Bergamotten, Quercetin, and Bioperine

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    Angry Bergamotten, Quercetin, and Bioperine


    Supp companies are putting quercetin and bergamotten and bioperine in just about every other supplement that I come across. While these black pepper and grapefruit juice extracts and metabolites do increase the effect of the supps to which they are added, they do so in an arguably stupid and dangerous way. Just inhbit the CYP450 enzymes-duh.

    Except that lots of drugs are metabolized by this pathway, including oral anabolics (if you take dbol with grapefruit juice, you better cut back the dose-elitefitness substantiates this) and drugs like diazepam/valium (which I take for muscle spasms) are so affected that you cannot take a supplement containing any of the above safely with diazepam and similar drugs. I found a study yesterday that showed that bergamotten increased plasma levels of diazepam in beagle by a factor of -100- when coadministered (10mg dose of diazepam given (I take 45mg a day), and the control group of diazepam only had levels of 2.5ng/dl or something and the coadministration group had levels of ~250ng/dl).

    Granted, this would not kill most people, but you would be somewhat comatose for a day or two after just a single occurrence. One patient given 500mg of diazepam didn't have any serious effects except that he was in the hospital and in a light coma state for 3 days. DTHC, Animal Stak Flex, hell even a lot of COQ10 has Bioperine now, and lots of other supps that I would like to try just have to throw these ingredients in, and then I cannot take them. That is what irritates me; if people like it that way, that's fine. But why not have some versions of the above without these crude mechanism additives that are too dangerous for me to even take? More dangerous than real anabolics, no question, cuz I take those. And they don't even come with anything except a generic consult your physican label just like Centrum Silver or some similar crap! Thank the FDA and the DSHEA for not allowing more specific stuff like "medicines that interact with grapefruit juice will interact with this product, possibly dangerously so".

    In my mind, the only purpose these chemicals serve is to make an inefficient product efficient (crudely) or to make an efficient product (like dbol) more efficient so that less is needed. At least dbol doesn't come with 5mg of bioperine per 5mg tablet!

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    Interesting read, I was wondering about your opinion on Bergamottin with Furazadrol.. I found a Furazadrol Supplement by German American Technologies (GAT) That contains 50.5mg Fura & 200mg Bergamottin per capsule..

    Now to the question; since Bergamottin enhances the Furaz effects could I stick to a 150-250mg dose instead of 300mg like most people suggest?

    5caps (250mg Fura would result in a consumption of1g Bergamottin per day, is there any recommended dosage on Bergamottin?

    I'd appreciate your opinion on this

    //CC
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    Bergamottin is a principle ingredient in grapefruit juice that is consequently responsible for most of the CYP3A4 enzyme inhibition caused by consuming grapefruit juice.

    Taking 1g a day of bergamottin should be no more harmful than consuming the equivalent number of glasses of grapefruit juice a day (whatever that is).

    However, you want to be sure that you aren't taking any medications (esp. RX ones) that are metabolized by CYP3A4. You can google to find a list of RX drugs metabolized by this enzyme. Valium and Xanax and many others are metabolized by this enzyme and taking them with grapefruit juice would be a minor to major disaster (plasma levels increased up to 100-fold in beagles-your 1 xanax just turned into 100 IOW).

    If you aren't taking anything that would interact, it should be fine. However, you may want to do some digging on furazadrol (and the steroid furazabol) b/c many steroids are metabolized by CYP3A4 (probably the "reasoning", if any was used, for including bergamottin with the furaz). For instance, many bodybuilders will take their d-bol with a glass of grapefruit juice and reduce their dose of d-bol (25mg without a glass of grapefruit juice seems to be about the same as 15mg of dbol with the juice, no pun intended). Furaz is pretty safe, so possibly increased plasma levels probably wouldn't hurt you. There isn't much research on furaz unfortunately. I would probably run it at 200mg the first week just to make sure that the bergamottin doesn't make it function like 600mg, and then go to 250 or 350 (300-350 seems to be the sweet spot, but I don't know if the bergamottin actually increases the effectiveness of a lesser dose or not).
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    Thanx for your opinion! I will take your advice and run it at 150-200 the first days and increase the dose by 50mg until I'm @ 250-300, depending on how I feel
    Thanx again!

