The long term safety of naringin and piperine?

[johnyq]

Both naringin and piperine are being added to almost any supplement and nutraceutical lately it seems. They both inhibit enzymes that metabolize drugs in the human body, improving the halflife and absorption of the drug/supplement they are paired with (although not in all cases).


naringin inhibits CYP3A4 and CYP1A2.
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piperine (piperidine/pepper extract) inhibits CYP3A4 and P-glycoprotein
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This gene, CYP3A4, encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and its expression is induced by glucocorticoids and some pharmacological agents. This enzyme is involved in the metabolism of approximately half the drugs which are are used today, including acetaminophen, codeine, cyclosporin A, diazepam and erythromycin. The enzyme also metabolizes some steroids and carcinogens. This gene is part of a cluster of cytochrome P450 genes on chromosome 7q21.1. Previously another CYP3A gene, CYP3A3, was thought to exist; however, it is now thought that this sequence represents a transcript variant of CYP3A4

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This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. The protein encoded by this gene localizes to the endoplasmic reticulum and its expression is induced by some polycyclic aromatic hydrocarbons (PAHs), some of which are found in cigarette smoke. The enzyme's endogenous substrate is unknown; however, it is able to metabolize some PAHs to carcinogenic intermediates. Other xenobiotic substrates for this enzyme include caffeine, aflatoxin B1, and acetaminophen. The transcript from this gene contains four Alu sequences flanked by direct repeats in the 3' untranslated region.

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P-glycoprotein (abbreviated as P-gp or Pgp) is a well-characterized human ABC-transporter of the MDR/TAP subfamily. It is extensively distributed and expressed in normal cells such as those lining the intestine, liver cells, renal proximal tubular cells, and capillary endothelial cells comprising the blood-brain barrier. P-gp is also called ABCB1, ATP-binding cassette sub-family B member 1, MDR1, and PGY1.
Contents

Function

ABCB1 is an ATP-dependent efflux pump with broad substrate specificity. It likely evolved as a defence mechanism against harmful substances.

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I have to wonder at the logic behind inhibiting enzymes that protect us from cancer and harmful substances in order to improve the absorption of a nutraceutical. It may have its use in sports supplements that are used sporadically for immediate benefits, but I'm curious as to the safety of daily ingestion of these products.


At the very least, avoid these supplements when taking any other drugs (legal or illegal). I'm personally considering removing these two ingredients from my cupboard. I'd like to hear what reps have to say however.

 

[Ziquor]

:goodpost: Piperine, a black pepper molecle, is also in grown peppers & other plants & vegi's naturally - it's harmless. It affects CYP3A4 enzymes very, very minimally. It very slightly increases ph levels of the stomach and speeds up the absorbtion of whatever else is taken with it which is why it's in mostly all supps. Naringin is actually somewhat frightening though. It works by enhancing absorbtion too, however it does so, as you stated, by inhibiting CYP3A4 AND CYP1A2 enzymes just like grapefruit juice which increases bioavailability of whatever it's in - but does so at the cost of your liver. Great info! On a side note, Wiki has some great info on it & a lot of it, but I (and many others for that) believe they aren't the most reliable source as there's many biased views on there straying away from real facts because in the end they're in this to make money unlike many non-profit informational companies. Though you'd never hear anything like that from their reps.

 

[poison]

by inhibiting CYP3A4 AND CYP1A2 enzymes just like grapefruit juice which increases bioavailability of whatever it's in - but does so at the cost of your liver.

How does that affect the liver negatively? Is the negative effect dependent on the substance who's absorbtion is being increased, or is naringin simply bad for the liver?

Good post, johnyq!

 

[Rodja]

Just as an anecdote, I have been taking either RPM and/or Drive since September and I have noticed a decreasing tolerance to alcohol. I used to be able to drink a 15 or so beers and wake-up without any sort of a hangover. Now, I have 6 drinks and I am still groggy and lethargic the next day. Or, if I go out and really have a good time, then I wake up still drunk.

My theory is that the enzymes are becoming either ineffective or production is lowered.

 

[Ziquor]

How does that affect the liver negatively? Is the negative effect dependent on the substance who's absorbtion is being increased, or is naringin simply bad for the liver?

Good post, johnyq!

Complicated - good Q. Naringin (an extract from grapefruit juice, so gf juice does this too) starts a strong inhibition of CYP3A4 enzymes increasing the workload on the liver. So liver strain is in regards to, but not soley because of, naringin. For example most compounds we intake are processed through hepatic (liver) processing. So if you take say a PH tab w/ naringin in it, the naringin will increase the liver enzymes which leads to the body absorbing more of the PH (increased bioavailability). Since the naringin increased the workload on the liver already, now the liver in turn also has to process the PH compound which as mentioned increases the bioavailabily of the PH but also puts double the strain on the liver as would be there without the naringin. So it's like a positive & a negative - you get improved absorbtion but also increased liver strain.

 

[poison]

obviously, if the substance being taken with naringin has negative sides, those negatives will increase. Let's say M1T with naringin, could be much harder on the liver than usual.

