58 replies to this topic

[Lufega]

Ginkgo is an inducer of CYP1A1

Ginseng is also a potent induce of both CYP1A1 and 1A2.

Deglycosylated ginsenosides are more potent inducers of CYP1A1, CYP1A2 and CYP3A4 expression in HepG2 cells than glycosylated ginsenosides.
Hao M, Ba Q, Yin J, Li J, Zhao Y, Wang H.

Abstract
Ginseng is one of the most commonly used herbal medicines worldwide. Ginsenosides are believed to be responsible for the therapeutic activities of ginseng. However, co-administration of other prescription drugs with ginseng products may give rise to ginseng-drug interactions. Cytochrome P450 enzymes are major Phase I enzymes involved in the metabolism of most currently used drugs. Inhibition or induction of P450 enzymes can lead to pharmacokinetic drug interactions. Previous reports on ginseng-drug interactions have been controversial and confusing. In the present study, we examined the effects of thirteen ginsenosides on the expression of CYP1A1, CYP1A2 and CYP3A4 in HepG2 cells. We found that eight ginsenosides and aglycones potently induced CYP1A1 expression, and that structure-activity relationships existed for these effects. Moreover, we discovered that the deglycosylated ginsenosides, some of which are putative ginsenoside metabolites, were more potent inducers of CYP1A1, CYP1A2 and CYP3A4 than the glycosylated ginsenosides. This finding indicates that ginsenoside metabolites may partially account for ginseng-drug interactions, and that the differences in composition of the intestinal bacteria and the extent of deglycosylation of the ginsenosides could be a contributing factor to the inconsistencies observed in the previous clinical and pre-clinical studies with regard to ginseng-drug interactions.

Full study: http://www.jstage.js...1012150131/_pdf

Edited by Lufega, 25 February 2011 - 07:17 PM.

[Lufega]

By the way, my 23andme results came in. I'm also a fast caffeine metabolizer [metabolized by the liver enzyme cytochrome P450 1A2 (CYP1A2)]. Ironically enough, it says I'm at low risk for essential tremor (AA) genotype for that particular risk marker.

Edited by Lufega, 25 February 2011 - 07:44 PM.

[rwac]

By the way, my 23andme results came in. I'm also a fast caffeine metabolizer [metabolized by the liver enzyme cytochrome P450 1A2 (CYP1A2)]. Ironically enough, it says I'm at low risk for essential tremor (AA) genotype for that particular risk marker.

You should run your raw data thru promethease. No point in trying to increase activity of an enzyme that is non-functional.
For instance, I am a CYP3A5 non-expressor.

[KimberCT]

By the way, my 23andme results came in. I'm also a fast caffeine metabolizer [metabolized by the liver enzyme cytochrome P450 1A2 (CYP1A2)]. Ironically enough, it says I'm at low risk for essential tremor (AA) genotype for that particular risk marker.

Same here... although there is debate on the LINGO1 results posted by 23andme. Most studies say A is the risk allele, while others say it's C. 23andme must only have looked at the latter.

[Lufega]

I've tried increasing my enzyme activity against the beta-carbolines by eating alot of broccoli sprouts, brussel sprouts, etc. and seasoning my meat with herbs like rosemary (which prevent harmane from forming).

Have you considered using a rosemary extract or rosmarinic acid ? Not sure if it has any action against harmane in vivo.

Edited by Lufega, 26 February 2011 - 01:30 AM.

[KimberCT]

I've tried increasing my enzyme activity against the beta-carbolines by eating alot of broccoli sprouts, brussel sprouts, etc. and seasoning my meat with herbs like rosemary (which prevent harmane from forming).

Have you considered using a rosemary extract or rosmarinic acid ? Not sure if it has any action against harmane in vivo.

You're definately reading the same research I am! Just started supplementing rosemary last week. I like how it upregulates both phase 1 and phase 2 enzymes. I am seeing improvement lately, but rosemary is just part of my recent enzyme induction stack.

[KimberCT]

Linking my M&M thread on ET for anyone else who stumbles across this...

http://www.mindandmu...showtopic=43447

[Lufega]

Linking my M&M thread on ET for anyone else who stumbles across this...

http://www.mindandmu...showtopic=43447

Thanks for the link. You may be on to something with the CYP2A6. I also have the slow metabolizing variant *2. What else are you using to induce these enzymes aside from rosemary and riboflavin ?

