19 replies to this topic

[doug123]

Source

Steroids 'kill off brain cells'

Using steroids to build bulging muscles can also trigger "catastrophic" loss of brain cells, research suggests.

The drugs are known to raise levels of the male sex hormone testosterone.

A study published in the Journal of Biological Chemistry by Yale School of Medicine found high levels of the hormone killed off nerve cells.

The researchers believe the effect might explain why some steroid users become aggressive and suicidal - a condition known as hyperexcitability.

[Steroids] are known to have a major negative effect on people's health 

The condition is well known in the bodybuilding world, where it is referred to as roid rage.

Lead researcher Professor Barbara Ehrlich said: "Next time a muscle-bound guy in a sports car cuts you off on the highway, don't get mad, just take a deep breath and realise that it might not be his fault."

The Yale team exposed cultured nerve cells to testosterone, and found that it triggered programmed cell death (apoptosis).

This is a natural process that in normal circumstances plays a key role in clearing away damaged cells which might be harmful.

However, when healthy cells also become suicidal, it can cause severe problems, and has been implicated in neurological illnesses, such as Alzheimer's and Huntingdon's disease.

Apoptosis is characterised by membrane instability, DNA fragmentation, and the activation of "executioner proteins", known as caspases.

Aggressive hamsters

A recent US study published in the journal Behavioural Neuroscience found normally placid adolescent hamsters given anabolic steroids become incredibly aggressive.

The effects lasted almost two weeks - the equivalent of half their adolescence.

Post-mortems revealed changes in the hamsters' brain activity.

Dr Richard Melloni, who led the research at Northeastern University in Boston, said it was likely the findings applied to humans.

John Brewer, director of the Lucozade Sports Science Academy, said the findings were not surprising.

"People think steroids are banned because they are performance enhancing, but the second, equally important, reason is that they are known to have a major negative effect on people's health.

"This study provides further evidence for why we should never give in to people who want to use steroids and drugs in sport. The moment we do that we will have a major hit on the health services, as use will cascade down the pyramid of sports."


Story from BBC NEWS:
http://news.bbc.co.u...lth/5398174.stm

Published: 2006/10/02 09:30:52 GMT

© BBC MMVI

[eternaltraveler]

http://www.ncbi.nlm....l=pubmed_docsum

[FunkOdyssey]

Two things to keep in mind: these are merely in vitro results, and in the human brain, testosterone aromatizes to estrogen (which is neuroprotective) at a high rate. Taken together, you have strong reason to doubt this would apply to humans in vivo. Behavioral changes observed in steroid users suggest testosterone has an influence on the brain (surprise!), but this article seems to conclude that brain cell death is the mechanism of action there -- the author is irresponsible in attempting to make that connection without supporting evidence.

[doug123]

A recent US study published in the journal Behavioural Neuroscience found normally placid adolescent hamsters given anabolic steroids become incredibly aggressive.

The effects lasted almost two weeks - the equivalent of half their adolescence.

Post-mortems revealed changes in the hamsters' brain activity.

Dr Richard Melloni, who led the research at Northeastern University in Boston, said it was likely the findings applied to humans.

This recent Yale study that reports on exposure of nerve cells in culture to elevated levels of testosterone found that such levels trigger programmed cell death (apoptosis).

Elevated levels of testosterone change brain activity...we know this from hamsters brains from post mortem (after death) analysis. The only reason we can't say "for sure" that the same effect happens in humans is because it is unethical to slice open human brains on demand.

These results support other research that suggest that brain damage is induced by steroid use, as they seem to increase testosterone levels to higher than natural levels in the brain and elsewhere.

[FunkOdyssey]

Here are the facts you are working with here: Elevated levels of testosterone change brain activity in hamsters (no mention of apoptosis here). Hamsters given anabolic steroids become aggressive. Isolated nerve cells on a dish flooded with testosterone die.

How and why is the leap made to conclude that humans taking anabolic steroids are suffering from a catastrophic loss of brain cells?

