With all of the common product questions and less of the product use theory occuring on the board as of late, I thought I would post a recap to an old problem with a potentially new angle.

With original LD-Y, there was alot of discussion about the problem of accelerated fat rebound to the area of product application, upon cessation of use. This was presumably due to local up-regulation of the alpha-2 adrenoceptor, a result of the Yohimbine antagonism (quick side note -- although this is indeed a problem, it attests to the effectiveness of the LipoDerm-Y formula, in its ability to locally deliver and concentrate Yohimbine). This problem seems to be highly individualistic, with some users reporting major rebound problems and others reporting virtually none. Now, whether or not this is as much of an issue with the new LipoDerms (LD-Ultra and LD-Ultra O.D.B.) I do not know, however I would presume it is either very similiar or slightly less of an issue, so the following is still indeed relevant. Another thing is that some of this would probably be useful for Skulpt users as well (maybe even moreso).

See this thread and the references I posted = http://forum.avantlabs.com/index.php?act=S...st=0#entry61510 for more info.

In response to the problem, it has been suggested that a period of continued caloric deficit be maintained for some time after use of LD-Y (i.e. a 4-6 week period of use should warrant an additional 2 weeks of caloric deficit) to prevent the accelerated rebound and allow the alpha-2 receptor levels to normalize before returning to maintenance or surplus calories. This is definately a good method to use if you are prone to the accelerated rebound problem.

An additional method was discussed [somewhat long ago] that involved the use of an aromatase inhibitor upon cessation of LD-Y use, to decrease alpha-2 receptor expression and aid in prevention of accelerated rebound. This was based on the connection/theory between estrogens and their induction of alpha-2 receptor expression. Although I don't have any direct references to support this link, I feel this is a valid theory and a decent idea. However, and I don't believe this was discussed in our earlier threads on this, the timing factors of how long it takes altered estrogen levels to influence alpha-2 receptors could mean that starting the aromatase inhibitor at the end of LD-Y use may not be optimal. What I mean is that it might be better to start the aromatase inhibitor a few days or even a week+ before cessation of use because the decrease in alpha-2 receptor expression from decreased estrogen action may not be immediate (i.e. we are dealing with gene expression and receptor turnover rates -- usually take some time, in general). If anyone has some relevant references/data on some of the specifics of this, please post it. Regardless, the use of something like 6-OXO will have numerous benefits to a diet/lean state in general due to the increase in endogenous androgen production, although too much a decrease in estrogen action is arguably bad for lipolysis.

Now, the real reason for this thread is a potential third angle. And that is to drastically increase FFA levels towards the end of the LD-Y use and continue this state through the post-use window (the time which accelerated rebound often occurs). Naturally your caloric deficit (both during the LD-Y use and for the period following it) will increase FFA levels, but, a significant decrease in carbs and increase in fat intake (while still maintaining the same deficit) along with some Ab-Solved use and/or an oral lipolytic agent (that is 'adrenergic independant') will really bring the FFA levels up (*think TKD + Absolved).

Lyle mentioned in his UD2 book that increased plasma FFA levels have an inhibitory effect on alpha-2 receptors (I'm not going to elaborate on how this is useful and implemented within the contex of the UD2 -- buy the book if you wish to know, its very good). I have had trouble finding direct references to support this, and I've had even more trouble trying to figure out the specific mechanism(s) responsible for this effect. Does FFA bind and antagonize the alpha-2 receptor? Does it decrease alpha-2 receptor expression/mRNA? If it is the former case, then most likely increasing FFA post-LD-Y use will have a counter-productive effect on the rebound problem, as it would potentially further up-regulation of the alpha-2 receptors (theory). However, if it is the later case, then dramatically increasing FFA levels could be perfect for preventing the accelerated fat rebound to the areas of topical product application. If anyone has any references to this, please post them or PM me as the specifics of this phenomenon will determine if this will work or not.

Assuming it is not a direct inhibition, a sample outline of how to implement all of this into a 10 week cutting cycle could potentially be as follows:

-Weeks 1 through 7-

normal LD-Y or LD-Ultra or LD-Ultra ODB or Skulpt use
diet and macro ratios of your personal choice - hypocaloric

-Week 8-

normal LD-Y or LD-Ultra or LD-Ultra ODB or Skulpt use
diet and macro ratios change to cause dramatic increase in FFA levels (such as TKD) - hypocaloric
start any additional FFA increasing products/agents/AB-Solved use
start 6-OXO/aromatase inhibitor

-Week 9 through 10-

cease any and all topical Yohimbine product use
diet and macro ratios same as week 8 (such as TKD) - hypocaloric
continue any additional FFA increasing products/agents/AB-Solved use
continue 6-OXO/aromatase inhibitor

-End-

diet and macro ratios return to personal preference - maintenance or hypercaloric
end 6-OXO/aromatase inhibitor

----------------------------------------------

Now, this may be alot of hassle for many or too much theory for a small issue, but I think this could be helpful for the strict dieter or competitive bb'er who has problems with post-Yohimbine use accelerated fat rebound (there have been posts from people saying they cannot use LD-Y at all due to this issue, for example). I also should be studying right now and in order to further my procrastination, I thought I would post this as I was thinking about it lately.

