Is intermittent fasting right for you?

Internet docs and nutritional gurus are promoting intermittent fasting as a way to lose weight and get healthy. The recommendations are often for intermittent fasting, for example, a 24-hour fast every week, or sometimes for longer fasts, like a week-long water fast.

There are some real, science-based benefits to fasting.[ref]

But is it right for you? Your genes may hold the answers.

Hunger and Mood

Everyone gets hungry at first when they fast, but most people lose the intense desire to eat after fasting for a while. However, some people have more hunger and a poorer mood (hangry!) when fasting, because a specific genetic variant is to blame.

A study looked at a group of 108 patients undergoing a modified medical fasting treatment for 8 days. The participants had a total energy intake of fewer than 350 calories/day.  When looking at the daily recordings of both hunger and mood, researchers found that a genetic variant in the GNB3 gene was associated with a greater hunger and worse mood when fasting.  This same GNB3 variant also links to an associated increased risk of being obese. Often, you will see it referred to as a metabolically ‘thrifty genotype. The fasting diet did work for weight loss regardless of the genotype, but those with the genetic variant had ‘pronounced mental discomfort’.[ref]

GNB3 Genetic Variant:

Check your genetic data for rs5443 (23andMe data)

  • C/C: best mood, least hunger
  • C/T: somewhere in the middle with more hunger than C/C
  • T/T: worst mood, most hunger when fasting

Members: Your genotype for rs5443 is .


Getting into Ketosis: Genes related to KETO

 

Fasting will put you into ketosis, which is when your body depletes its glucose stores and starts burning fatty acids for fuels. This is what normally happens when we fast or when we stop eating all carbohydrates.

For most people, going into ketosis isn’t a problem. But some people carry genetic variants that make it harder to burn fat for energy. These ‘Inborn Errors of Metabolism’ affect the genes associated with either long, medium, or short-chain fatty acids. The mutations are in the ACADS and ACADM genes, causing short-chain acyl-CoA dehydrogenase deficiency (SCADD) and medium-chain acyl-CoA dehydrogenase deficiency (MCADD). Other mutations cause problems with long-chain fatty acids.

Carrying two copies of the mutations usually has a big impact on your well-being, and this is one type of genetic disease that is now commonly checked at birth through newborn screenings. Children with inborn errors of metabolism need to eat regularly and avoid fasting.

But carrying just one copy of the SCADD or MCADD mutation as an adult – a ‘carrier’ of the disease – may also make you prone to hypoglycemia and to having less energy with a poor response to fasting.

How many people does this affect? There are multiple mutations in each gene that are possible to inherit.  While carrying two copies of the mutations are rare, being a carrier may be more common than you think. Some mutations are found in 1 out of 100 people, others are closer to 1 out of 1000. But when you add them all together, there are a few people in every crowd that will be affected by this and have a hard time maintaining their blood glucose levels when fasting.

23andMe data just covers a handful of these mutations… so you could still carry SCADD mutations even if none of the variants below show it.

Short-chain acyl-CoA dehydrogenase deficiency (SCADD) genetic variants:

Check your genetic data for rs1800556  c.511C>T (23andMe data v4, v5)

  • T/T:  possibly pathogenic for short-chain acyl-CoA dehydrogenase deficiency[ref]
  • C/T: carrier of SCAD deficiency variant
  • C/C: typical

Members: Your genotype for rs1800556 is .

Check your genetic data for rs28940874, c.575C>T (23andMe data v4, v5)

  • T/T:  pathogenic for short-chain acyl-CoA dehydrogenase deficiency[ref]
  • C/T: carrier of SCAD deficiency mutation
  • C/C: typical

Members: Your genotype for rs28940874 is .

Check your genetic data for rs61732144, c.319C>T (23andMe data v4, v5)

  • T/T:  pathogenic for short-chain acyl-CoA dehydrogenase deficiency[ref]
  • C/T: carrier of a SCAD deficiency mutation
  • C/C: typical

Members: Your genotype for rs61732144 is .

Check your genetic data for rs28941773, c.1058C>T (23andMe data v4,v5)

  • T/T:  pathogenic for short-chain acyl-CoA dehydrogenase deficiency[ref]
  • C/T: carrier of a SCAD deficiency mutation
  • C/C: typical

Members: Your genotype for rs28941773 is .

Check your genetic data for rs28940872, c.1147C>T (23andMe data v4, v5)

  • T/T:  pathogenic for short-chain acyl-CoA dehydrogenase deficiency[ref]
  • C/T: carrier of a SCAD deficiency mutation
  • C/C: typical

Members: Your genotype for rs28940872 is .

Check your genetic data for rs121908005 (23andMe i5007491 v4; AncestryDNA):

  • A/A: possibly pathogenic for short-chain acyl-CoA dehydrogenase deficiency[ref]
  • A/G: carrier of one variant for short-chain acyl-CoA dehydrogenase deficiency[ref]
  • G/G: typical

Members: Your genotype for rs121908005 is .

Check your genetic data for rs121908006 (23andMe i5007492 v4; AncestryDNA):

  • T/T: possibly pathogenic for short-chain acyl-CoA dehydrogenase deficiency[ref]
  • C/T: carrier of one variant for short-chain acyl-CoA dehydrogenase deficiency
  • C/C: typical

Members: Your genotype for rs121908006 is .

Check your genetic data for rs1799958 (23andMe i5007490 v4; AncestryDNA):

  • A/A: increased susceptibility to SCADD (along with other mutation)[ref]
  • A/G: increased susceptibility to SCADD (along with other mutation)
  • G/G: typical

Members: Your genotype for rs1799958 is .


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Related Articles and Genes:

Genes Involved in Autophagy:

Autophagy is a general term for cellular pathways that move something from the cytoplasm of the cell into the lysosome for degradation. The term comes from the Greek ‘auto’ (self) and ‘-phagy’ (to eat).  So when you see articles touting ‘autophagy diets’ as the latest and greatest for longevity or beautiful skin, realize that the term is just a general one that applies to a cellular process that goes on all the time in our cells.

Short-chain Acyl-CoA Dehydrogenase Deficiency:

If you have tried fasting or a ketogenic diet and felt really horrible, this article may apply to you. The human body is wonderfully made and resilient enough to get energy from either carbs or fats — for most people.  But there are certain genetic mutations that can cause people not to burn fat for energy as efficiently.


About the Author:
Debbie Moon is the founder of Genetic Lifehacks. Fascinated by the connections between genes, diet, and health, her goal is to help you understand how to apply genetics to your diet and lifestyle decisions. Debbie has a BS in engineering and also an MSc in biological sciences from Clemson University. Debbie combines an engineering mindset with a biological systems approach to help you understand how genetic differences impact your optimal health.