12.27: summary:
. fish oil has long-chained omega-3
that is very valuable for reducing disease;
you can make some yourself with
plant-based omega-3, but not much.
. plant-based omega-3 was not helpful for
reducing the risk of circulation disorders
yet one study showed it reduced the risk of
macular degeneration.
. some studies showed that supplements did not help
reduce risk of cerebrovascular disease,
only a diet of whole fish helped.
. one study showed high-dose supplements
did help with macular degeneration,
while another study showed that
low dose supplements did not help.
. fish is a source of mercury, PCB's and dioxins;
fish oil supplements that are 3rd-party tested
may help with heart disease, cancer,
arthritis, macular degeneration
and mental illness.
Am J Clin Nutr. 2006
n-3 Fatty acids from fish or fish-oil supplements,
but not alpha-linolenic acid,
benefit cardiovascular disease outcomes in
primary- and secondary-prevention studies:
a systematic review.
A systematic review of the literature on the effects of
n-3 FAs (consumed as fish or fish oils
rich in eicosapentaenoic acid
and docosahexaenoic acid
or as alpha-linolenic acid)
on cardiovascular disease outcomes and adverse events
was conducted.
Evidence suggests that increased consumption of
n-3 FAs from fish or fish-oil supplements,
but not of alpha-linolenic acid,
reduces the rates of all-cause mortality,
cardiac and sudden death, and possibly stroke.
The evidence for the benefits of fish oil is stronger in
secondary- than in primary-prevention settings.
Adverse effects appear to be minor.
Biomed Pharmacother. 2002
The importance of the ratio of
omega-6/omega-3 essential fatty acids.
Several sources of information suggest that
human beings evolved on a diet
with a ratio of omega-6 to omega-3 essential fatty acids (EFA)
of approximately 1
whereas in Western diets the ratio is
15/1 - 16.7/1.
Western diets are deficient in omega-3 fatty acids,
and have excessive amounts of omega-6 fatty acids
compared with the diet on which human beings evolved
and their genetic patterns were established.
Excessive amounts of omega-6 polyunsaturated fatty acids (PUFA)
and a very high omega-6/omega-3 ratio,
as is found in today's Western diets,
promote the pathogenesis of many diseases,
including cardiovascular disease, cancer,
and inflammatory and autoimmune diseases,
whereas increased levels of omega-3 PUFA
(a low omega-6/omega-3 ratio)
exert suppressive effects.
In the secondary prevention of cardiovascular disease,
a ratio of 4/1 was associated with
a 70% decrease in total mortality.
A ratio of 2.5/1 reduced rectal cell proliferation
in patients with colorectal cancer,
whereas a ratio of 4/1 with the
same amount of omega-3 PUFA had no effect.
[ie, what is more helpful than more fish oil
is getting less omega-6.]
The lower omega-6/omega-3 ratio in women with breast cancer
was associated with decreased risk.
A ratio of 2-3/1 suppressed inflammation
in patients with rheumatoid arthritis,
and a ratio of 5/1 had a beneficial effect on
patients with asthma,
whereas a ratio of 10/1 had adverse consequences.
Nutrients. 2016 Mar 2
An Increase in the Omega-6/Omega-3 Fatty Acid Ratio
Increases the Risk for Obesity.
In the past three decades, total fat and saturated fat
intake as a percentage of total calories
has continuously decreased in Western diets,
while the intake of omega-6 fatty acid increased
and the omega-3 fatty acid decreased,
resulting in a large increase in the omega-6/omega-3 ratio
from 1:1 during evolution to 20:1 today or even higher.
This change in the composition of fatty acids
parallels a significant increase in the
prevalence of overweight and obesity.
Experimental studies have suggested that
omega-6 and omega-3 fatty acids elicit divergent effects
on body fat gain through mechanisms of adipogenesis,
browning of adipose tissue, lipid homeostasis,
brain-gut-adipose tissue axis,
and most importantly systemic inflammation.
