Testosterone and hemoglobin / hematocrit issues
and
The Vorck Ferritin Restoration Protocol

This guide is for people on Testosterone Replacement Therapy. It is NOT for people with low iron, low hemoglobin anemia or iron disorders. If you have C282Y Hereditary Hemochromatosis (H63D is ok), do NOT do this; you might learn a couple new things though.

Debut: May 2021
Current revision: July 2024
As long as I am alive, this gets changed as new sources become available. Change log at bottom..

Part 1: High hematocrit (HCT) / hemoglobin (HGB)

Skip down to Part 2: Raising ferritin

The 10 second quick version for healthcare providers who don't know why Testosterone induced erythrocytosis occurs:
Exogenous Testosterone increases EPO.
Increased EPO causes the marrow to produce more RBCs.
When more RBCs are produced, more erythroferrone is also produced.
When erythroferrone is produced, hepcidin is suppressed.
When hepcidin is suppressed, ferroportin in cells will allow stored iron (ferritin) to exit the cell very easily, re-bind to transferrin, and be used for hemoglobin. This will also prevent iron from being stored as ferritin normally in the first place.
When more iron released from ferritin is available in serum, it is channeled into hemoglobin.
Eighty percent of ferritin is stored in the liver. Retired RBCs are often stored as ferritin. Because of suppressed ferritin, the recycled iron also contributes to high hemoglobin.
This process does not always stop on its own. In some individuals, phlebotomy is the only way to keep it in check. Rusfertide, a synthetic hepcidin analogue, will solve this entire cyclic problem, but the drug has not been approved by the FDA.

I recommend All Things Testosterone with Brandon Church and his FB group TRT Community. I also recommend Nelson Vergil's community. Avoid Reddit like it's cancer, it's a cesspool of misinformation.

PART 1: High H&H

Hemoglobin and hematocrit ("H&H") explained
Hemoglobin (HGB) is the protein contained in red blood cells that is responsible for delivery of oxygen to the tissues.

Hematocrit (HCT) measures the volume of red blood cells compared to the total blood volume (red blood cells and plasma). This is the one that is highly affected by hydration. It is a ratio, and by the way, donating plasma will increase HCT.

Both hemoglobin and the hematocrit are based on whole blood and are therefore dependent on plasma volume. [Source] If a patient is severely dehydrated, hematocrit (and to a lesser extent, hemoglobin) will appear higher, and if the patient is fluid overloaded, they will be lower than their actual level.

What exactly is the issue with Testosterone raising hemoglobin and hematocrit?
Men (and some non-menstruating women) on TRT sometimes develop a problem with elevated hematocrit (HCT). This often first happens three months into TRT. Testosterone (T) drives what is known as "secondary erythrocytosis" (SE). In older research literature, this issue was sometimes referred to as Polycythemia or Polycythemia Vera. PV is actually a separate condition. Physicians who are older may have had medical training on Androgen replacement that conflated the two, something older textbooks actually do. Because of this, some physicians may recommend donating blood when hematocrit gets above 45. This "keep it 45" guidance was appropriate for Polycythemia Vera, not for secondary erythrocytosis.

Yes, there is a difference between Polycythemia and Polycythemia Vera. When you see the word Polycythemia without the "vera" in medical literature, it absolutely means erythrocytosis. It's just an older term. The guys who keep mindlessly parroting "Erythrocytosis and Polycythemia are different things!" have never read a medical textbook or study though, so it's best to let it drop with them.

The issues related to high H&H relate to stroke (debatable, read on about why), cardiac problems (also debatable, read on about why), and temporary pulmonary hypertension (OMG they didn't mention that in that YT video!)

Do I have to donate blood for high hematocrit?
I'm actually not even saying you do or don't. This is an options document to guide you in decision making.

What drives Testosterone to make Red Blood Cells?
There are multiple contributors to erythrocytosis while on TRT.

[Source]

We need to define some terms in an overly-simplistic way before we proceed.
Erythropoietin (EPO) - a hormone secreted mainly by the kidneys, this stimulates red blood cell production (erythropoiesis) in the bone marrow.
Hepcidin - the master regulatory peptide of iron in the body. It is the cellular "iron drain plug" that keeps iron in cells. When the hepcidin level is high, it can block iron absorption in the intestine (from food and supplement pills) while simultaneously preventing iron transport out of liver and spleen cells. It helps when building ferritin. If hepcidin is too low all the time, iron stored in those cells will flow out, and into serum and then hemoglobin.
Ferritin - a protein that stores iron in liver, spleen, and other cells. Ferritin is iron in a molecular "cage" and is safe (it is not toxic like RCP / Morley Robbins people are telling you). The liver's cells (hepatocytes) hold 80% of the body's ferritin. (A little bit exists in serum. More on that later.) Ferritin in men tends to stay pretty constant for extended periods, weeks or even months, but blood donations and high levels of Testosterone will lower it.
These definitions will be repeated later as a reminder.
RBCs - Red Blood Cells

The largest contributor of increased RBCs is the stimulation of erythropoietin.

"Testosterone stimulates red blood cell production (erythropoiesis) by stimulating erythropoietin (EPO) and recalibrating the set point of EPO in relation to hemoglobin and by increasing iron utilization for erythropoiesis.

The 7%-10% increase in hemoglobin and hematocrit, respectively, with testosterone administration was associated with significantly increased erythropoietin (EPO) levels and decreased ferritin and hepcidin levels at 1 and 3 months. (Ferritin and hepcidin are explained further down.) At 6 months, EPO and hepcidin levels returned toward baseline in spite of continued testosterone administration, but EPO levels remained nonsuppressed even though elevated hemoglobin and hematocrit higher than at baseline, suggesting a new set point." [Source]

The study is from 2014, the same year erythroferrone was discovered, which is the missing link here and the reason the connection between RBCs and hepcidin is vague in the link. Erythroferrone is produced by erythroblasts (immature RBCs) in response to erythropoietin (EPO) and it (Erythroferrone) acts directly on the liver to suppress hepcidin via the BMP6 pathway [Source]. Lower hepcidin means iron tends to flow out of cells and into hemoglobin. Here's that erythroferrone-hepcidin relationship explained [Source]

Testosterone-induced suppression of hepcidin expression is independent of its effects on erythropoietin or hypoxia-sensing mechanisms in mice. [Source] Also in mice: hepcidin suppression by testosterone increases iron availability and erythropoiesis, but hepcidin suppression is not essential for mediating testosterone's effects on erythropoiesis in healthy mice. Hepcidin suppression did however make elevated hemoglobin and RBCs vastly worse. [Source]

The literature does say this tends to normalize after 6 months to a year on TRT. I and others have been on TRT for decades and I still have to donate though. Eventually normalizing is not guaranteed. It can get worse as you age. [Source]

Source

The subjects in this EPO setpoint study did not go above a TT of 500! You can imagine higher levels of Test. The study, linked right below, has similar graphs showing major impacts on hepcidin and ferritin as well.

TRT alters iron metabolism as well: Testosterone Enanthate at 125 mg per week reduced serum ferritin 32% within 3 months of treatment initiation without altering iron, transferrin, or transferrin saturation. (It does this because hepcidin was suppressed 57%. Hepcidin is the cellular "iron drain plug" that keeps iron in cells. More about this later.) [Source] 

THIS MEANS TRT ITSELF CAN DEPLETE FERRITIN OVER TIME WITHOUT ANY BLOOD DONATION.

What if I stop TRT, will my EPO fall quickly or take years?
Kidney function varies among men of course, but I stopped for 21 days just to see what would happen to my EPO. 21.9 to 9.9. I picked 21 days randomly. At this point I had been injecting for 20 years. I moved up from 160 to 240 at age 50 to get to the same amount of Total.

How come this doesn't happen to young men with presumably high Testosterone?
Because their Test levels, even if high, vary throughout the day. [Source] When you're on TRT, your Total level is steady high and only your Free varies a very little over the course of the day. Young guys with naturally high Test levels are not at that 900 level 24/7. Gel and Natesto do not have high incidences of HCT issues and that's because they are TRT methods where levels are up and down. Not the case on injections. Here's a study that used 25 year old males. [Study]

The problem of high hemoglobin/hematocrit is not always due to Testosterone
A special note about another possible cause of erythrocytosis: Sleep Apnea.

"In humans and other mammals, hypoxia modulates EPO levels by increasing expression of the EPO gene." [Source] Simplified: snoring increases RBCs.

Common causes of secondary erythrocytosis include a handful of things other than using Testosterone, but the two you need to evaluate in your own life are smoking and Sleep Apnea. The problem with apnea is low Oxygen saturation while you sleep. [Source, source] The best avenue is getting a sleep study as quickly as possible and getting on a CPAP or APAP machine. Unfortunately, these devices are by prescription only per FDA rules. Yes, you need the government's permission to breathe at night. Current practice favors fixing sleep apnea before TRT if hematocrit is over 52. [Source]

Is a hematocrit of 54 a risk?
NO. A hematocrit of 54 (HGB 18) is not a risk. But you go past that, you end up dumping blood and being right back at 54 a month later. So 54 isn't a problem, but the smart thing to do is to knock it back before you get too far past 50. Multiple phlebotomies deplete ferritin fast but in Part 2 I address that.

What is a "normal" HCT level?
The whole reason for donation is to avoid a negative cardiovascular event such as stroke or heart attack. We will see further down that the science on whether this is an actual risk on TRT is equivocal.

The normal lab ranges in human beings are based on population averages that were set decades ago. The common normal ranges that we are concerned with are:
hematocrit (HCT) as a percent
Men: 42-52* (some labs use 50, some 54, I've seen 60)
Women: 37-47

hemoglobin (HGB) in g/dL
Men: 13.5-18.0*
Women: 12.5-16.0

Red Blood Cells (RBCs) x10E6/uL
Men:4.7-6.0
Women: 4.2-5.4

Platelets x10E3/uL
Men: 150-450
Women: 150-450

Note that any doctor that wants an early warning about problematic blood values will have lower ranges in their labs. For example, an oncologist will probably have flags on other values of red and white blood cells because many cancers can increase these cells and chemotherapies can reduce them.

*18 x 3 = 54. Some guidelines say HGB of 18 or HCT of 52 needs phlebotomy.
HCT should be calculated directly but some labs derive it using one of two formulas:
Hct = (0.0485 × concentration of hemoglobin in mmol/L + 0.0083) × 100 or
Hct = MCV × RBC × 0.1.

I heard that high HCT on TRT is the same as living at altitude, and those people don't donate.
Because the average male HCT at elevation in Bolivia is 52.

Healthy persons living at 4,000 meters (13,100 feet) in Bolivia:

hematocrit (HCT)
Men: 45-61 (average 52.7%)
Women: 41-56 (average 48.3%)

hemoglobin (HGB)
Men: 13-21 g/dL (average 17.3)
Women: 12-19 (average 15.8)

[Source] Comparison: Breckenridge, CO is 9,600 ft. Santa Fe, NM is 7,200 ft.

