Exogenous Ketones — Friend or Foe?
The science behind what exogenous ketones do, and how they can be gamed for maximum benefit.
Ok. I admit it. I used to be a skeptic when it came to exogenous ketones.
But hear me out — it wasn’t without reason.
My BS meter and involuntary shoulder twitch on the topic was birthed from seeing everyone and their mother taking exogenous ketones, joining MLM companies and promoting them without first being fat adapted.
That is to say, taking ketones as a supplement without first being able to produce your own ketones.
Ketones are the end product of fat oxidation. Meaning, when you are burning fat as your fuel source, your body will break the fat down into fatty acids, which are converted to ketone bodies which are then used to create energy in your cells.
Producing your own ketones is primarily achieved through fasting, the ketogenic diet, or both.
Why Is This An Important First Step?
Simply put, being fat adapted, or in a state of ketosis is another way to say that you are metabolically flexible.
You are in line with your evolution as a Homo Sapien.
There were many times when our ancestors had no food, often for long periods of time. Being metabolically flexible was a necessary adaptive strategy in our evolution, allowing us to burn our own stores of fat as an energy source.
When we burn our fat for fuel we produce ketones that are used for energy. This is what is referred to as endogenous ketone production.
Or simply, ketones that your own body is creating.
This is important. I still maintain (with a much less obvious twitch nowadays) that this should be done before any ketone supplements are taken because:
- It is important to be able to build out the capacity and strengthen the pathways required to convert fat to ketones.
- It takes time, trial and error, and adaptation
If you are in a glycolytic state (meaning that you are burning sugar for energy), and you decide to skip doing the work to produce your own ketones first…you are flooding the blood stream with ketone bodies while it has higher levels of glucose and insulin in it.
This is not a natural state.
In fact, you would be hard pressed to try and naturally replicate a situation where you had ample amounts of glucose, insulin, and ketone bodies in the blood simultaneously with food alone.
So…
I say all of this to preframe that YES — exogenous ketones are awesome.
BUT simply taking exogenous ketones is not a free pass to skip actually doing the work yourself.
It is not as simple as, I take an exogenous ketone supplement, I measure my blood ketones and SURPRISE! There are ketones, so I must be burning fat now!
First things first. Start at the start:
- follow a ketogenic diet,
- practice regular periodic fasts,
- and exercise — steady state, HIIT, and heavy weights — take your pick.
THEN add in exogenous ketones to supercharge your results and amplify the natural physiological state you have created.
It just makes good sense to have the body’s physiology in a state that already mimics ketones being produced and circulating.
Ok. With that preamble out of the way, there are 3 main ketone bodies that we produce endogenously. Of these, we are going to talk about one on the a nerd safari we are going on today — β-Hydroxybutyrate, or BOHB for short.
There are some super cool, interesting benefits that BOHB has on the body, ranging from making you feel like a superhero about 30 minutes after drinking it, all the way to helping to increase your lifespan.
Yes. I know. Lifespan.
Here are my 4 favourite benefits of BOHB on the body.
1. It Keeps Brains Big, Thick, And Juicy (AKA- It Activates BDNF)
“The root of all health is in the brain. The trunk of it is in emotion. The branches and leaves are the body. The flower of health blooms when all parts work together.” — Kurdish Saying
When we are talking about playing the long game with your health, that is to say, doing things that will activate our health and life span, brain derived neurotropic factor (BDNF) plays a central role.
BDNF is involved in the preservation of nerves that you already have, as well as stimulating the growth of new neuronal cells.
In other words, BDNF keeps your brains big, thick, and juicy.
Exactly what you want for your main organ that directs and receives all communication in your body, right?
When we think about the diseases of an aged brain, Alzheimers and Parkinsons being the top 2 in the category of neurodegenerative diseases, both feature a progressive decrease in cortical mass.
In other words, both see a decrease in mass, and size of the brain.
In Alzheimer’s, we see an initial decrease in the hippocampus (an area involved in long term memory), and eventually areas that control language, reasoning, and executive function.
In Parkinson’s, we see a focal decline in areas of the brain that produce dopamine. Followed by areas involved in reasoning, memory, learning, and motor control, giving rise to the classic Parksonian tremor.
One of the awesome features of BOHB is it can cross the blood brain barrier and be used by the brain as a fuel source.
Circling back to creating and maintaining big juicy brains, BDNF is activated by ketones like BOHB to upregulate its activity.
Therefore there is a neuroprotective affect of having increased levels of BHB in the brain.
2. It Helps You Live Longer (AKA - It Activates FOXO3)
“Life well spent is long.” — Leonardo Da Vinci
Scientists have discovered — FOXO3 — a pretty awesome gene that, when activated, is associated with increased lifespan.
This is in part because FOXO3 regulates a whole bunch of factors related to longevity, including metabolism, reduction in oxidative stress, and also plays an important role in stem cells proliferation in the brain.
