Ketosis is an alternative means of fueling the body and one where ketones act as the primary fuel for the central nervous system (your brain). The switch to this alternative fueling state occurs when carbohydrate availability drops and fats remain plentiful; this is important because fats need carbohydrates in order to enter the energy-production pathway in the mitochondria (the energy furnace of each cell). Without enough carbohydrate products, the ‘regular’ entry point shuts down. What happens when entry to the energy pathways are blocked, but fats keep arriving? The breakdown products of fat accumulate in front of these pathways and are cleverly swept away by ketone-generating enzymes in the liver to form a new type of fuel: ketones.
These ketones enter the energy production pathways easily. However, besides simply being a fix to keep energy production going, these special compounds have unique metabolic effects that have attracted a lot interest in medical research and those interested in managing their health. They are preferentially used by brain cells, for which they represent an extremely efficient fuel source (generating more energy per unit of oxygen, relative to glucose). Beyond raw efficiency, ketones can upregulate oxygen delivery to the brain, increase metabolic rate, reduce inflammation and improve mitochondrial health.
Is ketosis dangerous?
No. There has been some alarm raised due to a minority of doctors who confused nutritional ketosis with diabetic ketoacidosis and then, somewhat embarrassingly, went public with their concerns. This was a big error: diabetic ketoacidosis is a life-threatening condition and occurs due to a lack of available insulin to push glucose into the cells; this sees a problematic rise in glucose in the bloodstream but, on top of this, also sees the liver pump out a huge amount of ketones (and is defined by substantial rises blood glucose, blood ketones and drops in blood pH, in an entirely different picture to that seen in nutritional ketosis).
However, the potential for acidosis it is a theoretical concern for individuals with Type 1 Diabetes who are embarking upon a ketogenic diet; while the ketogenic diet can be extremely helpful in diabetes, enjoys an excellent safety profile and indeed has been shown to reverse the condition in some, the transition should be done under medical supervision.
Is ketosis better than carb-based intake?
No. However, for many, it will be a more appropriate tool to achieve their aims. Ketosis is a alternative means of fueling our body’s energy needs. However, we have evolved in environments that put us into ketosis for sustained periods of time (experts still argue over exactly how much of the year was spent in ketosis, with many pointing to the outliers that spent all year in ketosis – the Inuits, for example – with others making the case that populations near the Equator may have been carb-fueled on an ongoing basis). The most basic principles of evolution dictate that modern humans are those who have a) found a way to exploit these spells in ketosis and b) compensate for periods of ‘low-carb winters’ through increased storage activities during the ‘high-carb summers’.
And this is indeed what we see. The human body pairs the breakdown of stored energy with the breakdown (and subsequent recycling/renewal) of cellular structures; this is often referred to as autophagy, as is the primary driver of the beneficial effects of fasting. Equally, the human body has evolved impressive capacities for energy storage. In short, while sustained metabolic ‘winters’ represents a challenge to the body, permanent ‘summers’ deny the body the opportunity to efficiently replace worn-out cellular machinery and also push us towards a state of energy mis-management (which would explain the strong link between carbohydrate intake and diabetes, also that between carbs and obesity).
In other words, when you have spent three decades in ‘summer’ mode, your metabolism stands to gain a huge amount from catching up on all the ‘winter’ tasks by undertaking a ketogenic diet for a sustained period of time. The housework tasks that take place in this mode include a reduction in inflammatory activity, an overhaul in mitochondrial health and an increase in total mitochondrial number. This explains why the keto diet is often used to rehabilitate energy metabolism, with legacy effects on the rate of baseline fat burning, leptin and insulin signalling and appetite management. Most importantly, after 160 years of research into weight management techniques, the ketogenic diet remains the only dietary approach studied that did not induce ‘yo-yo’ weight gain. Equally, it remains the most reliable approach to induce dramatic weight loss without cutting calories and how an unrestricted ketogenic diet can achieve the amount of weight loss as a calorie-restricted low-fat equivalent (without the impending ‘rebound’ weight gain made inevitable by the calorie-restricted approach).
