Fish Oil

[Julie G]

Ageing and apoE change DHA homeostasis: relevance to age-related cognitive decline.
http://www.ncbi.nlm.nih.gov/m/pubmed/24 ... ated%20fat

"Compared with young adults, blood DHA is often slightly but significantly higher in older adults without any age-related cognitive decline. Higher plasma DHA in older adults could be a sign that their fish or DHA intake is higher. However, our supplementation and carbon-13 tracer studies also show that DHA metabolism, e.g. transit through the plasma, apparent retroconversion and β-oxidation, is altered in healthy older compared with healthy young adults. ApoE4 increases the risk of AD, possibly in part because it too changes DHA homeostasis. Therefore, independent of differences in fish intake, changing DHA homeostasis may tend to obscure the relationship between DHA intake and plasma DHA which, in turn, may contribute to making older adults more susceptible to cognitive decline despite older adults having similar or sometimes higher plasma DHA than in younger adults

[Julie G]

I had an opportunity to read the full-text of the link above & had a few thoughts. Inadequate DHA levels have long been associated with lower levels on cognitive testing. Surprisingly, AD patients showed normal levels of DHA in the temporal and frontal cortices of the brain, while the AD hippocampus (central to memory processing and learning) consistently demonstrated low levels. (This is also the area of the brain that shows shrinkage prior to symptom onset.)

It is now emerging that the apoE4 status also affects DHA metabolism in human subjects. This interaction may help explain why the protective association of higher dietary intake of fish or higher erythrocyte total n-3 fatty acids is generally limited to non-carriers of apoE4. ApoE4 seems also to supress the plasma DHA response to a fish oil supplement. After a marked single DHA dose, E4s show lower levels, for a full 28 days, than controls. After a 2nd dose (5 months later) E4s show higher levels than control. These erratic levels demonstrate impaired transport and clearance- which is precisely what research on the E4 apolipoprotein has shown. E4s transport and clear lipids poorly.

This may be why some researchers (like the UCLA team) suggest that E4s should take higher doses to get the same benefit. This group recommends taking fish oil with curcumin (to prevent oxidation) on an empty stomach. More testing needs to be done to demonstrate efficacy on our population.

[James]

It is now emerging that the apoE4 status also affects DHA metabolism in human subjects...

This popped up last week:

http://www.ncbi.nlm.nih.gov/pubmed/24345162

Reduction in DHA transport to the brain of mice expressing human APOE4 compared to APOE2.
Vandal M, Alata W, Tremblay C, Rioux-Perreault C, Salem Jr N, Calon F, Plourde M.
J Neurochem. 2013 Dec 18. doi: 10.1111/jnc.12640. [Epub ahead of print]

Abstract
Benefits on cognition from docosahexaenoic acid (DHA, 22:6 n-3) intake are absent in humans carrying apolipoprotein E ε4 allele (APOE4), the most important genetic risk factor for Alzheimer's Disease (AD). To test the hypothesis that carrying APOE4 impairs DHA distribution, we evaluated plasma and brain fatty acid profiles and uptake of [14 C]-DHA using in situ cerebral perfusion through the blood-brain barrier in 4 and 13-month-old male and female APOE-targeted replacement mice (APOE2, APOE3 and APOE4), fed with a DHA-depleted diet. Cortical and plasma DHA were 9% lower and 34% higher in APOE4 compared to APOE2 mice, respectively. Brain uptake of [14 C]-DHA was 24% lower in APOE4 versus APOE2 mice. A significant relationship was established between DHA and apoE concentrations in the cortex of mice (r2 = 0.21) and AD patients (r2 = 0.32). Altogether, our results suggest that lower brain uptake of DHA in APOE4 than in APOE2 mice may limit the accumulation of DHA in cerebral tissues. These data provide a mechanistic explanation for the lack of benefit of DHA in APOE4 carriers on cognitive function and the risk of AD.

