#122

How do I know my immnue system is not overly suppressed by rapamycin?
One of things I watch is my NRL ratio of Neutrophils/Lymphocytes. Normal range is 0.78 to 3.5, I think. Doctors? @DrFraser

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#123

Wonder if you have any noticeable benefits though? I ask because I did about over a year, and I did NOT have any benefits that I could attribute to RAPA. I could name over 10 other supplemented where I could specifically attribute benefits to, but not Rapa, as such been doing it only once per couple months or so. I also wonder if the weekly high dose might be wrong way to go.
Maybe it is better to do couple mg’s twice per week?

Is anybody doing smaller doses but more frequently and what is your experience if doing it that way?

#124

I took rapamycin to reduce my joint pains. All the pains on my fingers and shoulders are gone. My psoriasis is almost gone. Do I feel better… hmmmmmm probably not until I lose more weight lol.

I have been on rapamycin since Feb 2024. Initially on a weekly dose… it probably took me 3 months to get the right amount… but did not help since I got the worse brand (Siroboon). I was having 20mg rapamycin with GFJ (+my routine) which gave me a 24 hour blood test of 40ng/mL… and I took that probably for a good 2 months… now with the new Zydus rapamycin, I am reducing the dose to 4mg a fortnight. I will have the blood test results later in the week which I am confident it will not be too high. 2 weeks ago I took 8mg and go a result of 13ng/mL after 3.5 days which is very high.

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#125

I think this is mechanistically wrong in that inhibiting mTOR can improve mitochondrial quality, but if mTOR functions normally there is no particular damage caused to mitochondria.

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#126

My average longevity patient has a total WBC count of about 3K, which is great, irrespective of whether on rapamycin. I like to see lymphocytes higher than neutrophils as this does correlate with better health outcomes. Most of my patients have <60% Neutrophils, but only a few have <50% in regard to the ratio with Lymphocytes.

In regard to the original question, how do I know my immune system isn’t suppressed - check a blood level, my experience is 70% of the time with level <3 ng/mL I’ve not seen any complications - and it isn’t immunosuppression, it is modulation. T cell immunity improves, which is great, as this recognizes malignancies and avoids death/disability from viral illnesses. It will suppress humoral immunity while >3 ng/mL or so, and yes, be vigilent and if one has something that could be a bacterial infection, treat it early.

14 Likes
#127

Does not have to improve it. Only help inhibit cells from turning to cancer. It is strongly believed in literature that Tor inhibition helps delay cancer.

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#128

That may be relevant in terms of cell division.

#129

" how do I know my immune system isn’t suppressed": what ratio of NLR is better then given the preferred lab range is 0.78 - 3.5 per internet?

Per Gork:

  • Rapamycin primarily suppresses lymphocyte activity, particularly T cells, by inhibiting their proliferation and function through the mTOR pathway. This effect can be seen as modulation in lower doses, where it might enhance certain aspects of immune memory while reducing overall T cell expansion during immune activation.

  • Neutrophil function is not directly targeted by rapamycin to the same extent, though it might influence neutrophil behavior indirectly through changes in the immune milieu or cytokine environment.

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#130

Got confused here. My understanding was that in a healthy person neutrophils count is higher than lymphocyte count (to have a healthy NLR under3). My NLR is 2. Am I wrong?

#131

My NLR (15 years on Rapa) is 2, which is healthy. My WBC are usually 3.9.

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#132

Frankly, I don’t understand why a healthy 20 year or even 30 year old would want to use rapamycin…

The same reason anyone else here would want to use it—slowing the aesthetic and functional changes associated with aging. Does every piece of data support taking rapamycin from a young age? No. That said, it still seems riskier to not take rapamycin.

Sure, you could stick to exercise, eat clean, socialize, avoid environmental toxins, manage stress, etc, but to me those things go without saying. And they aren’t going to move the needle past the existing lifespan limit anyways.

7 Likes
#133

@LaraPo would be a better N than BJ having on Rapa for 15 years. What are your overall take rapa as a long term user?

N = Neutrophil (innate) L = lymphocytes (acquired and innate)
Rapamycin mainly affect Neutrophil (?) @DrFraser

As to NLR , my understanding per Gork is you want your L higher than R but the ratio between 0.78-3.5 is considered normal.
And FWIW, my own blood works has shown little change in lymphocytes over the course of rapamycin, but my neutrophil to some degree is a function of rapamycin dose (suppressed lower but still normal). Hence, I monitor the trend and ratio of my NLR as a way to gauge my rapamycin dosing.

#134

He is supposedly worth $400 million, I can’t imagine he needs to shill for any company.

2 Likes
#135

No the opposite, here is the data, want lymphocytes to be close to neutrophils, even better if they predominate.

