Could ypu give us the math behind 11 - 17 donations of 800 ml twice a week equalling one 2000-3000 ml dilution?
I threw the paper out where I did the calculations last spring. I no longer know what I used as starting numbers and I’m certain I was unclear on how plasma volume scales with body weight. It must because for persons 175lbs and greater they take an 800 ml donation, for those in the 150-175 lbs range it is 750 ml, and 110 - 150 lbs is 625 ml. But, the idea went something like this.
Estimate total plasma volume is 2.75 liters. The phlebs take 30% (800 ml). You need to replace/remove 90% of the old plasma to be the equivalent of one of the Conboy dilution treatments. Your body can keep up with replacing that much plasma at the twice in 7 days donation rate.
Visit 1 - 30% old plasma gone, 70% old plasma remains
Visit 2 - 30% existing plasma taken. That’s 0.3* 0.7 of the old stuff and 0.3* 0.3 of the newly generated. Now 1-0.3- 0.3*.0.7 old plasma remains (49% old plasma).
Visit 3 - 35% remains (49% -0.3*49%)
Visit 4 - 25% remains
Visit 5 - 18% remains
Visit 6 - 13 % remains
Visit 7 - 9% remains - Victory
So, my memory may be off and it seems like it was probably 7 -11, not 11 to 17. Obviously the estimate for total plasma volume is going to strongly influence the percentages as is your donation size.
Scheduling, not getting turned away for high pulse or low protein, etc. means getting those 7-11 in within 4 - 6 weeks is pretty tough. At least for me it is.
In Australia it’s once every 2 weeks.
I’d be careful…
“ Repeated plasmapheresis with albumin replacement will deplete a patient’s reserve of immunoglobulins for several weeks, and this, combined with complement removal, could result in an immunodeficient state.”
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There’s some fuzziness on what volume is removed by TPE but I think it is on the order of 2/3rds of total plasma volume. That is because you are continuously removing plasma and replacing with blood cells and saline (and anti coag). My plasma volume is about 3 liters (average of two methods). Conboy’s animal experiments did 50% replacement and saw positive effects. In any case, if you look at the graphs and heat maps in the paper you can see clear changes after one or two TPEs. R0 is before the first TPE. If you donate in the US at a regular blood bank they will take 800 mls of plasma (for 175 lbs and over) every 4 weeks. This is plasma-only donation, not whole blood which has only about 250 mls of plasma per donation. There are plasma-only donation centers (CSL Plasma for example) which will take 2 plasma donations every week. In any case, you can do plasma donation and test blood markers like DNA damage and immune cell markers to check effects. In a year’s time one could donate approximately 3 to 4 plasma volumes. Free.
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When I went and did my series of 6 TPE treatments they said the target was around 90% of total plasma. Details here: Plasmapheresis Startup Looking for Clinical Trial Participants SF Bay Area
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Actually to look only at plasma volume is to miss some of the picture. There is a lot of fluid in between cells which drains into the circulation system. Being in close proximity to any senescent cells the fluid will be carrying progeroid factors. So, after plasma removal, the progeroid factors will be partly replaced by extracellular fluid. This explains why several rounds of plasma exchange are advised.
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Yes. I have been trying to understand the interplay between blood plasma and interstitial fluid. And, for example, what affects sweating might have on both. There’s some evidence that sweating will remove certain toxins suggesting (pure speculation on my part) that chronic sauna use or exercise which promotes sweating might help remove some of the negative proteins/metabolites that plasma donation does. In any case, for the older among, us routine removal of old plasma (optimum volume and frequency unknown) might have significant positive long term effects which would not be obvious over the course of a few weeks or months. And part of this effect could be, and it makes sense to me, the effect on interstitial fluid.
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I think oddly enough the key cytokine is il-10. There was a phd thesis that did not get into a journal that showed il10 created senescence. Noting senescence is patchy it seems that a lot of progeroid tranafer is very local.
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Hmmm. That didn’t come across as very sensible.
“So, after plasma removal, the progeroid factors will be partly replaced by extracellular fluid.”
Should have read that the “plasma will be partly replaced…”
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Chronic sauna use could cause a lot of things (including dehydration!) However, as no Finns feature in the current list of Supercentenarians (and very few are documented at all) I doubt that lifelong sauna use has ANY effect on longevity.
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I’ve donated about 20 liters since mid '21, not always on a 4 week basis. My blood work continues to look good except for a one time dip in ferritin, which went way too low. Albumin drops a bit after each donation but quickly recovers. All other marker in a basic CBC and CMP panels are good or very good. Conboy’s work has some gaps which they acknowledge, such as how long the effects last, and what volume of plasma removal is needed in one exchange (i.e is there a threshold effect). The animal NBE experiments were with 50% plasma loss and still saw effects with one exchange. Rob Flickenger posted a very small human study (2021 “Plasma donation induces a protein expression
profile shift in circulating human blood”) mimicking 800 ml plasma donation which seemed to show many of the same proteome changes the Conboys showed in their 2020 paper. But routine plasma donation is likely (not guaranteed) pretty safe as it is FDA approved and been used for many years. My blood bank limit is about 13 liters per year of plasma based on FDA regs. Also, we should be doing routine blood work along with any intervention. Some of the markers (DNA damage etc) in the 2022 Conboy paper may good to add to routine CBC and CMP.
