T Nation

Does Novedex XT Increase Testosterone?

Novedex XT remains the top selling natural test booster on the market, however there remains grey area on the products effectiveness.

3 questions:

  1. Does Novedex XT actually increase testosterone levels or decrease estrogen levels as the producer claims? Or are the increases in testosterone more likely an error due to cross reaction.

(Baylor study shows huge increses in Test and Free Test, No change in LH, slight increase in estradiol, no change in lean body mass, slight reduction in body fat %) gasparinutrition.com/files/pdfs/NovedexArticle.pdf

  1. Is the main ingredient in Novedex XT (ATD) in itself androgenic? Will it produce androgenic side effects on it’s own without manipulating hormone levels?

  2. Does product Novedex XT or it’s main ingredient ATD play any positive role in the world of bodybuilding? As a standalone or part of PCT?

Any responses are greatly appreciated.

There are other posts on elitefts by Justin Harris that also talks about the product. Might want to check it out. I would be interested in hearing what others have to say as well.

ATD is an effective anti-aromatase at a modest dose. If I recall correctly that’s about 25 mg/day. It’s also an anti-androgenic compound, which is to say it counters the effect of testosterone, but this is not important at such a low dose. It reportedly is problematic at higher doses than have been tried.

A friend and owner of a small supplement company of his own had tests done for T levels and got absolutely ridiculously high reported levels – I don’t recall what but maybe it was 20 or 30 times baseline, just completely impossible – which he attributed, and I agree, to the analysis falsely picking something else up as testosterone.

Who knows, maybe that happened with the Baylor study. Has anyone read the actual thing, as opposed to the article, and can report what analytical method was used? That could resolve the question of whether they were falsely picking up some non-testosterone compound in the blood as being testosterone. ??

Anyway, on your question if ATD is androgenic: No, in fact the opposite, it is anti-androgenic but not problematically so at modest doses.

Just read through the Baylor study, here is what it says about analytical method used:

Serum samples were assayed for the hormones total and free testosterone, dihydrotestosterone (DHT), total prostate specific antigen (PSA), E1, E2, estriol (E3), SHBG, LH, growth hormone (GH), cortisol (Diagnostics Systems Laboratories, Webster, TX), and FSH (Alpco Diagnostics, Windham, NH), using enzyme-linked immunobsorbent assays (ELISA) and enzyme-immunoabsorbent assays (EIA) with a Wallac Victor- 1420 microplate reader (Perkin-Elmer Life Sciences, Boston, MA), and the assays were performed at a wavelength of either 450 or 405 nm, respectively.

The thing that gets me is the fact that in the study, estrogen levels didn’t decrease and LH did not increase. However Testosterone and DHT increased 500%. That leaves me wondering what the mode of action is?

Also, How effective of an AI would you say ATD is at a dose of 25mg/day? Would it be sufficient enough to reduce estradiol by 50%? Would a reduction of that magnitude compromise joint health?

Immunological assays are crap for measuring increases in this kind of case. It can readily mistake one compound for another. For example, unless proven otherwise ATD or ATD metabolites may bind to the antibodies used, falsely driving up readings. In other words, the measurement for testosterone may really be for testosterone plus some ATD-related species. They really should have known better. So should the “peers” who reviewed the article before publication. This is worthless.

So there is absolutely no way to have confidence that a single thing that was said to increase, did increase.

I never did a measurement of effect on estrogen of ATD and neither did my friend. I’m not subject to estrogenic problems, nor am I one of those who, for example, will experience a difference in fit of the shoes between normal estrogen and lowered estrogen, so I really couldn’t tell from usage. I erred in how I put things: I should have said that I understood a dose of 25 mg/day to be effective based on the opinion of someone I’ve found reliable. That would have made things clearer.

Reducing estradiol by 50% would be fine in almost all cases (unless really unusually low in the first place.) I don’t believe there’s an adverse effect on joint health from it.

