Health benefits & pitfalls of intermittent fasting — and how to time it for maximum effects

Mirthe Precision Health
9 min readFeb 18, 2023

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A dive into what research says on its effects on hormones, ageing and circadian rhythm

Chances are you have by now heard of intermittent fasting, or are already implementing some form of it, due to its many touted health benefits. Or you may be tempted, but are wary, having read that it can mess with hormones, metabolism and more. I have done a dive into the scientific literature, and am summarising the findings on intermittent fasting’s benefits, pitfalls, and how best to time it for maximum effect for you in this post.

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Some of the top and most often cited health benefits of intermittent fasting are:

1) Increased cellular recycling (also called autophagy) = anti-ageing and lowered risk of all cause morbidity (ill health)

2) Improved programmed cell death (apoptosis) — which may sounds bad, but is actually a good thing. We want old, mutated and worn out cells to die when their time is up, in order to make space for new and healthy ones.. rather than sticking around as ‘zombie’ cells (senescent cells), causing havoc!

3) Increased insulin sensitivity, which is wonderful for increased cellular health, fat burning and so much more.

4) Reduced inflammation

5) Increased fat burning, in particular of the ‘bad’ visceral kind

But there is more! Some of the lesser known benefits of intermittent fasting include:

· Increased fertility, ovarian function and egg quality

· Improved ovarian reserve and with it delayed menopause onset

· Gut microbiome reset.

Research has spent a lot of time on looking at the importance of having the right type of bacteria in our gut, and not too much of the bad kind, and its knock on effects on brain health, mood, reduced risk of autoimmune conditions, cardiovascular health and so much more. Excitingly research shows that intermittent fasting can help to lower the inflammatory types, such as Enterococcocus and Streptococcus, and increase the good type called Lactobacillus.

· Brain health reset: Ageing is often associated with cognitive decline and recurrent cellular and molecular impairments. While life-long caloric restriction (CR) may delay age-related cognitive deterioration as well as the onset of neurologic disease, recent studies suggest that late-onset, short-term intermittent fasting (IF), may show comparable beneficial effects as those of life-long CR to improve brain health.

· Anti-ageing effects via increased NAD+ and sirtuin pathways and stem cell rejuvenation

· Supports detox pathways

· Turns white adipose cells (the fluffy big fat cells that can become inflammatory (and not the best look!)) into beige cells, which act more like the anti-inflammatory, metabolism boosting brown fat cells.

· Supports estrogen receptors and balances them with testosterone receptor activity, which can be beneficial in conditions like PCOS and acne, where androgens (like testosterone) are upregulated.

However, if overdoing intermittent fasting, research suggests that these great benefits can turn into pitfalls, such as:

· Excess upregulation of estrogen, both their signalling (receptor activity) and their actual levels via an enzyme called CYP17a1, resulting in estrogen dominance symptoms.

· Stressing our bodies out, dysregulating our cortisol levels, with knock on effects on lowered progesterone, thyroid and ovulation.

· Suboptimal progesterone, and in particular in combination with excess estrogen, can contribute to symptoms like irregular cycles, PMS, endometriosis, fibroids and cysts, anxiety, difficulty conceiving, and more.

· I even often see patients that have lost their period due to getting too excited about fasting.

· An upregulation of belly fat accumulation, even in otherwise skinny individuals (aka ‘skinny fat’).

· And lastly, a degradation of red blood cells and their capacity to transport oxygen to our cells.

Much of whether fasting becomes our best friend, or enemy, has to do with timing. Let’s have a look at that, so that you can make educated choices on …

… when best to fast, how often and how long for!

In its most basic definition, any form of extending the time between each meal is technically an intermittent fast. However, the below three are the most often cited:

1) Alternate day fasting: Having one day of ‘ad libitum’ (unrestricted) food intake, followed by a water only fast day

2) The 5/2: 5 days of unrestricted food intake, with 2 non-consecutive days of a restricted number of calories (usually around 500–700 calories/ day)

3) Time restricted eating: One compresses ones daily time window of eating to anywhere between 1 meal per day to eating up to 8 hours, leaving between 23 and 16 hours of fasting between the next day’s meal(s). Within TRE (time-restricted eating), one can practise early TRE (eating only during the first part of the day) and delayed- TRE, delaying the first meal until the second half of the day.

Most research indicates that both the alternate day and 5/2 fasting approaches can be effective measures to reducing overall calorie intake and thereby losing weight in overweight individuals, without having to constantly count calories. However, it seems hard to stick to, and compliance rates are low. Most people seem to find this a difficult approach to maintain in the long run, as they feel deprived on those days. Furthermore, there appears to be a drop in lean body mass, as the days with little to no calories. Lean body mass is an important predictor of long-term health span and health outcomes, and as we get older we want to make sure to keep enough of it.

Time-restricted eating on the other hand appears to be more easily incorporated into one’s routine, and to be stuck to in the long run, plus research suggests that if done right, one does not risk losing muscle mass.

