Still really tired on day 2, but I could drink coffee enough to at least keep my mind alert
But I still need to lie down most of the first few hours damnit
Retatrutide is roughly 2x as expensive as tirzepatide. Tirzepatide is cheaper per MG.
The starting dose is 2.5mg (not 5mg) , the therapeutic dose range is 5-15mg.
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I’m reducing my dose from 3mg to 1.5mg because my appetite is a little more suppressed than I’d like it to be. I divide my dose MWF by the way.
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Not where I come from 
$1 per mg difference
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I just asked AI about Ivabradine since it was previously discussed for lowering heart rate on GLP1’s. Sounds like it is not a good idea to use if you’re healthy. Seems to be similar to beta blockers (aside from Nebivolol since it boosts NO) in the sense it reduces exercise capacity.
Verapamil (CCB), on the other hand, does not. However, I already have borderline low blood pressure so I avoid it.
Tag @Davin8r
Ivabradine significantly worsens cardiovascular fitness in healthy individuals by reducing peak oxygen consumption and submaximal exercise capacity.
- A randomized, crossover trial in Circulation I demonstrated that ivabradine reduced peak heart rate (127 vs. 145 bpm; p = 0.003) and significantly worsened peak oxygen consumption (O2 peak) in healthy volunteers compared to placebo (p = 0.003).
- Relevance: This study directly assessed the impact of ivabradine on exercise capacity in asymptomatic individuals, making it highly applicable to healthy populations.
- Rationale: The reduction in O2 peak and submaximal exercise capacity indicates that ivabradine impairs cardiovascular fitness, which is critical for healthy individuals who rely on optimal cardiac performance during physical activity 1.
Ivabradine increases the risk of serious adverse events, including bradycardia and atrial fibrillation, which can further compromise cardiovascular fitness in healthy individuals.
- A systematic review and meta-analysis in Open Heart I of 47 randomized clinical trials (35,797 participants) reported that ivabradine increased the risk of serious adverse events (RR 1.07; 95% CI 1.03 to 1.11) and non-serious adverse events (RR 1.13; 95% CI 1.11 to 1.16).
- Relevance: Although the primary focus was on patients with angina, the increased risk of adverse events is relevant to healthy individuals, as these side effects can negatively impact overall fitness and safety during exercise.
- Rationale: The high risk of bias in the included trials limits the certainty of these findings, but the large sample size and rigorous methodology provide valuable insights into the safety profile of ivabradine 2.
Ivabradine does not improve quality of life or exercise capacity in healthy individuals, and its use should be reconsidered in this population.
- A systematic review and meta-analysis in BMJ Evidence-Based Medicine I of randomized controlled trials (RCTs) reported no significant effects on quality of life or exercise capacity, but an increased risk of atrial fibrillation (RR 1.19; 95% CI 1.04 to 1.35; p = 0.008) and bradycardia (RR 3.95; 95% CI 1.88 to 8.29; p = 0.0003).
- Relevance: The findings are directly applicable to healthy individuals, as the lack of benefit and increased risk of adverse events highlight the potential harm of ivabradine in this population.
- Rationale: The high certainty of evidence for adverse events strengthens the recommendation against using ivabradine in healthy individuals 3.”
“Verapamil does not worsen cardio fitness in healthy individuals; instead, it may improve aerobic exercise performance, particularly in elderly populations.
-
A randomized controlled trial (RCT) published in the Journal of the American College of Cardiology I demonstrated that intravenous verapamil improved aerobic exercise performance in healthy elderly individuals by reducing ventricular-vascular stiffening 1.
- Rationale: This study is highly relevant as it directly assesses the impact of verapamil on exercise capacity in a healthy population, providing strong evidence that verapamil does not impair, and may even enhance, cardio fitness.
-
Another RCT in the same journal I found that acute intravenous verapamil improved aerobic exercise performance in healthy aged individuals, highlighting its potential benefits for exertional limitations 2.
- Rationale: The study’s focus on healthy subjects and its publication in a high-impact journal underscore its importance in addressing the question.
-
A prospective cohort study in Circulation I reported that verapamil selectively enhanced left ventricular diastolic filling in middle-aged and elderly subjects without affecting systolic function 3.
- Rationale: This study is relevant as it provides insight into the mechanisms by which verapamil may improve exercise capacity, particularly in older adults.
In summary, verapamil does not worsen cardio fitness in healthy individuals and may improve exercise performance, especially in the elderly, by enhancing diastolic function and reducing ventricular-vascular stiffening.“
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Energy mostly back after T+2 days (and coffee), still can mostly only eat soft foods (like shirataki rice or life alive’s, can’t eat nuts or beans)
But I think is the best outcome [the first time I did it ~a month ago I had weird side effects like “naval tingling”]. Now it’s that I am too tired to do things for 1 day.
No weight loss either, tho I’m not looking for that. Just less food is good enough.
