Iron, Inflammation, and MGUS.

So I had to go get some blood taken for the Dana Farber - IMPACT - study. So I decided to get a few more limited blood tests. I retested Ferritin, tested Vitamin D and, TSH. 

For the last two weeks I have not had any red meat and I am happy to say that my Ferritin dropped down, from 245 to 211.  That is still higher than I would like but I think shows a clear issue with iron and red meat.  Both my Vitamin D and TSH were great.  Mainly, not having red meat really dropped the value in a short time period. 

There is great controversy about red meat for health. And I happen to find results all over the map. Based on those I was pretty confident that red meat would not be an issue and, since I was alternate day fasting, I assumed I would not over do it.  But thank god I tested it and it was an issue. Now I know. 

I was overdoing it. Primarily because of changes to the food supply. 

• Recently I have been having trouble finding veggies.  What ended up happening is I tended to eat either "cauliflower" or "creamed spinach".   Cauliflower has a ton of Vitamin C which allows absorption of iron and Spinach has iron. I was eating the entire bag, not just a serving.  In addition at one point I was told that the oxalates in the Spinach stop the iron from absorbing, but that only applies to raw Spinach, not cooked. 

• Recently I got into a nasty habit of having a burger for lunch (no bun) this is not my normal but, McDonalds no longer has grilled chicken food wraps and I was doing keto.  Typically I don't even eat at McDonalds but it was a nice ride every day in the pandemic.

• I have added red meat to my listing of food that I can eat and I switched to having red meat more frequently than chicken. And I would have like a 5 oz serving. In addition, I think I was having cuts that were more muscle (which has a lot of iron). 

A lot of people tell me that food cannot make your iron stores go up. The truth is, they are just wrong.  It is often said that once iron goes into your body there is no way to get rid of it - that is even more true that one might know. Even though you supposedly need a lot of iron per day... just recently it was discovered that we already have a massive source of iron.... our own blood cells.  Our bodies recycle blood cells and the iron in them. Thus, the vast majority of iron that you get each day is from this recycling.  Like 80%. So, if you are eating a lot of iron and absorbing it, you are continuing the build up of iron - that basically - unless you donate blood - is hard to reduce.  This means it is VERY easy to over do it with iron. 

After looking into iron more I am horrified that it is so ignored as a health concern. I am rather furious that my doctor never ran this test.  Imagine if I hadn't?  I would have been unknowingly hurting myself? As it is, I have no idea if I did hurt myself.  I had an issue with this once. I started taking a multivitamin that had iron it it and I started turning brown. My iron was wayyyy high. I stopped taking the vitamin and all was well.  So I feel like my doctor should have been looking for that. 

But it is apparently well known as something that should be watched in women post menopause. Especially if they have had issues before.  Yet, even with my much higher RBC and hemoglobin counts being on the high side... nothing. I will have to be careful in the future. Keto without red meat is not easy. I can have things that block the absorption of iron but I don't fully trust them. 

I happened also to come upon some science in this area last night and our understanding of iron has radically changed in the last ten years.  In particular, they have discovered a hormone that controls the amount of iron in your body... and this hormone being high, is not necessarily a good thing.  Hepcidin helps to control the expression of iron in the body and recently it was shown to be unregulated in gastric cancer.  The cancer that took out my mother. Hepcidin is a key regulator of the entry of iron into the circulation in mammals. Hepcidin is typically elevated with inflammation. 

Blood Donation: Part Four

So what happened to me when I gave blood and then had my MGUS blood tests go out of wack. As we saw in the previous post: no plasma cells are usually in circulation. The only way to get a direct look at them is to do a bone marrow biopsy. But MGUS patients use markers in the blood to determine what is going on with those clonal cells. The clonal cells produce "excess junk" that shows up in our blood stream. From looking at the junk we can reverse engineer what is going on with the clonal cells. 

So it is my belief that my tests were thrown off by my having a reduction in the absolute value of the blood, but not necessarily the absolute value of the junk. The "junk" remained relatively stable... my blood volume did not. It is possible also that the absolute value of the junk changed slightly as well. 

The measurement of the M-protien is in grams per liter. So if your liters drop down... your measurement of protein per liter is going to go up. 1 liter = 2.11 pints. So losing a pint of blood means that you will be losing 1/2 a liter. Mine did hardly move, from .3 to .5 g/dl.

The measurement of light chains however is.. milligrams per liter so it would seem that this might have a larger absolute amount since the unit of measurement milligrams is smaller than grams. Losing 1/2 a liter of blood from the body may have had a slight effect.  My results seemed wrong since I am IGM-kappa, you would expect to see an increase in Kappa and a stable Lambda. Instead my Lambda went way down. That would seem to be wrong. Since this blood test it came up. 

