The power and pitfalls of omics part 2: epigenomics, transcriptomics and ME/CFS
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DHEA lowers inflammatory cytokine IL6 late-onset B cell neoplasia, RA, etc

Discussion in 'General Treatment' started by heapsreal, Nov 6, 2011.

  1. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    Interleukin-6 (IL-6) is one of the pathogenetic elements in inflammatory and age-related diseases such as rheumatoid arthritis, osteoporosis, atherosclerosis, and late-onset B cell neoplasia. In these diseases or during aging, the decrease in production of sex hormones such as dehydroepiandrosterone (DHEA) is thought to play an important role in IL-6-mediated pathogenetic effects in mice. In humans, we investigated the correlation of serum levels of DHEA, DHEA sulfate (DHEAS), or androstenedione (ASD) and IL-6, tumor necrosis factor-?, or IL-2 with age in 120 female and male healthy subjects (1575 yr of age). Serum DHEA, DHEAS, and ASD levels significantly decreased with age (all P < 0.001), whereas serum IL-6 levels significantly increased with age (P < 0.001). DHEA/DHEAS and IL-6 (but not tumor necrosis factor-? or IL-2) were inversely correlated (all patients: r = ?0.242/?0.312; P = 0.010/0.001). In female and male subjects, DHEA and ASD concentration dependently inhibited IL-6 production from peripheral blood mononuclear cells (P = 0.001). The concentration-response curve for DHEA was U shaped (maximal effective concentration, 15 10?8 mol/L), which may be the optimal range for immunomodulation. In summary, the data indicate a functional link between DHEA or ASD and IL-6. It is concluded that the increase in IL-6 production during the process of aging might be due to diminished DHEA and ASD secretion. Immunosenescence may be directly related to endocrinosenescence, which, in turn, may be a significant cofactor for the manifestation of inflammatory and age-related diseases.
    http://jcem.endojournals.org/content/83/6/2012.short

    Interleukin 6 is also involved in insomnia as well, which is part of the reason im looking into this.

    cheers!!!
     
  2. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    DHEA and Immune Function

    DHEA levels decline 80-90% by age 70 or later. DHEA has demonstrated a striking ability to maintain immune system synchronization. Oral supplementation with low doses of DHEA in aged animals restored immunocompetence to a reasonable level within days of administration. DHEA supplementation in aged rodents resulted in almost complete restoration of immune function (Danenberg et al. 1996).

    DHEA has been shown in numerous animal studies to boost immune function via several different mechanisms. Only limited human studies have been done to measure DHEA's effect on the immune system.

    In one study that focused on men, scientists proposed that the oral administration of DHEA to elderly men would result in activation of their immune system: nine healthy men averaging 63 years of age were treated with a placebo for two weeks followed by 20 weeks of DHEA (50 mg a day). After two weeks on oral DHEA, serum DHEA levels increased by 3-4 times. These levels were sustained throughout the study. Compared to the placebo, DHEA administration resulted in: An increase of 20% in IGF-1. Many people are taking expensive growth hormone injections for the purpose of boosting IGF (insulin-like growth factor) levels. IGF is thought to be responsible for some of the antiaging, anabolic effects that DHEA has produced in previous human studies.
    An increase of 35% in the number of monocyte immune cells.
    An increase of 29% in the number of B immune cells and a 62% increase in B-cell activity.
    A 40% increase in T-cell activity even though the total number of T-cells was not affected.
    An increase of 50% in interleukin-2.
    An increase of 22-37% in natural killer cell (NK) numbers and an increase of 45% in NK cell activity.
    No adverse effects were noted with DHEA administration.
    The scientists concluded: "While extended studies are required, our findings suggest potential therapeutic benefits of DHEA in immunodeficient states" (Khorram et al. 1997).

