Low omega-3 index and polyunsaturated fatty acid status in patients with CFS/ME

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Prostaglandins Leukot Essent Fatty Acids. 2018 Dec;139:20-24. doi: 10.1016/j.plefa.2018.11.006. Epub 2018 Nov 9.
Low omega-3 index and polyunsaturated fatty acid status in patients with chronic fatigue syndrome/myalgic encephalomyelitis.
Castro-Marrero J1, Zaragozá MC2, Domingo JC3, Martinez-Martinez A4, Alegre J4, von Schacky C5.
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Abstract

BACKGROUND:
Several studies have suggested that low levels of omega-3 fatty acids (n-3 PUFAs) including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are associated with cardiovascular risk, major depression, sleep problems, inflammation and other health-related issues. So far, however, erythrocyte PUFA status in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) has not been established. This study aimed to determine whether n-3 PUFA content and omega-3 index are associated with measures in CFS/ME patients.

PATIENTS AND METHODS:
PUFA levels and omega-3 index were measured in 31 Spanish CFS/ME patients using the HS-Omega-3 Index method. Demographic and clinical characteristics and self-reported outcome measures were also recorded.

RESULTS:
A low mean omega-3 index (5.75%) was observed in 92.6% of the sample. Omega-3 index was inversely correlated with the AA/EPA ratio (p = 0.00002) and the BMI (p = 0.0106). In contrast, the AA/EPA ratio was positively associated with the BMI (p = 0.0038). No association for FIS-40 and PSQI measures was found (p > 0.05).

CONCLUSION:
The low omega-3 index found in our CFS/ME patients may indicate increased risks for cardiovascular health, which should be further investigated. A low omega-3 index also suggests a pro-inflammatory state in these patients. Attempts should be made to increase the omega-3 index in CFS/ME patients, based on intervention trials assessing a potential therapeutic value.

Copyright © 2018. Published by Elsevier Ltd.

KEYWORDS:
Cardiovascular health; Chronic fatigue syndrome; Inflammation; Myalgic encephalomyelitis; Omega-3 index; Polyunsaturated fatty acids

PMID:
30471769
DOI:
10.1016/j.plefa.2018.11.006
 
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Full paper attached to this comment.

A few thoughts:

1. I know people love an actionable idea. here's one: Eating omega-3.

"The low levels of the n-3 PUFAs EPA and DHA recorded in this sample support a potential therapeutic role for omega-3 fatty acid supplementation in CFS/ME patients, given the role of these PUFAs in cardiovascular health and their anti-inflammatory effect."

2. As we know, Davis has found reduced red blood cell deformability. There is loads of evidence that taking omega 3 can improve your red blood cell deformability

https://www.ncbi.nlm.nih.gov/pubmed/4015748 (This paper is from 1985, this is old news!)

3. More broadly, this study ties in with the whole big story about the role of lipids in cell membranes and other kinds of barrier tissues. They went looking for Omega-3 in the cell walls of red blood cells and found it wanting.

Data on the omega-3 index and PUFA composition in erythrocyte membranes are shown in Table 2. The mean omega-3 index was 5.75%. Most subjects (n= 25; 80.6%) had an omega-3 index in medium risk range (4- 8%). Three cases (9.7%) had an omega-3 index in high risk range (≤ 4%).

4. Theory time.

Omega-3s are related to phospholipids. When you obtain omega 3 from fish it comes in phospholipid form. What if we have a metabolic problem that leaves us short of phospholipids (Naviaux's metabolomics finding), such that all our barrier tissues are weakened?

Wikipedia: "Phospholipids are a class of lipids that are a major component of all cell membranes."
  • Our blood vessels don't contract and expand like they should.
  • Our gut walls don't work properly.
  • Our endothelial cells are feeble.
  • Maybe even our blood brain barrier is compromised and we have brains full of lipopolysaccharides or other ~shit~ exogenous matter that should not be there?

Big problems at barriers are well known in diabetes, as this 2014 paper on diabetes describes:

One cause of the reduction of the unsaturation index (switch from unsaturated to more saturated fatty acids) of cell membranes could be related to a decreased activity of delta-5 and delta-6 desaturase enzymes that are responsible for the biosynthesis of LCPUFAs. Indeed, the activity of these enzymes was shown to be modified in diabetes[28].

Such biochemical modifications in red blood cell membranes are suspected to play a key role in the pathophysiology of diabetes as they alter the permeability and the viscoelastic properties of membranes[29],[30]. A direct consequence would be a reduction of erythrocytes deformability, thus promoting microvascular complications of diabetes as cellular deformability is a critical factor modulating blood flow in microcapillaries[31]. This hypothesis was corroborated by two works showing an association between reduced deformability of erythrocytes and microvascular complications in diabetic patients[32],[33]. It was also hypothesized that increased membrane rigidity resulting from a decreased unsaturation index inhibits the integration of insulin-dependent glucose receptors (GLUT4) into plasma membrane, thus reducing glucose effectiveness and resulting in increased insulin secretion. This was confirmed by Borkman et al., who described a correlation between LCPUFA concentrations in membrane phospholipids of skeletal muscle cells and insulin sensitivity[34].

