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  • Jefferson Adams
    Jefferson Adams

    Study Looks at Iron Levels and Celiac Disease Development

    Reviewed and edited by a celiac disease expert.

    A Mendelian randomization study helps researchers examine the role of iron status in the development of celiac disease.

    Study Looks at Iron Levels and Celiac Disease Development - big iron by eschipul is licensed under CC BY-SA 2.0.
    Caption:
    big iron by eschipul is licensed under CC BY-SA 2.0.

    Celiac.com 02/14/2024 - Rising celiac disease rates pose a significant health challenge, yet the environmental triggers behind the rise remain elusive. Among the various potential factors, iron deficiency has emerged as a potential contributor to the development of celiac disease. A recent study, employing Mendelian randomization (MR), sought to investigate the intricate relationship between iron status and the prevalence of celiac disease.

    Understanding Mendelian Randomization

    Mendelian randomization (MR) is a powerful method that explores potential causal relationships between an exposure and an outcome. In this case, the researchers delved into the connection between genetic variants associated with iron status and the presence of celiac disease.

    Research Design

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    The study adopted a two-sample MR approach, utilizing single nucleotide polymorphisms (SNPs) linked to iron status. These SNPs were derived from a meta-analysis of three genome-wide association studies (GWAS). The association between these SNPs and celiac disease was then assessed using GWAS summary statistics from the UK Biobank, which included data from 336,638 white British individuals, 1855 of whom had celiac disease.

    Key Findings - Higher Iron Status Inversely Related to Risk of Celiac Disease

    The team identified four SNPs strongly associated with systemic iron status. Notably, these were not linked to known risk factors for celiac disease. The harmonized analysis revealed a compelling association: higher iron status was inversely related to the risk of celiac disease. The odds ratio per one standard deviation increase in serum iron was 0.65, with a 95% confidence interval of 0.47 to 0.91. Crucially, leave-one-out analyses consistently supported these findings, and no single SNP disproportionately influenced the association. Importantly, all three assumptions of MR appeared plausible, strengthening the credibility of the study's conclusions.

    Conclusion and Implications

    The study's groundbreaking discovery that genetically lower iron levels are associated with an increased risk of celiac disease holds significant implications for prevention strategies. By shedding light on the potential role of iron status in the development of celiac disease, this research opens avenues for targeted interventions and preventive measures.

    As the scientific community continues to unravel the complex factors contributing to celiac disease, studies like these pave the way for a deeper understanding of the condition and, ultimately, more effective strategies for its prevention and management. This research not only adds valuable insights to the celiac disease puzzle but also underscores the potential impact of addressing iron status in the broader context of preventive healthcare.

    Read more in BMJ Open Gastroenterology



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    Auldtwa

    This is weird.  I had no sign of iron deficiency until I developed celiac disease.  And yet this is saying that somehow my iron levels triggered the disease?  

    Isn't it more likely that whatever gene it is is simply associated with people who present via iron deficiency?? So if I have a "tendency" to low iron, when celiac is triggered that's what's going to be affected first? 

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    sc'Que?
    6 hours ago, Auldtwa said:

    This is weird.  I had no sign of iron deficiency until I developed celiac disease.  And yet this is saying that somehow my iron levels triggered the disease?  

    Isn't it more likely that whatever gene it is is simply associated with people who present via iron deficiency?? So if I have a "tendency" to low iron, when celiac is triggered that's what's going to be affected first? 

    I was thinking the same thing.  

    In fact, after nearly two years of upset stomach and other trickledown side-effects (c.2007), the sudden intense craving for beets one night while I was at work was what indicated to me that I  was tending toward anemia and that I had an iron deficiency.  This was when I became determined to find out what was wrong with me.  

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    Ronnie d

    even more weird too me, is i actually ate a bowl of beets before my diagnosis many years ago....

    i don't even know how long they'd been in the pantry, lol

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    MrsRose
    23 hours ago, Auldtwa said:

    This is weird.  I had no sign of iron deficiency until I developed celiac disease.  And yet this is saying that somehow my iron levels triggered the disease?  

    Isn't it more likely that whatever gene it is is simply associated with people who present via iron deficiency?? So if I have a "tendency" to low iron, when celiac is triggered that's what's going to be affected first? 

    I was diagnosed with genetic hemochromatosis 5 years ago about the same time I was diagnosed with Celiac (I am 58) I have to have 3-4 phlebotomies a year because my body holds on to every ounce of iron I consume. It's the ferritin levels in the iron that are deadly for me. Maybe this info will help with further research.