[Lufega]

If lithium toxicity can cause essential tremor, maybe a deficiency can do the same. I checked my lithium levels a couple of years back and I was severely deficient. I never figured out the clinical relevance of it but this study seems interesting. I'm not making a causation here but this may have some therapeutic like riboflavin or even rosemary.

Pharmacological characterization of harmaline-induced tremor activity in mice.

Abstract
Harmaline-induced tremor in rodents is a model of essential tremor. We utilized a novel assay to quantify tremor activity in mice and found that tremor activity was dependent on harmaline dose. The first-line clinical essential tremor treatments propranolol, primidone and gabapentin and gamma-hydroxybutyrate (GHB) significantly attenuated harmaline-induced tremor. The anticonvulsants valproate and carbamazepine and the mood stabilizer lithium suppressed harmaline-induced tremor. The gamma-amino-butyric acid (GABA) receptor subtype A receptor agonist muscimol attenuated harmaline-induced tremor. By contrast, the GABA(B) receptor agonist R-baclofen increased tremor at the lowest dose tested, but had no effects at higher doses. Administration of the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists phencyclidine or 5R,10S-(+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5,10-imine hydrogen maleate (MK-801) attenuated harmaline-induced tremor. The competitive NMDA antagonist D-4-[(2E)-3-phosphono-2-propenyl]-2-piperazinecarboxylic acid (d-CPPene) dose-dependently blocked harmaline-induced tremor, as did the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide disodium salt (NBQX). The metabotropic glutamate subtype 5 (mGlu5) receptor antagonist 6-methyl-2-(phenylethynyl)pyridine (MPEP) was inactive against tremor. The dopamine reuptake inhibitor GBR12909 and the dopamine D(1)/D(2) receptor agonist apomorphine attenuated harmaline-induced tremor. Follow-up studies indicated that dopamine D(2)/D(3) but not dopamine D(1) receptor activation likely mediates the effects of apomorphine and GBR12909. Administration of compounds with sedative side-effects had no effect on tremor activity. In summary, the present data confirm the pharmacological validity of harmaline-induced tremor in mice, quantified via a novel assay, as an animal model of essential tremor. Further, these data provide additional evidence for the roles of ionotropic glutamate, GABA(A) and dopamine D(2)/D(3) receptors in the neurobiology of harmaline-induced tremor.

PMID: 19497322 [PubMed - indexed for MEDLINE]

[Lufega]

Based on your MM post, it's the GABA receptors that are target. Found this:

LiCl promotes survival of GABAergic neurons from cerebellum and cerebral cortex: LiCl induces survival of GABAergic neurons.
Volonte C, Ciotti MT, Merlo D.

Institute of Neurobiology, CNR, Rome, Italy.


Abstract
Previous studies showed that LiCl promotes short-term survival of PC12 cells after NGF or serum deprivation. In the present work, we investigate the survival effect of lithium on cerebellar granule primary cultures. While the total population of cerebellar neurons, mainly granule cells, showed only a short-term survival (about 20 h) in the presence of LiCl, the survival of 65-100% of the GABAergic interneurons originating from cerebellum and cerebral cortex at two different developmental stages was prolonged by 1-2 weeks. Optimal activity was elicited between 5 and 7 mM LiCl. The action of lithium required the presence of serum and persisted also after medium renewal. By direct visual inspection, LiCl promoted neuronal survival without apparently altering the morphological differentiation of the cells. Our studies thereby suggest a means to obtaining enriched populations of GABAergic neurons.

Chronic lithium treatment robustly protects neurons in the central nervous system against excitotoxicity by inhibiting N-methyl-D-aspartate receptor-mediated calcium influx.
Nonaka S, Hough CJ, Chuang DM.

Section on Molecular Neurobiology, Biological Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, 10 Center Drive, MSC 1272, Bethesda, MD 20892-1272, USA.


Abstract
Lithium is the most commonly used drug for the treatment of manic depressive illness. The precise mechanisms underlying its clinical efficacy remain unknown. We found that long-term exposure to lithium chloride dramatically protects cultured rat cerebellar, cerebral cortical, and hippocampal neurons against glutamate-induced excitotoxicity, which involves apoptosis mediated by N-methyl-D-aspartate (NMDA) receptors. This neuroprotection is long-lasting, occurs at therapeutically relevant concentrations of lithium with an EC50 of approximately 1.3 mM, and requires treatment for 6-7 days for complete protection to occur. In contrast, a 24-h treatment with lithium is ineffective. The protection in cerebellar neurons is specific for glutamate-induced excitotoxicity and can be attributed to inhibition of NMDA receptor-mediated calcium influx measured by 45Ca2+ uptake studies and fura-2 fluorescence microphotometry. The long-term effects of lithium are not caused by down-regulation of NMDA receptor subunit proteins and are unlikely related to its known ability to block inositol monophosphatase activity. Our results suggest that modulation of glutamate receptor hyperactivity represents at least part of the molecular mechanisms by which lithium alters brain function and exerts its clinical efficacy in the treatment for manic depressive illness. These actions of lithium also suggest that abnormality of glutamatergic neurotransmission as a pathogenic mechanism underlying bipolar illness warrants future investigation.