Prospective studies clearly show
an increase in the risk of obesity as the level of
omega-6 fatty acids and the omega-6/omega-3 ratio
increase in red blood cell (RBC) membrane phospholipids,
whereas high omega-3 RBC membrane phospholipids
decrease the risk of obesity.
Recent studies in humans show that in addition to
absolute amounts of omega-6 and omega-3 fatty acid intake,
the omega-6/omega-3 ratio plays an important role
in increasing the development of obesity
via both AA eicosanoid metabolites
and hyperactivity of the cannabinoid system,
which can be reversed with increased intake of
eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).
A balanced omega-6/omega-3 ratio is important for health
and in the prevention and management of obesity.
Am J Epidemiol. 1998
Adipose tissue omega-3 and omega-6 fatty acid content
and breast cancer in the EURAMIC study.
European Community Multicenter Study on Antioxidants,
Myocardial Infarction, and Breast Cancer.
The fatty acid content of adipose tissue in postmenopausal
breast cancer cases and controls from five European countries
in the European Community Multicenter Study on Antioxidants,
Myocardial Infarction, and Cancer (EURAMIC) breast cancer study (1991-1992)
was used to explore the hypothesis that
fatty acids of the omega-3 family inhibit breast cancer
and that the degree of inhibition depends on
background levels of omega-6 polyunsaturates.
Considered in isolation,
the level of omega-3 or omega-6 fat in adipose tissue
displayed little consistent association with
breast cancer across study centers.
The ratio of long-chain omega-3 to total omega-6 fat
showed an inverse association with breast cancer
in four of five centers.
In Malaga, Spain, the odds ratio for the highest tertile
relative to the lowest reached
0.32 (95% confidence interval 0.13-0.82).
In this center, total omega-6 fatty acid
was strongly associated with breast cancer.
With all centers pooled,
the odds ratio for long-chain omega-3 to total omega-6
reached 0.80 for the second tertile
and 0.65 for the third tertile,
a downward trend bordering on statistical significance
(p for trend = 0.055).
While not definitive, these results provide evidence
for the hypothesis that
the balance between omega-3 and omega-6 fat
may play a role in breast cancer.
N Engl J Med. 1985
The inverse relation between fish consumption
and 20-year mortality from coronary heart disease.
The low death rate from coronary heart disease among
the Greenland Eskimos has been ascribed to
their high fish consumption.
An inverse dose-response relation was observed
between fish consumption in 1960
and death from coronary heart disease
during 20 years of follow-up.
Mortality from coronary heart disease
was more than 50 per cent lower
among those who consumed at least 30 g of fish per day
than among those who did not eat fish.
We conclude that the consumption of as little as
one or two fish dishes per week
may be of preventive value in relation to coronary heart disease.
Circulation. 2004
Accumulated evidence on fish consumption and
coronary heart disease mortality:
a meta-analysis of cohort studies.
Compared with those who never consumed fish
or ate fish less than once per month,
individuals with a higher intake of fish had lower CHD mortality.
The pooled multivariate RRs for CHD mortality were
0.89 (95% CI, 0.79 to 1.01) for fish intake 1 to 3 times per month,
0.85 (95% CI, 0.76 to 0.96) for once per week,
0.77 (95% CI, 0.66 to 0.89) for 2 to 4 times per week, and
0.62 (95% CI, 0.46 to 0.82) for 5 or more times per week.
Each 20-g/d increase in fish intake was related to
a 7% lower risk of CHD mortality (P for trend=0.03).
fish consumption is inversely associated with fatal CHD.
fish oil supplements not as good as fish for heart?:
BMJ 2012
Association between fish consumption,
long chain omega 3 fatty acids,
and risk of cerebrovascular disease:
systematic review and meta-analysis
Studies published before September 2012
identified through electronic searches using
Medline, Embase, BIOSIS, and
Science Citation Index databases.
... concerning cerebrovascular disease
(defined as any fatal or non-fatal ischaemic stroke,
haemorrhagic stroke, cerebrovascular accident,
or transient ischaemic attack).
. high fish consumption was significantly associated with
a reduced risk of cerebrovascular disease,
but long-chain omega-3 fatty acid supplements were not.
