty fish is better than modest intake; more does not appear to be better than less. These findings are consistent with a threshold effect at modest dietary n-3 PUFA intake from seafood, rather than a dose-response effect. Additionally, we recently reported that in contrast to fatty fish, consumption of fried fish, typically low in n-3 PUFAs and not associated with n-3 plasma phospholipid levels, was not associated with a lower risk of fatal CHD or arrhythmic death among older adults.15 The available evidence, therefore, supports the clinical and public health recommendation for dietary intake of at least 1 fatty fish meal (high in n-3 PUFAs) per week."

Given the inherent unreliability of people's dietary recall and the inherent weaknesses of epidemiological studies, any conclusion is far from definitive. It is particularly interesting seeing nootropics slammed in one forum because of lack of quality proof and this advanced here.

Edit: not that what Jay is doing is necessarily unreasonable. But if his lipids are OK, no evidence of inflammation, etc them he might be getting enough.

[tedsez]

"I do recall reading a study on Avant that basically stated , DHA's anti inflammatory action reduces the number of NK cells"

So not only is fish oil both helpful and potentially harmful, but so is anti-inflammatory activity in general? Man, you just can't win!

[stellar]

"I do recall reading a study on Avant that basically stated , DHA's anti inflammatory action reduces the number of NK cells"

So not only is fish oil both helpful and potentially harmful, but so is anti-inflammatory activity in general

Not always, there are actually some supplements that are anti-inflammatory but at the same time also enhance your immune system. Lactoferrin might be one, curcumin is another I believe. There are others, I think Aged Garlic too.

[scottl]

"I do recall reading a study on Avant that basically stated , DHA's anti inflammatory action reduces the number of NK cells"

So not only is fish oil both helpful and potentially harmful, but so is anti-inflammatory activity in general? Man, you just can't win!

There is a delicate balance in many things e.g. blood clotting too quickly is bad, as is too slow. Many supps we take effect clotting. Think it is great to stimulate the immune system ad lib? THink again. Long term immune stimulation might not be a great thing as their are certain tumors of the immune system that might result from long term immune stimulation. Inflammation is needed, but again for many too much ismore of an issue then too little. So instead of demonizing things as black or white, reaize there is a balance.

Bhudda's way is the middle way.

[tedsez]

I was being a little bit facetious there.... But while I agree that it's important to find a balance, that can be difficult, especially when you start distilling natural products or synthesizing new ones. How much is enough to have an effect, but not too much? How do you figure in your body weight and metabolism, the amount of active ingredients in any particular brand, interactions with food and whatever other supplements you're taking at the same time, and the possibility that you might be getting some effects that you want and others that you don't?

Living forever is hard, that's all I'm saying.

[zoolander]

Just for the record



I haven't read MR's stand on DHA yet but will do so tonight.

As far as I understand his stand is based on a hypothesis and not on direct research. This does not make his stand invalid but rather open to discussion, which is what we are doing here. I curious though to know how much of the information presented in his stand with DHA supplementation has been taken on board because he is well respected and has this "God" factor attached to his name and how much was taken on board for its insightfulness based on a collection of studies brought together.

And considering he works on a supplement company research team it's going to hard to determine whether the information presented is there to drive sales or whether the information presented/assumed is accurate and the supplement companies supplements are based on this presented/assumed information. I'm not sure.

There is a little bit of doubt in my mind. This doubt results from the fact that he works for a supplement company and the fact that he may just be able to present convincing arguments to support his case. The fact of the matter is that he is a very knowledgable man and most would not be able to challenge his stand even if it were wrong.

[zoolander]

Sorry about the huge diagram above

I'm still reading MRs stand (MiFRAA). What does MiFRAA stand for? I would have gone for Micheal R Long chain Fatty acid hypothesis or MiLF

Found this though. Research released today

Nutr Rev. 2006 May;64(5 Pt 2):S24-33; discussion S72-91. 

    Nutrition in brain development and aging: role of essential fatty acids.
    Uauy R, Dangour AD.

