Yes it’s not an issue at 1.25 mg/day (if swallowed).
I wrote that whole page, very interesting link indeed! 
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I take1.25mg selegiline (1/4 of a 5mg pill swallowed) most days and eat about 8 ounces of tofu without any issues.
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I’m gonna resume 10mg/day now, unitedpharmacies has it
Selegiline, by irreversibly inhibiting MAO‑B, markedly reduces the formation of 3,4‑dihydroxyphenylacetic acid (DOPAC)—the immediate deamination product of dopamine—which in turn decreases downstream production of homovanillic acid (HVA) by COMT (SpringerLink).
Clinical (CSF) data (DATATOP study):
- In early, untreated Parkinson’s patients receiving 10 mg/day selegiline, cerebrospinal fluid (CSF) HVA concentrations fell by an average of 9.2 ± 12.7 ng/mL (from a baseline mean of ~34.7 ng/mL), compared with a 3.2 ± 14.4 ng/mL drop in placebo‐treated controls when measured 4 weeks after the study endpoint (i.e., shortly after medication withdrawal) (epistemonikos.org).
- This represents a roughly 25–30 % reduction in CSF HVA under ongoing selegiline exposure.
- After discontinuation of selegiline, CSF HVA levels gradually recover toward control values over ~60 days (epistemonikos.org).
Peripheral (plasma/urine) data:
- Plasma and urinary HVA also tend to decline under selegiline, though the magnitude of change is smaller and more variable than in CSF.
Time course:
- The suppression of HVA persists for weeks after stopping selegiline, reflecting the drug’s irreversible binding to MAO‑B and the slow synthesis of new enzyme.
- Full recovery of HVA production (and thus levels) typically takes 1–2 months post‐withdrawal.
Bottom line:
Under typical doses (5–10 mg/day), selegiline will decrease HVA concentrations—by roughly 25–30 % in CSF—with the effect emerging within days, peaking over weeks, and dissipating over 1–2 months after cessation.
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Ok if it takes months for HVA levels to return back to normal after stopping selegiline, then can i take breaks from selegiline and have minimal increase in HVA/DOPAC? [selegiline tastes nasty, the blister packs make it WAY more effortful to get each pill out, and also it’s nice to do more with less]
Short answer
Yes—because selegiline binds MAO-B irreversibly, you can stop taking it for days (even a couple of weeks) before brain MAO-B activity and the downstream markers DOPAC → HVA rebound appreciably. Strategic “drug holidays” or intermittent-maintenance schedules (e.g., 5 mg every 3–4 days, or 10 mg on two non-consecutive days each week) keep HVA/DOPAC suppressed while cutting total exposure.
Below is the reasoning and the numbers so you can judge how long a break is safe before HVA starts climbing.
1 How fast does MAO-B activity come back?
| Tissue | Half-time for new MAO-B synthesis | Back to baseline |
|---|---|---|
| Platelets (lab surrogate) | 5–14 days (varies by study & dose) (PubMed) | ~1 week (single 10 mg dose) (PubMed) |
| Human brain (PET with [¹¹C]-deprenyl) | ≈ 40 days (PubMed) | 3–4 months for full recovery |
Because brain MAO-B turns over so slowly, only ≈ 12 % of the enzyme is replaced in the first week after you stop, ≈ 22 % after two weeks, and ≈ 40 % after one month (first-order kinetics, t½ ≈ 40 d).
2 What happens to HVA and DOPAC?
-
CSF data (DATATOP, 10 mg/day):
Immediately after withdrawal CSF-HVA is still ≈ 25–30 % below baseline, reflecting lingering MAO-B blockade.
By ~60 days HVA rises back to placebo levels as new enzyme accumulates (PubMed). -
Plasma / urine: Parallel but smaller changes; most studies show partial rebound within 2 weeks, full by 1–2 months.
3 Intermittent-maintenance schedules that actually work
Because selegiline’s binding is irreversible, you only need to redose often enough to “keep ahead” of enzyme resynthesis.
| Schedule (oral) | % platelet MAO-B still blocked after ≥ 1 week | Comment |
|---|---|---|
| 5 mg × 1 daily | 99 % (steady state) (PubMed) | Standard low dose |
| 10 mg × 2 per week (e.g., Mon + Thu) | 96–99 % (PubMed) | Keeps near-max block with 60 % fewer doses |
| 10 mg × 1 per week | ≈ 76 % by day 7 (PubMed) | HVA begins creeping up—borderline |
| Single 10 mg pulse then 10-day gap | > 90 % block for ~5 days; falls toward 70 % at day 10 (Wikipedia) | OK for a short break |
Rule of thumb:
Re-dose once brain MAO-B has regained ~15–20 % activity.