The beneficial effects of fish might come from
a wide range of nutrients found in them.
The conclusions are likely to be reliable.
[but reliable about what?
what was the quality of supplements,
the form(ethyl ester, triglyceride, phospholipid),
the rancidity, etc]
Funding received from Gates Cambridge PhD scholarship,
the UK Medical Research Council, and Pfizer Nutrition.
N Engl J Med. 2010
n-3 fatty acids and cardiovascular events
after myocardial infarction.
. we randomly assigned 4837 patients,
60 through 80 years of age (78% men),
who had had a myocardial infarction
and were receiving state-of-the-art
antihypertensive, antithrombotic, and
lipid-modifying therapy
. patients consumed, on average,
18.8 g of margarine per day,
[ a hefty dose of omega-6 or monounsaturate? ]
which resulted in additional intakes of
226 mg of EPA combined with 150 mg of DHA,
[trivial amounts of fish oil]
1.9 g of ALA, or both,
[moderate dose of plant-based omega-3
During the follow-up period,
a major cardiovascular event occurred in
671 patients (13.9%).
Neither EPA-DHA nor ALA reduced this
primary end point
(hazard ratio with EPA-DHA,
1.01; 95% confidence interval [CI], 0.87 to 1.17; P=0.93;
hazard ratio with ALA,
0.91; 95% CI, 0.78 to 1.05; P=0.20).
In the prespecified subgroup of women,
ALA, as compared with placebo and EPA-DHA alone,
was associated with a reduction in
the rate of major cardiovascular events
that approached significance
(hazard ratio, 0.73; 95% CI, 0.51 to 1.03; P=0.07).
The rate of adverse events did not differ significantly
among the study groups.
Low-dose supplementation with EPA-DHA or ALA
did not significantly reduce the rate of
major cardiovascular events
among patients who had had a myocardial infarction
and who were receiving state-of-the-art
antihypertensive, antithrombotic, and lipid-modifying therapy.
more:
The margarines were developed by Unilever R&D
(Vlaardingen, the Netherlands).
In our trial, 85% of the patients were receiving statins.
also [circ 2010]:
Although the 30-day case fatality improved markedly,
long-term survival did not change,
and the cause of death shifted from
cardiovascular to noncardiovascular.
[related to "state-of-the-art care"]
fish oil no help without a low-insulin diet:
N Engl J Med. 2012
n-3 fatty acids and cardiovascular outcomes
in patients with dysglycemia.
. those at high risk for cardiovascular events
and had impaired fasting glucose, impaired glucose tolerance,
or diabetes to receive a 1-g capsule containing at least
900 mg (90% or more) of ethyl esters of omega-3 fatty acids
and to receive either insulin glargine or standard care.
The primary outcome was death from cardiovascular causes.
. did not reduce the rate of cardiovascular events.
Nat Commun. 2015
Longer-term outcome in the prevention of
psychotic disorders by the Vienna omega-3 study.
Long-chain omega-3 polyunsaturated fatty acids (PUFAs):
a lack of these fatty acids has been implicated in
a number of mental conditions including schizophrenia.
We have previously shown that a 12-week intervention with
omega-3 PUFAs reduced the risk of
progression to psychotic disorder in
young people with subthreshold psychotic states
for a 12-month period compared with placebo.
. brief intervention with omega-3 PUFAs
reduced both the risk of progression to psychotic disorder
and psychiatric morbidity in general in this study.
The majority of the individuals from the omega-3 group
did not show severe functional impairment
and no longer experienced attenuated psychotic symptoms at follow-up.
10 g MaxEPA for mental health:
Human Psychopharmacology: Clinical and Experimental 1996
Omega-3 fatty acid supplementation
in schizophrenic patients.
. supplementation of the diet for 6 weeks
with 10 g/day of concentrated fish oil (MaxEPA)
resulted in significant amelioration of both
schizophrenic symptoms and tardive dyskinesia.
