Category Archives: ketosis

are ketones insulinogenic and does it matter?

There has been a lot of chatter around the interwebs lately about exogenous ketones and whether they are health promoting, particularly for people with conditions that relate to excess insulin such as diabetes, traumatic brain injury, Alzheimer’s, cancer, epilepsy, obesity etc.

exogenous ketone are trendy
exogenous ketones, Pruvit and Keto//OS are becoming trendy.

Exogenous ketones are becoming trendy, particularly in the low carb scene!

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A couple of people recently asked me whether I thought exogenous ketones are insulinogenic.  Roger Unger’s 1964 paper the Hypoglycemic Action of Ketones.  Evidence for a Stimulatory Feedback of Ketones on the Pancreatic Beta Cells[1] indicates that ketone levels are controlled by insulin and that ketones suppress lipolysis:

Ketone bodies have effects on insulin and glucagon secretions that potentially contribute to the control of the rate of their own formation because of antilipolytic and lipolytic hormones, respectively.  Ketones also have a direct inhibitory effect on lipolysis in adipose tissue.[2]

It seems that exogenous ketones are insulinogenic to some degree.  But how do we test this hypothesis to find out whether they are just slightly insulinogenic like fats or more insulinogenic like carbohydrates?

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how to test the insulin response to exogenous ketones in someone with Type 1 Diabetes

If someone with Type 1 Diabetes stops taking their insulin both their blood glucose levels and blood ketones spiral out of control as they slip into ketoacidosis[3] which can be dangerous and fatal before very long without exogenous insulin injection.[4]   In metabolically healthy people,  high levels of ketones suppress mobilisation of body fat (lipolysis).[5]

In someone with Type 1 Diabetes, taking exogenous insulin brings both ketones and blood glucose under control.  So, based on what we see in people with Type 1 Diabetes, it seems logical that exogenous ketones would provoke an insulin response to keep ketones and glucose under control.

One way to test whether exogenous ketones are insulinogenic would be to have an Type 1 Diabetic to take a significant amount of exogenous ketones and monitor how much additional insulin they would need to keep the continuous blood glucose stable with the same amount of calories in glucose.

I initially became interested in exogenous ketones after hearing a number of podcasts with Patrick Arnold and Dominic D’Agostino thinking that it may be a useful alternative source of energy that does not rely on insulin for my wife, who has Type 1 Diabetes.  However the one time she tried it resulted in such bad gut distress she never touched it again.  So scratch that n = 1.

food insulin index testing with exogenous ketones

Another way to test whether exogenous ketones are insulinogenic would be to run a food insulin index test[6] [7] using ketones rather than food.  This would involve giving 1000kJ of exogenous BHB (e.g. 48g of KetoCaNa) and measuring the insulin response over two or three hours.

The chart below compares the results of previous food insulin index tests undertaken for different foods.[8]   Comparing the area under the curve insulin response for the exogenous ketones to the insulin area under the curve for glucose would give you the insulin index for exogenous beta hydroxybutyrate.  I’m surprised that the companies marketing exogenous ketones to people with metabolic issues, as part of their due diligence, haven’t already done this testing to understand to what degree exogenous ketones are insulinogenic.

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but wait, the food insulin index testing with exogenous ketones has already been done!

Then I came across this figure in a paper, Nutritional Ketosis Alters Fuel Preference and Thereby Endurance Performance in Athletes (Cox et al, 2016)[9],  where they have effectively done the food insulin index testing with exogenous ketones.

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Thirty-nine athletes took an isocaloric dose of ketone esters, carbs and fat in three different sessions. In the chart on the right (G) we can see that the ketones provoked about half the insulin response compared to the carbohydrate drink.  This test is different to normal food insulin index testing in that the participants started to exercise ten minutes after taking the drinks (i.e. at T = 0) at which point insulin and glucose start to rapidly decline.

updated insulin load formula, including exogenous ketones

The chart below shows the relationship between the food we eat and our insulin response based on the previous food insulin index testing.

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In lieu of more thorough food insulin index testing, I think we can update the insulin load calculation formula to:

insulin load = carbohydrate – fibre + 0.56 * protein – 0.725 * fructose + 0.5 * exogenous ketones

It appears that exogenous ketones provide about half the insulinogenic impact of carbohydrates (i.e. about the same as protein).


So, if you’re avoiding protein because of its impact on insulin, should you also consider exogenous ketones for the same reason?  Mike Julian added:

Exogenous ketones stimulate insulin, but BHB also inhibits lipolysis directly via the nicotinic acid receptor PUMA-G in adipose.[10]

While exogenous ketones may be equally as insulinogenic as protein, they’ll also be a counterproductive use of insulin.

Whereas the insulin response to protein is a positive use of insulin to build and repair muscle, with exogenous ketones, insulin simply reduces oxidation of other fuels to allow ketones to be burned.

Exogenous ketones displace the burning of other substrates.  You know what else displaces the burning of other substrates?  Glucose. Carbs reduce the amount of fat you burn. Similarly, exogenous ketones displace both fat and carbs/glucose.

That’s a double whammy in the wrong direction! Substrate competition is key.

total energy = glucose + ketones

In a healthy metabolism, endogenous ketones are generated as fat stores are mobilised to compensate for a decreased energy availability from glucose.  When glucose is not available, ketones come to the rescue to ensure survival.

If you’re insulin resistant, you might have trouble releasing free fatty acids due to the high levels of insulin circulating in your blood stream.  This inability to access your own fat stores will reduce your ability to create ketones and likely lead you to be more hungry and eat more than you otherwise would if you were insulin sensitive.  If you are insulin sensitive you can more easily access your own body fat stores.

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This chart demonstrates the concept of total energy (i.e. glucose + ketones) using more than a thousand combined ketone and glucose readings from people following a low carb / keto lifestyle.  Other than in the extremes of extended fasts or major feasting, the body seems to use insulin to maintain a homeostasis of around 5 to 6 mmol/L of total energy in the blood.

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On the left hand side of the chart, when our blood glucose levels drop, we get a rise in ketones, but an increase in autophagy and all the good stuff that comes with fasting and ketosis.

On the right hand side of the chart, when we drive our total energy high with excess energy (be it from processed carbs, Bulletproof Coffee, or exogenous ketones) the body releases insulin to bring the energy out of our blood stream and back into our liver.

People with the highest levels of metabolic health tend to walk around with a lower total energy in their bloodstream.  It seems you don’t need to buffer lots of energy in the blood if you can easily mobilise body fat and glycogen stores quickly when required.  Further, having high levels of energy sitting around in the blood stream is far from ideal and leads to glycation in the case of high blood glucose levels and oxidation in the case of free fatty acids.

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The total energy concept also seems to hold up with laboratory testing in rat pancreas islet cells, where exogenous ketone bodies promoted insulin secretion when there was greater than 5.0 mmol/L of glucose.[11]

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It appears that if your blood glucose levels are greater than 5.0 mmol/L (or 90 mg/dL), then exogenous ketones will be insulinogenic (at least if you’re a rat, but we have no reason to believe this wouldn’t occur in humans as well).

So if your blood glucose levels are greater than 5.0mmol/L (or 90 mg/dL),  then those expensive exogenous ketones may just be working as quick burning insulinogenic fuel, just like a dose of simple carbs.

do exogenous ketones “help” with fasting?

Mike Julian again:

If exogenous ketones raise insulin and reduce blood glucose, then where does the glucose go?  It gets stuffed back into the liver. 

Think about all of these people who fast with the intent of depleting liver glycogen but drinking Keto/OS. They’re literally preserving glycogen stores! No wonder we were seeing whacky glucose and ketone response to fasting with exogenous ketones.

Instead of the normal trajectory of a fast that would result in depleted liver glycogen we see exogenous ketones keeps this from happening, so you would get purges of glucose out of the liver throughout the fast when people were fasting using exogenous ketones.”

Let’s take a quick look at what Mike means by “the normal trajectory of glucose”.    In the chart below, we can see that blood glucose levels drop and ketone increase in four people.

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Where things get interesting is when you step look at the longer-term glucose and ketone trajectory of the fourth person who was taking exogenous ketones during the fast.

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What’s causing this anomaly in glucose and ketone response?   Is it a unique level of insulin resistance, or could this simply be explained by the use of exogenous ketones which are down regulating release of free fatty acids and endogenous ketone production?

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One theory is that exogenous ketones are switching off lipolysis, which drives the liver to release more glucose and ramp up gluconeogenesis to fuel the system during fasting?

The glucose : ketone index is the measure that Dr Seyfried encourages cancer patients to use during a fast to measure its therapeutic effect.  The lower the better.  For most people the GKI continues to drop during extended fasting, but in this case the GKI dropped and then starts to rise over time when taking exogenous ketones.

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I would like to see some more thorough studies to understand if this is typical in people taking exogenous ketones during extended fasting.  It’s not conclusive, but n = 1s are useful to build a hypothesis that can be tested in a more controlled environment.

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oxidative priority

Ray Cronise and David Sinclair recently published an intriguing article, Oxidative Priority, Meal Frequency, and the Energy Economy of Food and Activity: Implications for Longevity, Obesity, and Cardiometabolic Disease (2016)[12] where they detailed the basis for the oxidative priority of different fuel substrates.

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  1. Alcohol will be burned first because the body has limited storage capacity for it. It sees it as a toxin that needs to be cleared.
  2. Protein will be burned second because you can only store a few hundred calories worth of amino acids in the bloodstream (though I think most people struggle to overeat protein when from whole food sources).
  3. Carbohydrate will then be burned before we can access our virtually unlimited stores of body fat.

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So, I think it would be logical that exogenous ketones would be first in line (before or just after alcohol) to be burned off because the body has no way of storing the exogenous ketones other than circulating in the blood stream.

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So, it seems that exogenous ketones neither lower insulin nor promote fat burning.  They’re just another fuel that will be burned before the fat on your bum and your belly.

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do exogenous ketones boost exercise performance?

Exogenous ketones in sports performance is an interesting area of research.  Rumour has it the Tour de France cyclists and British Olympic rowers are using ketone ester drinks (though it’s worth noting that the people spreading these rumours are selling the ketone esters).[13]

Some people use exogenous ketones as a preworkout, like caffeine, to give them a cognitive boost.  Research by Richard Veech and Kieren Clarke suggests that there may be a small athletic boost if you provide both exogenous ketones and exogenous glucose at the same time to provide a “dual fuel”.[14] [15]  This situation provides a fuel oversupply that would force the body to burn off the excess fuel quickly.  However other people like Dr Mike T Nelson suggest that driving a chronic energy surplus from high ketones and high glucose might be problematic in the long term as there is no precedent in nature for this condition.[16]

I have dabbled with exogenous ketones (i.e. KetoCaNa, Pruvit and the Ketone Aid ketone ester).  The chart below shows  how my blood ketones rose to 3.5mmol/L and then back down to normal levels after about 3 hours.  Note how my body tries to remove the excess energy from the blood stream and bring the total energy back down to around 5.0mmol/L.

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I didn’t find a massive boost in performance in my workouts with any of the ketone products.  My best performance is when I was fasted without supplementation and it seems I could easily access my fat stores and breath more effortlessly.

I’m far from a high level athlete, but when I perform at my best cycling or in my kettlebell workouts, my breathing seems effortless and my time to exhaustion increases.   When we are insulin sensitive and / or don’t have excess glucose in our system and burn more fat for fuel we use less oxygen than when we burn glucose for energy.[17]  That reduction in oxygen usage is critical to make sure you don’t get out of breath and fatigue.  It seems that too much exogenous ketones or glucose in the system will mean that we’re less reliant on burning our own body fat.

I think the future of exogenous ketones in athletic performance will revolve around finding the right dose to boost ketones enough to get a performance benefit, without switching off lipolysis, which is where the real performance powerhouse lies.   If you put in so much fuel in line in front of your virtually unlimited fat stores, then you may risk gassing out because you can’t access your fat stores as easily.