Once again, the effectiveness of the increasing FFA levels will depend on the way that it inhibits alpha-2 receptors, so we really need some data on this.

I used LipoDerm-Y for 2 weeks at a moderate application and got good results with absolutely no noticable rebound.

-cj

I recall the rebound issue being discussed/asked about quite a bit (I remember inquiring about it myself when I first joined the board) and there were a number of threads/posts about a2 regulation - so it does seem to be an issue with some people; a board member named Derek, for example, says he experiences a major rebound effect from Y-HCL. But as said, some people [like yourself] seem to have little or no problem at all, which is nice.

Maybe I'm just too long-winded for anyone to read this I still have not discovered specifically how FFA inhibits alpha-2 receptors, although I haven't had much time to really dig...

Would really like to see what Par et al. think of this, was unaware of this interplay between FFAs/alpha-2s.

Anyway, I am using Lipoderm-Y every other day, on low calorie days, and if rebound is a significant issue I could really be shooting myself in the foot (by flooding myself with calories/carbs at the same time that rebound may be an issue).

I cannot recall anything, off-hand, on FFA's and alpha 2's, though prolonged dieting, which would increase FFA levels, has been found in quite a few studies, to down regulate alpha2 levels -- this dieting would also initially increase NE, which would be expected to downregulate them, as well.

That aside, the reports consistent with upregulation, with Lipo use that I have seen, have been miniscule, in number, given the amount sold and the amount of feedback.

Individuals prone to the rebound may want to be wary of using on their chest to reduce gyno, it could rebound worse than before. That being said, I had no rebound when using it on my abs, lovehandles, and chest.

Hmm, if the downregulation is mediated solely through increased NE from dieting, then my strategy will probably not work very well or in fact my be counterproductive. As the NE induced downregulation of the alpha-2 receptor would most likely be due to NE agonism, which is the last thing we want in a state of increased alpha-2 receptors.

The whole point of what I was thinking and am hoping for, is that there is some direct or indirect effect of FFA which down-regulates the alpha-2 receptor by means totally independant of ligan-binding -- I haven't found anything to support such a mechanism unfortunately.

I wish Lyle would chime in on this, as the way he talks about it in his book is rather unclear. I have a bad feeling that the following will turn out to be the case (although maybe I should give Lyle more credit).

Possible line of reasoning:

1. low carb dieting increases FFA levels and catecholamines (such as NE)
2. catecholamines agonize/activate the alpha-2 receptor and this agonism results in a downregulation of the receptors
3. therefore, usually when you have high FFA levels you also experience a downregulation of the receptors (this is quite different from FFA directly inhibiting the receptors)

If this is the case, well yeah that is great but unfortunately we have to go through agonism of the receptor to get the downregulation... If LD-Y or any other topical yohimbine product is resulting in significant and problematic upregulation of the alpha-2 receptor, then this is an unacceptable method to use to downregulate the receptor.

Hopefully my three points above is not what Lyle's reasoning was, as it appears in his book that he is implying a direct effect of FFA on the fat cell -- almost as if FFA was acting like an antagonist on the receptor (which seems quite odd).

Good thread.

I've just finished UD2 and have been wondering about the FFA->A2 antagonism effect as well. Any updates on this from anyone?

If this is in fact a problem, there are a couple of strategies I can think of to avoid issues.

One is to gradually ramp down the amount used in your application of L-Y/L-U/Napalm. Maybe reduce the number of squirts by 25% every few days.

Another strategy would be to cycle with a topical that doesn't contain yohimbine - e.g. 3-4 weeks Lipoderm Ultra, 3-4 weeks Fogo (you wouldn't be able to do this with Napalm/Fogo, unfortunately).

Why not Nap/Fog Kimbo?

Similiar MOA.

Both contain glycyrrhetinic acid, which must be cycled, so it would defeat the purpose of switching between two topicals to cycle the yohimbine.