    //CC
    SNS - Serious Nutrition Solutions
    My advice is exclusively my own and may not correspond with the views of SNS
    Questions or concerns? → conny[@]seriousnutritionsolutions.com
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    Quote Originally Posted by dumbhick3 View Post
    Bergamottin is a principle ingredient in grapefruit juice that is consequently responsible for most of the CYP3A4 enzyme inhibition caused by consuming grapefruit juice.

    Taking 1g a day of bergamottin should be no more harmful than consuming the equivalent number of glasses of grapefruit juice a day (whatever that is).

    However, you want to be sure that you aren't taking any medications (esp. RX ones) that are metabolized by CYP3A4. You can google to find a list of RX drugs metabolized by this enzyme. Valium and Xanax and many others are metabolized by this enzyme and taking them with grapefruit juice would be a minor to major disaster (plasma levels increased up to 100-fold in beagles-your 1 xanax just turned into 100 IOW).

    If you aren't taking anything that would interact, it should be fine. However, you may want to do some digging on furazadrol (and the steroid furazabol) b/c many steroids are metabolized by CYP3A4 (probably the "reasoning", if any was used, for including bergamottin with the furaz). For instance, many bodybuilders will take their d-bol with a glass of grapefruit juice and reduce their dose of d-bol (25mg without a glass of grapefruit juice seems to be about the same as 15mg of dbol with the juice, no pun intended). Furaz is pretty safe, so possibly increased plasma levels probably wouldn't hurt you. There isn't much research on furaz unfortunately. I would probably run it at 200mg the first week just to make sure that the bergamottin doesn't make it function like 600mg, and then go to 250 or 350 (300-350 seems to be the sweet spot, but I don't know if the bergamottin actually increases the effectiveness of a lesser dose or not).
    99% of the prescribed RX users would know not chase their Zanax or Valium with grapefruit juice. Unless they are trying to get buzzed, or take a dirtnap.

    Where is the half-life of the Bergamotten, Quercetin, and Bioperine that you are speaking of?

    This, to me, would be the most relevant data needed. That way one could manage the supplements that included them and RX meds effected by them, more safely.
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    Quote Originally Posted by Kristofer68SS View Post
    99% of the prescribed RX users would know not chase their Zanax or Valium with grapefruit juice. Unless they are trying to get buzzed, or take a dirtnap.

    Where is the half-life of the Bergamotten, Quercetin, and Bioperine that you are speaking of?

    This, to me, would be the most relevant data needed. That way one could manage the supplements that included them and RX meds effected by them, more safely.
    For the poster above, I think the most important question is whether he takes any CYP3A4-extensively metabolized RX drugs. If no, then the significance of berg's half-life is less important unless you are worried about OD'ing on a grapefruit juice component.

    The half-life of the RX drug in question is also relevant; diazepam's half-life is something like 48-96 hours.

    BTW, I take diazepam and don't drink grapefruit juice or take any of the above three "filler" additives (berg, querc, biop). I originally made this post b/c I was getting irritated by the trend towards so many great supps including one or more of the above which automatically means I can't risk taking what might otherwise be a great product for me. I got over it, but as a result, I generally avoid multi-ingredient supps other than multi-vitamins.

    What you say about 99% of benzo users is possibly accurate (though not everyone reads the RX monogram and they don't always stick an "avoid grapefruit juice..." sticker on the bottle), but the bergamottin in grapefruit juice is I think the primary potent inhibitor of CYP3A4 (the juice has several ingredients that can affect CYP3A4, but berg alone seems to duplicate the results). 99% of benzo users don't know what the hell bergamottin is, but it has found its way into a multitude of supplements nonetheless.

