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The Deformability of Red Blood Cells in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) - Thesis: Brendan Robert Schmidt 2019

Discussion in 'BioMedical ME/CFS News' started by Sly Saint, Feb 10, 2020.

  1. Sly Saint

    Sly Saint Senior Member (Voting Rights)

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    https://scholarworks.sjsu.edu/etd_theses/5079/

    currently under embargo
    (says Available for download on Friday, August 05, 2022 ?)
     
  2. Andy

    Andy Committee Member & Outreach

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  3. rvallee

    rvallee Senior Member (Voting Rights)

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    Not clear whether they used patient plasma or a standard solution. Which seems to be the key.
     
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  4. InfiniteRubix

    InfiniteRubix Senior Member (Voting Rights)

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    Thought I'd flag this again here, not just because it's tangentially relevant. Although I've noticed it in my research, I've never seen it mentioned in ME circles (might be my insufficient reading):

     
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  5. Aslaug

    Aslaug Senior Member (Voting Rights)

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    I've brought it up in Norwegian fb group, and have seen others mention it as well.

    I wonder if vitamin E, omega 3 or other nutrients positive for cell membranes can be of any help. I also think about the metabolomics study that found free heme in ME patients was significantly different than in controls. Free heme is very reactive and could lead to the oxidative damage required to stiffen cell membranes. Vitamin E is an antioxidant that specifically protects cell membranes. But there are issues with too much vitamin E as well.. I'll still eat my nuts and seeds and think they're helpful in some way :)
     
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  6. DokaGirl

    DokaGirl Senior Member (Voting Rights)

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    @Aslaug, Dr. Leslie O. Simpson proposed impairment in the deformability of RBCs in the 1980s/90s.

    From MEpedia:

    "Non-deformable erythrocytes[edit | edit source]

    Simpson became interested in ME as some of the disease symptoms were suggestive of impaired microcirculation. In 1986 he reported impaired filtration of red blood cells in a sample of ME patients. His pioneering paper suggested ME to be “associated with changes in blood rheology which could impair microcirculatory blood flow.”[1] This study sparked the interest of T.M. Mukherjee and colleagues in Australia. In a letter published in The Lancet, they reported red cell deformities in some ME patients that they had never seen before.[2] The report by Mukherjee was however criticized for not using a proper control group. Lloyd et al. tried to replicate the findings in 12 patients with CFS and 10 healthy controls, but found that most of the cells from patients and controls had normal, smooth biconcave morphology.[3]

    Interest in blood cell deformity and impaired circulation in ME patients waned with only Simpson publishing about the topic. In a 1989 study he compared a large sample of patients with (self-reported) ME with multiple sclerosis (MS) patients and healthy controls. Samples from subjects with myalgic encephalomyelitis had the lowest percentages of normal shaped red cells and the highest incidence of cup-shaped forms.[4] Through collaboration with ME organizations in New Zealand, Australia, South Africa and England, Simpson managed to test more than 2000 ME patients. Once again he found red cell shape transformation. “The results reported here, he wrote, “would support a proposal that ME is a hemorrheological disorder in which symptoms are manifestations of the consequences of impaired capillary blood flow.”[5] Because the study was uncontrolled, the British Journal of Haematology refused to publish it.
    ... Simpson does thinks red cell deformity is an important pathological mechanism in ME and he recommended research into treatment, to focus on the issue of blood circulation. Simpson suggested that evening primrose oil could improve the flow properties of blood.[6]" (my bolding of "evening primrose oil")

    https://me-pedia.org/wiki/Leslie_Simpson

    If I recall correctly, he may have also recommended omega 3 fish oils.
     
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  7. Amw66

    Amw66 Senior Member (Voting Rights)

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    Be aware that vitamin E comes in natural and synthetic forms.

    The synthetic form is an isomer and the body can only use around half of it - can lead to issues disposing of it for some.

    Vit E an also provoke a humoural.immune response.
     
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  8. InfiniteRubix

    InfiniteRubix Senior Member (Voting Rights)

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    I was 1000% right about that possibility. My reading was insufficient.
     
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  9. Ravn

    Ravn Senior Member (Voting Rights)

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    He did.
    FWIW I've been put on high-dose fish oil for a different reason by my doctor. It helps the other condition. Does nothing at all for my ME, unfortunately.
    So while there may well be an issue with red blood cell deformability in ME, there isn't a solution as simple as fish oil. Pity.
     
  10. Snow Leopard

    Snow Leopard Senior Member (Voting Rights)

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    RBC deformability is also a function of age, with older RBC having lower deformability.

    "Squeezing for Life – Properties of Red Blood Cell Deformability"
    https://www.frontiersin.org/articles/10.3389/fphys.2018.00656/full

    Sounds kind of impressive when you think about it like that!

    So less RBC damage can lead to higher average RBC age, leading to lower deformability...