People at elevation do not all have HCT's of 60 if the average is 52. In addition, some Andeans do have altitude sickness and produce massive amounts of Red Blood Cells. [Source] Also, there aren't medical centers for people to donate blood.

Just because they don't have Starbucks there, does that mean they must not drink coffee?

The whole altitude issue is vastly more complex than people summarize it to be. [Explanation] TL;DR - doing TRT doesn't make you exactly like a Peruvian who lives his whole life at 30,000 feet. They literally have evolutionary adaptations (explained in these links). [Source]

High elevation and high RBCs occurred where there was a higher T to E2 ratio contributing to the erythrocytosis. Study on ratio. Androgens may be linked to mountain sickness [Study]

I heard that high HCT on TRT just means I'm like Lance Armstrong, an endurance athlete.
Lance Armstrong's hematocrit during competititons never went above 50. This is documented in various places [source] [source] and he himself has noted it in interviews. [source] In the video, note what he says about Everest climbers. Do you really think there are people LIVING on top of Everest with an HCT of 70? Living there. NO ONE lives on top of Everest. And do you really think performance athletes let their HCT climb and climb and climb to the point where they suffer pulmonary hypertension? That's what will happen on TRT, because the effect of EPO isn't going to just magically stop.

I heard that Testosterone dilates blood vessels because of nitric oxide.
Low testosterone causes endothelial issues. [Source] Nitric oxide is mediated in part by testosterone. [Source] What I am not clear on, and cannot find research on, is whether running a Total from 500 to over 1,200 eliminates any risks from high hematocrit. If it worked that way, wouldn't a higher Total cause hypotension? And yet it doesn't seem to. If you have a source showing higher T means more vessel dilation, please send it to me.

What are the symptoms of a high hematocrit?
Not everyone experiences them. Hypertension, itching and tingling in your extremities, headaches, getting winded more easily. The hypertension is from both EPO and more RBCs.

I have some pressure below my bottom left rib...
Your body recycles the iron from RBCs when the RBCs are filtered and "retired" in your spleen (the liver playes a role here as well). When your RBCs get too high, you can experience splenomegaly, an enlarged spleen, which feels like slight pressure below the lowest left rib. This is transient and not harmful, in and of itself. A doc can check it by feel (in less than one minute) or CT scan. It can be a warning sign for people not on TRT though. [Further spleen size reading]

(I would source this, but it appears in the research literature as an effect of PV, and explaining that it's really just the Red Cells as opposed to WBCs and platelets would be another 6 paragraphs. If you ask your doc if erythrocytosis can cause splenomegaly with RBCs over 6.5, he will say 'yes,' I assure you.)

There are people who say to never donate. Why?
They think that if they don't have symptoms, then no one will have symptoms. They may say "my hematocrit is at 54% and I never feel anything. Therefore, NO ONE feels anything, ever, at any level. High HCT can be ignored because I ignore mine. Literally everyone is exactly just like me."

I mean, I'm not diabetic -- that means no one needs to inject insulin. Makes sense, right?

They also believe that cardiovascular events simply cannot occur because of secondary erythrocytosis. The science on this one says "maybe."

I read a study showing that phlebotomy doesn't help.
No you didn't, because that's not at all what the study says. The study observed that of repeat donors on TRT, 44% had persistently elevated hemoglobin levels at subsequent donations. They reached the conclusion that "repeat blood donation was insufficient to maintain a hematocrit below 54%."

That makes about as much sense as "repeatedly filling your car's gas tank is inufficient to maintain a full tank."

Donors are on TRT. That's why they donate repeatedly. No one on TRT ever said that blood donation will maintain hematocrit below 54%. No one. Ever. TRT raises it, and you have to repeatedly donate, so why would anyone think donating would permanently solve the problem?

Someone in a FB group says you rebound faster after donating.
Yes, people not on TRT do, that's true. (The reason is due to erythroferrone.) Those of us on TRT are already in permanent rebound because our EPO is always elevated. To repeat myself: if you are on TRT, you are ALWAYS in "rebound mode." Even if a rebound happened to us, my protocol further down eliminates this concern anyway post-donation.

Wait, did you say rebound happens to people NOT on Testosterone?
Yes. When you're on TRT, your erythroferrone is already high. A blood dump doesn't make it higher. Guys on TRT do not rebound that much. My protocol overrides erythroferrone anyway for the week you do it.

What is thought to be the risk of a high hemoglobin/hematocrit?
The risk, as conventional wisdom goes, is that SE could cause blood clots, heart attacks, and strokes: "Much of the concern surrounding increases in blood viscosity resulting from increased red blood cell mass centers on the potential increased risk for venous thromboembolism (VTE) (symptoms), myocardial infarction (MI), and cerebrovascular accidents (CVA) (symptoms)." [Source] A U-shaped relationship exists between haematocrit and mortality shown in a large prospective cohort study: [Source] Hypertension is also a risk, very common on TRT. [Source]

Note that quote didn't have the word "platelets" in it, by the way. Hyperviscosity due to increased red cell mass is a problem in and of itself.

Post 2010 research is casting some doubt on the absolute risk of stroke and heart attack:
"No evidence exists that a high hematocrit is harmful and a direct cause of thrombosis; in addition, many conditions that lead to a very high hematocrit are not associated with thromboses." [Source]

Large scale studies show no association between TRT and thromboembolism. The first study done in 2015 is here: [Source] A 2018 study that included six Randomized Controlled Trials (n = 2,236) and five observational studies (n = 1,249,640) is here: [Source] "There was no evidence of a statistically significant association between [venous thromboembolism] and testosterone."

"Several lines of evidence suggest that an isolated elevation in hematocrit does not, per se, lead to thrombosis. [...] Coronary blood flow is decreased in secondary erythrocytosis, but there is equivocal evidence as to whether the risk of coronary thrombosis is increased in patients with a high hematocrit." [Source]

"Increased Hct is associated with increased blood viscosity, reduced venous return and increased platelet adhesiveness. [...] Based on Endocrine Society Clinical Practice Guidelines, once a Hct > 54% is reached, TTh should either be discontinued, or therapeutic phlebotomy offered to reduce the risk of potential future thromboembolic events." However, "...few data support an increased risk of CV events resulting from testosterone-induced erythrocytosis." [Source]

HOWEVER. None of these studies controlled for phlebotomy or blood donation. I'll repeat that: none of these studies controlled for phlebotomy or blood donation. In other words, these high hematocrit studies were done on Testosterone users and some of those men in the studies were giving blood. So they showed that guys on TRT, some of whom gave blood, didn't have strokes. Probably because they were giving blood. (Hey, don't shoot the messenger here.)

"But platelets!" RBC values like MCV and MPV, not just raw platelet count, factor into risk. Also, high HCT (heart risk) versus high PLT (brain risk) are considered here in the Copenhagen study separately. Read this one carefully and scroll to 4, Discussion.
"Neither high platelet count nor high hematocrit was associated with risk of venous thromboembolism. When excluding individuals with myeloproliferative neoplasia from the main analyses, results on risk of thrombosis were similar. In this prospective study, high platelet counts were associated with 1.8-fold risk of arterial thrombosis in the brain, whereas high hematocrit was associated with 1.5-fold risk of arterial thrombosis in the heart."

Some temporary health conditions like Covid can raise platelets for a short time. [Source]

So the science does NOT simply say that you do or don't need to donate.

If you become symptomatic with flushed red skin and shortness of breath, are you just going to deal with that and not donate? (This is the biggest problem I have with the Rouzier video, by the way.) High hematocrit levels make the blood more viscous (thicker). This increased viscosity can make it more difficult for the heart to pump blood through the pulmonary arteries, leading to higher pressure in these vessels, meaning having an HCT of 60 can mean you're tired all the time because you have (temporary) pulmonary hypertension!

It is interesting to note that even in PV, the adverse health event risk isn’t even correlated to RBCs: "The best single blood cell parameter that correlates with thrombosis in polycythemia vera is the leukocyte [White Blood Cell] count." [Source] Note that in most cases of PV, there is not only Red Cell overproduction, but White Cell and Platelet overproduction as well.

It is important to note that hematocrit is determined by multiplying hemoglobin by three, and if hematocrit is over what the predicted value should be, you are likely dehydrated (though this rule of 3 is a little controversial). That is to say, if your HGB is 16, your HCT should be 48. If it’s higher, then you are probably dehydrated. Your red blood cells are not driving the high HCT, it’s a lack of plasma from a lack of drinking enough water. [Source] Some sources now dispute this "3 times rule" as a source of determining dehydration.

Ultimately, when to donate (or ask for therapeutic phlebotomy) is up to you and your doctor working together. You can have a need to donate and not feel any symptoms. If you need to donate, you can take every other day Aspirin in an 81mg dose until you have the procedure. Aspirin does NOT lower your hemoglobin or hematocrit, but it can help prevent advserse cardiovascular events because it inhibits thromboxane, which promotes platelet aggregation. [Source]

Do not overdo Aspirin. It's effect on platelets lasts the life of the platelet, or 10 days. Daily Aspirin over 81mg is too much, and some would argue even 81mg daily is also too much and every other day is better. Your body is always making platelets of course, but stopping daily Aspirin means the effect tapers off, it doesn't stop right away. Stop regular Aspirin a week before you go and give blood. Too much Aspirin in your blood and you could find yourself giving blood and still bleeding six hours later after you are done and bandaged. No joke.

Will my doctor order me to stop TRT if my hematocrit gets too high?
As of this writing in 2023, two guidelines say "stop Testosterone at a HCT of 54"

• the Endocrine Society May 2018 Clinical Practice Guidelines (the most current), state that clinicians should "Check hematocrit at baseline, 3–6 mo after starting treatment, and then annually. If hematocrit is >54%, stop therapy until hematocrit decreases to a safe level; evaluate the patient for hypoxia and sleep apnea; reinitiate therapy with a reduced dose." [Source] It doesn't matter whether it's true (reduce dose? It ain't that simple, kids) so much as this is what some doctors choose to go by.

• the European Association of Urology (EAU) Guidelines state that "if testosterone is prescribed then testosterone levels should not exceed the mid-normal range and the haematocrit should not exceed 0.54%. Testosterone dose adjustment may be required and/or venesection (500 mL) should be considered and repeated if necessary, if the haematocrit is greater than 0.54%. The haematocrit value of > 54% is based on the increased risk of cardiovascular mortality from the Framingham Heart Study, which was recently confirmed in another study." [Source] NOTE! The Framingham Study [source] examined high hematocrit and the risk of cardiovascular disease -- in smokers and NOT Testosterone users -- and did NOT reach a conclusion. Does that seem like a good study to base Testosterone dosing on?

Canadian Guidelines just quote these other two. [Source]

Should I reduce my Testosterone dose?
Here is a study of 7,000 men on injected TRT whose HCT level normalized between 605–1051 ng/dL.There were 60 (sixty) of them. That's .86% or LESS THAN ONE PERCENT. Do you want to go into the 500s? We still see guys with erythrocytosis with Total Testosterone levels in the 400s too. At what point do you stop lowering the dose? Why not use gel or Natesto instead? You won't have high hematocrit as these mechanisms aren't associated with high HCT.

