How Keto, Fasting and Genetics can ‘biohack’ health, ageing and performance

An introduction to Functional Medicine, Epigenetics, Pro’s and Con’s of Keto and Fasting

Terms like keto, intermittent fasting, healthy living according to your genetics, gut health and microbiome get thrown around a lot these days, but what really do they mean, and should you consider incorporating them into your lifestyle?

I recently did a talk at Soho House in London, where I promised to upload the content so people could go back through the info afterwards, but this is also for the ones that missed it. Here you go.

Let’s start by getting some definitions sorted, so we know what we are talking about throughout the rest of this write-up.

Biohacking

‘The art and science of changing the environment around and inside us so as to optimise health, performance and longevity.”

Biohackers originally evolved from tech entrepreneurs in Silicon Valley that did not want to accept the status quo of their mortality, but use the newest technology and science to ‘hack’ their body and, particularly, brain’s capacity and performance, with the view that illness, fatigue, excess weight really were rather ‘annoying’ expressions of suboptimal health. Biohackers, which now include both tech people and scientists still are on the forefront of the newest discoveries with the aim to optimize and push boundaries where previously not deemed possible.

Epigenetics

Epigenetics is the study of changes in gene expression that do not involve changes to the underlying DNA sequence — in geeky words, a change in phenotype without a change in genotype — which in turn affects how cells read the genes.

In easier to understand words, epigenetics are all the factors prior to birth and during life that can change which genes we turn on or off, which of all our many genes get to express. They act like ‘bookmarks’ to tell our cells which parts of the DNA to read and express.

More concretely, you may have a genetic predisposition for a certain illness, but, unless it is part of the very few genetic illnesses that always express and which you usually know about from an early age on, your lifestyle choices determine whether that particular predisposition gets ‘turned on’ or will be ‘bypassed’. This is where the Functional Medicine way of looking at genetics comes into play, which is different than most of the ‘DNA Health and Exercise’ analyses that are currently out there, that still operate on the ‘old’ viewpoint of our health being set in stone, depending on what genes we have. Rather than looking at genes as destiny, Functional Medicine looks at epigenetics as an empowering tool to make targeted lifestyle choices to thrive, and potentially prevent or delay illness.

Functional Medicine

Functional Medicine aims to looks for and address the root underlying causes of illness and degenerative processes like ageing by considering gene-environment interactions and biochemistry of the individual, rather than to focus on the name of the disease.

In the functional medicine model, the word function aligns with the understanding that disease is an endpoint, and function is a process and a web-like interaction between the different biochemical pathways that make up life.

Functional Medicine can also be considered the ‘clinical backbone’ to biohacking, with Functional Medicine Practitioners being the first point of reference when it comes to the safe and clinical application of the newest dietary and biotech approaches, and they can help guide you through making the right choices by ordering the right labs and drawing conclusions for you according to the newest data out there.

Within Functional Medicine, the term ‘Health’ implies optimal health, performance, wellbeing and quality of life, rather than merely the absence of disease.

Functional Medicine looks at the actual labs and biochemical interactions of all the biohacking trends. It takes the guess work out of your health.

Fundamentals of ageing, energy metabolism and what role ketones can play

But what actually makes up health, and, on the contrary, ageing and illness? We will go into the fundamentals of biochemistry here, some of which you may remember from biology class at high school. We will also look at what ketones are, and why they may be an important tool for optimal health.

Optimal health equates feeling strong, happy and pain-free. It also means that everything in the body (and mind) functions just as it should, and all cells receive just what they need to work at their best, and the body’s cleaning service can keep up with any sludge that may develop throughout the day.

AGE’s and free radicals- what really is ageing?

Ageing, on the contrary, means that the body is unable to stay on top of housekeeping. Old, sick, mutated cells accumulate and overall function starts to deteriorate, potentially leading to what we commonly refer to as ‘ageing: cardiovascular disease, degeneration of brain and cognitive function, eye sight, wrinkles, type 2 diabetes, join pains, all the way to cancers.

On a less dramatic level, suboptimal cellular functioning may showcase as that stubborn belly fat you just cannot get rid off, fertility issues, or brain fog and fatigue.

One of the lead players in ‘ageing’ are substances called ‘advanced glycation end products’, in short ‘AGEs’, which are sugar molecules attaching to protein. Our entire body is largely comprised of protein, so this occurs throughout. It is much like when you put a steak on the grill and it goes brown, or if you leave metal in the rain, it rusts. That ‘browning’ or ‘rusting’ happens in our body whenever we are exposed to sugar molecules. This is obviously inevitable, as we do need some sugars, but it is about the balance between how much ‘AGEs’ we create in comparison to the body’s ability to get rid of them, whether we tip the scales towards ‘ageing’ or ‘thriving’.

