Spot Reduction Revisited: Removing Stubborn Thigh Fat

Is it possible to remove fat from specific areas of the body? (Photo of low-fat legs: Kirikiri)

(Preface: This is one of the “bonus chapters” for The 4-Hour Body. My sincerest apologies for the confusion! All bonus materials can be found here. Enjoy! New forums and more coming very soon…)

I’m allergic to food. Every time I eat it breaks out into fat.

—Jennifer Greene Duncan

Does History record any case in which the majority was right?

—Robert Heinlein

In the early 1900s, a 12-year-old girl burned the back of her hand. You are right: this is not newsworthy.

It’s what followed the burn, documented in the medical records, that fascinated me:

Doctors used skin from her abdomen as a graft over the burn. By the time this girl turned thirty, she had grown fat, and the skin that had been transplanted to the back of her hand had grown fat as well. “A second operation was necessary for the removal of the big fat pads which had developed in the grafted skin,” explained the University of Vienna endocrinologist and geneticist Julius Bauer, “exactly as fatty tissue had developed in the skin of the lower part of the abdomen.”

The plight of women and fat is the stuff of legend.

Female fat deposition in the legs and buttocks increases with age, as does abdominal fat and the so-called saddle bags—fat just beneath the hips—in perimenopausal and menopausal women.

How is it that women can eat peanut butter, for example, and seemingly bypass the stomach to put it directly on their asses? Why doesn’t this happen to men, who seem to put fat directly on their would-be six-pack, which ends up resembling more of a one-pack (or “six-pack in the cooler”), even if they have bodybuilder-like veins on their arms?

To paraphrase Gary Taubes: some biological factor must regulate this. One candidate is the A-2 receptor, and that is what I decided to look at for practical experimentation…

The A-2 receptor, or alpha-2 andrenergic receptor, is the party spoiler when it comes to fat-loss in gender-specific problem areas. From the journal Obesity Research (bolding is mine):

The fat on women’s thighs is more difficult to mobilize due to increased alpha-2 adrenergic receptor activity induced by estrogen. Lipolysis [fat-loss] can be initiated through adipocyte receptor stimulation (beta adrenergic) or inhibition (adenosine or alpha-2 adrenergic) or by inhibition of phosphodiesterase.

In plain Ingrish, this means that estrogen helps pesky fat-mongering A-2 receptors do their work, and there are three effective gambits for losing fat despite this.

For decades, the consensus among exercise professionals has been that spot reduction—reducing fat in one specific body area—is impossible, a myth. I long assumed this was the case until I asked the hypothetical question: if we assume there might be an effective mechanism for spot reduction, what would it look like if we focused on the three above pathways?

It seemed that one answer would be a topical lotion that inhibits the A-2 receptor or blocks phosphodiesterase (1). Another potent and supporting mechanism might be reducing the availability of cortisol at the level of the fat cells themselves (2).

Guess what? There are compounds that can be used for either: aminophylline for the former and glycyrrhetinic acid for the latter.

The two are quite different. Aminophylline is a bronchodilator used for asthma that contains theophylline, a stimulant found in tea that is similar to caffeine. Glycyrrhetinic acid, on the other hand, prevents the breakdown of specific prostaglandins (PGE-2 and PGF-2a) and is derived from licorice; it can be used as a base for expectorants or even artificial sweeteners.

Fat-loss is an off-label use for the latter in particular, but clinical studies indicate that both can selectively reduce thigh fat in females and males when applied as a cream.

During the process of researching this book, I saw firsthand the empirical evidence of spot reduction with low-dose, high-frequency injections of human growth hormone (HGH), but the potential legal ramifications and side effects (like bone and organ growth) make HGH unattractive. If you see bodybuilders with distended abdomens that make them look like they’re nine months pregnant, you’ve probably seen drug-induced visceral organ growth. It’s not a look I recommend.

I’d also experimented on three occasions with converting yohimbine HCL into a topical cream based on the writing of Dan Duchaine, but the side effects, including excessive salivation (thank you, autonomous nervous system), weren’t worth the negligible fat-loss.

Feeling like a Pavlovian dog about to vomit is no way to spend your life, and abs won’t help your sex appeal if you’re drooling on yourself.

It Rubs the Lotion on Its Skin

I took a nine-year hiatus from experimenting with spot reduction, until The 4-Hour Body gave me the excuse to fuss with it again.

The research led me to aminophylline and glycyrrhetinic acid. All that remained was to get my hands on both, which I did.

The easiest-to-purchase source of a 2% aminophylline cream was the extremely scammy-sounding Celluthin™, which I ordered on Amazon.

Glycyrrhetinic acid was much harder to locate, as I could only find it through prescription as Atopiclair™, which is used for dermatitis and has a single U.S. distributor in Tennessee, Graceway Pharmaceuticals LLC. Even with prescription-writing doctors willing to indulge me, Graceway made it almost impossible to find the product details and prescribing information for dosing. The latter is needed to write a “script,” of course. Eventually we ferreted it out of some subpage on the website, and I was able to fill candidate B at a local Walgreen’s within 48 hours.

