Cyproheptadine Exacerbates Fatty Liver And Can Increase Estrogen

ddjd

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I mentioned this recently in a thread but thought I would make a separate post about it.

Cyproheptadine and other antihistamines like benadryl, because of their strong anticholinergic properties, will increase fatty liver in those predisposed to low Choline levels.

I myself have a genetic predisposition for very low Choline, meaning the anticholinergics peat often recommends are a terrible idea because Choline is essential for estrogen detoxification and reduction of fatty liver.

For years I was using cyproheptadine without understanding it was making my fatty liver and overall estrogenicity much much worse.

I've just started supplementing phosphatidylcholine and at last my belly is getting flat, manboobs reducing a lot, etc.

For those with a well functioning PEMT enzyme and good choline levels I can absolutely see the benefits of cyproheptadine, but anyone with possible fatty liver issues and low Choline, I would strongly recommend to avoid.
 
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ddjd

ddjd

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whats a tasty source of choline
Mitolipin from idealabs is a good choice.

I'm currently testing the phosphatidylcholine product Essentiale Forte, with good results. It's widely available over here in Europe and reasonably priced without the crazy pufa levels of sunflower Lecithin
 

Mito

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I myself have a genetic predisposition for very low Choline, meaning the anticholinergics peat often recommends are a terrible idea because Choline is essential for estrogen detoxification and reduction of fatty liver.
Which SNP do you have that is associated with low PEMT enzyme activity?
 
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ddjd

ddjd

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michael94

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Mitolipin from idealabs is a good choice.

I'm currently testing the phosphatidylcholine product Essentiale Forte, with good results. It's widely available over here in Europe and reasonably priced without the crazy pufa levels of sunflower Lecithin
what about pfood?
 

Mito

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3 different PEMT SNPs. Next to each one it states the frequency of that dysfunction in general public- 8%, 22% and 4%
Yes but rs7946 seems to be the one associated with decreased PEMT enzyme activity and the frequency of dysfunction may only be 22% in the general public but it’s about 50% for Caucasian European’s.
 
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ddjd

ddjd

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@Mito From what I understand all the PEMT genes are relevant, not just one. At least those are the three important ones according to self decode.

Also I'm homozygous in all three. How popular do you think that would be amongst Caucasian Europeans? Much less than 50% I expect.

Furthermore, even if it is a common SNP, that only supports the argument of how important it is because non alcoholic fatty liver disease is incredibly prevelant, and is probably related to low choline levels in this section of the population
 
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Mito

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Genetic Variants Related to Choline

PEMT – phosphatidylethanolamine N-methyltransferase

The PEMT pathway is responsible for the body’s production of phosphatidylcholine which is part of the phospholipid bilayer making up the membranes surrounding our cells. Note that 23andMe does not cover all of the SNPs in PEMT that are relevant to choline levels.

rs7946: (v.4 and v.5) CT and TT variants have somewhat decreased PEMT enzyme activity [ref]

CHKA – Choline kinase alpha

The first step of the CDP-PC pathway.

rs10791957: (v.4 and v.5) AA and AC variants have a lower turnover of methionine to PC
“Specifically, the variant appears to decrease the use of dietary choline for PEMT-PC synthesis relative to CDP-PC synthesis. Variant individuals displayed decreased turnover of choline-derived methionine → PEMT-PC over the study period, indicating decreased activity of PEMT relative to women without the variant, and also tended to exhibit lower relative PEMT-PC/CDP-PC enrichment as compared to non-variants.”[ref]
In another study, those with CC were found to be “less likely to have clinical symptoms after consuming a low-choline diet.” [ref]

BHMT – Betaine-homocysteine S-methyltransferase

rs3733890: (v.4 and v.5) AA and GA variants have lower conversion of choline to betaine and more conversion of choline to CDP-PC
“Together, these results indicate that the variant favors the use of dietary choline for CDP-PC synthesis at the expense of betaine synthesis.” [ref]