Multiple regression analysis showed that
improvement in schizophrenic symptoms
was importantly related to the increased level of n3 fatty acids.
Schizophr Res. 2001
Two double-blind placebo-controlled pilot studies of
eicosapentaenoic acid in the treatment of schizophrenia.
. the metabolism of phospholipids and
polyunsaturated fatty acids (PUFA)
is abnormal in schizophrenia.
The first study was designed to distinguish between
the possible effects of two different n-3 PUFA:
eicosapentaenoic acid (EPA) and
docohexaenoic acid (DHA).
Forty-five schizophrenic patients on
stable antipsychotic medication
who were still symptomatic were treated with
either EPA, DHA or placebo for 3 months.
Improvement on EPA measured by the
Positive and Negative Syndrome Scale (PANSS)
was statistically superior to both DHA and placebo
using changes in percentage scores on the total PANSS.
EPA was significantly superior to DHA for
positive symptoms using ANOVA for repeated measures.
In the second placebo-controlled study,
EPA was used as a sole treatment,
though the use of antipsychotic drugs was
still permitted if this was clinically imperative.
By the end of the study, all 12 patients on placebo,
but only eight out of 14 patients on EPA,
were taking antipsychotic drugs. Despite this,
patients taking EPA had significantly lower scores
on the PANSS rating scale by the end of the study.
It is concluded that EPA may represent
a new treatment approach to schizophrenia,
and this requires investigation by
large-scale placebo-controlled trials.
Eur J Clin Nutr. 2009
Reduced mania and depression in juvenile bipolar disorder
associated with long-chain omega-3
polyunsaturated fatty acid supplementation.
Eighteen children and adolescents with JBD
received supplements containing
360 mg per day eicosapentaenoic acid (EPA) and
1560 mg per day docosahexaenoic acid (DHA)
for 6 weeks in an open-label study.
Clinician ratings of mania and depression were significantly lower
and global functioning significantly higher after supplementation.
Parent ratings of internalizing and externalizing behaviours
were also significantly lower following supplementation.
A larger randomized controlled trial appears warranted.
Arch Gen Psychiatry. 1999
Omega 3 fatty acids in bipolar disorder:
a preliminary double-blind, placebo-controlled trial.
Omega3 fatty acids may inhibit
neuronal signal transduction pathways
in a manner similar to that of lithium carbonate and valproate,
2 effective treatments for bipolar disorder.
A 4-month, double-blind, placebo-controlled study, comparing
omega3 fatty acids (9.6 g/d) vs placebo (olive oil),
in addition to usual treatment, in 30 patients with bipolar disorder.
A Kaplan-Meier survival analysis of the cohort found that
the omega3 fatty acid patient group had a significantly
longer period of remission than the placebo group
(P = .002; Mantel-Cox). In addition,
for nearly every other outcome measure,
the omega3 fatty acid group performed better than the placebo group.
Int J Prev Med. 2016 May 19
Effects of Omega-3 Supplement in the Treatment of
Patients with Bipolar I Disorder.
. bipolar I disorder (BID).
In addition to the other standard treatments,
1000 mg of omega-3 supplement was given.
The Young Mania Rating Scale was completed
before and after the intervention.
Since omega-3 supplement was effective for the treatment of BID,
it is suggested to use omega-3 supplements as an adjuvant therapy
along with the other pharmacotherapies.
1.2 g per day fish oil prevented some expected psychoses:
Arch Gen Psychiatry. 2010
Long-chain omega-3 fatty acids for
indicated prevention of psychotic disorders:
a randomized, placebo-controlled trial.
The use of antipsychotic medication for the prevention of
psychotic disorders is controversial.
Long-chain omega-3 polyunsaturated fatty acids (PUFAs)
may be beneficial in a range of psychiatric conditions,
including schizophrenia. Given that omega-3 PUFAs
are generally beneficial to health
and without clinically relevant adverse effects,
their preventive use in psychosis merits investigation.
. omega-3 PUFAs reduce the rate of progression to
first-episode psychotic disorder
in adolescents and young adults aged 13 to 25 years
with subthreshold psychosis
(at ultra-high risk of psychotic disorder).
