Weight Loss

How to turn on your skinny genes

By Kim Crawford, M.D. Last updated: September 6, 2018
how to turn on your skinny genes

Introduction to the genetics of weight:

Do you want to know how to turn on your skinny genes? Do you want to know what your skinny genes likely are or are not, first? I thought so. Let’s talk about the genes that control your weight. Believe it or not, there is quite a lot of research in this area, despite the non-incorporation of any data by the big weight loss corporations. I’m not expecting them to care about curing your weight problem anytime soon.

There are literally about 50 gene variants related to weight gain. Some of us have more than one. As a result, more variables need to be taken into account. As you will see, the skinny gene hunt started with the original skinny gene I’ll discuss first. However, recently, there have been two genetic pathways elucidated involving multiple genes which affect a much larger group of people. I’ll go in order of detection, giving you the “fixes” for each gene. It’s not all that hard to figure out which weight loss solutions you need to implement. As always, if you need help, just be in touch. Now, let’s discuss the skinny gene that started this whole conversation.

The original skinny gene:

how to turn on your skinny genesThe FTO gene, the most significant weight gain-related gene identified then and even now, was given the moniker of the original “skinny gene” back in 2007.

Note “the fat gene” wasn’t the terminology used, even though it is indeed more fitting. Stay with me on this, though. You “get” skinny genes by suppressing the fat genes.

Anyway, back to the first gene we all came to know and if not love, at least, embrace.

Early studies demonstrated the presence of the FTO gene had an appetite fueling effect on the brain’s hypothalamus, even after people consumed a meal and felt “full.” In 2013, the culprit was named.

A study led by scientists at University College London (UCL), the Medical Research Council (MRC), and King’s College London Institute of Psychiatry revealed people with the obesity-risk-gene FTO had measurably higher blood levels of the “hunger hormone,” ghrelin. This is the reason why those with the FTO gene start to feel hungry again soon after eating a meal.

“Eating and reward” brain imaging studies show the FTO gene variation changes the way the brain responds to ghrelin, as well as to images of food. The findings from brain imaging explain why people with the obesity-risk variant (2 copies) of the FTO gene eat more and prefer higher calorie foods. Yes, having one copy was associated with weighing a little more but not significantly more. Experts have estimated that carrying two copies of this gene (one from mom and one from dad) puts individuals at a 70 percent higher risk of obesity.

Despite this, the most recent studies show having two copies of the FTO gene might only pack on 6-7 pounds of body weight. It might not be much of a real risk, after all. The bottom line is definitive studies are pending. If you are looking to have genetic testing, I suggest not wasting money on this one. You want to suppress ghrelin to lose weight and keep it off, anyway. It’s a very common gene to have. In fact, up to 70 percent of those of European ancestry have at least one on “SNP” testing.

How to turn on your skinny genes for FTO:

Let’s review “epigenetics” for a moment. This is what we all do when we activate “good genes” or suppress “bad genes.” For example, turning off the diabetes genes happens when we eat a healthy salad. We would turn on those same genes if we ate ice cream. So, as far as skinny genes go, we want to shut down the activity or at least reduce it. That means we want to suppress levels of ghrelin.

Here is how we reduce ghrelin:

These are easy. We get regular exercise, control our stress, and get restorative sleep. Avoid the appetite stimulants MSG and aspartame which are bad for your health, anyway. Unlike some non-ghrelin-related weight gain (such as more leptin-oriented), the ghrelin secreter should avoid Very-Low-Calorie Diets (1000 calories or less day).

Ghrelin is produced and secreted on a four-hour schedule. You’ve heard the suggestion about eating every 3-4 hours, right? Well, this is aimed straight at the ghrelin over-secreters. To keep ghrelin low, you need to eat every 3-4 hours. You also should avoid fructose until your hunger normalizes. I am revealing this to make a point about ghrelin, but if you are following a healthy anti-inflammatory diet plan, you are avoiding fructose other than low-fructose whole fruits (berries, apples), anyway.

Those with high ghrelin usually have low “happy brain chemical” dopamine levels. You can increase your dopamine with l-tyrosine and SAMe. When you have a meal, eat high fiber foods to feel fuller, longer. Protein takes longer than “carbs” to digest, and it is the most effective food group at lowering ghrelin. Reducing ghrelin for a chronic over-secreter may increase the risk of leaky gut syndrome. Therefore, it’s a good idea to consume good omega-3 supplements as well as prebiotics and probiotics. If you are developing any GI tract symptoms, there are several other steps to heal your gut.