Now of course I had these blood tests about six to eight weeks after the blood donation and frankly it is questionable as to whether, at that point, there would have been any real difference.  But the absolute minimum between blood donations is sixty days and that is right at the edge of when these tests were done. 

Blood Donation: Part Three

So what did we learn from this (and further research)

Your body is replacing blood cells all the time naturally.  In fact, I was curious and I looked it up - red blood cells are replaced every 120 days But white blood cells are replaced much more frequently - almost daily.  All white blood cells are derived from cells in the bone marrow known as hematopoietic stem cells. The bone marrow then stores an estimated 80–90% of white blood cells. But some still circulate in the blood. 

It is these hematopoietic stem cells that are damaged in the first instance. These stem cells have mutations that may not allow the stem cell to turn into a normal functioning b cell / plasma cell (differentiate). The stem cells work fine for every other kind of White Blood Cell. They only have a mutation that effects differentiation B/ Plasma Cells. When the body calls for new b cells / plasma cells it calls up damaged stem cells and these stem cells can become clonal cells. The particular type of White Blood Cells that we have issues with are B cells: also known as B-lymphocytes, also known as Plasma B cells, these cells produce antibodies to help the immune system mount a response to infection.  There are like 7 different white blood cell types but MGUS people only have a defect with regard to the WBCs that are B cells / Plasma cells. 

So Dr. Kyle did help me figure some of this out... when he said that he doubted that plasma cells would be in the blood with a small MGUS. That gave me the hint that the white blood cells in the blood would be less than red. 

Googling it, I found out 

Most people will produce around 100 billion white blood cells every day. There are normally between 4,000 and 11,000 cells in every microliter of blood, although this can vary according to race.

 And, in fact

Plasma cells are not normally found in the blood circulation. Notably, B cells, the precursors of plasma cells, also undergo much of their early development in the bone marrow.   

Ok so now we are getting someplace, it would seem that in the first place... that blood donation is likely to have zero effect on B /Plasma cells. As this particular type of WBC is not in circulation anyway.  But, even if they were... losing a pint of blood is not going to effect your white blood count very much.  You have about 7 to 10 pints of blood in your body. Looking it up.. since there are about 4000 WB cells in 1 milliliter of blood, and a pint of blood  is 473 or 568 milliliters.... you probably will loose about 1,892,000 white blood cells in one pint of blood.  If we produce about 100 billion white blood cells daily well, it would seem the body might hardly notice a million cell loss.

So finally I think I have an answer. Blood donation will not effect the plasma cells / clone cells because they are "walled off" from the blood stream.

It does make sense. If you want to get a count of your clonal cells you cannot just test the blood. The only thing that will be in the blood are after effects of clonal cells, M-Protien,  immunoglobulins, and Light Chains. To see what is going with clonal cells you need to get a bone marrow biopsy. 

The B / Plasma cells will not react to blood donation but, they will react to viral or bacterial infection - when bacteria or viruses enter the body, some of the B cells will change into plasma cells. The plasma cells make antibodies to fight bacteria and viruses, to stop infection and disease.  There is a great chart on this link that gives a good idea -- Chart

Blood Donation: Part Two.

So I went to a Myeloma foundation and the person there tried to answer my question on her own. She did advise me to bring this up with my doctor but, as we saw in part one... that is a non-starter.

She stated:

Our bone marrow is constantly producing new hematopoietic cells to replenish the cells that are currently in circulation, working at their various jobs; red cells carry oxygen in the blood stream, various white blood cells fight infection and platelets help our blood clot if we get cut. Each different cell type has a different life span, but they all need to be replaced whether they live days or weeks.

Ok so far so good. 

I have trouble understanding why donating a physiologically safe amount of blood would cause abnormal stress on the bone marrow. 

So here is the problem. I have trouble understanding why they can't understand my concern and they simply NEVER TELL ME WHY? So frustrating. Presumably losing a lot of blood cells at once is going to stress the factories that will need to make new ones in quick time and, under stress, I worry it would be more likely they would go for broken stem cells to make new WBCs that were lost. 

She continues:

I have not read any studies showing blood transfusions caused myeloma to become active. 

Here is the problem with this. People with MGUS will be advised not to donate blood to other persons. So it is very likely that no one with MGUS will donate blood and therefore no one will ever find out if it causes issues. Never mind that with the limited funds for MGUS research NO ONE is going to do a study on this.   

Later on, without my requesting her to she

I wrote to Dr Robert Kyle, who was with the Mayo Clinic for many many years and is most knowledgeable regarding MGUS. He responded to your questions as follows. 

