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TCF7L2

Do Your Genes Favor the Mediterranean Diet? (TCF7L2)

Written by Aleksa Ristic, MS (Pharmacy) on March 10th, 2020

The TCF7L2 gene controls glucose and fat metabolism. Variants in this gene may determine how well you respond to different nutrients and diet types — read on to discover if your TCF7L2 gene favors the Mediterranean diet.

TCF7L2 in Metabolic Health

The TCF7L2 (transcription factor 7 like 2) gene, previously known as TCF4, codes for a vital transcription factor. It controls the expression of other genes in digestive organs such as the gut and pancreas, with a particular role in glucose metabolism and insulin secretion [R, R].

TCF7L2 research has mostly focused on its strong association with type 2 diabetes. However, variants in this gene—such as rs7903146 and rs12255372—also correlate with impaired lipid metabolism and heart disease [R, R, R, R].

From what we currently know, TCF7L2 variants can impair insulin secretion but not insulin sensitivity. This gene controls the activity of GLP-1, an intestinal peptide that stimulates insulin secretion in response to food [R, R, R].

Besides its crucial role in glucose control, TCF7L2 impacts fat metabolism. It regulates the production of signaling proteins—such as leptin and adiponectin—for weight gain, appetite, and more. The exact mechanisms behind this control are still unknown [R, R].

TCFL2 plays central roles in glucose and lipid metabolism. It controls the GLP-stimulated insulin secretion and impacts the signaling proteins in the fat tissue: leptin and adiponectin.

TCF7L2 Variants and the Response to Nutrients

Carbs

From studies on TCF7L2, diabetes & carbs, we learned that people with the “T” alleles at rs7903146 and rs12255372 might want to:

Avoid foods with a high glycemic index (starchy foods, sweets, juices).
Limit the intake of grains, especially refined grains and white flour
Increase the intake of fish, meat, olive oil, and eggs.
Consume a variety of fruits in moderation
Consume a good amount of non-starchy vegetables.

Dietary Fat

According to studies on TCF7L2 & dietary fat, people with these variants may want to:

Limit the intake of total and saturated fat (fatty meat, butter, palm oil, coconut oil).
Limit the intake of omega-6 fatty acids, mainly from sweets, pastries, and fried foods.
Replace the above with fish, olive oil, nuts, and seeds in moderation.

What is the Ideal Diet for People With TCF7L2 Variants?

At first, the above findings may seem contradictory and impossible to fit in a diet plan. However, one diet comes close to ideal: the Mediterranean diet.

It is low in saturated and processed fats, focusing on fish (omega-3s), olive oil, nuts, and seeds. Instead of refined grains and other starchy food, carbs come from a variety of vegetables, fruits, legumes, and whole grains. Moderate intake of eggs and lean meat also suit people with TCF7L2 variants.

Not surprisingly, the Mediterranean diet has shown beneficial metabolic effects in this population.

Mediterranean Diet, TCF7L2, and Metabolic Health

In a study of over 7,000 Spanish people, the Mediterranean diet reversed the harmful metabolic effects of this gene.

As expected, people with the “TT” genotype at rs7903146 had higher blood sugar, LDL, and triglycerides. However, those with high adherence to the Mediterranean diet didn’t significantly differ from other genotypes [R].

In another trial of 1,120 subjects, the “T” allele carriers had significantly lower body weight and waist circumference on the Mediterranean diet. On the other hand, people on the usual diet showed no difference between rs7903146 and rs12255372 genotypes [R].

Mediterranean vs. Low-Fat Diet

Certain people with TCF7L2 variants showed metabolic improvements on a low-fat diet. Still, it may not be the best choice for this population, given the high carb content, which can hinder their blood glucose control [R, R].

In the above Spanish study, “TT” subjects on a low-fat diet still had a higher stroke incidence than “CC” subjects. Conversely, those following the Mediterranean diet had their risk annulled [R].

According to the research, the quality of dietary fat and other nutrients in the Mediterranean diet may be more important than total fat content [R, R, R].