Could injecting subcutaneously instead of IM help?
It may possibly help you or delay the inevitable. SC dosing using a subcutaneous testosterone enanthate autoinjector (like Xyosted) "was associated with 41% and 26.5% lower post-therapy increases HCT and Estradiol levels respectively when compared to IM injections." [Source] The study compared the same amount of Testosterone used both IM and SC, and the study's numbers show an average TT of 536.4 and HCT of 48.4 in IM users and an average TT of 552.5 and HCT of 46.3 in SC injection users. Overall we are looking at 2 points lower HCT with SC dosing. That's significant in the world of TRT.

Could different Testosterone dosing help?
Studies that compare different TRT delivery methods show injection correlates to the highest frequency level of Erythrocytosis compared to gel or pellets. [Source] The problem is that the studies compare once weekly dosing of Enanthate and Cypionate (pictured below). That's not steady delivery of TRT; once weekly means huge peaks and troughs.

Link to original
Link to the study I got this from (see page 421 of the PDF)

As such, when trying to figure out SE, comparisons between gel, oral undecanoate, IM undecanoate, pellets, and shots don't really have much value. All it shows is that (1) lower doses of TRT (2) taken daily are less likely to cause SE. Note the numbers -- both size of dose AND frequency are factors. If you don't want to give up your dose size, split it into more frequent doses first. That might eliminate your SE.

Exercise could potentially help. [Source] But some exercise raises EPO.

Can I take any drug or supplement instead of donating blood?
The answer is a qualified maybe.

5α-Reductase inhibitors. These reduce DHT. Remember at the top of the page, that box showing the different factors that contribute to rising red cells? These drugs reduce DHT, and that might help a bit, but then again, LOTS of guys on TRT use drugs in this class like Cialis, and still get erythrocytosis. Don't expect a miracle. Note the study didn't even track EPO levels. That actually makes the study next to worthless. We don't know the Total and Free Test levels the men took, all they measure was DHT. But for what it's worth, here's the study anyway. [Source]

Angiotensin II Receptor Antagonists. (Telmisartan etc) "Various mechanisms have been offered to explain why ACE inhibitors might affect the response to erythropoietin." [Alt link] This class of drug is used to lower blood pressure. Because TRT stimulates RBC production in a lot of men, blood pressure usually elevates, and many men take some kind of drug to treat this. Different BP drugs have different advantages, and it’s probably not a good idea to mix them. Someone in a forum said these drugs give you ED. Not true. Many Telmisartan users in forums have reported that at 40mg and above, their need to donate slowed significantly or stopped. Losartan appears to work as well in some users. Losartan 20 didn't work for me, Telmisartan 40 did.

Other BP drug: Amlodipine lowers HCT. [Source]

Arimidex. Don't go overdosing and make me regret adding this, guys. This drug reduces Estradiol. Estrogen can affects hematopoietic stem cells, which are the precursor cells for erythroblasts. Estrogen receptors are present on hematopoietic stem cells, and estrogen signaling can impact their proliferation and differentiation. This can indirectly influence the production of erythroblasts. [Source] The amounts of Arimidex TRT users take doesn't significantly lessen erythrocytosis. By the way, while I'm at it, Estrogen also suppresses hepcidin. More details on Estrogen appear in the appendix at the bottom.

Grapefruit. This was an unexpected finding in a study on eating grapefruit. Many men do have success, despite that the study’s results have never been replicated. Naringin is the presumed agent in the Grapefruit, but it hasn’t even been confirmed. The study used whole fruit. Note that because Grapefruit is a CYP3A4 inhibitor, it can cause other drugs to stay in your body much longer, potentially very serious for some classes of drug. This is a discussion of the drugs affected. Some guys have tried and had success with grapefruit seed extract which is different than Naringen. (Grape seed is different from grapefruit seed by the way. That seems obvious when you read it here but it's easy to make the mistake when you're shopping and distracted. By the way, the aromatase inhibiting effect of grape seed has never been confirmed in humans.) Warning: it appears to be a chelator as powerful as desferrioxamine. [Source] "But that's in mice!" Well, scroll to the molecular structure of naringin in Figure 6 and see if you think that matters!

Naringen. See grapefruit above.

Divesiran. TMPRSS6 upregulator, increases hepcidin. Not yet approved. Currently in Phase III trials.

Rusfertide. Not yet approved. Currently in Phase III trials. Formerly known as PT-300. This is an injectable synthetic peptide. In PV patients, it was found that Rusfertide eliminated the need for therapeutic phlebotomy. This peptide is a human hepcidin mimetic (this detail will be important later). Rusfertide's structure is here. (Although PV isn't SE, Rusfertide throttles erythropoiesis and elevates ferritin which is what we want.)

Ginger - Did not make a difference in erythrocytosis in guys taking it.

Quercetin. Stronger chelator than naringen. Also causes issues with drugs that use the CYP3A4 pathway.

Maca - a perennial plant (Lepidium meyenii) that grows in high altitudes of Peru. "Red maca reduced hemoglobin levels only in highlanders with abnormally high hemoglobin levels." [Source]

Chelating agents. Strictly speaking these bind to iron and cause you to excrete it in feces and urine. Since your RBCs are still going to go up on TRT, chelating iron just forces your body to take iron from recycled RBCs and ferritin. As this can make you anemic and keep ferritin from going up, using chelating agents is NOT a good idea on a regular basis. [Discussion]

Turmeric. Chelating agent. In high doses of 500mg daily, it will keep iron low and therefore hemoglobin low. It can make normies anemic and prevent ferritin from rising. [Source]

IP-6. Chelating agent. It chelates iron and will keep your hematocrit low over time by keeping you iron deficient. IP-6 binds with iron in the gastrointestinal tract so that's also going to keep you from raising ferritin. [Source]

Milk Thistle (silymarin). Chelating agent. [Source]

Cayenne - Didn't work.

Finasteride. (Maybe). Don't take this for managing SE. That would be foolish. I am including it for completeness' sake. One study showed an impact on H&H [Source] and one study showed no difference. [Source]

Pentoxifylline. Don't take this, I am including it for completeness' sake. This drug works by reducing blood viscosity and by decreasing the potential for platelet aggregation and thrombus formation (decreases plasma fibrinogen concentrations). [Source]

Hydroxyurea. Don't take this, I am including it for completeness' sake. Hydroxyurea is used to treat PV (and some other diseases like Sickle Cell) and works by "inhibit[ing] the formation of DNA by blocking an enzyme known as ribonucleotide reductase. This results in the decreased ability of the bone marrow to produce red blood cells."

Unfortunately, Hydroxyurea lowers everything -- erythrocyte [Red Blood Cell], leukocyte [White Blood Cell], and platelet counts. Since PV and SE are different, you won’t find a physician who will prescribe this drug to you. Additionally, although it appears not to show the effect in low doses, taking Hydroxyurea has been associated with causing leukemia, one of the diseases it’s designed to treat.

Aspirin and Nattokinase can be taken to avoid cerebrovascular events. They don't play a role in managing hemoglobin or hematocrit, they are for prevention. I don't know if they play well together. Remember, you can get hemorrhagic strokes too, not just strokes from clots. Don't overdo clotbusters.

Supplements you should probably avoid when trying to manage erythrocytosis

Ashwaganda increases "both the red blood corpuscles (RBC) and hemoglobin count." [Source]

B-12 can increase erythropoeisis, so let your source be dietary. Don't add more in a pill. And for Christ's sake do NOT do B12 injections.

Curcumin. It lowers hepcidin for as much as 24 hours post ingestion. [Source]

Garlic seems to stimulate RBC production independently of erythropoietin. [Source] The jury is still out on this one.

N-acetyl-cysteine (NAC) "increases intracellular reduced glutathione, decreasing reactive oxygen species and enabling EPO production." [Source] Experience, both personal and in the discussion group, illustrate that using NAC does increase RBCs at a faster rate.

I read aerobic exercise helps.
This is true; exercise induced hemolysis reduced red blood cells. [Source]

Do I donate whole blood or do I do this 'Power' or Double Red donation?
Donating double red takes twice as much of only red cells (it's actually based on your weight) and gives you your plasma back. You then drink a lot of water and after 24 hours you could discover that the 55 HCT you walked in with is now 50.

Days between regular donations: 56, and you're taking plasma, whites, and platelets too
Days between double red donations: 112, and you're only taking reds

If you do double, remember that your doctor can still order phlebotomy if you need it. Don't let the "I have to wait 112 days" freak you out.

I am going to repeat that because it doesn't seem to sink in with some guys.

If you do double, your doctor can still order phlebotomy if you need it. "But I'll crash my ferritin!" Who cares, we can fix that now.

Here is a calculator that will also tell you your blood volume. Here is a study on donor motivation. So you do it for the free keychain. [Source]

If you can't donate because you got blacklisted / you're flagged / you're gay / you like prostitutes / it's too far / etc
If you cannot donate and want to do it at home, you need a home phlebotomy kit and a friend who is a phlebotomist, or a nurse, or an EMT-Intermediate or EMT-Paramedic. Yeah, I know you want to do it by yourself. I just can't recommend it.

Could low ferritin be making me feel bad?
Yes, remember that starting TRT can lower ferritin... But if you only started to feel bad when your HCT got to 55, then the HCT is the real problem.

A guy on Youtube said low ferritin from donating is really why I feel bad!
Literally who the hell cares. We now know how to raise ferritin 30 to 50 points in about a week. If TRT docs gave a damn about this problem it wouldn't have taken a guy like me to publish a solution.

Should I tell Red Cross I am on Testosterone Replacement?
The person measuring your hemoglobin might ask you how it gets so high. Even though TRT is not against the rules, I suggest that you don't mention it. On paper donating blood while on prescribed TRT is allowed, in my experience, mentioning it is a great way to start a fight with the technician. They are not all professionals who understand TRT. And under NO circumstances should you say that you benefit from donating. That's a whole separate issue with them.

My story: a Red Cross tech noted that I have high hemoglobin and I volunteered that it's because I am on prescribed TRT. I guess she decided that she didn't like Testosterone users, because I was told to sit and wait until I could be interviewed by the site's Medical Director, who came and had me answer several pointless questions after which she re-took my vitals (think about why -- if she raised my BP, she could reject me for donation. I stayed calm). I'm telling you, it has happened to plenty of us. If they remark that your hemoglobin is high and you think they're 'fishing' for a reason, just say you're a smoker or that you snore.

During a different visit, I also once made the mistake of saying "I need to donate" and had to backpedal when a tech explained that they cannot proceed if donation is medically necessary. They are not allowed / licensed to perform any kind of therapeutic intervention. There may be a blood shortage, but never underestimate how satisfied someone can feel after telling a TRT user to fuck off. We are lower than dirt to some of these people.

If you completely skipped Part 1, I recommend that you read it at some point.