Yeh that is right, Robert A. Kyle, MD, Luminary in Myeloma Research -- that guy, you know the FATHER of MGUS.  He stated:

There is no evidence to his knowledge that donating a sample of blood on an ongoing basis would cause the MGUS to progress.  In fact, he doubts that there is any harm to the recipient, but there is no data in this regard.  As a prospective blood donor, one should tell the Blood Bank that they do have a MGUS and the Blood Bank will probably turn them down as a donor. A larger MGUS could have circulating plasma cells, but that is unlikely to be a problem for the recipient.

Ok but here is the problem... of course there is no evidence. People with MGUS are advised not to donate blood - as he rightly states (and completely contradicts my hematologist /oncologist team).

He goes on to incorrectly state that there is no benefit to donating blood.

There is no benefit in giving a research sample other than “participating” in the research project. 

I have to disagree. There is a lot of benefits to blood donation, in particular with regard to cardiac issues. 

In closing he did provide another good nugget of information:

[he had] wondered if you were referring to the use of plasmapheresis if there is too high a protein level in the blood, thinking it would be similar to donating blood and might explain benefit. He explained that hyperviscosity does not occur in MGUS except for extremely rare situations.

That is good to know. At this point I figured I better just shut the heck up over it. My name was on the e-mails and I don't want to get a "reputation" - I had decided that maybe I just shouldn't donate blood at all.   More in Part 3.

Blood Donation: Part I.

This is raring its ugly head again. Due to my high ferritin level I might want to donate blood again.  The simple fact is that ever since I stoped getting my period, my RBCs, Hemoglobin, etc are frighteningly high. Now my ferritin level is high and, that means, my iron is high. None of that is good. So you might say, well, do you have Hereditary hemochromatosis? I doubt it. First, I did "23 and me" and it didn't have the variants for it.  Second, no one in my family has it. I think it is just that my body naturally is good at accumulating iron and frankly I probably over did it on the red meat. 

Blood Donation has a ton of health advantages that are proven. Benefits of Donating Blood  Lower risk for heart disease. Lower risk for stroke.  Lower damage from blood sugar. More flexible red blood cells. Heck my job will even give me leave time to do it. IMHO this is particularly important to someone like me who has IGM and can have increased blood viscosity. Unfortunately, I am depressed to say that even some of the most esteemed doctors don't know anything about this and deny it (without knowing the facts). 

You might say, well ask your doctor about the high iron / ferritin but my doctor is imho far too liberal with her allowances for my body.  She wants to see massively bad results before she will do anything. A small overage is imho time to act.  I get that sometimes blood tests are off and you shouldn't take action based on one blood test, but, I also feel like all these little damages to my body will result in worse health over years and I have seen issues with high iron before (due to a supplement with it).

Also, I fear that blood donation could make my MGUS worse and no matter how hard I try, I cannot get an answer to this. 

First, I asked my hematologist / oncologist. Not only did that incompetent tell me that it was perfectly fine to donate to other people... BUT her boss, who was covering on the day I asked - the head of the hematology / oncology department - told me it was perfectly fine to donate to other people.  They even put their money where their mouth was by writing me a letter stating it was ok. It was clear to me this was not a scientific pronouncement but both HER and her bosses' - Uninformed Opinion.  This was the first sign I had that these doctors were incompetent.  Needless to say I didn't do that.

So I decided to donate to research. The research company was happy to have my MGUS blood and all was disclosed. They did ask me for a letter to insure that it was safe for ME to donate. (This was the first time it dawned on me there could be a danger) and all was fine. Until I got my first labs afterwards and they weren't fine. 

The problem imho was that my incompetent doctor put in labs for my MGUS without specifying a date when they would be run.  So when I went for labs for something else - 6 weeks after blood donation and months early for them - they were run. I suspect that messed up the results. Causing me needless worry.  My light chains came back high and my M-spike went up.  I suspect now this was because the volume of the blood was decreased slightly making them appear to go up. 

The good news... my numbers have returned to normal - 3 months later - but it still worries me. What if this was a sign that blood donation can cause problems with the donor. 

It seems like that could be the case. As far as I understand MGUS... it is a disease of your hematopoietic stem cells. Thus, when and if your body needs new plasma cells, such as an infection, your body sends out damaged stem cells in greater quantities than normal stem cells. (your body mistakenly selects damaged ones first) Thus you create "clonal cells" with your broken stem cells. Now your body creates new plasma cells all the time so you cannot stop this process, but, it would seem that perhaps you want to limit the "call" for mass creation of new plasma cells: less you simply keep creating new clonal cells.  Just like in a situation where you have an infection, it would seem that donating blood gets rid of a lot of white blood cells, and your body will then say *we need to make new white blood cells" - just like an infection. 

