I am finally done with Keto.

Since the start of the pandemic I have been heavily invested in Keto and fasting. What captured my interest was the book, "Anyway you can" which was about someone who had Leukemia going on a Keto diet and dramatically improving her numbers. And, to be frank, I could see amazing improvements on my numbers in the short term. My liver and kidney health is good on Keto. For the three years I have been doing Keto and fasting my M-spike has not progressed and the other factors have remained stable.  I also lost 40 lbs... but gained it back. 

But there was a massive problem.

Fasting (or more properly) being in Ketosis... has sent my HS-CRP and some other inflammatory factors through the roof.  Cholesterol too. But I could almost immediately lower it by eating carbs or being in mild ketosis.  Finally this week I had it... I tested again after two short weeks of being in Ketosis and my HS-CRP was through the roof and my cholesterol was massively elevated. 

I suspect that these two things will, some day, turn out to be harmless. However, I can no longer keep potentially damaging myself this way. 

This does not mean that I am going back to HFCS or going to eat a ton of carbs. After all my Metabolic Health is strong. I have a low A1c - 5.3% and I have a low C-Peptide.. at 1.2.  It does not mean that I will not be careful with sugar. It doesn't mean I will not lose weight. But, I will go back to the calorie counting model and have more *good* carbs. My diet I will be aiming for low carb. Not Keto. 

Of course, decided to test my IGM.

Because my doctor decided that I only needed to be seen every year I decided to test my IGM as a short cut way of making sure I was not progressing during this time. 

To my shock and horror... my IGM came back at 316.

That is the highest I have ever seen. In fact, for over three years my IGM has only, and I mean ONLY, been anyplace from 240 to 270. NEVER above 270. 

At the same time, my only other high blood test was HS-CRP. So I do know I have inflammation hanging around, but I think it is "acute" inflammation because my Ferritin is not high.  So it is possible the IGM is higher because of inflammation and or infection. 

But that was it... I decided I need to be seen 2x per year and I need to know what my m-spike is right now. So I called up Dana Farber and got an appointment for next week.

I suspect I know what is causing the inflammation and I will cut that out and get my tests next week. 

I hope that it is inflammation / infection but I am scared it isn't. IGM has been creeping up more and more every time I go and there were more 270s than 240s. 

Another interesting study - Fatty Bone Marrow causes CP.

In 2021 a study came out that honed in on how blood cancers basically begin, suggesting that inflammation messes up the creation of blood cells and causes clonal hematopoiesis. Good to know, and I then concentrated on reducing inflammation and weight loss. 

For me though that confused me.  I am overweight but have had very low inflammation markers and do now.  Well,  just got another piece of the puzzle. 

Inflammatory signals from fatty bone marrow support DNMT3A driven clonal hematopoiesis

https://www.nature.com/articles/s41467-023-36906-1?fbclid=IwAR3ichvOW0E-AzcHIWRLrNSLRzzBk3NU0V5SPo_js4QCBcMz_H_i61C3V0s

This study basically suggests that we have "fat" in our bone marrow. Who knew that? And that there is such a thing as "fatty" bone marrow - like fatty liver.  And it is THIS fat which puts out the inflammatory signals corrupting the bone marrow.   So you see your overall body could be relatively low in inflammation - and not really make a difference to your bone marrow. 

The accumulation of FBM with age is ubiquitous, however, large variability exists in its extent58. Epidemiological studies suggest that several factors can explain this high variability including: the age-related decline in renal function, increased body mass index (BMI), andropenia and menopause. Interestingly, FBM continues to increase steadily in males, while in females it increases dramatically following menopause. This phenomenon might be related to the rapid estrogen deficiency during menopause as oppose to the gradual decrease of testosterone in males. Previous studies demonstrated enrichment of DNMT3A mutations among females. The sharp increase in FBM during menopause could suggest that it is the dynamics of FBM accumulation that shape CH rather than the actual FBM mass. Interestingly, a recent report suggested that DNMT3A mutations were significantly associated with premature menopause.

So we see that the increase in fatty bone marrow is essentially a side effect of menopause and reduction in estrogen. And my MGUS started after menopause. However, it can also be contributed to by a decline in renal function (guessing this relates to sugar), increased body mass index (likely insulin resistance). 

The study concludes with 

Based on the results presented here, it is becoming clear that FBM is more than just hypocellular marrow, and that it can shape CH evolution and contribute to other adverse metabolic effects. More research could be directed toward the prevention of FBM accumulation and its interaction with other mutations and with human HSCs. With the ultimate goal of correcting the very first steps in leukemia evolution and aging.

I completely agree. I wonder if we could reduce the FBM by increasing estrogen. HRT might be an option but I still worry about that for other cancers... but perhaps just changing the foods we eat and increasing estrogen slightly could assist.  Though I am hesitant to take any action until we know for sure. To me it doesn't make sense that your body would essentially "screw" you in this way at Menopause. I have a feeling that it could simply be related to massive weight gain at Menopause in a great number of women. And perhaps fatty bone marrow, like fatty liver, could be drastically reduced eating less and eating less sugar / reducing insulin. Fatty liver is caused by

Too much refined sugar and high-fructose corn syrup causes a fatty buildup that can lead to liver disease. 