[eternaltraveler]

testosterone induced different concentration-dependent Ca2+ signaling patterns: at low concentrations of testosterone (100 nm), Ca2+ oscillations were produced, whereas high concentrations (1-10 microm) induced a sustained Ca2+ increase.

ummm they are using 100 nm as the low concentration of testosterone and 1-10 mm as the high concentration. Normal free testosterone in males is 10 nm if i remember correctly. So just to reach their low side that had no effect on killing neurons it would have to be 10 fold of normal.

[doug123]

Full paper FREE by clicking
here

Neurol Neurosurg Psychiatry. 2005 Feb;76(2):272-5.
Sex hormones modulate brain damage in multiple sclerosis: MRI evidence.omassini V, Onesti E, Mainero C, Giugni E, Paolillo A, Salvetti M, Nicoletti F, Pozzilli C.
Department of Neurological Sciences, University La Sapienza, viale dell'Universita 30, 00185 Rome, Italy.

BACKGROUND: Sex related differences in the course and severity of multiple sclerosis (MS) could be mediated by the sex hormones. OBJECTIVE: To investigate the relation between serum sex hormone concentrations and characteristics of tissue damage on conventional magnetic resonance imaging (MRI) in men and women suffering from relapsing-remitting MS. RESULTS: Serum testosterone was significantly lower in women with MS than in controls. The lowest levels were found in women with a greater number of gadolinium enhancing lesions. A positive correlation was observed between testosterone concentrations and both tissue damage on MRI and clinical disability. In men, there was a positive correlation between oestradiol concentrations and brain damage. CONCLUSIONS: The hormone related modulation of pathological changes supports the hypothesis that sex hormones play a role in the inflammation, damage, and repair mechanisms typical of MS.
PMID: 15654051 [PubMed - indexed for MEDLINE]

The point is, increasing testosterone levels can change the way your brain works. Methamphetamine abusers, for example, (over a 10 year period of abuse) lose about 10% of their brains, distributed into different regions...however, white matter is also increased by 10% -- thus little or no net loss. However, losing part of your hippocampus and cerebral cortex changes the way your brain works by setting up different signaling pathways...so...

Edited by nootropikamil, 02 October 2006 - 08:05 PM.

[eternaltraveler]

That paper shows that testosterone may be bad for women with MS but not bad for men with MS. In men estrogen was what may be bad.

conclusion: If you are a woman with MS you probably shouldn't take steriods, if you are a man with MS you probably shouldn't take estrogen

[FunkOdyssey]

In patients with multiple sclerosis? That is not a good example to use -- the disease itself causes brain damage. That's like pointing to evidence that protein fuels the growth of tumors and claiming that protein causes cancer (some people actually try to do this with casein).

[doug123]

Changes in MRIs indicate your brain does not work the same -- a change in the way your brain works is definitely damage...unless this change benefits you somehow.

A recent US study published in the journal Behavioural Neuroscience found normally placid adolescent hamsters given anabolic steroids become incredibly aggressive.

The effects lasted almost two weeks - the equivalent of half their adolescence.

Post-mortems revealed changes in the hamsters' brain activity.

Dr Richard Melloni, who led the research at Northeastern University in Boston, said it was likely the findings applied to humans.

If a post mortem analysis reveals changes in brain activity, that means the brain is technically "broken" -- at least compared with normal controls. Technically, brain damage.

[eternaltraveler]

those are hamsters. And I'd like to see the article. If they misrepresented it anything like the first article I wouldn't buy it.

[eternaltraveler]

there are plenty of negative consuquences of steriod use that are well supported.

I don't think this is one of them however

[doug123]

I believe the BBC article is well written and accurate. Of all Internet news sources, they are in the top 3, in my opinion.

[FunkOdyssey]

there are plenty of negative consuquences of steriod use that are well supported.

Of course... I am just not convinced that "broken brains" belong on that list.

I suppose it won't be long before we see something like the 80's anti-drug commercials: "This is your brain..." (holds up an egg) "This is your brain on steroids..." (cracks egg and cooks it in a frying pan)

[xanadu]

I think Funk has a point in that the researchers used high levels to show the effect. But, they did show that it had this effect and to say that this will never happen in humans is whistling in the dark. I'd say this study is indicative but not the final word. Steroids are major bad news and the negative efects on the brain are another nail in the coffin. It kind of reinforces the stereotype of the musclebound neanderthal.