Perhaps someone who is a normal carb burner might benefit from having ketones raised to the 3 or 4 mmol/L range, while someone who is more fat adapted might benefit more with ketones in the 1 to 2 mmol/L range so as to get a dual fuel boost without switching off fat burning?

It’s still early days.  Time and more experimentation will tell.

does it matter?

If you’re metabolically healthy and you enjoy the brain buzz of exogenous ketones more than alcohol or caffeine and want to use exogenous ketones as a pre-workout, then I say go your hardest if you can afford it.

However, if you are looking for improvements in your metabolic health or magical weight, I think you should be cautious.

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Companies like Ketopia are marketing exogenous ketones as a “bridge” through the keto flu, which I think is a more ethical approach (although many people say you can eliminate the ‘keto flu’ with good mineral supplementation).

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But you probably haven’t heard of Ketopia, because selling seven days’ worth of exogenous ketones isn’t a great business model in comparison to getting people to sign up for an ongoing subscription as a distributor buying thousands of dollars of ‘inventory’ up front so they can take it… Every.  Single.  Day.

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If you’re using exogenous ketones with the hope of reducing insulin levels or reversing metabolic disease (e.g. Type 2, cancer, Alzheimer’s, obesity), then maybe think again.  Exogenous ketones may alleviate your symptoms while they’re in your system (about 2 hours), but I fear they might worsen the conditions that people are using them for in the hope of improved metabolic health.

Mike Sheridan’s article in T-Nation makes a number of excellent points:

Ketones may be depressing dieters’ hunger and giving them a hit of energy and cognitive enhancement, but it’s INHIBITING their ability to burn fat, providing zero nourishment, and doing nothing for their metabolic health. There’s an assortment of evidence suggesting that it’s probably making things worse.

Think of exogenous ketones kind of like alcohol. When they’re consumed, everything is stored and nothing else is burned. So any lipolysis (fat burning) that would be taking place is halted; any glucose and fatty acids in your blood that were circulating are stored; and the ingested ketones are burned until there aren’t any left.

But suggesting individuals already fasting, restricting calories, or cutting carbs will get anything other than a brain buzz is misleading. And to serve up exogenous ketones to an obese, insulin-resistant general population with promises of fat-burning and disease prevention is potentially damaging.

Sure, it might suppress hunger and give a damaged brain a useable fuel source, but what happens when pre-diabetic Pete starts adding ketones to his glucose-rich blood? Or anaerobic Andy continues reloading with the same amount of carbs post-workout even though the liver glycogen he normally burns during his sessions is now suppressed?[18]

Sure, exogenous ketones might provide energy to the muscles or brain cells of someone with Type 2 or Alzheimer’s who can’t use glucose well because of decades of hyperinsulinemia.  But, if someone already has super high glucose and insulin levels, will they worsen the condition by chasing high ketone levels with large doses of insulinogenic exogenous ketones?

If someone is trying to shrink their brain tumour by reducing growth stimulating insulin, will ingesting large amounts of exogenous insulinogenic ketones accelerate growth in the brain tumors?  Recent studies suggest that this may in fact be the case.[19]

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At the current rate, it looks like we will be able to confirm the long term effects of exogenous ketones sooner rather than later.


But by then, the people running the MLMs will have driven off into the sunset and be on to another scheme.

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good news… endogenous ketones for free!

The good news is that all the benefits of endogenous ketosis is freely available risk free!

It’s not easy, but you can get the benefits of ketosis (e.g. autophagy, apoptosis, increased NAD+, mitogenesis etc) by keeping the insulin load of your normal diet down to the point that you can maintain normal blood glucose and insulin levels, then occasionally you can push the time between meals than usual in order to derive some extra benefits (i.e. intermittent fasting).

references

[1] https://www.dropbox.com/s/287bftreipfpf29/jcinvest00459-0078.pdf?dl=0

[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC441933/

[3] http://www.webmd.com/diabetes/type-1-diabetes-guide/ketoacidosis

[4] http://www.webmd.com/diabetes/tc/diabetic-ketoacidosis-dka-topic-overview#1

[5] https://www.dropbox.com/s/hnycwc6b5pw37hr/Inhibition%20of%20Ketogenesis%20by%20Ketone%20Bodies%20in%20Fasting%20Humans.pdf?dl=0

[6] http://ajcn.nutrition.org/content/66/5/1264.abstract

[7] http://ses.library.usyd.edu.au/handle/2123/11945

[8] http://ajcn.nutrition.org/content/90/4/986.short

[9] https://www.ncbi.nlm.nih.gov/pubmed/27475046

[10] https://www.dropbox.com/s/j66y3osyasvq3b3/KETONES%20and%20NICOTINIC%20ACID%20receptor.pdf?dl=0

[11] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1152056/

[12] https://www.ncbi.nlm.nih.gov/pubmed/27869525

[13] http://www.nutraingredients.com/Markets-and-Trends/Ketones-get-rough-ride-at-Tour-de-France

[14] http://journals.lww.com/acsm-msse/Abstract/publishahead/A_Ketone_Ester_Drink_Increases_Postexercise_Muscle.97232.aspx

[15] http://www.nourishbalancethrive.com/blog/2016/10/10/instant-ketosis-04-62mm-30-minutes/

[16] http://www.nourishbalancethrive.com/podcasts/nourish-balance-thrive/high-ketones-and-carbs-same-time-great-performance/

[17] http://www.freemocean.com/2017/02/22/oxygen-and-your-dna/

[18] https://www.t-nation.com/diet-fat-loss/avoid-this-ketogenic-rip-off

[19] https://link.springer.com/article/10.1186/s40170-017-0166-z

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are exogenous ketones right for you?

Endogenous ketosis occurs when we go without food for a significant period of time. Our insulin levels drop and we transition to burning body fat and the ketones in our blood rise.

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Exogenous ketosis occurs when we drink exogenous ketones or consume a ketogenic diet.

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I’ve spent a lot of time lately analysing three thousand ketone vs glucose data points trying to determine the optimal ketone and blood sugar levels for weight loss, diabetes management, athletic performance and longevity.

In this article I share my insights and learnings on the benefits, side effects and risks of endogenous and endogenous ketosis.

ketones vs glucose

The chart below shows three thousand blood glucose vs ketone values taken at the same time from a range of people following a low carbohydrate or ketogenic diet.  As blood glucose levels decrease your the ketones in your blood will increase to keep our energy levels stable.

BHB ketones vs blood glucose

Each person has a unique relationship between their blood glucose and ketone values that gives us a unique insight into a particular person’s metabolic health.   Some people produce more ketones as their blood sugar drops.  Some people have higher blood glucose levels than others.

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what our ketone and glucose values tell us about our metabolic health

Hyperinsulinemia has been termed as the “unifying theory of chronic disease” [1] [2] [3] [4] [5].  It’s useful to understand where you stand on the spectrum of metabolic health and insulin sensitivity.

The chart below shows the typical relationship between blood glucose and ketone for a range of different degrees of insulin resistance / sensitivity.

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If your blood glucose levels are consistently high it’s likely you are not metabolising carbohydrate well.   When you go without food, endogenous ketones are slow to kick in because your insulin levels are high.  You feel tired and hungry and you are likely to eat again sooner and not stop until you feel better.  By contrast, if you are insulin sensitive you may be able to naturally go longer between meals and you will not feel as compelled to eat as much or as often.

If someone is insulin resistant a lower insulin load dietary approach will help with satiety and carb cravings while keeping blood glucose levels and insulin under control.

hyperinsulinemia and metabolic disorders

Exciting research is coming out underway looking at the use of EXOGENOUS ketones as an adjunct treatment for cancer or to provide energy directly to the mitochondria for people with epilepsy, dementia, Alzheimer’s and the like.[6]  [7]  

EXOGENOUS ketones may help to relieve the debilitating symptoms and side effects of acute hyperinsulinemia, Alzheimer’s, dementia, epilepsy or other conditions where glucose is not being metabolised well.

exogenous ketones and the low carb flu

Patrick Arnold, who worked with Dr Dominic D’Agostino to develop the first ketone esters and ketone salts, has noted that exogenous ketones may help alleviate the symptoms of the ‘keto flu’ during the transition from a high carb to a low carb dietary approach.


However, once you have successfully transitioned to a lower carb eating style it may be wise to reduce or eliminate the exogenous ketones to enable your body to fully up-regulate lipolysis (fat burning), maximise ENDOGENOUS ketone production and access your body fat stores.

As discussed in the article, Are ketones insulinogenic and does it matter?, it appears that exogenous ketones require about half as much insulin as carbohydrate to metabolise (i.e. about the same amount as protein).  Hence continual use of exogenous ketones will not allow our insulin levels to reduce as much.

Someone with diabetes who follows with a nutrient dense low insulin load dietary approach may be able to successfully normalise their blood glucose and insulin levels. When this happens, your body will be able to more easily release ENDOGENOUS ketones which will help improve satiety between meals, and decrease appetite which will in turn lead to weight loss.  Exercising to train your body to do more with less is also helpful.

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my experience with exogenous ketones

The light blue “mild insulin resistance” line is based on my ketone and glucose values when I started trying to wrap my head around low carb / keto.

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I enthusiastically started adding generous amounts of fat from all the yummy stuff (cheese, butter, cream, peanut butter, BPC etc) in the hope of achieving higher ketone levels and therefore weight loss, but I just got fatter and more inflamed as you can see in the photo on the left.  My blood tests suggested I was developing fatty liver in my mid 30s!  And I thought I was doing it right with the bacon and BPC?!?!?

The photo on the right is after I worked out how to decrease the insulin load of my diet and learning about intermittent fasting.  I realised that ENDOGENOUS ketosis and weight loss is caused by a lower dietary insulin load, not more EXOGENOUS fat on your plate or in your coffee cup.

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I recently had my HbA1c tested at 4.9%.  It’s getting there.  But knowing what I know now about the importance of glucose control,  I would love to lose a bit more weight and see my HbA1c even lower.

I recently purchased a couple of bottles of KetoCaNa after hearing a number of podcast interviews with Dominic D’Agostino and Patrick Arnold.[8] [9]

Part of the reasons shelling out the money for the exogenous ketones was to see if it would provide a fuel source that didn’t need insulin for my wife Monica who has Type 1 Diabetes.

This metabolic jet fuel is definitely fascinating stuff!  My experience is that it gave me a buzz like a BPC, but also has an acute diuretic effect.

I had hoped it would have a weight loss effect like some people seemed to be saying it would.

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I did find it had an amazing impact on my appetite.  While it was in my system I didn’t care as much about food.  However once the ketones were used up my appetite came flooding back.  It was like I had ‘bonked’ all of a sudden and needed LOTS OF FOOD NOW!

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Unfortunately my hunger and subsequent binge eating seemed to offset the short term appetite suppression that had occurred while the exogenous ketones were in my system.  And it was not going to be financially viable for me to maintain a constant level of artificially elevated ketone levels which return to normal levels after a couple of hours.

do exogenous ketones help with weight loss?

I asked around to see if anyone had come across studies demonstrating long term weight loss effects of exogenous ketones.[11]   It was a VERY enlightening discussion if you want to check it out here.  Wow!

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The Pruvit FAQ says that one of the benefits of Keto//OS is weight loss, however no reference to the research studies was provided to Pruve this claim.

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Also, the studies that were referenced in the Pruvit FAQ all appeared to relate to the benefits of ENDOGENOUS or nutritional ketosis rather than EXOGENOUS ketone supplementation.

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According to a Pruvit tele-seminar the EXOGENOUS ketone salts were not designed to be a weight loss product and hence have not been studied for weight loss after all!

The only studies that we could find that mentioned EXOGENOUS ketone supplementation and weight loss were on rats and they found that there was no long term effect on weight loss.[12]   

So in spite of my hopeful $250 outlay it seems that exogenous ketones ARE just a fuel source after all.