Such modifications in LCPUFAs bioavailability make also attractive the hypothesis of an impact of the reduced unsaturation index on endothelial function. This idea is supported by data from a study on human retinal vascular endothelial cells treated with VEGF and pro-inflammatory cytokines, and showing that a pre-treatment with DHA inhibits cellular inflammation through the NF-κB pathway.
 

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alex3619

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Hi, this was my pet topic for about two decades. I first encountered this theory in 1993, and might have been one for the first ME patients to try high dose edible linseed oil as a treatment. It only helped a tiny bit.

Missing from this story is the issue about arachidonic acid versus eicosapentaenoic acid. Its why they refer to the AA/EPA ratio.

The most basic, most important, and least understood hormones in the body are eicosanoids. They are essential to life, and even sea sponges, etc., have them. They are how cells communicate with both themselves and nearby cells.

There are three branches of these, and many are immune mediators including inflammatory mediators. These three branches are labelled simply series 1, series 2, and series 3 eicosanoids.

Just some of the hormone families within eicosanoids are prostaglandins, thromboxanes, leukotrienes and lipoxins. Each of these has a series 2 and series 3 variant. EPA leads to series 3, and AA leads to series 2.

Contrary to the study claim this is not new. What is new is the kind of testing they are doing.

ALL these paths lead to inflammatory states, but the body preferentially processes omega 3s over omega 6s, so when it does this the inflammation is decreased. Some specific eicosanoids are antiinflammatory though, but its hard to force the body to make those over others.

This ties into salicylate sensitivity, a risk factor for which is decreased glutathione, as salicylates inhibit the enzymes delta-5- and delta-6-desaturase. This ties into peroxynitrate and nitric oxide theories, or nitrosative stress, as these affect the cyclooxygenase enzyme.

I think that we have trouble turning short chain PUFAs into long chain PUFAs and arachidonic acid, but our biochemistry drives increased use, which means the intermediates are low. Raising dietary intake therefore raises the substrate, but also raises the consequences.

Its hard to find a balance. These problems are non-linear, and a bit chaotic. I was a subject in ongoing research into this in 1993. Disturbing the balance has a non-linear response, and more can mean less because it may alter the enzyme response.

Trying to understand all this is part of what drove me back to uni to finish my biochem degree.
 
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alex3619

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Actually they are connected I think, but also I looked at membrane research in the late 90s. I got into a disagreement with an "expert" that is occasionally cited, proved him wrong, and he never spoke to me again.

Omega-3 and also omega-6 are easily damaged by oxidative stress. So there is that angle too. You might have enough of the fat and its still too damaged to be useful even as a membrane component. This is one time you really do need cold processed PUFAs.
 

mariovitali

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Great post @Murph

This finding makes sense to me. Professor Hanson also found Phospholipid metabolism disruption (if i am not mistaken) apart from Naviaux.

According to the hypothesis i've been trying for the past 4 years to communicate is that we have a Liver Injury originating from certain viruses, medications or even toxic substances such as organophosphates. Any of these can lead to Liver Injury.

The Liver Injury (along with the multitude disruptions of key metabolic pathways it brings) sets the stage for ME/CFS. An example of what happens during a Hepatitis B infection-induced Liver Injury (among them is fat metabolism):





Screen Shot 2018-11-27 at 08.26.28.png
 

pattismith

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@alex3619
@Murph


I noticed high dose DHA supplementation is more effective than EPA to resolve inflammation in canine atopic dermatitis. (canine atopic dermatitis is also a consequence of a skin barrier defect with altered cell jonctions, so I wonder if omega 3 could improve skin cell jonction, this may apply to gut cell jonction as well, and these jonctions are thought to be altered in ME/CFS with increased translocation of bacterial LPS etc)


It seems that DHA may have better anti inflammatory effect for human too:

DHA is Better than EPA at Reducing Inflammation


original study is here
 

alex3619

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It seems that DHA may have better anti inflammatory effect for human too:
This is something new, and was not what was thought 20 years ago. Interesting. DHA was always thought of as an important component of brain cells, so was billed as good for brain health.

If this is correct, then some of the mechanisms of DHA and EPA might have be to rethought.
 

prioris

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I use a water soluble Omega 3 called DHA Omega 3 Ultra says 6 times more absorbable that is encapsulated in vesisorb.
 