A 12-week intervention period of
1.2 g/d omega-3 PUFA or placebo
was followed by a 40-week monitoring period;
The ratio of omega-6 to omega-3 fatty acids in erythrocytes
was used to index pretreatment vs posttreatment
fatty acid composition. By study's end (12 months),
2 of 41 individuals (4.9%) in the omega-3 group and
11 of 40 (27.5%) in the placebo group
had transitioned to psychotic disorder (P = .007).
omega-3 Polyunsaturated fatty acids also significantly reduced
positive symptoms (P = .01), negative symptoms (P = .02),
and general symptoms (P = .01) and improved functioning (P = .002)
compared with placebo.
clinicaltrials.gov Identifier: NCT00396643.
Invest Ophthalmol Vis Sci. 2014
Circulating omega-3 Fatty acids and
neovascular age-related macular degeneration.
We included 290 patients of the
Nutritional AMD Treatment 2 Study (NAT2)
with neovascular AMD in one eye
and early AMD lesions in the other eye.
. intake of seafood was estimated by food frequency questionnaire.
Dietary oily fish and seafood intake were significantly lower in
AMD patients than in controls.
After adjustment for all potential confounders
(age, sex, CFH Y402H, ARMS2 A69S, and ApoE4 polymorphisms,
plasma triglycerides, hypertension, hypercholesterolemia,
and family history of AMD),
serum EPA was associated significantly with a lower risk for
neovascular AMD (odds ratio [OR] = 0.41;
95% confidence interval [CI], 0.22-0.77; P = 0.005).
Analysis of RBCM [fish oil in the blood] revealed it
significantly lowered risk for neovascular AMD:
EPA (OR = 0.25; 95% CI, 0.13-0.47; P < 0.0001)
EPA+DHA (OR = 0.52; 95% CI, 0.29-0.94; P = 0.03).
The RBCM EPA and EPA+DHA,
as long-term biomarkers of n-3 dietary PUFA status,
were associated strongly with neovascular AMD
and may represent an objective marker identifying subjects at
high risk for neovascular AMD,
who may most benefit from nutritional interventions.
chia may increase your blood levels of 18:3n3
and that is associated with reduced risk of
late age-related macular degeneration.
J Nutr. 2013
High concentrations of plasma n3 fatty acids
are associated with decreased risk for
late age-related macular degeneration.
We assessed the associations of late AMD with plasma n3 PUFA,
a nutritional biomarker of n3 PUFA status.
After adjustment for age, gender, smoking, education,
physical activity, plasma HDL-cholesterol,
plasma triglycerides, CFH Y402H, apoE4,
and ARMS2 A69S polymorphisms, and follow-up time,
high plasma total n3 PUFA
[both long and short chain from both plant and fish]
was associated with a reduced risk for late AMD
[OR = 0.62 for 1-SD increase (95% CI: 0.44-0.88); P = 0.008].
Associations were similar for plasma 18:3n3*
[that is plant-based omega-3]
[OR = 0.62 (95% CI: 0.43-0.88); P = 0.008]
and n3 long-chain PUFA [fish oil]
[OR = 0.65 (95% CI: 0.46-0.92); P = 0.01].
This study gives further support to the potential role of
n3 PUFAs in the prevention of late AMD
and highlights the necessity of randomized clinical trials
to determine more accurately the value of n3 PUFAs
as a means of reducing AMD incidence.
* 18:3n3 is alpha-Linolenic acid (ALA),
an omega-3 oil but not a fish oil.
linseed oil is 46.9% 18:3n3.
another source is chia seed.
Arch Ophthalmol. 2003
Progression of age-related macular degeneration:
association with dietary fat, transunsaturated fat,
nuts, and fish intake.
Higher total fat intake increased the risk of progression to
the advanced forms of AMD, with a relative risk (RR) of
2.90 (95% confidence interval, 1.15-7.32)
for the highest fat-intake quartile relative to the
lowest fat-intake quartile,
[getting more fat from the modern diet
contributes to excessive omega-6.]
after controlling for other factors (P trend =.01).