It may not be a ‘better’ diet but, for many Westerners with energy metabolism obstacles, it is a very appropriate option and sometimes the only realistic option of achieving their goals. So when your 99-calorie cereal bars just ain’t doing it…
How quickly can you get into ketosis?
I am aware that there are bloggers who maintain that ‘it takes four days to get into ketosis’. This is BS, and has emerged as a myth since a 1967 study on fasting, which showed that this was the average time it took to record sufficient ketones in the volunteers they studied. The average time is not the time it will take for you. Just as importantly, fasting is not the same as eating a high-fat diet; the more fat you have, the more build-up of energy compounds each cell has and therefore the more building blocks we have with which to produce ketones.
I have observed only two primary factors that influence the rate that people enter ketosis:
- the speed at which ketogenic conditions are achieved. This ultimately means forming an excess of fat-derived energy compounds (namely, Acetyl-CoA). Translated into real-world concerns, this means making sure that there is a lot of fat arriving at the liver and very little carbohydrates. Therefore, it figures that the lower the glucose stores in the liver (eg. which relates to the amount of carbohydrates and calories you have eaten in recent days), the quicker you can achieve these conditions. Equally, the more your muscles remove glucose from the bloodstream (either due to increased muscular mass, recent exercise, or both), the quicker you can achieve these conditions. However, the supply of fats to the liver is equally important, which demands that a) you eat lots of fat, b) you digest this fat and c) your fat cells permit the release of fats stored there. If everything is working optimally, this can see you eat carbs ‘as usual’ on Sunday and arrive at ketogenic conditions by Monday morning.
- the efficiency of the ketogenic enzymes. Once ketogenic conditions are achieved (eg. you have an excess of Acetyl-CoA), there are four ketogenic enzymes that actually generate the ketones. The activity of these enzymes ultimately determines how easily you will reach nutritional ketosis. Like most enzymes, these are only expressed as required, meaning that they share a similar pattern to trained muscles and become stronger with regular use. In individuals that have previously not used these enzymes, it typically takes around two weeks of ketogenic conditions to see them become optimally active (what we describe as ‘keto-adapted’). However, these enzymes are active enough after a few days; this explains why most people will find that they can achieve nutritional ketosis in 2-6 days but get the maximal benefits of ketosis after a fortnight. However, those who have ‘trained’ these enzymes (through regular carb-draining exercise, eg. any form of sustained high-intensity output) may find that they reach nutritional ketosis in just a matter of hours.
The above factors should explain why athletes consuming a carbohydrate-rich diet can still wake up each morning in a state of light ketosis and, should they choose to then switch to a high-fat-low-carb intake, will be in full nutritional ketosis by lunchtime. It also explains why individuals with metabolic difficulties or a history of dieting (both of which tend to shut down the release of fats from storage), those with poor digestive function (which might see malabsorption of fats, meaning they stay in the gut rather than reach the liver) might take longer to achieve ketogenic conditions. And why individuals who have not been subject to recent high-intensity exercise (most in society and almost all my CFS individuals) may need to wait for the ketogenic enzymes to reach full activity.
Bottom line? If you are an athlete who is in full training and not suffering from metabolic issues, I would expect you to reach nutritional ketosis on the first day of making dietary changes. If you are looking to ketosis as a tool to remediate long-standing energy issues and difficulties losing weight, then I expect the transition to take two weeks. I don’t expect the transition to happen if digestive issues are present and remain unattended to.
What happens if I do not produce sufficient ketones?
This is a vital issue, because it effects so many people attempting a ketogenic diet. In 2015, I began tracking the ketone levels of each individual who had been employing a ketogenic diet prior to starting work with me. I was shocked to find that 19/20 who thought they were on a ‘ketogenic’ diet were not generating sufficient ketones. Yes, that’s 95%. Now I appreciate that this is figure produced from a population that may have more metabolic challenges than others, although it is also a population that have (on average) been forced into undertaking more research and becoming more informed. However, based on this and my conversations with other practitioners and with my audiences at conferences, I suspect that a lot of people eating are ketogenic diet are not in nutritional ketosis. The big implication of this is that most people offering opinions on the ketogenic diet have never been in ketosis. Let that sink in.
