Time to do some research

Interesting............I actually only get a dramatic drop in HDL when using AA-17 steroids, hence my reasoning to avoid them but is there some connection to liver function and this enzyme? (just thinkin out loud here).

well it "hepatic" . although on test my liver enzymes are good to go.

jb

The good old stand by: Fish Oil!!

I haven't read anything bad about it and seem to remember reading about it's ability to suppress htgl. I can't find the article at the moment but will work on it when I have time.

W.

now that you mention it that is most likely the pathway it uses to it effect. pfizer had a new drug is phase II trials that had incredible results particularly when teamed with atorvastatin(lipitor). torcetrapib use was resulting in huge increases in hdl (100%) when the trial monitors noticed that a significantly high(much higher) proportion of the torcetrapib group were dying from coronary events. bummer. the stuff really showed promise.

jb

The dyslipoproteinemia of anabolic steroid therapy: increase in hepatic triglyceride lipase precedes the decrease in high density lipoprotein2 cholesterol.

Applebaum-Bowden D, Haffner SM, Hazzard WR.

Department of Medicine, University of Washington School of Medicine, Seattle.

Administration of the androgenic anabolic steroid,Stanozolol, is associated with decreased high density lipoprotein (HDL) cholesterol (primarily due to decreased HDL2 cholesterol) and increased levels of postheparin plasma hepatic triglyceride lipase (HTGL) activity. Since HTGL appears to play a role in HDL metabolism, we examined the temporal relationship between these changes. HDL cholesterol remained stable during the first two days of stanozolol administration, but decreased 14% (P less than .01) by the third day and 39% (P less than .01) by the seventh day of stanozolol. HDL2 cholesterol paralleled the total HDL cholesterol level and remained stable for the first two days, but decreased 22% (P less than .01) after three days and 71% (P less than .01) after seven days of stanozolol. In contrast, HTGL increased 62% (P less than .001) during the first day, 161% (P less than .001) with two days, 230% (P less than .001) with three days of stanozolol administration, and remained elevated thereafter. Thus, during stanozolol administration HTGL increased dramatically and clearly before any change in HDL or HDL2 cholesterol.

Posted by: PsyChem

Since this question generated some interest in one of the threads in the Anabolic forum, I thought it would be more appropriate to discuss it here. This has probably already been addressed ad nauseam here and elsewhere, but so far I could not find a satisfactory explanation.

Research performed in the 80s showed that methylated steroids upregulate the activity of hepatic triglyceride lipase (HTL), probably through induction of gene transcription. This lipase catalyzes the hydrolysis of triglycerides and phospholipids, in particular those from HDL-2a and -2b particles, hence reducing their plasma concentration (J Lipid Res. 1999 Feb;40(2):229-34) and leading to the unfavorable lipid profile observed in users of methylated steroids.

I have always wondered how and why (only) 17-aa steroids have this effect. Everybody seems to take this for granted.

The expression of the hepatic lipase gene is tighly regulated, both positively and negatively, and only recently some of the various regulatory regions of this gene have been identified (J Lipid Res. 2006 Apr 7, PMID 16603721). Since almost nobody does any research on steroids anymore (at least at the academic level), we can only speculate about the exact mechanism behind steroid-induced dyslipidemia. Additionally, it is not yet clear whether the induction of expression is triggered by the parent steroid or by one of its metabolites. Since Anavar (which is relatively resistant to liver metabolism compared with other 17aa-AAS) was shown to affect HDL levels to a similar extent as other methylated steroids, the effect should be either due to the parent compound or is independent of the conjugated moiety (glucuronate, sulfate).

Also, one of the questions raised in the original thread was whether it could be possible to inhibit the upregulation of HTL (Thank you, Josh, the question kept me busy a good while wink.gif ). Beside its activity as a lipase, HTL plays also an important role in the process of reverse cholesterol transport by promoting hepatic uptake of lipoproteins. Taken together, this explains why HTL expression is tighly regulated: both low (impaired hepatic uptake of lipoproteins -> high serum cholesterol) and high (hydrolysis of HDL-2a and -2b particles -> unfavorable HDL:LDL ratio) levels of HTL activity would lead to dyslipidemia. Therefore, simply inhibiting the activity of HTL would not be an option.

