AAS: Hitting a dozen pins with a sledge hammer
You guys are toying with insulin control of the liver cholesterol cascade, and hence the trans-sulfuration and re-methylation pathways are dysregulated by unintended binding of steroid analogs to key nuclear receptors.
You are inducing hypogonadal insult and cardiovascular disease. Not correlated here, but also understood: changes in liver tryptophan metabolism, and the cascade of serotonin and dopamine down-regulation that is a key contributor to various neurochemical symptoms and disorders observed among chronic AAS users.
Know your tradeoffs.
Homocysteine induced cardiovascular events: a consequence of long term anabolic-androgenic steroid (AAS) abuse. Graham MR, Grace FM, Boobier W, Hullin D, Kicman A, Cowan D, Davies B, Baker JS. Br J Sports Med. 2006 Jul;40(7):644-8.
OBJECTIVES: The long term effects (>20 years) of anabolic-androgenic steroid (AAS) use on plasma concentrations of homocysteine (HCY), folate, testosterone, sex hormone binding globulin (SHBG), free androgen index, urea, creatinine, haematocrit (HCT), vitamin B12, and urinary testosterone/epitestosterone (T/E) ratio, were examined in a cohort of self-prescribing bodybuilders. METHODS: Subjects (n = 40) were divided into four distinct groups: (1) AAS users still using AAS (SU; n = 10); (2) AAS users abstinent from AAS administration for 3 months (SA; n = 10); (3) non-drug using bodybuilding controls (BC; n = 10); and (4) sedentary male controls (SC; n = 10). RESULTS: HCY levels were significantly higher in SU compared with BC and SC (p<0.01), and with SA (p<0.05).
--->Fat free mass was significantly higher in both groups of AAS users (p<0.01).
Daily energy intake (kJ) and daily protein intake (g/day) were significantly higher in SU and SA (p<0.05) compared with BC and SC, but were unlikely to be responsible for the observed HCY increases. HCT concentrations were significantly higher in the SU group (p<0.01). A significant linear inverse relationship was observed in the SU group between SHBG and HCY (r = -0.828, p<0.01), indicating a possible influence of the sex hormones in determining HCY levels. CONCLUSIONS: With mounting evidence linking AAS to adverse effects on some clotting factors, the significantly higher levels of HCY and HCT observed in the SU group suggest long term AAS users have increased risk of future thromboembolic events.
Steroids, sex hormone-binding globulin, homocysteine, selected hormones and markers of lipid and carbohydrate metabolism in patients with severe hypothyroidism and their changes following thyroid hormone supplementation. Bicikova M, Hampl R, Hill M, Stanicka S, Tallova J, Vondra K. Clin Chem Lab Med. (2003) 41(3):284-92.
Laboratory markers of thyroid function, selected steroid hormones, sex hormone-binding globulin (SHBG), homocysteine, prolactin, major markers of lipid- and glucose metabolism and of insular-growth hormone axes were investigated in fasting sera from 16 female patients with severe hypothyroidism after thyroidectomy because of thyroid cancer. The results obtained in severe hypothyroidism within 5-6 weeks after withdrawal of thyroid substitution therapy before control scintigraphy were compared with those obtained after correction of thyroid function. Elevated levels of homocysteine and prolactin in hypothyroidism significantly decreased after correction, while SHBG concentration increased.
--->Correction of thyroid function led to significant changes of growth hormone and immunoglobulin F1 (decrease and increase, respectively), while insulin and proinsulin increased only insignificantly. Elevated levels of total cholesterol and triglycerides in hypothyroidism were normalized, along with a significant increase in high density lipoprotein (HDL)-cholesterol.
--->As revealed by correlation and factor analyses, different relationships characterizing both states were found in hypothyroidism and after correction of thyroid function. A strong inverse relationship between homocysteine and free thyroid hormones confirms the effect of thyroid hormones on homocysteine metabolism. No such inverse relation was found in euthyroid state, however. Similarly, in hypothyroidism only, dehydroepiandrosterone sulfate correlated positively with immunoglobulin F1 and homocysteine and negatively with thyroid hormones and SHBG.
