Often vilified, the so-called “anti-nutrients” like oxalates, phytates and tannins can be strategically employed in the diet to inhibit iron and toxic metal absorption and successfully lower ferritin in iron overload as a part of an overall plan for hereditary hemochromatosis (HH).
Meet Our HH Case
A 49-year-old man recently presented to the clinic with a variety of significant musculoskeletal complaints, including tendinitis, arthritis, osteochondritis, and cervical degenerative disc disease with radiculopathy. He complained that pain & damage would occur (i.e. rotator cuff tendonitis) without apparent injury, and “nothing heals”. He also suffered from severe seasonal allergies and complained of fatigue. He generally followed a gluten-free, dairy-free diet and supplemented daily with quercetin, magnesium, and EPA/DHA.
A baseline workup revealed an elevated ferritin at 404 (20-380 ng/mL) and a higher-normal total iron at 137 ug/dL. Total RBC count, hemoglobin, and hematocrit were elevated, demonstrating erythrocytosis. WBCs and platelets were within normal limits. There was no evidence of splenomegaly. He was heterozygous for the H63D hemochromatosis gene (see more on genetics below). Causes of secondary polycythemia (causing elevated RBC count) including sleep apnea, smoking, diuretics or dehydration were ruled out.
Inflammatory markers were within normal limits, including hsCRP, ESR. He was negative for HLAB27. ANA, RF, and anti-CCP antibodies were all negative. RBC zinc, magnesium levels were at acceptable levels.
Whole blood metals, including lead, cadmium, mercury and arsenic were undetectable or acceptably low.
Dr. Alex Vasquez has written extensively on iron overload, including establishing useful reference ranges for diagnosing mild, moderate and severe cases. Refer to his 2007 document or purchase his newer writings.
Hemochromatosis isn’t well-documented to be associated with erythrocythemia, but there a handful case reports demonstrating the finding in the literature, and research suggests that those with hemochromatosis undergoing phlebotomy can increase erythropoiesis six- to eightfold over basal rates due to the presence of excess iron. My working diagnosis for this patient includes hemochromatosis, but a more detailed work-up for polycythemia (including the JAK2 V617F mutation) is still in order given his less-common presentation.
While my patient has agreed to complete phlebotomy, the standard intervention for hemochromatosis or polycythemia, we concurrently started him on a low iron, hypoallergenic, ketogenic (for inflammation, allergy) diet where we utilized the so-called “anti-nutrients” that are known to bind iron and inhibit absorption. From Lara Zakaria, our lead nutritionist for this patient:
His nutrition plan was a layered approach, combining a ketogenic diet, with the removal of specific IgG food sensitivities, as well as focusing on reducing iron absorption. He continued to avoid gluten and dairy.
Our initial target was 65-70% fat, 15-20% protein, and 15% carbs. Within a few days, he was able to achieve ketosis, and reported improvement in inflammation symptoms, increased energy, and significantly reduced sugar cravings.
To reduce iron overload, we focused on food coupling that would take advantage of the iron absorption blocking properties naturally found in foods, including calcium, oxalates, polyphenols, tannins and phytates. Raw kale, legumes, and black tea, were some examples of foods that could be combined with iron food sources. Furthermore, we reduced exposure to the more bioavailable heme iron sources, and minimized or avoided foods with properties that increase iron absorption (i.e vitamin C and alcohol).
It’s worth noting, that sugar can increase iron absorption, so the ketogenic approach may have had an added benefit in that regard.
Our patient reported marked improvement in his previously refractory musculoskeletal pain after one month on the diet. He was able to exercise without pain,and reported himself as being “much less creaky”. He also noted that allergies had considerably lessened and energy improved.
The patient requested that we obtain his ferritin level after one month on the diet, prior to starting phlebotomy. We were pleased to see ferritin drop down to 345 (still too high, but now within normal limits), and total iron down to 57. His RBC indices were, not surprisingly, still elevated, if very slightly lower.
Note that we concurrently prescribed essential minerals with this plan, as creating an insufficiency is theoretically possible with the higher “anti-nutrient” approach.