    So lower catecholamine stimulation of RBC can lower RBC deformability.
     
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  11. Aslaug

    Aslaug Senior Member (Voting Rights)

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    Too much vitamin E was also mentioned as something that could reduce restorative capacities of athletes in a study I read, I didn't check the source they provided, but sounds like something that could be relevant for us.

    For vitamin E i definitely prefer natural source, it's easy to come by in nuts and seeds.

    I think it's important it is mentioned many times.

    The problem with only taking fish oils is that the fatty acids in the oil will be incorporated into cell membranes (presumed to be good for flexibility), but they do nothing to protect it from oxidative harm.

    Cell membranes become stiff when the fatty acids they are composed of become oxidized (and other reason like fatty acid composition). So if there is something reactive in our blood like free heme, we might not get the cell membrane benefits of the fish oil. Vitamin E is an antioxidant that is fat soluble and found in membranes, and is capable of protecting the membranes from damage like that. However if there is a lot of oxidative agents, vitamin E might not be enough. It gets depleted. There are several other antioxidants in the body, but they would need to be at the right place at the right time, which might not be the case. Perhaps they're needed elsewhere.

    Since we don't know why the cells are less flexible (I'm quite sure at least one study have found this was not the case), I don't do more than take my daily spoon of fish oil/eat a fatty fish meal, and I eat a lot of nuts. My diet as a whole include a lot of antioxidants from food. I'm not expecting any miracles, I've been doing this for years, I have good periods and bad periods all the same. I do believe I would be worse of with a less nutrient dense diet, but I'm not too keen on figuring that one out.
     
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  12. FMMM1

    FMMM1 Senior Member (Voting Rights)

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    I've only glanced at this but I'm not sure what this tells us.

    Ron Davis's group are currently working on isolating, and identifying, the "something in the blood", which may affect red blood cell deformability. So things may get a little clearer, or not.

    @Snow Leopard (above) highlights a study showing that glucose consumption affects RBC deformability and @InfiniteRubix (above) highlights that RBC deformability is affected by diabetes.

    From memory Chris Armstrong found higher levels of glusose in the plasma of people with ME. Theory was that glucose was not being utilised for cellular energy production; hence the level in the blood increased.

    So maybe a little more evidence will clarify things.
     
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  13. alex3619

    alex3619 Senior Member (Voting Rights)

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    I had this debate with him back then, maybe around 2000. He was primarily recommending omega-6 oils such as evening primrose oil, at least at that time, and I pointed out this could be very dangerous. He was not interested in the biochemistry, he liked his pet theory. We did not get along, and he quit the scientific forum I was on, because nobody took his advice seriously, only his findings.
     
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  14. GloriaDG

    GloriaDG Established Member

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    If RBC deformability is an issue in ME, then drugs like Pentoxifylline should improve the symptoms, shouldn't they? I'm sure they have been used in ME patients already though.
    https://link.springer.com/article/10.2165/00003495-198734010-00003
    "Pentoxifylline acts primarily by increasing red blood cell deformability, by reducing blood viscosity and by decreasing the potential for platelet aggregation and thrombus formation."
    Cinnarizine is another one (it's available over the counter in some countries), and it also crosses the BBB: https://www.ncbi.nlm.nih.gov/m/pubmed/6672999/.
     
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  15. alex3619

    alex3619 Senior Member (Voting Rights)

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    I have spent weeks trying to buy quality vitamin E. Nearly all of it is synthetic alpha tocopherol now, and the rest is "natural" alpha tocopherol. All pharmacists and health food stores in my area no longer seem to sell quality vitamin E. Alpha tocopherol is actually worse than useless, as it blocks absorption of natural vitamin E. Bio-absorption is low, it blocks absorption of natural vitamin E via competition, and bio-activity is low too. Natural sources are still the best for me, including nuts and seeds.

    Decades ago there was a discussion by local doctors that when they tested ME patients for vitamin E it was either low or undetectable. We have a high need for it. I think this was the early 90s, so this info has been around for a while. I wonder what more modern studies such as with OMF have found.
     
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  16. InfiniteRubix

    InfiniteRubix Senior Member (Voting Rights)

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    At what kind of doses would it be dangerous?

    I know that menopausal women should take 3g from studies I've seen before
     
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  17. DokaGirl

    DokaGirl Senior Member (Voting Rights)

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    Hi @alex3619, yes Dr. Simpson recommended evening primrose oil. And, in a later work, (2013), Ramsay's Disease, co-authored with Nancy Blake, he also recommends "fish oil (6 grams daily)"; page 210. He probably talks about this supplement earlier in the book, but my energy fails me in searching for this additional notation.
     
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  18. alex3619

    alex3619 Senior Member (Voting Rights)

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    That was at least eight years after we stopped communicating. I wonder if he actually listened to me? I doubt he would have admitted it, he was quite hostile to contrary views.
     
