An Alert on Morning Blood Testing - Low Neutrophil Counts & Rapamycin

My default time of day for blood tests is usually early in the morning simply because in San Francisco I find that the local Lab Corp office I go to fills up and the later in the day I go, the longer the wait times (which has been up to 2 hours)…and because I’ve been fasting. So I try to be at the LabCorp as soon as they open (typically between 7am and 8am).

I stumbled upon this, something to be aware of if you are on rapamycin and getting blood tests. I will still likely continue to do morning blood testing, but will do some afternoon ones also to see the variation in certain metrics…

See this paper:

Diurnal variation in white blood cells (WBC), particularly neutrophils, is well-described [1]. WBC levels are lower in the morning and increase through the day [1, 2]. Drugs with immunosuppressive effects, such as sirolimus, may further lower WBC counts. This phenomenon has been observed in clozapine and related atypical antipsychotic medications, drugs with known immunosuppressive effects [3, 4]. For patients receiving these drugs, blood counts measured in the early morning may lead to a false impression of low WBC/neutrophil counts (“pseudoleukopenia/pseudoneutropenia”) [48] that may result in discontinuation or a reduction in dose and suboptimal treatment. Of importance, isolated morning neutropenia is not known to increase the risk of infection [6, 9].

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Very interesting. I’m particularly curious about the “well described” part. I’ve been a physician for 35 years and never heard of this, and never heard another physician say it.

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The reference (1) from that last paper on this point:

Circadian control of the immune system

The term circadian rhythm (from the latin circa diem, which means ‘for about a day’) was coined by Halberg to describe endogenous oscillations in organisms that were observed in approximate association with the earth’s daily rotation cycle1. Circadian rhythms are hypothesized to have evolved in aerobic organisms to anticipate changes of environmental oxygen levels driven by photosynthetic bacteria and the solar cycle2. They present competitive advantages to organisms, by handling energy supply more efficiently and enhancing their ability to survive respiration-associated cycles of oxidative stress. In mammals, it has been estimated that approximately 10% of the genome is under circadian control3, 4.

Over the past fifteen years, evidence for circadian oscillations of components of the immune system has emerged as an integral regulator that has the potential to impact disease onset and therapies5, 6. Recent studies suggest that cyclical recruitment of immune cells to tissues can affect disease. Rhythms in tissues appear to be synchronized globally while acting locally via sympathetic nerves to orchestrate tissue-specific oscillations in the expression of adhesion molecules and chemokines by endothelial cells7. These rhythms are matched by endogenous oscillations in the expression of pro-migratory factors by immune cells, thus increasing the likelihood of their homing to tissues at specific stages in the circadian cycle. Additional data point to the importance of circadian expression of components of the innate immune system for the onset of inflammatory diseases8, 9.

In this article, we review the components of the immune system that have been shown to be oscillating over the course of a day and will discuss the implications of these fluctuations as potential factors in the circadian onset of diseases.

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There is always going to be some compromise as to the ideal time to test. It would be impractical to schedule the ideal time for testing each factor. For convenience, I always have my tests in the morning before 10 am.

The effect on my WBC is quite different. There are of course many variables affecting WBC, but I don’t see that rapamycin has any lowering effect.

I continue to use a number of labs simply because each Lab has its own selection of problems. This involves blood draw ranging from 8am through to 3pm or later.

Apart from the fact that I am always quite low on WBC (which according to Levine is a good thing) it is not really that consistent.

Here are the figures. The first is 2021 and the rest in 2022/3

4.34		3.82		2.71		3.74		3.04		2.97				3.47		2.82		3.32	exercise?	2.57		2.75		3.41		3.4		3.12		3.01				3.01		2.48	query if affected by citrate			3.4		3.2		3		3.5	Rapamycin on 4 Sep	2.31	is this rapamycin?			3.08				2.98				2.58				2.83		2.69		3.2		2.83		2.95		3		3.58				3.62		2.7		2.26		2.32		2.67		3.35		2.7	post rapa taken 10th Jan	2.67		3.37		3.33		4.2		3.23		3.5		2.62		2.7		3.2				2.32				3.1		2.7		3.2		2.8		3.2		3.3		2.6				3.5		3.45		3.4		3.66		4		2.88		2.8		2.62		2.61		2.5		2.4		2.8
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Interesting. Since I’ve been taking Rapa I have noticed that my Lymphocytes have been low and that’s concerned me although I haven’t gotten a cold or flu (other than a very mild bout with Covid). I always do my labs in the morning.

This is important information…and new to me. Thanks for posting this information about the dirunal variation in WBCs.

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I’ve had low WBC counts for a long time, not taking rapa. In a consult with Dr. Gundry, he said it can be an indicator of “leaky gut,” caused by LPS. A search on this brings a number of hits in the integrative health world.

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Spermadine is great at fixing the gut barrier. Also it’s expensive as a supp. Cheddar cheese aged at least 3 years (sharp), pistaccio nuts, some mushrooms, actually the best is BB12 yogurt with added arginine, these are the best foods for spermadine. BB12 converts arginine into spermadine.

Or you could take the chlorella pills. I’m thinking about it.

Good luck,

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Hmmm… My WBC count is 4.9 which is within the range, but much less than @desertshores. If you’re within the range is that bad? I did catch a cold in Japan while the rest of my family did not. Same with the time I caught COVID. Other than that, I feel I’ve been pretty healthy…

Here is Lustgarten’s presentation on WBC for low all cause mortality. 3.5k -6.0k WBC total is LCM

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