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Even the experts don’t seem to think exogenous ketones help with fat loss.

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Confused?  I don’t blame you.

Metabolically healthy

The “metabolically healthy” line in the chart above is based on RD Dike man’s ketone and glucose data when he recently did a 21 day fast.

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Due to his hard earned metabolic health and improved insulin resistance RD has developed the ability to fairly easily release ketones when goes longer periods between meals.  Going without food is not easy, but it is easier than when his insulin levels were higher which prevented his body from accessing his fat stores.

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RD has achieved a spectacular HbA1c of 4.4%.  Perhaps a two or three day water only fast testing blood glucose and ketones with no exercise would be a useful test of your insulin status?  You could use RD’s glucose : ketone gradient as the gold standard.

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In spite of his improvement in insulin sensitivity and blood glucose control, he still says the “siren” of hunger is incredibility difficult to resist and mastering appetite is more challenging than particle physics.  As a Chief Scientist at Lockheed Martin, he would know.

RD also told me that when he is not fasting and is eating his regular nutrient dense higher protein meals his ketone levels are not particularly high. While RD fairly easily produces ketones when fasting, it seems they are also quickly metabolised so they do not build up in his bloodstream.  I know Luis Villasenor from Ketogains finds the same thing.

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total energy = ketones + glucose

Where this gets even more interesting is when we look at the glucose and ketone data in terms of TOTAL ENERGY.  That is, from both glucose and ketones.

optimal fasting ketone and blood sugar levels in ketosis

The average TOTAL ENERGY of the three thousand data points from these healthy people working hard to achieve nutritional ketosis is 6.1mmol/L. It seems the body works to maintain homeostasis around this level.

When the TOTAL ENERGY in our bloodstream increases outside of the normal range it appears the body raises insulin to store the excess energy.  That is, unless you have untreated type 1 diabetes, in which case you end up in diabetic ketoacidosis with high blood glucose and high ketones due to the lack of insulin available to keep your energy in storage.

Regardless of whether your energy takes the form of glucose, ketones or free fatty acids they all contribute to acetyl-coA which is oxidized to produce energy.  Forcing excess unused energy to build up in the bloodstream is typically not desirable and can lead to long term issues (e.g. glycation, oxidized LDL etc).

I’m not sure if ketones can be converted to glucose or body fat, but it makes sense that excess glucose would be converted to body fat via de novo lipogenesis to decrease the TOTAL ENERGY in the blood stream to normal levels.

A number of studies seem to support this view including Roger Unger’s 1964 paper the Hypoglycemic Action of Ketones.  Evidence for a Stimulatory Feedback of Ketones on the Pancreatic Beta Cells.[14]

Ketone bodies have effects on insulin and glucagon secretions that potentially contribute to the control of the rate of their own formation because of antilipolytic and lipolytic hormones, respectively.  Ketones also have a direct inhibitory effect on lipolysis in adipose tissue.[15]

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Looking at the glucose and ketones together in terms of TOTAL ENERGY was a bit of an ‘ah ha’ moment for me.  It helped me to understand why people like Thomas Seyfried and Dominic D’Agostino always talk about the therapeutic benefits and the insulin lowering effects of a calorie restricted ketogenic diet. [19] [20] [21] [22]

Dealing with high ketones and high glucose is typically not a concern because it doesn’t happen in nature or when eating whole foods.  But now we have refined grains, HFCS, processed fats and exogenous ketones to ‘biohack’ our metabolism and send it into overdrive.

While fat doesn’t normally trigger an insulin response, it seems that excess unused energy, regardless of the source, will trigger an increase in insulin to reduce the TOTAL ENERGY in the blood stream.

I am concerned that if people continue to enthusiastically zealously focus on pursuing higher blood ketones “through whatever means you can[24] in an  effort to amplify fat loss they will promote excess energy in the bloodstream which will lead to insulin resistance and hyperinsulinemia.

Using multi-level marketing tactics to distribute therapeutic supplements to the uneducated masses who are desperate to lose weight with a ‘more is better’ approach also troubles me deeply.

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My heart sank when I saw this video.

MORE investigation required?

There are anecdotal reports that use of exogenous ketones provide mental clarity, enhanced focus and athletic performance benefits.  At the same time there are also people who have been taking these products for a while that don’t appear to be doing so well.

A July 2016 study Ketone Bodies and Exercise Performance: The Next Magic Bullet or Merely Hype? didn’t find that EXOGENOUS ketones to be very exciting.

Recently, ketone body supplements (ketone salts and esters) have emerged and may be used to rapidly increase ketone body availability, without the need to first adapt to a ketogenic diet. However, the extent to which ketone bodies regulate skeletal muscle bioenergetics and substrate metabolism during prolonged endurance-type exercise of varying intensity and duration remains unknown. Therefore, at present there are no data available to suggest that ingestion of ketone bodies during exercise improves athletes’ performance under conditions where evidence-based nutritional strategies are applied appropriately.

However, another study by Veech et al (who is trying to bring his own ketone ester to market) from August 2016 Nutritional Ketosis Alters Fuel Preference and Thereby Endurance Performance in Athletes found in favour of ketones.

Ketosis decreased muscle glycolysis and plasma lactate concentrations, while providing an alternative substrate for oxidative phosphorylation. Ketosis increased intramuscular triacylglycerol oxidation during exercise, even in the presence of normal muscle glycogen, co-ingested carbohydrate and elevated insulin. These findings may hold clues to greater human potential and a better understanding of fuel metabolism in health and disease.

I can understand how exogenous ketones could be beneficial for someone who is metabolically healthy and consuming a disciplined hypo-caloric nutrient dense diet. They would likely be able to auto regulate their appetite to easily offset the energy from the EXOGENOUS ketones with less food intake.

While it seems that EXOGENOUS ketones assist in relieving the symptoms of metabolic disorders I’m yet to be convinced that a someone who is obese and / or has Type 2 Diabetes would do as well in the long term, especially if they were hammering both more fat and exogenous ketones (along with maybe some sneaky processed carbs on the side) in an effort to get their blood ketones as higher in the hope of losing body fat.

Some questions that I couldn’t find addressed in the Pruvit FAQ that I think would be interesting to answer through a controlled study in in the future are:

  1. What is the a safe dose limit of EXOGENOUS ketones for a young child?  How would you adjust their maximum intake based on age and weight?
  2. IF EXOGENOUS ketones do have a long term weight loss effect what is the upper limit of intake of EXOGENOUS ketones to avoid stunting a child’s growth?
  3. Is there a difference in the way EXOGENOUS ketones are processed in someone is metabolically healthy versus someone who is very insulin resistant?
  4. Does the affect on appetite continue beyond the point that the ketones are out of your system?
  5. Do you need to take EXOGENOUS ketones continuously to maintain appetite suppression?  Does the effect of ENDOGENOUS wear off as your own ENDOGENOUS ketone production down regulates?  Do you need to keep taking more and more EXOGENOUS ketones to maintain healthy appetite control?
  6. How should someone with Type 2 Diabetes adjust their medication and insulin dose based on their dose of EXOGENOUS ketones?  Should they be under medical supervision during this period?
  7. Is there a difference in health outcome if you are taking EXOGENOUS ketones in the context of a hypo-caloric ketogenic diet versus a hyper-caloric ketogenic diet?  What about a diet high in processed carbs?
  8. Is there a minimum effective dose to achieve optimal long term benefits to your metabolic health or is MORE better?
  9. Are the long term health benefits of EXOGENOUS ketones equivalent to a calorie restricted ketogenic diet?

Unfortunately, I think we will find the answers to these questions sooner rather than later with the large scale experiment that now seems to be well underway.

Perhaps the burden of proof is actually on Pruvit to prove it rather getting their Pruvers to demonstrate that within 59 minutes they are successfully peeing out the product they’ve just paid some serious money for!

The lower the better?

Alessandro Ferretti recently made the observation that metabolically healthy people tend to have lower TOTAL ENERGY levels at rest (and hence have a lower HbA1c), but are able to quickly mobilise glycogen and fat easily when required (e.g. when fasting or a sprint).

Metabolically healthy people are both metabolically flexible[25] and metabolically efficient.[26]   These people would have been able to both conserve energy during a famine and run away from a tiger and live to become our ancestors, while the ones who couldn’t didn’t.

image29

Similar to RD Dikeman, John Halloran is an interesting case.  Recently he has been putting a lot of effort into eating nutrient dense foods, intermittent fasting and high intensity exercise.

image13

He is also committed to improving his metabolic fitness to be more competitive in ice hockey.  His resting heart rate is now a spectacular 45 bpm!

image08

And he’s been able to lose 10kg (22lb) during July 2016!

image12

At 5.2mmol/L (i.e. glucose of 4.0mmol/L plus ketones of 1.2mmol/L) John’s TOTAL ENERGY is well below the average of the 26 people shown in the glucose + ketone chart above.  It seems excellent metabolic health is actually characterised by lower TOTAL ENERGY.

MORE is not necessarily BETTER when it comes to health.

fast well, feed well

To clean up the data a little I removed the ketones vs glucose data points for a couple of people who I thought might be suffering from pancreatic beta cell burnout and one person that was taking exogenous ketones during their fast that had a higher TOTAL ENERGY.  I also removed the top 30% of points that I thought were likely high due to measuring after high fat meals.

So now the chart below represents the glucose and ketone values for a group of reasonably metabolically healthy people following a strict ketogenic dietary approach, excluding for the effect of high fat meals, BPC, fat bombs and the like.

image22

The average ketone value for this group of healthy people trying to live a ketogenic lifestyle is 0.7mmol/L. Their average glucose is 4.8mmol/L (or 87mg/dL). The average TOTAL ENERGY is 5.5mmol/L or 99mg/dL.

ketones (mmol/L)

blood glucose (mmol/L)

total energy (mmol/L)

average

0.7

4.8

5.5

30th percentile

0.4

4.6

5.2

70th percentile

0.9

5.1

5.8

The table below shows this in US units (mg/dL).

ketones
(mmol/L)

blood
glucose (mg/dL)

total
energy (mg/dL)

average

0.7

86

99

30th percentile

0.4

83

94

70th percentile

0.9

92

104

It seems we may not necessarily see really high ketone levels in our blood even if we follow a strict ketogenic diet, particularly if we are metabolically healthy and our body is using to ketones efficiently.

the real magic of ketones

When we deplete glucose we train our body to produce ketones.

This is where autophagy, increased NAD+ and SIRT1 kicks in to trigger mitochondrial biogenesis and ENDOGENOUS ketone production (i.e. the free ones).[27]   The REAL magic of ketosis happens when all these things happen and ketones are release as a byproduct.

I do not believe that simply adding EXOGENOUS ketones will have nearly as much benefit to your mitochondria, metabolism and insulin resistance as training your body to produce ENDOGENOUS ketones in a low energy state.

Everything improves when we train our bodies to do more with less (e.g. fasting, high intensity exercise, or even better fasted HIIT).  Resistance to insulin will improve as your insulin receptors are no longer flooded with insulin caused by high TOTAL ENERGY building up in your bloodstream (i.e. from glucose, ketones and even free fatty acids).

image01

Driving up ketones artificially through EXOGENOUS inputs (treating the symptom) does NOT lead to increased metabolic health or  mitochondrial biogenesis (cure) particularly if you are driving them higher than normal levels and not using them up with activity.

You may be able to artificially mimic the buzz that you would get when the body produces ketones ENDOGENOUSLY, however it seems you may just be driving insulin resistance and hyperinsulinemia if you follow a “MORE is better” approach.

Simply managing symptoms with patented products for profit without addressing the underlying cause often doesn’t end well.