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  19. alex3619

    alex3619 Senior Member (Voting Rights)

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    This is impossible to give a firm answer to because its entirely variable. Its an unstable result, possibly due to large numbers of hormonal and other influences. That is its subject to lots of interference including feedback loops, not all of which are probably identified yet ... just a guess, but I doubt we know enough even now to figure it out.

    I would argue that any amount is dangerous, but its also an essential food ... omega-6 and omega-3 fats are called essential because without them you die. So small amounts are great.

    So its about finding a balance, and its a moving target. There is no stable balance here. I tried to find an omega-6 balance in the mid 90s before I realised the issues with the biochemistry. A similar thing happens with omega-3s. Taking both together only has a slightly better reaction. I was probably one of the early ME patients who tried high dose omega-3 treatments, which gave initial benefit then failed. So did omega-6s.

    I used to know a lot on this topic, but I have forgotten nearly all of it. It was my pet topic for many years. Keep in mind that I am very out of date, and the science would have changed a lot. I could never keep up with the research as there was so very much, with new hormones being discovered almost every year.

    There are two impacts of polyunsaturated fats that are important I think. Simpson was focusing on the cell membrane deformability. I am much more interested in cell hormone regulation. Both main types of polyunsaturated fats lead to hormone synthesis. Omega-6 leads to series one and series two eicosanoid synthesis, and omega-3 leads to series 3. Series 2 and 3 are predominantly inflammatory, both of them. So omega-3s are inflammatory, not anti-inflammatory ... so why is the other story so commonly claimed?

    Series 1 leads to PGE1, which was the outcome I think Simpson wanted. I pointed out he should directly supplement with PGE1 and not try to get it from evening primrose oil as a source. He didn't like that. I made that suggestion to a vascular surgeon once as well, as this can restore blood flow and remove the need for some amputation.

    We have at least one and maybe several issues with eicosanoid synthesis. There has a been a lot of debate on this, but not a lot of firm answers. Secondary evidence indicates we may over-produce series 2 eicosanoids, including the nitrosative stress findings. I certainly do ... if I consume rendered animal fat by accident, due to bad restaurant choices by the chefs, then I collapse in pain for many many hours, unable to move.

    Eicosanoids are several families of hormones, including prostaglandins and several types of immune signalling molecules. Eicosanoids are critical for sleep, in particular you need PGED2 or sleep is impossible. These hormones frequently have a half-life of only seconds. So you have to keep making them. If you supply too much free substrate (its usually bound), especially arachidonic acid, you will rapidly make too much of these hormones, and this can induce a frightening sequence of hormonal disasters. Inject a rabbit with even tiny amounts of this stuff, not bound, and its a rapid screaming death. Alcohol poisoning most often kills this way, because alcohol releases free arachidonic acid and death from alcohol poisoning is reliably blocked by drugs that block eicosanoid synthesis.

    Some series 2 eicosanoids are anti-inflammatory, but its the balance that matters. So far as I know we do not have any reliable means to direct which are made and which are not.

    So the typical result of series 2 eicosanoids is a complex mix of inflammatory problems.

    Series 3 have the same profile, but here is the important part ... they are much less active. Also, critical enzymes process both types of fat, with a preferential binding to omega-3. So omega-3 induces something called competitive inhibition. So less omega-6 eicosanoids are made. THIS is why it often has an anti-inflammatory effect.

    If you are salicylate sensitive then there are a number of known factors, possibly more because I have not kept up to date. Glutathione is required to regulate the two critical desaturase enzymes, delta-5 and delta-6 desaturase. It also requires, I think, vitamin C and magnesium, but I would need to go back and check that to be sure. If for any reason you do not have enough of these enzymes, or not enough glutathione, they cannot make enough eicosanoid substrate to keep up with demand if they are challenged. Salicylates and similar substances inhibit these two enzymes, that has been known for 34 years now. Suddenly your supply of critical hormones at the cellular level is halving every few seconds. Instant symptoms. A lot of chemical intolerance is explained by this and similar substances and their impact on cellular hormones.

    The short answer is if you are healthy then small amounts of both fats are great, with not too high a poly-6 to poly-3 ratio. If you are sick with issues involving oxidative and nitrosative stress then you may have very big problems. Its a gamble. Its also variable over time. I could say more but this post is already too long. There is lots more on oxidative stress and trans fats that are important here, much of which I have forgotten.
     
    Last edited: Feb 12, 2020
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  20. Mij

    Mij Senior Member (Voting Rights)

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    I don't know if my RBC are deformed, but I was very deficient in Omega 3 based on my elaborate RBC fatty test in 2000. All my other fatty acids were normal, except for one that was 'high'. Taking omega 3 regularly has improved my cognitive function.

    I took a fair amount Efamol back in the early 1990's rec'd by my ME doctor, it didn't help me, but it did offer some improvement for my friend with FM.
     
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