Finally, I asked a Myeloma organization that put me in touch with the Doctor that discovered MGUS... and even though he states that I should be fine, yup, I can't trust what he is saying. More on that in part two.  

Trying to Sleuth Out how this happened: Part two.

Potential #2

Occurred as a result of increased stomach adipose tissue and the increased inflammation. 

I have always known it was dangerous to be overweight in the 40s to 60s age group.  Thus, in 2012 I decided I was going to get thin. I did a liquid diet and, I got thin, I dropped to 155 lbs. The problem, it took me 9 months to do so eating 800 cals per day. And my metabolism absolutely adjusted downward. Through pure will power, I managed to keep it off until 2014 but several jolts to my willpower made it difficult and I quickly added weight. 

2015 I tried again but I realized something was wrong. I was just not losing weight easily. I went to a weight program and had my metabolism tested - 1100. They literally thought the machine was broken. Thus I realized I had to increase my eating to get it up.

So from 2015 to 2019 I did that, and unfortunately I gained most of the weight back. But by the summer of 2019 I had the metabolism tested and my metabolism was back up around 1590. Now the question was, how do I lose it once and for all so that I do not have my metabolism reduce? 

I never got the chance. During my first attempt (time restricted eating) I was diagnosed with MGUS. 

I believe what happened was this:

• From 2016 to 2019 I started down the menopause road and that helped form where the increased weight went (mostly stomach).
• The increased adipose tissue in the stomach increased inflammation and that sustained increased inflammation over years caused damage to my Haematopoietic stem cells.
• During this time I indulged in sugar and sweets - increasing inflammation. 
• In late December 2019 I came down with an extremely aggressive cold of some sort that is highly unusual for me. I had a high fever and cough and it lasted a week.  My body called for new B-cells and the body created clonal cells from the damaged stem cells. 
• Two months later, I was diagnosed with MGUS. It appeared to just have started as almost all other tests came back normal but for the M-spike which was low. .5 g dl.

Evidence Supporting this

1. New research is laying the feet at MGUS and progression at Chronic Inflammation. Obesity causes chronic inflammation.
2. It just seems to me that whatever happened, happened as a direct result of that "illness" in 2019 which was quite aggressive and unlike anything I had seen before, possibly an early version of Covid-19. 
3. My MGUS results are extremely low, suggesting that whatever happened, happened close in time to discovery.

Evidence against

1. WBC seemingly reducing in summer 2018 could have been the reason that the "cold" I caught in December 2019 was so aggressive... my immune system was not as good as pre menopause.
2. Given that my m-spike hasn't moved in a year, it could be that the problem happened far earlier than December of 2019 and I simply do not know it yet. 

To me, this seems like the most likely explanation given what I know about the health of the body. Things usually take a long time to break and many surveys done on the MGUS board tell me that people usually have a LOT more vaccinations than I do... so one random vaccine seems unlikely to have caused an issue. 

Trying to Sleuth Out how this happened: Part one.

I am sure you're asking what does it matter how it happened? Well, frankly because I don't want to make it any worse and if I have a hint how it happened, maybe I can avoid it.

Potential #1

Occurred as a result of a Tetanus Shot (and cat bite) I had in February 2018. 

Why this seems like a possibility.

• Prior to June of 2018 my White Blood Count (WBC) was consistent and normal at around 6.0. And I have a long history to refer to thanks to a medical monitoring diet plan that did CBCs frequently. 
• I always have a bad reaction to a Tetanus Shot. For two days afterwards I have a relatively high fever and feel very bad. This February 2018 was no different. I actually scheduled it on a Friday so I wouldn't need to take time off.  To me this indicates a strong immune reaction. 
• January 2018, my WBC came back at 6.0 so I know that it was normal then. I had the shot in late February.
• June of 2018, it dropped to 5.5... and has steadily gone down since. 

Why this seems unlikely.

• A reduction in WBCs is associated with menopause due to a reduction in reproductive hormones. I had an FSH test (generally a test to tell you if your body is asking for more sex hormones) in August 2017. It was a tiny.. 3.0. And up to that time it was always lower than 7.  But in January 2018 I had an FSH test and, for the first time, it was up around 45. It has never been close to under 20 since that time. IMHO showing that I truly started the process of lowering hormones in Winter of 2018. 
• I have a theory that after you stop bleeding your RBCs increase and perhaps there is "less room" for WBCs in the blood flow and they naturally reduce. 
• My WBC has gone down, but, it is still normal. 

Conclusion: The WBC reduction is a natural change seen in menopause due to less reproductive hormones.  The reduction coincided with indications of menopause and is likely not related to MGUS.