    A study published in the Journal of Clinical Endocrine Metabolism showed that when old female mice were treated with DHEA, melatonin, or DHEA and melatonin, splenocytes (macrophages) were significantly higher as compared to young mice. B-cell proliferation in young and in old mice significantly increased. DHEA, melatonin, and DHEA and melatonin helped to regulate immune function in aged female mice by significantly increasing the cytokines interleukin-2 and interferon-gamma and significantly decreasing the cytokines interleukin-6 and interleukin-10, thus regulating cytokine production (Inserra et al. 1998).

    Interleukin-6 (IL-6) is one of the pathogenic elements in inflammatory and age-related diseases, such as rheumatoid arthritis, osteoporosis, atherosclerosis, and late-onset B-cell neoplasia. According to a report in the June 1999 issue of the Journal of the American Geriatrics Society , "higher circulating levels of IL-6 predict disability onset in older persons." The authors suggest that IL-6 may cause a reduction in muscle strength or contribute to specific diseases such as congestive heart failure, osteoporosis, arthritis, and dementia, which cause disability (Ferrucci et al. 1999).

    DHEA has consistently been shown to boost beneficial interleukin-2 and suppress damaging interleukin-6 (IL-6) levels. Interleukin-6 is overproduced in the aged, which contributes to autoimmune disease, immune dysfunction, osteoporosis, depressions in healing, breast cancer, B-cell lymphoma, and anemia. Continuous DHEA administration maintained immunocompetence in aged animals (by boosting interleukin-2 and other beneficial immune components and suppressing interleukin-6 and other detrimental immune components). Suppression of interleukin-6 with 200 mg a day of DHEA was shown to be effective against systemic lupus erythematosus (Van Vollenhoven et al. 1998).

    Researchers compared levels of IL-6 in 283 subjects with a mobility or functional disability with IL-6 levels in 350 adults without a disability. The investigators found that adults in the highest third of values of IL-6 had a 76% higher rate for mobility disabilities and a 62% higher rate for inability to perform daily activities than subjects in the lowest third of values. "These data suggest that IL-6 is a global marker of impending deterioration in health status in older adults," wrote a team led by Dr. Luigi Ferrucci at the National Institute on Aging in Bethesda, MD (Ferrucci et al. 1999).

    In a study in the Proceedings of the Society for Experimental Biology and Medicine, DHEA has been shown to restore normal cytokine production in immune system dysfunction induced by aging by suppressing the excessive production of cytokines (IL-6) by 75%, although increasing IL-2 secretion by nearly 50%, during a leukemia virus infection in old mice (Inserra et al. 1998).

    Another study in normal healthy individuals over the age of 40 found an opposite relationship between plasma DHEA levels and the presence of detectable levels of IL-6. Studies also revealed that low doses of DHEA and DHEA-S inhibited the production of IL-6 in unstimulated human spleen cell suspension cultures and enhanced its release by cultures transferred from organs of the same tissue (James et al. 1997).

    The age-related increase in circulating IL-6 levels in humans, which has been attributed to decline in DHEA production by the adrenal gland, is currently attracting attention because of its possible relevance to the etiology and management of a number of age-related clinical disorders. The potential importance of these observations and suggestions has prompted us to perform more detailed studies on the relationship between IL-6 and DHEA. Using immunoassay techniques, scientists found in normal healthy individuals over the age of 40 that low levels of plasma DHEA levels predicted levels of IL-6 (James et al. 1997).

    http://www.lifeextensionvitamins.com/dhrethpa2.html
     
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  3. rydra_wong

    rydra_wong Guest

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    This is great, Heaps. I'm going to save a copy of this.

    I read somewhere that all CFSers are low in DHEA-S. (DHEA-Sulfate). I do not know if this is from not getting enough sulfate or enough DHEA or something else. So when you get your labs, you might want to select a lab that shows DHEA-S instead of just DHEA just to make sure you are personally getting all the benefit you can from DHEA.