Does it not make sense that another fatty build up could be caused in a similar way? Your body has to find places to put the fat as you keep showering it with sugar and the mere fact that it tends to happen at menopause could be related to a lowering of the metabolic rate while not lowering the level of food. 

This seems to be a very promising study. 

Update: my M-spike went away.

So at my December 2022 Dana Farber appointment I was stunned and very happy to get this result...

Protein Electrophoresis:

-Immunofixation shows a faint M-spike that is not apparent on the

electropherogram and, therefore, cannot be quantitated.

Now I know, a previous doctor already warned me, the electrophoresis is just an interpretation and not an exact value.  So it might show up slightly more more or slightly less depending on the judgment of the person looking at it.  And I know... plenty of people on the MGUS group have had the Mspike go away and come back. 

But, this is the first time in 3 years that the spike could "not be quantitated."  I feel like this means progress.

My light chains are still slightly high and my IGM is also slightly high. But I would imagine it would take time to clear if the clone went away. 

I guess we will see. My doctor doesn't want me coming back for a year but I am still planning on getting IGM tests every 4 months to make sure that isn't increasing. 

Fourth Visit with Dana Farber: Great Results

So it is going on just about 2 years and four months and, so far, my numbers are quite stable. 

My M-Spke: is basically from 0.2 g/dl to 0.28 g/dl. It bumps around a bit but never really goes into the 3s.

My Light Chains are going down... so excited by this. All last year they were going up... and now... they are back in the normal range. 

My immunoglobins... same deal. Last year was heading up.. but this year... almost normal. 

Knock on wood. My doctor is now seeing me every 6 months. 

New Study Showing BMI correlates with progression

One of the issues with MGUS is that it is new and there is not a ton of good studies... so we have a few studies that contradict each other. One seemed to have suggest that being overweight was a risk factor for MGUS progression. One said the opposite. 

Now we have a new study supporting increased BMI with progression.

https://pubmed.ncbi.nlm.nih.gov/35440099/

In conclusion, high BMI is a prognostic factor for MGUS progression, independent of isotype, M protein, and FLCr. This association may be stronger among females.

This study does, imho have a number of problems. 

1. First it is just an association with Body Mass Index? We have no idea if Body Mass Index is the issue OR... something else that may lead to high Body Mass Index. Such as Insulin Resistance or Diabetes.
2. It doesn't give a good measure as to how high the BMI needs to be to cause a problem. For instance, my BMI is 27. I am just slightly overweight. I have a feeling that isn't as dangerous as someone who say is at 30.
3. The data was from long ago.... 1995 to 2003, which was the height of high sugar guidelines.
4. It seemed that most of the patients died during the time period... so, this suggests that the MGUS patients were all older. And we know with age the immune system fails... was that the true cause of progression?

Nevertheless, it is well established that more weight leads to more inflammation and more inflammation leads to more MGUS. So, I have to get my BMI down to 25.

Inflammation appears to be the cause of my MGUS

People ask a lot "what causes MGUS?" and I think that has a different answer for everyone. 

1. Family History: There is no doubt that if you have family history of blood cancers or MGUS, you are at a higher risk.
2. Auto Immune: There is absolutely a link with auto immune and MGUS. This would seem to be due to the constant antigen stimulation of the body. 
3. Environmental: clearly survivors of the 911 attacks and people exposed in the military etc are in danger.  Some people who are exposed at work, handymen / construction.
4. Obesity: There are many studies on the books that show that obesity is a risk factor. 

So when people say, I am thin and I have MGUS... well of course... you can have it for reasons other than being obese.

For me, there is only one thing that I can see as being the cause of my MGUS... that appears to be obesity / inflammation.  I have no history of blood cancers in my family (or MGUS), no auto immune, unlikely to be the environment as I am very careful... but I have been obese... and for the years leading up to my diagnosis... I was eating like a pig.  

In 2012 I did a liquid diet and got down to 155. But I was STARVING and I couldn't lose any more weight. I realized... I had done a biggest loser and had no choice but to restore my metabolism. This took a lot longer than I expected. I quickly got back up to 217... but my metabolism was low (I had it tested). So for 8 years I was shoving food in there daily to try to wake my metabolism up.. and also try to figure out how to lose the weight without falling into the trap.  The plan was to start dieting before I hit 50. And I did that.. at 49 I started fasting.  But within just a few weeks, I was diagnosed with MGUS. 

I didn't realize the effect this was having on my body and perhaps... this period of obesity coming during menopause.. (or peri) didn't help.

I don't have a ton of blood tests (yes doctors for some reason didn't care) but I have some results from when I was younger and thinner and those were not the results I had the first time I started testing my inflammation makers. 

It is my belief that inflammation is both cause and way to avoid progression. It is the driver of the disease.. so everyone can benefit from a reduction.