Just to make sure you get the message loud and clear:
Raised concentrations of C reactive protein in anabolic steroid using bodybuilders. Grace FM and Davies B. (same two labs as the first citation, clever Brits). Br J Sports Med. (2004) Feb;38(1):97-8.
OBJECTIVE: To examine levels of C reactive protein in users of anabolic androgenic steroids (AAS) compared with age matched control groups consisting of AAS using (but abstinent)/resistance trained and non-drug using/sedentary controls. METHOD: Subjects included AAS using bodybuilders (n = 10); bodybuilders who denied AAS use (n = 10); sedentary controls (n = 8). Venous blood was sampled, from which serum concentrations of C reactive protein, male sex hormones, and cardiac troponin T were determined. RESULTS: A significantly altered hormonal profile in the AAS using group provided indirect confirmation of AAS use. C reactive protein concentrations were significantly (p<0.05) higher in the AAS using bodybuilders. There was no relation between C reactive protein and cardiac troponin T.
CONCLUSION: AAS using bodybuilders had significantly higher C reactive protein concentrations, indicating a greater propensity to develop peripheral arterial disease.
http://bjsm.bmjjournals.com/cgi/content/full/38/1/97
(unfortunately, these Brits don't seem to understand the effect of androgen induced upregulation of LOX and COX pathway induced inflammation in erythrocytes. Remember, this also leads to red blood cell hyperplasia.
CRP and PAI expression are upregulated by sterol nuclear receptor protein SRC-1; I have laid out a nice, albeit technically dense, explanation on M2 (Mind and Muscle forums), in several threads on X-Factor/arachidonate metabolism and the nuclear receptors activated by its presence.
Sex steroids alter AA expression, via several routes, all of whose buttons are pushed by supraphysiological doses of steroid analogs.
Effect of homocysteine on arachidonic acid release in human platelets.
Signorello MG, Pascale R, Leoncini G. Eur J Clin Invest. (2002) 32(4):279-84.
BACKGROUND: It has been suggested that homocysteine is implicated in the risk of atherosclerosis and thrombosis. The pathogenic mechanism has not been clarified, but oxygen-free species produced by the homocysteine metabolism and auto-oxidation could have a role. DESIGN: We have studied the effect of homocysteine on arachidonic acid release in human platelets. Two important products of arachidonic acid metabolism - thromboxane B2 (TXB2) and reactive oxygen species (ROS) - have been assayed.
RESULTS: Results indicate that homocysteine induces arachidonic acid release that is partially inhibited by 5,8,11,14-eicosatetraynoic acid (ETYA). Platelet incubation with homocysteine significantly increases basal levels of TXB2 and ROS. The effect is time- and dose-dependent. The TXB2 formation is strictly correlated with the arachidonic acid release. Moreover, ROS accumulation is largely inhibited by ETYA and partially reduced by diphenyleneiodonium (DPI), suggesting the involvement both of enzymes metabolising arachidonic acid (cyclooxygenase (COX), lipooxygenase (LOX), and cytochrome P450 monooxygenase) and of NAD(P)H oxidase).
(technical insert by moderator- note that hyperglycemia induced glycation, a primary cardiovascular alteration process, is carried out by iron (not heme, free iron) catalyzed free radical promotion by NADPH attack on glucose. Secondary fuckup, fibrinogen is attacked by ROS produced by AA, and that leads to "remodeling" of the vascular system = becomes stiffened and unable to relax, inducing *permanent* blood pressure changes. If you do a PubMed search on homocysteine and AAS, you will pull up fairly recent citations that verify this cascade.
This explanation is provided specifically for dg and to provide further connections between AAS use and side effects reported from its chronic use.
Ask the logical question: why is iron elevated? Because its part of a chain reaction cascade, previous cellular damage to red blood cells attacks at heme centers in hemoglobin proteins, and this releases iron from its porphorin complex, as free iron. Back to the cited abstract....
CONCLUSION: Homocysteine induces oxidative stress in human platelets in vitro. The unbalance in platelet redox-state and the increased TXB2 formation may generate hyperactivation, contributing to a thrombogenic state leading to cardiovascular diseases.
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god, the beauty of these biochemical connections is staggering.