[FunkOdyssey]

Anecdotally (read: nearly meaningless but still interesting), the exceptionally high level of intelligence displayed by certain steroid using/abusing Mind & Muscle members seems to fly in the face of all this doesn't it? I'd love to see some of them throw their .02 into this discussion.

[Mind]

Safety is a concern. In our authoritarian society, a lot of things are banned over safety concerns (sometimes over blown - ephedra?). What worries me is the extremism that threatens the supplement world. Steroids have many known problems, but people still use them because they want to excel. Professional athletes use them because there is big money to be made. It is worth the risk to use steroids (for a few years) in order to bring in multimillion dollar contracts. People want to excel and they will use any means possible. What regulatory agencies should be doing is weeding out dangerous supplements, while not getting in the way of the safe ones. Sports leagues should define a list of safe performance enhancing supplements that players can use. Instead the whole push seems to be toward keeping everything "natural"...whatever that means. No enhancement whatsoever is their mantra.

I don't use steroids, but I would use safe performance enhancers to up my game, if the need ever arose, and it didn't conflict with longevity.

Anecdotally (read: nearly meaningless but still interesting), the exceptionally high level of intelligence displayed by certain steroid using/abusing Mind & Muscle members seems to fly in the face of all this doesn't it? I'd love to see some of them throw their .02 into this discussion.

Arnold seems pretty smart. Joe Wieder too. More anecdotal evidence?

[doug123]

With respect to this BBC news article, I believe it suggests:

1) Testosterone induces programmed cell death (apoptosis) in culture. This might suggest that such programmed cell death may occur in living organisms as well if their brain cells come into contact with elevated levels of testosterone.

2) The journal Behavioural Neuroscience recently published some data that suggests that hamsters given anabolic steroids had different brain activity in a post mortem assay.

More info can be found below:

Plasticity in Anterior Hypothalamic Vasopressin Correlates With Aggression During Anabolic–Androgenic Steroid Withdrawal in Hamsters (PDF: 129KB), February 2006
http://www.apa.org/j.../bne1201115.pdf

An important distinction for dudes like myself, it seems, is to ensure that my testosterone blood levels stay within the "normal range" at all times, ideally somewhere between 250 to 1,200 nanograms (ng) per deciliter (dl). Yes, the upper and lower limits are spread quite far apart; but that does not mean necessarily that one should strive to take steroids to keep ones testosterone levels towards the upper limits at all times; we know little about what kind of effect -- short or long term -- this may have on overall natural testosterone production as we age.

If one does not have normal blood testosterone levels (I believe it's a similar case with HGH levels), this could be problematic, as testosterone seems to play some roles in regulating brain growth and protection...in fact, if they are too low (or too high), it seems the evidence might suggest that one might expose oneself to higher risk of becoming afflicted with neurodegenerative disorders such as Alzeheimer's disease; as is described below:

http://www.ncbi.nlm....l=pubmed_docsum

Endocrine. 2006 Apr;29(2):233-41.

Androgens, aging, and Alzheimer's disease.Pike CJ, Rosario ER, Nguyen TV.

Andrus Gerontology Center, University of Southern California, Los Angeles, CA 90089-0191, USA. cjpike@usc.edu

Testosterone depletion is a normal consequence of aging in men that is associated with senescent effects in androgen- responsive tissues. We discuss new evidence that one consequence of testosterone depletion in men is an increased risk for the development of Alzheimer's disease (AD). Furthermore, we discuss two candidate mechanisms by which testosterone may affect AD pathogenesis. First, testosterone has been identified as an endogenous regulator of beta-amyloid, a protein that abnormally accumulates in AD brain and is implicated as a causal factor in the disease. Second, findings from several different paradigms indicate that testosterone has both neurotrophic and neuroprotective functions. These new findings support the clinical evaluation of androgen-based therapies for the prevention and treatment of AD.

PMID: 16785599 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm....l=pubmed_DocSum

Neuroscience. 2006;138(3):957-65. Epub 2006 Feb 20. 