PART 2: Raising Ferritin while on Testosterone Rev 4

You need:
• to be on Testosterone or have erythrocytosis from something (smoking, PV, sleep apnea, ideopathic secondary polycythemia, etc)
• to have RBCs over 5.5 for men and women
• to regularly have a hemoglobin of 16+ for men and women (you can dip if you donate but keeping your ferritin relies on a high HGB)

This won't work if:
• you have C282Y hemochromatosis (H63D is ok)
• you have thalassemia (of any type)
• you are a normie who has iron deficiency and came here from the Hartigan Iron Protocol Facebook Group, go ahead and read but DO NOT do this. Seriously, this protocol is for people with a hemoglobin of 16 or higher.

Why can low ferritin be a problem and what does it feel like?

SHORT VERSION
How to raise ferritin, the short "just tell me how" version
Three 70mg doses per day of Ferrous bisglycinate chelate spaced apart at 9am, 3pm, and 9pm all on the same day, at least 5 days in a row (most guys are doing 7 days as of Sept 2023). 70/70/70 every day for five, six, or seven days. One week BEFORE doing the protocol, stop all vitamin D supplements. DURING the protocol, do not use any vitamin C or vitamin D supplements. (I'm not saying never take vitamins C and D. Just no D before and no C and D during these 5 days.) Be aware while doing this that having above normal Estradiol [Source] works against you. The times of day do matter. You cannot skip a dose. If you can, space things so you take your iron two hours away from food.

This adds up to a daily total of 210mg (if you used 70mg) to 240mg (if you used 80mg) PER DAY. (Overload level is 400. Don't freak out here.)

YOUR BODY IS NOT ACTUALLY ABSORBING THE IRON. WE DO NOT WANT TO ABSORB THE IRON ANYWAY. YES, REALLY.

THE IRON IS BOOSTING HEPCIDIN. HEPCIDIN CAN ACT LIKE AN IRON DRAINPLUG.

YOUR FERRITIN (TRAPPED IRON) RISING IS FROM YOUR OWN RECYCLED RBC IRON.

When you're done -- stop. Get a blood draw, see where ferritin is.

Do NOT take an iron pill that is "slow release" to kick this off (you need an initial 'hit' of a lot of iron all at once). Do NOT take a 'combo' iron pill that has extra vitamins in it like C, D, B12, whatever. Just take a plain non-heme iron pill (most iron pills are non-heme. No meat sources). Just above 70mg please. I have used:
Klaire Labs and Kirkman both 5mg AND 30mg and combine two of each for a total of 70mg (5mg, 5mg, 30mg, 30mg, is 70mg
Nutricost 36mg x 2 = 72mg

Yes, you can go over 70mg. But since you're excreting nearly all of it, you'll be making yourself miserable. I've had guys use 80mg with success.

Getting timing or dose wrong means that you'll raise hemoglobin and have to donate again and your ferritin didn't even go up. "Don't be That Guy." Why non-meat? Heme iron doesn't boost hepcidin much, which is how this whole trick works.

The amount of iron you take daily after this (to maintain your new ferritin level) is extremely variable between men so read the full explanation below to decide how much, or even if, you take iron at all when you're done with your 4 or 5 days. Most guys should just get their iron from their diet.

You may have heard about the "rebound effect" after donating where RBCs go up a little faster than before. (It happens in non-TRT users. Your erythroferrone is already high. In other words, you are already having this "rebound effect" 24/7/365.) My protocol eliminates this concern anyway while you're doing it.

If this didn't work. If you followed this exactly and your hemoglobin went up and your ferritin is unchanged, get checked for an HFE gene mutation such as for C282Y hemochromatosis (H63D is ok). 23andme is a cheap way to do this (example). So far we've had about 6 guys accidentally discover they have iron disorders. (Relax, that's uncommon given the hundreds of guys who used this successfully.)

Questions I get after guys read the short version:
Can I just ask a really stupid question? Why don't we want to absorb the iron? Because your hemoglobin will shoot right back up again.
So where is the iron in the ferritin coming from if we don't absorb the oral iron pills? Your body recycles 80% of its daily iron from RBCs, happening literally every second.
Can I use another kind of iron? My grandmother has ferrous fumarate / sulfate / whatever pills. Yes, but you need the right amount of elemental iron minimum which is 65 to 70mg. Read the back label to figure that out.
Can I take iron with food? Try to avoid this on days 1 and 2 when hepcidin is being driven up. Space two hours from food. The other days appear not to be so criticial.
Can I take less than 70mg? NO. Less and your hemoglobin will go up, not ferritin! (60mg works but again, most makers are putting less in their pills)
Didn't this used to use 60mg? YES but using a sensitive gram scale, I discovered manufacturers are putting less iron in their pills than they advertise.
Can I just take the pills once per day? NO. This won't work.
Are the times of day flexible? Technically, yes. But don't get creative here. You can do a first dose between 8am and 10am. Second dose can be between 3pm and 4pm. Third dose can be between 9pm and midnight.
Can I take heme iron instead of non-heme? NO. The reason is in the long four thousand word explanation further down.
What happens if I go over 80mg? Well, I have a counter-question, do you enjoy shitting roofing tar? You can take more, but I don't recommend it.
Can I take an iron pill with a bunch of extra shit in it like B12 and vitamin C or D? NO. STAY AWAY FROM "BLOOD BUILDER."
What do you have against vitamin D? Vitamin D suppresses hepcidin, so it would work against you here. A vitamin D3 pill has a serum half life of 24 hours, but it converts to 25-hydroxyvitamin D which has a MUCH longer half life,so daily D3 dosing gave you a constant level of D which is why I say to stop your supplement a week before. Vit D from foods like eggs is not a serious issue because it's not enough to impact this. A 12-ounce glass of fortified milk typically contains about 150 IU of vitamin D, not a big deal. The RDA daily is 600 units. I prefer you not go above that for the week before and of the protocol.
Didn't this used to be a 3 day process? Yes, when I first published, but gaining only 10 points of ferritin isn't worth your time. That's nothing. We tested 4 days, and then moved to 5. Most guys choose 7. We have several moving to 10 days.
What kind of result can I expect? Sample feedback: "... I recently did your ferritin protocol and wanted to share my results. I am 36, been on TRT since 2018. My ferritin started to plummet since then (mainly due to blood donations every 2-3 months). The last time I checked, it was 10. However, I can't say I really felt low ferritin symptoms. Nonetheless, I tried your protocol last week. I used Iron bisglycinate, 75mg at 9am, 3pm, 8pm, for 7 days. Throughout this whole time I only ate egg whites, tilapia, tuna, whey, plain rice cakes. The result was great, my ferritin is now 94, and my Hb/Ht did not budge... " I do this and only get 40 points myself. It varies.
How long will I keep my new ferritin level? It varies dramatically. I keep my ferritin for one month. Another guy loses 20 points in a month. It is tied to EPO and Estradiol which are tied to your TRT dosing.

LONG VERSION
How to raise ferritin, the long "I'm ready for technical details" full explanation version
Before we dive into this, let's step through some basics.

Eighty percent of your iron comes from your own recycled Red Blood Cells.
"Most of the body’s iron is bound to hemoglobin in erythrocytes. Iron from senescent red blood cells is recycled by macrophages in the spleen, liver and bone marrow. ... Most of the iron in the human body is associated with erythrocyte hemoglobin (~80%). ... As the circulating iron pool is comparably small compared to the daily iron demand, iron has to be continuously recycled from old red blood cells to reach the daily requirement of iron to maintain erythropoiesis and other bodily needs." [Source] This iron is what we're going to use for ferritin. We are literally going to divert it from hemoglobin.

Hepcidin is the master regulatory peptide of iron in the body.
It can block iron absorption in the intestine while simultaneously preventing iron transport out of liver and spleen cells (it does both no matter what. It is never one or the other). This will be explained further below, but for now, that's what you need to know. This means it regulates iron by withholding it in liver cells and blocking absorption of it in the gut.

Iron stored in tissue ("ferritin") versus iron in the blood
Ferritin is a protein that stores iron and is found mostly in tissue. The liver's cells (hepatocytes) hold 80% of the body's ferritin. (A little bit exists in serum. This amount in serum is reflective of tissue stores and is overflow.) [Source] Ferritin in men tends to stay pretty constant for extended periods, weeks or even months.

On the other hand, serum iron is iron in the blood, and it changes hourly. Iron in the blood serum is going to get put to use primarily in hemoglobin and myoglobin. Serum iron varies in everyone from day to day -- that iron value on your "iron panel" blood test would have been different the next day. Iron is transported through the blood by transferrin. On an iron panel, you will see a Transferrin Saturation Percentage (TSat%). That is a good indicator of your serum iron. In normal people, it's between 20 and 45. TSat% can stay relatively steady over the course of a few days in some people.

If your TSat% is persistently higher than 55, or goes high a lot seemingly randomly when you aren't supplementing, you have something wrong. You might have a disorder using hepcidin, such as hemochromatosis. This is an early sign that you are developing iron overload. We've had a few guys discover they carry hemochromatosis genes after reading this guide and getting tested. 23andme will also tell you.

For our purposes, it's best to think of serum iron and ferritin as opposites. Iron is either in the blood, or it's stored in tissue. That's not 100% accurate, but it's helpful to think of it this way.

You can't have a piece of cake in front of you after eating it. It's one or the other. Similarly, iron is either in blood or it's in tissue as ferritin.

I want to emphasize: (serum) iron, aka just "iron" on a blood test, changes HOURLY. Is "iron" on an iron panel meaningful? NO. Why? Because "iron" on a blood test changes HOURLY.

When you read "[X] inhibits iron absorption," it's a misleading phrase.

When research says such-and-such can "inhibit iron absorption and make you anemic," that means that iron didn't make it into serum which holds it until it is transferred to hemoglobin or ferritin.

Two examples:
- If you drank tea, the tannins bound with the iron and your body excreted that unabsorbed iron in feces. That is "inhibited absorption."

- You took iron repeatedly, so hepcidin went up and your body blocked iron at the small intestine and also trapped iron in cells. That cellular iron is not available to be transferred to serum (via ferroportin) and will end up as ferritin. That is also "inhibited absorption."

Forcing iron to go into ferritin (rather than letting it go into serum, then hemoglobin) can cause anemia in normal people not on TRT. In normies, ferritin would drop like a rock in a pond after you finished your 5 days as your body stole all of the iron in the ferritin for use in hemoglobin. That's why a normal person with low hemoglobin would be foolish to follow this protocol.

You cannot 'take' ferritin, you can only make ferritin
Ferritin is an intracellular protein that binds to (wraps around) iron like a ball and releases that iron on demand in a controlled fashion. Ferritin is your iron bank account. You can't take bank account pills.

There are different types of ferritin in different tissues (heavy chain and light chain). This guide will not go into that. We are entirely concerned with the ferritin found in the liver, spleen, and bone. Just know that the ferritin you lose when you donate blood (or have a period as applicable) is systemic.