Animal fat intake was associated with a
2-fold increased risk of progression
(RR, 2.29 for the highest quartile compared with the lowest quartile;
95% confidence interval, 0.91-5.72),
although the trend for increasing risk with higher animal fat intake
was not significant (P=.09).
Higher vegetable fat intake had a stronger relationship
with increased risk of AMD progression
with an RR of 3.82 (95% confidence interval, 1.58-9.28)
for the highest quartile
compared with the lowest quartile (P trend =.003).
[vegetable oil is a major source of omega-6]
Processed baked goods, which are higher in some of these fats,
increased the rate of AMD progression
approximately 2-fold.
. the likelihood of progression of AMD was
RR, 2.09 and P trend =.07 (not statistically significant)
RR, 2.21 and P trend =.04;
RR, 2.28 and P trend =.04;
RR, 2.39 and P trend =.008, respectively for:
Saturated [but see nuts]
monounsaturated, [but see nuts]
polyunsaturated, [but see fish oil]
transunsaturated fats.
Higher fish intake was associated with
a lower risk of AMD progression among subjects with
lower linoleic acid [omega-6] intake;
[ having high omega-3 doesn't help
if your omega-6 levels are too high.]
and nuts were protective.
Erratum: [trivial: unrelated to abstract]
olive oil seems to be good like a nut:
(assuming you can find real olive oil)
PLoS One. 2016:
Olive Oil Consumption and Age-Related
Macular Degeneration: The Alienor Study
fish helps most in those with low omega-6 oil:
Arch Ophthalmol. 2006
Cigarette smoking, fish consumption, omega-3 fatty acid intake,
and associations with age-related macular degeneration:
the US Twin Study of Age-Related Macular Degeneration.
The US Twin Study comprises elderly male twins
from the National Academy of Sciences
-National Research Council World War II Veteran
Twin Registry.
. food frequency and risk factor questionnaires.
This environmental component of the study includes 681 twins:
222 twins with AMD (intermediate or late stages)
and 459 twins with no maculopathy or early signs.
Increased intake of fish reduced risk of AMD,
particularly for 2 or more servings per week (P trend = .04).
Dietary omega-3 fatty intake was inversely associated with AMD
(odds ratio, 0.55; 95% confidence interval, 0.32-0.95)
comparing the highest vs lowest quartile.
Reduction in risk of AMD with higher intake of omega-3 fatty acids
was seen primarily among subjects with
low levels (below median) of linoleic acid intake,
an omega-6 fatty acid (P trend<.001).
high-dose fish oil supplements prevented dry AMD:
PharmaNutrition 2014
Pilot study for treating dry age-related
macular degeneration (AMD) with
high-dose omega-3 fatty acids.
patients with dry AMD using
3.4 g of eicosapentaenoic acid (EPA) and
1.6 g of docosahexaenoic acid (DHA)
on a daily basis for 6 months.
In patients with dry AMD, significant improvement in vision acuity
occurred in 100% of patients was observed within
four and half months after omega-3 supplementation.
-- one of the authors is Dr.Barry Sears
author of the omega-3 Rx zone; founder of
Inflammation Research Foundation.
. he promotes supplements because they
pull out the dioxins and mercury in fish.
lower-dosed supplements had no effect:
JAMA. 2013
Lutein + zeaxanthin and omega-3 fatty acids
for age-related macular degeneration:
the Age-Related Eye Disease Study 2 (AREDS2)
randomized clinical trial.
Age-Related Eye Disease Study 2 Research Group.
Erratum in JAMA. 2013 Jul 10;310(2):208.
Participants were randomized to receive
lutein (10 mg) + zeaxanthin (2 mg),
DHA (350 mg) + EPA (650 mg),
lutein + zeaxanthin and DHA + EPA, or placebo.
Addition of lutein + zeaxanthin, DHA + EPA, or both
to the AREDS formulation in primary analyses
did not further reduce risk of progression to advanced AMD.
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