Thanks for the response, a couple more questions and I’ll put this discussion to rest.

Another group in Ohio performed a Novedex XT study, this group also obsevered large increases in testosterone and no decrease in estrogen. Here is what it says about their analytical method used:

“Blood samples obtained at baseline (prior to supplementation), and at weekly intervals thereafter for 28 days, were analyzed for TT, BT, and E2 by radioimmunometric and chemilluminetric assays.”

Is this test any better or worse than the test used in the Baylor study? Looks like the first one is RIA, but the second chmeilluminetric assay I am unsure of.

Also, I found this on pub med:

In an article from 1980, ( http://www.ncbi.nlm.nih.gov/pubmed/7210060 ) it was shown that 1,4,6-androstatriene-3,17-dione (ATD) does interfere with a RIA for testosterone.

“Radioimmunoassay (RIA) for testosterone (T) in unchromatographed plasma extracts from ATD-treated rats gave spuriously high values for T. Cross-reaction and chromatographic studies subsequently showed that ATD and, to a much greater extent, its metabolite(s) were responsible for this overestimation. Celite column chromatography proved to be an effective way of separating T from ATD and its product(s) of metabolism.”

One more question, is it possible for natural total testosterone to increase without a rise in LH levels?

Your responses are very appreciated.

Great topic and thread, goinyayowithshow !

And good to see Bill Roberts himself getting back into the discussions, thanks Bill.

Carry on!

Thanks, NewDamage!

And,

[quote]goinyayowithshow wrote:
Another group in Ohio performed a Novedex XT study, this group also obsevered large increases in testosterone and no decrease in estrogen. Here is what it says about their analytical method used:

“Blood samples obtained at baseline (prior to supplementation), and at weekly intervals thereafter for 28 days, were analyzed for TT, BT, and E2 by radioimmunometric and chemilluminetric assays.”

Is this test any better or worse than the test used in the Baylor study? Looks like the first one is RIA, but the second chmeilluminetric assay I am unsure of.[/quote]

The only chemiluminometric assay method I know of – which doesn’t mean that must be the only one that exists – is immunological.

So, probably not any better.

[quote]Also, I found this on pub med:

In an article from 1980, ( http://www.ncbi.nlm.nih.gov/pubmed/7210060 ) it was shown that 1,4,6-androstatriene-3,17-dione (ATD) does interfere with a RIA for testosterone.

“Radioimmunoassay (RIA) for testosterone (T) in unchromatographed plasma extracts from ATD-treated rats gave spuriously high values for T. Cross-reaction and chromatographic studies subsequently showed that ATD and, to a much greater extent, its metabolite(s) were responsible for this overestimation. Celite column chromatography proved to be an effective way of separating T from ATD and its product(s) of metabolism.”[/quote]

Cool! Great find.

That settles that.

The authors and reviewers of the Baylor study really should have known. Even aside from the question that one would hope they’d have had a basic knowledge of the limitations of their analytical method of choice, when they saw increases of (or to, I don’t recall which) an apparent 500%, they should have figured something is screwy.

[quote]One more question, is it possible for natural total testosterone to increase without a rise in LH levels?

Your responses are very appreciated.

[/quote]
Total, yes, because the amount bound to SHBG is strictly a function of the free amount and the amount of SHBG. So if SHBG goes up while free stays the same, the total goes up, but the biological activity is unchanged.

As to whether free can rise without increase in LH levels, I don’t have specific evidence but I would imagine there is variation according to how responsive the testes are at any given time, which may vary, and according to rate of metabolic elimination, which may vary. But I wouldn’t expect extremely large variance.

Also, as a practical matter, LH measurements are almost always only vague approximations of biological reality.

Typically a reported value is from only a single blood draw. Yet in an individual, LH levels change very substantially over very short time periods. So it is luck whether the draw happens to be at a high, a low, or an average moment.

