Here is an interesting way to boost your test levels - natural or not.
Testosterone is broken down in the body by an enzyme called Cytochrome P450 3A,4,5,7. If you inhibit the activity of this enzyme, the testosterone in your body will not be broken down (at least not as quickly).
Here is an incomplete list of substances which inhibit the Cytochrome P450 3A,4,5,7 enzyme:
Star fruit was shown to almost completely inhibit this enzyme. Grapefruit juice was shown to be moderately inhibitory of this enzyme. Therefore, consuming these fruits may increase your test levels.
For completeness, the P450 3A,4,5,7 enzyme breaks down LOTS of substances in the body, not just testosterone. This includes the hormones estradiol, hydrocortizone, progesterone, as well as many antibiotics and other medications you may be prescribed, so be smart if you are taking other prescription meds. Here is the complete list: http://medicine.iupui.edu/flockhart/table.htm
That is the same enzyme that makes grapefruit a benzodiazepine potentator is it not?
ie. Isnt that the reason that grapefruit juice works to potentate many oral drugs? I realised that it might work for some oral anabolics, but i was not aware that testosterone itself is broken down by it... to what exactly is it broken down into? - Do you mean that this enzyme is what breaks down each of the hormones to allow them to become the inter-connected hormone or what?
^^ Basically yes, in answer to the first question. Grapefruit acts via P450 on a shitload of substrates, but it's actions are both to attenuate and inhibit reactions.
Also, P450 is really a family of related enzymes, not a single entity, potentially affecting almost every biochemical reaction in the body, so it gets complicated pretty quickly.
Grapefruit acts as an inhibitor of P450 3a4, so I assume it's preventing 3a4 from acting on testosterone substrate and catalyzing it's oxidation.
I don't know about the other P450 enzymes mentioned above(4,5 and 7).
Interestingly though, aromatase itself is a P450 enzyme. A small degree of inhibition of aromatase via red wine has been reported, and it's certainly possible that grapefruit may have an effect there as well.
ed - fwiw, i forgot to mention that 3a4 acts as a 6B hydroxylase to test... (test --> 6B hydroxytest). that's all i know
A person reading "a way to boost your test levels" and that testosterone would not be metabolized as quickly might have assumed it would be by something detectable, but it's such a minor pathway that that doesn't seem plausible, hence I thought the need to bring that out.
And not only is it minor, but I don't see where 6-hydroxytestosterone (the product of the CYP3A metabolism) is going to be eliminated any faster as a result than if it had remained unchanged testosterone.
If the question is about he effect of grapefruit on T or E metabolism, Prof Roberts is not totally wrong and Prof KSMan is not totally right. What follows is an exercise in estrogen CYT interaction:
A misconception arises from single-enzyme experiments; as it turns out that when CYT 3A4 is inhibited, 1A2 is induced by the presence of E (or T). Then 1A2 is the stronger metabolizer:
[i]1: Drug Metab Dispos. 2006 Sep;34(9):1606-14. Epub 2006 Jun 21.
Inhibition of the human liver microsomal and human cytochrome P450 1A2 and 3A4 metabolism of estradiol by deployment-related and other chemicals.
Cytochromes P450 (P450s) are major catalysts in the metabolism of xenobiotics and endogenous substrates such as estradiol (E2). It has previously been shown that E2 is predominantly metabolized in humans by CYP1A2 and CYP3A4 with 2-hydroxyestradiol (2-OHE2) the major metabolite. This study examines effects of deployment-related and other chemicals on E2 metabolism by human liver microsomes (HLM) and individual P450 isoforms. Kinetic studies using HLM, CYP3A4, and CYP1A2 showed similar affinities (Km) for E2 with respect to 2-OHE2 production. Vmax and CLint values for HLM are 0.32 nmol/min/mg protein and 7.5 microl/min/mg protein; those for CYP3A4 are 6.9 nmol/min/nmol P450 and 291 microl/min/nmol P450; and those for CYP1A2 are 17.4 nmol/min/nmol P450 and 633 microl/min/nmol P450. Phenotyped HLM use showed that individuals with high levels of CYP1A2 and CYP3A4 have the greatest potential to metabolize E2. Preincubation of HLM with a variety of chemicals, including those used in military deployments, resulted in varying levels of inhibition of E2 metabolism. The greatest inhibition was observed with organophosphorus compounds...