This is a huge deal, because we suffer when we are not producing enough ketones. This is a state affectionately known as ‘low carb limbo’, as describes the phase when you have taken away your main fuel (in the form of carbohydrates) but not yet replaced it (with the ketones). Now your body has coping mechanisms, such as the emergency breakdown of proteins into carbohydrates to maintain crucial life-sustaining activity (aka gluconeogenesis), but this is a costly process and thus used maintain crucial life-sustaining activity. This means a metabolic focus on surviving, not thriving. This means the rationing of energy, which means reduced investment in digestion, reduced healing and repair and reduced activity in high-demand areas like the prefrontal cortex. It is the latter that plays a central role in the low mood, poor sleep and cloudy thinking that is so common in cases of low-carb limbo.
However, it is also relevant that this state places us in a highly stressful state, which can result in undue activation of the adrenal response. For some, this is something that places a burden on them but is not a big deal. For anyone with challenges in mounting an affective adrenal response, this could result in a cascade of events that causes inflammatory chaos and further disturbance to energy production/signalling. It is a cruel irony that those who stand the most to gain from ketosis are also the ones that pay the biggest price for a poorly-executed transition. But, in all cases, we should be aware that the ketogenic diet may offer a bounty of benefits but that the transition into ketosis can be highly stressful.
How do you know you are in ketosis?
Having identified the importance of reaching nutritional ketosis as soon as possible, the obvious follow-on question is how we can know we have reached this destination. Thankfully, this is easy to do using two methods:
- measuring breath ketones. This is done with a breath monitor like the Ketonix device. You plug this into your computer, load up the software, then exhale into the monitor for about 8-10 seconds. You then see your ketone levels, which are measured in parts per million (ppm). Nutritional ketosis is 40-70ppm. This costs about £180 to buy the device. The benefits here is that there are no further strips or testing equipment required, the downsides is that you need to wait about 5 minutes for the device to ‘warm up’ and that any alcohol consumption will hugely distort the figures for several hours.
- Measuring blood ketones. This remains the ‘gold standard’ way to measure ketones, and is done with a fingerprick, followed by touching a ketone testing strip to your finger and then feeding this into the device. Nutritional ketosis is 0.5-3.0 nmol/L. Devices cost around £30 and then around £1 per test strip. The benefits here is that the test is relatively quick and does not require any computer or software. The downsides are that it can be fiddly and that regular testing can cost you more over time.
There are considerations between the two methods, such as the fact that the breath analysis devices measure acetone and the blood device measures beta-hydroxybutyrate (but this will not impact many people unless they have undertaken more detailed metabolic analysis, such as the Organic Acids test, or are undertaking steps to manipulate their NAD+/NADH ratio). These ketone markers rise and fall together, hence why both are valid options to measure.
Urinary strips are not useful. While they can be useful to measure the initial rise in ketones, the amount that makes it into the urine represents the net sum of ‘ketones produced’ minus ‘ketones used’. This will be low in someone who is not in ketosis and also low in someone who is in deep ketosis but is efficiently using these ketones. In short, we can’t make any fair conclusions with these urinary strips.
What can I do to get into nutritional ketosis quicker?
Carbohydrate-draining exercise, C8 Oil or exogenous ketones (see below).
What is C8 Oil?
C8 Oil is another label for caprylic acid; the moniker is derived from the fact it is an eight-carbon fatty acid. It is typically extracted from coconut oil, where it makes up 6% of the total fatty acids.
C8 Oil is unique in that, unlike other fatty acids, it does not take a long and drawn out journey to reach your circulation (most fats go from the intestines to the lymphatic system and then finally released slowly into the bloodstream attached to transport vehicles called chylomicrons… this takes some time). Instead, the fatty acids from C8 Oil go from the intestines direct to the liver; this is important, as it results an a massive increase in the availability of fatty acids at the liver, temporarily inducing ketogenic conditions regardless of your dietary balance.
