I read some time ago, that Dr. Blagosklonny recommended at least 100 mg weekly in one of his papers for health and longevity. It is a lower antibiotic, so the concerns of antibiotic resistance is not really an issue. Some teens take 100 mg daily for severe acne with great results and no real side effects.
I have taken for several years - 100 mg twice a week - so about every 3rd day. Been great.
@DrFraser has just dropped his video about the use of L.D. Doxy: “In this deep-dive longevity episode, we explore emerging science behind low-dose doxycycline (20–40 mg/day) and how it may protect the blood-brain barrier (BBB) by inhibiting MMP-9, a destructive enzyme linked to: Brain inflammation, Alzheimer’s diseas, Parkinson’s disease, Long COVID brain fog, APOE4-related cognitive decline” – from show notes.
B/c I’m pushing 81 and an E3/E4, I’m inclined to try this. Plus I have a load of 100mg doxy capsules left over from that doxy/azithro/Vit-C trial which didn’t work for me. Rather than trying to cut a capsule into parts and hoping the contents don’t spill out, I took one apart; the media weighs ~240mg. I may try making 3 new capsules from 1, so 80mg of media would approximate a 33mg doxy capsule (presuming the doxy is evenly distributed in the media). Of course there will be loss of a few mg in the reconstitution process, but it might be close enough to the middle of @DrFraser’s 20-40mg suggestion.
Got it. Yours came in capsules, mine actually was elongated tablets with a line in the middle. So, I guess I’ll cut mine in 1/2 and then again 1/2 for 25mg per day hoping it is enough. do we have to also take fish oil with it for best results? (which I tend to hate the after taste). I’ll make sure to order tablets with my next order as I don’t find splitting capsules very practical. Much rather split tablets.
The issue of taking DHA/EPA and getting it into your brain is important to brain health, and is more complex in those with ApoE4’s (especially homozygous). Doxycycline, through maintaining the integrity of the brain/blood brain barrier, theoretically will allow more DHA to get across into the brain.
I’ve been going with the lysoveta form (Accentrate Omega max) for those with ApoE4’s as it does get into the brain. Also eating fish works. The other standard supplements probably do not get much DHA into the brain of those with ApoE4’s.
So I personally have a few servings of fish/week, plus do the Omega Max plus have some Krill to get my Omega 3 Index up in the 8-12% range.
I took tetracycline as an adolescent for acne. But that’s my concern as well with the microbiome. Antibiotics have untoward consequences for the microbiome, and we very well are likely to be killing friendly species with indisciminate antibiotic use, and alterting the microbiome in unknown ways.
The idea with very low dose doxy (i.e. 20mg twice daily instead of 100mg twice daily) is to get the anti-inflammatory effect without the antibiotic effect. Minimal to no effect on the microbiome at these doses:
I bought 100 mg tablets, which I split in two. This is still a subclinical dose.
Perplexity Pro:
Yes, 50 mg/day is generally considered a subantimicrobial (subclinical) dose for a 70 kg adult male, as it falls below the threshold for meaningful antibacterial plasma levels and aligns with anti-inflammatory uses in clinical studies.
Definition of subantimicrobial dosing
Subantimicrobial doxycycline (often called SDD or SD) refers to doses producing steady-state plasma concentrations below the minimal inhibitory concentration (MIC) for most bacteria (typically 0.5–2 µg/mL), avoiding antimicrobial effects while retaining MMP-inhibiting and anti-inflammatory activity. Standard SDD is 20 mg twice daily (40 mg/day), with peak plasma levels around 0.48–0.79 µg/mL—well below antimicrobial thresholds.
Evidence for 50 mg/day
A clinical trial in Graves’ orbitopathy used 50 mg once daily for 12 weeks as an effective anti-inflammatory “subantimicrobial dose,” reporting good tolerability and efficacy without antibacterial side effects or resistance concerns. Other sources list 40–50 mg/day as SDD ranges for autoimmune/inflammatory conditions, confirming 50 mg/day stays subantimicrobial even for a 70 kg adult.
Relevance to 70 kg adult
Dosing for doxycycline’s anti-inflammatory effects (e.g., MMP-9 inhibition) is fixed in adults regardless of weight, unlike pediatrics. At 50 mg/day (~0.7 mg/kg for 70 kg), plasma exposure remains sub-MIC based on pharmacokinetics, similar to approved 40 mg/day Oracea for rosacea.
Thank you for researching this further. It’s a fascinating and unique drug. I use it as drug of choice for pneumonia and COPD exacerbations (at full dose) as there is the 2nd benefit - being an anti-inflammatory effect. It also has a very long 1/2 life, by my recollection about 18 hours.
I think that is a fair call - and looking further at this some studies show 50-70% inhibition at the 20 mg bid. Strongest inhibition is at the 100 mg bid; but then we are at a full antimicrobial dose. I agree - the middle ground here is 20 mg twice daily, as 20 mg daily will build up a bit, but is likely to only give the 50-70% inhibition for a proportion of the day.
I’ll be revising my approach to 20 mg twice daily. Thanks for the research – made me have to go back and look at this a second time.