    Also I forgot to mention in the other DHEA topic, but DHEA itself can keep you from sleeping. You are not supposed to take it late in the day (yet if you want to keep it in your system at all times, you need a divided dose because it only stays in your system 20 hours). Theoretically then taking it at breakfast adnd lunch would be ok, but I take it at breakfast and dinner and it does not keep ME awake...but if I actally take it past 7pm it does keep me awake. I find if I get less than 25mg in my system I can piss away a lot of time on nothing before I realise I have lost my edge diue to deficiency.

    For the record, I feel great today -- it has been two weeks since last flea product exposure and I am finally coming around (but unfortunately I have to reapply the flea product (translate DHEA blocker) tomorrow. (shoot me now)
     
  4. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    Yes dhea tests are dhea-s i get. I have read that dhea can cause sleep problems too, but im thinking that if there in the normal range it shouldnt be a problem(as of my last test my dhea levels were below range), trial and error again. Trialling low doses as well so i can monitor the effects, when i take a second dose i will look at taking in late afternoon and avoid night time dosages. I think optimising our hormones can help improve our overall health, may not be a specific cure as such but go's along way towards our health, as you pointed out all the positive studies that can be found. Low dhea levels like reverse T3 can be an indicator of poor health, chronic stress etc, so a generalised biomarker of our health statues.

    cheers!
     
  5. merylg

    merylg Senior Member

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    Thanks for this thread heaps. IL-6 has also been linked to Insulin Resistance, Type 2 Diabetes, Obesity, Increased Risk Coronary Heart Disease, Acute MI and Unstable Angina, Psoriasis & Psoriatic Arthritis.
    Here's an interesting paper reminding us that not only is fatty tissue part of the Endocrine System, but it is also part of the Immune System:

    http://www.skintherapyletter.com/2008/13.1/1.html

    meryl
     
  6. Waverunner

    Waverunner Senior Member

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    Thanks for the info. I just bought some DHEA but I'm not sure if I should take it after you posted that it has the following effect:

    "An increase of 29% in the number of B immune cells and a 62% increase in B-cell activity."

    If we look at the Norway study and that it probably was B cell depletion which cured some ME patients I'm not sure what to make of DHEA.
     
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  7. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    It depends if they get infected with whatever infection. Also improves NK function which also decreases viral activity, more positives then negatives for cfs. Like the whole hormone issue with xmrv, we are supplementing to get our low levels to normal, low levels have there own immune suppression effects. Also dhea effective in other auto-immune diseases, so its one of those decisions u have to make or trial and error.

    cheers!!!
     
  8. Waverunner

    Waverunner Senior Member

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    Thanks for the answer. Do you think it would be good to test for DHEA? Is there a good way to find out if levels are balanced?
     
  9. CBS

    CBS Senior Member

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    Heaps, Thanks for the info.

    I have to say that I second Waverunner's caution. I've tried both DHEA and testosterone several times at the urging of my endocrinologist. Every time I tried either I felt worse even though my DHEA levels and testerone levels are significantly lower than the reference ranges.

    Now that I'm on Valcyte, my monocyte level started dropping significantly within a month and I'm feeling much better. It was explained to me that the lowering of monocyte levels may be an important mechanism for eliminating reservoirs of herpes infection and/or inhibiting B-cell production.
     
  10. Waverunner

    Waverunner Senior Member

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    That's why I hate ME so much. You never know what to do. What can feel good in the short run can make you feel worse in the long run. What might seem good can actually be bad. Can someone please solve this disease?
     
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  11. rydra_wong

    rydra_wong Guest

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    Just fyi, but my DHEA is high. If my DHEA were "in range" for other people it would not work for me. What matters to my doctors is that the hormones I make out of it are cancer preventative rather than cancer causing (and there are supplements you can take to see that happens). (I do not look or sound male in any way in case you were thinking that btw). The DHEA IMHO is staving off what would be a precipitous meltdown into diabetes for me, as well as preventing glutamate toxicity, straightening out some neural issues, and possible regulating my CBS genes correctly. There is a HUGE difference to my productivity also on DHEA. My DHEA is not tremendously high, but it is above "normal" range. I think very littel of laboratory ranges because ALL THEY DO to "establish" them is throw out the upper and lower 5% of the results they receive. If you think about it, they receive an awful lots of results from sick people yet they have NO criteria to exclude sick people when they establish the ranges!

