Intermittent Fasting: Benefits from changing Gene Expression

Intermittent fasting (IF) seems to have taken the health and wellness industry by storm. However you define it, IF essentially means you don’t eat for a period of time (18 hours, a full day) and then you eat.

What is interesting about IF is that it can change the gene expression in different tissues in the body.  Something as simple as ‘not eating’ can cause an upregulation of proteins associated with longevity.

This article digs into the recent research on intermittent fasting, focusing on how it changes gene expression.

What does science say about intermittent fasting?

It is easy to get caught up in the hype from the experiences people share regarding their new favorite diet or lifestyle hack. But the proof is in the pudding – or rather not eating the pudding? (I have no idea where that idiom comes from!)

The latest research on intermittent fasting shows several interesting things:

Intermittent fasting may improve metabolism, in part, by changing the gut microbiome.[ref] The microbes in your gut are so important to your overall health, and balancing out the good and not-so-good bugs can help with your overall metabolism.

IF also has decreased plasma insulin levels in a clinical trial.[ref] With so much of the population falling into the pre-diabetes category, this could be a great way for many to prevent diabetes.

Defining intermittent fasting:

There are many ways that researchers define intermittent fasting – from a 16-hour break in eating to a two-day-long fast. Additionally, there are ways to mimic the effects of fasting through restricting protein intake as well as benefits from time-restricted eating.

Here is a graphical overview (Creative Commons license) from a recent Frontiers in Genetics article.


All of these methods of restricting food intake can affect gene expression and metabolic health.

Intermittent fasting and gene expression:

Digging into the ‘why’ and ‘how’ for intermittent fasting shows it changes the expression of a number of different genes. Essentially, your cells respond to the lack of nutrients by turning on and off different genes.

Why should you care about the changes in gene expression? Weight loss is one of the obvious effects of intermittent fasting. However, you may want to consider how the intervention affects specific biological pathways for your own objectives.

Inflammation: A trial of intermittent fasting for four months in a mouse model of stroke showed the expression of several inflammatory proteins (NLRP1, NLRP2, IL-1B, and IL-18) were decreased.[ref]

Longevity and health: The sirtuins are a family of genes acting as metabolic sensors of nutrient availability. Low levels of nutrients trigger certain SIRT genes to be expressed, and this is linked to healthy longevity.[ref] (Read more about your SIRT gene variants)

Animal studies also show that decreasing calories and/or protein restriction will increase AMPK and decrease mTORC1, two proteins important for overall energy-sensing.[ref] Increasing AMPK is important for burning fat and for making new mitochondria.[ref]

Brain health: Animal studies of intermittent fasting also show that BDNF (brain-derived neurotrophic factor) also increases.[ref]  BDNF is important for cognitive function, mood, and weight management. (Read more about your BDNF gene variants)

So what do human research studies show us about gene expression?

  • A three-week-long intermittent fasting clinical trial showed a small increase (~3%) in SIRT3.[ref]
  • A fasting and refeeding trial of healthy adults showed that fasting decreased the NLRP3 inflammasome activation. Additionally, inflammatory gene expression for NF-κB, TNF, and IL1B were all lower during fasting and higher after refeeding.[ref]
  • A clinical trial comparing fasting in obese vs. normal-weight participants found several differences between the two groups. For example, AMPK activity was reduced in lean individuals, but no change in obese people. Additionally, the shift to burning fat for fuel was blunted in people who were obese.[ref]
  • A clinical trial of early time-restricted eating (eating only between 8 am and 2 pm) showed SIRT1 gene expression was upregulated, as was the autophagy gene LC3A.  Additionally, it increased BDNF expression in the evening.[ref]

Not all clinical trials on intermittent fasting show amazing results.  A recent 8-week-long trial of IF in healthy adults showed no significant differences between IF and a control group other than a little bit of weight loss in the IF group. The researchers looked at a number of different parameters, including BDNF, liver enzymes, blood pressure, mood, etc.[ref]

Another clinical trial in obese women found the markers of inflammation (TNFα, IL6, and IL10) were not changed from intermittent fasting or from daily calorie restriction. In fact, inflammatory response increased in adipose tissue, possibly due to lipolysis.[ref]

(Check to see if you are likely to have genetically higher TNF-alpha)


What is autophagy in fasting?

A common term that you will see in conjunction with intermittent fasting is ‘autophagy’.

Autophagy is the way the cells can clear out or recycle cellular debris. For example, when oxidative stress damages mitochondria, the cells clear out the damaged mitochondria via autophagy pathways, clearing the way for the creation of new mitochondria.

Intermittent fasting is one way to promote autophagy.

People with diabetes often have damage to the insulin-producing beta cells in the pancreas.  Animal studies show that intermittent fasting restores autophagic-flux to the beta cells in the pancreas. This is a good thing – clearing out damaged mitochondria and enhancing beta-cell survival.[ref]

(Read more about your autophagy gene variants)

Should you do intermittent fasting if you are diabetic?

A recent randomized controlled trial on intermittent fasting in people with type 2 diabetes raises a couple of concerns. While the trial participants did have improvements in their weight, HbA1c, and fasting glucose, there was an increase in the rate of hypoglycemia.[ref]

If you have type 2 diabetes, talk with your doctor, and understand the risks of hypoglycemia when intermittent fasting. If your doctor isn’t familiar with the benefits (and risks) of intermittent fasting for type 2 diabetes, you could check out physician groups that specialize in IF for diabetes, such as Virta Health.

(Check out the free genetic risk report for diabetes)


There are definite benefits for weight loss and metabolic health for most people who do intermittent fasting. But it may not be right for everyone, especially if you have problems with low blood sugar. Additionally, the impact on inflammatory markers may not be the same for everyone.

If you have medical questions about whether IF is right for you, talk with your doctor.


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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.