    I've used benzos as the primary example but there are several other classes and types of RX drugs that should not be coadministered with potent cyp3a4 inhibitors such as bergamottin. If you are taking furaz+quercetin, I imagine that is 3 doses a day. That is pretty consistent with dosing frequency for daytime benzo use, so it would be hard not to coadminister them. There is also a repeated-doses effect with berg; check out the beagle study below.

    http://en.wikipedia.org/wiki/CYP3A4
    Interaction List

    http://dmd.aspetjournals.org/content/30/2/135.full
    The beagle study and some comments on humans and grapefruit juice in general and berg in particular.
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    Quote Originally Posted by dumbhick3 View Post
    Just google for some studies on coadiminstration of bergamottin and diazepam; the 100-fold increase in plasma concentrations of diazepam for any length of time answers the RX side of the equation in a nutshell IMO. The half-life of the RX drug in question is also relevant; diazepam's half-life is something like 48-96 hours so it would matter when you took the bergamottin if you took diazepam regularly.

    BTW, I take diazepam and don't drink grapefruit juice or take any of the above three "filler" additives; I originally made this post b/c I was getting irritated by the trend towards so many great supps including one or more of the above which automatically means I can't risk taking what might otherwise be a great product for me. I got over it, but as a result, I generally avoid multi-ingredient supps other than multi-vitamins.

    What you say about 99% of benzo users is possibly accurate (though not everyone reads the RX monogram), but the bergamottin in grapefruit juice is what potently inhibits CYP3A4. 99% of benzo users don't know what the hell bergamottin is, but it has found its way into a multitude of supplements nonetheless.
    Of the 3 "fillers" as you like to call them. You havent provided any real tangible data on any of them.

    For instance-The specific dosage amounts, clinical dosage along with possible side effects and half-lifes. This is very important and relevant data.

    Without trying to be too rude.

    I'm not making the case against them, you are. You google them.

    Seems to me you are extrapolating an awful lot from that one Beagle Study.
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    Quote Originally Posted by Kristofer68SS View Post
    Of the 3 "fillers" as you like to call them. You havent provided any real tangible data on any of them.

    For instance-The specific dosage amounts, clinical dosage along with possible side effects and half-lifes. This is very important and relevant data.

    Without trying to be too rude.

    I'm not making the case against them, you are. You google them.

    Seems to me you are extrapolating an awful lot from that one Beagle Study.
    Here is Concrete's question:

    5caps (250mg Fura would result in a consumption of1g Bergamottin per day, is there any recommended dosage on Bergamottin?

    I'd appreciate your opinion on this
    OK. Now, let me clarify something (two things actually).

    First, by "the poster above", I wasn't referring to you Kristofer, I was referring to ConcreteConny. So instead of just asking more questions and making rude, unhelpful, sarcastic comments to me, why don't you try to answer some questions for Concrete yourself since I am doing such a terrible job and provide some information to help him?

    Second, this thread is old as dirt; it isn't about me versus those 3 "fillers"; check the date of the OP relative to Concrete's post. ConcreteConny resurrected it with some questions about a supplement of his, and I tried to respond intelligently (sorry if I failed Concrete). I all but forgot about this thread until it showed up on my control panel. I am no longer trying to "make a case" against these substances and haven't been for some time (I simply don't use them-problem solved). I was just trying to help Concrete (a fellow AM member, you know?) out with his question, nothing more (I guess I failed). Why aren't you lending your expertise to the situation?

    The interactions of these 3 "fillers" with RX drugs is concern #1 in my mind. When in doubt about an interaction, the safest approach is to not take the potentially interacting supplement. What works for me may not work for others though. That is always my first concern with taking these substances or advising others about them. I wouldn't recommend to someone else that they take a CYP3A4 inhibitor with a CYP3A4 inducing drug under any circumstances and without the need for any further knowledge of these three chemicals given what I already know about them (and I read more than one beagle study BTW). As far as clinical doses, with the exception of quercetin, these aren't clinically used substance, so the clinical data in that regard lacketh. Go figure. So, given the nature of the supplement industry, and assuming no dangerous drug interactions, it's buyer beware. Probably safe to take 1g of bergamottin a day, but certainly no guarantees in the supp industry. That's why I advised to start with a lower dose to determine its effects with the furaz and then go up.