    My doctor thinks I need high DHEA for adrenal issues. We caught some adrenal issues on a lab but once I knew what it was I was able to identify it quite clearly as "those times when I reuquire salt to keep from passig out" and h"those times I have low blood pressure despite 3 genes that cause high blood pressure". By those (very easily observed) symptoms, I am able to say that I do not normally have adrenal issues but I periodically get very bad adrenal issues during such things as allergy season or chemical exposure.

    I take 75mg DHEA and 30mg pregnenolone. Freddd takes 100mg pregnenolone and 25mg DHEA, which sounds like a more sensible dose to me (but it won't work for me -- I tried it...the amount of progesterone this makes causes water retention and affects my blood pressure and the low DHEA is not enough to stave off my issues).

    There are different issues in hormone replacement between men and women. To sort them out, I would highly recommend finding out what you can from Dr. Jonathon Wright, the pioneer in bioidentical hormone replacement. He is with Meridian Valley Labs (which I access through www.lef.org). The lab web site used to have a paper by him on things to affect your hormone cascade. The lab also send out an e newletter you can sin up for. He has written books (I haven't yet read). And he appears at conventions and gives seminars.

    Second resource I woul drecommend is www.lef.org. Their whole focus is bioidentical hormone replacement and they have reams of info on it separated out into "male hormone replacement" and "female"... topics.

    It might be worth considering whether you can't tolerate it due to that you need aromatase inhibitors and/or 5-alpha-reductase inhibitors. There are things you can do about that - not sure how well they work. I personally wouldn't take drugs to do it. I never take drugs -- too many adverse reactions. For instance I think men need more zinc because it's an aromatase inhibitor.

    Cheerz.

    Oh,. P.S. I get lab range information from www.lef.org. They look at the studies to determine ranges, not what the lab lists as "normal"
     
  12. FunkOdyssey

    FunkOdyssey Senior Member

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    For the time being, with consideration of the preliminary rituximab results, I'd consider any supplement that dramatically increases B-cell number and activity to be contraindicated in CFS. Just my opinion.
     
  13. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    Its hard to know what to do because we are all so different, all you can do is try things sometimes in a few different ways like lower doses or having day off here and there etc, we need to play around with somethings until we find what works. for me i could tolerate adrenal treatments like pregnenolone or even ginseng etc as it over stimulated me but now with antivirals lowering my viral load i can tolerate small doses. I havent got anything nailed down yet as still adjusting everything but i feel there is some value in there as it is improving energy. for me i have to dial in the dose or i can get overstimulated and have problems sleeping.

    CBS many things can make you feel bad when using androgens like testosterone and dhea, it common that there can be too much convertion to estrogen from them which then negates there positive effects, good reason for getting blood work to see whats going on as 1 hormone can greatly effect others. I had this problem with dhea, i actually had high estrogen even when not on supplements. I have a good doc who put me on medication to control this extra estrogen and its now within normal limits. So now im trialling dhea again. Even alot of endocrinologists dont understand hormone replacement that well, intergrative doctors seem to have a better handle on it. You may find after being on valcyte awhile and everything comes down to within normal range that you will better handle dhea and or testosterone.

    Adrenal fatigue is apart of what keeps cfs going. personally we need to get sorted with infections and then need to improve adrenal function which is controlled by the hypothalamus which controls many things within the body and is either damaged in cfs or depressed and needs waking up. Its function is involved in hormone secretion, sleep, blood pressure etc etc This is the neuro part of neuro-immune illness.

    cheers!!!
     