We do not use heme or meat iron for this protocol
There are some iron supplement pills on the market confusingly called "ferritin." Even if you consume animal organs (i.e. liver pills) to try to consume ferritin, your stomach breaks the protein down and it is treated as heme iron. We do NOT use heme or meat derived iron in this protocol. Heme iron does not boost hepcidin effectively. It has an entirely different absorption method so it won't work.

How ferritin works in normal people, vastly oversimplified
Ferritin going up when you're healthy and take iron
You take iron. Transferrin transports iron through serum. Hemoglobin normalizes and everyone is happy. If iron keeps going up, TSat% or transferrin saturation reaches a peak (which varies but is in the 40% area for most people), triggers a hepcidin increase, and the body starts storing any extra iron as ferritin. [Source] Transferrin reaching a peak, by the way, can take 24 hours or 12 months. It's all up to how much iron you ingest and how much iron is being "stolen" such as from heavy periods in women or phlebotomy in men. Ferritin is not just mere iron storage, all tissues need ferritin, but that's a much longer story you can read about here: [Source]

Ferritin going up when you're sick
Your body enters an inflammatory state where levels of cytokines, such as Interleukin 6 (IL-6) and C-reactive protein (CRP), increase. This inflammation increases hepcidin which stores iron as ferritin even if your body needs it elsewhere. This is an evolutionary response where the body is trying to deprive pathogens of iron, necessary for the pathogens to survive. When the inflammation subsides, a high ferritin will fall unless your hemoglobin is high (like 17 or above).

As was explained and sourced right at the beginning in Part 1, this ferritin building process is different for people on Testosterone.

If you crash ferritin while on TRT, it is VERY difficult to raise it using conventional methods. Erythropoietin takes every bit of iron in the body and puts it into your blood. Suppressed hepcidin means iron enters circulation whether you want it to or not. Iron is never withheld in cells to build or maintain ferritin. On TRT, all that iron in serum means hemoglobin can keep increasing past 17, 18, 19... the body never stores any extra iron you take as ferritin.

But I'm going to explain how to force the body to build ferritin.

The problem: TRT itself depeletes ferritin, and donating blood can crash ferritin
This is the possible double-edged sword when you donate: "hematocrit, hemoglobin concentration, ferritin, and red blood cell count (RBC), all key hematological parameters for oxygen transport, were lowered by a single donation and cumulatively further affected by the repetition of the donations. The maximal decrease after a blood donation was 11% for hematocrit, 10% for hemoglobin concentration, 50% for ferritin, and 12% for RBC." [Source]

Pretty much the only time a healthy male presents with normal iron but low ferritin is because he's on TRT and he donated to the point where his stores are depleted. This can cause fatigue, mainly. (If it's happening and the person is not on TRT, then it could possibly be a symptom of a disease. If you're a male on TRT and always anemic, get checked for colon cancer or another blood disorder. If you always have high iron and low ferritin and you aren't on TRT, you might be in the early stage of one of four known types of hemochromatosis. ("But hemochromatosis is when ferritin is high!" Actually high ferritin can be a LATE sign. By the time it's discovered, iron has overloaded you. This is why so many males get diagnosed after age 50.)

There is ordinarily a "rebound effect" from repeated phlebotomy (where HGB gets worse faster), which does not happen in the presence of elevated hepcidin. [Source] Because my protocol elevates hepcidin, this rebound is eliminated.

The solution: hepcidin
We need to take iron but we need something to divert that iron from the blood and into ferritin stores instead. That something is called "hepcidin." [Read about iron] [Read about hepcidin]

Since its purpose was discovered in 2001 by Dr. Tomas Ganz MD, the peptide hormone hepcidin has been identified as the principal regulator of iron availability in the body. [Source] It isn't that important here, but this peptide as it happens is antimicrobial and can help fight bacteria within macrophages.

In order to regulate iron levels, the body responds to iron ingestion by increasing the amount of hepcidin. "Hepcidin levels rise in response to iron ... such that iron absorption and release are reduced." [Source] How does the body know you keep taking iron? The iron ingestion signaling process is outlined here.

After you take iron, hepcidin starts to circulate in the blood. Hepcidin acts principally on transmembrane glycoproteins ferroportin (FPN) and divalent metal transporter (DMT1). When it does, this temporarily prevents iron export in all cells that express FPN and DMT1.

"Translate that!" This means that hepcidin:

1. traps iron in cells of the small intestine (duodenal enterocytes) by binding to and degrading ferroportin and by inhibiting DMT1 transcription. [Source] DMT1 is expressed not only in intestinal lining, but also kidneys, and dendrites. We still don't know all of the locations. "This iron would be eventually lost [in feces] through the routine sloughing of enterocytes, which turn over approximately every 3 days in humans." [Source]

2. blocks iron release by liver cells (hepatocytes) by binding to and degrading ferroportin. Hepatocytes are liver cells, and 80% of the body's ferritin is the iron in these cells. [Source] [Source]

3. traps iron in certain macrophages also by binding to and degrading ferroportin. Macrophages are immune system cells that recognize and consume cell debris, viruses, bacteria, etc.

This last one is a big deal, because "FPN is abundantly expressed in reticuloendothelial macrophages of the liver, spleen, and bone marrow, [meaning] that this protein serves as an iron exporter in cells that recycle iron from senescent [aging] red blood cells." [Source]

In all of these cases, trapped iron cannot enter the blood. Elevated hepcidin means that this irontemporarily has nowhere to go, so hepcidin is "effectively shunting cellular iron into ferritin stores and preventing its absorption into the blood." [Source]

This obviously means that hepcidin will restrict iron availability for erythropoiesis ... and result in iron accumulation in tissue macrophages... Once [hepcidin is] bound to ferroportin, ... cellular iron export ceases." [source]

[Source of graphic]

The major regulators of hepcidin blood levels are iron status and consumption, anemia, hypoxia, and inflammation. We will be using the first avenue, iron consumption, to raise ferritin.

This is the key to the whole protocol: you want to take an iron pill consistently so that you keep hepcidin elevated and every day the iron in the pill gets excreted, and the iron in the body from old RBCs is transferred to ferritin rather than going into your blood and elevating your hemoglobin (and hematocrit too).

But if you time it wrong, obviously, it will just make your high hemoglobin worse.

If there were a way to keep hepcidin high without taking iron, like injecting pure hepcidin subcutaneously, I would have you doing that instead.

This "Take Iron Every Other Day" Thing you probably saw in a blog
When doctors tell women and anemic men (who have hemoglobin levels of 13 or below) to take iron every other day, that’s because the hepcidin level is back down after 24 hours, so the iron will be absorbed into the bloodstream. [Source] They didn't even try to suppress hepcidin with Vitamin C or D in the study. Hopefully you the reader understand why the study conclusion is less than useful. (All they had to do was take Vitamin D and the iron blocking by hepcidin wouldn't have been an issue.)

We on TRT want high hepcidin for 5 days, though. For us on TRT, every other day iron dosing will raise hemoglobin and hematocrit and will keep ferritin low. That’s the opposite of what we want.

Remember from earlier -- think of iron in the blood as the opposite of ferritin.

This "Take Copper" Thing you probably saw in a blog
I cover this at the end. Copper does NOT play a significant role in this protocol. Yes, it's necessary for hephaestin, but again, it plays no significant role in THIS protocol. We are NOT building ferritin from the iron we take, we are building from our own recycled RBC iron. The way that process works, a shortage of Copper is not a factor here. The iron still enters hepatocytes.

What happens in iron overload? In iron overload conditions, such as hereditary hemochromatosis and thalassemia major, unregulated iron entry into the plasma overwhelms the carrying capacity of transferrin, resulting in non-transferrin-bound iron (NTBI), a redox-active, potentially toxic form of iron. [Source] When TSat% gets too high, that is what is happening. High circulating NTBI.

Things aren't going to be simple in people who are on TRT. We've seen that Testosterone stimulates Erythropoeitin. Unfortunately, high Erythropoeitin lowers hepcidin [source, source] indirectly by inducing erythropoiesis. [Source] One study found a TRT lowering effect of 57% on hepcidin. [Source] EPO aside, Testosterone itself suppresses hepcidin. [Source] (Interesting item in this source: note the use of Lupron and replacement with low dose Enanthate in study subjects.)

"Increased erythropoietic activity suppresses hepcidin, which leads to increased iron absorption and release of iron from stores, matching iron supply to increased demand." [Source]

Fortunately, if we force hepcidin up, it appears to inhibit / throttle back erythropoiesis (not for long though). This was a consistent finding by Protagonist Pharmaceuticals and is how Rusfertide works.

Things that work against raising ferritin (only DURING the protocol)
Elevated Estrogen. "This has been attributed to the ability of estrogen to suppress hepcidin synthesis, maintain ferroportin integrity and enhance iron release from iron-absorbing duodenal enterocytes and iron-storing macrophages and hepatocytes." [Source] [Source] [Source] Note that women with normal levels of Estrogen have lower levels of hepcidin; this link disappears after menopause. [Source]

Vitamins C and D lower hepcidin for several hours, and we want to avoid that, so don't take C or D supplements while you are trying to raise hepcidin to restore your ferritin level. I'm not saying don't ever take them, I'm saying skip them while you're working to restore ferritin. [Vit D lowers hepcidin] [Vit C lowers hepcidin] Vitamin D takes 2 days to clear from your system. Spending time in tanning beds or outdoors in intense sunlight may invalidate this protocol. UVB creates Vitamin D, as much as 15,000 IU in a 15 to 30 minute time span. I've had two reported failures in the protocol due to sunlight exposure and tanning bed use.

I get asked about foods. I eat boring foods when I do this protocol, like protein powder or chicken, that kind of thing. You can use this tool to find low C and then match results with low D foods I suppose.

Drinking alcohol during the protocol. [Source] There are multiple studies on how alcohol lowers hepcidin, but the magnitude is hard to pin down. Any alcohol downregulates hepcidin. Bing drinking really craters it. So, out of diligence, I am recommending you not drink for your 7 day protocol run.

For now, there are no drugs or supplements that help us to raise ferritin other than iron
Adenine - doesn't work. Adenine is a known strong hepcidin agonist. [Source] Adenine is sold as a supplement and is sometimes incorrectly called Vitamin B4. There is a bulk chemical supplier selling it on Amazon. A lot of hits will come up for NADH. It actually isn't the same thing. I grabbed toxicity info from a 1940's study that was the best one I could find (and remember, I have full access to the National Library of Medicine.) I tried 400mg per day split up at "the iron times" for 5 or 6 days and it had zero effect on my ferritin. Dr. Tomas Ganz (I wrote to him) said you would have to take a kidney-killing dose.

Capsaicin - Capsaicin administration significantly increased hepcidin levels in a rat study. [Source] Unfortunately 1 gram per day did not increase ferritin or lower hematocrit in myself or other testers.

Genistein - doesn't work. Apparently an Estrogen mimetic that is also a hepcidin agonist. 1,000mg per day produced no rise in ferritin.