Most people use C8 Oil in doses of 5-20g per day.
Two considerations with C8 Oil:
- some products will be over 95% C8 Oil and will list the C8 Oil content. Other products, often labelled as MCT Oil (Medium Chain Triglyceride Oil) will contain only half this amount; there is no need to avoid these lower-grade products, but you will need to double the dose if using them to augment ketone production.
- The caprylic acids in C8 oil can easily interfere with the membrane composition of common intestinal microbes, which gives this product a reliable anti-microbial effect. While this is theoretically a good thing, it can result in noticeable discomfort (often gurgling, sometimes nausea, potentially diarrhoea). For this reason, it can be helpful to start taking C8 Oil at a low dose before starting the ketogenic diet, rather than finding that need it but are struggling to tolerate these initial effects. Any discomfort tends to settle in a matter of days.
What are exogenous ketones?
In recent years, we have seen an explosion of exogenous ketone products. These provide the ‘main’ ketone body, BHB (beta-hydroxy butyrate), in a salt form and give individuals the option to supply ketones to their central nervous system through their diet. The advantage here is that they offer a guaranteed method of fueling the brain during the transition into ketosis, and therefore avoid the undesirable effects of ‘low carb limbo’.
This holds particular promise in individuals whose insulin sensitivity or mitochondrial function stands to benefit from the ketogenic diet, yet simultaneously causes delays in their ability to produce enough ketones. Previously, this may have left them at a Catch 22, but this stop-gap allows them time to upregulate ketone production without suffering the starvation state (and the stressful reactions that this automatically induces) from the classic ‘low carb limbo’. Such usage is not without problems – typically, exogenous ketones see ketones rise for only a few hours at a time and therefore don’t fully replicate the ongoing benefits seen with nutritional ketosis – but they remain a potentially useful tool in these situations.
Unfortunately, these products have also become the focus of several multi-level marketing companies who push these products as a shortcut to weight loss, and a way of achieving ketosis without having to change your diet. There are certain circumstances where adding exogenous ketones to a non-ketogenic diet may help (primarily in neurological conditions related to energy metabolism, such as migraine or epilepsy), but it is important to note that the most common obstacle to weight loss occurs due to excessive oxidative stress at the mitochondrial ‘furnace’, which triggers a protective shutdown of metabolic activity and means that there is a substantial drop in the burning of fats. A ketogenic diet side-steps the main site that is responsible for this oxidative stress, thus avoiding the need for any protective shutdown of mitochondrial activity, and this helps explain why a ketogenic diet averages a 15% increase in basal metabolic rate. It is impossible for the same advantageous changes to occur if the individual is still consuming a carbohydrate-rich diet. It’s just not possible and anyone promising weight loss from exogenous ketones alone is talking BS.
I’ve taken C8 Oil/done some exercise but I’m still not producing ketones. What is going on?
There are three common obstacles that see people fail to produce enough ketones. These are:
- Imbalance of proteins, fats and carbohydrates. This is by far the most common obstacle. Due to years of fat phobia, many individuals underconsume fats. Ketosis calls for a minimum of 140g fats per day, but often closer to 200g and sometimes even more. If you are not sure how much you are consuming, track your intake using one of the many apps/websites available to do so (myfitnesspal, fatsecret, cronometer, etc). It is surprising how many times these ‘unexplained’ problems in producing ketones are explained by the person eating less than half the fat they need. Another common issue is the over-consumption of proteins. Ever since Dr Atkins popularized the ketogenic diet, it has been sloppily characterized as a high-meat diet. This is not accurate. Protein products can be converted into ‘carb replacements’ and therefore inadvertently distort the fat-to-carb ratio where it matters. While athletes and those exercising regularly have more flexibility, our ability to produce ketones will be compromised once we consume more than 90g of protein per day. And finally, this leaves carbohydrate intake, which need stay beneath 45g per day in those who are not exercising regularly (slightly lower if there are insulin sensitivity issues).