Found these through his new stubborn fat book:

Acute exposure to long-chain fatty acids impairs {alpha}2-adrenergic receptor-mediated antilipolysis in human adipose tissue.
Polak J, Moro C, Bessière D, Hejnova J, Marquès MA, Bajzova M, Lafontan M, Crampes F, Berlan M, Stich V.

Franco-Czech Laboratory for Clinical Research on Obesity, French Institute of Health and Medical Research (Institut National de la Santé et de la Recherche Médicale U858), Charles University in Prague, Prague, Czech Republic.

The acute in vitro and in vivo effects of long-chain fatty acids (LCFAs) on the regulation of adrenergic lipolysis were investigated in human adipose tissue. The effect of a 2 h incubation, without or with LCFA (200 mumol/l), on basal and hormonally induced lipolysis was tested in vitro on isolated fat cells. The lipolytic response to epinephrine was enhanced by suppression of the antilipolytic alpha(2)-adrenergic effect. Then, healthy lean and obese male subjects performed a 45 min exercise bout at 50% of their heart rate reserve either after an overnight fast or 3 h after a high-fat meal (HFM: 95% fat, 5% carbohydrates). Subcutaneous adipose tissue lipolysis was measured by microdialysis in the presence or absence of an alpha-antagonist (phentolamine). In vivo, a HFM increased plasma levels of nonesterified fatty acids in lean and obese subjects. In both groups, the HFM did not alter hormonal responses to exercise. Under fasting conditions, the alpha(2)-adrenergic antilipolytic effect was more pronounced in obese than in lean subjects. The HFM totally suppressed the alpha(2)-adrenergic antilipolytic effect in lean and obese subjects during exercise. LCFAs per se, in vitro as well as in vivo, suppress alpha(2)-adrenergic-mediated antilipolysis in adipose tissue. LCFA-mediated suppression of antilipolytic pathways represents another mechanism whereby a high fat content in the diet might increase adipose tissue lipolysis.

PMID: 17625217 [PubMed - indexed for MEDLINE]



In vitro and in vivo impairment of alpha2-adrenergic receptor-dependent antilipolysis by fatty acids in human adipose tissue.
Gesta S, Hejnova J, Berlan M, Daviaud D, Crampes F, Stich V, Valet P, Saulnier-Blache JS.

INSERM U317, Rangueil Hospital, Paul Sabatier University, 31403 Toulouse Cédex 4, France.

The aim of the present study was to study the influence of fatty acids on the adrenergic control of lipolysis both in vitro and in vivo. Human subcutaneous adipose tissue explants were cultured for 48 h in the presence of 100 microM bromopalmitate (BrPal), and lipolysis was measured in isolated adipocytes. In control conditions, beta-AR-dependent activation of lipolysis by epinephrine was almost undetectable, and could be fully restored by pharmacological blockade of alpha2-AR-dependent antilipolysis. After BrPal treatment, epinephrine became fully lipolytic and was no longer influenced by alpha2-AR-blockade. Radioligand binding analysis revealed that BrPal treatment led to a significant reduction in the coupling of alpha2-AR to G proteins. In parallel, a chronic and significant increase in plasma fatty acids resulting from a 4-day high-fat diet (HFD) was accompanied by an impairment of the amplifying effect of the alpha2-AR antagonist phentolamine on exercise-induced lipolysis (measured in the subcutaneous adipose tissue with the use of a microdialysis probe) normally observed after a low-fat diet. In conclusion, in vitro and in vivo studies showed that fatty acids impair alpha2-AR-dependent antilipolysis.

PMID: 11753754 [PubMed - indexed for MEDLINE]

What do you think of the book?

Lyle is entertaining to read, but he dumbs down his books quite a bit to get a wider reader-base.

I enjoyed the read, and especially the reference section at the end (a few pages of studies that show where he gets his ideas), but I don't see anything terribly novel. He introduces 4 protocols for "stubborn fat loss," 3 of which I've seen before or thought of myself exactly, and the final (the big exciting one) is just a slight variation of one of those, very similar.

If you're a vet M&M reader, you probably won't get $40 worth of new material from this book. If you're a newbie or not so well versed in exercise physiology and adipocyte metabolism, I think it would be great guide.

EDIT: Then again, Lyle knows his stuff and he seems pretty proud of this book. Maybe his tweaks will produce major results, who knows.

I got the new book as well. At first I did what every eager beaver would do...skip straight to the protocols. They are good, but even with the latest, I have shot around similar ideas in my head (though I did not know so much the mechanisms at work and/or had them wrong; I just thought it would work)

anyway, upon going back to the other sections I realized it is a valuable enough resource to keep around. He explains everything in basic enough terms for a newb, but I still think its valuable to higher level readers/fitness enthusiasts