The next skinny gene-the MC4R gene

Mutations in the MC4R gene account for 6-8% of cases of obesity and an unknown amount of cases of being overweight. A common variant of the MC4R gene is found in approximately 22% of the population. By reasonable inference, I think it’s fair to say that close to one-quarter of the population is at increased risk for excess weight due to this not-so-skinny, skinny gene. MC4R codes for a protein called the melanocortin 4 receptor,  found in the brain’s hypothalamus. The presence of MC4R means less of the melanocortin receptor protein than “normal.”

As a reminder, the hypothalamus is the area of the brain which is responsible for controlling appetite and satiety. When the gene was first isolated, we knew that it increased appetite and decreased satiety. People with this gene tend to eat larger amounts of food, snack more frequently and like to eat fatty foods.  Now, we know why. Because we now know the answer, I can also tell you how to fix the problem.

It’s all about your BDNF:

It’s not a bad thing if this genetic mutation is the reason you have weight issues. As with all genes, you can now check anything you’d like with the well-known “23 and me” genetic testing kit or ask your doctor to run a check. If you have this “skinny gene,” then the elucidated mechanism of action is (at least in part) through a decrease in the brain-derived neurotrophic factor (BDNF). BDNF decreases food intake and increases energy expenditure.  BDNF is also quite inter-related to leptin regulation. If you have low BDNF levels, this correlates with higher leptin levels which make you more hungry and more likely to store fat more “efficiently.”

Find the whole BDNF story here, “How low BDNF makes you fat“. Suffice it to say that low BDNF will give you a sub-optimally functioning brain and will make you weigh more. To sharpen up your cognitive skills and lose weight, you obviously want to raise your BDNF level.

Fight the MC4R gene by increasing BDNF:

Your diet:

The typical American diet is high in refined sugar and saturated fat. This alone will decrease your level of brain-healthy BDNF.  You can improve your overall health, improve brain health and facilitate weight loss if you cut out refined sugar and eat only “good” saturated fats. Reducing your daily caloric intake or practicing various proven ways to do intermittent fasting can also increase levels of BDNF.  If you are “lucky” enough to also have the FTO gene, then you should avoid very low-calorie diets. However, if you practice intermittent fasting then following my instructions is best. You can find some lifestyle advice in the BDNF article, and the complete anti-inflammatory diet plan in my ebook found at the end of this article.


Green tea has EGCG as it’s active ingredient to increases BDNF, decrease leptin and improve mental focus. The omega-3 fatty acids found in fish oil are called DHA and EPA. It is specifically the DHA (docosahexaenoic acid) which increases your BDNF and, of course, also lowers your leptin level. For your health, BDNF and leptin, you need supplemental vitamin D + vitamin K.

Acetyl-l-carnitine increases levels of BDNF. It is used for many health reasons, including weight loss! Here is how l-carnitine works for weight loss specifically. It is one of the most commonly used weight lifting supplements to build muscle mass, too. Curcumin and resveratrol both lower leptin levels through not just BDNF elevation but via the SIRT1 pathway as well. How was that for a transition? So, if you haven’t heard of the sirtfood diet plan, made famous by the singer, Adele, you have missed out on the cool science. Let’s discuss how our next skinny pathway, affecting genes are involved. Hint: It’s a leptin issue.

Behold the SIRT1 pathway:

Everyone with any fatiguing or chronic illness will have a decrease in their SIRT1 pathway activity. This means if you’re mildly diabetic, or have any sort of illness, requiring constant pharmaceutical support, your SIRT1 enzymes will be down. So, how many people are in “this situation?” A large comprehensive study published in 2016 revealed decreased hippocampal signaling (less BDNF=higher leptin) due to “obesity” in the subjects studied. Obesity and even being overweight are inflammatory conditions. By definition, these conditions would decrease SIRT1 activity, right? Well, that’s sure what the literature strongly suggests. I’ll bet you that in total, we’re talking about 75%+ of the adult population, here. We can think of the SIRT1 pathway as a collection of skinny genes.

SIRT1 enzymes “turn off” specific “bad genes”:

The genes that turn off when SIRT1 levels are sufficient include those which promote aging and weight gain. These genes are involved in oxidative stress, inflammation, blood sugar management and mitochondrial dysfunction. The genes which specifically interested the sirtfood diet plan founders were the SIRT1 pathways which affected appetite, fat synthesis, and fat storage. That sounds like leptin-associated genes, doesn’t it? Well, it turns out, you’re right! The founders called the chosen SIRT1 enzyme genes, “skinny genes”! (Again, just the opposite of what you would think!)

