32 ms·

I believe most nootropics work for Alzheimer's, probably Huperzine A, too. Perhaps even Noopept. NMDA agonists and acetylcholinesterase (they inhibit the break

I believe most nootropics work for Alzheimer's, probably Huperzine A, too. Perhaps even Noopept. NMDA agonists and acetylcholinesterase (they inhibit the breakdown of the neurotransmitter acetylcholine) in general. Benadryl (DPH) and first-generation antihistamines are the opposite of that, they can cause delirium (and it messes up your memory and cognition in general) and whatnot, they are anticholinergic, some more than others. I had anticholinergic toxicity from DPH before. I take Alpha-GPC (a very soluble form of choline) and Huperzine A for cognition / memory, others couple it with racetams (e.g. piracetam, pramiracetam, aniracetam, etc.).

TechDebtDevin 2y ago
My primary care doctor is telling all of her patients not to take Zyrtec for an anti-histamine because it is causing dementia side effects in her older patients. Antecdotal but interesting.
- johnisgood 2y ago
  For the reasons I mentioned, yes. :) But Zyrtec is second-generation. It shows 20,000-fold or greater selectivity for the H1 receptor over the five muscarinic acetylcholine receptors, and hence does not exhibit anticholinergic effects, so it should be OK. May still cause drowsiness, however.
  - wildylion 2y ago
    What about desloratadine?
    - johnisgood 2y ago
      Desloratadine (Clarinex, Aerius) is a selective H1-antihistamine which functions as an inverse agonist at the histamine H1 receptor. From Wikipedia: > At very high doses, it is also an antagonist at various subtypes of the muscarinic acetylcholine receptors. This effect is not relevant for the drug's action at therapeutic doses. Thus, it is an anticholinergic only at very high doses, and it does not readily pass the BBB, therefore drowsiness is NOT likely (probably at very high doses only). At any rate, it does not affect the CNS at therapeutic doses, so memory / cognition issues, along with drowsiness are not an issue. FWIW "2% of Caucasians and 18% of people from African descent are desloratadine poor metabolizers.", meaning "In these people, the drug reaches threefold higher plasma concentrations at seven hours after intake, and it has a half-life of 89 hours (compared to a 27-hour half-life in normal metabolizers). Adverse effects were reported at similar rates in poor metabolizers, suggesting that it is not clinically relevant.".
      - throwaway2037 2y ago
        Is BBB == "blood-brain barrier"?
        johnisgood 2y ago
        Yes.
      - TechDebtDevin 2y ago
        Do you know if there are any SNPs correlated with poor desloratadine metabolizers?
        johnisgood 2y ago
        I do not think that there are any definitive single nucleotide polymorphisms (SNPs) currently known to be specifically correlated with poor desloratadine metabolism. I think perhaps the genetic variation in the enzymes involves in its metabolism like UGT2B10 and CYP2C8 may contribute to differences in metabolism. There is just no conclusive identification of specific SNPs that definitively determine poor metabolizer status. The precise genetic variants (if any) have not yet been definitively pinpointed. For all we know, the differences may be attributable to variations in study design, sample sizes, definition of what constitutes a "poor metabolizer", and genetic heterogeneity among populations. Some reported rates of poor metabolizers vary, some studies report around 7% overall and 20% in African descent individuals, while others suggest the figures I have mentioned. There was a somewhat recent randomized study in healthy Chinese subjects, and found no statistically significant association between the UGT2B10 or CYP2C8 genotypes. What is clear is that while genetic factors are likely involved and poor metabolizer phenotype exists for the drug, no single genetic marker has yet been found to predict poor metabolism of this drug, and there is a notable interethnic difference in desloratadine metabolism. TL;DR: Currently there is no definitive evidence linking specific SNPs to poor desloratadine metabolism, but genetic variation in enzymes like UGT2B10 and CYP2C8 is implicated, but further research is needed. I hope this answers your question, but the bottom line is that more research is needed. If you know something, let me know though!
OutOfHere 2y ago
I advise against taking aGPC because it is very much associated with TMAO production due to adverse gut fermentation, leading to harmful effects on blood vessels. Switch to citicoline which doesn't look to have this issue.
- johnisgood 2y ago
  Yes, Citicoline is great, too, I agree. As long as it is not Choline bitartrate (most common form) which is pretty useless, the body cannot utilize it whatsoever. As for what you said regarding alpha-GPC, it is somewhat true: > Although alpha-GPC is largely considered to be safe due to its structural feature, multiple studies have indicated that a high plasma choline level is associated with an increased risk of cardiovascular disease through trimethylamine-N-oxide (TMAO) produced by gut microbiota from choline. Some studies have highlighted that TMAO increases the likelihood of stroke and cardiovascular disease.11 > In line with this observation, a recent animal model study revealed that even though alpha-GPC supplements improved neurological functions, they increased the risk of atherosclerosis in hyperlipidemic rats. In the future, scientists must elucidate the possible mechanism that associates alpha-GPC with increased cardiovascular risks. https://examine.com/supplements/alpha-gpc/?show_conditions=true https://examine.com/supplements/alpha-gpc/?show_conditions=t... https://www.news-medical.net/health/Alpha-GPC-What-Science-Says-About-Its-Role-in-Brain-Health.aspx https://www.news-medical.net/health/Alpha-GPC-What-Science-S... https://pmc.ncbi.nlm.nih.gov/articles/PMC8708068/ https://pmc.ncbi.nlm.nih.gov/articles/PMC8708068/ https://www.sciencedirect.com/science/article/pii/S0021925824024670 https://www.sciencedirect.com/science/article/pii/S002192582... That said, "However, the currently available evidence is preliminary in nature, so randomized controlled trials and large cohort studies are needed to confirm these findings.".
  - johnisgood 2y ago
    BTW Citicoline's other name is CDP-Choline, forgot to edit in time.
  - johnisgood 2y ago
    Oh also, it says "multiple studies have indicated that a high plasma choline level is associated with an increased risk of cardiovascular disease", but I wonder why it does not apply to CDP-Choline (Citicoline) since it does increase plasma choline level, too, but perhaps not as highly? I am not sure of the exact mechanisms.