Perhaps most interestingly (at least to me),is that FOXO3 works by decreasing insulin and IGF-1.
When insulin and IGF-1 are constantly and chronically elevated (as they are in a standard American diet) it has been linked to everything from Diabetes to cancer.
In other words, through a ketogenic diet, fasting, or BOHB supplementation, you increase the activity of a gene that is strongly correlated with lifespan
3. Its stops “Inflammation and Aging” (AKA -Inflammaging)
“I may be a senior, but so what? I’m still hot.” — Betty White
When we look at centenarians (people who live over the age of 100), and super-centenarians (people who live beyond 110), one of the hallmarks of their physiology is their lowered inflammation levels.
In fact, lower levels of systemic inflammation is one of the biggest predictors of lifespan, cognitive function, and independence.
In other words, finding ways to lowering inflammation is an important aspect in how we age.
Now inflammation can come from many sources. The ones we can look at and control with the most ease are nutrition (what you eat and supplement with), fitness (how, how often, and how long you move), and your ability to appropriately respond to perceived stress levels.
Interestingly, supplementing with BOHB has been shown to lower inflammation levels through suppression an inflammatory pathway associated with aging.
It has also been noted for its neuroprotective effects by exerting anti-oxidative effects and improving mitochondrial function, which is an essential part to staying young.
Lastly, BHB has been cited for its role in reducing inflammatory cytokines, which have been strongly correlated with depression.
Let’s unpack this a bit.
What we know is most chronic diseases have inflammation as a core physiological feature.
This is particularly true when we think of the big 3 categories that most of us will succumb to: cerebrovascular, cardiovascular, and neurodegenerative diseases.
That is to say, strokes, heart disease, and conditions like Alzheimers.
All of which are associated with major inflammation over a long period of time.
When we look at some of the differences in the lifestyle in centenarians, super-centenarians, or populations in the blue zones, we see they eat foods consistent with The Longevity Diet — meaning they consume foods high in fats, meat proteins are not consumed daily, and they consume nutrient dense plants and vegetables daily.
Other hallmarks is that they are active most of their lives, and live close to or with family members.
As such, these populations are able to successfully reduce and delay the onset of the biomarkers of aging that can elicit and propagate the progression of disease.
This is particularly important to consider for people growing up today, since our lifestyle is drastically different than what it was 30 or 40 short years ago.
Our lifestyle now is very much pro-inflammatory.
North Americans typically live pro-inflammatory, pro-disease lives (think about your everyday: likely sitting in a flexed position for hours on end, not enough natural sunlight, not enough movement, artificial food stuffs, artificial colouring, going to bed late, blue light exposure, less in-person contact with our loved ones, late night snacks, the list goes on and on).
So, we know there are a compendium of strategies that can help with reducing inflammation — most involving our nutrition, our fitness, and how we respond to stress.
One of the nutrition strategies we can use to get ahead of and potentially game the lower the inflammatory process is by supplementing with, or generating our own ketones.
4. Maintains Strong Skeletons (Via Osteoclastic Inhibition)
“To succeed in life, you need three things: a wishbone, a backbone and a funny bone.” — Reba McEntire
It goes without saying, that having a strong frame, namely in the form of your skeleton, is an advantage as we age.
Up until about the age of 25, we have more osteoblastic activity (the making of new bones) than we do osteoclastic (the process by which bones are broken down).
After this, the tides begin to slowly turn. We begin to have more osteoclastic than osteoblastic, and the quality, density, and strength of our bones begin to decline.
This changing skeletal landscape affects important risk factors related to balance and muscular strength.
Bone density is inversely related to fracture risk. Meaning, the better your bone density, the less likely the risk of fracture.
Strategies like weight lifting are a great way to retard this process.
And so is BOHB (be it exogenous or endogenous sources).
BOHB has been shown to slow down osteoclastic activity, with the cumulative effect over time being the improving strengthen and integrity of the bone itself.
This is because BOHB slows the rate at which the bone breaks down relative to bone formation.
BOHB has also been shown to improve calcium deposition within the bone, and improved internal density of the bone.
Conclusion
So, while a late adopter, I have become a superfan of exogenous ketone supplementation, provided you are already following a ketogenic diet, and regularly fasting.
- They help with brain health
- They help by activating longevity pathways
- They help with reducing inflammatory pathways
- They help preserve bone mass and density
Now remember, exogenous ketones can be BOHB salts, esters (but be forewarned, esters taste like swamp juice), and MCT oil.
Tread with caution when first starting with supplementation, and figure out what your gut tolerance is. Too much too soon and you will need to be in close proximity to a toilet.
A good strategy is to spread them out over your meals — drizzle MCT in your salads, blend salts with your pre-workout shake, or sip through the day for cognitive brain juice it affords.
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