About Iron Overload
Iron overload (iron toxicity) is an extremely common issue. Indeed, hereditary hemochromatosis is one of the most common genetic disorders in the US. Although it most often affects Caucasians of Northern European descent, other ethnic groups are also affected. About 1 in 200 of the U.S. Caucasian population carries two copies of the hemochromatosis gene and is susceptible to developing the disease.
The main treatment for hemochromatosis is very straight-forward: phlebotomy. Yet, if left untreated, hemochromatosis results in death from cirrhosis, liver cancer, or cardiomyopathy.
About 1 in 10 persons in the U.S. is heterozygous for a hemochromatosis mutation in the HFE gene that can indeed cause increased iron absorption. For this reason, I obtain a CBC plus full iron panel on all of my patients and check genetics if I see evidence of iron overload.
Hemochromatosis is a condition of high intestinal iron absorption due to an upregulation of iron transport proteins (which toxic metals can also utilize to gain entry into circulation) resulting in accumulations of iron system-wide: Think massive, uncontrolled oxidative damage. Basically, the body is rusting. Primary affected areas include the liver, heart, and pancreas. Free metal ions in the tissues will increase the rate of free radical generation, which may account for much of the tissue damage seen in hemochromatosis and toxic metal overload.
Toxic metal accumulation with hemochromatosis is not uncommon, as gastrointestinal uptake may occur via shared transport proteins, such as divalent metal transporter 1 (DMT1), which is increased in quantity in the disease. DMT1 is also found in the blood-brain barrier, and thus accumulation of iron and toxic metals may be seen in the central nervous system as well, contributing to neurodegenerative conditions. Excessive consumption of alcohol is often associated with hemochromatosis for unknown reasons, and alcohol increases iron uptake.
Hemochromatosis is characterized by a variety of seemingly unrelated symptoms and conditions, including severe fatigue (74%), arthralgia/musculoskeletal disorders, cardiomyopathy, diabetes (65%), and many other issues, including hyper- or hypothyroidism, adrenal insufficiency, hypogonadism, infertility, and skin bronzing.
Increased toxic metal uptake has also been associated with HH, and should be concurrently monitored.
Given the high incidence of hemochromatosis in the U.S., routine screening for evidence of iron and toxic metal accumulation in vulnerable populations is prudent.
In my practice, I screen everyone for iron status using a full panel. I rule out inflammation with CRP and ESR, among other markers. I look for autoantibodies and other pertinent biomarkers such as A1C, insulin, thyroid, cortisol etc. as well.
Evidence of iron overload, even mild-to-moderate, is a concern.
A few thoughts on genetics…
The 23&Me SNP panel– commonly obtained by many of our patients– includes the C282Y HFE gene, which accounts for about 85% of HH cases. Open the raw data text file and search for RS1800562. Look for AA (variant) or AG (carrier). GG is wild-type.
H63D (RS1799945) and S65C (RS1800730) are both associated with a milder form of HH (H63D is also on 23&Me).
Additional genes that may influence the course of HH included: RS4880 TT (associated more closely with the development of cardiomyopathy) or RS235756.
C282Y, H63D, and S65C may all be obtained through Quest or LabCorp. Insurance coverage is generally very good.
*There is a great case report submitted by John Cline, MD on hereditary hemochromatosis with severe toxic metal accumulation in Case Studies in Integrative and Functional Medicine. I borrowed liberally from the references in that case report for this blog.
Fantastic overview and very helpful for this population. Thank you!
Thanks for sharing this case study. Do you ever test for levels of inflammatory cytokines like IL-6?
How much does this blood work generally cost your patients out of pocket? Does insurance cover some or all of it?
I would like to order more of these labs but often see even basic labs denied for medical necessity. For example, many insurances no longer cover vit D testing unless the patient has osteoporosis, prior documented vit D deficiency, kidney disease, or parathyroid disease.
Hello MM. Yes, I order IL-6. I have never seen vitamin D denied and I order it all of the time. But coverage does vary by state. There are cost-saving ways to get standard labs we can discuss if needed.
