Dear Mark: Iron Followup

Last week’s post on iron levels got a big response and garnered a ton of questions from you guys. Today, I’m going to clarify a few things and answer as many questions as I can. First, do iron and ferritin levels mean different things for men and women? If so, how do those differences manifest? What about premenopausal women vs postmenopausal women? Second, what do we make of the fact that ferritin is also increased in times of inflammation? Is there a way to distinguish between elevated ferritin caused by inflammation and elevated ferritin caused by high iron? Third, is desiccated liver a good option for liver haters? And finally, I share some exciting plague news.

Let’s go:

Emma wrote:

I’d love to see more info on iron levels as they relate to men and women differently. I recently had an iron infusion for low ferretin, not thinking much would change I actually experienced so many positive effects I didn’t even know were coming my way. I’m less cold, no more afternoon fatigue, less hair falling out, no more random palpitations, improved restless leg syndrome and the number one big change is it improved anxiety levels – in fact my anxiety is now gone. The last two are due to a connection between iron and dopamine. I learnt that children with mental health issues are often treated for low ferretin where possible, elevating levels to around 100 showing positive results (would love to see literature on this), for me my ferretin went from 20 to 130 and its changed my life, at 31 I haven’t felt this good in years. Yay iron!

That’s awesome to hear. Yes, it’s important to stress the very basic essentiality of iron. Without it, we truly cannot produce energy. And since energy is the currency for everything that happens in the body, an iron deficiency makes everything start to fall apart.

As for gender and iron, there’s a lot to discuss.

A good portion of women with hemochromatosis never actually express it phenotypically, meaning their lab tests don’t show evidence of dysregulated iron metabolism or storage. According to one study of hemochromatosis homozygotes (people who inherited the mutation from both of their parents), being a woman makes it 16x more likely that your hereditary hemochromatosis won’t actually present as iron overload.

Another study found that among mostly-age-matched men (42 years) and women (39 years) with hemochromatosis, 78% of the men had iron overload while just 36% of the women had it. Iron overload was defined as transferrin saturation over 52% combined with ferritin levels of 300 ng/mL for men and 200 ng/mL for women.

High iron levels are more of an issue for postmenopausal women than premenopausal women. The latter group regularly sheds blood through menstruation, and if anything, they’re at a higher risk of low iron. Plus, estrogen is a key regulator of iron metabolism. As menopause sets in and estrogen diminishes, that regulation suffers.

For instance:

In postmenopausal Korean women, high ferritin levels predict metabolic syndrome and subclinical atherosclerosis.

High ferritin predicts metabolic syndrome in postmenopausal but not premenopausal women.

In premenopausal Korean women, higher ferritin levels predict better bone mineral density; menopause nullifies this relationship.

Remember that ferritin is actually a measurable protein bound to iron, so testing a ferritin level is technically an indirect way to measure iron. Why is this important? Another characteristic of ferritin (the protein) is that it is an ACUTE PHASE REACTANT. This means that ferritin levels can fluctuate with illnesses and other inflammatory states in the body that drive up a ferritin value that is not related to an actual iron level fluctuation. Don’t get ferritin checked when you are sick with a cold or other illness.

This is a great point.

Ferritin is marker of long term iron storage, but it’s also an acute phase reactant that up regulates in response to inflammation or oxidative stress.

If you want to be really careful, you should get a HS-CRP test—that measures your overall inflammatory status. If CRP is elevated, ferritin can be elevated without saying anything about your iron status.

Come to think of it, if elevated ferritin can be a marker of inflammation and oxidative stress, the inflammation could be responsible for some of the negative health effects linked to high ferritin. Or, if having too much iron in the body can increase oxidative damage, it may be that high iron levels are increasing inflammation which in turn increases ferritin even further. Biology gets messy. Lots of feedback loops. However, the fact that many studies cited in the previous iron post that use blood donation to treat high ferritin have positive results indicates that for most people, ferritin can be, in most situations, an accurate estimation of your iron status.

To make sure it’s an iron problem, get a transferrin saturation test as well. That indicates the amount of iron you’re absorbing, with below 20% being low and over 45% being high. People with high ferritin and high transferrin saturation do have high iron levels. People whose ferritin is artificially enhanced by inflammation will have normal transferrin saturation levels.

I have one last question on this. You say “Don’t stop eating liver every week.” If you can’t stand the taste of liver, what do you think about taking liver capsules made from grass-fed New Zealand beef every day instead?

That’s a great option. Go for it.

People should generally aim for 4-8 ounces of fresh liver a week. Note the amount of desiccated liver in your capsules and multiply by 3 to get the fresh liver equivalent, then take enough each day (or all at once) to hit 4-8 ounces over the week. I hear good things about this one.

Mark,
Thank you for your article on HH. I carry the gene but have been managing my iron levels through phlebotomies. I am full Keto, meat and all and have found my iron levels have not been effected by going Keto. Early detection is the key and ongoing monitoring. Bring on the plague!!!

You joke about that now, but there’s a startup that’s breeding heritage rat fleas that produce a mild strain of the plague that evades the attention of the immune system and proliferates throughout the body to keep iron levels in check without killing you. I’m an early investor, have a couple swarms installed in my condo, and (knock on wood) so far have avoided anything worse than a sore throat and maybe a mild open sore or two. There’s actually a big rift forming between the techs who want to keep the fleas heritage and those who want to go ahead with CRISPR and engineer them. One variant has had a deer tick gene inserted that adds an anesthetic compound to the flea’s saliva. That way you can have a personal swarm on you and never feel any bites or itches.

I’m not sure about CRISPR just yet, but I gotta say it’s pretty nice to be covered in fleas and not feel the bites. Time will tell.

Ok, I’m joking.

That’s it for today, folks. I hope I’ve answered some of your concerns, and if not, let me know down below. Thanks for reading!