[/i] And then, in men and women, the metabolites of E2 are short-lived potent estrogens, and it may not be important "clinically": [i] 3: Br J Clin Pharmacol. 2003 Sep;56(3):334-6.
The effect of ketoconazole and diltiazem on oestrogen metabolism in postmenopausal women after single dose oestradiol treatment.
The AUC and Cmax of oestrone tended to increase on treatment with diltiazem although this did not reach the level of statistical significance. CONCLUSIONS: The small increase in the plasma concentrations of oestrone formed from 17beta-oestradiol during co-administration with ketoconazole is unlikely to be clinically significant. [/i]
Ketoconazole, is a much more powerful inhibitor of 3A4 than is grapefruit. So grapefruit would have a small or no effect on E2 degradation and elimination.
Prof KSman raises the issue of cimetidine, a notorious cause of gynecomastia. Can we predict the risks of gynecomastia, based on these enzyme inhibition? Gosh, someone has done that experiment:
[i] 4: Anal Biochem. 2000 Nov 15;286(2):179-86.
Studies on the interactions between drugs and estrogen: analytical method for prediction system of gynecomastia induced by drugs on the inhibitory metabolism of estradiol using Escherichia coli coexpressing human CYP3A4 with human NADPH-cytochrome P450 reductase.
To establish a prediction system for drug-induced gynecomastia in clinical fields, a model reaction system was developed to explain numerically this side effect. The principle is based on the assumption that 50% inhibition concentration (IC(50)) of drugs on the in vitro metabolism of estradiol (E2) to its major product 2-hydroxyestradiol (2-OH-E2) can be regarded as the index for achieving this purpose. By using human cytochrome P450s coexpressed with human NADPH-cytochrome P450 reductase in Escherichia coli as the enzyme, the reaction was examined. Among the nine enzymes (CYP1A1, 1A2, 2A6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4) tested, CYP3A4 having a V(max)/K(m) (ml/min/nmol P450) value of 0.32 for production of 2-OH-E2 was shown to be the most suitable enzyme as the reagent. The inhibitory effects of ketoconazole, cyclosporin A, and cimetidine toward the 2-hydroxylation of E2 catalyzed by CYP3A4 were obtained, and their IC(50) values were 7 nM, 64 nM, and 290 microM, respectively. The present results suggest that IC(50) values thus obtained can be substituted as the prediction index for gynecomastia induced by drugs, considering the patients' individual information. [/i] So cimetidine is a comparatively weaker inhibitor of E2 catabolism, by this assay. I do not know if cimetidine or grapefruit is a powerful inhibitor of the inducible 1A2 enzyme, which may be important.
But the original question was about grapefruit, no? It all depends on what you choose to measure, and in this case, estrone formation was not inhibited but the (usually less important) estriol was inhibited by grapefruit. [i]
5: Eur J Drug Metab Pharmacokinet. 1995 Jul-Sep;20(3):219-24.
Flavonoids in grapefruit juice inhibit the in vitro hepatic metabolism of 17 beta-estradiol.
Naringenin, quercetin and kaempferol, which may be found in glycoside form in natural compounds such as grapefruit, are potent inhibitors of cytochrome P-450 metabolism. The influence of these flavonoids on the metabolism of 17 beta-estradiol was investigated in a microsome preparation from human liver. The flavonoids were added in concentrations of 10, 50, 100, 250 and 500 mumol/l to the microsome preparation. The metabolism of 17 beta-estradiol was concentration dependently inhibited by all the flavonoids tested. Addition of the flavonoids to the microsome preparation did not influence estrone formation, while a potent inhibition of estriol formation was observed. At the highest concentrations tested of the respective flavonoid, there was approximately 75-85% inhibition of estriol formation. ... These hydroxylation processes represent the predominant steps of the hepatic metabolic conversion of endogenous as well as exogenous 17 beta-estradiol. This interaction would be expected to inhibit the first-pass metabolism of 17 beta-estradiol, and this has recently been demonstrated after oral administration of 17 beta-estradiol to women.[/i]
(There is an error in the last sentence: in 1995, they did not know that intestinal absorption of E2 was increased by CYT 3A4 inhibitors.)
Simple questions merit simple answers. You can drink your grapefruit juice...sometimes.
I hadn't interpreted KSman's post as saying or providing anything showing that I was wrong on this (not that that could never happen). I had taken his "totally wrong" statement as applying, rather, to the original thesis.