- Poor fat absorption. It is not how much fat that you put in your mouth, it is how much fat arrives at your liver (the site of ketone production). This requires efficient fat digestion, which means efficient release of bile from the gall bladder. This is known to be lower in low-energy states and in those subject to stress. Therefore, if you adopt the ketogenic diet and then notice intestinal distress, oily/floating stools and a distinct lack of ketones, then this should be the first question to ask. See the fat digestion question (below).
- Poor fat breakdown from storage. The total sum of fatty acids that arrive at the liver should be made up of the fat you eat and that released by your fat cells. However, we often see the fat cells become ‘defensive’ of their energy; I often see this in those dealing with inflammatory issues, high stress levels and especially those who have dieted long term. This is manifested by issues in the AMPK pathway, the body’s breakdown pathway, and can sometimes be compensated for through the use of AMPK activators (Gynostemma is especially useful in these circumstances), thyroid support and overcoming mitochondrial blockages.
What if I do not digest fat well?
I have mentioned the role of low-energy states and excessive stress responses in gall bladder function above. It therefore figures that the long-term aim is to attend to both, although this is rarely an overnight thing and often the low-energy state actually calls for a spell in ketosis. As a consequence, we are often looking at compensating for these issues to reach a state of ketosis.
Thankfully, this is easily achieved with a bile supplement. Ox Bile is commonly added to digestive enzymes (as part of a wider blend of support), otherwise found as a stand-alone item for those looking for larger doses. Most people will find that they need bile support for a short period of time (until energy and stress issues are resolved) and can then remove it. You can be confident that fat digestion is working well if you can remove this support and maintain good ketone readings (and digestive comfort).
What is ‘keto flu’ and is this normal?
Keto flu is not ‘normal’ but it is common. The term is used casually to refer to any incidence of feeling ill/tired/fluey during the transition into ketosis. In most cases, this is caused by:
- Low carb limbo, the state where you have removed the carbohydrate source but not yet replaced it with sufficient ketones (see above).
- Electrolyte imbalance. Insulin is well known to push glucose into cells. However, it also pushes potassium into cells, something that can have a knock-on impact on sodium balance too. Because a ketogenic diet is almost always a low-insulin diet, we can easily see a drop in electrolyte status. Low sodium tends to leave people feeling dizziness upon standing, low blood pressure, cold hands/feet, frequent urination and general lethargy, while low potassium may manifest as dry mouth/lips, constant thirst, weak/shaky limbs, increased sock marks (‘dents’ after removing socks) and frequent urination. Individuals who exercise (and sweat) a lot during the transition are especially likely to notice these issues. It is worth noting that almost all humans I work with, those doing keto or not, benefit from magnesium supplementation and that magnesium plays a major role in controlling sodium/potassium status.
- Herxheimer response. While it is an over-generalization that intestinal imbalance can be solved by eliminating sugar, a substantial number of microbes (such as candida albicans) thrive in conditions of high sugar availability. As you might imagine, removing sugar overnight can result in these species becoming severely weakened and this may see your immune system kill them. This is a good thing, at least in theory, but can see the yeast (and bacterial) cells burst their cell membranes; any chemical they would have released slowly is now released in one go, resulting in localizing poisoning. Binders like Charcoal (best taken mid-afternoon, away from food) can be extremely helpful in these circumstances.
While most episodes of ‘keto flu’ are actually one of the three outcomes above, it’s worth noting that anyone adopting a ketogenic diet will have undertaken a profound shift in the foods they eat. This means adding foods (oils and fats) and removing others (grains, fruit and sugary snacks). It is entirely possible that, in making this change, individuals will remove a food that they were allergic too. Due to the under-discussed opioid effect observed in allergies, removing such foods can result in withdrawal. This same concept can be found in some individuals that lack key enzymes that break down morphine-like compounds found in wheat and milk. The same enzyme defect might explain why no-one has ever reported back a difficulty in eliminating porridge… bread and pasta, on the other hand…
Do genes affect my ability to get into ketosis?