One of the benefits of time restricted eating seems to be that it makes it easier to consume less calories overall, ie caloric restriction, without feeling deprived as one may feel if keeping to 3 meals per day with less calories in each. Research suggests that from a weight loss perspective, whether one eats three smaller meals spread throughout the day (ie 8am, 1pm, 6pm) or has the same calories in 2 meals, makes not much difference in terms of weight loss. However, sticking to 2 meals that results in being bigger each, often results in less hunger, less feelings of deprivation, and may make it easier to stick to an overall reduced calorie intake in the long run, compared to smaller meals three times per day.

A study done at the University hospital in Tubingen, Germany, looked at what different lengths of fasting did to female participants (Source).

What they found was intriguing, and lines up with what I have seen working with patients over and over. Fasting up to 24 hrs, cortisol, the main stress hormone plus heart rate variability stayed the same. Heart rate variability (HRV) is a measure of our nervous system’s status, whether we are more in fight or flight (sympathetic), or rest-digest and heal (parasympathetic) mode. Increased HRV has been associated with better cardiovascular fitness and resilience to stress. A lower HRV has been linked to depression, anxiety, ageing and all cause morbidity (ill health).

Once they fasted MORE than 24 hours, their sympathetic response went up (their brain thought they were in danger, and shifting over to the fight-or-flight mode), the healing parasympathetic tone went down. They further saw a shift of cortisol to the right, meaning less of a spike in the morning when we should have it to get out of bed, boost energy and ‘get-shit-done mode’, and in exchange stayed higher later in the day when it should go down to allow for digestion, healing, sleep. I have elaborated on the importance of a good daily rhythm of cortisol in other posts and videos, have a read or listen if you missed them.

Once the fast continued more than 48 hours, their heart rate variability, signalling resilience, started to go down. Not great at all!

Let’s have a look at a few other studies, before we summarise and come up with a conclusion on how best to include and time fasting for its many health benefits, without running into trouble!

A recent study done in mice showed after 24 hours of fasting, their subcutaneous fat started to be more like visceral (the inflammatory type), rather than the shorter term fasting induced browning (Source).

Apart from the lengths of the fast, timing it with our circadian rhythm seems to make all the difference too.

Circadian rhythms are physical, mental, and behavioral changes that follow a 24-hour cycle. These natural processes respond primarily to light and dark and affect most living things, including animals, plants, and microbes. Chronobiology is the study of circadian rhythms (Source).

Now research indicates that when during the day we eat may be just as important as what we eat. The exact same meal consumed at a different time of the day can have an entirely opposing effect on our metabolism, hormones and more. This is where the research (and debate) about early time restricted eating vs delayed time restricted eating comes into play, and makes matters somewhat complicated.

Research is fairly conclusive on the finding that early time restricted eating, ie starting to eat in the morning and finishing by mid afternoon, with the biggest meal around noon when our cells are most apt at utilising the energy coming in, appears to be the healthiest way of eating and fasting. That way of eating demonstrates the most stable blood sugar control, cholesterol, cortisol levels, sleep quality and more.

Delaying the first meal of the day to 4pm seems to have detrimental effects as compared to having that same meal by noon, or ideally, before. Delaying the first meal to late in the day seems to be making one more insulin resistant, which spikes blood sugar even though one is fasted, pumps out cortisol, messes with our sleep and wake cycle, signals the brain to store fat around the waistline, and more. Simple, brunch at 10, linner (lunch + dinner) at 3pm?

Not so fast, that simply isn’t realistic for most people, as a large part of socialising evolves around having (family) dinners together. Researchers also acknowledge this, and are conducting more research into that topic, so stay tuned to what’s to come. So far, it appears that if one makes sure to have the first meal, ‘break fast’ by noon (and no later), and makes that the biggest meal of the day (‘breakfast like a king, … as the saying goes), and aims for an as early as possible dinner, while making sure to eat foods that help stabilise blood sugar (enough protein, fiber in vegetables and good fats, such as found in a balanced Mediterranean style diet), rather than gorging on simple carbohydrates that will make blood sugar control that much harder.

Furthermore, while exercise (especially resistance training) can at least partially alleviate the loss of lean muscle mass, it is also necessary to ensure that daily protein intake is sufficient, at ≥1.6 g/kg [67]. The observational data point to even higher intakes for this purpose. This will also allow for a more steady blood sugar control.

So what should one aim for?

Aim for 2 or 3 meals per day (2 works best for most, once metabolically flexible! More on metabolism and intermittent ketosis in the next blog post!), with the first meal no later than noon, and the last meal no later than 7pm to allow for a good and deep slumber.

No snacking between meals. Make each meal count, put as many nutrient dense foods, including protein, colourful vegetables and good fats (omega 3s, olive oil, etc) into each to get all the right building blocks, plus to keep your blood sugar stable and your brain satiated!

I will dive into the actual content of the meals in a future blog, such as intermittent ketosis, carb cycling, eating to feed your gut microbiome and more, stay tuned xxx.

As always, let me know if you have questions, or if you found this helpful so I know to produce more of what you enjoy, and share with anyone you think could benefit from reading this!

In Health,

Mirthe

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Mirthe Precision Health

Functional Medicine Practitioner. Hormones, epigenetics, health optimisation. IG/ TikTok/ Youtube/ Fb: @mirthe_precisionhealth, www.functionalmedicine.me.uk,