    Why don't I google all the things you mention Kristofer? I don't have any questions that need answering about these substances. I do have limited time and do try to answer the questions of others to the best of my ability though. I would have even tried to answer some of the questions you raised but did not answer if not for the attitude.

    Good luck with your cycle Concrete and maybe glance at the last quote block below (its for quercetin, but there may be some cross-similarity between it and bergamottin).

    http://dmd.aspetjournals.org/content/30/9/977.full.pdf
    EFFECTS OF BERGAMOTTIN ON HUMAN AND MONKEY DRUG-METABOLIZING ENZYMES IN PRIMARY CULTURED HEPATOCYTES
    YUAN HUA WEN, JASMINDER SAHI, ELLEN URDA, SHAILA KULKARNI, KELLY ROSE, XIANXIAN ZHENG, JACQUELINE F. SINCLAIR, HONGBO CAI, STEPHEN C. STROM, AND VSEVOLOD E. KOSTRUBSKY
    Departments of Drug Safety Evaluation (Y.H.W., E.U., S.K., V.E.K.), Pharmacokinetics, Dynamics, and Metabolism (J.S., K.R), and Molecular
    Sciences (X.Z.), Pfizer Global Research and Development, Ann Arbor, Michigan; Veterans Administration Medical Center, White River Junction,
    Vermont (J.F.S.); Departments of Biochemistry and Pharmacology/Toxicology, Dartmouth Medical School, Hanover, New Hampshire (J.F.S.);
    and University of Pittsburgh Medical Center, Department of Pathology, Pittsburgh, Pennsylvania (H.C., S.C.S.)
    (Received March 21, 2002; accepted May 29, 2002)
    This article is available online at http://dmd.aspetjournals.org
    ABSTRACT:
    We investigated the effect of bergamottin, a major furanocoumarin in grapefruit juice, on phase I and phase II drug-metabolizing enzymes using cultured human and monkey hepatocytes. Both cultured systems were compared and evaluated for the direct effects of bergamottin as well as control treatments on liver enzymes. Treatment of hepatocytes with 0.1, 1, 5, and 10 M bergamottin resulted in a concentration-dependent reduction in CYP3A4 activity (40–100%) in both human and monkey cells, as measured
    by testosterone 6-hydroxylase activity. Bergamottin was potent at eliciting these inhibitory effects at both basal and induced states of CYP3A. Bergamottin (5 M) completely inhibited -naphthoflavone-induced ethoxyresorufin O-dealkylase (EROD) and methoxyresorufin O-dealkylase (MROD) activities in human hepatocytes and caused a 100% decrease in EROD activity in monkey hepatocytes. A 48-h exposure of cultured human hepatocytes to bergamottin resulted in increased levels of immunoreactive
    CYP3A4, CYP1A1, and CYP1A2 proteins, and CYP3A4, CYP1A1, CYP1A2, CYP2B6, and UDP-glucuronosyl transferase mRNAs. There was only a 20 to 30% reduction in glucuronidation and sulfation of 4-methylumbelliferone in human hepatocytes by 10 M bergamottin and no effect on conjugation in the monkey hepatocytes. These results suggest that bergamottin causes both inhibition of CYP3A and CYP1A1/2 enzymatic activities and induction of
    correspondent proteins and mRNAs.
    http://www.nature.com/clpt/journal/v...t2004537a.html

    Bergamottin contribution to the grapefruit juice|[ndash]|felodipine interaction and disposition in humans|[ast]|
    Theunis C. Goosen , Dor|[eacute]| Cilli|[eacute]| , David G. Bailey , Chongwoo Yu , Kan He , Paul F. Hollenberg , Patrick M. Woster , Lucinda Cohen , J. Andrew Williams , Malie Rheeders & H. Paul Dijkstra

