Selectively losing/removing fat
Current review of treatments for decreasing fat in certain spots selectively.
In this post, I try to describe some of the research in compounds used for selectively reducing fat more from some places than others. Part of this is in relation to weight cycling, but some of it is more specific.
If you are losing weight, you also want to try to make sure you are losing it from the right places.
This can be broken down in two ways: altering the hormones that push some fat cells to empty faster than others, and actually removing adipocyte cells rather than emptying them.
The single biggest factor is having your hormones correct. If your body has a hormone profile of the wrong gender, you will not get good effects, and other things will be marginal. You should be on HRT1. There is detailed information on this. Many of the things listed here are marginal, and would be achieved anyway were you to have the correct hormone profile for a longer period of time.
There are a lot of things NOT worth trying based on current evidence, so I add all of those in a footnote
Removing Adipocyte Cells
By default, losing weight does not kill adipocyte cells. They instead just lose some of the fat that they contain and get smaller. This makes it harder to control where weight will be regained in the future.
There are a few methods actually removing adipocyte cells, but they are all somewhat costly and invasive.
Liposuction fat removal and fat transfer
You can directly remove fact cells from the body surgically, and doesn’t require weight loss otherwise. This is the main baseline.
For health effects, this does not have the same effect as losing weight, since it only covers external fat, and not visceral fat on organs. There are also is issues with skin tightness/laxity, and complications rates are still non-zero for surgical procedures.
Generally people prefer to get fat-transfers rather than pure fat removal, as some tend to regain weight in other parts of the body later, but the removed fat stays removed.
Subtype: Laser-assisted liposuction
You can possibly help skin-tightening somewhat with lasers, but there is no medical consensus yet. There is some an increase in surgical complication. I have yet to look into this more.
Cryolipolysis Fat Freezing
One can cause fat cells under the skin to die by lowering them to a temperature that causes them to die and be cleared up. Shows losses on the order of ~3.56 cm circumference; ~5.22 mm fat thickness in this review.
There is however some risk of a paradoxical reaction too, where one
Fat killing injections
There are some injectable compounds that can cause a similar effect to fat freezing. These are still usually kind of specific and experimental. Some treatments have been called out by FDA as dangerous. There are a few that I will note as perhaps use-case specific but these mostly will not be helping with local fat loss.
Deoxycholic acid
KYBELLA is “FDA-approved use for persistent SMF” (submental fat) and “appears to be a safe and efficacious alternative to surgical reduction of unwanted adipose tissue in non-submental areas”. I have yet to do much of a deep dive on this, but it seems not worth considering yet.
CBL-514
It is not yet available. “has shown promising efficacy and safety for subcutaneous fat reduction” in phase 2 clinical trials.
Retatrutide
This is a triple agonist peptide acting at GIP, GLP-1, and glucagon receptors. It is mainly used to help lose weight in general (see previous post for this), and helps somewhat to stimulate fat loss more when losing weight as a whole (by losing less muscle). It can help lose more weight in general, but it’s not a solution for sculpting specific areas.
There are other procedures, but I did not find them particularly worth considering, I add them to the Appendix2
Burning the right fat
There are some more marginal things that help stimulate lipolysis, but these are less pronounced.
Topical Aminophylline
Aminophylline is most commonly use is in the treatment of airway obstruction from asthma. But it has been shown to inhibit dual phosphodiesterase (PDE) which causes cAMP to break down more slowly and thus to surge, and thus increase lipolysis locally.
Link to Meta-analysis of a few studies
In particular, one study on 25 men/women, when on a 1200kcal diet, achieved a reduction in waist circumference of 11 ± 1.0 cm when using 0.5% aminophylline cream, compared to a reduction of 5.0 ± 0.6 cm in the control group.
The only double-blind study done showed null results when it was not paired with weight loss. Some say this invalidates the effectiveness of aminophylline, but I guess I disagree. Based on my understanding of the mechanism this just means that you need to be already losing weight for there to be any effect.
I think it seem worth trying, paired with weight loss, but the data is limited. See the wiki for more info.
But more than anything, I think aminophylline just needs to be studied more. If anyone wants to fund this or to contribute data, that would be extremely helpful.
Topical Caffeine
Caffeine appears to affect the same PDE pathway as aminophylline.
There are a lot more studies on topical caffeine for various things, often mixing it with various other compounds like retinol, carnitine, glycyrrhetinic acid.
Some amount does get systemically absorbed, so do note that it will cause a raise in blood caffeine levels too.
However the evidence base is also pretty mixed, so I’m not sure.
I think overall, it is worth trying to get a topical creme that contains aminophylline and caffeine and other things.
Considerations
This currently only covers things that are useful for the down cycle.
In the next couple of posts, I will consider things that are useful for the up-cycle instead.
Overall, the main thing you should be worrying about is your hormone levels. You can then do some surgical things like cryolipolysis and liposuction, which are costly, and I think that aminophylline is promising, but it needs more study.
There is just a lot of content in this direction, so I could not look at everything. Many attempts to try different things, but most of them seem not that promising.
It’s worth noting that some people have variations in hormone receptors, and if you are reading this page you are more likely to have such variations, and this perhaps not get the effects you want.
Other adipocyte targeting treatments
These are not particularly worth considering, but that i at least briefly looked at.
Adipotide. Phase 1 terminated at 4 patients over 6.5 years with no posted results. One publicly named case of death (Bostin Loyd, 2022, dialysis). While the mechanism is potentially interesting, it seems dangerous and not worth pursing.
Spot reduction via targeted exercise. 2022 meta-analysis found “Localized muscle training had no effect on localized adipose tissue depots” despite some small RCTs showing “Abdominal endurance exercise utilized more local fat than treadmill running, indicating that spot reduction exists in adult males”.
Glycyrrhetinic acid. small trial of 9 vs 9 patients without weigh loss, ~0.3 cm waist difference. no replications since 2005. plausibly works similar to aminophylline, but not worth worrying about based on data.
Things I didn’t look at deeply
but these also seem not worth worrying about, though I haven’t looked enough to really rule them out either.
Thermal HIFU / focused ultrasound: Has some studies but non-industry funded studies show very little effect, on the order of 1cm waist circumference loss
Radiofrequency electric-field: still in early days. doesn’t seem to have a large effect though.
Aqualyx, Lipodissolve, Lipo Lab, and Kabelline. FDA issued an consumer safety communication against these in early-2024. Banned in brazil too. Not worth considering.
1060 nm hyperthermic laser: Loss in studies was only about ~1.3mm in 12 weeks, probably not enough to be worth considering, not sure.
Low-level laser therapy (LLLT). independent study showed bad results idk.
Chromium/CLA/garcinia. I didn’t see anything to show these have effects other than small/inconsistent, but I haven’t tried to dive that deep on this.
Topical capsaicin. spicy sauce on your skin to lose fat? tested on mice? sounds sus to me. No human evidence so far so not worth considering.
5-amino-1MQNNMT inhibitor. Mouse-only studies so far. No human trials.
AOD9604. There was one trial in phase 2 that came out negative.
Yohimbine and α2 antagonists. maybe similar plausible mechanism to aminophylline. I didn’t look deeply, but supposedly some safety concerns include anxiety, hypertension, and monoamine-drug interactions, and not that good.
HIFEM alone (Emsculpt). supposedly used to help when there is muscle hypertrophy to lose muscle. I did not look in detail
remember that these footnote things are things that, afaik, are NOT worth considering, there may be further evidence that proves me wrong on these, and I didn’t look at all of these in depth.