Celluthin cost $49.99, and Atopiclair topped out at more than $100.

Here’s what happened. We’ll look at the prescription drug first, for reasons that will become clear.

The Results

Glycyrrhetinic Acid Cream (Atopiclair®)

FIRST, A WARNING FOR WOMEN: Glycyrrhetinic acid inhibits the breakdown of several prostaglandins, including PGF-2a, which therefore increases their levels. Since PGF-2a is known to stimulate uterine activity during pregnancy and can cause miscarriage, glycyrrhetinic acid should not be taken by those who are pregnant or attempting to become pregnant.

I applied Atopiclair thrice daily—upon waking, again at 5:00 P.M., and again before bed—for 13 days. I believe both the effects and potential side effects would have been even more pronounced for a woman:

Before (November 10, 2009) and After (November 23, 2009)

Treated right chest: 5 mm –> 4.43 mm (-.57 mm)

Untreated left chest: 5 mm –> 5.5 mm (+.5 mm)

All measurements were taken at least three times and then averaged. For example, the first “5mm” was derived from readings of 4.9, 5.0, and 5.1 millimeters. But back to our story…

To account for systemic changes, such as diet-induced fat loss or gain, and to create a control, I treated only the right side of my chest on the upper torso. Sites were as far apart as possible and therefore near the armpits.

I lost more than 10% total fat on the treated side and gained exactly 10% on the untreated side. These measurements were clear, and the fat gain on the untreated area made sense, as I was in an overfeeding phase.

The next set of measurements, however, were confusing.

Treated right abdominal: 7.0 mm –> 5.93 mm (-1.07 mm)

Untreated left abdominal: 6.3 mm –> 5.13 mm (-1.17 mm)

The abdominal area I measured is the mid-tier of the six-pack, the second “bump” up from the bottom in the rectus abdominus, or the first “bump” above the navel. I chose this area instead of the usual one inch to either side of the navel because it produced more consistent readings with the ultrasound device I used (4).

You read the data right: though I lost fat on both sides, I lost more fat on the untreated side. No matter how many times I repeated the measurements, that was the conclusion.


I have no explanation, other than a possible crossover effect from the topical application, as the measured areas were separated by no more than one inch. I knew this would be a risk—hence the decision to measure the opposing sides of the chest as well.

Can we reconcile the apparent benefit on the chest and the conflicting data from the abs? Not with this alone. There is really only one solution: repeat the test.

Fortunately, our other candidate gave much clearer results.

Aminophylline Cream

Celluthin™ has the following ingredients listed on the label in (assuming this was done as the FTC requires) descending order of volume:

Purified water, Aminophylline, Yerbe Matte, Coleus Forskohli Extract, Oil of Peppermint, Carbomer, Triethanslamide, Liposomes, Butylparaben, Isobutylparaben, Isopropylparaben, Phenoxyethanol, D & C Red #28

I was particularly impressed with the misspellings of both “yerba mate” and “coleus forskohlii.” Needless to say, I did not expect this product to have an effect, and I couldn’t find clinical support for topical spot reduction use of the ingredients besides aminophylline.

I used the product twice daily on my right thigh only, upon waking and before sleep, for 18 days.

Before (October 12, 2009) and After (October 30, 2009) Measurements:

Treated right thigh midline, six inches above kneecap upper limit: 8.1 mm –> 7.4 mm5 (-0.7)

Untreated left thigh (same measurement): 7.9 mm –> 7.8 mm6 (-0.1)

On the treatment thigh, I lost 8.64% of my fat thickness, as opposed to a 1.26% loss on the control leg. Even more incredible was the apparent persistence of effect after cessation of use.

Here are the same measurements 11 days after I stopped application of the cream:

Right thigh: 7 mm (additional 5.71% reduction, or 0.4 mm)

Left thigh: 8.3 mm (a gain of 0.3 mm)

In other words, even though I was in an overeating phase and gained fat on my left thigh (0.3 millimeters), I continued to lose fat, almost an additional 6%, on the right thigh, which had been previously treated. I didn’t believe this outcome and remeasured the sites three times, but the data were consistent.

Consider me a believer.

Based on my experience, using a 2% aminophylline cream for two and a half weeks, applied twice daily, accelerates thigh fat-loss more than 10 times compared to a control.

I’ll leave the Atopiclair to the dermatitis sufferers.

Tools and Tricks

Celluthin – The topical lotion containing aminophylline that effectively inhibits the A-2 receptor. Use carefully, as it appears to continue to inhibit this receptor for at least several days after you’ve stopped using it.

Non-affiliate Amazon link

Affiliate Amazon link (I get a small commission)

Atopiclair (Glycyrrhetinic Acid Cream) ( Here’s where you can find more information about Atopiclair. You won’t be able to order the product directly, but you can get rebates on the official site if you decide to apply for a prescription.

Footnotes and References:

1 – This increases cAMP, which facilitates catecholamine stimulation of lipolysis.

2 – Via inhibition of 11beta-hydroxysteroid dehydrogenase type 1.