Just like having low blood glucose is not necessarily good if it is primarily caused by high levels of EXOGENOUS insulin coupled with a poor diet or having lower cholesterol due to statins, having high blood ketone values is not necessarily a good thing if it is achieved it by driving up the TOTAL ENERGY in your blood stream with high levels of purified fat and / and EXOGENOUS ketones.

nutrient density

When we feed our body with quality nutrients we maximise ATP production which will make us feel energised and satisfied.  Nutrient dense foods will nourish our mitochondria and reduce our drive to keep on seeking out nutrients from more food.  Greater metabolic efficiency will lead to higher satiety, which leads to less food intake, which leads to a lower TOTAL ENERGY, greater mitochondrial biogenesis, improved insulin sensitivity and lower blood glucose levels.

Prioritising nutrient dense real food is even more important in a ketogenic context.[28]  While we can always take supplements, separating nutrients from our energy source is never a great idea, whether it be soda, processed grains, sugar, glucose gels, HFCS, protein powders, processed oils or exogenous ketones.

Based on my analysis of nutrient density I don’t think you should be trying to avoid protein and carbohydrates in the pursuit of higher ketone levels unless you have a legitimate medical reason for pursuing therapeutic ketosis (e.g. cancer, Alzheimer’s, epilepsy, dementia etc).

image09

I believe the best approach is to maximise nutrient density as much as possible while working within the limits of your metabolic health and your pancreas’ ability to maintain normal blood glucose levels.

image14

the best exogenous ketone supplement

If your goal is metabolic health, weight loss and improving your ability to produce ENDOGENOUS ketones, then developing a practice of FEASTING and FASTING is important.

To start out, experiment by extending your fasting periods until your TOTAL ENERGY is decreasing over time.  This will cause your circulating insulin levels to decrease which will force your body to produce ENDOGENOUS ketones from your ENDOGENOUS fat stores.

best exogenous ketone supplement

Check out the how to use your glucose meter as a fuel gauge article or how to use your bathroom scale as a fuel gauge for some more ideas on how to get started with fasting.

If you really want to measure something, see how low you can get your glucose levels before your next meal.  Then when you do eat, make sure you choose the most nutrient dense foods you possibly can to build your metabolic machinery and give your mitochondria the best chance of supporting a vibrant, active and happy life.

As my wise friend Raymund Edwards keeps reminding me, FAST WELL, FEED WELL.

 

epilogue

Like most people dabbling in this low carb thing, I’m still on a journey.

I’d love to be able to share shirtless photos like Ted and Dom but I’m still working to overcome my own genetic propensity for diabetes, obesity, Alzheimer’s and Parkinson’s. I’m still learning and working out how to apply these things in my own life.

Although I do sometimes check blood glucose levels before meals to see how I’m tracking I haven’t been testing ketones much for a year or so after I realised chasing high ketones with more dietary fat wasn’t helping me lose weight.

However after writing this article, I was intrigued to see how my ketones were travelling.

This was mid-morning after a kettlebell session.

I was able to get my heart rate up to 190 bpm which is my highest ever!

My aim is to train my mitochondria to pump out more power with less inputs (i.e. fasted) to improve insulin sensitivity as well as mitochondrial efficiency and drive  mitochondrial biogenesis.

You can get a lot of work done in an intense 25 to 30-minute session with these weapons of torture that I keep downstairs in my garage.  I don’t think it really matters what you do as long as you push your body to do more with less).

My appetite today was great so I didn’t feel the need to eat until I had dinner with my family.

Previously I would have not been happy with these ketone readings and would have wanted to drive my ketones higher to get into the ‘optimal ketone zone’.  I would have wondered “Maybe I should have eaten some MORE butter or had a BPC to drive ketones higher to facilitate fat loss?”

But given I’d still like to lose some more body fat I’m pretty happy with these numbers.

  • My total energy is low (4.5mmol/L and 5.1mmol/L).  Check.
  • Ketones are present but not too high which means I’m able to mobilise fat but not building it up in my bloodstream.  Check.
  • Blood glucose is low.  Check.

All good!  Feeling crisp, happy and vibrant thanks to ENDOGENOUS ketones!

(Sorry.   I can’t sell you mine.  You’ll have to make your own.)

references

[1] http://www.thefatemperor.com/blog/2015/5/6/the-incredible-dr-joseph-kraft-his-work-on-type-2-diabetes-insulin-reigns-disease

[2] http://www.thefatemperor.com/blog/2015/5/10/lchf-the-genius-of-dr-joseph-r-kraft-exposing-the-true-extent-of-diabetes

[3] https://profgrant.com/2013/08/16/joseph-kraft-why-hyperinsulinemia-matters/

[4] https://www.amazon.com/Diabetes-Epidemic-You-Joseph-Kraft/dp/1425168094

[5] https://www.youtube.com/watch?v=193BP6aORwY

[6] http://fourhourworkweek.com/2016/07/06/dom-dagostino-part-2/

[7] http://www.thelivinlowcarbshow.com/shownotes/10568/848-dr-dominic-dagostino-keto-clarity-expert-interview/

[8] http://superhumanradio.com/579-shr-exclusive-patrick-arnold-back-in-the-supplement-business.html

[9] http://superhumanradio.com/shr-1330-best-practices-for-using-ketone-salts-for-dieting-performance-and-therapeutic-purposes.html

[10] http://docmuscles.shopketo.com/

[11] https://www.facebook.com/groups/optimisingnutrition/permalink/1574631349504574/

[12] https://nutritionandmetabolism.biomedcentral.com/articles/10.1186/s12986-016-0069-y

[13] https://www.facebook.com/groups/optimisingnutrition/permalink/1574631349504574/

[14] https://www.dropbox.com/s/287bftreipfpf29/jcinvest00459-0078.pdf?dl=0

[15] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2129159/

[16] https://www.facebook.com/BurnFatNotSugar/

[17] http://www.dietdoctor.com/obesity-caused-much-insulin

[18] http://www.lowcarbcruiseinfo.com/2016/2016-presentations/Hyperinsulinemia.pptx

[19] http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0115147

[20] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1819381/

[21] http://healthimpactnews.com/2013/ketogenic-diet-in-combination-with-calorie-restriction-and-hyperbaric-treatment-offer-new-hope-in-quest-for-non-toxic-cancer-treatment/

[22] https://www.google.com.au/url?sa=t&rct=j&q=&esrc=s&source=web&cd=1&cad=rja&uact=8&ved=0ahUKEwjK8Jvku7DOAhUJspQKHS5-DkwQFggbMAA&url=http%3A%2F%2Fwww.rsg1foundation.com%2Fdocs%2Fpatient-resources%2FThe%2520Restricted%2520Ketogenic%2520Diet%2520An%2520Alternative.pdf&usg=AFQjCNFuTA7xmWX1pFr6wBTV_hsS7C5j_w&sig2=pcBN_f_kCLSgFKYUy–uug&bvm=bv.129391328,d.dGo

[23] https://www.facebook.com/DocMuscles/videos/10210426555960535/?comment_id=10210431467003308&comment_tracking=%7B%22tn%22%3A%22R9%22%7D&pnref=story&hc_location=ufi

[24] https://www.facebook.com/DocMuscles/videos/10210426555960535/?comment_id=10210431467003308&comment_tracking=%7B%22tn%22%3A%22R4%22%7D&hc_location=ufi

[25] http://guruperformance.com/episode-3-metabolic-flexibility-with-mike-t-nelson-phd/

[26] http://guruperformance.com/tag/metabolic-efficiency/

[27] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2852209/

[28] http://ketotalk.com/2016/06/23-responding-to-the-paleo-mom-dr-sarah-ballantynes-claims-against-the-ketogenic-diet/

post last updated: May 2017

Jimmy Moore’s keto eggs

During his yearlong n=1 ketosis experiment Jimmy Moore in 2012 didn’t give too much away about exactly what he was eating.

What was he doing to keep his blood glucose consistently low and ketones high?  Could this help me lose some weight or perhaps my type 1 diabetic wife normalise her blood glucose levels

Jimmy did  publish a list of healthy high fat foods (i.e. avocados, butter, whole eggs, coconut oil, bacon, sour cream, 70% ground beef, full fat cheddar cheese and coconut) on the Carb Smart blog but he didn’t give away much more detail.

I suppose it’s part of what drove me to dig into the food insulin index to create a ranking of all foods.

One meal he did blog as one of his favourites was his “keto eggs” which he included in Keto Clarity and on his blog here.  He says it helps him “rock the ketones”.  This was often his meal for the day with intermittent fasting.  The recipe is shown below:

  • 4-5 pastured eggs
  • 2-3 oz grass-fed butter and/or coconut oil
  • sea salt
  • parsley (or your favorite spice)
  • 2 oz full-fat cheese (optional)
  • 2 Tbs Sweet Chili Sauce
  • 3 Tbs sour cream
  • 1 whole avocado

The nutritional analysis for the recipe below shows that it’s certainly ketogenic with 83% fat, 13% protein and 4% carbs.  This keto egg recipe provides a solid protein score though the vitamins and minerals aren’t as high as some of the other meals.  However if your primary aim is therapeutic ketosis then this meal will likely be great for you.

2016-07-18 (2)

The ranking for the keto eggs recipe, compared to the 241 other meals that have been analysed so far,  for each of the approaches is:

  • therapeutic ketosis – 18 / 242
  • diabetes – 54 / 242
  • weight loss – 175 / 242
  • nutrient dense (maintenance)  – 159 / 242

net carbs

insulin load carb insulin fat protein

fibre

6g 31g 21% 83% 13%

3g

REVERSION Y REMISION DE LA DIABETES TIPO 2 CASO DE ANTONIO C. MARTINEZ II

¿Puede el ayuno intermitente optimizar los niveles de glucosa en la sangre y reducir la necesidad de medicamentos para la diabetes? Antonio Martínez estaba ansioso por descubrirlo, por lo que se propuso realizar un experimento con él mismo.

[for the English version of this post click here]

El Dr. Antonio C. Martinez II., es un Abogado reconocido de nivel distinguido por Martindale Hubbard, y de la Red Legal de los Mejores Abogados (Top Lawyers) en Nueva York y un hombre de negocios que trabajó para el ya fenecido Dr. Robert C. Atkins MD en relaciones gubernamentales y apareció en su programa de radio en los años 90. Fue uno de los principales cabilderos que logró la aprobación de la Ley de Educación y Salud de los Suplementos Dietéticos de 1994 (DSHEA). Ha participado activamente en cuestiones de salud en las leyes y políticas a lo largo de su carrera. En los años 90 Antonio adoptó un enfoque bajo en carbohidratos para bajar de peso durante un tiempo, pero luego retomó una dieta moderada en carbohidratos. No fue hasta que Antonio comenzó a tener sus propios problemas de salud, como la diabetes tipo 2 y un ataque cardíaco, que se dio cuenta que necesitaba intensificar sus esfuerzos para elevar la calidad de su nivel de vida con respecto a su salud.

image07

DIAGNOSTICO: DIABETES TIPO 2

Antonio tiene antecedentes familiares de diabetes tipo 2, ya que ambos padres sufren de la enfermedad, así que es diagnosticado con diabetes tipo 2 en 2002, por lo que los médicos le indicaron inicialmente empezar a tomar Metformina y a partir del 2008 utilizar Janumet. Con la ayuda de éstos Antonio mantenía un HbA1c (HbA1c se refiere a la hemoglobina glucosilada ( A1c ), que identifica la concentración promedio de glucosa en plasma)  en los 6s y fue elogiado por sus médicos por su gran control de la glucosa en sangre, sin embargo, a pesar de que los mantuvo por debajo de los recomendados por la Asociación Americana de Diabetes (un máximo de HbA1c del 7%) ,  Antonio en realidad estaba en el rango de alto riesgo para la enfermedad cardiovascular, como se muestra en la siguiente tabla. Durante este tiempo él siempre fue informado por sus médicos de que su A1c estaba entre 6 y 7 se encontraba dentro de las directrices médicas.

image05

Si bien los medicamentos antidiabéticos ayudan a disminuir los niveles de glucosa en la sangre (es decir, el de los síntomas) estos datos que se muestran a continuación muestran que los medicamentos no reducen necesariamente el riesgo de enfermedades o permiten que la grasa de sus órganos puedan ser lanzados para restaurar la sensibilidad a la insulina (es decir, la solución).

image09

Como se muestra en la tabla a continuación, la insulina es una hormona anabólica que permite que el cuerpo construya reservas de energía en el cuerpo. Sin embargo, si su problema es la hiperinsulina, la diabetes tipo 2 o hígado graso, entonces su objetivo debe ser reducir el nivel de glucosa en la sangre y los niveles de insulina para permitir que la grasa almacenada se metabolice a energía. Parece que simplemente tomando medicamentos para reducir el alto nivel de glucosa en la sangre sin cambios en la dieta va a conducir la energía de nuevo en el almacenamiento en forma de grasa, incluso dentro el corazón, el hígado y el páncreas.