Your TCF7L2 Results for Response to the Mediterranean Diet

SNP Table

variant	genotype	frequency	risk allele
rs7903146
rs12255372

SNP Summary and Table

Primary SNP:

TCF7L2 rs7903146

‘C’ = typical response to the Mediterranean diet
‘T’ = great response to the Mediterranean diet

Other Important SNP:

TCF7L2 rs12255372

‘G’ = typical response to the Mediterranean diet
‘T’ = great response to the Mediterranean diet

Population Frequency

These two variants are almost always inherited together, which means they act as a single genetic factor.

About 40% of European descendants carry one copy of the “T” allele while 10-12% carry both copies. In East-Asian populations, this allele is much less common (2-4%).

Recommendations

Diet

As discussed, the Mediterranean diet may be particularly beneficial for people with TCF7L2 variations. According to the basic principles of the Mediterranean diet, you should [R, R, R]:

Eat a variety of vegetables, fruits, whole grains, herbs, and spices.
Consume healthy fats from fish & seafood, olive oil, nuts, and seeds.
Eat poultry, eggs, legumes – and dairy in moderation (if you’re not sensitive).
Limit the intake of saturated fat.
Avoid refined oils and grains, processed meat, fast food, and sweets.

These guidelines fit nearly all TCF7L2-specific dietary tips, based on its interactions with different nutrients.

Gene-Based Modifications

To further optimize your diet around the TCF7L2 variants, you may want to eat grains (cereals, bread, pasta) more sparingly and increase the intake of fish, olive oil, seafood, and eggs.

Mediterranean diet is a healthy choice for people that don’t carry the ‘problematic’ TCF7L2 alleles, too. They can enjoy the original version: higher in vegetables, whole grains, and legumes and lower in animal products.

Lifestyle

Specific lifestyle adjustments may work in synergy with diet to beat the negative metabolic effect of TCF7L2. In two studies examining diabetes risk, weight reduction and moderate exercise likely contributed to positive results [R, R].

The American Diabetes Association recommends the combination of moderate aerobic and resistance training, at least 150 min/week. Also, it’s crucial to reduce the sedentary lifestyle and interrupt longer periods of sitting every 30 min [R].

The American Heart Association recommends 150 min/week of moderate aerobic activity (or 75 min intense) plus strength training on at least two days a week [R].

Supplements

If your intake of fatty sea fish is low (less than three servings/week), consider supplementing with fish oil/omega-3. It has beneficial effects on blood lipids, high blood pressure, and different inflammatory conditions [R, R, R].

Aleksa Ristic

MS (Pharmacy)

Aleksa received his MS in Pharmacy from the University of Belgrade, his master thesis focusing on protein sources in plant-based diets.

Aleksa is passionate about herbal pharmacy, nutrition, and functional medicine. He found a way to merge his two biggest passions—writing and health—and use them for noble purposes. His mission is to bridge the gap between science and everyday life, helping readers improve their health and feel better.

Disclaimer

The information on this website has not been evaluated by the Food & Drug Administration or any other official medical body. This information is presented for educational purposes only, and may not be used to diagnose or treat any illness or disease.

Also keep in mind that the “Risk Score” presented in this post is based only on a select number of SNPs, and therefore only represents a small portion of your total risk as an individual. Furthermore, these analyses are based primarily on associational studies, which do not necessarily imply causation. Finally, many other (non-genetic) factors can also play a significant role in the development of a disease or health condition — therefore, carrying any of the risk-associated genotypes discussed in this post does not necessarily mean you are at increased risk of developing a major health condition.

Always consult your doctor before acting on any information or recommendations discussed in this post — especially if you are pregnant, nursing, taking medication, or have been officially diagnosed with a medical condition.

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Content

TCF7L2 in Metabolic Health TCF7L2 Variants and the Response to Nutrients What is the Ideal Diet for People With TCF7L2 Variants? Your TCF7L2 Results for Response to the Mediterranean Diet

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