With a 40-day half-life that’s about every 10–14 days; shorter if you want to stay > 90 % inhibited; longer if you can tolerate a small HVA rise.
4 Practical take-aways
- “Weekend holiday” (skip 1–2 days) – HVA/DOPAC barely move; essentially no loss of MAO-B inhibition.
- Skip up to ~10 days – still > 70 % central inhibition; HVA creep is modest.
- Skip a full month – MAO-B activity may be ~40 % restored, and CSF-HVA approaches baseline; you’ve effectively “washed out.”
- Maintenance trick: After an initial loading phase (5-10 mg/day for 4–5 days), many clinicians use 5 mg Q 48–72 h or 10 mg twice weekly to minimise pill burden without losing efficacy.
- Watch the dose ceiling. Bigger pulse doses (> 10 mg) start to hit MAO-A, raising tyramine/serotonergic risk even if given infrequently.
Caveats
- Peripheral platelet data ≠ brain, but platelet kinetics give a conservative estimate.
- Intermittent schedules haven’t been formally approved; discuss with a clinician before changing any prescription.
- If you’re stacking other dopaminergics (levodopa, tolcapone, etc.), the optimal timing can shift.
Bottom line: Thanks to the very slow turnover of brain MAO-B, you can indeed take periodic breaks from selegiline (days to a couple of weeks) with minimal rebound of HVA/DOPAC. A pulse-or-twice-per-week regimen is enough to keep MAO-B—and therefore HVA—suppressed in most people while reducing cumulative exposure and metabolite load.
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Can someone please explain (very short) what is Seleglinine good for? to contextualize the above paragraph: Even though it is written in English, I know for a fact that I would understand it better if it were written in French even though i do not understand one single word in French. 
Edit: Never mind, for those in same boat as me what Seleglinine does, it basically prevents dopamine from breaking down in the brain as such it helps with mood and neurological disorders.
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Is 5 mg every 48 h enough to keep MAO‑B shut down?
Practically yes. Because selegiline binds MAO‑B irreversibly and the enzyme is replaced only slowly, redosing every two days keeps central and peripheral MAO‑B > 90 % inhibited while still sparing MAO‑A.
Reference finding Why it matters A single 5 mg oral dose knocks out ≈ 85–90 % of platelet MAO‑B within 2 h and that suppression stays > 90 % for ~5 days; baseline activity is not regained until ≈ 14 days (Wikipedia) 10 mg twice weekly (20 mg wk‑¹) maintained 96 % inhibition after four weeks, whereas 10 mg once weekly (10 mg wk‑¹) slipped to 76 % (Wikipedia) Platelet MAO‑B returns to normal 5–7 days after stopping, showing the window before meaningful rebound begins (Drugs.com) Brain MAO‑B turns over far slower—half‑time ≈ 40 days—so central inhibition decays much more gradually than platelet data suggest (PubMed) 5 mg every 48 h = 17.5 mg wk‑¹ sits just below the 20 mg wk‑¹ schedule that kept platelet MAO‑B at > 95 %. Given that:
- Each 5 mg pulse restores near‑maximal blockade long before any appreciable enzyme resynthesises.
- The next dose arrives at 48 h, when platelet MAO‑B is still ≳ 90 % inhibited and brain MAO‑B has scarcely budged.
You therefore stay in the same pharmacodynamic range as 5 mg daily, but with ~50 % less cumulative drug.
Expected biochemical effects
Marker At 5 mg q48 h Notes MAO‑B activity ≈ 95 % inhibited continuously Slight trough before each redose, but still > 90 % HVA / DOPAC Remain ~25–30 % below baseline (similar to daily dosing) Suppression relaxes only after weeks without drug β‑Phenethylamine Still markedly elevated (indicator of central MAO‑B block) MAO‑A Remains largely unaffected; tyramine pressor risk unchanged Oral selectivity lost only as total daily dose approaches ≥ 20 mg
How to implement safely
- Loading week: take 5 mg once‑daily for 4–5 days to saturate MAO‑B, then switch to q48 h.
- Monitor co‑meds: the schedule is still incompatible with SSRIs, meperidine, linezolid, etc.
- Watch levodopa dose: if you’re on L‑dopa, you may need a small downward adjustment once MAO‑B is maximally blocked.