Other lead players in damaging and wearing our cells down are inflammation and free radical damage.

Free radicals are actually a normal occurrence, and are even important in small amounts to keep our body and immune system on their edge. However, if more get produced than can get dealt with through strategies like antioxidants, cellular damage and potentially mutations occur.

You may have heard of substances like environmental pollutants and sun rays, that cause free radical damage in our body. However, we actually produce it ourselves when we produce energy. Whether damage occurs depends on our overall load of them, and the ability to quench the free radicals through antioxidants.

Energy metabolism basics

We create energy inside something called mitochondria, that you may remember from biology class. Mitochondria function as our body’s energy producing factories, utilizing sugars, proteins and fats to create the energy every cell and process in our body needs many times each split second to function optimally.

When we burn sugars, protein and fats as ‘fuel’, we create free radicals, much like a factory or car engine produces exhaust. However, the different types of fuels vary in the amount of free radicals they produce. Sugars produce a lot more than for example ketones, making ketones a more favourable energy source in most instances. The less ‘sludge’ we produce, the less our body has to work to clean up after it.

When we eat our standard Western, carb heavy diet, we not only constantly create ‘age’s- advanced glycation end products, we also create more free radicals along the way. One way to reduce the load we place on our housekeeping system, is to go into a ketogenic state more often than not.

What are ketones, and how does one get into a ketogenic state?

The ketogenic diet

The keto diet is a fats, moderate protein and very low carb diet. Eating a lot of fat and very few carbs puts you in ketosis, a metabolic state of burning fat instead of sugar for energy. When your body can’t get glucose from carbs, your liver converts fatty acids from your diet or your stored fat into molecules called ketones, an alternative energy source.

We can get into a ketogenic state by either

• Fasting, also called ‘Starvation Mode’,
• Reducing our sugar and carb intake to below 20-50g net carbs per day and keeping protein intake moderate (not high).
• Intense exercise that depletes sugar stores

The low sugar content in our blood forces the body to start tapping into our fat stores for energy, by a process called ketogenesis. In the absence of insulin, the liver produces these ketones to be readily available to supply the brain and other organs with energy. Fats themselves, before they are converted into ketones, cannot be utilized by the brain for fuel.

Ketones burn a lot cleaner and faster within the mitochondria, which is one of the reasons they are being touted as a super weapon against so many illnesses these days.

The obvious one is that it may help reverse insulin resistance and metabolic syndrome, and related conditions such as type 2 diabetes and cardiovascular illness. In a ketogenic state, we barely eat sugars, and as such we retrain our cells to become more sensitive to insulin, allowing it to do its job again properly.

Being in a ketogenic state has also been linked to weightloss,

As described above, in order for the body to get into a ‘ketogenic’ state, our blood sugar levels need to be low (other than if you add exogenous ketones, which we will cover shortly), and with it low insulin levels. Without going into too much detail here, insulin is the hormone that shuttles nutrients into cells for use, and, if excess nutrients are present, shuttles them into fat cells for storage. Insulin is the key that allows them to enter cells. The opposite happens when there is a lack of sugar floating around in the blood stream. That shuts down insulin production, but increases its counter-hormone glucagon. Glucagon helps liberate stored energy back into the blood stream to provide steady energy when energy supply is low, and to make sure the brain and heart can keep doing their vital function to keep us alive.

How does that relate to weightloss? Insulin is our ‘fat storage hormone’, glucagon our ‘fat burning’ hormone. We shift towards a glucagon dominated state when we are in ketosis.

Our entire body relies on the mitochondria to produce energy, however we often hear about certain areas of performance being affected by being in a ‘ketogenic’ state, including cognitive (brain) performance and improved mood. In fact, a ketogenic diet was originally prescribed to children with epilepsy in the 1920s and 30s century to reduce fits.

This is partly due to the fact that our brains have a very high density of mitochondria and heavily rely on constant and clean energy. The brain does need some sugars, but it works best having the majority of fuel in the way of ketones, as they burn very clean and efficiently.

Being in a ketogenic state has also been linked to reduced brain degeneration, ADHD, anxiety and improved mood, resilience and cognitive performance.

But what about the often spoken about keto- cancer connection?

