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 .


Autophagy and Your Genes:

Autophagy is the body’s way of recycling cellular waste and getting rid of the breakdown products as the cell ages. It is a good thing to have working well — just imagine what your home would look like if you never took out the trash!

Fasting is one way to increase autophagy, and many think that this is one of the primary health benefits of periodically fasting.[ref]

Jump over and read the whole article on autophagy — or just check out your genes below:

ATG16L1 gene:

ATG16L1 is necessary for the initiation of the process to create an autophagosome as well as being integral to the process of closing the membrane.[ref]

ATG16L1 genetic variants have been linked in quite a few studies to an increased risk of Inflammatory Bowel Diseases including Crohn’s disease.  One theory on why the autophagy variant is a risk in Crohn’s is that it causes a decreased clearance of bacteria in the cells lining the intestine.[ref]

Check your genetic data for rs2241880 (23andMe data v4, v5):

  • A/A: typical
  • A/G: increased risk of IBD, decreased risk of gastric cancer
  • G/G: increased risk of IBD[ref], increased risk for palmoplantar pustulosis[ref], decreased risk of gastric cancer, possibly due to the decreased inflammatory response towards h. pylori.[ref]

Members: Your genotype for rs2241880 is .

Check your genetic data for rs10210302 (23andMe data v4, v5):

  • T/T: increased risk of Crohn’s disease [ref][ref]
  • C/T: increased (slightly) risk of Crohn’s disease
  • C/C: typical

Members: Your genotype for rs10210302 is .

ATG5 gene:

Autophagy-related 5 (ATG5) is involved in autophagy and apoptosis. Lack of ATG5 due to genetic variants is linked to inflammatory and degenerative diseases due to the build-up of cellular junk that isn’t cleared out.

Check your genetic data for rs573775 (23andMe data v4 only):

  • A/A: increased risk of lupus*[ref] lower ATG5
  • A/G: somewhat increased risk of lupus
  • G/G: typical

*a second study showed that the increased risk of lupus with the A allele is only for those who also are IL-10 high producers (rs1800896 G allele).[ref]
Members: Your genotype for rs573775 is .

Check your genetic data for rs6568431 (23andMe data v4 only):

  • A/A:  increased risk of cerebral palsy, lower ATG5 levels[ref]
  • A/C: increased risk of CP
  • C/C: typical

Members: Your genotype for rs6568431 is .

IRGM (immunity-related GTPase M) gene:

This gene acts as a regulator of autophagy.  The genetic variants below have been linked to the susceptibility to pathogens and inflammatory bowel diseases (Crohn’s and ulcerative colitis).

Check your genetic data for rs13361189 (23andMe data v4, v5):

  • T/T: typical, decreased susceptibility to M. tuberculosis bacteria[ref]
  • C/T: increased(slightly) risk of Crohn’s, increased susceptibility to leprosy
  • C/C: increased risk of Crohn’s disease[ref][ref], increased susceptibility to leprosy[ref], increased risk of Grave’s disease[ref], increased risk of glioma[ref]

Members: Your genotype for rs13361189 is .

Check your genetic data for rs10065172 (23andMe data v4 only):

  • T/T: increased risk of TB[ref], increased risk of Crohn’s disease[ref]
  • C/T: increased risk of TB, increased risk of Crohn’s
  • C/C: typical

Members: Your genotype for rs10065172 is .

Check your genetic data for rs4958847 (23andMe data v4 only):

  • A/A: increased risk of Crohn’s disease[ref][ref]
  • A/G: increased risk for Crohn’s disease
  • G/G: typical

Members: Your genotype for rs4958847 is .


Lifehacks:

There are many health benefits to periodic fasting, but if it isn’t right for you, there may be other ways to reap some of the benefits.[ref]

Time-restricted eating:

If fasting doesn’t work for you – especially if you carry the SCADD or MCADD mutations –  then the idea of time-restricted eating may appeal to you.  Basically, this involves just eating during a certain ‘time window’ each day. Health benefits have been shown for eating during an 8 to12-hour time slot. For example, begin your eating in the morning around 8 am and finish by 6 pm for a 10-hour eating window. Both mouse and human studies have shown that this has health benefits for insulin resistance and for weight loss.[ref][ref]

Support for fasting:

If you are wanting to try a longer fast, it may be beneficial to either join an online group or talk a friend into doing it with you. Support may keep you on track longer!

There are also fasting-mimicking diets and products that are geared towards keeping you on track with enough calorie restriction to still get the benefits of fasting.

Autophagy options without fasting:

While fasting is one way to increase autophagy, there are other ways to also reap the benefits of autophagy.

Exercise can increase autophagy.[ref]

Olive oil has been found to increase autophagy. This may be one mechanism by which the Mediterranean diet decreases the risk of Alzheimer’s disease.[ref][ref]

Resveratrol inhibits mTOR and increases autophagy.[ref]

CBD oil, cannabidiol, induces autophagy in intestinal epithelial cells.[ref]

Reishi mushrooms have also been found to increase autophagy.[ref]

Luteolin, a flavonoid found in abundance in broccoli, parsley, and celery, was found to activate autophagy after a traumatic brain injury (TBI).[ref]


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 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.