We know when SIRT1 is low, we see patients with fatigue, insulin resistance and increased fat storage who struggle to lose weight. Low SIRT1 means high leptin or leptin “resistance” which means big-time fat storage. Since high leptin, leptin resistance, and low SIRT1 levels are such a common feature in everyone struggling to lose weight, you can assume that you have this issue (unless your doctor measures your leptin level and tells you it’s normal). By the way, I routinely obtain leptin levels on “everyone,” including those who consult me for weight loss via this website. It takes away the guesswork!

Amping up your SIRT1:


The same anti-inflammatory diet discussed above will get the process going. Reduction in oxidative stress and inflammation augments SIRT1 and you can do this with your food choices. Intermittent fasting helps the cause as well. Find many foods (such as red wine and chocolate) that are SIRT1-boosting in the SIRT-diet plan above. However, it appears that polyphenols are a large part of the SIRT-boosting and you need quite a bit of “sirt food” to make any headway. Now, I’m not knocking the foods in the diet as they all are healthy! Still, though, don’t go as calorie-low as the original plan recommends.


Although not a supplement, let me first mention that bioidentical estrogen amps up SIRT1. Supplements containing ECGC (the active ingredient in green tea), forskolin, mitochondria-energy-amping PQQ, berberine, alpha lipoic acid, Vitamin D (with K), lycopene, resveratrol, curcumin, nicotinamide riboside, zinc, fish oils, and quercetin are all great. When choosing, choose supplements that do “double duty.” For example, a strong curcumin supplement reduces inflammation, dissolves amyloid and tau brain plaques, increases SIRT1, increases BDNF, decreases leptin and more!  Now, let’s turn to our last skinny gene.

Our last and perhaps most ubiquitous skinny gene—the AMY1 gene:

We all possess a lot of diversity in one specific gene responsible for the breakdown of carbohydrates, alpha-amylase (AMY1).  AMY1 is a salivary enzyme that begins the breakdown of starch in the mouth. We all can have anywhere between 2 and 15 copies of the AMY1 gene. This means there is a huge difference from one person to the next regarding what their blood glucose level is following the exact same intake of starch including amylose. (I’ll explain.) When I say starch, I mean “high glycemic carbs” such as white potatoes, rice, and pasta. I also mean high amylose containing foods we don’t generally think of as “high carb” such as foods that grow underground.

I’m not just talking about white potatoes. For those with few AMY1 genes (and these are indeed skinny genes) sweet potatoes are also the enemy when it comes to weight loss. I know, I know—I love them too! You can indeed eat them on “maintenance” if you figure out this is your main issue. Other verboten vegetables are beets, rutabagas, turnips or parsnips.

Generally, no one misses eating radishes! However, carrots elevate glucose quickly due to their high amylose content. I know you have never seen a fat bunny rabbit, but I’m telling you the truth about carrots. This list goes on: no peanuts and no grains. If you are eating Paleo, you are already avoiding grains. If not, this is the way to lasting weight loss. Studies on people with histories of unsuccessful weight loss show a massive (4:1) weight maintenance success rate using a low-amylose diet. It might very well be the best weight loss program you have never heard of. Please access the previous link for details to this low amylose diet plan.

The individuality of carbohydrate digestion and absorption is new to the scientific world, even though bodybuilders and fitness gurus have written about it for “eons.” We know that genetically different people respond to the same meal of high-glycemic and high-amylose starch quite differently. We don’t know the number of copies of the AMY1 skinny gene needed to potentially not restrict starches on a weight loss diet.

Further, we are still unaware of the extent this gene (or the lack thereof) contributes to weight issues. Oddly enough, of all of the genes discussed, the AMY1 is the only actual  “skinny gene”—the gene we want to have! If you don’t have genetic testing and have trouble losing weight, I would suggest you follow the low-amylose diet plan above. It is very much like “eating Paleo,” with the added exclusion of root vegetables and nuts.


Now you have a list of the skinny or not-so-skinny genes. You also have instructions on how to turn on your skinny genes. So, figure out what your issues are. If you’re not sure about one and don’t feel like genetic testing, just add that “skinny gene regimen” to your weight loss diet and maintenance plan. See my articles, books and webinars for other factors. Find the supplements you need. Send me a question via email if you’re not sure. Good luck. It’s all here for you. Just do it!

FREE email consultation with Dr. Kim included with every purchase & FREE shipping on all orders over $150