True or False: Yohimbine Sheds "Stubborn" Ab & Thigh Fat in Women (+Men)? Plus: Is the Way You Administer the Alpha-2 Antagonist the Main Determinant of Fat Loss?

If all the training and dieting in the world won't let the thigh-fat (women) and abdominal blubber (men) melt, it's about time to buy some yohimbine...true?
It's part of the bro-scientific basics: If you use yohimbine, its effects on the alpha-receptors will help you to preferentially burn "stubborn" body fat. This is supposed to be true for women, in particular. Unlike men, who are carrying most of their body fat in the abdominal region, the ladies are usually battling their "healthy", but ugly fat stores in the thigh region.

Now, this wouldn't be so much of a problem, if those nasty fat pads didn't persist until other, certainly more aesthetic "fat pads" in the upper body shriveled away. So, if yohimbine, which is usually combined with a whopping dose of caffeine, would work the way the bros say it does, this would certainly be an awesome thing for both ladies and gents ;-)
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Studies that investigate the effects of yohimbine on fat loss are scarce and the number of studies comparing upper-body vs. lower-body fat loss is almost non-existent.

The phrase "almost non-existent", does yet imply that there are a handful of studies, which investigated both the amount of fat the subjects lost and the body part(s) where this fat came from. Unfortunately, the over-cited soccer-player study by Sergej M. Ostojic (2006).
Figure 1: Body fat (%) before and after the 21-day 20mg/day yohimbine intervention in (20 top-level male soccer players; note: there were no statistically significant changes muscle mass between trials (Ostejic. 2006)
In the said study the administration of 20mg/day of yohimbine HCL was associated with a reduction in body-fat percentage (see Figure 1). Notwithstanding the potentiating effects of α-adrenergic blockade by yohimbine on lipolysis and exercise energy expenditure (Zahorska-Markiewicz. 1986), these effects are so pronounced that I have my doubts about the validity of the skinfold measures, of which a recent study shows that they are only accurate, when they are performed by "an experienced skinfold assessor" (Shim. 2014).
The pharmacology of yohimbine (Tam. 2001): If you want to use it appropriately, you will obviously have to know something about its bioavailability (20-30%, orally), its half-life (15-50 min) and the time it takes for the serum levels to achive maximal concentrations (20-40 min). Furthermore you should keep in mind that the ingestion of food will blunt all the neat "fat burning effects" of yohimbine. To make the most of your yohimbine, you should thus use it fasted and refrain from eating for at least 2h after the ingestion.
And even if the data from the Ostejic study was accurate, the absence of body-part specific data makes it impossible to judge if the guys lost abdominal, thigh or back fat.

Figure 2: Effect of alpha-2 agonist stimu- lation on glycerol levels in dialysate from human subcu- taneous adipose tissue (Galitzky. 1993) - Note: As an alpha-2 antagonist, yohimbine, unlike clonidine, an alpha-2 agonist, will increase not decrease the release of glycerol from abdominal adipose tissue!
Theoretically speaking the notion to use alpha-2 adrenoreceptor modulators like yohimbine to selectively burn thigh or but fat is sound. As the data from a 1993 study by Galitzky et al. clearly shows, the increased expression of alpha-2 receptors in the abdominal fat has direct consequences on the amount of lipid that is released, when corresponding fat cells are exposed to alpha-2 agonists (see Figure 2). Administering an antagonist, on the other hand, will inhibit the blockade and thus result in an increased release of fat from "stubborn" fat depots in the abdominal area.

Theory and practice are yet oftentimes two very different animals, which is probably why it is very difficult to find data from controlled trials to confirm that orally administered yohimbine will lead to a local increase in fat loss.
Yohimbine is considerably safe, but still not harmless: When it's used in reasonable amounts (0.1mg/lbs body weight in the non-obese), the cardiovascular and nervous system side effects of yohimbine are well-tolerable. Upon dose-escalation and in individuals with a high susceptibility to alpha-adrenergic stimulation it can yet have pretty nasty side effects. The latter is particularly true, when it's used as an adjunct to the classic ephedrine + caffeine stack, where it leads to significant increases in cardiac work during dynamic exercise (Waluga. 1998). This is a pitty because the lipid-mobilizing action of yohimbine is reinforced during physical exercise (Galitzky. 1998)
Obviously, I am not the first person to realize that there is a lack of data on the long(er) term effect of yohimbine supplements on overall, let alone regional fat loss in men and women. In an extensive review of the literature that appeared in the peer-reviewed scientific journal Medical Hypotheses in 2002 McCarthy voices similar complaints, when he points out that yohimbine will elevate the serum levels of FFAs as well as those of glycerol and norepinephrine (but not epinephrine), when it is administered as a single oral dose of 0.2 mg/kg during a fast. He goes on to point out that ...
"this dose of yohimbine likewise markedly potentiates exercise-induced FFA and norepinephrine release, during and following exercise. The impact of yohimbine on post-exercise FFAs is  particularly marked, 30 minutes after a 30-minute aerobic exercise, FFA levels were virtually doubled in subjects who had ingested yohimbine prior to the exercise (Galitzky. 1988)."
The pro-lipolytic effects McCarthy describes are presumably triggered by (a) the central activation of sympathetic tone (the `flip-side' of the anti-sympathetic activity of the alpha-2 agonist clonidine; see Figure 2) (b) a direct interference with the feedback mechanism whereby pre-synaptic alpha-2 adrenoreceptors suppress further release of norepinephrine from sympathetic neurons and (c) the blockade of the adipocyte alpha-2 adrenoreceptors that suppress lipolysis (most notably in the gynoid depots of women; cf .Lafontan. 1992).
Transdermal application as a viable alternative? About five to ten years ago "fat loss" gels and cremes were all the rage in the fitness community. These days, however, many topicals carve out a miserable existence in the "clearance" section of the average supplement store. Wrongfully, if you put some faith into the results Frank L. Greenway and George A. Bray from the UCLA School of Medicine, and the University of Southern California present in a paper from the late 1980s (Greenway. 1987). The results of the corresponding experiments do yet only confirm that it is likely that yohimbine makes an excellent adjunct to a cream that's based on the combination of a beta stimulator with a phosphodiesterase inhibitor (forskolin and aminophylline + yohimbine) - a combination of which Greenway & Bray found that it reduces the thigh circumference by an additional 2.03 ± 1.36 cm compared to diet alone. The effects of yohimbine, alone (dosed at 10mmol/L), which were tested in a separate experiment, were albeit hardly significant.
Sounds pretty logical, right? Yohimbine unblocks the blocked release of fatty acids in the "stubborn fat" areas and allows you to shed the abdominal (men) and thigh (women) fat you've been battling for years... well, there is just one problem: There is not a single credible peer-reviewed study that would support the notion that orally administered yohimbine will do just that.