El siguiente diagrama del Dr. Ted Naiman ayuda a explicar cómo la resistencia a la insulina, los niveles altos de insulina (hiperinsulina) y azúcar en la sangre (hiperglucemia) están interelacionados y ambas cosas son malas noticias.

image04

ATAQUE CARDIACO

image03

Lamentablemente el 28 de marzo de 2014 Antonio sufrió un ataque al corazón, razón por la cual le colocaron un stent en una arteria. A su ingreso en el hospital pesaba 158 libras y tenía una HbA1c del 7%. Después de su ataque cardíaco, Antonio se le indicó tomar aspirina, medicamentos para la presión arterial, una estatina, un anticoagulante y un bloqueador beta. En poco tiempo comenzó a sentir los efectos secundarios de las medicaciones múltiples. Frustrado, volvió a leer una serie de materiales de salud y medicina y dijo a sus médicos que no estaría tomando medicamentos para el resto de su vida. También vio el documental “Cereal Killers – Asesinos del Cereales”, que fue como una luz en su camino para seguir dando los pasos necesarios en los cambios de sus hábitos para su restablecimiento.

Ver este video a continuación:

https://www.youtube.com/watch?v=dON-fPp5Hy0

DIETA BAJA EN CARBOHIDRATOS

En julio de 2014 Antonio dijo a su médico de cabecera y a su cardiólogo que iba hacer una dieta baja en carbohidratos y rica en grasas. Mientras que sus médicos no le aconsejaron nada en contra de ella, eran escépticos y le advirtieron que tendría que hacerse un análisis hecho con frecuencia para controlar el impacto de la dieta. A continuación, para septiembre de 2014 Antonio recibió una llamada de su médico quien le dijo: “¡felicidades, lo que sea que está haciendo, sígalo haciendo, tiene usted un HbA1c normal!, por lo que le recomendaron dejar de tomar el medicamento Janumet y como forma de control que siguiera tomando el Metformin”. Como se muestra a continuación, el HbA1c de Antonio había bajado del 6,6% al 4,9% con el enfoque de la dieta baja en carbohidratos, también había rebajado trece libras, por lo que se encontraba ahora con 145 libras, mientras que su presión arterial se había normalizado, su HDL aumentó en 20 puntos y sus triglicéridos habían disminuido por debajo de 100 mg / dl.

image00

ELIMINANDO EL FENOMENO DEL ALBA EN LA DIABETES TIPO II

A pesar de comer sólo dos comidas bajas en carbohidratos por día, Antonio observó que a finales del 2015 sus niveles de azúcar en sangre comenzaban a dispararse hacia arriba en horas de la mañana.

El fenómeno del amanecer es el proceso en el que el cuerpo segrega una serie de hormonas y la glucosa en el torrente sanguíneo, en preparación para el día, sin embargo, si usted es resistente a la insulina entonces la respuesta de la insulina puede no ser adecuada para mantener los niveles normales de glucosa en la sangre, por lo que Antonio después de haber sufrido un ataque al corazón se tomó esto en serio y estaba dispuesto a hacer lo que fuese necesario para revertir esta situación, así que para poner en marcha el nuevo año, Antonio adoptó un régimen regular de ayuno intermitente que involucró a ir a la cama sin cenar el domingo por la noche y luego no comer hasta el martes por la noche, ofreciéndole esto una ventana de ayuno de 44 a 48 horas cada semana. La siguiente tabla muestra los números de glucosa en la sangre de Antonio hasta diciembre antes del protocolo de ayuno y luego a través de enero y febrero con el protocolo de ayuno en su lugar.

image06

La vida real de los números de la glucosa en la sangre siempre van a rebotar, sin embargo, se puede ver que los valores promedio de glucosa en sangre de Antonio han mejorado mucho. Sus números de glucosa en sangre por la mañana se muestran a continuación. “Estoy consiguiendo los mejores números que he tenido y sin fenómeno del amanecer”, dice Antonio.

image11

Mientras que los ayunos más largos están trabajando bien para Antonio, también puede utilizar períodos de ayuno más cortos regulares para mantener su glucosa en la sangre hacia abajo. Echa un vistazo a la sección: usando el medidor de glucosa en su artículo como un indicador de combustible para que obtengan algunas ideas sobre cómo puede asegurarse de que su glucosa en sangre promedio sea una tendencia en la dirección correcta.

Una forma de ver los niveles de glucosa en la sangre y el fenómeno del amanecer es la manera del cuerpo de liberar el exceso de energía almacenada en el torrente sanguíneo para ser utilizado. Si usted es resistente a la insulina del cuerpo va a utilizar un proceso llamado gluconeogénesis para convertir el exceso de proteínas, grasas e incluso hasta cierto punto, en glucosa. Una vez que el exceso de grasa de las personas disminuye, la frecuencia será más sensible a la insulina y el cuerpo detendrá el bombeo de este exceso de glucosa en el torrente sanguíneo.

HBA1C

Comenzando con una HbA1c de 5,1% se notaba que Antonio ya había realizado buenas modificaciones con los cambios en su dieta debido a su baja ingesta en carbohidratos bajo un enfoque disciplinado. Sin embargo, la adición del protocolo de ayuno le ayudó a fundar sobre una buena base y a hacer posible que sus niveles de glucosa en la sangre disminuyeran aún más que los niveles óptimos y en base a esto sus valores de glucosa en sangre ahora tienen un HbA1c de alrededor del 4,6%.

image02

CETONAS

Las cetonas de Antonio son estables, pero en realidad con tendencia a la baja después de la introducción del régimen de ayuno. El hecho de que Antonio tiene valores más bajos de cetonas no es realmente una preocupación dado que él está probablemente utilizando sus cetonas de manera más eficaz de la energía en lugar de dejar que se acumulen en la sangre como podría ser el caso con una dieta alta en grasa y sin ayuno.

image01

Creo que muchas personas se meten en problemas persiguiendo a altos valores de cetona, añadiendo más grasa dietética sin mejorar su metabolismo y la sensibilidad a la insulina, hasta el punto en que realmente puede utilizar las cetonas. El ayuno da fuerzas al cuerpo para aprender a usar cetonas como combustible.

GLUCOSA: INDICE DE CETONA

La relación entre la glucosa y las cetonas (GKI) pueden ser una medida más útil cuando los niveles de glucosa en la sangre se están reduciendo. Un GKI reductor es una indicación de que los niveles de insulina están disminuyendo y su salud metabólica está mejorando. Podemos ver en el gráfico a continuación la glucosa de Antonio: relación de cetona (GKI) que mejora cada vez que ayuna y que está en una baja tendencia con el tiempo. Estos valores bajos GKI indican que él está logrando una excelente salud metabólica.

Thomas Seyfried GKI es una herramienta útil para el seguimiento de su salud metabólica una vez que sus valores de glucosa en sangre están acercando a los niveles óptimos. Seyfried apunta a sus pacientes de cáncer para tienen una GKI de 1,0, aunque un GKI debajo de 10 se considera que es un estado de insulina bastante bajo y que en menos de tres es excelente para la salud metabólica de alguien que no esté persiguiendo una cetosis terapéutica.

¿NO HAY VUELTA A ATRÁS?

Antonio sigue disfrutando de los ayunos semanales durante el cual se centra en beber grandes cantidades de té, café y un poco de caldo de hueso, ingiere también varios suplementos dietéticos y una aspirina diaria. Su peso ahora se ha reducido a 141 libras y ha vuelto a usar la misma talla de ropa que solía llevar durante estuvo en la universidad.

Cuando sus amigos le preguntan cómo ha logrado revertir su diabetes tipo 2 y cómo ha logrado perder peso, él responde: “lo he logrado al comer una dieta baja en carbohidratos y rica en grasas en base a comer comida de verdad. Yo trabajo para mantener la mayor cantidad de mis alimentos en el rango del 70% de grasa, 20% por ciento de proteínas y un10% de carbohidratos como mis objetivos ideales. Yo miro mi ingesta de proteínas, porque el exceso convertirá a través de la gluconeogénesis. “Yo me propongo mantener este enfoque para el resto de mi vida, pues amo los resultados que esta dieta ha proporcionado a mi nuevo estilo de vida! ”

Antonio dice: Otra manera de mirar la resistencia a la insulina es su cuerpo, ya que éste le dice que usted está comiendo en exceso, ya sean demasiadas cosas inadecuadas o simplemente comer demasiado a menudo. Nuestros antepasados ​​eran cazadores recolectores cuyos hábitos de alimentación eran más como escasez y abundancia, no de tres comidas con bocadillos. Conozca y respete la insulina, ya que ésta le dirá cómo puedo hacerlo y si no atiende a sus señales le podrá causar estragos en su salud metabólica.

También puede pensar en su medidor de glucosa en sangre como indicador de combustible. Si sus niveles de glucosa en la sangre son altos, entonces podría ser el momento de dejar de llenar el depósito de combustible por un tiempo. El ayuno intermitente es como ir a un gimnasio metabólico y de trabajo. El cuerpo obtiene la oportunidad de reparar, recuperar y regenerarse si se utiliza de forma inteligente lo que hará la diferencia para su salud y para los sensibilizadores a la insulina.

Estoy decepcionado en el establecimiento médico, ya que deben saber mejor que yo lo que hay que hacer y no lo hacen. ¿Por qué no es la educación en nutrición clínica y terapéutica obligatoria en la escuela de medicina y no es enseñado con el mismo énfasis que la farmacología?

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Con el ex líder de la mayoría del Senado EE.UU, Tom Daschle (SD) en Washington DC, febrero  2016.

¿CURADO?

¿Antonio está curado de su diabetes tipo 2? La respuesta depende de su definición de “curado”.

¿Antonio va a ser capaz de comer comida chatarra y alimentos procesados ​​cinco veces al día? Probablemente, no, sin embargo, si Antonio mantiene este protocolo en ayunas junto con su enfoque bajo en carbohidratos entonces él podría ser capaz de mantener los niveles óptimos de glucosa en sangre sin temor a otro ataque al corazón. Si ese es su definición de “curado”, la respuesta podría ser sí.

Felicidades Antonio y mantener el gran trabajo!

Referencias:

[1] http://www.thelivinlowcarbshow.com/shownotes/12960/997-attorney-Antonio-martinez-pushing-lchf-through-public-policy-and-the-law/

[2] http://www.cardiab.com/content/12/1/164

[3] http://www.fitnessunderoath.com/the-44-hour-diet/

[4] https://optimisingnutrition.com/2015/07/20/the-glucose-ketone-relationship/

Contacto:

Si usted está atravesando por una experiencia similar a la de Antonio, a él le encanta oír de usted a través de su correo email acmartinezlaw@gmail.com o su página web en www.acmartinez2.com

Agradecimientos:  A la Ing. Julia Angelica Mariñez por la traducción del ingles al español.

 

Fine tuning your diet to suit your goals – Darth Luiggi

It looks like Luis Villasenor is doing something right.

Luis (aka Darth Luiggi who runs the Ketogains Facebook Group) has been on a ketogenic diet for more than 14 years!