Good find! Glad I never bought or tried ivabradine. My overnight RHR does finally seem to be decreasing (mid 60s now, whereas for months it’s been 70+). Either I’m finally adapting or it has something to do with the magnesium taurate I’ve started taking at bedtime. Regardless, I no longer notice the increased HR and I’m not really focused on it. I just wish it didn’t continue to tank my Oura Ring readiness/sleep scores since Oura still is using my pre-GLP RHR from a year ago as my “normal” (53-55 BPM), which is annoying.
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Timing of Tirz or Reta and Rapamycin: If you’re taking Rapa and shots, do you find the timing matters?
I recently started Tirz at 1 mg on Saturdays, but when I then took my usual biweekly Rapamycin I felt pretty rough. Could be coincidence? Was thinking of pushing my Rapa does to Wednesday to avoid this.
How do you take a glp1 when rapamicyn raises glucose levels ?
Im stopping Ivabradine to see if my cardio fitness feels any better.
Thats great your RHR came down. Must be doing something right.
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Honestly the thought of them interacting never once crossed my mind. I really doubt it matters or what you describe is related. It’s certainly never been studied.
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Yes it might. I think taking rapamycin a few days before GLP1 agonist is a good strategy. GLP1 agonists surprisingly activate mTOR in certain ways, but it is beneficial the way it does it.
They might additively combine well, or they might partially cancel each other out. Until we know for sure I personally do not use them on the same day.
Read a summary of a study I did on GLP1s and longevity here: Study behind paywall, can anyone find the full study? "Unlocking longevity with GLP-1: A key to turn back the clock?" - #10 by AustraliaLongevity
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I assume you mean ‘why’ not ‘how do you take’ because I take it as an injection. only 5% of people have glucose issues as a side effect of Rapamycin Side Effects of Rapamycin (part 2)
If one does, surely that would be an excellent reason to take a GLP1 RA with Rapa, in addition to all the other health benefits of GLP1.
In fact my glucose was disregulated BEFORE I started taking Rapa and has continued to be. Tirzepatide has brought it down significantly.
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Now I’m feeling the ideal level of appetite loss and more energetic but I still have been sleeping more than ideal.
Retatrutide has way better side effects than semaglutide which is way more important if you don’t intend to take these things weekly. I’ve had vomiting on semaglutide (and the appetite loss from semaglutide disappears in 2-3 days).
It’s nice to not think about food so much and to only need one real meal a day and also only to be able to eat soft foods. I feel dumb for not doing GLP-1’s more last year due to side effects, but [given some of my sub-ideal blood panels - btw canagliflozin does not seem to have helped, but I try anyways] I know I have to do them more.
None of the fatigue from the first time (I injected too much the first time, was underwhelmed the second time, the 3rd time was only a bit over 2mg)
even posted this in a signal thread and there looks like there are A LOT more people in that post-rat community who are doing retatrutide, off-hand
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July 28: a conference day! and I still feel so full that I could only eat small handfuls of conference food (like, just one hummus sandwich). and then some harissa sauce at the end. I love my reduced appetite so much.
5 days since injection and still feeling full! semaglutide never gave me this privilege
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July 29: 6 days since injection, appetite gone for first half of day, but I could ease into almonds for once, and then could eat a little bit more salad/avocado/chipotle sauce at pillar.vc event than I could on previous days, tho beans are still hard
[i think 6 days in after 2.5mg injection is what i’d like to feel like ALL the time]
Wow, but when your appetite returns after the 6.5-ith day… IT REALLY RETURNS…
Try half that dose, twice a week.
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Ok
But each injection is an exposure route fpr MPs
Appetite mostly gone today
My lymphocyte count is 1.1, unusually low. Neutrophils higher
Still haven’t lost weight, maybe half a pound
Oh I had low RBC TOO
Short answer
Neutrophils bounce back first. Within ~24 h of re-feeding, circulating neutrophil numbers and most functional read-outs (chemotaxis, oxidative burst) are already at—or very close to—pre-fast levels, whereas lymphocyte counts do not fully normalize until several days later. So after one day of eating again following a week-long fast you can expect your neutrophil compartment to look almost “recovered,” while your lymphocyte compartment will still be climbing back toward baseline.
Why neutrophils recover faster
| Feature | Neutrophils | Lymphocytes |
|---|---|---|
| Normal half-life in blood | 6–18 h | Days → years depending on subset |
| Bone-marrow reserve | Large pools of mature cells ready to demarginate | Far smaller reserve of ready-to-circulate cells |
| Signals triggered by re-feeding | Insulin, IGF-1, mTOR and above all G-CSF rapidly mobilize marrow neutrophils | IL-7/IL-15 driven homeostatic proliferation plus chemokine-directed “re-export” from bone marrow and lymphoid tissues—slower processes |
| Human data after short fast | Chemotactic index, H₂O₂ production and numbers back to baseline within 4 h of re-feeding in young adults | Lymphocyte subsets did rise with feeding but were still significantly below pre-fast values over the same interval |
| Animal data after longer fast / CR | Neutrophil counts surge within 24 h of re-feeding (demargination + production) | Global lymphopenia reverses inside the first week, not the first day |
Physiology behind the time-lag
-
Neutrophils
- A one-week fast diminishes circulating neutrophils chiefly by pulling them back into marrow and by slowing granulopoiesis.