PMID: 9482940

Edited by Lufega, 27 February 2011 - 01:10 AM.

[KimberCT]

I have some experience with lithium. I'll make a more detailed post about it later as I'm posting from my phone at the moment.

As for other enzyme supplements...

Indole-3-carbinol
Red clover extract
Calcium-d-glucarate
NAC
Taurine
D-limonene
Armodafinil

[aaron_e]

Lufega, have you tried high dose riboflavin supplementation?

It's problamatic because you can only absorb about 25mg at a time, so you have to dose frequently, but it seems to upregulate all the flavin dependent enzymes. I've been taking 100mg 6x per day for a couple weeks now and have seen some improvement in tremor and general mental health. I'd really like to find a flavin pro-drug that's better absorbed...

have you tried riboflavin-5-phosphate?

[KimberCT]

Lufega, have you tried high dose riboflavin supplementation?

It's problamatic because you can only absorb about 25mg at a time, so you have to dose frequently, but it seems to upregulate all the flavin dependent enzymes. I've been taking 100mg 6x per day for a couple weeks now and have seen some improvement in tremor and general mental health. I'd really like to find a flavin pro-drug that's better absorbed...

have you tried riboflavin-5-phosphate?

It's really a poor solution for a riboflavin supplement. It simply passes through one's system until it reaches the colon and bacteria convert it to plain old riboflavin. Very little is actually absorbed.

[KimberCT]

I have some experience with lithium. I'll make a more detailed post about it later as I'm posting from my phone at the moment.

As for other enzyme supplements...

Indole-3-carbinol
Red clover extract
Calcium-d-glucarate
NAC
Taurine
D-limonene
Armodafinil

Still need to get around to a lithium post, but I have to dig out my notes first.


I wanted to add one more that I take... Kudzu induces CYP1A2.

[Lufega]

I added 15 mg lithium at night. It turns out lithium induces repair and regeneration throughout the body but especially the lung. I have a type of congenital emphysema and the shortness of breath was getting pretty bad but with the lithium and other things I'm using, it's going away. So for me, Lithium is a must.

[rwac]

I added 15 mg lithium at night. It turns out lithium induces repair and regeneration throughout the body but especially the lung. I have a type of congenital emphysema and the shortness of breath was getting pretty bad but with the lithium and other things I'm using, it's going away. So for me, Lithium is a must.

That's great news. Are you using Orotate or Aspartate ?

[Lufega]

I'm using orotate. The study I referenced used a concentration of 2 mM lithium chloride which I calculated to about 15 mg orotate.

[aaron_e]

found this poking around, perhaps cysteine supplementation could improve riboflavin absorption through increased human riboflavin transporter-2 expression? http://ajpgi.physiol...0.2011.abstract

[Lufega]

I started a new thread on Wemove forum in case anyone is interested. I would also like to continue the discussion here, in case it doesn't get picked up at the other forum. I think this lead is very, very promising. I found that using chlorophyllin binds to and removes carcinogens like the herecyclic amines we are discussing here. It's rather effective at doing so. I have no idea how I missed this for so long !

http://www.wemove.or...49660#Post49660

[nowayout]

Taking some supplement because it upregulates a particular enzyme acting on a particular substrate isn't smart unless you are sure that is the only thing it is doing. For the p450's, that isn't the case, since each typically metabolizes many substrates, so upregulating a particular enzyme may do good for the particular substrate you are interested in but may cause problems with some of the many otehr metabolic pathways it is involved in. Also, various drugs and supplements affect not one of the P450 enzymes but several, so in either case you are likely to be causing problems in other metabolic pathways you are not expecting.

For example, many of the p450s are active in the metabolism of hormonal pathways fundamental to health, and you might unintentionally throw those pathways out of whack. For example, there was a study where women were given DIM or I3C supplements. These upregulate one of the p450s, as mentioned several times in this thread. However, unexpectedly, the women's levels of cortisol doubled if I remember correctly. Chronically elevated cortisol will cause havoc on every single system in the body.