Here are a couple of video interviews where Luis explains his approach.

He is also very active in coaching the more than 7000 Ketogains members on his Facebook group and Reddit.

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Recently I was able to get a look at a few days of Luis’s food diary on My Fitness Pal so I thought it would be interesting to run some numbers on his diet.

My focus of the blog has been on optimising diet for diabetes management, however I wanted to also demonstrate that a nutritious low insulin load diet is also great for health and fitness.

The analysis below shows the combination of three meals.  Along with plenty of protein (beef, chicken, egg, pork) he also has a solid amount of vegetables (broccoli, lettuce and spinach) as well as a good amount of added fats (butter, olive oil and coconut oil) to maintain ketosis.

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The nutritional analysis of these three meals is shown below.  As you would expect from the dude who runs Ketogains, the carbs are low at 5% with the protein being fairly substantial at 29% of daily calories.

The protein score is excellent with 145% of the RDI being met with 1000 calories and 58% of the RDI for vitamins and minerals being met with 1000 calories.

A score of 100 means that you will meet the recommended daily intake (RDI) for all the nutrients with 1000 calories, as discussed in the previous ‘the most nutrient dense food for different goals’ article.

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The table below shows how Luis’s diet stacks up based on the nutritional ketosis weighting.

At 26g of fibre per day his fibre score is solid but not high compared to the other meals analysed.  His calorie density is high but that isn’t a big issue given that he is already fairly lean.

The insulin score is not extremely high as there is a solid amount of protein and he’s not worried about diabetes or achieving therapeutic ketosis.

The vitamin and mineral score is the one area that could be improved, though it is better than average.

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As you will hear on the videos, Luis is already a big advocate for leafy greens as an integral part of a ketogenic diet.

If we did want to improve the vitamin and mineral score we could simply add extra spinach and broccoli (or any of the nutrient dense veggies from this list).

I’ve dropped the lettuce (which is not as nutrient dense) and increased the broccoli and spinach so we have 400g of each across the three meals.

The resultant nutritional analysis for the revised food diary is shown below.  The nutrient balance score has increased from 58 to 70 and we’d only have 8g of net carbohydrates per meal in spite of the significant increase in vitamins and minerals.

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With the increase in non-starchy veggies we increase the fibre intake from 26g to 40g across the three meals which would mean that he would now meet the recommended daily fibre intake of 30g per day for men.

The other advantage of this approach is that it would be more filling which may lead to a decreased overall calorie intake.  While Luis knows the power of a ketogenic diet for weight loss he also knows that to get such a low percentage body fat you also need to run in a calorie deficit and this approach may assist in naturally controlling appetite and satiety.

He is currently in a ‘cutting phase’ which is why he is tracking his food intake in My Fitness Pal, so reducing his calorie density and increasing fibre might help him to spontaneously achieve a reduction in overall energy intake.

If you’re interested in using the ketogenic diet as part of a bodybuilding routine I would definitely recommend checking out Ketogains.  Even though he looks tough with all those muscles he’s really polite, gracious and only too willing to help other people on the journey.  And regardless of your goals, Luis’s Ketogains calculator is an excellent tool if you want to calculate your macros or target grams of protein, fat and carbs.

fine tuning your diet to suit your goals – Chris Kelly

I’m a big fan of Chris Kelly’s Nourish Balance Thrive podcast[1]

It’s sort of like listening to Jimmy Moore, Dave Asprey and Ben Greenfield all rolled into one, but even nerdier and more intellectually challenging.

I first heard the term “glucogenic protein” on one of Chris’s podcasts [2] and went searching  to learn more and the epic Insulin Index V2 article was the result.

I also have really enjoyed Chris’ discussion about heart rate variability (HRV), gut health and a range of other intriguing subjects. [3]

Chris is a software engineer who used to work for a hedge fund and has now chosen to go into full time nutritional therapy counselling with a bit of pro-mountain biking on the side!  He’s also into kettlebells.

He has basically mastered all my passions and hobbies and taken them to the elite level!  I’m not that jealous, really.

Chris is another endurance athlete who found he had pre-diabetic blood sugars (like Tim Noakes, Ben Greenfield and Sami Inkenen), and has turned to the ketogenic diet to normalise his blood sugars.

image001

Chris’s diet

Chris posted his daily food dairy outputs from cron-o-metre [4] on Facebook recently and gave me permission to run the numbers on it to see what we could learn.

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Using cron-o-metre is superior to MyFitnessPal because it tracks your micronutrients in addition to calories and macronutrients.

As shown in nutritional analysis below, Chris’s nutrient dense diet has achieved the RDI for all of the key micronutrients.   His protein intake is solid but not high at about 1.5g/kg LBM.

Chris uses MCT oil to fuel his cycling with some slow release Superstarch to top off his glycogen stores for races without throwing him out of ketosis.

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The plot of Chris’s macronutrients from his daily food diary shows that his diet is certainly ketogenic.  When he occasionally measures his blood ketones they’re pretty high at around 2.1mmol/L. [5]

At the same time he gets a really solid 46g of fibre per day (compared to the RDI of 30g for men), with a low 5% net carbs and a very low 16% insulinogenic calories.  One of the issues I see for a lot of people trying to reduce their carbohydrates is that they struggle to get enough fibre for digestion and good gut health.

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nutritional analysis

But can a diet that is so highly ketogenic also provide adequate nutrition?   I ran his daily food diary though nutrientdata.self.com and the results are solid.

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The nutritional content would depend heavily on the source of his beef ground  beef  which makes up most of his protein on the day I have analysed.  I know Chris also goes out of his way to eat organ meats, and the locally sourced grain feed beef that he gets would likely have a higher protein quality score than the ground beef profile in the USDA database.

It should also be noted that the data from his daily food diary entered into nutritiondata.self.com hasn’t captured everything given, because it didn’t seem to have yerba mate tea, kim chi and bone broth which would have a bunch more nutrients.

increasing the protein score

The table below shows how Chris’s food diary stacks up against the 200 or so other meals and daily diaries that I have analysed.  I have used the diabetic / nutritional ketosis weighting in the ranking which prioritises a low insulin load with solid vitamins, minerals and protein.

image011

The only area where the “base” food diary is lacking compared to the other meals is the protein score.  The score of 0.01 for protein means that it is about average for the 200 meals analysed.

The calorie density score is low, however this is not a problem given that Chris is already quite lean (as you can see from the photo above).

Chris uses MCT oil to fuel his cycling, and weight loss is not a goal.  Trying to get him to reduce the calorie density of his diet with more broccoli and mushrooms would mean that he just couldn’t physically get in enough fuel!

You can see from the comparison of the nutrients and amino acids from various protein sources below that muscle meat is not necessarily the most nutrient dense source of protein.

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If we replace the ground beef with sardines which have a higher quality of amino acids we get the updated nutritional profile shown below.  Both the protein score and the vitamin score has increased with the sardines.

image015

So overall, Chris’s diet is currently well suited to his goals; however, refining the quality of the protein source could further improve the vitamin and mineral content of his diet.

Overall, I think Chris’s diet is a great example of how someone can get great nutrition and high amounts of fibre while still achieving ketosis.

references

[1] http://www.nourishbalancethrive.com/podcasts

[2] http://www.nourishbalancethrive.com/blog/2014/12/29/protein-transcription/

[3] http://www.nourishbalancethrive.com/blog/2014/12/16/how-track-hrv-measure-progress/

[4] https://cronometer.com/

[5] https://www.facebook.com/groups/optimisingnutrition/permalink/1462501844050859/

optimal ketone and blood sugar levels for ketosis

  • A low carb helps reduce blood sugars and insulin levels and help with many common metabolic diseases (e.g. diabetes, heart disease, stroke, cancer, Parkinson’s and Alzheimer’s).
  • We become insulin resistant when our adipose tissue becomes full and can’t store any more energy.  Excess energy is then stored in the liver, pancreas, heart, brain and other organs that are more insulin sensitive.
  • Endogenous ketosis occurs when we don’t eat and we burn our own body fat (e.g. fasting).  While insulin and blood sugar levels are low we may have lower blood ketones flowing from our fat stores.
  • Exogenous ketosis occurs when we eat lots of fat (e.g. butter, MCT oil) or take exogenous ketones.   Our blood ketones may be higher, but our insulin levels will rise to remove excess energy from the blood.
  • Most of the good things associated with ketosis occur due to endogenous ketosis.
  • Most people following a ketogenic diet have lower blood ketone values than Phinney’s ‘optimal ketosis’ chart, especially once they become fat adapted.
  • If your goal is blood sugar control, longevity or weight loss then tending towards endogenous ketosis with lower blood sugars and lower ketones is likely a better place to be than targeting higher blood ketones.

Introduction

I have seen a lot of interest and confusion recently from people following a ketogenic about ideal ketone and blood sugar levels.

This article reviews blood ketone (BHB), breath ketone (acetone) and blood sugar data from a large number of people who are following a low carb or ketogenic diet to understand what “normal” and “optimal” really look like.

This understanding, based on real life data from people following a ketogenic dietary approach, will to help us fine tune our diet and lifestyle to suit our goals whether they be:

low carb diets reduce blood glucose levels

Many people initiate a low carb diet to manage their blood glucose levels, insulin resistance or diabetes.

As shown in the chart below, foods with less carbohydrate do in fact have a a smaller impact on our blood sugar.[1] [2] [3]

image

While not typically recommended by dieticians and diabetes associations, it would appear that, if you are insulin resistant, have prediabetes, or diabetes (Type 1 or Type 2) it make sense to reduce the carbohydrates in your diet to the point where you can achieve the blood glucose levels of a metabolically healthy person.

what are optimal blood sugar levels?

  • “Normal” blood sugar regulation is defined as having a HbA1c of less than 6.0%.
  • Prediabetes is diagnosed when you have a HbA1c between 6.0 and 6.4%.
  • Type 2 diabetes is diagnosed when you have a HbA1c of greater than 6.4%.

However, as you can see from the charts below, this definition of “normal” is far from optimal.

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By the time you have “prediabetes” with a HbA1c of greater than 6.0% you are at risk of many of the most common western diseases of aging and causes of death (i.e. heart disease, stroke, Parkinson’s, Alzheimer’s and cancer).[4] [5]

image

If you’re interested in optimal rather than that what currently passes for “normal” health, the table below shows some suggested HbA1c and average blood sugar targets for optimal health and longevity.

risk level

HbA1c

average blood sugar

(%)

(mmol/L)

(mg/dL)

optimal

4.5

4.6

83

excellent

< 5.0

< 5.4

< 97

good

< 5.4

< 6.0

< 108

danger

> 6.5

> 7.8

> 140

ketosis vs hyperinsulinemia

While high glucose levels are bad news in and of themselves (glucose toxicity and excessive glycation), high blood sugars typically go hand in hand with high insulin levels which are also bad news.[6] [7] [8]

A metabolically healthy person will store excess energy in their fat cells for easy access when required later.  But if we continue to fill our fat cells with excess energy, you will get to the point where they cannot expand to accept any more energy.  It is at this point that our adipose tissue becomes insulin resistant.

Ted Naiman does an excellent job explaining this.

The good news is that insulin resistance will slow the expansion of our fat cells (the excess energy can’t get in as easily).

The bad news is that once our fat cells become insulin resistant the excess energy will be re-directed to the parts of our body that are more insulin sensitive such as our liver, pancreas, heart, brain and other vital organs.

Our pancreas will work overtime secreting more insulin to try to keep the energy in the liver as well as put it back into storage.

High insulin levels mean that we will find it harder to release energy from our fat stores when we go without food.[9]  Without easy access to our body fat stores, we will be driven by our appetite to eat again sooner.

Someone who is insulin resistant is more likely to become obese because their chronically elevated insulin levels will drive them to eat more often because, without easy access to their fat stores, they feel bad without a constant flow of glucose for energy.