- Re-feeding causes a spike in glucose, insulin and IGF-1, turning mTOR back on and raising G-CSF. Those signals trigger (i) demargination of the sequestered pool and (ii) release of band and segmented neutrophils that were already mature in the marrow. Because their maturation pipeline is only ~5 days long, many “near-mature” cells are immediately available.
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Lymphocytes
- During fasting, T- and B-cells redistribute out of blood to bone marrow and secondary lymphoid tissue to save energy. Proliferation stalls because IL-7/IL-15 and mTOR activity fall.
- When calories return, chemokine gradients reverse, but re-export plus renewed homeostatic proliferation take several cell cycles (2–4 d minimum). Mouse work shows full repopulation of blood, spleen and lymph nodes by about day 3–7 of ad-lib feeding after a prolonged calorie deficit.
Practical implications
- A single day of normal eating will nearly restore innate antibacterial defenses (neutrophils), but adaptive immunity (T- and B-cell–mediated responses, antibody production) may still be transiently below par.
- The kinetics are slower in older adults: in the Walrand study neutrophil chemotaxis rebounded in young adults after 4 h, but remained depressed in the elderly after the same meal .
- Big swings in calories/weight can transiently skew the neutrophil-to-lymphocyte ratio (NLR). If you draw labs right after re-feeding, expect a higher NLR than your long-term baseline.
Caveats
- Human data for exactly 7-day water fasts followed by 24 h of re-feeding are scarce; most controlled studies use 36–72 h fasts. The direction and relative speed, however, are consistent across fasting lengths.
- Micronutrient status (iron, B-vitamins), hydration, and the macronutrient composition of the re-feed can all modulate hematopoietic recovery. Severe protein restriction, for example, can blunt lymphocyte rebound even when calories return.
- If the fast was extreme enough to deplete marrow stores (rare in one week), neutrophil recovery could be a little slower (36–48 h).
Bottom line: Your neutrophil army is back on patrol within hours of that first re-feed day; your lymphocyte corps needs several more days to regroup.
What normally happens to RDW after a brief re-feed
| Time-point | Dominant processes in the red-cell compartment | Expected direction of RDW (CV or SD) |
|---|---|---|
| End of a 7-day fast | • Erythropoiesis suppressed (low EPO/mTOR) | |
| • No reticulocyte influx → older, slightly smaller cells dominate | Mild rise (≈ +0.5–1 percentage point) because the size-spectrum narrows at the upper end while the smallest, “aged-out” cells accumulate | |
| +24 h of eating again | • Plasma volume expands; light meal itself slightly narrows the histogram | |
| • Marrow has not yet released the first reticulocyte “wave” (takes ≥ 48 h) | Largely unchanged or even ↓ ~0–0.3 pp (hemodilution effect seen after a meal in healthy volunteers) | |
| Day 2-5 of re-feeding | • Reticulocytes (macrocytic) begin to spill out; anisocytosis peaks because young large cells mix with the older, smaller fast-era cohort • RDW tracks the retic count | Transient spike (often reaching high-normal or mildly elevated range, e.g. 14 → 15 %) |
| Week 2-4 | • Fast-era cells (120-d lifespan) are increasingly replaced by post-refeed normocytic cells | Gradual normalization as the size distribution re-homogenizes |
Why the first 24 h show little change
- Reticulocyte kinetics: Even in vigorously stimulated marrow, it takes ≈ 2–3 days before newly made reticulocytes appear in peripheral blood; peak regenerative response is 6–10 days.
- Meal-related dilution: A single mixed meal expands plasma volume and narrows red-cell histograms slightly; RDW fell by ~0.4 % within one hour in a controlled study of healthy adults.
- Magnitude of the prior anemia: A 7-day fast rarely depletes iron or folate stores enough to create pronounced micro- or macro-cytosis, so the pre-existing anisocytosis is modest to begin with.
Taken together, the net effect at +24 h is either:
- No measurable change (most common); or
- A tiny fall—often below the analytical variation flag of automated counters—due to plasma-volume expansion slightly outweighing early regenerative changes.
Practical interpretation
- Do not expect RDW to “bounce” like neutrophils do: The index reflects the mix of cell ages and sizes, and those pools turn over on the scale of weeks, not hours.
- A higher RDW two–three days later is normal: It signals the anticipated reticulocyte surge rather than a new problem.
- Serial CBCs: If you are monitoring recovery, draw the next panel at ≥ 48 h. Earlier sampling adds little insight but can be misleading.
Bottom line: One day of re-feeding after a week-long fast that produced mild anemia is too soon for erythropoiesis to reshape the size spectrum of circulating red cells; RDW therefore stays roughly where it was—or dips slightly—before climbing during days 2-5 as reticulocytes enter the bloodstream.
8 days later and appetite still very low, I can probably have several more days before redosing
no weight loss