The neutrophil-to-lymphocyte ratio (NLR) is an emerging biomarker that has gained attention for its potential role in predicting longevity and overall health outcomes, particularly in older populations. The NLR is calculated by dividing the absolute neutrophil count by the absolute lymphocyte count in peripheral blood, serving as a simple and inexpensive marker of systemic inflammation.

Higher NLR values are generally associated with increased inflammation, which is linked to poorer health outcomes and reduced longevity. In contrast, lower NLR values are typically associated with better overall health and potentially increased longevity. This is because chronic low-grade inflammation, as indicated by higher NLR, may contribute to accelerated aging and age-related diseases
2
.

Research has shown that elevated NLR is associated with increased mortality risk in various populations, including healthy individuals and those with chronic diseases. A meta-analysis found that higher NLR was significantly associated with all-cause mortality and cardiovascular mortality in the general population. This suggests that NLR could be used as a marker to identify individuals at higher risk of age-related diseases and mortality
1
.

In the context of patients with lower-extremity artery disease (LEAD), NLR, along with nutritional status indicators like the Controlling Nutritional Status (CONUT) score and the Geriatric Nutritional Risk Index (GNRI), has been associated with two-year longevity outcomes. Higher NLR values, alongside poor nutritional status, were linked with worse outcomes, emphasizing the relevance of these factors in prognostic assessments in elderly patients
1
.

Furthermore, research on centenarians suggests that immune function parameters, including those linked to neutrophil activity, could predict survival. Surviving centenarians demonstrated higher neutrophil chemotaxis and microbicidal capacity, indicating that efficient immune responses may contribute to longevity
3
.

Overall, the NLR serves as a valuable, non-invasive marker for assessing inflammation and predicting health outcomes in elderly populations. Its integration with other clinical and nutritional assessments can improve prognostic accuracy and guide interventions aimed at enhancing longevity and quality of life in aging individuals.

References

  1. Association Rules Mining and Prognostic Stratification of 2-Year Longevity in Octogenarians Undergoing Endovascular Therapy for Lower-extremity Arterial Disease: Observational Cohort Study.
    Journal of Medical Internet Research
    Jhang et al.
    6 citations
    2019
    This study demonstrated the association and crucial role of MIS factors in assessing 2YL in elderly patients with LEAD and showed the interrelationships between neutrophil-lymphocyte ratio (NLR) and nutritional status, determined by the Controlling Nutritional Status (CONUT) score or Geriatric Nutritional Risk Index (GNRI), with 2YL.

Open Access
Influential Journal
Show more
2. Neutrophil, lymphocyte count, and neutrophil to lymphocyte ratio predict multimorbidity and mortality—results from the Baltimore Longitudinal Study on Aging follow-up study
GeroScience
Pellegrino et al.
3 citations
2024
This study supports the importance of the NL ratio and absolute neutrophil count as markers of aging health status, and as significant predictors of all-cause mortality and multimorbidity in aging individuals.

Open Access
Influential Journal
Show more
3. Immune function, oxidative and inflammatory markers in centenarians as potential predictors of survival and indicators of recovery after hospital admission.
The journals of gerontology. Series A, Biological sciences and medical sciences
Toda et al.
7 citations
2020
Results show that surviving centenarians display higher neutrophil chemotaxis and microbicidal capacity, NK activity, lymphoproliferation, glutathione reductase activity and basal IL-10 release, and these parameters have the potential to be used in the clinical setting as predictors of survival in centenarian.

Open Access
Show more

@Jonas The issue with that reference is that it relates to daily use of rapamycin, a very different thing than we are doing here. So long as you are doing cyclic rapamycin, and not at an absurd high dose, I don’t see a reason to have concerns unless you actually manifest symptoms of poor immunity (repetitive bacterial infections, getting ill and ending up in hospital with viral respiratory infections, for example).

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#136

Not exactly, bc I take Rapa after kidney transplant.

1 Like
#137

I was referring to NLR as in Neutrophiles-to-Lymphocytes Ratio. My point is that to get a healthy ratio (under 3), neutrophiles have to be higher than lymphocytes. And @DrFraser stated that he likes to see lymphocytes higher than neutrophils in his patients. I was confused about it.

#138

We need a prime on how each of those interact with each other and by rapamycin.

Here is a Gork summary which may not be entirely accurate.

Screenshot 2024-11-17 at 8.26.51 AM
Screenshot 2024-11-17 at 8.26.51 AM1198×1332 158 KB

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#139

Correction:

  • Neutrophils (N) - Innate

  • Lymphocytes (L) -

    • T cells and B cells - Adaptive or Acquired

    • NK cells - Innate

#140

These are my numbers per October bloodwork:

image
image1215×2188 204 KB

1 Like
#141

Got your point. Thanks.