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Relation of Fish, Mercury and Plant Omega-3s to Brain Health

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Like we've seen for cardiovascular disease, eating fish can be a mixed blessing. The omega-3 fatty acids (DHA/EPA) are thought to be beneficial, particularly for brain function. But the mercury, PCBs and other contaminants that bioaccumulate in the fat of fish may also have harmful effects. This new study[1] (thanks to Al Pater!) looks at the association between consumption of fish, plant omega-3s, brain mercury levels and Alzheimer's disease and brain mini-strokes.


What they found is a bit nuanced, but worth thinking about.


They gave 550 quite elderly but initially dementia-free people in several US nursing homes a yearly dietary questionnaire to measure their weekly intake of fish, DHA/EPA and the plant-derived omega-3 Alpha Linolenic Acid (ALA) until they died. Over an average follow-up of 4.5 years, 286 of the participates died (average age 89!). These folks' brains were autopsied to measure mercury levels and to look for physical signs of Alzheimer's disease (plaques and tangles) as well as brain injuries associated with other forms of dementia, in particular macroinfarctions and microinfarctions (i.e. strokes of various sizes). 


Here are the highlights of what they found:

  • The more fish meals per week a subject consumed, the higher their brain mercury level (P < 0.02). There was no correlation between intake of ALA or DHA/EPA supplements and brain mercury level.
  • For the majority of people (77%) who weren't carriers of the APOE4 allele that increases one's susceptibility to Alzheimer's disease, neither eating fish, dietary DHA/EPA nor consuming ALA had a significant effect (one way or the other) on the risk of Alzheimer's disease.
  • For the minority (23%) of subjects who were APOE4 carriers, eating more fish and more dietary DHA/EPA was associated with a decreased risk of Alzheimer's disease markers (P < 0.04). Neither DHA/EPA supplements nor dietary ALA impacted Alzheimer's risk in these folks.
  • Dietary ALA, but not fish or DHA/EPA, was associated with reduced prevalence of macroinfarctions (P < 0.03) and microinfarctions (P < 0.04) associated with non-Alzheimer's cognitive impairment, independent of APOE4 status.

Those were the major, statistically significant findings. There is one more thing I noticed looking at the table below that appears interesting/suggestive for the majority of us who are lucky enough not have the APOE4 gene. The cells I've highlighted below represent the level of various markers of Alzheimer's disease for APOE4-negative folks.




The red cells represent the level of Alzheimer's markers for people who ate the most fish (top red row), or the most dietary DHA/EPA (bottom red row). From the confidence intervals, you can see that none of them are individually significant. But also notice that all of them are positive, meaning there was a trend towards increased markers of Alzheimer's disease in APOE4-negative people who ate the most fish, especially fatty fish.


In contrast, now look at the green cells, representing markers for Alzheimer's disease in APOE4-negative people who consumed the most plant-derived ALA. Notice these too are not individually significant, but all of them are negative, pointing towards a reduced risk of Alzheimer's disease with increasing ALA intake.


From all this, my summary takeaway message from this study would be the following:

  • For people with the APOE4 gene and therefore increased risk of Alzheimer's disease, eating fish is likely to reduce one's risk of Alzheimer's disease, despite increasing brain mercury levels
  • For people without the APOE4 gene, fish consumption doesn't seem to reduce, and may even increase, one's risk of Alzheimer's disease
  • For people without the APOE4 gene, plant-derived omega-3 ALA (e.g. from walnuts, olive oil, flax, chia) consumption may reduce one's risk of Alzheimer's disease
  • For everyone, dietary ALA appears to reduce one's risk of brain markers for non-Alzheimer's cognitive impairment.

Or more succinctly, ALA is likely to be good for everyone's brain health, and fish is likely to be good for the brain health of only the minority of people who carry the APOE4 allele.


This seems like an illustration of a benefit of getting one's DNA sequenced with a company like 23andMe to determine whether one is a carrier of the APOE4 allele.





[1] JAMA. 2016 Feb 2;315(5):489-97. doi: 10.1001/jama.2015.19451.


Association of Seafood Consumption, Brain Mercury Level, and APOE e4 Status With Brain Neuropathology in Older Adults.