    AbstractObjectives: Our objectives were to evaluate the contribution of bergamottin to the grapefruit juice–felodipine interaction and to characterize bergamottin disposition. Methods: In this study 250 mL grapefruit juice; 2-, 6-, or 12-mg capsules of bergamottin plus water; or water was administered with 5 mg extended-release felodipine to 11 volunteers in a partially randomized, 5-way crossover study. Plasma concentrations of felodipine, its primary metabolite (dehydrofelodipine), bergamottin, and 6|[prime]|,7|[prime]|-dihydroxybergamottin were determined. Results: Grapefruit juice (containing 1.7 mg bergamottin) increased peak plasma concentration (Cmax) and area under the plasma concentration–time curve (AUC) of felodipine by 89% (P P max increased by 33% (P max was enhanced by 35% (P max increased by 40% (P P max values of 2.1 and 5.9 ng/mL, respectively, and times to reach Cmax of 0.8 and 1.1 hours, respectively. The bergamottin metabolite 6|[prime]|,7|[prime]|-dihydroxybergamottin was detected in plasma of some subjects after bergamottin administration. Conclusions: Bergamottin enhanced the oral bioavailability of felodipine and may cause a clinically relevant drug interaction in susceptible individuals. Grapefruit juice–drug interactions likely also involve other furanocoumarins, possibly acting in combination by additive or synergistic mechanisms. Bergamottin has systemic availability and is metabolized in vivo to 6|[prime]|,7|[prime]|-dihydroxybergamottin. Clinical Pharmacology & Therapeutics (2004) 76, 607–617; doi: 10.1016/j.clpt.2004.08.019
    If 6 and 12mg of bergamottin can do that, I wonder what 1,000mg can do, or 200mg in a drug-interaction context? Again, so far as I know bergamottin isn't clinically used, so I have seen little on recommended doses, toxicity levels, etc. Perhaps you could help us out Kristofer?

    http://www.webmd.com/vitamins-supple...CETIN&********2

    Quercetin is POSSIBLY SAFE for most people when up to 500 mg twice daily is taken by mouth for up to one month. It is not known if longer-term use or larger amounts are safe.

    Quercetin can cause headache and tingling of the arms and legs. Very high doses might cause kidney damage.

    Moderate Interaction Be cautious with this combinationAntibiotics (Quinolone antibiotics) interacts with QUERCETIN

    Taking quercetin along with some antibiotics might decrease the effectiveness of some antibiotics. Some scientists think that quercetin might prevent some antibiotics from killing bacteria. But it's too soon to know if this is a big concern.
    Some of these antibiotics that might interact with quercetin include ciprofloxacin (Cipro), enoxacin (Penetrex), norfloxacin (Chibroxin, Noroxin), sparfloxacin (Zagam), trovafloxacin (Trovan), and grepafloxacin (Raxar).

    Cyclosporin (Neoral, Sandimmune) interacts with QUERCETIN

    Cyclosporin (Neoral, Sandimmune) is changed and broken down by the liver. Quercetin might decrease how quickly the liver breaks down cyclosporin (Neoral, Sandimmune). Taking quercetin might increase the effects and side effects of this medication. Before taking quercetin talk to your healthcare provider if you take cyclosporin (Neoral, Sandimmune).

    Medications changed by the liver (Cytochrome P450 2C8 (CYP2C8) substrates) interacts with QUERCETIN

    Some medications are changed and broken down by the liver. Quercetin might decrease how quickly the liver breaks down some medications. Taking quercetin along with these medications that are changed by the liver might increase the effects and side effects of your medication. Before taking quercetin talk to your healthcare provider if you take any medications that are changed by the liver.
    Some medications that are changed by the liver include paclitaxel (Taxol), rosiglitazone (Avandia), amiodarone (Cordarone), docetaxel (Taxotere), repaglinide (Prandin), verapamil (Calan, Isoptin, Verelan), and others.