Icariin aka Horny Goat Weed - doesn't work. Icariin is a known moderate hepcidin agonist. 100mg per day for only a week (!!) raised my Estradiol from 40 to 70 though, and my Test was the same, so it wasn't a rising T level. Icariin upregulates Aromatase. [Source] If you overdid your Arimidex, this supplement would probably help you recover. Some Horny Goat Weed supplements are just crushed up plant with very little Icariin -- you have to be sure that what you buy has a significant amount of the active Icariin ingredient. People are asking me what brand I bought so here it is, Icariin from the seller. Amazon doesn't carry it.

Melatonin - apparently it is one reason hepcidin goes up at night. [Source] The problem is that the half life of melatonin is 40 minutes max. So should you take it at bed time for my protocol? I would say yes, but should it be a lot, and should it be extended release? Probably. It doesn't last long enough. I have no specific recommendation right now. I tried 60mg every night and got zero rise.

Omeprazole - doesn't work. The Proton Pump Inhibitor Prilosec (which increases hepcidin in mouse models [source] but apparently not in humans) has been found to reduce the need for phlebotomy in C282Y hemochromatosis. [Source] The problem is that in the human research it was found that "The mechanism of how PPIs influence iron metabolism seems not to affect hepcidin regulation but acts in the stomach and at cell level in the erythroblasts and macrophages." This works only over long periods of time. It won't help for our protocol.

Turkey Tail mushroom - I took 5 grams (grams, not mg) three times per day for 5 days with the idea that it might elevate my IL-6 levels and promote hepcidin elevation. Well, my WBC count went up from 7 to 10.3, but my ferritin levels didn't go up. At least the WBC elevation matches research showing the immunity boosting property, but I'm not particularly interested in that personally. (Yes, I "could have" been sick, but in the few days between blood tests, I don't think so. I'm 'that guy' who gets CBCs all the freaking time.)

Sulforaphane - No significant effect on ferritin while on my protocol. This supplement upregulates Nuclear factor erythroid 2-related factor 2 (NRF2). From this study, "Nrf2 regulates iron metabolism pathway in response to oxidative and electrophilic stress by activating transcription of genes coding for ferritin heavy chain (Fth1) and ferritin light chain (Ftl) [109], thus increasing ferritin levels [110]. As a result, Nrf2 indirectly promotes iron storage and reduces the intracellular levels of redox-active free iron atoms. Moreover, Nrf2 also regulates labile iron (redox active, exchangeable and chelatable) by altering its transport across the cell membrane by up-regulating the expression of ferroportin. [Source] The BROC stuff I bought from Amazon

What kind of iron you need to use for this protocol
Before I explain how much iron to take in order to drive up hepcidin, I need to explain that the type of iron matters, because the actual amount of iron in a supplement varies a LOT. That 300mg iron pill is NOT really going to give you 300mg of iron.

"There are multiple iron compounds available for supplementation over the counter, and they each yield different amounts of elemental iron. Below are some of the common forms and conversion to elemental iron:
Ferrous Sulfate - Contains 20% elemental iron
Ferrous Gluconate - Contains 12% elemental iron
Ferrous Fumarate - Contains 33% elemental iron
Polysaccharide-iron complex - Contains 46% elemental iron
Ferrous bisglycinate chelate - Amounts vary on the formulation
iron citrate - Amounts vary on the formulation"

Example: 325 mg of ferrous sulfate yields 65 mg elemental iron (i.e. 325 mg * 0.20 = 65 mg elemental iron). You can usually verify "elemental iron" on the product label. [Source] Some labels on the back just say "iron" without the word "elemental" though.

Those last two, bisglycinate and citrate, can be thought of as 100%. In other words, 5mg iron bisglycinate is 5mg of elemental iron.

The front label of the bottle usually pulls this "300mg" nonsense. The back label of an iron supplement bottle often states the actual iron content.

Important point: I suggest that you buy ferrous bisglycinate chelate over the other types because we have a lot of experience with it. As a bonus, it is not affected by foods such as tea, which is famous for binding to iron and making it useless. [Source] We want the body to sense the iron and block it, not have tea interfere. You can use other types of non-heme iron if you want, but you have to use 70mg elemental iron no matter what type you buy.

Do you HAVE to use bisglycinate? No. In second place, some guys have used Ferrous Sulfate with success too -- users have used 325 mg ferrous sulfate pills (really 65mg per pill) to do this. These users report fewer gastric side effects. This is 65mg but will work. I say 70mg because manufacturers are putting less iron in their pills than advertised. If you have 65mg in a single ferrous sulfate pill, it's probably fine.

Make sure your pills DO NOT have added other vitamins! No "slow release" iron either for a first dose! You need to have a 65mg to 70mg 'hit' delivered all at once like a bomb to boost hepcidin. Slow iron might work for the other days; I have no idea.

"An oral load of 65mg of iron in healthy volunteers caused >5-fold increase in hepcidin within 1 day. ... The assays established that hepcidin transiently rises 4-8 hours after oral iron administration and that it is subject to diurnal variation with a midday maximum, perhaps because of dietary iron ingestion." [Source]

"Wait, 65mg?" Yes, 60mg and up works, but I found that manufacturers are putting less iron in pills than advertised.

You can't use iron from meat for this. Meat is heme iron and is RAPIDLY absorbed by the body. [Source] This is an issue with ferritin boosting; you need to use a non-heme (vegetarian) iron pill. Heme iron doesn't appear to boost hepcidin [Source] (There are issues with this particular study but let's not lose focus here.) It's easy to use non-heme pills. Here is what I buy at Amazon, I do not get paid for referral, 5mg version here. I do two 30's and two 5's for my 70mg.

Bisglycinate chelate is confirmed to use the non-heme absorption pathway.

A note on "slow iron" or time release iron products. The body needs an initial blast of 60mg to raise hepcidin. I recommend 70mg because supplement manufacturers are 'shorting' their customers with less than the advertised amounts in their pills. If your slow release iron pill can release iron to keep hepcidin elevated, you'll be okay. But if not, that iron might get absorbed.

The Question of Iron Loading Dose
The studies show an initial loading dose of at least* 60mg of elemental iron [source, source] at 9am to elevate hepcidin way up 5 to 6 hours later. Should you then take 100mg at 3pm and magically the 100mg will get filed away for future use as ferritin? No (explained below). There's really no reason to do that. Hepcidin is raised even more, so we add dose three after that at 8pm. That dose could be 70mg or 80mg, because at that point hepcidin should be very high (unless you have a very specific type of hemochromatosis).

*Due to manufacturers putting less iron in their pills than they advertise, I recommend you take 70mg or 75mg too to kick this off. The old protocol from May to September was only 60/60 twice daily. I have a gentleman who kicked off with 75mg and then used 50mg for the other doses (4 day). It worked and rose his ferritin 30 points but it raised his hemoglobin from 13.5 to 14.5. If you insist on not following this faithfully, then you won't get as much ferritin as you should, and you risk raising hemoglobin.

How many days you do this is up to you and your doc. I now have some guys doing ten days. They report no rise in hemoglobin.

Why not just take monster doses after the first 70mg?
This iron we're taking is not the source of ferritin. All this iron is to keep hepcidin levels high. Remember from earlier that hepcidin blocks more iron from being absorbed in the small intestine and blocks iron release by hepatocytes and traps iron in liver, spleen, and bone marrow macrophages....

For us, recycled iron from RBCs that is trapped is what becomes ferritin. The liver recycles and recovers iron from RBCs, hepcidin keeps the recovered iron trapped in liver cells, trapped iron is stored as ferritin, ferritin goes up. If you think about it, having high RBCs actually works in your favor here. More RBCs retiring means a higher ferritin.

Bigger oral iron dosing is just being excreted in feces. (And I'll be honest, after 5 days, your bowels are going to hate you. But every guy who has done this will assure you that it's WORTH it.)

So yes -- we take a lot of iron to raise an iron blocker hormone (hepcidin) and recycled RBC iron piles up in our liver stored safely as ferritin. Kinda oversimplified.

Here it is: 70 / 70 / 70, The Vorck Ferritin Protocol
Good for a ~20 to 30 point boost in ferritin:
Take 70mg at 9am, 70mg again at 3pm, 70mg a third time at 9pm, for five to seven days.

The study team has come to a consensus that after two days, you're going to see 6 to 8 points of ferritin per day with minimal rise in hemoglobin. Doing this fewer than three days won't work.

There are 7 day users showing up with ferritins over 90. It is possible.

Since we are increasing ferritin and iron, we can't forget the whole point we do this protocol -- avoiding elevated hemoglogin. What would this do to your HGB if you screwed up and took too little or took everything at the wrong times? Let's look at a hypothetical and ridiculously high dose. "Theoretically, 500mg of absorbed iron should produce 500ml of packed cells, the amount in about 2 units of blood, or enough to raise the hemoglobin by about 2 g/dL." [Source]

IV iron infusion will work too [source] but no doctor would ever sign off on it for someone on TRT with erythrocytosis.

Are the times flexible?
Yes but not by much. You can do a first dose between 8am and 10am. Second dose can be between 3pm and 4pm. Third dose can be between 9pm and midnight.

When do I do the protocol?
You can do it ANY TIME. Most guys do it around blood donation which is logical. I asked my hematologist if I should do this just the week before donating. He suggested right after donating would be better, because it will eliminate any rebound effect (by overriding erythroferrone). Stay faithful; you cannot miss a dose in this for the first 3 days, but if you miss a single dose on day 4 or 5, it's not a big deal at that point.

If you are on TRT, your body is always flooded with erythroferrone, so you are always in a state of the same "blood donation rebound effect."

You can do this protocol when your HCT and HGB are normal. But remember, if you time it wrong or swallowed your pills with orange juice (8 ounces, 160mg vit C) or had sturgeon for dinner (8 ounces, 800IU vit D), you might end up boosting hemoglobin instead. This protocol requires strict attention to dietary detail for the days that you do it.

Heme iron helps non-heme to absorb so please don't go eating steak for three meals a day during your 5 to 7 day run. I can't get more precise than that because I don't know much more than 'heme iron works against you.' I use protein powder and salads for a week. Yes it sucks. Those of us who go vegetarian for that week seem to have really good results though.

What do I do afterward?
You STOP. And the first time you do this, you go get a CBC and an iron panel and a ferritin test to see what's what. Ideally, ferritin should be up and hemoglobin and TSat% should both be normal range (you did this after donating, so that's why I say you hemoglobin should be normal. Donating made HGB normal not my protocol).

The question of maintaining your shiny new ferritin level is explained further down.

I want to do it again. How long do I wait?
I am concerned that you make sure you didn't elevate hemoglobin. You might be doing things wrong your first time. You need to make sure you aren't elevating hemoglobin, so don't do a 14 day run your first time.

That said, if you know how your body reacts and you have done this before, you can start right away. I used to recommend a week off, but I don't see any reason to say that now.