Dr. Warburg in 1931 earned a Nobel Prize for his discovery back then that cancer cells need sugar to survive. Science now confirms that is still the case. Our other cells in the body can survive on a very low sugar diet, cancer cells don’t very well. There are obviously many more factors involved than just that, and it is not safe to assume that simply going keto will kick your cancer to the curb, BUT it may be one of the tools to consider in combination with other treatments, in accordance with your treating specialist.

Other benefits of being in a ketogenic state include:

• May support hormone related issues such as PCOS, acne, endometriosis, subfertility. Our bodies need good fats to produce our sex hormones such as estrogen, progesterone, testosterone. On a keto diet, we tend to include more fats into our diet to fill the gap of missing calories from carbs, which can also soften the drop of hormones with menopause.

• May allow for better endurance exercise and even, if done in a cyclical manner to refill glycogen stores, high intensity performance
• May support our HDL and LDL cholesterol ratio
• Ketones are anti-inflammatory, and as such may aid in improving many ailments. Some researchers call ‘ageing’ ‘inflammageing’ due to the strong link of inflammation to all cause mortality and ‘ageing’ increases.
• Autophagy- the cellular clean up state previously mentioned.

Intermittent Fasting

Another way of achieving autophagy, that cellular housekeeping, is fasting. By the same pathways as ketosis, being in a fasted state drops insulin and will in fact put our bodies into a ketogenic state. Cellular renewal is turned on more powerfully if we fast than if we add a bunch of fats.

You can think of it in the way that when you have kids, or kids visiting, it is much harder to keep the living room tidy, as they constantly pull out items to play with. It is much easier to make them play in the garden to do a proper tidy inside. Same goes for the body, if we are constantly eating, the body is busy digesting and tidying up after each meal, without having the ability to do a proper deep clean. Deep clean means getting rid of any old, sick or mutated cells by our intrinsic mechanism called autophagy. Our bodies are actually quite amazing at being able to stay healthy and ‘young’, if only we give it the chance to do its job.

As you are most likely well aware of, there are different forms of fasting that people talk about these days, from a daily intermittent fast where you compress the ‘feeding window’ into 2 to 8 hours by eating only one or two meals, to once a week a full day, to longer term fasting. There are real water fasts and fasting mimicking techniques out there. The shorter fasts allow our bodies to tap into the body’s cleaning up phase. A longer fast has been shown by research to even turn on our own stem cells, which conventional knowledge used to think to be inactive after our first years of life.

What are the con’s of fasting and keto?

This all may sound too good to be true, and it really has amazing health and longevity benefits. However, there are some potential downfalls to it.

Going long-term keto or prolonged, unsupervised fasting can

• Wreak havoc on our hormones, especially in females. Females, especially in their reproductive years, are hardwired, to, well, reproduce. If a female body gets the signals of ‘starvation’, it may shut down the production of our ‘sex’ hormones, estrogen and progesterone mainly, which can lead to niggly symptoms, and potentially even lowered fertility.
• Affect metabolism, weight loss stalling or even weight gain. Again, this is more so true for women than for men, but for both excessive fasting or long-term keto may lead to a lowered metabolism due to potential hormone downregulations like thyroid, leptin and kisspeptin. If the body gets the signal of starvation too long, it may start to downregulate the metabolism in order to ‘preserve’ resources, as it considers us to be in a famine.
• Cause hair loss. Again, this is due to a potential downregulation of thyroid hormone production.
• Fatigue (including what sometimes gets called ‘adrenal fatigue’) and dizziness when getting up. Being in a ketogenic state stimulates our kidneys to excrete more sodium (salt) and other electrolytes, plus it depletes our glycogen stores (the sugar stored for quick energy). For every gram of glycogen stored, we also keep 3-4g of water. Loosing this often accounts for the quick weightloss frequently experienced in the first few weeks of going keto. This gets rid of excess water weight and puffiness, but also may lead to electrolyte imbalances, that can tax the adrenal glands with the effects of potential fatigue, more hormonal issues, and blood pressure drops. Other symptoms of electrolyte imbalances include heart palpitations or a racing heart, feeling shaky and weak, headaches or migraines, leg or other muscle cramps, trouble with constipation and bloating. These are also commonly called the keto flu, which may occur during the initial period of adjusting to running on ketones rather than sugars.
• Cracking and painful joints, ‘empty looking skin’. Fasting may elevate uric acid levels if the body is not fat adapted yet. Further, as we dump glycogen stores, we make look slimmer but may risk loosing ‘too much hydration’. Our connective tissue that covers pretty everything in our body, from skin to organs to joints, needs small amounts of glucose in its structure. If we go too low in carbs for too long, we may loose excess amounts, making our skin wrinkly and joints aching.
• Diarrhea, floating stools or constipation from electrolyte imbalances, going dirty keto with too little fiber, or having pre-existing conditions that limit our capacity to break down fats properly.
• Keto breath, which happens when the body is not capable of converting acetoacetate into the ‘good’ ketone beta-hydroxybutyrate yet, but excessively produces acetones. It is also a sign that the body is not able to efficiently utilize ketones for energy, as once the mitochondria use ketones primarily, we should have lower levels of ketones floating around in the blood (and breath). Another common reason for that can be carnitine deficiency, as carnitine is crucial to pull fats into the mitochondria to get burned for energy.
• Going ‘dirty keto’ where only percentages of fats, protein and carbs count, but quality is overlooked, can in fact have the opposite effects as we’d like to achieve from going keto.