DrKF
Thanks for this very useful article – what wonderful results for your patient! I recently became acquainted with Dr. Alex Vasquez’s work when I figured out I have iron overload. I’m working with my doctor Dr. Jerry Bailey and plan to have phlebotomy done.
As a nutritionist I’m very interested in this nutritional approach using “anti-nutrients” that are known to bind iron and inhibit absorption. I’m impressed with the reduced ferritin results with this and the other nutritional interventions you share.
Unfortunately due to oxalate issues I can’t consume high oxalate foods. I have SIBO so it’s no to the legumes, and I am sensitive to caffeine so can’t consume black tea.
I’ve been looking for other nutritional approaches and found these iron inhibitors/chelators: ECGC, resveratrol, curcumin, quercetin and inositol hexaphosphate – with thanks to PD Mangan’s excellent book “Dumping Iron”. He also mentions fasting and exercise.
It would be interesting to see if your patient’s results would have been different had he not also reduced exposure to the more bioavailable heme iron source, and minimized or avoided foods with properties that increase iron absorption (i.e vitamin C). I hate to give up my grass-fed red meat, especially with my diet being as restricted as it already is! Alex Vasquez doesn’t seem to think dietary reduction of red meat makes much difference and nor does Dr. Bailey. How important do you think this step is?
I won’t be using cast-iron cookware.
I’m planning to document my journey/case via my blog and look forward to sharing a link and a few excerpts from this excellent article of yours – so thank you!
Great input, Trudy! I suspect that the reduction in heme iron food sources also had an impact- but note that we didn’t omit completely. Further, we don’t need to necessarily omit/reduce forever, just during the initial phase. That said, depending on how aggressively one absorbs iron, each plan is individualized. The best way to determine the ideal diet & phlebotomy schedule during active iron reduction and then maintenance is through testing. Best wishes – DrKF
Thanks Dr Fitzgerald – and I agree, as with any nutritional approach it’s very individualized. Good to hear it’s just during the initial phase!
Regarding testing during phlebotomy, what is the recommendation for how often you would retest and how soon after each phlebotomy?
Too bad there is no reply. While having zero credentials, I like to have at least four weeks after blood donation for iron labs.
Just circling back to this conversation- a little over a year late 🙂 It’s really a case-by-case basis– using ferritin levels as one guide. DrKF
I have hemochromatosis a about a year ago I had a really bad episode of reactive/rheumatoid arthritis. 1 week in the hospital and many months recovering from the pain. I’m 90% better but still have some remaining pain and still taking anti inflamatory drugs (naproxen, sulfasalazine and methotrexate).
I did a long effort to lose body weight and get to a decent fat percentage and now I’m resorting to playing with my diet.
I’ve started doing a paleo-like diet to help with inflamation but now I’m trying a meat only as a final trial for a month.
It worries me a bit how I will do on meat only while having hemochromatosis.
I also did a 72h fasting to kick start ketosis and so far I’m feeling well. Not tired or anything.
I really hope restricting down to keto/meat only works and then I can try to introduce a few vegies bit by bit.
My iron levels are a bit high at the moment I guess I should invest some time into taking some blood away to make it drop a bit.
My Grandma had issues with hemochromatosis very late in life when she was already old. I’m only 37 and already having all these issues with inflamation, depression, tiredness, etc.
I guess I’ve been just poisoning myself with bad food for longer. I wonder if my body will ever recover.
Thanks a lot for the info. It really gives me some hope.
Consider working with our nutrition team, if you want support balancing hemochromatosis and ketosis- it’s a lot to do. DrKF
I was wondering if you have a copy of the diet that the patients in this study used?
In this particular case, he worked with our nutrition team who designed a very personalized plan for him. They layered his special needs along with his likes/dislikes and lifestyle needs into the plan. We highly suggest working with Nutritionist familiar with this approach to help design a plan that works for your unique needs.
I have a question concerning vitamins and supplements for those with Hemachromatosis. I read an article in the BMJ that stated vitamins and supplements were not desirable for these patients. I have read other articles that said they are necessary. Do you think they are meaning all or just those that affect iron? It also occurred to me that maybe it’s from overworking the liver which must break them down and synthesize? I appreciate any insights you might have. Thx. Evelyn