So the lesson is beware, you are likely to bite off more than you can chew.

Edited by viveutvivas, 03 February 2012 - 03:21 AM.

[Lufega]

Taking some supplement because it upregulates a particular enzyme acting on a particular substrate isn't smart unless you are sure that is the only thing it is doing. For the p450's, that isn't the case, since each typically metabolizes many substrates, so upregulating a particular enzyme may do good for the particular substrate you are interested in but may cause problems with some of the many otehr metabolic pathways it is involved in. Also, various drugs and supplements affect not one of the P450 enzymes but several, so in either case you are likely to be causing problems in other metabolic pathways you are not expecting.

For example, many of the p450s are active in the metabolism of hormonal pathways fundamental to health, and you might unintentionally throw those pathways out of whack. For example, there was a study where women were given DIM or I3C supplements. These upregulate one of the p450s, as mentioned several times in this thread. However, unexpectedly, the women's levels of cortisol doubled if I remember correctly. Chronically elevated cortisol will cause havoc on every single system in the body.

So the lesson is beware, you are likely to bite off more than you can chew.

Thanks for the heads up. I moved away from that concept a while ago. I also realized it could do more harm than good. The new update I posted is a completely different concept and I think it has more applications that just ET.

[fighter]

This could be linked in what I have been experiencing, losing muscle mass very rapidly. I just found out today that Anastrozole inhibits CYP450 too and I started noticing muscle loss after taking a low dose of it. Then also found out that Berberine inhibits CYP450 which I also took the same time the area near my kidneys started having pain.

Any suggestion on what to take ? :( Artemisinin is that good? I read that in some enzymes it activates and to the rest it inhibits cyp450. :(

[anagram]

isn't mitohcondria function shunted by iron, which is why the iron chelator phytic acid is so good for parkinsons?
http://www.ncbi.nlm....pubmed/18255213
phytic acid should seriously up regulate your enzymes, phytic acid is very good for mitochondria.
Selegiline, a parkinson's medication, I found out recently, acts of the nrf2 pathway to protect ageinst oxidative damage, the mao-b inhibition is just a nice little side feature.
carnosine, chlorophyllin activate nrf2 and both are antigenotoxic.
the nrf2 pathway is linked to Ho-1(heme oxygenase 1) which produces Biliverdin, the antioxidant which I am guessing is responsible for the in vivo antioxidant effect from a lot of "antioxidants". biliverdin also gets rid of heterocyclic amines like harmene so yah, parkinsons might just be low levels of biliverdin in blood.

[niner]

phytic acid should seriously up regulate your enzymes, phytic acid is very good for mitochondria.

What makes you think that?

[anagram]

phytic acid should seriously up regulate your enzymes, phytic acid is very good for mitochondria.

What makes you think that?

isn't free iron what causes aging and senescence?

[anagram]

I was also suspecting that phytic acid increases the cyp system because it is protective against carcinogenesis by benzopyrene, aflatoxin. most of the chemicals which protect against these carcinogens are inducers of cyp enzymes, speeding up the metabolism of these compounds before they can abduct DNA.
http://www.ncbi.nlm....pubmed/11245634

Edited by anagram, 19 January 2013 - 04:09 AM.

[niner]

phytic acid should seriously up regulate your enzymes, phytic acid is very good for mitochondria.

What makes you think that?

isn't free iron what causes aging and senescence?

Free iron is bad, although it's not the only thing that causes aging. However, it has nothing to do with upregulation of CYPs.

I was also suspecting that phytic acid increases the cyp system because it is protective against carcinogenesis by benzopyrene, aflatoxin. most of the chemicals which protect against these carcinogens are inducers of cyp enzymes, speeding up the metabolism of these compounds before they can abduct DNA.
http://www.ncbi.nlm....pubmed/11245634

This link has nothing to do with phytic acid. Compounds like benzopyrene are not carcinogenic until they are metabolized by the appropriate P450. Inducing p450 will actually make them more carcinogenic, not less. Those carcinogenic metabolites need to be conjugated by one of the phase 2 enzymes in order to detoxify them. You use the word "abduct" a lot. Do you know that it means "kidnap"? You're probably thinking of "adduct", although that's a noun, not a verb.

[anagram]

was wrong

Edited by anagram, 19 January 2013 - 05:03 PM.

[fighter]

I've also read that Biotin upregulates cyp450 can't remember which one though