But lets say the substance is VitaminC. Will the increased absorbtion put a strain on the liver? At what point is that increased absorbtion a strain on the liver? And why is it worse to increase absorbtion by way of naringin, instead of mega-dosing the substance?

 

[Socrates44]

The problem does not necessarily come from the deregulation of enzymes so much as it has to do with the build of toxic intermediates that are no longer able to be destroyed properly, by the enzymes.

Being in pharmacy, I see a lot of problems with the liver and drug interactions and what not. I dont think messing with liver enzymes would be something I would do too much of. Certain interactions with burgamotin, another of constituent of GF juice can cause very bad reactions with certain SSRI's. Just be careful, its hard to lift if you have hepatitis or cirrhosis.

 

[Outside Backer]

Well ive been taking RPM since before it was RPM and it was in Beta.
Ive also been taking Drive since it was in Beta as well

In december I have a full panel done on me and My liver enzymes where just fine as Was BP cholest. yadda yadda

We are looking at almost a yr straight

plus ive eaten grapefruits all my life

Just personal flavor added

 

[Outside Backer]

Just as an anecdote, I have been taking either RPM and/or Drive since September and I have noticed a decreasing tolerance to alcohol. I used to be able to drink a 15 or so beers and wake-up without any sort of a hangover. Now, I have 6 drinks and I am still groggy and lethargic the next day. Or, if I go out and really have a good time, then I wake up still drunk.

My theory is that the enzymes are becoming either ineffective or production is lowered.

thats called age. at age 21 i could go on a party binge for 2 days straight and not miss a beat

at age 29 if i even attempt to party like i did when iw as young id need a week to recover

gettting old sucks :bb3:

 

[TheMyth]

btw, I think it has more to do with the caffeine/chocamine that effects the reaction to alcohol. It what makes Sparks Beer and Red Bull and Vodkas so popular.

 

[chainsaw]

I recieved this info about 6, 7-dihydroxybergamottin, it is not only from grapefruits. I was asking about their a few of their herbal extracts.

"Hi dear Sir,

Thanks for your ppt reply~

Yes,most of people don't belive that there has 6, 7-dihydroxybergamottin from nettle root etract,but it does exsit in nettle root in its infancy."

 

[Rodja]

thats called age. at age 21 i could go on a party binge for 2 days straight and not miss a beat

at age 29 if i even attempt to party like i did when iw as young id need a week to recover

gettting old sucks :bb3:

This is within the last 6 months.

 

[Ziquor]

All good info & points. You can't really say that naringin will screw up your liver. It just makes your liver work harder, & adds stress to whatever else you ingest with it that's also processed hepatically, and yes - many substances can do this. But I think the point of the original post that started this thread, if companines begin to put it in everything it could become an issue over time to ones body.

 

[joebo]

Well ive been taking RPM since before it was RPM and it was in Beta.
Ive also been taking Drive since it was in Beta as well

In december I have a full panel done on me and My liver enzymes where just fine as Was BP cholest. yadda yadda

We are looking at almost a yr straight

plus ive eaten grapefruits all my life

Just personal flavor added

Lots of things have shown no harm at first, but end up killing people. Look at the drug manufacturers and how many lawsuits they get after what they sell is proven harmful. I obviously don't expect you to say its harmful because your a rep for a company who uses the substance, but it is shown to cause issues.

 

[TheMyth]

honestly though, everything we take could cause harm later down the road, there is no way to tell what will happen in the long run from the supps we take today because they are all in their infancy of being used. But that's the gamble you take when wanting new innovative products. I would be more concerned with the food we eat now days. With all the processed food we eat, with all the artificial flavors, sweeteners, colors and preservatives, the health effects from eating those everyday far outway the health effects from a few weeks of using supplements. That's my 2 cents.

 

[Socrates44]

Yes I agree most of these supplements are in infancy, but there is something to be said with inhibiting enzymes necessary for liver function. In its moderation its fine, I just feel there is some uneccessary dangers when using products like this.

 

[rms80]

Both naringin and piperine are being added to almost any supplement and nutraceutical lately it seems. They both inhibit enzymes that metabolize drugs in the human body, improving the halflife and absorption of the drug/supplement they are paired with (although not in all cases).


naringin inhibits CYP3A4 and CYP1A2.
Invalid Link Removed

piperine (piperidine/pepper extract) inhibits CYP3A4 and P-glycoprotein
Invalid Link Removed


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I have to wonder at the logic behind inhibiting enzymes that protect us from cancer and harmful substances in order to improve the absorption of a nutraceutical. It may have its use in sports supplements that are used sporadically for immediate benefits, but I'm curious as to the safety of daily ingestion of these products.


At the very least, avoid these supplements when taking any other drugs (legal or illegal). I'm personally considering removing these two ingredients from my cupboard. I'd like to hear what reps have to say however.