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I used two methods to estimate plasma volume plus just general knowledge of the amount of whole blood someone my size (175 lbs) will have and came up with an estimate of roughly 3000 mls of plasma (a bit over 50% of whole blood volume). So a 50% exchange would be about 1500 mls. When I donate plasma, 800 mls a month, I can be reasonably confident I’m losing 25% of my old plasma. My albumin comes back to normal very fast, within a few days, based on lab work.
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Donating whole blood will rapidly reduce iron stores (ferritin) as you probably know. My blood bank (florida) is most in need of platelets and some plasma, so I donate both and rarely donate whole blood anymore. Platelets, I’m told, go preferentially to cancer patients and can only be stored a few days. For either platelets or plasma donation they also take about 50 mls of whole blood to test for various pathogens/toxins so over 9 to 10 donations you also give the equivalent of one whole blood donation, so ferritin will also go down. Either way, I 've found it helpful to check my ferritin level at least 2x/y to ensure its low but not too low. BTW, with single platelet donation, which can be done up to 24 times a year, you also loose about 270 mls of plasma, roughly the same as a whole blood donation (a bit over 50% plasma by volume) which can only be done 1x/8 wks. They will also do a double platelet or a platelet+plasma. All of these involve varying amounts of plasma lose, with plasma-only being highest volume, so it’s fairly easy to turnover at least 2 plasma volumes each year in addition to unloading toxins and Fe.
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@Peterz54 Yes, lowering my iron is my goal. I will watch for low iron. Thanks. I am able to give whole blood every 52 days (I think). I think you are saying I can give platelets (vs whole blood) more often and turn over more plasma?
@Joseph_Lavelle Yes, you can give platelets much more frequently. And plasma as well. Each of these involves a little whole blood lose as well. You can design your own regime. There may be delay (8 weeks) on all of these after whole blood donation, but otherwise you can donate fairly frequently. Each single platelet donation will result in a similar plasma lose as a single whole blood donation, so over the course of a year you loose about 4 times as much plasma donating platelets vs whole blood. You can increase plasma lose een more by doing platelet and plasma donations.
Your donor facility can help you sort out optimum schedule. Only downside is that it takes a little more time to donate plasma or platelets than whole blood.
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Ferritin is interesting. AIUI generally a lower level of Ferritin is preferable.
I do weekly blood tests which is perhaps 10ml to 20ml of blood. One lab uses 5 vials some of which are 4ml and some 5ml. Hence over a year that is 0.5-1 l of blood.
I wonder if that is behind my ferritin levels going down (although they vary week to week).
For anyone interested here they are:
420 337 358 329 332 404 371 412 325 204.6 364 202 337 176.2 176.2 319 172.9 205 253 205 145 175 157.9 165.7 171.4 190.9 180.4 173.4 222 176.7 ng/ml 298 291 mgc/L 202.5 187.8 174.9 140.4 155.4 170.5 123.2 150 152.6 147.6 168.7 177 201 165 203 168 165 164 154 142 ng/ml 164.16 129 126 134.42 118 116.07 115 120.45 96 going down? 102.5 93 79.02 95 122.54 166 109 95 115.63 161 112 105 97 110 96 99 112 92 68.3 99.5 103.21 96 101.3 108 93
I find it curious how they can vary a lot from test to test although they have trended down quite a bit.
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Every lab test will have different precision, so it’s not surprising to see some variability, although some of the swings are fairly large (your lab can clarify this). Also, not surprising to see some reduction in ferritin over time due to whole blood loss, but the magnitude of reduction is not in proportion to your whole blood loss. Much larger drop. There may be a reason for this, but don’t know why at this time - will have to check on expected ferritin change per unit volume of blood loss. As for the optimum level, I also need to revisit this issue, but I look to stay below 100 ng/ml and above the lower end of reference range (about 30 ng/ml). I have been as low as 7 ng/ml after a period of whole blood donation. Now I take a small dose of iron (via supplementation) for a few days after each donation, whatever donation type. Supplementation keeps me around low end of reference range. My diet is mostly plant based (a little fish) so I get very little heme iron via diet. I suspect the upper end of the lab reference range is way too high, but it’s time to revisit optimum ferritin levels
I would tend to agree that the drop is a lot more than would be expected merely as a result of a blood loss of 0.5-1 litres per year. I have not studied this in any detail, however,
I think there is a background metabolic issue that I have changed that is affecting ferritin levels.
I think that is a positive symptom, but I don’t know the details.
I do have good evidence that my attack on failures of transcription of mRNA (mainly through increasing cytosolic acetyl-CoA levels on a cyclical basis) is hitting a core gero pathway. This is not just from me but anecdotally from other people following the protocol.
In the US, there are two types of plasma donation rules. For bloodbanks which collect whole blood, platelets, or plasma for patients the plasma donation frequency is limited to no more than 1x/4 weeks. Other donation centers, like CSL plasma, collect plasma which does not go to patients, but to develop products, and they can take 2 donations per week. I am not clear as to why the FDA has two standards though. For blood banks we have a 13 liter per year limit which for me is about 4 plasma volumes. I used CSL plasma once but they are an hour away and it was crowded with people looking to get their cash for donating - much more convenient to use my local blood bank.