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I've also been using high dose DHA (3000mg per day) for around four months. I built up to that level over a few weeks. I haven't experienced any problems on this dose. I was already eating seafood a few times per week and fortunately I don't seem to have a negative reaction to omega 3's from fish. Have heard on many people with ME reacting badly to smaller doses though. :(

*I'm using this dose of DHA as part of Dr Patrick Nemechek's protocol....the premise of which is supplementing high oleic first cold press olive oil plus DHA and using tVNS may help shift primed microglia back to an M2 state. (Lowering excess propionate produced in the gut is part of the protocol too - mentioning for completeness.) He readily acknowledges the vagal nerve stim and DHA *could* be a useful strategy while we wait for something pharmaceutical to be developed or repurposed as a more effective treatment.
 

Moof

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I've used high dose DHA & EPA for about 15 years – apart from anything else, my skin's so dry that it cracks, flakes and gets incredibly sore if I don't take it. Even if it did nothing else, it would be worth it just for that!
 

Bedshaped

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Whenever I have tried Omega 3 supplements (Cod Liver oil, capsules) I get reflux and stomach issues at first, and then after a few days I get brainfog and, most prominent, a depressed feeling. I just don't feel good on it. Does anybody else have it like this or have an explaination what's happening?
 

alex3619

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have an explaination what's happening?
A known issue is omega-3 purity. All the cheaper brands are just fish oil, and contain toxic impurities. The minimum acceptable purity is typically found at about 60% active ingredient (EPA+DHA), and medical grade is 90%. That is what was used in all the early clinical trials, though I am not sure that is always the case.

However as I said earlier there is not a linear response. Its not more is good. So far as I am aware nobody has figured this out, especially not in ME. So, unfortunately, this supplement is suck it and see what happens, and responses can change over time.

I started out OK with short chain omega-3, then grew to really hate eating it. The worst I get from quality fish oil is a little heartburn.
 

Bedshaped

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A known issue is omega-3 purity. All the cheaper brands are just fish oil, and contain toxic impurities. The minimum acceptable purity is typically found at about 60% active ingredient (EPA+DHA), and medical grade is 90%. That is what was used in all the early clinical trials, though I am not sure that is always the case.

However as I said earlier there is not a linear response. Its not more is good. So far as I am aware nobody has figured this out, especially not in ME. So, unfortunately, this supplement is suck it and see what happens, and responses can change over time.

I started out OK with short chain omega-3, then grew to really hate eating it. The worst I get from quality fish oil is a little heartburn.
What benefits do you experience from taking omega-3?

I think that I have been eating quality brands in the past. Because I am sensitive to most stuff (medicine, food +++) and get all sorts of weird reactions and side-effects I've made sure I buy the best I get.... Really frustrating:(
 
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Just starting on DHA and EPA. I’m a vegetarian and have been taking flaxseed oil. I have found I can get the DHA and EPA from microalgae oil supplements. It might be an alternative for anyone who wants to avoid the potential contaminants in fish oil.

I am not sure what is the optimal dose or when omega 3s are best absorbed? With other food or without?
 

pamojja

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I am not sure what is the optimal dose or when omega 3s are best absorbed? With other food or without?
It's best absorbed with a fatty meal, or at least some fats along with it. Optimal dose is probably very individual, an omega-3 index blood test would rectify. Against CVD about 3 gram (of EPA and DHA combined) is used. Dr. Davis of the old 'TrackYourPlaque' forum recommended 6 g for 2-3 years in the case of high Lp(a), where he found in his clinical experience, that Lp(a) dropped very low in about 60% who tried (didn't work for me).

Personally as with many other supplements, don't 'feel' anything. Do however see in my blood-work that it lowers inflammation-markers and triglycerides.
 
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prioris

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people with high Lp(a) levels are more prone to developing blood clots that may manifest as heart attacks and strokes....

about 15 years ago around age 50 I could hardly walk due to peripheral artery disease ... I was walking fine after using high dose nattokinase and serrapeptase for 3 weeks

lumbrokinase is way way more potent than nattokinase (maybe 80 times more) so something to experiment with ... nattokinase has a more milder action

heart disease is complicated because there is calcification issuesand other causes also ... vitamin K2 MK4 and MK7 is something to consider ... one should provide body with some antioxidants also

the last thing one should do is get treatment from conventional medical system since like most things they don't treat underlying cause

i've had cholesterol readings in high 300s for my entire life ... almost all the cholesterol is goodness ...

i think cholesterol that builds up in liver gall bladder duct area is where real problems occur ... that needs to be cleared out with gallbladder cleanses
 
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I’ve been taking a capsule of EPA and DHA for about 10 days and have been feeling tearful and ill. Is this coincidence or could they be the cause somehow? I am a vegetarian so although it is a low dose it might be a big increase on what I have been getting. I will cut back and see how it fairs but wondered if anyone had experienced anything similar/had any thoughts?