Finally, in order to determine whether our 2c cocktail could also impact biological aging in vivo, we tested the effect of 2c treatment on the lifespan of a commonly used aging model organism, the nematode Caenorhabditis elegans . Towards this goal, we monitored survival in C. elegans treated with either 2c, Repsox, or TCP at three different concentrations (50, 100, or 200 μM) alongside a vehicle control. Strikingly, we observed that 2c treatment at 50 μM was sufficient to extend C. elegans median lifespan from 19 to 27 days, corresponding to a 42.1% increase relative to vehicle control ([Fig. 4a, e]. To a lesser extent, Repsox or TCP alone at 50 μM also increased C. elegans median lifespan to 25 days, a 31.6% increase over vehicle control ([Fig. 4a, e]. These results indicate that Repsox and TCP are each able to extend median lifespan in C. elegans , and when combined as part of the 2c cocktail, can lead to an even greater increase in median lifespan.
Another new story on Flow Neurosciences headset:
Could be just some random noise, but two of us here noticed that telmisartan 40 mg increased our motivation and decreased our apathy / low-grade depression. One small paper in PD suggests the same effect for candesartan 8 mg (equivalent in terms of dose to telmisartan 40 mg):
- Optimal Blood Pressure we Should Target? Systolic Under 110 or 100? - #324 by Virilius
- Optimal Blood Pressure we Should Target? Systolic Under 110 or 100? - #325 by adssx
So if your BP is not optimal (24h average > 115/75 mmHg) then treating it with telmisartan might come with this welcome side effect.
Let’s say your SBP ranges from 105-130 (depending on the day/time/machine) and DBP is between 60-80. Are there any downsides to having a potentially too-low BP from telmisartan.
Kind of like how you don’t mix viagra and BP meds?
Telmisartan has a safety profile similar to placebo so the risk is hypotension:
You don’t want to faint after standing up and hit your head on the corner of the table…
According to the FDA notice: “Following once daily administration of telmisartan, the magnitude of blood pressure reduction from baseline after placebo subtraction was approximately (SBP/DBP) 6-8/6 mmHg for 20 mg, 9-13/6-8 mmHg for 40 mg, and 12-13/7-8 mmHg for 80 mg.”
With your numbers, even telmisartan 20 mg might cause hypotension, but you can try and stop if you ever feel dizzy.
Do we know the potential mechanism of action?
It’s probably not homocysteine-lowering as “The findings argue against a causal role for homocysteine in the development of depression.” (Plasma homocysteine concentrations and depression: A twin study 2021)
Wikipedia says: “The exact mechanisms involved in the development of schizophrenia and depression are not entirely clear, but the bioactive folate, methyltetrahydrofolate (5-MTHF), a direct target of methyl donors such as S-adenosyl methionine (SAMe), recycles the inactive dihydrobiopterin (BH2) into tetrahydrobiopterin (BH4), the necessary cofactor in various steps of monoamine synthesis, including that of dopamine and serotonin. BH4 serves a regulatory role in monoamine neurotransmission and is required to mediate the actions of most antidepressants.”
Also: at which dose do the antidepressant effects start? Solgar sells metafolin 400 μg. Metafolin is the active ingredient of Deplin (15 mg). It’s just a branded version of levomefolate calcium, a calcium salt of levomefolic acid (aka L-5-MTHF or L-methylfolate).
I found this: “Folate supplements especially levomefolic acid (L-5-methylfolate) demonstrated improvement in clinical outcomes in certain mental health conditions, such as in major depressive disorder (including postpartum and post-menopausal depression), schizophrenia, autism spectrum disorder, attention deficit hyperactivity disorder and bipolar affective disorder. Daily dosage range is 50 microgram to 15 mg orally daily depending on the clinical diagnosis and clinical presentation.” (The potential use of folate and its derivatives in treating psychiatric disorders: A systematic review 2022)
And this: “Meta-regression analysis demonstrated that there is no evidence of a significant linear relationship between dose and duration of folic acid supplementation and changes in HAM. Also, based on the non-linear dose response, no evidence of a relationship between dose and duration of folic acid supplementation and changes in HAM was found. […] Folic acid supplementation could possibly have an effect on lowering depression in patients. However, the clinical trials thus far are insufficient for clinical guidelines and practice.” (The effects of folic acid supplementation on depression in adults: a systematic review and meta-analysis of randomized controlled trials 2023)
However, most clinical trials looked at high-dose L-methylfolate (> 2.5 mg/day) and only as an adjunct to antidepressants: Folate as adjunct therapy to SSRI/SNRI for major depressive disorder: Systematic review & meta-analysis 2021: “Adjunct therapy with l-Methylfolate or folic acid improves depression scale scores, patient response, and remission rates.”
And also iron deficiency.
Some of the 17 million US Americans who suffer from major depressive disorder each year may soon receive a surprising new prescription from their doctor:
Have fun with a virtual reality device!