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Fasting insulin levels in healthy populations range between 2 to 6 mIU/L.[10] [11] [12]  The average insulin levels in western populations are 8.6 mIU/L.   Meanwhile, the official reference range for “normal” fasting insulin is less than 25 mIU/L.[13] [14]  Given that the western world is going through a crisis of metabolic health, it is probably safe to say that, similar to the “normal” blood glucose levels, this cut off for insulin levels is also far from optimal.

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how to manage your dietary insulin load

To help manage your insulin levels and blood sugar you can tailor the insulin load of your diet to suit your current level of insulin resistance.   As shown in the chart below, our insulin response to the food we eat is proportional the net carbs plus about half the protein it contains.

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Reducing the insulin load of your diet can help to reduce your insulin and blood sugar levels to the point where your pancreas and current insulin resistance levels can keep up.  When our insulin levels are low, we can access our body fat for fuel, either from our body or our food.  We then see the ketone levels in our blood rise.  At this point we are deemed to be “in ketosis”.

A person with type 1 diabetes (like my wife Monica) is not able to produce enough insulin.  Without exogenous insulin injections they will see both their blood glucose and blood ketones rise to very high levels.  This is called ketoacidosis which is a dangerous state that requires exogenous insulin as soon as possible to prevent their body from falling apart.

Without insulin people with type 1 diabetes are unable to metabolise glucose and turn to their muscles for energy.  As shown in the image below of JL, one of the first children with type 1 diabetes to receive insulin, they quickly regain weight.

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It’s important to find the optimal amount of insulin.  Lowish blood ketones with healthy blood glucose levels is a normal healthy state where your body fat can more easily be accessed for fuel.

People who switch to a low carb dietary approach often find that their blood glucose and insulin levels plummet and they are not hungry because excess excessive amounts of energy can now flow out of storage (a little bit like someone with uncontrolled type 1 diabetes.

However the problem with a very low insulin load dietary approach (e.g. very high fat therapeutic ketogenic diet), is that it may not contain enough of the vitamins and minerals that you need for optimal function and avoid nutrient cravings in the long term.

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High fat foods also have a high energy density which can make it hard for some people to control portion sizes if their goal is weight loss.  Very high fat foods also tend to be less nutrient dense.

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blood glucose and ketones in fasting

When we go without food, our blood glucose levels will decrease as the glucose in our bloodstream and liver (glycogen) are used up.  The body then turns to our fat stores and our liver converts them into ketones for use.  This is termed “endogenous ketosis” (endogenous = originating from within an organism).

 

As explained by Dr David Sinclair in the video below, there are a ton of beneficial things that occur during endogenous ketosis such as autophagy, mitogenesis, mitophagy, upregulation of SIRT1 and increase of NAD+).

Ketones also increase during this low energy state to keep the brain and muscles well fuelled.  However, while ketones are present, they are not necessarily the cause of these benefits that are often associated with ketosis.

The chart below shows my blood sugar and blood ketone (BHB) during a recent seven day fast.  You can see that as glucose levels decrease, ketone levels rise.

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You can see that the sum of glucose and ketones continues to increase during fasting.  I have termed the sum of glucose and ketone as “total energy” (i.e. glucose + ketones).

Often in fasting it seems that the body will let the total energy in the blood go quite high.  This enables you to be on a state of very high alert ready to find food to survive.  It feels great and I typically feel at my sharpest after not eating for a few days.

exogenous ketosis vs endogenous ketosis

I think it’s important to understand the difference between exogenous ketosis and endogenous ketosis.  

  • Endogenous ketosis is when we eat less than the body needs to maintain energy balance and we are forced to use some of our body fat to make up the difference.  
  • Exogenous ketosis occurs when we eat lots of fat (or take exogenous ketones) and we see blood ketones (beta hydroxybutyrate) build up in the blood.  

Ketones in the blood occur when you are eating more fat than you are burning.  Lower blood ketones are not a cause for concern as long as your blood glucose levels are also low (i.e. low total energy).

The reality is that we will all be somewhere on the spectrum between exogenous and endogenous ketosis.  We need enough energy to get through the day and not fade away.  

But keep in mind that most of the really good stuff that we attribute to ketosis and the ketogenic diet occurs due to endogenous ketosis when fat is coming from our body.  

We may not have high blood ketone levels in exogenous ketosis, but that’s OK because that’s where the good stuff.  

what should your blood sugars and ketone levels be in ketosis?

The ketogenic diet is still evolving and fertile area of research.  Even Keto Clarity co-author Eric Westman recently admitted that there is still a lack of clarity around what constitutes ideal ketone levels.[15]

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The chart below shows the ‘optimal ketone zone’ from Volek and Phinney’s Art and Science of Low Carb Living which is typically referred to as the ultimate guide to optimal ketone values.  The problem, however, is that it is difficult for most people to achieve “optimal ketone levels” (i.e. 1.5 to 3.0mmol/L) without fasting for a number of days or making a special effort to eat a lot of additional dietary fat (which may be counterproductive if you’re trying to lose weight).

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Recently, I had the privilege of having Steve Phinney (pictured below in our kitchen making his famous blue cheese dressing) stay at our place for a night when he spoke at a Low Carb Down Under event in Brisbane.

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I quizzed Steve about the background to this optimal ketosis chart.  He said it was based on the blood ketone levels of participants in two studies.  One was with cyclists who had adapted to ketosis over a period of six weeks and another ketogenic weight loss study.

In both cases these ‘optimal ketone levels’ (i.e. between 1.5 to 3.0mmol/L) were observed in people who had recently transitioned into a state of nutritional ketosis.  

Since the publication of this chart in the Art and Science books, Phinney has noted that well trained athletes who are long term fat adapted (e.g. the athletes in the FASTER study) actually show lower levels of ketones than might be expected.

Over time, many people, particularly metabolically healthy athletes, move beyond the ‘keto adaption’ phase and are able to utilise fat as fuel even more efficiently and their ketone levels reduce further.

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Urine ketone strips are often considered to be of limited usefulness due to the fact that the body stops excreting ketones as it learns to use them.  Could it be a similar situation with blood ketones (BHB), albeit over a longer period of time?

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As our blood glucose levels decrease, our ketones increase to balance out the fuel deficit.   When we have less glucose available our insulin levels go down, more fat is burned and blood ketone levels rise.  The chart below shows the sum of the blood glucose and ketones (i.e. total energy) from nearly three thousand data points from a broad range of people following a low carb or ketogenic dietary approach.

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[note: In late 2015 I pooled a range of data from myself and a number of people on the Optimal Ketogenic Living (OKL)  Facebook group.  After sharing this data initially a number of other people sent me their data.  Later, Michel Lundell from Ketonix agreed to share a very large set of anonymised data for me to analyse.]

On the left hand side of the chart, we have a low energy situation where insulin levels are also low.  The body will be drawing on stored body fat for fuel to meet the shortfall and weight loss will occur.

On the right hand end of the chart, we have a high energy situation from both glucose and ketones.  This high energy situation causes the pancreas to secrete insulin to control lipolysis (i.e. the release of fat from storage) because there is more than enough energy floating around in the blood.

It’s a slight oversimplification to say that the left hand side of the chart is endogenous ketosis (which is good) and the right is exogenous ketosis (which is bad).

We may or may not see high blood ketone levels when we go without food for a long period.  However replicating high ketone levels with high levels of exogenous ketones or an oversupply of dietary fat is not the same, even though both situation are called “ketosis”.

Based on this data it seems the body tries to maintain a blood glucose level of around 4.9mmol/L and a blood ketone level (BHB) of around 1.5mmol/L.  The table below shows this data in terms of average as well as the 25th percentile and 75th percentile points (i.e. 50% of the values fit between the 25th and 75th percentiles).

 

ketones (mmol/L)

BG (mmol/L)

BG (mg/dL)

HbA1c

GKI

BrAc

total energy (mmol/L)

25th

0.6

4.2

76

4.3

1.8

46

3.4

average

1.5

4.9

89

4.7

7.3

56

6.4

75th

2.1

5.6

101

5.1

14

66

12.9

blood glucose and ketone levels during exogenous ketosis

Some people come to low carb or keto for therapeutic purposes (i.e. to manage chronic conditions such as cancer, epilepsy, traumatic brain injury or dementia).  These people will benefit from high ketone levels to feed the brain when glucose cannot be processed due to high levels of insulin resistance.

Most people however do not require this degree of therapeutic ketosis, particularly if managing insulin resistance or obesity is the priority.  People using low carb to manage diabetes or weight loss goals may end up driving excess energy consumption and a lower than necessary nutrient density, both of which may be counter productive.

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People following a therapeutic ketogenic diet may be fuelling up with MCT oils to achieve high ketone levels and low glucose : ketone index values (GKI) value for therapeutic purposes.  Others will target high levels of ketones for brain performance.  Others will load up on exogenous ketones and glucose to ‘dual fuel’ the system for athletic performance.

One of the benefits of a low carb or keto diet is that it tends to eliminate a lot of hyperpalatable processed foods, and lowers insulin levels which help many people normalise their appetite and eat less.

The danger, however, with trying to drive exogenous ketosis is that it will lead to an energy excess situation which will drive insulin to remove excess energy from your bloodstream, which can worsen insulin resistance.

Even though we are getting most of our energy from fat rather than carbs, the body will still work to bring the total energy back towards optimal levels using insulin, and stop the release of stored glycogen and body fat until you have used up the energy in your blood from your food.  This is why Thomas Seyfried and Dominic D’Agostino talk about the benefits of a calorie restricted ketogenic diet. [16] [17] [18]

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blood glucose and ketone levels for weight loss and endogenous ketosis

Many people embark on a ketogenic dietary approach to manage their diabetes and achieve long term weight loss.  They want lower insulin levels to enable them to burn more body fat for long term insulin sensitivity and health.

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On the left hand side of the total energy chart below we have a situation where we are generating endogenous ketosis, meaning that our own body fat is being burned for fuel.  With a lower total energy level in our blood, our body needs to pull fat from our body fat stores as well as use up the excess stored fat and old proteins in our liver, pancreas, brain and other vital organs (i.e. autophagy).

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In order to understand what all this means I have divided the three thousand data points into five quintiles, from lowest to highest total energy.  For each quintile I have calculated the average, 25th percentile and 75th percentile blood ketone (BHB) value.  Half of the ketone values will fit between the 25th and 75th percentile values.

optimal ketosis

The key takeaway from all this analysis is that the lowest blood sugar levels are associated with lower ketone levels and a lower total energy.

quintile

average BG (mmol/L)

BG (mg/dL)

ketones (mmol/L)

total energy (mmol/L)

25th

average

75th

1

4.5

80

0.3

0.6

0.7

5.0

2

4.9

88

0.4

0.8

1.1

5.7

3

5.1

92

0.6

1.1

1.5

6.2

4

5.1

92

1.2

1.8

2.3

6.9

5

5.1

91 2.2

3.2

4.0

8.3

In the discussion above we see that the lowest risk of the modern diseases of aging and metabolic health occurs when we have a HbA1c of less than 5%.  Dr Richard Bernstein recommends a blood glucose of 83 mg/dL or 4.6 mmol/L as optimal.  It seems that as a general rule (maybe other than when we are fasting or aiming for therapeutic ketosis) being somewhere to the left of this chart is optimal.

You may not always be able to live at a very low total energy level, but as you fast or increase the spacing between your meals your total energy levels will decrease and you will get all the positive benefits of fasting.  (See How to Use Your Blood Sugar Meter as a Fuel Gauge and How to Use Your Bathroom Scale as a Fuel Gauge for objective measures to refine your balance between feasting and fasting to achieve your goals).

You don’t achieve optimal ketone levels by adding fat with super high ketone levels, but rather by managing your energy balance, carbohydrate intake, and meal timing so you can dip into endogenous ketosis on a regular basis through fasting.