Androgen modulation of hippocampal synaptic plasticity.MacLusky NJ, Hajszan T, Prange-Kiel J, Leranth C.

Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA. nmaclusk@uoguelph.ca

This review briefly summarizes recent developments in our understanding of the role of androgens in maintaining normal hippocampal structure. Studies in rats and vervet monkeys have demonstrated that removal of the testes reduces the density of synaptic contacts on dendritic spines of cornu ammonis 1 (CA1) pyramidal neurons. This effect is rapidly reversed by treatment with either testosterone or the non-aromatizable androgen dihydrotestosterone, suggesting that maintenance of normal synaptic density is androgen-dependent, via a mechanism that does not require intermediate estrogen biosynthesis. Similar effects of these androgens are observed in ovariectomized female rats, except that in the female the actions of testosterone include a substantial contribution from estrogen formation. The ability to stimulate hippocampal spine synapse density is not directly related to systemic androgenic potency: thus, weak androgens such as dehydroepiandrosterone exert effects that are comparable to those of dihydrotestosterone; while partial agonist responses are observed after injection of the synthetic antiandrogen, flutamide. These data provide a morphological counterpart to observations that androgens enhance cognitive function and mood state, suggesting that these effects may result at least in part from hippocampal neurotrophic responses. The unusual specificity of these responses raises the possibility that effects of androgens on the brain may be mediated via different mechanisms than the masculinizing actions of these steroids in non-neural androgen target organs.

PMID: 16488544 [PubMed - indexed for MEDLINE]

So, if your testosterone levels are too low, you might consider supplementing. It's best to do this under doctor's care; I think.

[eternaltraveler]

1) Testosterone induces programmed cell death (apoptosis) in culture. This might suggest that such programmed cell death may occur in living organisms as well if their brain cells come into contact with elevated levels of testosterone.

yes but the levels of testosterone they used widely exceeded what would be found free even in a heavy steroid users blood.

[tracer]

Anecdotally (read: nearly meaningless but still interesting), the exceptionally high level of intelligence displayed by certain steroid using/abusing Mind & Muscle members seems to fly in the face of all this doesn't it? I'd love to see some of them throw their .02 into this discussion.

Well... I'm not an M&M reader... in my mind it's a publication whihc vascillates between advertisment-riddled gay porn and advertisment-riddled infantile drivel with a few exceptional articles thrown in to allow it to cling to credibility. In fact, reading one of those cover-to cover might induce apoptosis in brain tissue.

Rant aside, there are a couple of vital pieces we are missing:

From my reading of the abstract, it seems that this may have a lot more to do with induced calcium flux than de-facto agonisation of the androgen receptor leading to apoptosis. It would have been nice if they'd tried this in the presence of an AR antagonist.

However, other androgens have been shown to decrease proliferation of neurons in vitro... this effect was AR mediated, but all the androgen (19-Nortestosterone/Nandrolone) did was to attenuate the proliferation that was seen in the control in the presence of endothelial growth factor.

Right now there is nothing that convinces me one way or the other!

Also estrogen isn't the only related hormone here. Cortisol also needs consideration. Consider if you will that Testosterone is a Cortisol inhibitor, and that Cortisol is neurogenesis/neuroplasticity enemy number 1! Hence a reasonable dose of Testosterone (which is really all you need to induce body-composition effects) should decrease the effects of cortisol and produce washboard abs.

In addition, tests done on non-human cells, don't necessarily carry over that well to humans. This is especially true of androgens. Just look at Vida's Androgens

Furthermore, it is theorised that testosterone bound to sex-hormone binding globulin is as effective (if not more so) than free testosterone. The experiment above did not test bound testosterone, merely free testosterone.

Lastly, test is good as a bb drug - I reckon its one of the best and safest. However, there are many other alternatives out there, which vary in their levels of toxicity, their effects and their androgenicity... as I said, Insufficient data.

PS: Funk - is the aromatisation of test in the brain due to the presence of the aromatase enzyme in the brain (perhaps in higher concentrations than elsewhere) or is it due to something else?