  14. CBS

    CBS Senior Member

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    I would not be the least bit surprised if after having been on Valcyte for some time I tolerate DHEA or testosterone much better (or I might find that my levels normalize - see below - I was surprised that both actually made me feel a bit worse when my blood values were so low). I also agree that many patients need to get their adrenal issues addressed. I've been on low dose cortisol for 14 years. The cortisol (and very aggressive rest for over a year) had such a big impact in the early years that I had six years of nearly complete remission (return to work, married, honeymoon on the South Island of NZ touring via tandem - 800 miles in 25 days with lots of big 'hills,' remodeled my own house, etc.). Thought I'd beat this (huge crash when I pushed too hard). Cortisol still helps but there are a lot of other issues now. Interestingly, my endo first wanted to put me on thyroid meds (synthroid - High TSH value). The synthroid made me much sicker. When I started on the cortisol my TSH numbers dropped back to completely normal and I felt great.

    Best of luck with your trial of DHEA.
     
  15. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    Interesting with the thyroid, i have heard numerous people feel worse with thyroid and later find out they had adrenal problems, so its like whipping a dead horse. I could probably wait abit longer since having my viral stuff sorted and see if adrenals respond but i dont want to wait any longer and have also read that it can take 12-18 months to sort adrenal fatigue issues as well. This is why im chasing after it.

    How long have you been on valcyte and what viruses you tested for? I think it sounds like your on the right track, good luck dude.

    cheers!!!
     
  16. Sing

    Sing Senior Member

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    Not sure about DHEA supplementation and am taking some of this information with caution as one source is called Life Extension Vitamins. Unfortunately over the years I have read so many raves about different supplements, and have taken quite a few but rarely benefited. I can see the rationale for bringing one's levels (of anything) up to its "normal" range--that's about it. Hormones are so interactive with so many elements, it is not easy to establish a simple cause and effect relationship, a reliable benefit in all cases. Someone without ME/CFS might up their level of DHEA and benefit but maybe someone with it might not--Not long ago we were hearing from Dr. Mikovits about how androgens and cortisol stimulate the activity of XMRV. Wish I had one heck of a knowledgable doctor to lead me, instead of having to try to be my own doctor and figure all this stuff out on my own.
     
  17. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    Everything your saying is right, but i think we have to optimize our hormones that are low. I think initially they drop as a protective mechanism which them slows our metabolism. I think treating adrenal dysfunction once you treat infectious/immune problems is the way to go as there is now no need for a protective/slow metabolism, sometimes i think it just gets stuck in slow and for some once infections clear these hormonal problems correct themselves too. I also think that this adrenal fatigue problem can occur on its own. I think its something to look into and definately not a cure all, i think treating cfs includes a multitude of things in certains orders and adrenal hormones are one of them. Treating all these little dysfunctions hopefully adds up to better improvement, thats my philosophy. I have never got a great deal from supps but use them because there is some scientific backing like anti-oxidants and high levels of oxidation in cfs, i think it just helps slow the oxidative process down. I think treatment is going to come in a package not a silver bullet. Everyone is going to need a different package and theres going to be alot of trial and error. My philosophy is to try things that may help and if i dont try i want improve. More people seem to have been helped by dhea then hindered but theres probably more that have had no positive or negative effects from it. Theres know right answer which is a bugger, either roll the dice and play the game or sit back and watch i guess.

    good luck,
    cheers!!!
     
  18. Sing

    Sing Senior Member

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    Thanks, heapsreal! I have found a lot of benefit from Cortef, which I have taken for years. My DHEA is low too in recent years, but I don't much like supplementing it because it only seems to make my skin/scalp oily and smelly, plus make me somewhat interested in sex. The latter makes me sad because I don't have energy to have this in my life, which is why I have sent away each nice fellow who has come along. Clearly this hormone seems to be turning into androgens, which is what I have read it does in females, though not necessarily in males? I haven't noted any other effects. I have some 10 mg pills or caps and for a while took one every other day, with the effects above. A little bit seems to go a long way. So here is a much more specific response from me.