Morris MC, Brockman J, Schneider JA, Wang Y, Bennett DA, Tangney CC, van de Rest O.
Seafood consumption is promoted for its many health benefits even though its contamination by mercury, a known neurotoxin, is a growing concern.
To determine whether seafood consumption is correlated with increased brain mercury levels and also whether seafood consumption or brain mercury levels are correlated with brain neuropathologies.
Cross-sectional analyses of deceased participants in the Memory and Aging Project clinical neuropathological cohort study, 2004-2013. Participants resided in Chicago retirement communities and subsidized housing. The study included 286 autopsied brains of 554 deceased participants (51.6%). The mean (SD) age at death was 89.9 (6.1) years, 67% (193) were women, and the mean (SD) educational attainment was 14.6 (2.7) years.
Seafood intake was first measured by a food frequency questionnaire at a mean of 4.5 years before death.
Dementia-related pathologies assessed were Alzheimer disease, Lewy bodies, and the number of macroinfarcts and microinfarcts. Dietary consumption of seafood and n-3 fatty acids was annually assessed by a food frequency questionnaire in the years before death. Tissue concentrations of mercury and selenium were measured using instrumental neutron activation analyses.
Among the 286 autopsied brains of 544 participants, brain mercury levels were positively correlated with the number of seafood meals consumed per week (??=?0.16; P?=?.02). In models adjusted for age, sex, education, and total energy intake, seafood consumption (=?1 meal/week) was significantly correlated with less Alzheimer disease pathology including lower density of neuritic plaques (ß?=?-0.69 score units [95% CI, -1.34 to -0.04]), less severe and widespread neurofibrillary tangles (ß?=?-0.77 score units [95% CI, -1.52 to -0.02]), and lower neuropathologically defined Alzheimer disease (ß?=?-0.53 score units [95% CI, -0.96 to -0.10]) but only among apolipoprotein E (APOE e4) carriers. Higher intake levels of a-linolenic acid (18:3 n-3) were correlated with lower odds of cerebral macroinfarctions (odds ratio for tertiles 3 vs 1, 0.51 [95% CI, 0.27 to 0.94]). Fish oil supplementation had no statistically significant correlation with any neuropathologic marker. Higher brain concentrations of mercury were not significantly correlated with increased levels of brain neuropathology.
In cross-sectional analyses, moderate seafood consumption was correlated with lesser Alzheimer disease neuropathology. Although seafood consumption was also correlated with higher brain levels of mercury, these levels were not correlated with brain neuropathology.

PMID: 26836731
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Hi Dean and Grace!


Although fish is my principle food source, testing for heavy metals (which I do, because fatty ocean fish at the top of the food chain -- e.g., Ahi Tuna -- which I don't eat for exactly this reason) shows zero Hg, Pb, Cd, etc. -- but strangely high normal Arsenic.

My nephrologist is as puzzled as I am.


  -- Saul


P.S.:  I'm "one rat" -- so results just for me prove nothing.

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Thanks for this, Dean. Being E4/E4, I've found tremendous benefit to my lipids and some other health parameters by avoiding dietary cholesterol (vegan diet), and less so by reducing saturated fat, and no additional benefit from reducing total dietary fat. I've decided to consume a low-fat diet because this aids in ALA conversion to EPA, but only with quite low intakes of n-6 PUFA. It's also just easier for me to plan my diet.


I've decided to avoid EPA/DHA supplements for various reasons, but none so convincing that I'd avoid taking one if ALA alone wasn't adequate. It's nice to see another study showing ALA alone without EPA/DHA supplements shows some benefit. Sadly, as far as ApoE4 goes, almost no intervention seems to work in this population, including n-3 supplements--and if anything does show benefit it's usually less than for ApoE3.

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  • 3 weeks later...



Although fish is my principle food source, testing for heavy metals (which I do, because fatty ocean fish at the top of the food chain -- e.g., Ahi Tuna -- which I don't eat for exactly this reason) shows zero Hg, Pb, Cd, etc. -- but strangely high normal Arsenic.

My nephrologist is as puzzled as I am.


It shouldn't surprise either of you. As I pointed out last year in this post, your salmon likely contains a lot of arsenic. Al Pater just posted two studies showing that seafood is quite high in arsenic [1], especially compared with other foods (i.e. 68x higher than any other category), and almost all (89-96%) of the arsenic in people's diet comes from seafood [2].