- Skip length: you can safely miss one entire 48‑h cycle (i.e., 4 days between doses) with only a modest bump in MAO‑B activity and minimal HVA rebound; beyond about a week, inhibition begins to wane faster.
Bottom line
Taking 5 mg of selegiline every other day is usually enough to keep MAO‑B > 90 % inhibited—giving essentially the same dopaminergic and HVA‑lowering benefits as 5 mg daily, while trimming pill burden and metabolite exposure. It preserves MAO‑B selectivity, so tyramine sensitivity and MAO‑A–related side‑effects remain minimal. Always confirm any off‑label dosing schedule with a clinician, especially if other serotonergic or dopaminergic drugs are in the mix.
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@AlexKChen if you’re taking 10mg daily, is that high enough where you need to avoid eating cheese? I’m only on 1.25mg per day.
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This makes sense given that people who suffer ADHD respond well to amphetamines and Selegiline metabolizes into levomethamphetamine and levoamphetamine.
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I’ve started taking selegiline, 1.25mg qd in the am (1/4 of a 5mg tablet). As I get older (81) I find unexplained anxiety in my otherwise stable and unproblematic living situation. Giving it a try; 4 days (so far) is too early to tell if there is any effect.
At this low dose, doesn’t seem to be any issues with food. I also read that its pharmacokinetics are generally not significantly affected by CYP3A4 inhibitors.
After 9 days
Can’t see any effect; going to bump it up to 2.5mg (half tablet).
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I take 5mg Selegiline 3x weekly. Primarily for neuroprotective benefits. Because of the MAO inhibition, it’s the one med in my stack that “scares” me (not really scared, but always check for interactions with other meds & it’s the first thing I mention if ever asked “are you on any medications?”).
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I’m planning to use it, but it’s been sitting in a box for a while as I also am a bit scared of it. While 1.25mg is reportedly low and safe, I am a bit concerned about accidentally potentiating it with something else without realizing, boosting the effective dose such that tyramine or other interactions do become significant.
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I thought I would look at this particularly given Paul Kiesow’s recent promotion of it. As part of that I had chatGPT produce a research table of lifespan research that I copy below.
I think it clearly has an effect on mitochondrial function that slows down deterioration, but the way it does this has other potentially negative effects as well. Perhaps more of a curate’s egg than rapamycin.
I do, however, intend looking into this further and perhaps taking a small dose. It strikes me, however, that unlike rapamycin it is a continuous low level of dosing that matters rather than intermittent dosing.
chatGPT
Here is a compact table of the main lifespan experiments with selegiline / L-deprenyl that are commonly cited.
| Study | Species / model | Treatment details | Lifespan result | Takeaway |
|---|---|---|---|---|
| Bene et al., 2025 meta-analysis | Rodents, 22 lifespan experiments | Random-effects meta-analysis of published rodent studies | Overall positive effect on mean lifespan, but with high heterogeneity; larger effects tended to appear with higher doses and later-life treatment starts. (PMC) | Best overall summary: selegiline looks promising but inconsistent. |
| Knoll, 1988 | Male rats | Long-term L-deprenyl treatment | Positive lifespan extension reported in rats. (PubMed) | Early foundational positive rat study. |
| Knoll, 1989 | Male rats | Long-term treatment in aged rats | Mean lifespan reported as about 191.9 weeks in treated rats, with the longest-living rat dying in the 226th week; this was presented as exceeding the prior rat maximum cited by the author. (PubMed) | One of the strongest positive animal results. |
| Kitani et al., 1993 | Male Fischer-344 rats | Chronic (-)deprenyl treatment | Reported to prolong lifespan in male Fischer-344 rats. (PubMed) | Independent positive replication in rats. |
| Kitani et al., 1994 | Male Fischer-344 rats | 0.5 mg/kg/day, subcutaneous, 3x/week from 18 months | Remaining life expectancy increased; average lifespan after 24 months was 34% greater than controls. (PubMed) | Strong positive result, especially for late-life initiation. |
| Stoll et al., 1997 | Syrian hamsters | 0.05 mg/kg selegiline | Females lived longer, but males did not; MAO-B inhibition occurred in both sexes. (PubMed) | Clear sex-specific effect. |
| Archer et al., 1996 | Aging mice, two hybrid strains | 0.25 mg/kg, injected 3x/week; started at mean ages 26 months and 18.5 months depending on strain | Lifespan increased about 6–9%; not significant within each sex/genotype subgroup, but significant when all data were combined. (PubMed) | In mice, effect was small and statistically fragile. |
