July 19, 2021
Jennifer Ng, MD, Dipl of ABOM
Influencers say they know. Family and friends say they know somebody who knows. Everyone claims to have an answer for weight loss these days, but is it just the blind leading the blind? How can you find out what works best for you? There has to be a better way forward than trial and error. What if, you can take a test and uncover the secret to your weight loss? Now, science makes it possible.
One of the most important things to determine in weight loss (and test for) is a person’s obesity phenotype, which is the way in which our weight is controlled, based on the interplay between our genes and external factors1. These factors include things such as the timing of when we eat, our physical activity levels, sleep patterns and even our gut bacteria2. When these factors become disordered, they can cause changes in the regulation of our weight. What obesity experts, Drs. Andres Acosta and Michael Camilleri, recently uncovered was that ultimately when our weight spiraled out of control, this would manifest via 4 main phenotypes3:
1. “Hungry brain” – Raise your hand if you can’t seem to feel full despite how much you’ve eaten. This group has to eat more to feel full than other people.
2. “Hungry gut” – These are the folks who eat usual amounts during their meals, but are hungry again even though they have just eaten an hour or two ago.
3. “Emotional hunger” – We’ve all been there. People eat for many reasons but some of us lose control over how much we eat in response to our emotions.
4. “Slow burn” – Some people do all the right things (eating right, exercising, sleeping well, taking care of themselves), but just can’t seem to lose the weight. These are the people who, unfortunately, have a slow metabolism.
Of course, not all of us fit into neat little boxes and some of us may fall into one or more of these categories. In that case, Drs. Acosta and Camilleri recommend to see which phenotype predominates and start with that.
Knowing our phenotype means being able to target weight loss efforts more effectively. Medications are often a useful boost to lifestyle interventions, just like the snazzy shoes that give your outfit that extra touch. In a recent study, Drs. Acosta and Camilleri demonstrated that targeted therapy based on phenotypes led to almost two times more weight loss after 12 months, as compared to non-targeted therapy3. Participants in the phenotype guided therapy group lost about 16% of their original body weight versus only around 9% in the other group.
1. For the “hungry brain” group, the medication phentermine-topiramate is recommended3. Phentermine has known effects on stimulating the sympathetic nervous system aka the flight-or-flight response system, which suppresses hunger and boosts resting energy expenditure (meaning the calories we burn at rest)4. Topiramate, the other part of this combination, enhances the sensation of fullness and decreases impulsive eating5. In a study, this combo was shown to work especially well in weight loss for overeaters (those who eat more than 1000 kcal in a meal) as opposed to regular eaters6.
2. For the “hungry gut” crowd, the key is slowing down gut transit time3. If you empty your stomach more slowly, you will feel full for longer and overall, eat less, leading to weight loss. Here’s where medications such as liraglutide7 or semaglutide8 come in. These medicines work by boosting levels of a gut hormone called glucagon-like peptide 1 (GLP-1), which slows down stomach emptying. Recently, semaglutide was even shown to drop weights by around 15% long term.
3. For you “emotional hunger” folks, controlling weight involves improving how you feel on a day-to-day basis3. Hence, the combination naltrexone/bupropion is ideal. Naltrexone cuts down cravings while bupropion, which is a commonly used anti-depressant, improves mood. When our moods are better and we aren’t experiencing strong cravings, it’s a no-brainer that we live better/healthier, which leads to weight loss.
4. Finally, for those with “slow burn” issues, we want to try to speed up metabolism3. We already know that phentermine, as discussed above, does just this. It can be a useful addition to resistance/weight training exercises, which help build muscles. Muscles not only make us look leaner but also use more energy even while at rest, thereby boosting metabolism. Talk about having your cake and eating it too.
If you’re still not sure where to start after reading all this information, don’t worry – help is coming. Via their research, Drs. Acosta and Camilleri have come up with a “multi-omics” blood test to help guide your weight loss. This test looks at multiple obesity-related biomarkers found in the blood, including hormones, proteins and genes1. Based on these biomarkers and information about your diet/lifestyle, their proprietary artificial intelligence algorithm can give a pretty accurate estimate of what your obesity phenotype is. While this test is not yet available, it is expected to be out later this year.
Looking for something available now? One thing to remember is that lifestyle changes, such as diet/exercise/sleep, still remain the core of weight loss. Let’s go back to all those factors that we talked about before: the timing of when we eat, our physical activity levels, sleep patterns and even our gut bacteria. Try working on improving one or more of these things and take notes on what works and doesn’t work for you. Bring your findings to an obesity/weight management specialist (the Obesity Medicine Association has a list here for those interested) and jump start your routine now. Then, when better testing is available, use it if you need it, but hopefully, you’ll already be ahead of the game in uncovering your own secret to weight loss.
1. Phenomix Sciences (2019). https://www.phenomixsciences.com. Accessed 5 June 2021
2. Berry, S.E., Valdes, A.M., Drew, D.A. et al. Human postprandial responses to food and potential for precision nutrition. Nat Med 26,964–973 (2020). https://doi.org/10.1038/s41591-020-0934-0
3. Acosta, A., Camilleri, M., Abu Dayyeh, B. et al. Selection of Antiobesity Medications Based on Phenotypes Enhances Weight Loss: A Pragmatic Trial in an Obesity Clinic. Obesity 29(4), 662-671 (2021). https://doi.org/10.1002/oby.23120
4. Acosta, A., Streett, S., Kroh M.D., et al. White Paper AGA: POWER – Practice Guide on Obesity and Weight Management, Education, and Resources. Clin Gastroenterol Hepatol 15(5), 631-649.e10 (2017). https://doi.org/10.1016/j.cgh.2016.10.023. Epub 2017 Feb 27.
5. Shah, M., Hurt, R.T., Mundi, M.S. Phenotypes of Obesity: How it Impacts Management. Curr Gastroenterol Rep 19, 55 (2017). https://doi.org/10.1007/s11894-017-0598-1
6. Acosta, A., Camilleri, M., Shin, A., et al. Quantitative gastrointestinal and psychological traits associated with obesity and response to weight-loss therapy. Gastroenterology 148(3), 537-546.e4 (2015). https://doi.org/10.1053/j.gastro.2014.11.020. Epub 2014 Dec 5.
7. Acosta, A., Camilleri, M., Burton, D., et al. Exenatide in obesity with accelerated gastric emptying: a randomized, pharmacodynamics study. Physiol Rep 3(11), e12610 (2015). https://doi.org/10.14814/phy2.12610.
8. Wilding, J.P.H., Batterham, R.L., Calanna, S., et al; Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med 384(11), 989 (2021). https://doi.org/10.1056/NEJMoa2032183. Epub 2021 Feb 10.