The ultimate guide to going keto
Its health benefits and pitfalls, and how best to time it for maximum health effect
A dive into what research says on its effects on hormones, ageing and weight loss
The ketogenic diet (KD) has gained immense popularity during the last decade, primarily because of its successful short-term effect on weight loss, but also its many touted health benefits, from helping with epilepsy, to being an adjunct to cancer treatments, to its purported effects on slowing ageing and pretty much all sorts of illness.
Chances are you are already implementing some form of it, 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 for you, and am summarising the findings on ketosis’ benefits, pitfalls, and how best to time it for maximum effect in this post.
A lot of the benefits and pitfalls overlap with those of intermittent fasting, as they are inherently related. I recently wrote a post on intermittent fasting, head over if you missed that!
But in this post, let’s focus on ketosis.
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Some of the most often cited health benefits of ketosis are:
- Increased fat burning and weight loss
- Stabilised hunger and reduced cravings
- Improved insulin sensitivity and reduced blood sugar swings
- Increased mental clarity and reduced brain fog
- Stabilised mood, reduced anxiety
- Reduced inflammation
- Reduced free radical production and hence less cellular damage
- Improved mitochondrial function (parts of our cells that produce energy) and with it increased energy and reduced occurrence of illnesses linked to mitochondrial dysfunction
- Improves epilepsy
- Reduced risk of cancer, cardiovascular disease, Alzheimer’s and more
- Overall anti-ageing
But first of all, what is ketosis, and how does one get into it?
Ketosis is a process that happens when your body doesn’t have enough glucose (from sugars and carbohydrates) to burn for energy, but instead starts to burn fat, turn it into something called ‘ketone bodies’ to be used as alternative fuel source.
And how does this possibly relate to all these magic health benefits stated above?
Burning fat for fuel inherently puts us into a ‘fat burning’ state, and as such can result in weight loss, if done properly. The body only starts producing ketones once there isn’t a lot of glucose and insulin floating around the blood stream, making our cells sort of ‘crave’ insulin and therefor more ‘insulin sensitive’. I speak about the downsides of being insulin resistant (the opposite to insulin sensitivity) in other posts in more detail, but in a nutshell, insulin resistance has been linked to metabolic syndrome, type 2 diabetes, cardiovascular illness, abdominal fat accumulation, Alzheimer’s, arthritis and many more ailments best avoided if great quality of life and health span is your aim.
Thus, improving our cell’s insulin sensitivity is a great thing, and has been shown to happen very quickly once we switch to a very low carb, ketogenic lifestyle. (Make sure to read until the end of this post, as this may be reversed if one stays in keto for too long or does it the wrong way!).
Moreover, in experiments on the same amount of calories, but one group on a low fat yet high in carbohydrates, and the other on a ketogenic diet (ie low in carbohydrates yet higher in fats), individuals with insulin resistance showed dramatically improved markers of metabolic syndrome on the ketogenic diet (Source), such as reduced triglyceride levels (Source), total cholesterol, and increased high-density cholesterol (the good kind) (Source).
Did you know that our body produces cholesterol itself, and a key component of its upregulated production is insulin (3-hydroxy-3-methylglutaryl-CoA reductase). This means that an increase in blood glucose (sugars!) and consequently of insulin levels will lead to increased cholesterol production regardless of your cholesterol consumption. A reduction in dietary carbohydrate will thus have the opposite effect and this, coupled with the additional inhibition by dietary cholesterol and fats on production inside the body, is likely to be the mechanism by which physiological ketosis can improve lipid profiles (unless you are doing ‘dirty keto’ with bad quality fats and an overall excessive intake of fats such as often seen with ‘fat bombs’ — which will likely also increase your cholesterol levels! )
Another great benefit is that ketones ‘burn’ a lot cleaner inside our mitochondria — our energy producing engines in our cells — producing less free radicals and waste products than if other fuel sources (glucose) was to be used. Excess free radicals, exceeding the body’s ability to quench them via antioxidants, lead to cellular damage, mutated cells, inflammation, and if out of balance for a long time, potentially contribute to cancers, cardiovascular disease, neurodegeneration and more.
The most prominent example is the study of mitochondrial adaptations as a mechanism for the well-known anti-seizure effect of ketogenic diets (Source).