[1] Survey of arsenic in total diet food composites and estimation of the

dietary intake of arsenic by Canadian adults and children.
Dabeka RW, McKenzie AD, Lacroix GM, Cleroux C, Bowe S, Graham RA, Conacher
HB, Verdier P.
J AOAC Int. 1993 Jan-Feb;76(1):14-25.
PMID: 8448438
During a comprehensive total diet study extending from 1985 to 1988, foods
were collected in 6 Canadian cities (in one of them, a pilot study was
conducted twice). For each of the 7 collections, foods were processed into
112 composites (105 in the initial pilot trial). Total arsenic was
determined in all samples. The mean, median, and range of arsenic
concentrations in all samples were 73.2, 5.1, and < 0.1-4830 ng/g,
respectively. Food groups containing the highest mean arsenic levels were
fish (1662 ng/g), meat and poultry (24.3 ng/g), bakery goods and cereals
(24.5 ng/g), and fats and oils (19.0 ng/g). The estimated daily dietary
ingestion of total arsenic by the average Canadian was 38.1 micrograms and
varied from 14.9 micrograms for the 1- to 4-year-old group to 59.2
micrograms for 20- to 39-year-old males.
[2] Dietary arsenic intakes in the United States: FDA Total Diet Study,
September 1991-December 1996.
Tao SS, Bolger PM.
Food Addit Contam. 1999 Nov;16(11):465-72.
PMID: 10755138
The FDA has conducted the Total Dietary Study (TDS), a yearly market basket
programme, since 1961. It is designed to monitor the levels of toxic
chemical contaminants (pesticide residues, industrial and elemental
contaminants) and essential nutrients in the US food supply. It also
provides information on trends in dietary concentrations and exposures for
the general population. Foods are collected from retail stores once a year
from each of four geographic areas of the US and are analysed either after
preparation/cooking or as ready-to-eat. The latest TDS (1991-1997) data show
that arsenic (inorganic and organic, > or = 0.03 ppm) was found in 63 (24%)
of the 261-264 foods/mixed dishes analysed. The highest concentration was
found in seafood, followed by rice/rice cereal, mushrooms, and poultry.
Based on the United States Department of Agriculture's 1987-1988 Nationwide
Food Consumption Survey, the estimated daily total arsenic average intakes,
in microgram/day, are: 2 for infants, 23 for toddlers, 20 for 6-year-old
children, 13 for 10-year-old children, 15 for 14-16-year-old boys, 21 for
14-16-year-old girls, 57 for 25-30-year-old men, 28 for 25-30-year-old
women, 47 for 40-45-year-old men, 37 for 40-45-year-old women, 92 for
60-65-year-old men, 72 for 60-65-year-old women, 69 for 70-year-old men, and
42 for 70-year-old women. Of the estimated total arsenic intakes for
infants, 42% arise from seafood and 31% from rice/rice cereals. Of the
estimated total arsenic intakes, seafood contributes 76-90% for children
(2-10-year olds), 79-85% for 14-16-year olds, and 89-96% for adults (> or =
25-30-year olds); rice/rice cereals contributes 4-8% for children, 8% for
14-16-year olds, and 1-4% for adults (> or = 25-30-year olds).
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  • 6 years later...

Synchrotron-based study finds a high-fish diet may not be bad for you

A synchrotron-based study led by University of Saskatchewan (USask) researchers shows that the chemical form of mercury found in the brains of people who ate a lot of fish over a lifetime is completely different from the mercury form found in the brains of people who were poisoned.

However, a large exposure to this mercury species resulting in poisoning is hugely different than low level exposure from a diet of fish containing naturally low levels of mercury  [Emphasis added]

"The form of mercury in the brains of the two fish-consuming individuals is essentially unchanged from the form found in fish," said George. "There were no neuropathological consequences apparent in the Seychellois and neither had known neurological deficits that could be linked to mercury exposure."

But there were striking differences found in the brains of subjects poisoned with organic mercury, which contained mixtures of mercury compounds, including significantly elevated levels of mercury selenide compared with low-level exposures.

Selenium has a complex relationship with mercury, said George. Depending on the species of mercury, and whether selenium enters the body before or after exposure, it can cancel or increase the toxicity of mercury.

"There have been some papers that suggest that it is safe to eat fish with high levels of mercury if the selenium content exceeds that of mercury, but it does not appear to be nearly that simple," said George. "I would advise against eating anything that contains high levels of mercury."

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