Is intermittent fasting right for you?

There are many internet docs and nutritional gurus promoting 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. Some people, though, do have more hunger and a poor mood (hangry!) when fasting, and this is tied to a specific genetic variant.

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 is also associated with an increased risk of being obese and is often 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 23andMe data for rs5443:

  • 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

Getting into Ketosis

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 usually 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 effect? 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 23andMe data for rs1800556 (v4, v5),  c.511C>T

  • T/T:  pathogenic for short-chain acyl-CoA dehydrogenase deficiency [ref]
  • C/T: carrier (heterozygous) of SCAD deficiency allele
  • C/C: normal

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

  • T/T:  pathogenic for short-chain acyl-CoA dehydrogenase deficiency[ref]
  • C/T: carrier (heterozygous) of SCAD deficiency allele
  • C/C: normal

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

  • T/T:  pathogenic for short-chain acyl-CoA dehydrogenase deficiency[ref]
  • C/T: carrier (heterozygous) of SCAD deficiency allele
  • C/C: normal

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

  • T/T:  pathogenic for short-chain acyl-CoA dehydrogenase deficiency[ref]
  • C/T: carrier (heterozygous) of SCAD deficiency allele
  • C/C: normal

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

  • T/T:  pathogenic for short-chain acyl-CoA dehydrogenase deficiency[ref]
  • C/T: carrier (heterozygous) of SCAD deficiency allele
  • C/C: normal

i5007491 (v4 only)  rs121908005 -The A allele is listed as pathogenic for SCADD[ref]

i5007492 (v4 only) rs121908006 -The T allele is listed as pathogenic for SCADD[ref]

i5007490 (v4 only)  rs1799958 – This one is a more common variant and doesn’t cause SCADD by itself; the A allele adds to susceptibility to SCADD when combined with other A/CADS polymorphisms.  [ref]

Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) variants:

Check your 23andMe data for the following mutations in the ACADM gene. If you have one copy of the risk allele, you are considered a carrier for MCADD.


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 causes a decreased clearance of bacteria in the cells lining the intestine.[ref]

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

  • A/A: normal
  • 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]

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

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

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 23andMe results for rs573775 (v4 only):

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

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

Check your 23andMe results for rs6568431 (v4 only):

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

IRGM (immunity-related GTPase M) gene:

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

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

  • T/T: normal (wildtype). 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]

Check your 23andMe data for rs10065172 (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: normal(wildtype)

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

  • A/A: increased risk of Crohn’s disease[ref][ref]
  • A/G: increased risk for Crohn’s disease
  • G/G: normal(wildtype)

Lifehacks:

If you find that you are unable or unwilling to stick with intermittent or longer fasts, 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.

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. The support may keep you on track longer!

 

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