| Freisleben et al., 1997 | Immunosuppressed mice | Selegiline and lipoic acid studied for life expectancy | Study examined life expectancy in an immunosuppressed mouse model, but it is not one of the clearest standard positive longevity studies in healthy aging animals. (PubMed) | Harder to generalize to normal aging. |
| Carrillo et al., 2000 | Fischer-344 rats | High-dose long-term deprenyl | High dose lost the beneficial survival effect seen at lower doses. (PubMed) | Suggests a dose window / hormetic pattern rather than “more is better.” |
| Ruehl et al., 1997 | Elderly dogs (beagles) | 1 mg/kg oral selegiline daily | Authors suggested benefit when begun in relatively healthy dogs aged 10–15 years. (PubMed) | Often cited as positive, but not very secure statistically. |
| Bene et al., 2025 reanalysis of the dog study | Same dog dataset reanalyzed | Adjusted for age at enrollment and sex | After adjustment, the dog study no longer showed a significant survival effect, though the sample was small. (PMC) | The canine evidence is weaker than it first appeared. |
| Szepesy et al., 2021 | DBA/2J and BALB/c mice | Chronic oral selegiline | No beneficial effect on survival in either strain. (PMC) | Modern mouse evidence is negative for lifespan, despite some functional benefits. |
Bottom line
| Pattern | Conclusion |
|---|---|
| Rats | Mostly the strongest positive lifespan signals. (PubMed) |
| Hamsters | Positive in females only in the best-known study. (PubMed) |
| Mice | Mixed to negative overall; small positive pooled signal in one older study, but later work was negative. (PubMed) |
| Dogs | Suggestive historically, but not robust after reanalysis. (PubMed) |
| Overall | Selegiline has shown real lifespan extension in some animal experiments, but the effect is species-, sex-, dose-, and protocol-dependent, not a universally reproducible longevity intervention. (PMC) |
I can also do a second table with just these columns: species / dose / age treatment started / % lifespan change / significance.
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I had bought 5mg tablets about 1 year ago and never tried them and actually wasn’t going to until renewed interest and talk about it lately, so I decided to try this morning 1.25mg (1/4th of 5mg) I think i am being a bit more upbeat than early morning (i was kind of in a down mood). Other than that, I didn’t notice anything else (good or bad).
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When I took 1.25 mg/day, lunalae appeared on my fingers; they disappeared when I stopped. I stopped because I felt weird in my heart (very subjective, yes, but it does seem to have negative effects per this recent paper: MAO-B inhibition by selegiline blunts cardiac functions improved by high-fat diet: Role of inflammation, apoptosis, and calcium-handling 2025) and wasn’t sure about long-term safety. Unfortunately, we’ll only get the ITP results in September 2028…
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started taking 1.25 mg after seeing Paul Keisow’s talk. No noticeable effects after 3 weeks but I am looking for long term benefits as have a family history of PD
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There’s no evidence that selegiline can prevent PD before diagnosis or slow it down after diagnosis. For PD prevention, I would look at:
- SGLT2i (dapagliflozin or empagliflozin)
- Telmisartan
- Amlodipine
- UDCA
- Avoiding statins
- Lithium orotate
- Rapamycin
See the dedicated thread: Parkinson's disease
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I’m still taking 1.25mg tabs every morning upon waking. I think I have been taking this for almost ten years now. I don’t notice anything from it, but I’ve also been using it for such a long time.
It would be interesting if you were to stop it for couple months to see if you notice anything different.
BTW, since you started it such long time ago what was your reason (initially) for starting it?
For the sake of completeness, one can add a couple more things which are not decisive in any way, but might be helpful in some cases, just really throwing the kitchen sink at this terrible disease. One is to top up vitamin b1/b2 (I mention both because taking larger amounts of one can imbalance the other) to at least RDA. Keep inflammation low, perhaps add astaxanthin, maintain gut integrity against LPS with some probiotic additions or even direct tributyrin, avoid pesticides in general maybe eat organics in F&V. And super speculative - add some magnesium threonate (I’ll post a study in the PD thread). There’s a bunch others, but all speculative.
I initially started it because I saw an article in Life Extension magazine when I really started to get into health and they made it sound really good so I ordered some. I did stop at one point and then started it again. I can’t say I noticed too much of a subjective difference either way.