TechDebtDevin 2y ago

My primary care doctor is telling all of her patients not to take Zyrtec for an anti-histamine because it is causing dementia side effects in her older patients. Antecdotal but interesting.

johnisgood 2y ago
For the reasons I mentioned, yes. :) But Zyrtec is second-generation. It shows 20,000-fold or greater selectivity for the H1 receptor over the five muscarinic acetylcholine receptors, and hence does not exhibit anticholinergic effects, so it should be OK. May still cause drowsiness, however.
- wildylion 2y ago
  What about desloratadine?
  - johnisgood 2y ago
    Desloratadine (Clarinex, Aerius) is a selective H1-antihistamine which functions as an inverse agonist at the histamine H1 receptor. From Wikipedia: > At very high doses, it is also an antagonist at various subtypes of the muscarinic acetylcholine receptors. This effect is not relevant for the drug's action at therapeutic doses. Thus, it is an anticholinergic only at very high doses, and it does not readily pass the BBB, therefore drowsiness is NOT likely (probably at very high doses only). At any rate, it does not affect the CNS at therapeutic doses, so memory / cognition issues, along with drowsiness are not an issue. FWIW "2% of Caucasians and 18% of people from African descent are desloratadine poor metabolizers.", meaning "In these people, the drug reaches threefold higher plasma concentrations at seven hours after intake, and it has a half-life of 89 hours (compared to a 27-hour half-life in normal metabolizers). Adverse effects were reported at similar rates in poor metabolizers, suggesting that it is not clinically relevant.".
    - throwaway2037 2y ago
      Is BBB == "blood-brain barrier"?
      - johnisgood 2y ago
        Yes.
    - TechDebtDevin 2y ago
      Do you know if there are any SNPs correlated with poor desloratadine metabolizers?
      - johnisgood 2y ago
        I do not think that there are any definitive single nucleotide polymorphisms (SNPs) currently known to be specifically correlated with poor desloratadine metabolism. I think perhaps the genetic variation in the enzymes involves in its metabolism like UGT2B10 and CYP2C8 may contribute to differences in metabolism. There is just no conclusive identification of specific SNPs that definitively determine poor metabolizer status. The precise genetic variants (if any) have not yet been definitively pinpointed. For all we know, the differences may be attributable to variations in study design, sample sizes, definition of what constitutes a "poor metabolizer", and genetic heterogeneity among populations. Some reported rates of poor metabolizers vary, some studies report around 7% overall and 20% in African descent individuals, while others suggest the figures I have mentioned. There was a somewhat recent randomized study in healthy Chinese subjects, and found no statistically significant association between the UGT2B10 or CYP2C8 genotypes. What is clear is that while genetic factors are likely involved and poor metabolizer phenotype exists for the drug, no single genetic marker has yet been found to predict poor metabolism of this drug, and there is a notable interethnic difference in desloratadine metabolism. TL;DR: Currently there is no definitive evidence linking specific SNPs to poor desloratadine metabolism, but genetic variation in enzymes like UGT2B10 and CYP2C8 is implicated, but further research is needed. I hope this answers your question, but the bottom line is that more research is needed. If you know something, let me know though!

OutOfHere 2y ago

I advise against taking aGPC because it is very much associated with TMAO production due to adverse gut fermentation, leading to harmful effects on blood vessels. Switch to citicoline which doesn't look to have this issue.

johnisgood 2y ago
Yes, Citicoline is great, too, I agree. As long as it is not Choline bitartrate (most common form) which is pretty useless, the body cannot utilize it whatsoever. As for what you said regarding alpha-GPC, it is somewhat true: > Although alpha-GPC is largely considered to be safe due to its structural feature, multiple studies have indicated that a high plasma choline level is associated with an increased risk of cardiovascular disease through trimethylamine-N-oxide (TMAO) produced by gut microbiota from choline. Some studies have highlighted that TMAO increases the likelihood of stroke and cardiovascular disease.11 > In line with this observation, a recent animal model study revealed that even though alpha-GPC supplements improved neurological functions, they increased the risk of atherosclerosis in hyperlipidemic rats. In the future, scientists must elucidate the possible mechanism that associates alpha-GPC with increased cardiovascular risks. https://examine.com/supplements/alpha-gpc/?show_conditions=true https://examine.com/supplements/alpha-gpc/?show_conditions=t... https://www.news-medical.net/health/Alpha-GPC-What-Science-Says-About-Its-Role-in-Brain-Health.aspx https://www.news-medical.net/health/Alpha-GPC-What-Science-S... https://pmc.ncbi.nlm.nih.gov/articles/PMC8708068/ https://pmc.ncbi.nlm.nih.gov/articles/PMC8708068/ https://www.sciencedirect.com/science/article/pii/S0021925824024670 https://www.sciencedirect.com/science/article/pii/S002192582... That said, "However, the currently available evidence is preliminary in nature, so randomized controlled trials and large cohort studies are needed to confirm these findings.".
- johnisgood 2y ago
  BTW Citicoline's other name is CDP-Choline, forgot to edit in time.
- johnisgood 2y ago
  Oh also, it says "multiple studies have indicated that a high plasma choline level is associated with an increased risk of cardiovascular disease", but I wonder why it does not apply to CDP-Choline (Citicoline) since it does increase plasma choline level, too, but perhaps not as highly? I am not sure of the exact mechanisms.