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Intracellular Nutritional Biomarker Differences in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome ..., Krishnakumar et al, 2022

Discussion in 'ME/CFS research' started by LarsSG, Jun 18, 2022.

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  1. LarsSG

    LarsSG Senior Member (Voting Rights)

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    370
    Objectives
    A comparison of the nutritional biomarkers between ME/CFS subjects and healthy controls (HC) was undertaken on secondary data collected from an IRB approved cross-sectional study in ME/CFS patients.

    Methods
    ME/CFS participants were recruited per the 2018 revised Canadian Clinical Case Definition for ME/CFS along with age matched HCs. Self-reported information on demographics and supplement use was collected, and body mass index calculated. HEI was calculated from Willet FFQ and multiple day 24-hour recall data, and severity of fatigue measured by Multidimensional Fatigue Inventory (MFI). Lymphocyte transformation assay by SpectraCell Lab (Houston, TX) was employed for intracellular micronutrient status. A series of two-tailed Mann-Whitney U tests (ɑ = 0.05) were performed for the non-parametric data expressed as mean ± standard error of the mean. All statistical analyses were conducted in IBM SPSS Statistics version 25 (Armonk, NY).

    Results
    Out of the 21 participants (11 ME/CFS and 10 HC), 82% of ME/CFS and 50% of HC were female. Higher fatigue scores were observed in ME/CFS (16.64 ± 1.36) than HC (10.78 ± 2.14). ME/CFS had better HEI scores (63.36 ± 13.44) than the HC (38.55 ± 12.29). However, despite better diet quality and supplementation, ME/CFS group showed lower intracellular Vitamin B3 and manganese (Mn) (86.3 ± 2.42 and 53.6 ± 2.81 respectively) but higher calcium (Ca) (57.5 ± 3.55) as compared to HC (97.2 ± 2.31, 64.5 ± 1.87 and 46.5 ± 0.96 respectively).

    Conclusions
    The results align with the current literature on indications of mitochondrial dysfunction in ME/CFS. Reduced intracellular vit B3 provides suboptimal production of the NAD(P)(H)-cofactor family, thus affecting mitochondrial function and consequently energy production. The aberration in energy metabolism is compounded by other factors, such as reduced Mn but higher Ca intracellular levels seen in this study indicating disruptions in oxidative stress pathways, resulting in debilitating fatigue experienced by individuals with ME/CFS.

    Link (but nothing other than abstract available)
     
    LarsSG, Jun 18, 2022
    #1
    sebaaa, Snow Leopard, MeSci and 8 others like this.
  2. LarsSG

    LarsSG Senior Member (Voting Rights)

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    Interesting to see low manganese come up given the low manganese in hair samples from Ron Davis, but with 11 patients, who knows how meaningful that is. They must have been testing a lot of different nutrients, so they were bound to come up with some "significant" differences below 0.05 just by chance.
     
    LarsSG, Jun 18, 2022
    #2
    Snow Leopard, MeSci, Hutan and 7 others like this.
  3. Jaybee00

    Jaybee00 Senior Member (Voting Rights)

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    Jaybee00, Jun 18, 2022
    #3
    Hutan and Peter Trewhitt like this.
  4. Midnattsol

    Midnattsol Moderator Staff Member

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    Would have liked more than the abstract (I've previously been frustrated by that from this journal).

    For those unfamiliar with HEI, it stands for "Healthy Eating Index" and is a summary score of 13 different dietary components, that each can give between 5 to 10 points, with the maximum total score being 100. A higher score indicates a higher quality diet that is closer to the American dietary guidelines. Since the score is a sum of many different dietary components, people with very different diets could still get a similar score, while eating dfferent foods and getting different nutrients. A higher score would not automatically indicate a higher intake of all nutrients, so I don't really like their "despite better diet quality..." as that simply makes no sense.

    The control group has a low average HEI score, the average American scores >50 according to dietary data collected in NHANES from 2015-2016, with older age having a higher score. I wonder what the age of the participants in the study was. The average score is the same as ages >60 and up from NHANES.

    I do enjoy that they've looked at intracellular levels of nutrients and not blood, though I don't think we have reference ranges so with so few participants it's difficult to interpret. There are limits to how much of dietary vitamin B3 the body can utilise, so eating more or less of it is unlikely to contribute to NAD/NADH balance I think. That's why some advocate for pure NAD supplementation, to bypass the limitations on vitamin B3 metabolism.

    Great that they have actually collected dietary data, it is often missing from studies on metabolites and pwME. Though, FFQs and 24 hour recalls have som limitations :p I would have liked to see a comparison of nutrient intake, not just the HEI score and intracellular values. When I'm mostly housebound I eat ~1400 kcal, and that's not a lot although I reach the required daily intake values for all nutrients with a bit of planning. In contrast when I was active I would typically consume >2700 kcals in a day and didn't have to think that much about what I ate when it came to micronutrients as the volume of food meant it was easy to get enough. Differences in concentrations between groups could come from different absolute intake.
     
    Midnattsol, Jun 18, 2022
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  5. Creekside

    Creekside Senior Member (Voting Rights)

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    21 subjects, with vague sets of factors (fatigue and diet), and they're trying to claim meaningful results? I expect if they redid this with completely random subjects, they could find some similar correlations, with the astonishing conclusions that one group was suffering from snake venom or whatshisname's syndrome. Not impressed.
     
    Creekside, Jun 18, 2022
    #5
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  6. SNT Gatchaman

    SNT Gatchaman Senior Member (Voting Rights)

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    Given the established 3-4:1 ratio in ME I wonder if 80% of HCs female would be a better comparison. Perhaps differences and similarities are obscured.

    Key points from Sex differences in immune responses (Nature 2016)
    • Sex is a biological variable that affects the functions of the immune system.

    • Sex differences occur in both innate and adaptive immune responses and are evolutionarily conserved across diverse species.

    • Sex differences in immune responses change throughout life and are influenced by both the age and reproductive status of an individual.

    • Sex chromosome genes and sex hormones, including oestrogens, progesterone and androgens, contribute to the differential regulation of immune responses between the sexes.

    • Environmental factors, including nutrition status and the composition of the microbiome, also alter the development and functioning of the immune system differently in males and females.
     
    SNT Gatchaman, Jun 19, 2022
    #6
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  7. Midnattsol

    Midnattsol Moderator Staff Member

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    Sex differences could also impact HEI score, in general women have healthier diets than men. In pure calories, men would also likely eat more than women, though we don't know anything about the activity level and enery requirement of either the pwME or the control group. This is important as HEI looks at intake per 1000 kcal, so with a lower energy intake you need less absolute amounts of the healthy foods HEI includes to get a higher score. Of course the ratio is the same, but it could make quite a difference if you have a group of people who are mindful of eating healthy while also having a low energy intake vs someone with a normal intake who doesn't think about it.
     
    Midnattsol, Jun 19, 2022
    #7
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  8. MeSci

    MeSci Senior Member (Voting Rights)

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    Maybe nutrient (and other) studies should also take into account the generally low fluid levels which ME patients have.
     
    MeSci, Jun 19, 2022
    #8

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