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.