What ferritin level is ideal?
There is evidence that in women, a minimum level of 51 is where the body attempts to correct for low ferritin. No similar research exists for men that I am aware of, but for now that's a reasonable minimum target. People on TRT could have a difficult time getting 100 or higher because of how Testosterone causes the body to steal from ferritin, explained earlier. [Source] I see an awful lot of guys on TRT not being able to keep numbers higher than the 70's. That's probably the TRT 'set point' for many of us. Remember that your blood test may show a 90 from 7 days but I cannot guarantee you'll keep it. A popular FB group recommends a level of 125 for a minimum of 6 months. I just honestly think based on observation that on TRT, you will never hit 125.

How long can I expect to keep my new ferritin level?
I can pretty much guarantee you a month at least. You guys will get mad if I say it depends, so I will say that most guys with a hemoglobin of 15 or 16 will keep their level, plus or minus 3 points, for at least one month. Many are keeping it until their next donation, but don't hold me to that. We all do different amounts of Testosterone, and have different levels of Serum Test and EPO, and therefore different amounts of ferritin slipping out of cells. Personally, I have a trough T level of 750-800ng/dL and I lose about 3 points of ferritin per month.

I'm not happy with my 30 point result after 7 days, how long do I wait before I can run it again?
I used to say wait 2 weeks. I really had no basis for that, I just wanted to play it safe. When you stop, you have iron from your last day in your gut cells (entocytes). The body sheds them after three days. So technically when you stop, you have 2 days where iron pills you took on your last day can absorb. That's a constant. So waiting 3 days or 7 or 14 doesn't matter -- you want to go again, go ahead, no waiting is needed.

You do need daily iron to maintain ferritin. How much depends. It can be dietary only for some guys.
You have to have some iron every day in order to keep your body from "stealing" from ferritin. For most of us, food is enough (remember that vegetables are non-heme, I don't mean having steak every day). RBCs create an aggregate iron demand from the body; the higher the RBCs the greater the demand. (And remember, more RBCs means more iron recovered by the liver and spleen from recycling those RBCs). In fact, when you start TRT, don't be surprised if your ferritin plummets. Testosterone is essentially telling the body, through increased EPO, to empty the iron stores (ferritin). EPO keeps erythroferrone up which also keeps hepcidin low, essentially telling the body not to build ferritin back up.

In Part 1, I explained and sourced that the reason this doesn't happen to people with naturally high Testosterone who aren't on TRT is because exogenous Testosterone resets the EPO setpoint (usually temporary, it normally falls in a year). Natural Testosterone and EPO are normally in equilibrium. A constantly high T level as from injections keeps EPO high. An 18 year old male with a natural Test level of 900 doesn't have that level 24/7.

Important point: keeping iron low doesn't keep RBCs low. All it does is keep HGB close to normal (and that plays a role in keeping HCT low). So an iron poor diet that some doctors might recommend helps a little, but not in the way you might think. Same goes for people telling you to take chelating agents. It's just trying to be "iron poor." It doesn't solve the Runaway RBC Train. RBCs are still being cranked out because of high EPO, and they are requiring iron. If the iron isn't there every day, your body will deplete your ferritin. (Aside: if you keep iron too low, your body will subtitute Zinc on RBCs. That's bad.)

In my opinion, taking chelating agents is one of the worst ways to manage your erythrocytosis. They deplete ferritin FIRST and lower hemoglobin second.

If you are reading this guide, you have high RBCs -- and that means you have a natural iron load from these recycled cells than the average person. Always remember that iron is recovered from retiring RBCs which have a lifespan of about 120 days. (Aged Garlic Extract shortens that, apparently.)

So how much daily iron is needed? I have seen posts on this topic all over the road. Some guys just get their daily iron from meats (heme iron is fine, it's just that we use non-heme for the protocol). I know someone who uses cast iron cookware and says that works for him. Not terribly precise, but if it works, it works. Some say that they take 5mg to 28mg pills and they keep their iron and their ferritin in the lab-normal ranges. The RDA is 8mg for males (and 18mg for menstruating females). The RDA takes into account that you already get 20mg daily from your own RBCs. So now you understand why a guy with RBCs of 6.5 maybe doesn't need an iron pill every day.

I did 5mg daily for a week and then on and off and ended up needing to donate month earlier! So even a small 5mg pill was too much.

Since hepcidin is a peptide, can it be bought?
Tricking the body into making hepcidin would be unnecessary if we could just inject it subcutaneously.

Rusfertide, a mimetic, is being trialed as a drug treatment for erythrocytosis conditions. Human hepcidin, compare to Rusfertide. They could make an identical molecular knockoff but then you can't patent something like that so they make a mimetic.

However, actual real-deal hepcidin is apparently available for purchase as a lab research peptide. You have to use the older terminology for it to find it: LEAP-1 (liver-expressed antimicrobial peptide), sometimes also called hepcidin-25. Because animal experimentation with this is common, you will have to hunt for the human variant. It's out there but it's hard to find. I'm not going to link to it because I have idea how to direct you to use it safely. It is unbelievably expensive.

Here's an odd thing about hepcidin: research has confirmed that this peptide has functionality across species. Zebrafish hepcidin works in mice. Mouse hepcidin works on monkeys and human cells in a test tube.

A note on weight loss drugs (GLP agonists, Semaglutide / Tirzepatide / etc)
These slow the transit of food from the stomach and they also slow the iron pills. These drugs will skew the time that the iron "hits" and your body raises hepcidin. You do not need to stop your weight loss drug, but taking your iron on an empty stomach far from your food would be best for the first two days when you start. I have a reported failure of the protocol from a Mounjaro user.

A note on gastric bypass
Gastric sleeve shouldn't affect the protocol, but Roux en Y will cause iron supplements to bypass the body's sensing area in the gut. You won't see a meaningful increase in ferritin unfortunately.

Summary
If you are on TRT, you have multiple options for controlling erythrocytosis and the resulting high hemoglobin and hematocrit:
- modified dosing to be daily, or daily with a lower overall dose.
- regular phlebotomy or donation, with ferritin rebuilding.
- drugs like Telmisartan or grapefruit extract supplements.
- consider, as applicable, CPAP treatment or smoking cessation.

Show us a sample 5 day run
Here is a typical result. Remember, results depend heavily on following the protocol exactly for 5 days, and depend on your starting RBC load. Starting with RBCs at 4 won't have a good effect -- this whole process is driven by endogenous (your body's existing) iron, not exogenous (from supplements) iron.

This has been around since May 2021? Why am I hearing about this just now?
Because you spent time in the wrong online community. Trust me, I tried spreading the word. I got thrown out of groups and shadowbanned on Reddit. Blame your imbecile mods and brain dead filters.

I recommend All Things Testosterone with Brandon Church and his FB group TRT Community.

A Reddit post actually referenced this which was what made me try to post, but alas, no luck.

Criticism: use of iron raises RBCs
This one came via an April 2022 e-mail from Dr. Tomas Ganz, the MD who discovered the hepcidin peptide, after I asked him to review my protocol (yes, I really asked him about this). He acknowledged that raising hepcidin works, but he advocated using a mimetic like Rusfertide. Obviously he's not wrong, but ... we can't wait for the FDA on this.

Criticism: does this use inflammation? Won't ferritin fall again?
Your new ferritin level will stay in place if you have a high hemoglobin and you follow the directions. We are not using inflammation. Hepcidin is an acute phase reactant, but it is raised via a few different methods. The iron administration pathway is separate from the inflammation pathway. [Source] You can change a light bulb using a step ladder or standing on a milk crate but you wouldn't say step ladders are the same as milk crates.

Criticism: not all the studies you use took place in TRT subjects
Some studies were on women, for example, or trans F to M. Some were on people with diseases, such as kidney disease. If the thing being discussed is true independent of these things, I use it. One example is Angiotensin II receptor agonists for SE. This was a finding in chronic kidney patients on dialysis. However, the drug clearly creates a blockade of erythropoietic effects of angiotensin II on red cell precursors. The dialysis aspect of the study doesn't materially affect what we're looking at. In addition, I have access to full studies through my healthcare institution, so just because a paper is paywalled doesn't mean that I relied on the summary alone.

Criticism: a few studies that you cite were on mice
The model of iron homeostatsis that we have developed has been found to be remarkably identical broadly across mammals. Hepcidin, it has been found, even works cross-species. Mouse hepcidin will actually work in other animals. Mouse experiments by and large mirror what happens in humans vis a vis iron and hepcidin.

Criticism: ferritin is bad and you need copper not iron...
GTFO with that Morley Robbins horse shit. My process WORKS. Go try your Root Cause garbage and see how much worse you feel with a ferritin below 20. Copper has a minor role in transferrin and ferroportin and the ferritin cage and does not MOVE iron in any way. We aren't even trying to absorb the iron.

Criticism: a guy on YouTube said...
The guys on YT talking about ferritin just make me laugh. One actually said low ferritin doesn't matter if serum iron is high. Serum iron changes hourly. That video was made by a group that's 20 years behind on TRT anyway. At a point, you get too far behind to catch up.

Criticism: this page goes really light on how iron works
I admit this page is shorter than I would like, but I have to strike a balance between explaining fully and explaining just enough to show why this ferritin protocol actually works.

Some people like videos so here's one showing how iron is processed. [Iron metabolism video]

Appendix

Random notes

COVID increases ferritin [source] because your immune system fights the virus with a huge IL-6 response [source] which increases hepcidin [source]. The Spike protein is a hepcidin mimetic (no, seriously). [Source, source, source] Very high and low Testosterone -- both problems in Covid. [Source]

The process of iron absorption in the gut. [Source 1, Source 2]

Could elevated hepcidin be a biomarker for some cancers? [Source]

The action of hepcidin in the context of chronic inflammatory disease. [Source]

Persistently elevated hepcidin (high ferritin, low HGB and RBCs) is a mutation in the TMPRSS6 gene. [Source]

There is an iron protocol page on Facebook that says that you need Vitamins C and D. That's because they deliberately keep hepcidin low. The lady who runs it, Caitlin, is very knowledgeable about her community, but you should know that her forum is for people with low hemoglobin NOT on Testosterone. 95% of her community are women, many of whom have heavy periods with severe blood loss. If you follow her iron protocol while on Testosterone, your ferritin will NEVER go up, and you'll have to get phlebotomy every week. Her protocol is NOT for us.

Do Nandrolone (deca) and Oxandrolone (Anavar) contribute to SE? Nandrolone was first synthesized in 1950 and Oxandrolone was first synthesized in 1962. They were products that had limited applications out of the gate and were not for mainstream TRT use. The erythropoietic profiles of these drugs were studied in the context of seeking the best treatment for dialysis patients - in the 1960s. This research is available on PDFs containing scanned images of paper printouts and aren't searchable. If I get data I will include it but it's really hard to track down. The research does show they contribute to SE. How much, I don't know. (If you were curious: Cypionate first synthesized 1951; Enanthate, 1952)

Basic Iron Transport, oversimplified
The transport of iron in the human body involves specialized proteins that bind to iron and facilitate its movement across cell membranes and its distribution to various tissues and organs. The key iron transport proteins are:

1. Transferrin: Transferrin is a plasma glycoprotein responsible for transporting iron in the bloodstream. It binds to ferric iron (Fe3+) released from food in the small intestine or recycled from senescent red blood cells. The iron-transferrin complex circulates in the blood and delivers iron to cells expressing transferrin receptors.