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    MrsRose

    I had extensive gene testing done. I have what is called " the mother F" gene. Fascinating research but very scary to me because it's associated with alot of disease. I have been diagnosed with 5 diseases when I hit around 52. They are now looking at Lupus🤷🏼‍♀️

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    Auldtwa

    Yowsa.  I've just got three, one of them dormant.  And only one auto immune.  Good luck.

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    Dswaterman
    On 2/21/2024 at 1:04 PM, MrsRose said:

    I was diagnosed with genetic hemochromatosis 5 years ago about the same time I was diagnosed with Celiac (I am 58) I have to have 3-4 phlebotomies a year because my body holds on to every ounce of iron I consume. It's the ferritin levels in the iron that are deadly for me. Maybe this info will help with further research.

    Mrs Rose - I am a compound heterozygote carrier for Hemochromatosis. I was diagnosed with Celiac in 2013 and discovered my Hemachromatosis in 2019. I had celiac for many years prior but it took time to diagnose. I can confidently state my iron has never been on the anemic side although my 1-2 phlebotomies per year keep me very low on the ferritin scale. I would be interested in any correlation of the two but doubtful they are related. 

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    MrsRose
    1 hour ago, Dswaterman said:

    Mrs Rose - I am a compound heterozygote carrier for Hemochromatosis. I was diagnosed with Celiac in 2013 and discovered my Hemachromatosis in 2019. I had celiac for many years prior but it took time to diagnose. I can confidently state my iron has never been on the anemic side although my 1-2 phlebotomies per year keep me very low on the ferritin scale. I would be interested in any correlation of the two but doubtful they are related. 

    Thank you for sharing. I once heard in a health seminar, "genetics is the loaded gun, lifestyle and food pulls the trigger" I control my Celiac by strict diet, I control my HemoChom thru Calcium, which is an Iron blocker, and my Rh is almost non existing because I quit eating gluten...it's all about what goes in my mouth👍

    My ferritin last week was 236 down from 936. I'm in the normal range (11-300) but my oncologist wants me at 100, so I get a phlebotomy monthly until June, will see if I reach my 100 goal. 

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    Raquel2021

    My ferritin has always being lower than 9. It seats around 5 or 6. I have celiac disease and I am not able to raise it with supplements or food. Ferritin has been low since I can remember.  Always have had a lot of fatigue. 

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    MrsRose
    38 minutes ago, Raquel2021 said:

    My ferritin has always being lower than 9. It seats around 5 or 6. I have celiac disease and I am not able to raise it with supplements or food. Ferritin has been low since I can remember.  Always have had a lot of fatigue. 

    I wish my numbers were that low. I have tons of energy. I hiked today with my daughter and grandson, my grandson was the tired one who couldn't keep up.

    I have one concern,  my phlebotomies are causing 138 pulse, they can't let me go until my pulse gets under 100, so I sit there for an hour or 2, that stinks, that's cardiac arrest issues, so my doc is going to send me to a heart Dr....I'm very positive about all my medical issues, beautiful hike today in the Coachella valley with my family, life is good despite all this stuff.

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    Maria Deal

    I find this interesting. I had horrible monthly periods & anemia, then at age 19 was told my Endometriosis was so bad I should probably have a complete hysterectomy because I probably would not have children & yes my life was severely altered. Back then, 1982, there was no “autoimmune” connection.

    I never even heard of Celiac then, and yes even then I was desperately trying to find out what I could eat to feel human & not so sick. 
    For decades I was malnourished, anemic and told I had ‘Probable MS’. You all know that most regular doctors never seeked the cause of my multiple deficiencies… it was the Celiac, which I found out at around the age of 55! 
    So, was my Endometriosis/Adenomyosis/Fibroids and heavy/long periods to blame from age 13 to 33 (complete hysterectomy) then never getting back to homeostasis again?
    Or was Celiac to blame from the very beginning? 

    1 side of my family is huge, no Celiacs. Other side of my family very small, lots of GI & Pancreas issues. I suspect the small side of my family has the genetic component for Celiac. Interesting.

    I will say that since I eat primarily Clean Ketovore, after trying Carnivore for 130+ days last Spring, then deciding I do better with some variety, I am off more than half my medications & all my heart & stomach issues are mostly gone. 🙌🏼 So, the types of food we eat do make a difference. My body does not do well on most all starches, fake gluten-free ‘breads’, or too much fiber. 🤷🏻‍♀️ I know I will get flack & questions. I have tried just about every diet, & elimination diet there is. 