    If I knew it would slow down the development of arthritis, as is suggested above, I might want to take it. Wish my information was more certain.
     
  19. CBS

    CBS Senior Member

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    I started acyclovir in Nov, 2009. Some modest improvement but then a big crash. Started valcyte in May and felt headache and cognitive benefit within 48 hours. The improvement with Valcyte seems to be more steady and prolonged. Time will tell. I have several issues that I've had to address to optimize my situation and I fired a lot of doctors that weren't supportive. My main issues are adrenal (cortisol), Hypothalamus (diabetes insipidus - DDAVP), autonomic (BP - lisinopril), Gut (SIBO - Xifaxan - likely caused by enteroviruses - positive antibody tests via ARUP and positive stomach tissue staining (IHC) that I am just beginning to treat somewhat more directly with Equilbrant - herbal does not necessarily mean gentle - wow!), and viral (HSV-1 and likely HHV-6 - but titers are not all that impressive - given my response to Valcyte compared to acyclovir) and a few "lesser" infections - c pneumonae and CMV infections that we aren't trying to deal directly with at the moment. Given my Sx, there's reason to believe there has been growing CNS involvement. That might also explain the greater impact of Valcyte.

    Take good care!
     
  20. rydra_wong

    rydra_wong Guest

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    I am not saying that anyone else should raise their DHEA above normal range, I am just letting you know that you might not want to be boud by normal ranges. For instance, I had high estrogen when I was young and that is how *I* function best. I also want to mention that if it helps you know immediately - like withoin a half hour for me. So you need not try for days to be sure it works. (All bets are off if you're taking tiny doses though). When I tried it, I started with 50mg DHEA at one time and 30mg pregnenolone (because I wasn't sure how much pregnenolone since I was already taking the full tested dose of DHEA and pregnenolone itself will make DHEA). The 50mg at one time DHEA immediately cured panic and stabilized my blood pressure. But I noticed I would become ineffective - wasting time stupidly etc. in the mornings so I tried 25mg morning and 25mg at dinner. I was no longer effective at all (well maybe for a very short time right after each 25mg. I knew taking more had been tested in depressives, I knew that had not been tested adequately, but that it had bene tested, so I decided to try it. The 75 mg DHEA works very well for me. I then tried to raise the pregnenolone because I thought I should have more of a balance. I tried 50mg and it caused water retention. So I dropped back to 30. I talked to Fredd and found out he takes 100mg pregnenolone and 25mg DHEA so I decided that maybe if I drop my DHEA I can take more pregnenolone. I tried his regime...it did not work for me and it caused water retention (which I believe raised my blood pressure but I didn't really test that). I also tried DHEA 50 and oregnenolone 50. Again it did not work.

    Since I had a reaction to flea control products sometimes when I take DHEA it feels like going into a fun house with the mirrors that shrink you and make you bigger for a few minutes and then settles down to not working. I believe that is because it works for a second and then gets blocked and breaks through for a second and then gets blocked...end result is it can't get through. That's what it feels like anyway. So...if you feel like that for a few minutes after you take it, then I would think DHEA is what you need but something else is blocking it.

    I don't know what X**** is so I know nothing about any interactions between that and something else. I believe that when there is a disease for which there is no known cure that listening too closely to what the medical community says about that disease may not be beneficial (because they have not found the way), although of course all things must be considered.

    I do think fixing the top hormones first is the best way to get sorted out. This is not my idea but I can't remember what doctor I read it from. I can only point to ther things, like the fact that DHEA kills things (cann be used to treat flu for instance) and so will help with the inflammation cascade. (For instance as you said inhibiting IL-6).

    Gotta go
    Rydra
     

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