Naringin is a citrus bioflavonoid, in the same family as apigenin, rutin, hesperidin, and querecetin- all compounds in this family share similar anti-oxidant and anti-carcinogenic qualities, as well as sharing the quality of inhibiting certain enzymes (most notably the CYP3A4 and some others). The positive effects of citrus bioflavonoids on the body FAR outweigh the negative. Here are a few studies to take a look at:

Biological properties of citrus bioflavonoids pertaining to cancer and inflammation.
Curr Med Chem. 2001 Feb;8(2):135-53.
Manthey JA, Grohmann K, Guthrie N.
US Citrus and Subtropical Products Laboratory, USDA, ARS, SAA, Winter Haven, FL
Citrus bioflavonoids encompass a diverse set of structures, including numerous flavanone and flavone O- and C-glycosides and methoxylated flavones. Each of these groups of compounds exhibits a number of in vitro and in vivo anti-inflammatory and anticancer actions. These biological properties are consistent with their effects on the microvascular endothelial tissue. Evidence suggests that the biological actions of the citrus flavonoids are possibly linked to their interactions with key regulatory enzymes involved in cell activation and receptor binding. The citrus bioflavonoids show little effect on normal, healthy cells, and thus typically exhibit remarkably low toxicity in animals. Citrus bioflavonoid extend their influence in vivo through their induction of hepatic phase I and II enzymes, and through the biological actions of their metabolites. Evidence clearly indicates to the potential health promoting properties of these dietary compounds.

Citrus Bioflavonoid Research Update
Hesperidin, a citrus bioflavonoid, inhibits bone loss and decreases serum and hepatic lipids in ovariectomized mice.
J Nutr. 2003 Jun;133(6):1892-7.
The purpose of this study was to examine whether hesperidin inhibits bone loss in ovariectomized mice (OVX), an animal model of postmenopausal osteoporosis. Hesperidin administration did not affect the uterine weight. These results suggest a possible role for citrus bioflavonoids in the prevention of lifestyle-related diseases because of their beneficial effects on bone and lipids.

Antiproliferative activities of citrus bioflavonoids against six human cancer cell lines.
J Agric Food Chem. 2002 Oct 9;50(21):5837-43.
Manthey JA, Guthrie N.
U.S. Citrus and Subtropical Products Laboratory, South Atlantic Area, Agricultural Research Service, U.S. Department of Agriculture, Winter Haven, Florida
Citrus fruits contain high concentrations of several classes of phenols, including numerous hydroxycinnamates, flavonoid glycosides, and polymethoxylated flavones. The latter group of compounds occurs without glycosidic linkages and has been shown to inhibit the proliferation of a number of cancer cell lines. This antiproliferative property was further demonstrated against additional human cancer cell lines, and the antiproliferative actions of a series of synthetic methoxylated flavones were also studied. Similar to the naturally occurring compounds, the synthetic compounds exhibited strong antiproliferative activities. In many cases the IC(50) values occurred below 10 microm. Other hydroxylated flavone and flavanone aglycons also exhibited antiproliferative activities against the cancer cell lines, with the flavones showing greater activities than the flavanones. Glycosylation of these compounds removed their activity. The strong antiproliferative activities of the polymethoxylated flavones suggest that they may have use as anticancer agents in humans.

Citrus fruits are well known for providing ample amounts of vitamin C. But they also supply citrus bioflavonoids, substances that are not required for life but that may improve health. The major bioflavonoids found in citrus fruits are diosmin, hesperidin, rutin, naringin, tangeretin, diosmetin, narirutin, neohesperidin, nobiletin, and quercetin. Citrus bioflavonoids and related substances are widely used in Europe to treat diseases of the blood vessels and lymph system, including hemorrhoids, chronic venous insufficiency, leg ulcers, easy bruising, nosebleeds, and lymphedema following breast cancer surgery. Citrus bioflavonoids are thought to work by strengthening the walls of blood vessels.

Naringin in itself is an excellent source of anti-oxidants, and can also greatly enhance endothelial function, while getting decreasing hepatic lipids (fatty liver). Honestly, I wouldn't throw the baby out with the bath water on this one- it is a supplement that makes other supplements you are taking more effective, plus it has some very potent pro-health characteristics.

I would, however, limit:
1. alcohol intake
2. oral steroids/ph's
3. prescription drugs

-while taking anything containing naringin- as it may alter the effects of these 3 entities. The goal of supplementation is to improve athletic performance and help the body recover faster from serious bouts of training, while at the same time potentially improving your appearance, self-esteem, and overall health and quality of life.

Number 1 does none of the above As for Numbers 2 and 3- if you decide to take these compounds, simply be aware that naringin may alter the effects, and that you should be cognicscent of the effects on the body. But as whole, naringin does many more positive things for your health, rather than negative......

 

[strategicmove]

:goodpost:, rms80 :thumbsup:

 

[TheMyth]

BAM! (in my best Emerald voice!)

 

[Ziquor]

It's funny because a supp company who's realesed a lot of new ph's this past year write on the bottle of ALL their PH's: take 1-x tablets with grapefruit juice.