    Oh, I do have an adult miracle child, we both almost died during childbirth. She had 9 food allergies, so that was interesting ( probably why I was SOoo sick during whole entire pregnancy). I de-sensitized 7 of her allergies all by myself, before that was even a known thing. 🤓 So yep, pretty smart nerd here. 
     

    I do believe I have been undiagnosed Celiac my entire life, & now I am the very rare Airborne Reactive Celiac, besides the fact that I had the brain lesions of MS (and everything else) for decades…. My vote is Celiac first, anemia is just a common problem BECAUSE of Celiac. 

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    Wheatwacked

     

    On 2/22/2024 at 6:56 PM, MrsRose said:

    My ferritin last week was 236 down from 936

    Low serum 25-hydroxyvitamin D in hereditary hemochromatosis: relation to iron status  The results reveal that the low serum 25-OHD concentration in patients with hemochromatosis is directly related to the extent of iron loading and it is improved by venesection therapy.

    1,25 vitamin D may be associated with suppression of hepcidin expression 

      Serum 25-OHD levels in individual patients were inversely related to the size of body iron stores... removal of excess body iron by venesection therapy produced a significant increase in the mean serum 25-OHD from 20 ng/ml to 30 ng/ml ... mean serum 1,25-[OH]2D levels were similar in iron-loaded and control subjects, indicating that the regulation of this metabolite was intact in patients with hemochromatosis... The results reveal that the low serum 25-OHD concentration in patients with hemochromatosis is directly related to the extent of iron loading and it is improved by venesection therapy.

     "Cross-sectional analyses revealed that compared to participants with 25(OH)D concentrations of <50 nmol/L, those with 25(OH)D concentrations of 75 to <100, 100 to <125, and ≥125 nmol/L had SF concentrations that were 13.00, 23.15, and 27.59 µg/L lower respectively"

    In English:

    Compared to vitamin D <50 nmol/L baseline:

    • increase vitamin D, 25 hydroxy D, plasma to 75 to 100 nmol/L (30 to 40 ng/ml) had 13.00 less serum ferritin.
    • increase vitamin D to 100 to 125 nmol/L (40 to 50 ng/ml) had 23.15 less serum ferritin.
    • increase vitamin D to greater than 125 nmol/L (more than 50 ng/ml) had 27.59 less.

    Looks like increasing 25 hydoxy D for every 10 ng/ml the ferritin goes down by about 10.

    By extrapolation raising 25 hydroxy D3 to 80 ng/ml could lower ferritin by up to 60.

    Summer unprotected sun or lots of vitamin D3 supplements in the range of 10,000 to 20,000 IU a day.  Get vitamin D and PTH levels checked every few months to be safe, because you are supplementing calcium.

    On 2/21/2024 at 1:04 PM, MrsRose said:

    I was diagnosed with genetic hemochromatosis 5 years ago about the same time I was diagnosed with Celiac

    Inflammation causes ferritin to go up.  With inflammation under control and vitamin D level at normal level of 80 ng/ml instead of near deficiency you might reach the goal of under 100.

    I have to take 10,000 IU a day to maintain 80 ng/ml, since 2014.

    Vitamin D modulates gene expression.

    Sunshine is your friend.  Unless you specifically have issues with skin cancer, avoiding sun is hurting you.  Enjoy those hikes.

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  • About Me

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    Jefferson Adams is Celiac.com's senior writer and Digital Content Director. He earned his B.A. and M.F.A. at Arizona State University. His articles, essays, poems, stories and book reviews have appeared in numerous magazines, journals, and websites, including North American Project, Antioch Review, Caliban, Mississippi Review, Slate, and more. He is the author of more than 2,500 articles on celiac disease. His university coursework includes studies in science, scientific methodology, biology, anatomy, physiology, medicine, logic, and advanced research. He previously devised health and medical content for Colgate, Dove, Pfizer, Sharecare, Walgreens, and more. Jefferson has spoken about celiac disease to the media, including an appearance on the KQED radio show Forum, and is the editor of numerous books, including "Cereal Killers" by Scott Adams and Ron Hoggan, Ed.D.

    >VIEW ALL ARTICLES BY JEFFERSON ADAMS

     


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