Diet- induced weight loss is generally accompanied by compensatory changes, which increase appetite and encourage weight regain. However, during a ketogenic, very low energy diet, the weight loss induced increase in grehlin was suppressed, making it easier to stick to a lower caloric diet, stabilising hunger and reducing cravings (Source 1, 2).
Another great effect is that, as being in a ketogenic state inherently means we must be low in sugar intake, we have less of the bad effects that excess sugars can have on our bodies, such as a dampened immune response, damage to our blood vessel linings, and a process called glycation. Glycation is when glucose (our main sugar body, also produced from the breakdown of carbohydrates) attaches itself to our cells, in particular proteins — and most of our body is made up of protein! Glycation results in advanced glycation end products, short ‘ages’ — which literally make us ‘age’ from the inside — much like a beef patty placed on a grill, our cells rust during glycation. So less sugar spikes means less glycation.
Ketones have also been shown to stimulate mitochondrial health. Remember, mitochondria were those energy producing engines in our cells. Research has found many associations between mitochondrial problems and a whole range of ill health conditions, including chronic fatigue syndrome, fibromyalgia, cancers, Alzheimer’s and more (Source).
Being in a fasted or caloric deficient state has been shown to stimulate a few anti-ageing and health promoting processes via FOXO3, AMPK and sirtuins. These support mitochondrial health, our immune system (by improving T cells), promote fat burning and other anti-ageing benefits such as improved autophagy, which helps cellular housekeeping, such as clearing out old and worn out cells. Being in a ketogenic state equally appears to stimulate the same processes (Source 1, 2).
Exercise is another inducer of AMPK (with above benefits), and this effect appears to be enhanced when exercise is performed in a glycogen depleted state (ie in a fasted or low glucose state).
Furthermore, beta-hydroxy-butyrate (our main ketone) treatment has been shown to extend lifespan and decrease tumors and age-associated losses of physical and cognitive performance (possibly via inhibiting something called HDAC, histone deacetylases), all in conjunction with increased content of FOX enzymes. Beneficial effects of inhibiting HDACs may also be transmitted via its role in keeping our DNA healthy, and deciding which genes should be read and turned on, and which turned off, increasing antioxidant expression such as superoxide dismutase (SOD2) and thereby reducing free radical damage (Source).
Being in a ketogenic state on a regular basis has also been shown to support and preserve brain health, in particular as it relates to epilepsy, but also Alzheimer’s, post-concussion and all cause neurodegenerative conditions.
Ketones represent an important alternative fuel for the brain and have been shown to increase the NAD+/NADH ratio in the brain of healthy young adults by slowing the conversion of NAD+ to NADH.
NAD+ is an important molecule involved in health and repair (Source).
NAD+ is further needed for mitochondrial health, and as such may be another pathway by which ketosis can support our mitochondria. NAD+ usually declines with age.
Lastly, intermittently being in a state of ketosis also has been shown to result in a healthier and more resilient immune system, by helping to cope with severe viral infections that have been linked to a higher risk of all cause morbidity (ill health trajectory) and ageing, plus has been shown to lower the risk of autoimmune conditions (Source).
This all sounds almost too good to be true, doesn’t it? Who doesn’t want healthy, young cells, plenty of energy, a strong immune system, a slim body? Thus, you may just jump right into a ketogenic lifestyle and cut out carbs, for good? Not so fast!
As with many things in life, just because something is good if done occasionally or in small amounts, does not mean that going to the extremes of it is better. The dose makes the poison… or potion, and this applies to keto too.
I have seen numerous patients come in to see me because they had run into hormonal or other issues from overdoing keto.
Most initially had wonderful benefits, such as improved mood, weight loss, focus, less bloating, etc, and then it turned.
Some of the most common pitfalls of ketosis:
- An initial period of ‘keto flu’ with constipation, lack of energy, headaches
- Hormone imbalances including stalled weight loss, hair loss, irregular cycles
- Gut microbiome imbalances such as gas, bloating, foul smelling and sticky bowel movements
… and some of the lesser known potential downsides:
- Becoming insulin resistant (yes, the contrary of what I wrote as one of its benefits!)
- More wrinkles and joint aches
- To even the extremes of heart muscle cell degeneration
How so?
