Fasting and inflammation

Dietary Restriction

Dietary restriction has been shown in humans as well as animals, to downregulate inflammatory pathways in skeletal muscle (2, 15, 16) when followed long term. 

Throughout history the human body has become accustomed to fasting due to food shortages and only recently have humans had a surplus of food. 

Water Fast

A water fast is when an individual does not consume anything but water for a set amount of time.

In a five day water only fast study done by Jiang et al with 45 subjects, the investigators found that the frequency of T cells increased, which are anti-inflammatory, while insulin-like growth factor 1 (IGF-1) decreased (4). IGF-1 influences growth of bones and tissues in the body, and if in excess, can promote inflammation (17). Though it is worth noting that too little IGF-1 can also cause problems in adults, like low bone density and low muscle mass according to MedlinePlus.

In the same study by Jiang et al, there were also indications of increased triglycerides, cholesterol and non-esterified fatty acids during the actual water fasting period. All levels eventually returned to baseline after refeeding, but should be noted as to proceed with caution or not at all in individuals with dyslipidemia. 

Intermittent Fasting (IF)

Intermittent fasting is when no food is consumed for a set amount of time, then during “eating hours” that calories needed for the day are consumed. For example, fasting (not eating) for 18 hours per day, then eating during a 6 hour window.

Intermittent fasting has been said to protect against obesity, cardiovascular disease, hypertension, diabetes and neurodegeneration. 

Fasting has also been shown to improve mitochondrial function. This is important since mitochondria are the main source of ATP production, or energy in the body’s cells (11), which we NEED to function. Without proper function of mitochondria, one is at risk for cardiovascular diseases, neurodegenerative disease and cancer (which are all influenced by inflammation!) (12).  

ATP cannot be stored, so the mitochondria must work hard every second of every day to produce this vital energy. The most important nutrients for ATP production include (18):

• Riboflavin
• Niacin
• CoQ10
• Iron
• Magnesium
• Manganese
• Vitamins B1, B2, B3
• Glutathione 

When these nutrients are missing, the mitochondria cannot function properly, and therefore cannot produce ATP effectively. Load up on leafy greens, asparagus, eggs, nuts, and lean meats to get plenty of good and varied nutrition so your mitochondria can properly function, leaving them protected from oxidative stress.

Fasting and Weight Loss

An 8-12 week trial found that when fasting was done every other day, it lowered body weight, fat mass, and risk factors for cardiovascular disease in those of normal weight and those with obesity (3). While intermittent fasting has been found to result in moderate weight loss over short periods of time, other studies have found that intermittent fasting does not have any additional benefits over traditional diet plans (20).  The science is still new on intermittent fasting and weight loss so there is still very limited information as most of the studies were done over a short period of time and long term results are still unknown.

You may even know some people in your life who have found success with IF. Alexa likes to point out to anyone who is looking for the “next best weight loss secret” that IF is not the answer for everyone. She says, “many people lose weight on IF because there is structure, and not room for snacking at regular intervals. The hope is that the individual practicing fasting will ALSO make healthy choices during the eating hours promoting feelings of satiety and fullness so as not to over consume calories during this time period”. 

IF also requires some dedication to a regimented eating/fasting schedule, and may not be suitable for people who have intense hunger pangs regularly. 

Fasting and Insulin/Leptin Response – THIS IS COMPLICATED and there is A LOT more to it than what is explained here.

In those with metabolic syndrome, many hormonal changes occur in response to diets high in sugar and fat.  The excess sugar and fat require an increase in both the hormones insulin and leptin. 

Insulin itself is anti-inflammatory (24). It lowers glucose levels in response to hyperglycemia, which is a pro-inflammatory state. In individuals who are insulin resistant, glucose continues to circulate in the blood while the pancreas continues to secrete more insulin in an attempt to “unlock” cells in order for glucose uptake to occur. Prolonged higher glucose levels = prolonged inflammation. 

Now, insulin stimulates lipogenesis (25), or the formation of fat, and stimulates the release of leptin, which makes us feel full. Plus, leptin does the opposite of insulin and breaks fat down (called lipolysis). Leptin also reduces the secretion of insulin by the pancreas. These two hormones are constantly working together in the body.

It is worth noting that leptin is pro-inflammatory (26). But…

The release of leptin is NATURAL and SUPPOSED to happen. Leptin is released by adipocytes (fat cells), and essentially affects hunger by suppressing appetite (again, SUPPOSED to happen). 

Insulin stimulates leptin, and leptin inhibits insulin secretion while having a whole body effect of glucose uptake independent of insulin. In simple terms and at the risk of oversimplifying, when the insulin is gone, leptin ceases to be secreted. That specific inflammatory pathway is done for now.

The body is complex, and has MANY processes in place in order to return to homeostasis. Eating plenty of anti-inflammatory fruits and vegetables, as well as a well rounded diet balanced with all macronutrients, helps our bodies perform these innate natural functions properly and efficiently so we can remain healthy. 

Now, think about someone who may have a genetic abnormality that makes them leptin deficient, or even leptin resistant. Leptin resistance affects the brain’s response (23) to satiety as insulin and leptin both normally cross the blood brain barrier (22). 

So in those with leptin resistance, leptin is not able to cross the blood-brain barrier as effectively (25), thus preventing the feeling of fullness, and just like in insulin resistance, the body produces more leptin to try and compensate. Obese individuals have more fat cells, so more leptin production, but the brain has a harder time detecting leptin in those with obesity, and this contributes to leptin resistance (27). So an increase in leptin secretion can lead to an increase in weight or even to obesity, as well as promote prolonged physical inflammation in the body. 

In essence, if an individual has insulin resistance and there is more and more insulin being secreted into the blood, then more leptin is being stimulated to be released, possibly leading to leptin resistance one day (similarly to how an overproduction of insulin can lead to insulin resistance; again, risk of being oversimplified), and constantly staying in the inflammatory state.

While fasting, insulin and leptin are reduced as there is no intake of food (namely fat and sugar). Subsequently, fasting could suppress inflammation, stimulate autophagy (which allows for cell regeneration), and has been shown to reverse the effects of metabolic syndrome in rodents (1). Additionally, fasting can make changes in the microbiota located in the gut that can protect against metabolic syndrome.  

As a result, “fasting for 3 or more days causes a 30% or more decrease in circulating insulin and glucose” (1).

*If you are living with diabetes, please work with your doctor and registered dietitian to personalise a fasting plan if that is what you are interested in. Fasting may not be appropriate for all individuals living wth diabetes. 

Fasting and Women’s Health

And now for a little snippet regarding women’s health. Women with PCOS who fasted were able to decrease their chronic overactivity of the sympathetic nervous system which resulted in lower stress hormone levels, improving physical and mental health (21). Short-term fasting has also been shown to increase luteinizing hormone in obese women which helps promote the effect of fasting in women with PCOS (21).

Fasting and Chemotherapy

Some new evidence has found that short-term fasting before going through chemotherapy can help by protecting normal cells from toxicity (2). This, in essence, helps the body’s healthy cells protect themselves from chemotherapy, allowing the treatment to target the cancer cells. Because fasting changes the landscape of growth factors and metabolite levels, cancer cells have a harder time adapting and surviving which helps improve cancer therapies (6). Fasting also encourages regeneration in normal tissues (6) so the body can continue to produce healthy cells which can help prevent life-threatening side effects of treatment.