Microbiome

Your gut microbiome is a vast community of trillions of bacteria and fungi that inhabit every nook and cranny of your gastrointestinal tract, and have a major influence on your metabolism, body weight, propensity to illness, immune system, appetite and mood.

How to use keto and fasting for optimal health, without running into trouble.

• Focus on real foods, vegetables and nutrient quality.
• After an initial period of going strict ketogenic for 3-4 weeks, research recommends adopting a cyclical ketogenic approach. It mimics evolutionary periods throughout the week and year where we feast or famine, as food wasn’t always accessible. It appears that we want to aim for metabolic flexibility, which is the state where our body knows how to easily tap into its own fat stores for energy and shift into a ketogenic state when we fast or ingest little carbs, while having ‘feast’ days that reset our hormones, metabolism and glycogen stores.

• In practice, this often means going keto for 5-6 days per week but then adding one or two carb refeed days per week

Basics of keto:

• • Keep net carb intake being between 20 to 50g. Net carbs are Total carbs minus fiber, as they don’t get converted into sugars.
  • Ideally also add intermittent fasting
  • Ratios should roughly be: 75% of calories from fats, 20% from protein and 5% from carbs.
  • However, this seems to be difficult to do for many, and also takes the intuition out of eating. I prefer following strategy:

Fill your plate with low starch vegetables, at least 1 cup of leafy greens, one cup of cruciferous vegetables and one cup of colourful vegetables such as purples and dark red.

If you are having 2 meals per day, have roughly a large handful of protein with each meal.

Don’t skimp on natural occurring fats, but don’t overdo it neither.

Allow one portion of starchy carbs per day such as a cup of potatoes or a handful of berries, if you choose to be on the higher range of keto.

• Women may do better with sticking to sticking to the higher side of carbs throughout the week, such as making sure to include the 50g per day, such as found roughly in 1 cup of carb rich foods like rice, quinoa, buckwheat, potatoes, plus the small amounts of carbs found in low starch vegetables.
• Men can often go lower in carbs on their 5-6 days per week, unless they train hard.
• Women often do better adding some good fats into their morning coffee or tea to turn a fast into a ‘modified fast’, to keep hormone and metabolism running at their best, while still technically being in a ketogenic state and getting many of the cellular clean up benefits.
• If you are a power athlete whose sports performance relies on short bursts of high intensity energy, you need to make sure your glycogen stores are filled, and you may need to modify this slightly.

Carb-refeed day:

One day per week, we want to increase our carb intake to above 120g of carbs, more if you are training at high intensity. At the same time we want to avoid adding in too much fat that day, as the sugar in the carbs will increase insulin that opens our cells to store energy. We do not want to add to much fat when we are in energy storing mode, as that is what we would do. Store energy as fat.

• Make sure to add in enough hydration and electrolytes. Scientists that look into keto suggest 1-2 teaspoons of high quality salt per day (3-5g of sodium), roughly 2-3g of potassium such as found in leafy greens, avocados, seafood, and 300-450mg of magnesium per day such as found as well in leafy greens, avocados, nuts and seafood, dark chocolate. A great way to do this is for example having a keto coffee several times per week instead of breakfast, which packs in a punch of good fats (gut bacteria feeding butter, antimicrobial and fat burning coconut oil) plus the important first hit of good quality salts, along with caffeine that supports your body to tap into its own fat stores. Just make sure not to overdo either the caffeine or the external fats, as in the end of the day.
• If long-term health is your goal, choose high quality fats, protein and vegetables that are minimally processed, pesticide free, and nourish your body on different levels. Make sure that the majority of your plate is filled with low carb vegetables, eating the rainbow to benefit from the amazing plant power nutrients like free radical quenching antioxidants, and gut microbiome feeding fiber. This may have to be adjusted temporarily if you suffer from gut bacterial imbalances.