For an individual to have a reading that is more reliable, yet still hardly really closely correlated with testosterone level, the method of choice is draws every 15 minutes over several hours. But this is rarely done, and even this is probably not necessarily identical with or predictably-corresponding with 24 hour average level.

My answer above was based on the effect of actual LH levels – what if actual LH does not change.

But if considering the possibility of a study’s reported free testosterone changing while reported LH stays the same, another reason this could happen is that real LH did increase but the measurements happened to occur at low points.

Is it possible to have a cross reaction for DHT as well using the same analytical methods?

Thanks a ton for your responses Bill, that helps out a lot.

It’s always possible, unless and until proven NOT to be the case in the particular instance, that an immunological method will mistake one compound for another.

So, yes it’s possible that the study was wrong on not just T, but DHT as well.

This problem has a lot to do with the fact that doctors and exercise scientists, and no doubt many others, have the horrible habit of only referring to tests according to what they are INTENDED to measure, and never stop and think about what is actually measured.

What is actually measured here is binding to an anti-testosterone (or anti-DHT) antibody.

If they reported what was actually measured, level of binding to anti-testosterone antibody, then this would be accurate. The error would be on the reader’s part if he ASSumed that everything that bound to the antibody was testosterone.

But instead, because the test is INTENDED to measure testosterone and they don’t stop and think about what is actually measured, they claim that testosterone was measured and was such and such a value.

It gets even worse in medicine. For example, before testing for HIV DNA, which so far as I know comes out positive only when HIV is present, the only test used to be one for presence of antibodies that bound HIV. This was on the theory that well, if a person has antibodies that bind an HIV antigen, then probably they have them on account of their immune systems having been exposed to HIV, though in fact there are other ways this can happen.

But of course, instead of calling this a test for HIV antibodies, they called it a test for HIV, and doctors in general did not think about what was being measured, probably 95% of them did not know what was being measured, and treated it as if HIV were what was being detected.

So a lot of people were told they had HIV when they did not, where instead they had been exposed to some other antigen for which it happens that the resulting antibody will also bind the HIV antigen. Imagine how fun that is, being told you have HIV when you don’t, the error occurring because the doctor did not understand what the test measures.

For that matter, a doctor told my family that my father had a cyst in the brain “the size of a grapefruit” of which he accoridng to the doctor had only a 1 in 5000 chance of surviving, when he had nothing but swelling with water from a stroke, because the doctor did not understand what an MRI measures.

It seems very basic, and it is, that someone involved in the sciences, whether directly or as an end-user as a doctor is, would understand it’s important to know what tests actually measure. But it’s an enormously high percentage of the time that they do not and don’t even have a clue that they are missing anything.

The most generous explanation for the Baylor study is this, that they did not understand what their analytical method measured. (If they did understand it but published this anyway, then that is worse, so let’s assume it was lack of understanding.)

By the way, though it’s getting away from the “Novadex” (how sleazy is it to give supplements mis-spelled versions of drug names? Well at least not as bad as companies that give their products ACTUAL drug names, such as one that actually names their products Dianabol, Anavar, and so forth), the reason why this situation occurs with immunological-based tests is interesting and possibly helpful.

Animal immune systems, including humans, generate vast numbers of differing what you might call “trial” antibodies. They are made with fairly random binding properties. Just as, for example, hormone and other receptors have binding sites with particular shapes that some substances fit into and bind but most do not, these antibodies have binding sites with specific, pretty much random shapes. Vast numbers of them are generated.

In an infant’s development, the immune system treats binding as being “proof” that the thing bound to is OK, it’s part of the body. And so the immune system learns that it should pay no attention, develop no immune response, to these things.

Relevant binding occurs only with quite large binding subtances such as proteins, sugar residues attached to cell membranes, this sort of thing. Small molecules are exempt.

After birth (approximately) the immune system now knows what is natural to the body, and ordinarily will never attack it as those antibodies have been selected against.