On the contrary, if you do a database search, you will even find studies which found no effects of yohimbine on total and/or regional body fat, at all. A study in Lancaster General Hospital, for example, reports no difference in body fat and fat distribution as measured both by waist-to-hip ratio and by CT scan (Sax. 1991)  - and that in spite of the fact that the subjects in the Sax study consumed an incremental amount of yohimbine (16–43 mg), exercised thrice a week and consumed an energy-restricted diet (1,800kcal / day) for 6 months!

In view of the results of the Sax study and a hand full of other studies with similar results (e.g. Berlin. 1985), in which yohimbine produced only side (impaired sleep, nervousness, headache, arthralgia; Sax. 1991) but not the desired fat loss effects, the notion that yohimbine would do anything in terms of fat loss and/or redistribution must be considered to be debunked - at least for the male part of the population.
Particularly useful over- weight female slow weight losers? An examination of the metabolic properties of the adipocytes obtained from slow and fast weight losers by Hellstrom et al. (1997) revealed that the fat cells of the slow weight losers were ten-fold more sensitive to the anti-lipolytic effects of alpha-2 agonists than those of rapid weight losers. This finding is clearly consistent with the possibility that increased expression and/or activity of adipocyte alpha-2 adrenoreceptors is a key reason for the relative resistance to fat loss noted in many obese women, for whom the use of yohimbine may thus be a particularly promising weight loss strategy.
Bottom line: Based on the contemporary evidence, it's difficult to say whether yohimbine will help you burn fat "locally". Theoretically, its effects on the alpha-receptor laden fat stores in the female lower body should facilitate local fat loss. Practically speaking, most people will probably compromise their own results by not following McCarthy's advice to "administer a moderate dose of yohimbine (perhaps 5±10 mg) once per day, in the morning just prior to exercise" (McCarthy. 2002) and fast for at least 4 hours afterward.

In view of the fact that it's unlikely to hamper weight loss, it may thus be worth a try to use 200mg of caffeine and 10mg of yohimbine HCL for a month before each of your morning cardio sessions. Without the exercise and the subsequent fast, however, you will probably be wasting time and money - even if you are an overweight female slow weight loser or older individual in whom the classic beta-agonists lose their efficacy while the anti-lipolytic response to alpha-2 agonists and thus the potential beneficial effects of yohimbine are fully preserved (Lönnqvist. 1990)
  • Berlin, I., et al. "[Lack of efficacy of yohimbine in the treatment of obesity]." Journal de pharmacologie 17.3 (1985): 343-347.
  • Galitzky, J., et al. "α2‐Antagonist compounds and lipid mobilization: evidence for a lipid mobilizing effect of oral yohimbine in healthy male volunteers." European journal of clinical investigation 18.6 (1988): 587-594. 
  • Galitzky, J., et al. "Role of vascular alpha-2 adrenoceptors in regulating lipid mobilization from human adipose tissue." Journal of Clinical Investigation 91.5 (1993): 1997. 
  • Lafontan, Max, et al. "Alpha-2 adrenoceptors in lipolysis: alpha 2 antagonists and lipid-mobilizing strategies." The American journal of clinical nutrition 55.1 (1992): 219S-227S. 
  • Lönnqvist, F., et al. "Catecholamine-induced lipolysis in adipose tissue of the elderly." Journal of Clinical Investigation 85.5 (1990): 1614.
  • Ostojic, Sergej M. "Yohimbine: the effects on body composition and exercise performance in soccer players." Research in Sports Medicine 14.4 (2006): 289-299.
  • Sax, L. "Yohimbine does not affect fat distribution in men." International journal of obesity 15.9 (1991): 561-565. 
  • Shim, Andrew, et al. "Assessing Various Body Composition Measurements as An Appropriate Tool for Estimating Body Fat in National Collegiate Athletic Association Division I Female Collegiate Athletes." American Journal of Sports Science and Medicine 2.1 (2014): 1-5. 
  • Tam, S. William, Manuel Worcel, and Michael Wyllie. "Yohimbine: a clinical review." Pharmacology & therapeutics 91.3 (2001): 215-243.
  • Waluga, Marek, et al. "Cardiovascular effects of ephedrine, caffeine and yohimbine measured by thoracic electrical bioimpedance in obese women." Clinical Physiology 18.1 (1998): 69-76. 
  • Zahorska-Markiewicz, B., C. Kucio, and D. Piskorska. "Adrenergic control of lipolysis and metabolic responses in obesity." Hormone and metabolic research 18.10 (1986): 693-697.
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