What’s the deal with ‘fat bombs’, exogenous ketones and all the extra fat that people indulge in often on a keto diet?

When you are first starting out on a keto diet, your body most likely will not be used to tapping into its fat stores for energy. If you are like most of us Westerners, our metabolism is primed to burning carbs and sugars, constantly needing more to prevent the blood sugar from dropping too low, which gives us cravings and the notorious ‘hangriness’.

During that transition period, adding in more dietary fats and exogenous ketones found in powders and supplements to keep up satiety and energy can be an important way to minimize blood sugar drops and to help us keep going.

Once our body is metabolically flexible, we don’t really need all that additional fat anymore, as long as we have body fat stores we want to burn. We simply want to make sure we get some good fats like omega 3s and omega 6s in, but we do not have to go overboard, but instead should go back to a more natural diet, including whole foods that are naturally higher in fats, rather than adding pure fats excessively.

How do you know you are doing it right? Blood vs urine vs breath ketone testing

You can test your ketones in the beginning, to see if you are actually getting into the ketogenic state, or whether you further have to adjust factors in your diet and lifestyle. Sometimes you can be eating the perfectly correct foods, but still not get into keto, because of stress or lack of sleep, or other factors. Testing in the beginning helps us get in tune with our bodies. Once we have done it for a while, we won’t have to keep doing it.

You can test ketones in the blood, urine or saliva. I prefer blood, as it is the most accurate. There are three different ketone types, beta-hydroxybutyrate, acetoacetate and acetone. Beta-hydroxybutyrate is the one we actually want the most of, as most of the health benefits discussed earlier can be linked back to this one. Acetone are produced when there are too many of the other ketones floating around in the blood for too long. It is what gives you a bad breath. It only gets produced in noticeable amounts when the body is not very efficient in utilizing ketones for fuel (yet). Hence a breath measurement of acetone may show that we are in ketosis, but not necessarily the kind of ketones we want.

Urine testing looks at acetoacetate, which is the first ketone produced in the liver. Urine testing is cheap and easily done, but again, it may not give us an accurate picture of blood ketones, only what ‘spills over’.

Blood testing is currently still considered the gold standard, and you can do this with an easy at home finger prick device.

Mild ketosis starts at measurements of 0.5 mmol/l, a good level of ketosis ranges from 0.5-3.0 mmol/l, and this is the level you would like to achieve on a regular basis for most health benefits. Going into deeper levels of ketosis will require either longer periods of fasting or extra fat intake, and should only be done under medical supervision for specific health conditions.

How to use genetics and predictive biomarker testing to personalize healthcare

Genetics, as initially discussed, may make us more prone to certain problems if we are not aware of them. This can include an increased genetic predisposition towards free radical damage if exposed to certain environmental substances like bbqing, smoking, increased anxiety if exposed to synthetic flavor enhancers, increased risk of lacking good gut bacteria if not eating enough fiber.

It can also tell us if, once free radical damage has occurred, we may have a harder time getting rid of the damage.

Specifically in relation to the topic discussed today, genetics can point us in the right direction whether it may be better for us to get into a ketogenic state with higher fat intake, or by whether opting for the restricting calories and fasting way of getting into ketosis may be safer. Genes can also tell us if we need to be especially strict with a low carb approach, whether we can get away with more omega 6s than others before we get inflamed, and if we can convert some of the plant-based version of omega 3 found in for example flaxseeds into the active and brain protective form otherwise found only in fish and algue.

If we know our own genes, we can then take the right measures to

1. Track ‘predictive biomarkers’. Predictive biomarkers are lab tests in blood, urine, stool, that show us where on the spectrum between optimal health or chronic illness we are. Genetics determine which markers may be more important for an individual to look at on a regular basis, and address in case these markers aren’t in optimal ranges.
2. Make an educated decision on our vices. You may be ok to ‘cheat’ with one thing, but another may be very harmful. It also allows you to bypass and strengthen certain weak spots in a very targeted and personalized manner.

This is a powerful way of taking our health into our own hands, and being proactive about it. Personalised precision healthcare is here, so why not use it as a tool to make the most of your lives.

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