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CFS severity driven by leptin

Discussion in 'Latest ME/CFS Research' started by MeSci, Apr 11, 2013.

  1. Ema

    Ema Senior Member

    Midwest USA
    Apparently people with anorexia have high leptin levels...hypothalamus dysfunction not sensing need to bring in more calories which is one type of resistance.

    Bulimic people have low leptin levels...and hypothalamus senses this as needing to bring in more calories.

    And obese people have high leptin levels again...and hypothalamus doesn't seem to respond to leptin signals at all which is a different type of resistance.

    What's interesting to me is that time and time again it comes back to the hypothalamus...where the nervous system and the endocrine system meet and communicate. Broken, again.
    Iquitos, rosie26 and Valentijn like this.
  2. heapsreal

    heapsreal iherb 10% discount code OPA989,

    australia (brisbane)
    Not sure if its already been mentioned but reverse t3 can also cause issues with leptin also??
  3. Sing

    Sing Senior Member

    New England
    I wonder how a partial methylation block and lack of glutathione in the system may be connected with hunger or lack of it? When I took NAC for a month to help me sleep (worked wonders) it also reduced my appetite. But it made my hypotension worse and is actually not a good way to try to restore glutathione in the system. It ends up having the reverse effect after awhile, is my understanding. If Richvank was still with us, he could explain if there is a connection. Perhaps Fredd can?
    aimossy and rosie26 like this.
  4. alex3619

    alex3619 Senior Member

    Logan, Queensland, Australia
    The hypothalmic hypothesis goes back to the 80s. Our internal biochemical regulation is tied to a large extent to the hypothalamus, and its very sensitive to oxidative stress, which would include inflammation.
    Last edited: Apr 7, 2014
    rosie26 likes this.
  5. rosie26

    rosie26 Senior Member

  6. Simon


    Monmouth, UK

    I know, the party's over, the debris cleared away, but I have finally read this paper, and I like it.

    Why Leptin?
    The interesting thing about Leptin in general is that (as others pointed out here) it's involved in energy metabolism regulation and immune regulation, where it acts like an inflammatory cytokine. It's also been linked with fatigue in a number of conditions, including IBS and chronic hepatitis C.

    On top of that, in animal studies leptin has been shown to increase cytokine secretion by microglia, the brain's immune cells and so contributing to sickness response (gratuitous plug for my recent blog: Brain Cells Making us Sick? The microglia connection in ME/CFS & Fibromyalgia). So Leptin is a plausible candidate for playing a role in mecfs.

    Good things about this study
    Tracking fluctuations
    The most impressive thing for me about this study isn't the Leptin finding at all, but the longitudinal, 25-day design looking at correlation between leptin levels and fatigue. We all know about fluctuations in this illness so it makes sense to probe this by following individuals over time.

    One reason this is particularly important is that there is huge variation in cytokine levels between healthy people, or to put it another way, a lot of noise in the data. Tracking one person over time really helps, as you are using the same individual at each time point (such 'within-patient' designs are generally reckoned to be a good thing)

    In fact, there was no overall difference in leptin levels between patients and controls in this study.(as @Valentjin pointed out).

    Strong correlations
    Overall, there was a modest correlation between leptin and fatigue in CFS patients (r=0.3 [0-1.0 scale], p<0.01).

    However, what really stands out is the data for individuals: there was a strong to very strong positive correlation in 5 of the 10 patients, and strong negative correlation in one and a marginal correlation in one other patient. By contrast, there was a marginal correlation in one control only. So this looks like something is going on.

    Not data mining
    The study looked at 51 cytokines in all, but the primary outcome was designates as just leptin in advance. There are some good theoretical reasons to suspect leptin (as above), plus pilot data on 3 fibromyalgia patients indicated that leptin alone correlated with fatigue. So the researchers didn't just get a stack of cytokine data and cherry-pick for interesting results, which is encouraging.

    Other points about the study
    Obviously, it's very, very small with just ten patients, and one patient had lower levels of leptin with more fatigue while 5 had higher levels with more fatigue. Plus 4 more had no strong pattern, so it's a bit of a mixed bag.

    However, at the IACFS/ME conference Jarred Younger reported that a larger, NIH-funded replication is planned. Which is fantastic news, and exactly what's needed.

    It's a little surprising that there was no difference in leptin levels overall between patients and controls - given that patients were much more fatigued than controls. Mady Hornig and Ian Lipkin have reported that Leptin levels were higher in patients than controls in their large but as-yet-unpublished study.

    8/10 patients had fibromyalgia too; they also had more other illnesses than controls eg arthritis and Graves disease, and took more medication, though I'm not sure if these factors could explain the leptin correlation.

    Finally, numerous cytokines have been implicated with fatigue eg IL-1, Interferon gamma, and it's a little surprising that none of these cytokines correlated with fatigue either. But maybe that's how it is.

    • An innovative study design, tracking fluctuations in fatigue and cytokines, that other researchers might want to follow.
    • Fascinating results because of the very strong positive correlation between fatigue and Leptin in half of patients.
    • What's really needed now is replication, and it appears that is in hand.
    I just wanted to add a really important point made by @searcher about this study. The levels of leptin, and the range of leptin levels was similar in patients and controls. What seemed to be different was how patients responded to those fluctuations in leptin - as if patients were hypersensitive to changes in leptin. This might be because they have 'primed', excitable microglia (blog on microglia priming hypothesis).

    Also, we don't know if leptin is driving this or just correlated, perhaps as a downstream effect of something that is driving the process. The authors of this paper suggest that this could be tested by injecting paitents with synthetic leptin (synthetic cytokines are often used in medicine, eg as a treatment such as interleukin 1 in cancer and interferon-alpha in hepatitis C).
    Last edited: Jun 3, 2014
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  7. user9876

    user9876 Senior Member

    Sometimes when looking at correlations between time series its useful to have a delay factor. If one factor triggers a slower process then it may not appear to correlate with fatigue on whatever basis they are sampling but may well correlate over say a 2 day window. It may also be that changes correlate rather than absolute levels (this may be particularly the case where levels are very variable over the whole population).
    natasa778, MeSci and Dolphin like this.
  8. Dolphin

    Dolphin Senior Member

    I thought it might be worth pointing out that patient advocate, Lily Chu MD MSHS, was one of the co-authors of this paper.
    Simon likes this.
  9. natasa778

    natasa778 Senior Member

    London UK
    few tidbits on leptin from wiki that might be interesting and possibly relevant in the light on some other recent findings, discussed on several other threads

  10. stevesayshi


    Thread is a bit old, and some of this has probably been mentioned elsewhere, but
    Omega 3 lowers leptin
    Omega 3 is low in CFS
    Some bodybuilders swear by Omega 3 mega dosing for mass gain and more
    Aside from the autoimmune diseases mentioned, leptin can be elevated in autism (I know it's not elevated in CFS per se, but it's not really a thread until autism gets mentioned ;))

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