[James]

This also popped up last week.


http://www.ncbi.nlm.nih.gov/pubmed/24353345

Cognitive Performance in Older Adults Is Inversely Associated with Fish Consumption but Not Erythrocyte Membrane n-3 Fatty Acids.
Danthiir V, Hosking D, Burns NR, Wilson C, Nettelbeck T, Calvaresi E, Clifton P, Wittert GA.
J Nutr. 2013 Dec 18. [Epub ahead of print]

Abstract
Higher n-3 (ω-3) polyunsaturated fatty acids (PUFAs) and fish intake may help maintain cognitive function in older age. However, evidence is inconsistent; few studies have examined the relation in cognitively healthy individuals across numerous cognitive domains, and none to our knowledge have considered lifetime fish intake. We examined associations between multiple domains of cognition and erythrocyte membrane n-3 PUFA proportions and historical and contemporary fish intake in 390 normal older adults, analyzing baseline data from the Older People, Omega-3, and Cognitive Health trial. We measured n-3 PUFA in erythrocyte membranes, and we assessed historical and contemporary fish intake by food-frequency questionnaires. We assessed cognitive performance on reasoning, working memory, short-term memory, retrieval fluency, perceptual speed, simple/choice reaction time, speed of memory-scanning, reasoning speed, inhibition, and psychomotor speed. Cognitive outcomes for each construct were factor scores from confirmatory factor analysis. Multiple linear regression models controlled for a number of potential confounding factors, including age, education, sex, Apolipoprotein E epsilon 4 allele, physical activity, smoking, alcohol intake, socioeconomic variables, and other health-related variables. Higher erythrocyte membrane eicosapaentonoic acid proportions predicted slower perceptual and reasoning speed in females, which was attenuated once current fish intake was controlled. No other associations were present between n-3 PUFA proportions and cognitive performance. Higher current fish consumption predicted worse performance on several cognitive speed constructs. Greater fish consumption in childhood predicted slower perceptual speed and simple/choice reaction time. We found no evidence to support the hypothesis that higher proportions of long-chain n-3 fatty acids or fish intake benefits cognitive performance in normal older adults.

I don't have access to the full-text to see what they say in the discussion. From what I can tell the above paper is the first publication of data from the 2011 EPOCH trial.

http://www.ncbi.nlm.nih.gov/pubmed/22011460

The older people, omega-3, and cognitive health (EPOCH) trial design and methodology: a randomised, double-blind, controlled trial investigating the effect of long-chain omega-3 fatty acids on cognitive ageing and wellbeing in cognitively healthy older adults.
Danthiir V, Burns NR, Nettelbeck T, Wilson C, Wittert G.
Nutr J. 2011 Oct 20;10:117. doi: 10.1186/1475-2891-10-117.

BACKGROUND:
Some studies have suggested an association between omega-3 long-chain polyunsaturated fatty acids (n-3 LC PUFAs) and better cognitive outcomes in older adults. To date, only two randomised, controlled trials have assessed the effect of n-3 LC PUFA supplementation on cognitive function in older cognitively healthy populations. Of these trials only one found a benefit, in the subgroup carrying the ApoE-ε4 allele. The benefits of n-3 LC PUFA supplementation on cognitive function in older normal populations thus still remain unclear. The main objective of the current study was to provide a comprehensive assessment of the potential of n-3 LC PUFAs to slow cognitive decline in normal elderly people, and included ApoE-ε4 allele carriage as a potential moderating factor. The detailed methodology of the trial is reported herein.

METHODS:
The study was a parallel, 18-month, randomised, double-blind, placebo-controlled intervention with assessment at baseline and repeated 6-monthly. Participants (N = 391, 53.7% female) aged 65-90 years, English-speaking and with normal cognitive function, were recruited from metropolitan Adelaide, South Australia. Participants in the intervention arm received capsules containing fish-oil at a daily dosage of 1720 mg of docosahexaenoic acid and 600 mg of eicosapentaenoic acid while the placebo arm received the equivalent amount of olive oil in their capsules. The primary outcome is rate of change in cognitive performance, as measured by latent variables for the cognitive constructs (encompassing Reasoning, Working Memory, Short-term Memory, Retrieval Fluency, Inhibition, Simple and Choice-Reaction Time, Perceptual Speed, Odd-man-out Reaction Time, Speed of Memory Scanning, and Psychomotor Speed) and assessed by latent growth curve modeling. Secondary outcomes are change in the Mini-mental State Examination, functional capacity and well-being (including health status, depression, mood, and self-report cognitive functioning), blood pressure, and biomarkers of n-3 LC PUFA status, glucose, lipid metabolism, inflammation, oxidative stress, and DNA damage.