The HTL gene is under the negative control of at least three different transcription factors: The estrogen receptor alpha (ERa), the activator protein-1 (AP-1) and the farnesoid X receptor (FXR). So, theoretically, supplementing with an agonist of one of these factors should downregulate the HTL gene. Would targeting these negative regulators of HTL be a possibility for compensating its steroid-induced upregulation ? Any ideas ?

(I'm perfectly aware that supplementation with polycosanol, panthenine, citrulline/arginine,... would help minimize the consequences of an unfavorable lipid profile, but I'm just curious to see whether it could be possible to address the cause instead of the effects).

---

I haven't had the time to go through this, but it might be a start (I only had a few mins).

i have come across studies wherein estrogen was noted as a factor, this would be why women(pre-menopausal) have such high hdl and have lower risk factors than men. we might wnat to revisit the edxcessive use of ai's as a result. The other studies that i have seen wrt to htl inhibitors do NOT note any negative cholesterol impact, i believe theincrease in blood cholesterol to proceed increased metabolism of the cholesterol in the liver.

I am currently adding citrulline to my supplement list for other reasons as well.

jb

I have to study this issue much more, but I guess that we have to fight against that negative adaptation (while on orals) by increasing cardio training, smart nutrition and suplemmentation.

I'm not sure, maybe I'm crazy, but it seems that weight gain is a must for increasing LDL and lowering HDL, most oral promotes rapid and dramatic weight gain like the legendary Anadrol so I might speculate that there's a correlation betwen weight gain and this negative adaptation.

CheCk this out JB. They asked for a login and password, but I have the access for the whole paper . And by the way, Volek is a genious, IMO.

Westman EC, Volek JS, Feinman RD. Carbohydrate restriction is effective in improving atherogenic dyslipidemia even in the absence of weight loss. Am J Clin Nutr. 2006;83(5):1025-31.

LETTER TO THE EDITOR

Dear Sir:

Krauss et al (1) are to be congratulated on the data presented in their recent article in the Journal, one of the strongest cases for dietary carbohydrate restriction to date. At the same time, we have concerns about the misleading and confusing way in which the data were presented and interpreted and about the scarcity of citations of other publications that are supportive of these findings (2-4). Because of the significance of these data for health, careful and appropriate conclusions are extremely important.

The abstract conclusion, "Moreover, beneficial lipid changes resulting from a reduced carbohydrate intake were not significant after weight loss," is in contradiction to their data, which showed that HDL cholesterol is significantly increased by weight loss after carbohydrate restriction, and even more so in the subjects receiving a greater percentage (15%) of energy from saturated fatty acids (SFA). The negative conclusion stands in stark contrast to the data in the paper that show that carbohydrate restriction is effective for improving atherogenic dyslipidemia even in the absence of weight loss. The reason most markers were less responsive to weight loss induced by the low-carbohydrate diet was that they had been improved by carbohydrate restriction before weight loss was instituted.

Krauss et al chose not to mention their data on a comparison between the high-carbohydrate diet and the low-carbohydrate diet higher in SFA. SFA are generally considered atherogenic, but the question of whether such an effect would be manifest when carbohydrates are restricted remains unanswered (5, 6).

The increase in LDL peak particle diameter reported by Krauss et al (1) shows the substantial advantage of low carbohydrate (with or without SFA) over low fat, again a finding previously reported (2, 4, 6-9) but not cited by Krauss et al.

Given how difficult it is to lose weight, the data of Krauss et al support the notion that carbohydrate restriction is the default diet for treatment of atherogenic dyslipidemia. Because low-carbohydrate strategies are at least as effective at fat reduction as are low-fat diets, it is reasonable to conclude that carbohydrate restriction, lower or higher in SFA, is the preferred diet for most people and especially those with the complex of health markers referred to as metabolic syndrome, as we previously suggested (10).