    Nutrition and Public Health Intervention Research Unit, London School of Hygiene & Tropical Medicine, United Kingdom. ricardo.uauy@lshtm.ac.uk

    The essential fatty acids (EFAs), particularly the n-3 long-chain polyunsaturated fatty acids (LCPs), are important for brain development during both the fetal and postnatal period. They are also increasingly seen to be of value in limiting the cognitive decline during aging. EFA deficiency was first shown over 75 years ago, but the more subtle effects of the n-3 fatty acids in terms of skin changes, a poor response to linoleic acid supplementation, abnormal visual function, and peripheral neuropathy were only discovered later. Both n-3 and n-6 LCPs play important roles in neuronal growth, development of synaptic processing of neural cell interaction, and expression of genes regulating cell differentiation and growth. The fetus and placenta are dependent on maternal EFA supply for their growth and development, with docosahexaenomic acid (DHA)-supplemented infants showing significantly greater mental and psychomotor development scores (breast-fed children do even better). Dietary DHA is needed for the optimum functional maturation of the retina and visual cortex, with visual acuity and mental development seemingly improved by extra DHA. Aging is also associated with decreased brain levels of DHA: fish consumption is associated with decreased risk of dementia and Alzheimer's disease, and the reported daily use of fish-oil supplements has been linked to improved cognitive function scores, but confirmation of these effects is needed.

    PMID: 16770950 [PubMed - in process]

[opales]

I'm still reading MRs stand (MiFRAA). What does MiFRAA stand for? I would have gone for Micheal R Long chain Fatty acid hypothesis or MiLF

No it's actually MiRFAA (not MiFRAA) and stands for Michael Rae's Fish oil-Accelerated Aging (hypothesis). It is an obvious pun of Aubrey de Grey's MiFRA which stands for Mitochondrial Free Radical theory of Aging.

Aubrey and Michael are btw some sorts of SENS co-workers at the moment I think.

[zoolander]

I know this I was just playing dumb so that I could twist the abbreviation and try for a joke.

Lots of reading to do. this could take weeks

[doug123]

Just for the record

I haven't read MR's stand on DHA yet but will do so tonight.

As far as I understand his stand is based on a hypothesis and not on direct research. This does not make his stand invalid but rather open to discussion, which is what we are doing here. I curious though to know how much of the information presented in his stand with DHA supplementation has been taken on board because he is well respected and has this "God" factor attached to his name and how much was taken on board for its insightfulness based on a collection of studies brought together.

And considering he works on a supplement company research team it's going to hard to determine whether the information presented is there to drive sales or whether the information presented/assumed is accurate and the supplement companies supplements are based on this presented/assumed information. I'm not sure.

There is a little bit of doubt in my mind. This doubt results from the fact that he works for a supplement company and the fact that he may just be able to present convincing arguments to support his case. The fact of the matter is that he is a very knowledgable man and most would not be able to challenge his stand even if it were wrong.

Good lucking reading all of that.

Hmm...I consider myself pretty skeptical...I don't believe pretty much anything I read or hear -- and every idea is also open to interpretation too. That's also why talk is so cheap.

It's easy to make claims. To support them...however...requires evidence...if folks are self proclaimed anonymous "experts"-- on the web -- I tend to be even more skeptical than usual.

When someone uses a scientific reference, I first check to see it even exists.

Real scientists don't sell out to sales, if they are remotely concerned with thier credibility. If someone makes a lofty claim based on inconsistent evidence today; and we find out tomorrow that their claim was inaccurate, do you think we'd look to them again for a source of informatation regarding such an issue in the future?

Sure, it's easy to speculate...we see all kinds of anecdotes spread all over the web. Very few support their arguements with real evidence...

[scottl]

Zoo,

I do not think MR works for a supp company any more.

From brief interactions with him I consider him of high integrity and can't see him advocating things just to sell stuff even when he did work for them. Having said that, I do not agree with him on everything e.g. as you may gather by my comments on dosing of B vits in AORs multi.

[zoolander]

I agree Scott. he is indeed a very intelligent well researched man.

[FunkOdyssey]

And considering he works on a supplement company research team it's going to hard to determine whether the information presented is there to drive sales or whether the information presented/assumed is accurate and the supplement companies supplements are based on this presented/assumed information. I'm not sure.

AOR sells DHA and EPA supplements, so if anything, MR's arguments against their use are exceptionally counterproductive from a sales perspective.