From this point on, if antibodies bind to something, it will be to foreign substances such as proteins or sugar residues on bacteria or viruses. When this happens, the immune system recognizes that it’s a foreign substances, and produces more antibodies to enable attack on the invader.

Small molecules being generally ignored, if a researcher wants to develop antibodies to a small molecule, he attaches it to a large one so that it can stimulate the immune system. Sooner or later, on injection into an animal, an antibody will happen to have a suitably-shaped binding site to bind the small molecule, and the animal’s immune system will then produce more of it, lots more. This can be recovered and used for immune-based assays.

Just as with receptors, though, it isn’t just one thing that can fit into a given binding site.

So if you produce an anti-testosterone antibody, for example, not only is there no guarantee that testosterone is the only thing that can bind it, that probably is not the case. There may well be nothing else naturally present in the body that binds it, but when it comes to foreign chemicals of at-all similar structure, it’s entirely possible.

Nice discussion. I haven’t read the Baylor study report - at least not recently, but I do remember seeing a graph of the purported increase in testosterone levels (posted by a company rep) and noting from the scale that the initial levels were extremely low. I can’t remember if they were total or free, but it immediately made me suspicious and I remember that they were about the levels one would expect in a distinctly female.

It made me laugh and no-one in the (not T-Nation) thread picked up on it.

EDIT: I guess the Gaspari web site has ‘correct’ units, but still increasing T-levels to 1700ng/dL, or 2500ng/dL? I think the subjects might just have noticed something there! How the f**k they kept their weight basically constant I have no idea.

OK, found the Baylor study. I guess they swapped the units on the Free and Total T graphs - which is what I saw (Total T= 25 pg/ml, yikes!).

Anyway another thing that strikes me is the initial starting point of 520ng/DL with a bio-available of only ~160ng/dL. That’s a pretty large SHBG, especially with reasonable T levels.

Also the Baylor study quotes large E2 numbers with just a bit of error - stuff ~60pg/ml for the placebo and 80-100pg/ml for the Novedex (actually goes up slightly). Laughably the errors are generally larger (or about the same) than the actual values.

Actually the more I look at the Baylor numbers, the more I smell BS.

Anyway, my 2cents worth of drivel.

Bill, that makes a lot of sense. Thank you very much for your responses.

Glad it was helpful!

Because ATD is a compound related to testosterone, is there any way ATD could interact with the 5 alpha reductase enzyme to produce DHT?

I believe it’s almost certainly impossible for ATD (androst-1,4,6-trien-3,17-dione) to convert to DHT itself, as this would require not only the reduction of the 4-ene double bond that 5alpha-reductase accomplishes with testosterone, but reduction of the 1-ene and 6-ene double bonds as well, processes that I don’t think occur and certainly not be 5-AR. It would also require reduction of the 17-keto, though that at least is doable with another enzyme, 17b-HSD.

It’s possible that an analogue to DHT, 17b-hydroxyandrost-1,6-diene-3-one might be formed, though, by action of both those enzymes (the order of reaction would not matter, just that the molecule was acted upon by both enzymes in the course of time.)

And it’s possible that that might bind an anti-DHT antibody.

It’s also possible it might bind with either or both of those enzymatic reactions being unnecessary.

[quote]Bill Roberts wrote:
“Novadex” (how sleazy is it to give supplements mis-spelled versions of drug names? Well at least not as bad as companies that give their products ACTUAL drug names, such as one that actually names their products Dianabol, Anavar, and so forth)[/quote]

Or slightly misspelled steroid names. Which is why I have a standard distrust for a lot of products on the market.

I lot of dumb kids think they can use this product as part of a PCT for a full blown steroid cycle. I really doubt the manufacturer didn’t think this would happen.

Oh, I’m sure Rich Gaspari never heard of Nolvadex. The similarity in name surely must be a coincidence.

:wink:

Does anyone have any ideas as to why estrogen goes up slightly in the study done on this product? Perhaps that is part of the normal daily variation for E levels?