    Medications changed by the liver (Cytochrome P450 2C9 (CYP2C9) substrates) interacts with QUERCETIN

    Some medications are changed and broken down by the liver. Quercetin might decrease how quickly the liver breaks down some medications. Taking quercetin along with these medications that are changed by the liver might increase the effects and side effects of your medication. Before taking quercetin talk to your healthcare provider if you take any medications that are changed by the liver.
    Some medications that are changed by the liver include celecoxib (Celebrex), diclofenac (Voltaren), fluvastatin (Lescol), glipizide (Glucotrol), ibuprofen (Advil, Motrin), irbesartan (Avapro), losartan (Cozaar), phenytoin (Dilantin), piroxicam (Feldene), tamoxifen (Nolvadex), tolbutamide (Tolinase), torsemide (Demadex), warfarin (Coumadin), and others.

    Medications changed by the liver (Cytochrome P450 2D6 (CYP2D6) substrates) interacts with QUERCETIN

    Some medications are changed and broken down by the liver. Quercetin might decrease how quickly the liver breaks down some medications. Taking quercetin along with these medications that are changed by the liver might increase the effects and side effects of your medication. Before taking quercetin talk to your healthcare provider if you take any medications that are changed by the liver.
    Some medications that are changed by the liver include amitriptyline (Elavil), codeine, flecainide (Tambocor), haloperidol (Haldol), imipramine (Tofranil), metoprolol (Lopressor, Toprol XL), ondansetron (Zofran), paroxetine (Paxil), risperidone (Risperdal), tramadol (Ultram), venlafaxine (Effexor), and others.

    Medications changed by the liver (Cytochrome P450 3A4 (CYP3A4) substrates) interacts with QUERCETIN

    Some medications are changed and broken down by the liver. Quercetin might decrease how quickly the liver breaks down some medications. Taking quercetin along with these medications that are changed by the liver might increase the effects and side effects of your medication. Before taking quercetin talk to your healthcare provider if you take any medications that are changed by the liver.
    Some medications that are changed by the liver include lovastatin (Mevacor), clarithromycin (Biaxin), cyclosporine (Neoral, Sandimmune), diltiazem (Cardizem), estrogens, indinavir (Crixivan), triazolam (Halcion), verapamil (Calan, Isoptin, Verelan), alfentanil (Alfenta), fentanyl (Sublimaze), losartan (Cozaar), fluoxetine (Prozac), midazolam (Versed), omeprazole (Prilosec), lansoprazole (Prevacid), ondansetron (Zofran), propranolol (Inderal), fexofenadine (Allegra), amitriptyline (Elavil), amiodarone (Cordarone), citalopram (Celexa), sertraline (Zoloft), ketoconazole (Nizoral), itraconazole (Sporanox), and numerous others.

    Medications moved by pumps in cells (P-glycoprotein Substrates)) interacts with QUERCETIN

    Some medications are moved by pumps in cells. Quercetin might make these pumps less active and increase how much of some medications get absorbed by the body. This might cause more side effects from some medications.
    Some medications that are moved by these pumps include diltiazem (Cardizem), verapamil (Calan, Isoptin, Verelan), digoxin (Lanoxin) cyclosporine (Neoral, Sandimmune), saquinavir (Invirase), amprenavir (Agenerase), nelfinavir (Viracept), loperamide (Imodium), quinidine, paclitaxel (Taxol), vincristine, etoposide (VP16, VePesid), cimetidine (Tagamet), ranitidine (Zantac), fexofenadine (Allegra), ketoconazole (Nizoral), itraconazole (Sporanox), and others.
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    You didn't fail dumbhick, you provided me with your own opinion the matter and gave me an example of how you would dose the Fura containing the Bergamottin. I highly appreciate your opinion and you gave me the answers I was looking for.
    I don't know why someone must come in start debating about something else that is totally irrelevant to my question.
    I asked for your opinion and you provided me with an answer - you didn't fail me.
    And as for the RX Drugs - thanks for the heads up, but I ain't taking any

    //CC
    SNS - Serious Nutrition Solutions
    My advice is exclusively my own and may not correspond with the views of SNS
    Questions or concerns? → conny[@]seriousnutritionsolutions.com
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