It’s possible but, after years of tracking, I am yet to see a single gene that impacts someone’s ability to produce ketones.
Do my genes affect my ability to benefit from ketosis?
Potentially. The APOE4 gene is most known as an increased risk factor for Alzheimers but, if you are a carrier of this gene variant, this may also influence your response to the ketogenic diet. Why so? Because this APOE gene encodes fat transporters, meaning that reduced function here can lead to excessive build-up of fats in both the brain and liver (which could, depending on circumstances, result in plaque formation that is a hallmark of the neurogenerative condition). However, individuals with this gene variant are much more likely to show substantial rises in cholesterol if they consume a high-fat diet. It is important to note that his is not necessarily bad in itself but, should there be slow cholesterol turnover and excessive oxidative stress in play, this increases the likelihood of the cholesterol proteins becoming oxidized (which is definitely something we wish to avoid, as this is the way through which cholesterol can be a risk for cardiac health).
This does not mean that all carriers of the APOE4 mutation must avoid the ketogenic diet. After all, ketosis still remains one of the most promising approaches to counter risk of neurodegeneration and has even demonstrated direct value in APOE4 carriers with Alzheimers. It’s clear that APOE4 individuals can get either positive or negative effects from a ketogenic diet and the metabolic conditions will determine this. Therefore, it may be helpful to discuss the pros and cons of such an approach with a practitioner that understands both the role of the APOE4 gene and also the conditions that influence its impact. This, together with monitoring of cholesterol status (not just the basic lipid panel, but also the oxLDL and LDL subfraction test), thyroid status and redox status, allows for clear understanding of its effects and easy conclusions on what may be suitable for you going forward.
Do I automatically lose weight in ketosis?
No. If you consume sufficient amounts if ketosis, you should easily maintain your weight if this is your goal. However, ketosis removes two of the most common obstacles that stop people from losing weight. These obstacles are:
- Impaired sensitivity at the hypothalamus, the energy management centre of the body. If a state of low-grade inflammation is sustained, the hypothalamus can become insensitive to energy signals like leptin (a hormone released from the fat cells to communicate how much energy reserves currently exist; the more fat stores you have, the more leptin you release). This results in the hypothalamus believing that you are about to starve to death and, as a consequence, it downregulates energy usage and increases appetite (reduces fat burning and increases cravings). A ketogenic diet can restore leptin sensitivity and induce markers of good energy stores in the hypothalamus, which reverses such problems.
- Mitochondrial slowdown. It’s no good being given the permission to use up your energy reserves if the furnace cannot use it. The mitochondria are limited in the amount of energy they can burn (oxidize), because the energy-releasing process also forms ROS (aka Reactive Oxygen Species, aka oxidants aka oxidative stress) that can damage the cell. Thankfully, evolution equipped the mitochondria with safety mechanisms that sees the flow of energy compounds shut down when the level of ROS exceed a safe level. The processing of fat results in much less ROS relative to the processing of carbs, at this is why we see an increase in metabolic rate of around 5-16% simply from switching the fuel source. This should be seen as removing the slowdown rather than boosting the metabolic rate above ‘normal’.
For this reason, many people find that they struggle to lose weight until they undertake a ketogenic diet. However, it is possible to remove these obstacles without using the ketogenic diet (albeit less efficient). It is also worth mentioning that ketones have appetite-suppressing effects and, should an individual suffer with a low appetite, they may accidentally undereat. In my experience, this appears particularly likely in people suffering from intestinal disturbances.
The weight loss effects are generally seen as a ‘weight normalization’ response as the obstacles in energy management have been removed. This is why overweight individuals are likely to see their weight drop and underweight people (who may struggle with the processing of carbohydrates, normally due to intestinal/microbial issues) often see their weight increase on a ketogenic diet. However, it is important to note that the obstacles mentioned above are the most common but not the only obstacles; if you happen to have other issues affecting your metabolism, you will not see the normalization response until these are identified and removed.