TRIAL REGISTRATION:
Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12607000278437.

[Julie G]

Head spinning, James The first study corroborates what I've long suspected about the inefficiency of the ApoE4 allele to carry and deliver fish oil...and all lipids.

The 2nd study (from EPOCH) contradicts MUCH previous work. I'd love to see full-text on that. Might speak to the toxicity and radioactivity of our modern fish supply...not to mention unhealthful preparation

[Gilgamesh]

From James, at the CR Society email list. I've been moving towards less EPA/DHA supplementation and more chia seeds/walnuts/fish. This gives me an additional reason to continue with this change.


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I don't have access to the first article, but the second one is a great
free full-text review.

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http://www.ncbi.nlm.nih.gov/pubmed/23863036

Effect of omega-3 dietary supplements with different oxidation levels in
the lipidic profile of women: a randomized controlled trial.

García-Hernández VM, Gallar M, Sánchez-Soriano J, Micol V, Roche E,
García-García E.
Int J Food Sci Nutr. 2013 Dec;64(8):993-1000. doi:
10.3109/09637486.2013.812619. Epub 2013 Jul 18.

The oxidation level of omega-3 fatty acid supplements commercialized in
capsules may be a risk to consumers' health. For this purpose, we have
designed a single-blind, parallel-group, randomized controlled trial in
which 52 women participated. Volunteers were randomly distributed into
three groups consuming: (1) less oxidized oil pills, (2) highly oxidized
oil pills and (3) no capsules. All groups consumed a fish-rich diet.
Circulating glucose, total cholesterol, triglycerides and glutamic pyruvic
transaminase were determined at the beginning and end (30 days) of the
study. As a result, the ingestion of less oxidized ω-3 supplements reduced
circulating triglyceride and cholesterol levels, as opposed to the highly
oxidized omega-3 capsules, which had a negative effect on cholesterol
levels. In conclusion, the level of oxidation of the supplements is a key
factor in controlling circulating lipid profile. Therefore, manufacturers
must pay attention to the quality of the prime product prior to
encapsulation.

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http://www.ncbi.nlm.nih.gov/pubmed/23738326

Oxidation of marine omega-3 supplements and human health.

Albert BB, Cameron-Smith D, Hofman PL, Cutfield WS.
Biomed Res Int. 2013;2013:464921. doi: 10.1155/2013/464921. Epub 2013 Apr
30.

Marine omega-3 rich oils are used by more than a third of American adults
for a wide range of purported benefits including prevention of
cardiovascular disease. These oils are highly prone to oxidation to lipid
peroxides and other secondary oxidation products. Oxidized oils may have
altered biological activity making them ineffective or harmful, though
there is also evidence that some beneficial effects of marine oils could be
mediated through lipid peroxides. To date, human clinical trials have not
reported the oxidative status of the trial oil. This makes it impossible to
understand the importance of oxidation to efficacy or harm. However, animal
studies show that oxidized lipid products can cause harm. Oxidation of
trial oils may be responsible for the conflicting omega-3 trial literature [Emphasis mine. -GB],
including the prevention of cardiovascular disease. The oxidative state of
an oil can be simply determined by the peroxide value and anisidine value
assays. We recommend that all clinical trials investigating omega-3 harms
or benefits report the results of these assays; this will enable better
understanding of the benefits and harms of omega-3 and the clinical
importance of oxidized supplements.
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James

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GB

[Julie G]

Thanks for sharing James & G- our first duo-posting (How's that for " bro-science?"- Mark's term ) Do you think there's any benefit to using plant based DHA?

[Julie G]

Quick housekeeping question; should this be merged with our "fish oil" thread under the supplement category? It's always nice to have all info in one place.

Also, I'd still love to hear anyone's opinion on whether or not Algae DHA is just as susceptible to oxidation as that derived from fish Seems like it would be more stable...

[SpunkyPup]

take you vitamin E and axasthanin at the same time as fish oil which we only need a small dose <1000mg

[Gilgamesh]

Quick housekeeping question; should this be merged with our "fish oil" thread under the supplement category? It's always nice to have all info in one place.

Yes! But we change the description of the topic from "Discuss and share your supplement regime" to just, well, "supplements". Too narrow otherwise.

GB