FMO3 – Flavin-containing monooxygenase

rs2266782: (v.4 and v.5) GA and AA variants have greater turnover of betaine to methionine and greater turnover of choline-derived methionine to PEMT-PC
“While a previous study from our group suggested that the variant might be associated with increased use of choline as a methyl donor in men (based on increased DMG pool size) [43], results from the present study, indicate that women with the variant actually use choline less as methyl donor. Variant women tended to have a lower turnover of betaine → methionine over the study period. In addition, variant women exhibited a greater turnover of choline-derived methionine → PEMT-PC over the study period, which is consistent with previous findings from our lab that have identified lower methionine excretion among variant individuals (i.e., a greater use of methionine may reduce excretion)” [ref]

MTHFD1 – methylenetetrahydrofolate dehydrogenase, cyclohydrolase and formyltetrahydrofolate synthetase 1

rs2236225 (G1958A): (v.4 and v.5) Carriers of the A allele are more likely to have choline deficiency on a low choline diet (modified by folate intake) [ref] [ref] In one study with premenopausal women, those with an A-allele were 15 times more likely to show choline deficiency symptoms on a diet low in choline.

Choline – An Essential Nutrient
 

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Dose. H1 antagonism vs m1 or cholinergic.
 
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ddjd

ddjd

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Genetic Variants Related to Choline

PEMT – phosphatidylethanolamine N-methyltransferase

The PEMT pathway is responsible for the body’s production of phosphatidylcholine which is part of the phospholipid bilayer making up the membranes surrounding our cells. Note that 23andMe does not cover all of the SNPs in PEMT that are relevant to choline levels.

rs7946: (v.4 and v.5) CT and TT variants have somewhat decreased PEMT enzyme activity [ref]

CHKA – Choline kinase alpha

The first step of the CDP-PC pathway.

rs10791957: (v.4 and v.5) AA and AC variants have a lower turnover of methionine to PC
“Specifically, the variant appears to decrease the use of dietary choline for PEMT-PC synthesis relative to CDP-PC synthesis. Variant individuals displayed decreased turnover of choline-derived methionine → PEMT-PC over the study period, indicating decreased activity of PEMT relative to women without the variant, and also tended to exhibit lower relative PEMT-PC/CDP-PC enrichment as compared to non-variants.”[ref]
In another study, those with CC were found to be “less likely to have clinical symptoms after consuming a low-choline diet.” [ref]

BHMT – Betaine-homocysteine S-methyltransferase

rs3733890: (v.4 and v.5) AA and GA variants have lower conversion of choline to betaine and more conversion of choline to CDP-PC
“Together, these results indicate that the variant favors the use of dietary choline for CDP-PC synthesis at the expense of betaine synthesis.” [ref]

FMO3 – Flavin-containing monooxygenase

rs2266782: (v.4 and v.5) GA and AA variants have greater turnover of betaine to methionine and greater turnover of choline-derived methionine to PEMT-PC
“While a previous study from our group suggested that the variant might be associated with increased use of choline as a methyl donor in men (based on increased DMG pool size) [43], results from the present study, indicate that women with the variant actually use choline less as methyl donor. Variant women tended to have a lower turnover of betaine → methionine over the study period. In addition, variant women exhibited a greater turnover of choline-derived methionine → PEMT-PC over the study period, which is consistent with previous findings from our lab that have identified lower methionine excretion among variant individuals (i.e., a greater use of methionine may reduce excretion)” [ref]

MTHFD1 – methylenetetrahydrofolate dehydrogenase, cyclohydrolase and formyltetrahydrofolate synthetase 1

rs2236225 (G1958A): (v.4 and v.5) Carriers of the A allele are more likely to have choline deficiency on a low choline diet (modified by folate intake) [ref] [ref] In one study with premenopausal women, those with an A-allele were 15 times more likely to show choline deficiency symptoms on a diet low in choline.

Choline – An Essential Nutrient

"CHKArs10791957, CHDH rs9001, CHDH rs12676, PEMT rs4646343, PEMT rs7946, FMO3 rs2266782, SLC44A1 rs7873937, and SLC44A1 rs3199966 altered the use of choline as a methyl donor; CHDH rs9001 and BHMT rs3733890 altered the partitioning of dietary choline between betaine and phosphatidylcholine synthesis via the cytidine diphosphate (CDP)-choline pathway; and CHKA rs10791957, CHDH rs12676, PEMT rs4646343, PEMT rs7946 and SLC44A1 rs7873937 altered the distribution of dietary choline between the CDP-choline and phosphatidylethanolamine N-methyltransferase (PEMT) denovo pathway. "
 

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