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After reading grok’s answer to what I asked, I think I will increase my dose to 2.5 mg. I feel like the 1.25mg isn’t really doing anything. The human equivalent doses used in the studies were mostly 1.5-3mg for a 70kg human (I’m 94kg)
Grok
The evidence for selegiline (L-deprenyl) extending lifespan in animals is moderately strong overall, primarily driven by a 2025 meta-analysis synthesizing decades of rodent data, though results show notable variability and are weaker/less consistent in non-rodents. 
A random-effects meta-analysis (published in Ageing Research Reviews) of 22 rodent lifespan experiments (covering mice, rats, and hamsters across 8 strains, 6 countries, 27 years of research, 6 doses, and 2 delivery methods) found that L-deprenyl significantly increases average lifespan with a moderate effect size (standardized mean difference [SMD] = 0.6773, p = 0.0002). There was no significant publication bias, but substantial heterogeneity between studies. Effects were dose- and age-dependent: higher doses and starting treatment later in life produced larger benefits. Short-lived control groups did not explain the results.  
Key supporting studies include:
• Joseph Knoll’s seminal 1988 work (and follow-ups): Male rats treated with 0.25 mg/kg s.c. three times weekly from ~24 months of age showed dramatic extensions (average lifespan ~147–148 weeks in controls vs. ~192–198 weeks in treated; some individuals exceeded the species’ estimated maximum of ~182 weeks). Sexual activity and other markers also improved markedly.  
• Replications by Kitani et al. and others in F344 rats (e.g., 0.5 mg/kg s.c. three times weekly from 18 months): ~10–34% increases in average remaining lifespan, with parallel upregulation of antioxidant enzymes (SOD/catalase) proposed as a mechanism. 
• Positive but smaller effects in mice (e.g., ~7–9% in aged animals at 0.25 mg/kg), Syrian hamsters (especially females at low doses like 0.05 mg/kg), and other rodent strains. 
Limitations temper the strength:
• High heterogeneity: Some studies (especially in mice) found null, minimal, or even negative effects at improper doses (hormetic/inverted-U response—too high a dose can shorten life). 
• One beagle dog study (Ruehl et al., 1997): 1 mg/kg oral daily in elderly dogs (10–15 years at start) showed apparent survival benefit in a subset (80% treated vs. 39% controls survived study period), but reanalysis adjusting for age/sex found only a non-significant trend (limited power, small n).  
• No consistent effects across all protocols or species; mechanisms (MAO-B inhibition, catecholaminergic enhancement, antioxidant upregulation) are plausible but not fully proven as causal for longevity.
Overall, this is one of the more robust pharmacological lifespan datasets in mammals (far more studies than most compounds), but replication inconsistencies and lack of modern standardized trials mean it’s not “conclusive” like caloric restriction or certain genetic interventions. No human longevity trials exist (though selegiline is FDA-approved/safe for Parkinson’s/depression at low doses).
Human equivalent doses (HED) from the effective animal studies are low and overlap with or fall below standard clinical doses.
Allometric scaling (FDA body surface area method: rat Km=6, human=37 → multiply animal mg/kg by ~0.162; adjust for intermittent dosing) from the most common/effective rodent protocols (0.25–0.5 mg/kg s.c. three times weekly, or daily averages ~0.1–0.2 mg/kg) yields ~1.5–3 mg/day oral for a 70 kg (~155 lb) human. This matches statements from summaries of the meta-analysis. 
• Knoll’s classic 0.25 mg/kg rat dose (3x/week) ≈ ~1–1.5 mg/day HED.
• Kitani-style 0.5 mg/kg ≈ ~2–3 mg/day HED.
• These are roughly equivalent to (or below) typical Parkinson’s oral tablets (1.25–10 mg/day) or well below the transdermal patch (6–12 mg/day). The meta-analysis notes that higher animal doses (and later start) were more effective, so the patch range might align better if translating directly. 
Dog doses (1 mg/kg oral daily) scale higher (~30–40 mg/day HED) but are less relevant given the weaker evidence. Low “enhancer-only” doses (e.g., 0.001–0.1 mg/kg in later Knoll work) had smaller or inconsistent effects.
Bottom line: Solid preclinical signal in rodents (meta-supported moderate extension, dose/age optimized), translatable to very low human-equivalent oral doses already used safely in medicine. Human anti-aging trials would be needed to confirm any benefit—none exist yet. Consult a physician before any off-label use, as selegiline has interactions (e.g., with certain antidepressants/foods at high doses).
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