2. Transferrin Receptor: Transferrin receptors are found on the surface of cells, especially those with high iron requirements, such as red blood cell precursors in the bone marrow and certain other rapidly dividing cells. These receptors bind to the iron-transferrin complex and facilitate its internalization into the cells through receptor-mediated endocytosis.

3. Ferritin: Ferritin is an intracellular protein found in most cells, particularly in the liver, spleen, and bone marrow. It acts as an iron storage protein, sequestering excess iron in a non-toxic and bioavailable form. When the body needs iron, ferritin releases stored iron to be utilized for various cellular processes.

4. Hepcidin: Hepcidin is a hormone produced in the liver that regulates iron homeostasis. It controls the absorption of dietary iron in the intestines and the release of stored iron from macrophages and hepatocytes. Hepcidin binds to the iron exporter ferroportin, leading to its internalization and degradation, thereby reducing iron export from cells.

5. Ferroportin: Ferroportin is the only known cellular iron exporter and ferroportin plays an essential role in the export of iron from cells to blood. Iron trapped in a cell becomes ferritin. Iron cannot be trapped in a cell if ferroportin is always letting it out of the cell. This is why low hepcidin is a problem for building ferritin.

Iron Absorption and Metabolism: Iron is predominantly absorbed in the duodenum and upper small intestine. When dietary iron is present in the ferrous (Fe2+) form, it is transported across the enterocyte membrane by a transporter called DMT1 (divalent metal transporter 1). Once inside the enterocyte, ferrous iron can either be stored as ferritin or exported into the bloodstream bound to transferrin.

Hepcidin plays a crucial role in iron metabolism by regulating the activity of ferroportin, the cellular iron exporter. When iron levels are sufficient, hepcidin is synthesized and released into the bloodstream. It binds to ferroportin on the surface of enterocytes and macrophages, leading to ferroportin's internalization and degradation, which reduces iron absorption from the diet and iron release from stores.

Iron Recycling: The human body has a highly efficient system for iron recycling. When red blood cells reach the end of their lifespan (about 120 days), they are engulfed and broken down by macrophages in the spleen, liver, and bone marrow. The iron released during this process is either stored in ferritin or transported back to the bone marrow for erythropoiesis (red blood cell formation).

Basic Overview: Copper's Role in Iron Transport, oversimplified (because sometimes people ask about copper)
Ceruloplasmin serves as the primary carrier of copper in the blood. It binds to copper ions, which are released from food in the digestive tract or released during the breakdown of old red blood cells. By binding to copper, ceruloplasmin ensures its safe transport through the bloodstream to different tissues and organs. Besides its role in copper transport, ceruloplasmin also participates in iron metabolism. It has ferroxidase activity, which helps convert Fe3+ to Fe2+. This conversion is essential for proper iron utilization and storage in the body.

Hephaestin is primarily expressed in the enterocytes (cells lining the small intestine responsible for absorbing nutrients from food) and hephaestin regulates the release of iron into the bloodstream from the enterocytes via ferroportin. The mechanism by which hephaestin facilitates iron absorption involves its ability to oxidize ferrous iron (Fe2+) to ferric iron (Fe3+). Ferric iron is the form of iron that can be effectively transported across the enterocyte membrane and subsequently bound to transferrin, a protein that transports iron in the bloodstream.

Copper Absorption and Metabolism: Copper is obtained through the diet, mainly from foods such as nuts, seeds, whole grains, shellfish, and organ meats. Once ingested, copper is absorbed in the small intestine, where Ctr1 facilitates its entry into the enterocytes. From there, Atox1 and ATP7A transport copper within the cells and direct it to various cellular compartments, such as the mitochondria and the Golgi apparatus, where it is incorporated into copper-containing enzymes.

Excess copper is either stored in the liver, bound to proteins like metallothionein, or eliminated through bile secretion. ATP7B plays a significant role in copper excretion by transporting excess copper into the bile for removal through feces.

If someone says you need to supplement copper to build ferritin, immediately stop listening to them.

Some notes on Estrogen
I am not anti-Estrogen but people aren't being told the truth by the TRT users who are 20 years behind and advocating high Estradiol.

A woman's body, during pregnancy, raises Estrogen to create more RBCs and put them into hemoglobin because the maternal blood load and O2 needs to be high. That doc on Youtube that goes on and on and on and on and ON about the benefits of E2? Did you ever read the E2 levels in the studies he flashes on the screen? No? Maybe ask yourself why he's touting the benefits of Estrogen when those benefits are highest at pregnancy levels. Yes, E2 is neuroprotective. Great! But is it really smart to have an E2 so high that you get erectile dysfunction just in case you get into a car crash and need the neuroprotective benefit?

For women: Estrogen lowers hepcidin and makes ferritin difficult to build, prioritizing hemoglobin. [Source]

Do NOT go too low on your Estradiol level

You need E2 for your bone density. Many in the anti-Aromatase Inhibitor crowd actually believes, incredibly, that AI users are attempting to get their E2 to zero. (I'll give you all a minute stop laughing at the anti-AI crowd.) The question is, WHAT minimum levels of E2 are needed to prevent bone density issues?

From Aromatase Activity and Bone Homeostasis in Men by Luigi Gennari, Ranuccio Nuti, John P. Bilezikian
"A review of several studies showing that in most but not all cases, elimination of Estradiol using AIs negatively impacts Bone Mineral Density... The data argue that men need a sufficient concentration of estrogen, defined as a threshold value, for normal skeletal remodeling. In all of these studies, the required concentration of bioavailable estradiol appears to be remarkably similar, ranging from 10 to 14 pg/mL."

Normal bioavailable E2 is 21 to 38 pg/mL. 2 to 3% is bioavailable and 3% corresponds to a serum total of 41 to 75 pg/mL.
The minimum required concentration of bioavailable E2 is 10 to 14 pg/mL and 3% corresponds to a serum total of 20 to 28 pg/mL. In other words, having an E2 below this minimum level presents a risk to bone density.

What's a healthy E2 level? This formula gets used a bit. It is set up to use the most common units that people quote their lab values in.

E2 in pg/mL divided by Total Testosterone in ng/dL should be between .03 and .1

For example: E2 is 60, Total Test is 600, this ratio is therefore .1 and so this E2 should not be causing symptoms of high Estrogen. Maybe check other factors before using an AI.

Second example: E2 is 133, Total Test is 1,100, the ratio is .12 and so it is possible that if you have symptoms, your E2 might be causing those symptoms.

Third example: E2 is 18, Total Test is 850, the ratio is .02 and it would not be a surprise if you had zero libido because of this low Estradiol level. Elsewhere on the page you'll see using Icariin to raise E2 indirectly by upregulating Aromatase.

"But Estradiol is an intracrine hormone!"
Yup. It is. So what? Oh, were you about to make an "argument" that using an AI reduces Estradiol in tissues and that's the literal end of the world? Were you going to say stuff about tissue biopsies to figure out the E2 levels you need? Different tissues express different amounts of Aromatase, and serum E2 corresponds to Free Estradiol. Yup, Free E2 is a 'thing' just like Free Testosterone. (And I suppose we need tissue biopsies to see if we need to inject a higher dose of Test too, right?) There goes the 'biopsy argument,' if you can even call it an argument.

"But AIs are approved for cancer! Therefore, they are bad!"
Your Uncle Arthur's Methotrexate that he takes for his arthritis was approved for cancer first.

Change log
September 2023, added notes on DHT and Estrogen contributing to erythrocytosis. Added info on Telmisartan and notes about Losartan. Added 5a reductase inhibitors and Arimidex to the beneficial drug list. Added "notes on Estrogen." November 2023, notes that most users are doing 7 days. Added notes about stopping vitamin D for the week before the protocol as well as during. Minor note on ferroportin added. Note on semaglutide/tirzepatide added. Amlodipine added. December 2023, melatonin discussed. Feb 2024, Cayenne evaludated (didn't) work, ginger being trialed for controlling speed of RBC rise. March 2024, Mounjaro failure documented and gastric bypass notes added. March 2024, grapefruit / naringen is a chelator which is why it works. This can reduce ferritin too. July 2024 added statement on how long you wait before going again. Added Divesiran reference. August 2024 statement on alcohol throwing off the protocol. September 2024 Jeremy M. recommended Quercetin which has research support for lowering hemoglobin.

My thanks
I leveraged studies and anecdotal data and received a LOT of help from Kyle V. and Keith R. You two have my sincere thanks. Also thanks to Doctor Ali who told me my info and ideas made sense and said "it could work" and encouraged me to go full bore when this protocol clearly did work. Thanks to Jeremy M. for testing out various supplements and sending me info on drugs and supps that can lower HCT. And of course to Dr. Tomas Ganz who personally answered several key questions I couldn't find answers to online.

About the author
I started TRT in 2001.

My opinions are my own and not those of my employer.

Some loser who refused to click and read once asked what my credentials are. Like that guy, I'm pretty much a nobody. The difference is that I'm the one who reads all of the studies other people don't want to read.

For 20 years, I waited for someone to write about iron and donation issues surrounding TRT and how to increase ferritin.

And for 20 years, no one did.

So in January 2021, I did the research myself, I developed a protocol myself, I hired a hematologist myself, I tried my protocol on myself in May, and then I uploaded it.

Failures: several males with C282Y hemochromatosis (body does not make or makes but does not use hepcidin). One male who used a UVB tanning booth religiously twice per week (vitamin D, guys). One male who uses a LOT LOT of supplements. (We never did figure out which one was the culprit). One male who took 40mg pills the whole time. (It takes 60mg minimum to raise hepcidin and most iron pills don't contain the full advertised amount). One who did the protocol and ate meat all the time for every meal. (Well, I did say that heme iron can cause you to absorb your non-heme pills.)

Links to unit converters

Testosterone units

Free Test

Estradiol units

Prolactin units

SHBG

Calculate T to E2 ratio

Labs to get on TRT

Get before and after starting TRT:
• Total Testosterone
• Free Testosterone
• SHBG
• Estradiol (specify “sensitive” assay for males)
• Prolactin
• PSA
• Vitamin D
• You will get a CBC as part of the test anyway; note CBC values of HCT, HGB, RBC

Also get before starting:
• LH
• FSH
• DHEA-S
• Cortisol
• Thyroid Panel
• Metabolic Panel
• Lipid Profile

If you get phlebotomy often (these are separate tests):
• Iron
• Ferritin

Iron related reading

Hepcidin

Transferrin

Ferroportin

Hepcidin and ferroportin interaction

Erythroferrone

Hemoglobin

Red Cell morphology

Lactoferrin

Ceruloplasmin

Ferritin light chain, heavy chain, hemosiderin