3 – All measurements were taken at least three times and averaged, in this case from

readings of 4.9, 5.0, and 5.1 millimeters.

4 – Using ultrasound higher than the standard abdominal point, the ultrasound echo

from the fascia (connective tissue) layer can get weaker, which reduces the risk of

the software switching between the fascia and the true fat-muscle interface.

5 – Averaged from measurements of 7.0, 7.3, 7.4, and 7.5 millimeters.

6 – Averaged from measurements of 8.0, 7.8, and 7.8 millimeters.

The Tim Ferriss Show is one of the most popular podcasts in the world with more than 900 million downloads. It has been selected for "Best of Apple Podcasts" three times, it is often the #1 interview podcast across all of Apple Podcasts, and it's been ranked #1 out of 400,000+ podcasts on many occasions. To listen to any of the past episodes for free, check out this page.

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515 Replies to “Spot Reduction Revisited: Removing Stubborn Thigh Fat”

  1. For most recent information you have to visit world-wide-web and on world-wide-web

    I found this web site as a most excellent site for latest updates.

  2. Hi Tim,

    I’ve always been a small build. I’m 165cm and used to weigh 53kg, a few years ago I started putting on weight and was eventually 63kg. I lost most of that weight following the 4HB and am around 57kg. Considering that I now have a lot more muscle, I am happy with my weight. However I’m really struggling to lose the excess fat from my upper arms and also under my chin.

    Could celluthin be used for upper arm and chin fat? Are there any particular exercises I could do to focus on these areas?


  3. Do you think this would work for reduction of fat beneath the nipple area of a male? I’m a 22yr old male, was an athlete all through high school and am still in good shape and maintain a body fat of around 8%, but have been plagued by ‘puffy nipples’ since sophomore year of high school. I have a very clean diet, drink seldomly and stopped smoking marijuana a couple months ago.



    – Brian

  4. So interesting. sorry to bring this up two years later-just shows your article is still relevant.

    Is there a way to find a cream that also does the opposite i.e. increase subcutaneous fat, so that the excess fat has somewhere to go… like your face.

  5. I’m wondering what has happened to Celluthin? It seems to be unavailable now. The answer may be in these comments, but I might have to spend an hour scrolling through them, and I’m not that patient.

  6. Any ” quick” fixes within human body will never work in the long run, and women are not exception, as hormonal changes in women’s body are more frequent due to the age, genetics and llifestyle choices…..

    There is no magic …..but hard work and understanding , what will work for your own body….only….

  7. How about the women that have skinny legs, skinny butt and fat upper back and arms? How to solve that? If I lose more weight I’d only look skinnier on the legs, if I gain weight I get fatter arms, belly is average.

    Spinach, not spinach? I do weight training and yoga, arms look hard but still fat same as back. HELP

  8. Is Celluthin still being sold? The following message is on Amazon: “Currently unavailable We don’t know when or if this item will be back in stock.”

  9. Hi Tim! Spot reduction is most definitely possible. I ran a business doing just that and cellulite reduction. Creams are cool and they have made a lot of improvements in getting to the cellular level and penetrating versus slathering on the Sratum Corneum and being useless. The issues are a combination of factors including hormonal, fascia based and loose skin because of elastin and collagen issues which all need to be addressed. So the approach needs to be in these areas and you can fix a lot of these issues. With supplements, creams and tools. Diet and exercise as well but as we know that isn’t enough to get rid of problem areas and dimpling. Thanks for opening this up for discussion! I love your Podcast and books! 🙂

  10. Hi Tim. Big fan! 🙂 Do you recommend anything for tendinitis of the hand? (I don’t do any repetitive movements – I guess my body is prone to tendonitis). I experimented with Bromelain (a proteolytic enzyme) but it made me gain a ton of weight. It really helped, but gaining about 4 pounds a day on it wasn’t worth it…. Any help would be greatly appreciated! Thanks for everything! (BTW, I lost that weight using ice! 🙂

  11. Great the book. I just got it and have not tried anything in it yet, but I will. On a side note I love the photo with the hurly too cool I have been playing on a small team!

  12. Hi Tim- Just thought you’d like to know that the Celluthin has not be available via your links for at least a year- not sure if it is available at all anymore (??). I used it for a while (about 6 months) about 4 years ago and had actual measurement reduction results around stubborn thighs while also following other ‘slow carb’ protocols including supplements, diet, and kettle-bell training- it was a great addition. (followed slow-carb religiously for about 6 months prior to trying the Celluthin)

  13. Thank you for sharing such a useful blog post. It is true that thigh fat is increasing its amount with ageing. However, improper lifestyle, alcohol, fatty foods can benefit to more fats even if the patient is young enough. There are numerous treatments that are able to help young and not so young people without affecting their health.

  14. Hi Tim,

    I’m a fan and have read and enjoyed all of your books.

    ‘Ingrish’ is a really racist word and you’re better than that.


    Genoa Davidson

  15. Hey Tim,

    It doesn’t look like it’s possible to get Celluthin anymore in the US! Do you recommend a different product to replace Celluthin for spot reduction?