Why is the generic advice ‘eat right and exercise” bad advice?

As practitioners, you all know it is never this simple-eat right and exercise. What works for one client can completely fail for another. Even those who “follow all the rules” or adhere to proven programs like Paleo or Keto often struggle to lose weight.

Why?

Genetic differences may be a key to understanding why weight loss methods work for some and fail others. Even more importantly: if we understand these genetic differences, practitioners can tailor their recommendations for each patient, giving your patients better results.

It’s not a matter of having “good genes” or “bad genes”for weight loss. It’s about understanding the differences and working with them, not against them. This is crucial in the patient’s journey to write their destiny.

Today, I will explain 3 of the most common gene variants that impact weight loss, and provide solutions for working with patients to improve weight loss results.

3 genetic variants to know about for weight loss

While there are many variants that can impact weight loss like TCF7L2, ADIPOQ, PPARG, ADRA2A, there are 3 Single Nucleotide Polymorphisms (aka SNPs) that I want to highlight today: FTO, MC4R, and APOA2. See more explanation here

If you’re new to genomics, be sure to go back and check out these resources for more context:

• Read the blog post Connecting the Genomics Dots for Mood and Weight-Management
• Listen to Episode #5 Feeding on Fear, with Morgan Knull of FeedYourGenes.ca, about genetic variants that impact dopamine and play a role in increased appetite and diminished satiety.
• Listen to Episode #6 with Dr. Penny Kendall-Reed to learn about the metabolic hormones ghrelin and leptin.

Let’s dig into how each of these SNPs can impact weight management:

FTO can guide your protein needs

FTO influences all three metabolic hormones: ghrelin, leptin, and adiponectin. To put it simply, ghrelin means, “I’m hungry.” Leptin means, “I’m satisfied.” And adiponectin is the fat-burning, thermogenesis hormone.

FTO variant A/A is associated with:

• Food obsession
• Increased appetite and diminished satiety
• Slower fat burning

In real life, a person with the A/A variant may feel like they are always thinking about food and can’t lose weight. Just the sight of food can be enough to move someone with this variant to eat, even if they just ate a full meal. See the Genotype Classification Reference Sheet here.

Fortunately, there are things that we know can help offset these effects. FTO also dictates how much protein an individual needs. Those with the A/A variant need the most protein, and significantly more than those with a T allele. Eating more protein can decrease ghrelin and increase leptin (decreasing hunger and increasing satiety). Also, saturated fats and sugar will augment the adverse ghrelin, adiponectin, and leptin ratios and switch this gene to its adverse setting.

Dr. Penny Kendall-Reed, author of Fix Your Genes to Fit Your Jeans, recommends the highest amount of protein –  about 1 to 1.2 grams for every kilogram of body weight (2.2 pounds) – for those with the FTO A/A variant. Divide that number by three for a per-meal goal of grams of protein.

When recommending a high protein diet, remember the importance of increasing fiber with vegetables and possibly a pre-probiotic.

Mc4r impacts ghrelin and leptin levels

The MC4R variant C/C also impacts ghrelin and leptin levels increasing ghrelin and decreasing leptin significantly. Compared to FTO A/A, however, the effects of MC4R C/C are much more extreme and the effects can be seen at a younger age. Research has even shown a 43% increase in weight and obesity entirely independent of diet and exercise in those with the MC4R C/C variant. They produce so much more ghrelin and so little leptin.

High ghrelin, the hunger hormone, stimulates the dopaminergic pathways. So high ghrelin will stimulate the need for more dopamine. And if a patient already has less dopamine biologically available due to a risk variant in their COMT and DRD2/ANKK1 SNPs, then the patient will be driven to eat again as a way to increase dopamine.

Patients with this variant are constantly dieting and exercising with little weight loss. They are the patients who really get afraid of food because even a small amount of food can have a big impact on their weight.

Diet and lifestyle changes alone aren’t usually enough for people with this variant to lose weight, but supplements can help. Dr. Penny recommends a combination of three ingredients; Piper betle, Dolichos biflorus, acetyl-L-carnitine. Acetyl-L-carnitine in particular can help to balance leptin, which is key because both too high and too low levels of leptin can be problematic.

This supplement formula combines all 3 ingredients to help MC4R C/C variant patients alter the production of leptin and ghrelin.

APOA2 controls your response to saturated fats

Both FTO and MC4R risk variants can be “turned on” by the consumption of saturated fat, which is why the gene APOA2 is so important: it not only impacts ghrelin but also the absorption of fat through the intestines.

If a patient has the G/G APOA2 SNP variant, ghrelin production is increased and fat absorption is increased, leading to increased production of LDL cholesterol and resulting inflammation. Interestingly, this gene is shown to be triggered by the consumption of 22 grams of saturated fat per day or more. If a person eats less than 22 grams of saturated fat daily, the G/G variant is not triggered.

Essentially, eating a high-fat diet can trigger this variant and lead to a cascade of weight gain and weight loss resistance.

This is key to consider when recommending a high-fat diet like Paleo or Keto. Just one cup of Bulletproof Coffee has 21 grams of saturated fat, which alone brings a person with the G/G variant to their threshold!

According to Dr. Penny, once the G/G variant is triggered by eating 22+ grams of saturated fat, anything else eaten the rest of the day will be absorbed as fat and lead to an increase in ghrelin. Not only will eating make them hungrier, but the G/G variant will also trigger FTO and MC4R, further reducing leptin and increasing ghrelin. And then, of course, high ghrelin, the hunger hormone, stimulates the dopaminergic pathways; so high ghrelin will stimulate the need for more dopamine. Thus, the reward-seeking unhealthy behaviors escalate.

For those with the risk variant APOA2, Dr. Penny recommends less than 22 grams per day of saturated fat. If a patient doesn’t have the risk variant for APAO2 but does have risk variants for MC4R or FTO, Dr. Penny recommends limiting saturated fat to 28 grams per day or fewer.

Genetics as a key to unlocking weight management

Once you understand the larger picture of the SNPs that influence metabolic hormones, it is clear that recommending nutrition advice is difficult without first understanding the neurotransmitter and the genetic variations that affect the metabolic hormones: FTO, MC4R, and APOA2.

Just having this information can be the difference between frustrated patients who aren’t seeing results and effective weight management. And weight management is just one of the many ways the use of genomics can strengthen and transform your practice.

Where is Good Medicine On the Go going next?

Can your genes impact which kinds of exercise benefit you most? Yes! Learn what kind of exercise can help gain muscle mass versus what kind is inflammatory in the next Episode #7 – Personalizing Exercise  Good Medicine On the Go podcast seasons are written for functional medicine providers to build dynamic functional medicine practices. Check out all seasons that cover why and how to integrate a health coach, how to market your practice, and how to integrate cannabis into the functional medicine tool box.