In addition to the short-term transitioning problems known as keto-flu, which generally go away as one becomes ‘keto-adapted’, I want to focus on the lesser spoken about, more serious (potential) implications of staying in a ketogenic state continuously for too long.
Insulin resistance and non-alcoholic fatty liver disease
As noted above, low-carbohydrate diets have been shown to promote weight loss, decrease triglyceride content, and improve metabolic parameters. However, long-term maintenance on a ketogenic diet has been shown in studies to stimulate the development of non-alcoholic fatty liver disease and systemic glucose intolerance in mice. The relationship between ketogenic diets and systemic insulin resistance in both humans and rodents remains to be elucidated (Source 1, 2).
More studies seem to come to the same conclusion. And even though animals fed with a ketogenic diet appear to be healthy in the fasted state, they exhibit decreased glucose tolerance when fed.
Chronically stressing out the body, activation of the HPA axis and cortisol mismatch
When in a fasted or ketogenic state, the brain activates our HPA axis (stress response) to mobilise stored energy, to fuel an appropriate behavioral and/or physiological response to the perceived threat.
For example one study showed that nutritional manipulations signaling a relative depletion of dietary carbohydrates, thereby inducing nutritional ketosis, acutely and chronically activated the HPA axis. Male rats and mice maintained on a low-carbohydrate high-fat ketogenic diet (KD) exhibited markers of chronic stress (Source).
Estrogen dominance, low progesterone and thyroid, and more
This chronic stress can dysregulate our cortisol levels, with detrimental knock on effects on other hormones such as progesterone and thyroid, abdominal weight gain, and much more.
When we are chronically stressed out, our brain thinks we are running away from an imaginary tiger, and doesn’t think it is safe to procreate — stalling ovulation and progesterone levels in the second half of our cycle. This can cause issues with fertility, PMS, anxiety and more.
We also need some insulin (ie carbohydrates) to keep our thyroid functioning optimally. Our thyroid basically equals our metabolism, and a sluggish thyroid equals a sluggish metabolism! To add to this puzzle, thyroid functioning is needed for optimal progesterone activity.
Furthermore, staying in a ketogenic state for too long, much like excess fasting, has also been shown to contribute to estrogen dominance, via upregulation of both its signalling (receptor activity) and its actual levels via an enzyme called CYP17a1.
Estrogen dominance, which is when there is too much estrogen in relation to progesterone, can further worsen symptoms like irregular cycles, PMS, endometriosis, fibroids and cysts, anxiety, difficulty conceiving, and more.
Increased inflammation via messing with our gut microbiome
One of the challenges of low-carbohydrate diets is that these can (if not well designed, and in particular if one does ‘dirty keto’) have a lower intake of vegetables, and fiber. This can help with bloating in the short term, as it can starve off bacterial overgrowth like SIBO (small intestinal bacterial overgrowth) and candida albicans in the gut, but if continued too long, may stimulate inflammatory pathways and hence promote biological ageing by lowering healthy gut bacteria, reducing bacterial diversity, and resulting increased permeability of the gut lining (Source).
Increased wrinkles and joint aches
Prolonged glucose deficiency inhibits glycosaminoglycans synthesis in fibroblast cultures — needed substances for connective tissue health, such as found in skin, muscles, tendons, cartilage, and pretty much all linings throughout the body (Source).
There are also reports of micronutrient deficiency and cardiovascular safety (Source). Even more troubling, staying in a ketogenic state for a prolonged period of time may in fact induce cardiac (heart) muscle remodelling and fibrosis, increasing the risk of atrial fibrillations and more — ouch! (Source)
Hence, in my humble opinion, much more research needs to be done before safely recommending staying in a ketogenic state continuously on an ongoing basis.
If you’d like more information on how to put your diet and lifestyle together for best health outcomes, such as how and when to eat, fast, incorporate keto, sleep, move, manage stress, and more, join me for my next 4 week health reset course, where I will teach you all of these, plus more! How to test, rather than guess, how to turn this into a (non-restrictive) lifestyle you can actually stick to, and access to a community of other like-minded individuals with group Q&A access to me throughout these 4 weeks! Find out more here, or email support@functionalmedicine.me.uk
I look forward to having you join, and to help you on your journey to health!
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