Remarkably, despite these data on the advantages of carbohydrate restriction, the report concludes with tired "concerns" about low-carbohydrate diets and a tribute to exercise and fiber, variables not included in the study. Overall, the authors seem to have had a goal of trying to support current official health guidelines rather than a goal of trying to bring those guidelines into concordance with the scientific data. As suggested by the results of the study by Krauss et al, further research should concentrate on the lower-carbohydrate, higher-saturated fat diets as a therapy for atherogenic dyslipidemia.

ACKNOWLEDGMENTS

None of the authors had a personal or financial conflict of interest with respect to the study by Krauss et al.

REFERENCES

Krauss RM, Blanche PJ, Rawlings RS, Fernstrom HS, Williams PT. Separate effects of reduced carbohydrate intake and weight loss on atherogenic dyslipidemia. Am J Clin Nutr 2006;83:1025�31.

Seshadri P, Iqbal N, Stern L, et al. A randomized study comparing the effects of a low-carbohydrate diet and a conventional diet on lipoprotein subfractions and C-reactive protein levels in patients with severe obesity. Am J Med 2004;117:398�405.

Volek JS, Sharman MJ, Forsythe CE. Modification of lipoproteins by very low-carbohydrate diets. J Nutr 2005;135:1339�42.

Westman EC, Yancy WS Jr, Olsen MK, Dudley T, Guyton JR. Effect of a low-carbohydrate, ketogenic diet program compared to a low-fat diet on fasting lipoprotein subclasses. Int J Cardiol 2006;110:212�6.

Volek JS, Forsythe CE. The case for not restricting saturated fat on a low carbohydrate diet. Nutr Metab (Lond) 2005; 2:21.

Feinman RD, Volek JS. Low carbohydrate diets improve atherogenic dyslipidemia even in the absence of weight loss. Nutr Metab (Lond) 2006;3:24.

Hays JH, DiSabatino A, Gorman RT, Vincent S, Stillabower ME. Effect of a high saturated fat and no-starch diet on serum lipid subfractions in patients with documented atherosclerotic cardiovascular disease. Mayo Clin Proc 2016;78:1331�6.

Volek J, Sharman M, Gomez A, et al. Comparison of energy-restricted very low-carbohydrate and low-fat diets on weight loss and body composition in overweight men and women. Nutr Metab (Lond) 2004;1:13.

Wood RJ, Volek JS, Liu Y, Shachter NS, Contois JH, Fernandez ML. Carbohydrate restriction alters lipoprotein metabolism by modifying VLDL, LDL, and HDL subfraction distribution and size in overweight men. J Nutr 2006;136:384�9.

Volek JS, Feinman RD. Carbohydrate restriction improves the features of metabolic dyndrome. Metabolic syndrome may be defined by the response to carbohydrate restriction. Nutr Metab (Lond) 2005;2:31.

Just a reminder while on pubmed.com. Keywords: hdl cholesterol nutrition.

Posted by: jboldman

i have come across studies wherein estrogen was noted as a factor, this would be why women(pre-menopausal) have such high hdl and have lower risk factors than men. we might wnat to revisit the edxcessive use of ai's as a result. The other studies that i have seen wrt to htl inhibitors do NOT note any negative cholesterol impact, i believe theincrease in blood cholesterol to proceed increased metabolism of the cholesterol in the liver.

I am currently adding citrulline to my supplement list for other reasons as well.

jb

This is one reason why I include 20mg PD of nolva in all of my cycles. Besides the fact the nolva has itself shown to help lipid profiles (all studies were conducted with post menapausal women) as you noted estrogen itself plays a role. I have never needed to take an AI while on cycle, nolva does everything I need it to.

this is great stuff guys:

GJ- i am interested in the application of the increased sf in a carbo restricted diet, it would make my life easier. i am going to try to track down their reference. a little quantification and verification is in order. I like those guys style.

When i read about the estrogen, i was thinking along the same lines. I still have some lingering issues with Nolvadex that i have not quite reolved, a matter of just tracking down some studies but i have long been an advocate of estrogen in appropriate q's being good for you and have been concerned that inexperienced bbrs going on hersay may be suppressing their estrogen to an unhealthy level.

jb

Interesting............I actually only get a dramatic drop in HDL when using AA-17 steroids, hence my reasoning to avoid them but is there some connection to liver function and this enzyme? (just thinkin out loud here).