When you do eat, you should try to maximise nutrient density to ensure you get the nutrients you need without needing to overeat.  Your blood ketone levels will decrease when you are using insulin to build and repair your muscles.  When you stop eating for a while you will see them rise again as fat flows out of storage.

image14.png

Anecdotally it seems that people who are very physically fit may find they have lower blood ketone levels.  Lower blood ketone levels (say greater than or equal to 0.2mmol/L) with low blood glucose levels seems to be a healthy place to be.

image21.png

In fact, you could even save your money on testing ketones and just focus on making sure your blood sugars are closer to optimal.

is it the ketones or NAD+ that is really doing the good stuff?

A smart friend of mine, Robert Miller, has been influencing my thinking recently around ketones.

Robert’s theory is that the benefits that people attribute to ketones are actually largely due to an increase in nicotinamide adenine dinucleotide (NAD+).[19] [20]

Adequate levels of NAD are critical to moving energy around our body, from our food to our mitochondria.[21]

image

NAD+ declines with age, increases in fasting, during a ketogenic diet or in response to exercise.

When NAD+ rises, SIRT1 helps our body to repair and improve our insulin resistance.[22]

Our NAD+/NADH balance is critical to controlling our appetite and telling the body whether we need more fuel, or if it’s time to tap into our body fat stores.

image

We can increase our circulating levels of NAD+ by eating a nutrient dense diet, particularly with adequate niacin (vitamin B3).[23]

There are also a range of NAD+ supplements that seem to have positive benefits for a lot of people.

Nicotinamide Riboside is a close precursor to NAD+ which can be helpful for people who struggle to make NAD+ directly from food.

Image result for niacel

However, Nicotinic Acid (i.e. full flush niacin) is a much cheaper supplement that will work just as well for most people.

NAD+ metabolism is a fascinating rabbit hole if you want to do some research, but for now let’s say that it’s important to have adequate NAD+ to enable your mitochondria to convert the food you eat to energy rather than having it back up in your body.

what about breath ketones (acetone)?

You will likely be aware that three separate types of ketone bodies:

  1. acetone (breath ketones),
  2. acetoacetic acid, and
  3. beta-hydroxybutyric acid (BHB in the blood).

image

Fatty acids come to the liver either from our food or lipolysis (mobilisation of fat from our body) and converted to acetoacetate.   Unfortunately, we have no way to directly measure acetoacetate, only BHB in the blood and acetone in the breath.

image

The Ketonix is a device that you blow into that measures the acetone which is akin to an exhaust that is released when you burn acetoacetate.

Special thanks to Michel Lundell from Ketonix for sharing the data and Alessandro Ferretti and Weikko Jaross for help with number crunching.

image27

Blood ketones (BHB) are the most well known form of ketone bodies.  There is some relationship blood ketones and breath ketones, but it is not direct.  The chart below is from a study Measuring Breath Acetone for Monitoring Fat Loss: Review (Anderson, 2015)[24] which states

“Endogenous acetone production is a by-product of the fat metabolism process… Breath acetone concentration (BrAc) has been shown to correlate with the rate of fat loss in healthy individuals…  A strong correlation exists between increased BrAce and the rate of fat loss.”  

image

The Ketonix data shows a similar relationship but with a lot of scatter!

image

Most people at this point throw in the towel and go back to blood ketones (BHB) which appear to be more reliable, but it’s important to note that breath acetone is a stronger marker of burning ketones for fuel, not just buffering energy in the blood.

What I’m trying to illustrate with the dodgy clipart in the chart above is that having high blood ketones and low levels of breath acetone appears to be a sign that you are not burning the fat you’re eating.

By contrast, a high level of breath acetone with a low level of blood ketones (BHB) and low blood glucose may be a sign that you are very effectively burning the fat you eat.

If you had a choice, I think it’s better to have high breath acetone (BrAce) and lower blood ketones (BHB) (which would indicate that you were efficient at burning fat) than high BHB and low BrAc (which would indicate that you were good at eating fat but not necessarily burning fat).

The figure below shows BHB vs BrAc for the different purposes that people nominate for using the Ketonix.  What we see is that people with diabetes (red trend line) have both higher blood glucose and higher blood ketone (BHB) levels (i.e. higher total energy).   Fuelling the mitochondria with the right nutrients that increase NAD+ will both help to burn off the excess energy and manage appetite through the NAD+/NADH ratio.

image

The second law of thermodynamics states that the total entropy (chaos) of an isolated system can only increase over time.  The total energy concept is novel, but it seems that an organism that is aging will decay and not be able it’s energy packed in storage but rather we will see increasing levels of energy floating around in the blood stream.

image

summary

  • Metabolic related diseases such as heart disease, cancer, stroke, diabetes, Alzheimer’s disease, kidney disease are the major causes of death.
  • People with the best metabolic health (i.e. low HbA1c, insulin and blood sugar levels) have the lowest risk of dying from these common western diseases of aging.
  • Keeping your processed and starchy carbohydrates low will help to keep your blood glucose and insulin levels and reduce your risk of obesity.
  • When we fast, our glucose levels decrease and ketones increase to maintain our energy levels.
  • People who are metabolically healthy and insulin sensitive typically have a lower level of total energy (i.e. glucose + ketones) in their bloodstream.
  • We can mimic the rise in ketones with added fats or exogenous ketones that we see in fasting, however the real benefits occur when the body is forced to draw on its own stored energy and we experience autophagy, upregulation of SIRT1, and a rise in NAD+.
  • The benefits that we generally attribute to ketones may also be due to increased NAD+ levels which occur in fasting and / or with a nutrient dense diet.
  • We can only measure beta hydroxybutyrate (in the blood) and acetone (in the breath). We can think the BHB as a buffer ready for use, and acetone as the exhaust showing that the ketones have been burned for fuel.  Higher levels of fat burning with a lower need for buffering is a better place to be than a high buffer in the blood and minimal fat burning.

post last updated May 2017

references

[1] https://optimisingnutrition.com/2015/06/29/trends-outliers-insulin-and-protein/

[2] https://www.researchgate.net/profile/Peter_Petocz/publication/13872119_Holt_SHA_Brand_Miller_JC_Petocz_P_An_insulin_index_of_foods_the_insulin_demand_generated_by_1000-kJ_portions_of_common_foods_Am_J_Clin_Nutr_66_1264-1276/links/00b495189da41714fa000000.pdf/download?version=vs

[3] http://ses.library.usyd.edu.au/handle/2123/11945

[4] http://www.cardiab.com/content/12/1/164

[5] http://www.nejm.org/medicine-and-society-data-watch

[6] https://intensivedietarymanagement.com/tag/hormonal-obesity-theory/

[7] http://carbsanity.blogspot.com.au/2011/09/24hr-profiles-insulin-secretion.html

[8] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC329588/

[9] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC329589/

[10] http://wholehealthsource.blogspot.com.au/2009/12/whats-ideal-fasting-insulin-level.html

[11] https://www.ncbi.nlm.nih.gov/pubmed/11994907

[12] https://www.ncbi.nlm.nih.gov/pubmed/10535381

[13] http://emedicine.medscape.com/article/2089224-overview

[14] http://www.newhealthadvisor.com/Normal-Insulin-Levels.html

[15] https://www.facebook.com/AdaptYourLife/videos/vb.1608140252761871/1899686180273942/?type=2&theater

[16] http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0115147

[17] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1819381/

[18] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1819381/

[20] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2852209/

[21] http://www.ketoisland.com/blog/all-aboard-nad/

[22] https://selfhacked.com/2015/09/06/nad-and-sirt1-their-role-in-chronic-health-issues/

[23] http://mitofuel.co.za/mitofuel/

[24] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4737348/

[25] https://nutritionandmetabolism.biomedcentral.com/articles/10.1186/s12986-015-0009-2

[26] http://care.diabetesjournals.org/content/24/2/362

[27] https://en.wikipedia.org/wiki/Homeostatic_model_assessment

[28] http://www.thebloodcode.com/homa-ir-calculator/

trends, outliers, insulin and protein

  • The carbohydrate content of a food alone does not accurately predict insulin response.  Protein and fibre content of food also influence in insulin response.
  • The food insulin index data indicates that dietary fat is the one macronutrient that does not does not require a significant amount of insulin.
  • Net carbohydrates plus approximately half protein correlates well with observed insulin response.
  • This knowledge can be used to help select low insulin foods and more accurately calculate insulin doses for diabetics.

background

Back before the GFC I used to dabble in share trading.  I don’t know much about financial systems, but I spent a good deal of time designing and testing “trend following” trading systems.

One of the pitfalls for newbies is to design a system with excessive “curve fitting”.  That is, to design a complex system that would work fantastically on a specific set of historical data.  If you ran an overly curve fitted system on another set of data or tried to trade it in real time it would fail because it was too finely tuned to the discrete set of historical data.

“Everything should be as simple as possible, but no simpler.”

Albert Einstein

Another lesson from trading is that you should be able to describe simply why a good system works.  My trading system scanned the market for stocks that were moving up quickly over a number of time periods with minimal volatility so that I could place a close ‘stop loss’ that would take me out of the trade quickly if the trend turned.

When the GFC hit things got too volatile and I got out of the market.  It was no longer fun.  However the skills I learned as an amatuer a quantitative trader (along with my day job running multi criteria analyses to identify motorway alignments, road investments and the like) have given me an interesting angle on nutrition that I hope people find useful.

On the Optimising Nutrition blog I have tried to describe a system to manage nutrition that makes sense to me.  I want to document the things that I wish someone had shown us when we started out trying to understand diabetes and nutrition.

If we want to understand and predict the behaviour of insulin, the master regulator hormone of the human body, we need to first determine what we know that is accurate, significant and useful that we can use.

Kirstine Bell’s PhD thesis Clinical Application of the Food Insulin Index to Diabetes Mellitus[1] (Sept 2014) details the results of the latest food insulin test data for more than one hundred foods.  It also evaluates the relationship between insulin demand and protein, fat, carbohydrates, glycaemic index, glycaemic load, indigestible fibre, individual amino acids and blood glucose.

Previously I have discussed in a moderate amount of detail how to calculate how much insulin may be required based on the carbohydrate, protein and fibre ingested.  Given the importance of this issue, this article looks in more detail at what can be learned from the test data included in this thesis about the relationship between these parameters, with a view to better manage blood glucose and insulin demand.  You will see that I have tried to look at the issue from a number of different directions and have also included a more rigorous statistical analysis.

carbohydrate

Most people know that carbohydrates require insulin.  As shown in the chart below, carbohydrates goes some way to explaining insulin response.  However it is far from a perfect relationship (R2 = 0.44, r = 0.67, p < 0.05).

image001

indigestible fibre

Taking indigestible fibre into account (i.e. net carbohydrates) improves the relationship (R2 = 0.48, r = 0.69, p < 0.05).  The best correlation is achieved when we subtract all the indigestible fibre from the total carbohydrate value.  However we can see from the cluster of data points on the vertical axis there is something going on that is not explained by carbohydrates alone.

image002

The importance of dietary fibre should not be discounted, especially when trying to reduce insulin demand.  Some recommend that diabetics limit total carbohydrates, rather than considering net carbohydrates, or non-fibre carbohydrates.  The danger with a total carbohydrates approach is that people will avoid fibrous non-starchy vegetables that provide vitamins and minerals that cannot be obtained from other foods (unless you’re consuming a significant amount of organ meats), as well as feeding the gut bacteria which is also important to help improve insulin sensitivity and the body’s ability to digest fats. [2]

fat

The food insulin index data indicates that foods that are largely comprised of fat have a negligible insulin response (R2 = 0.38, r = 0.631, p < 0.001).

image003

To put this another way, the chart below shows the sum of carbohydrate plus protein (i.e. the non-fat content of foods) versus the insulin index (R2 = 0.38, r = 0.62, p < 0.001) indicating that:

  • the greater the proportion of fat in a particular food the less insulin is required; and
  • the more carbohydrates and / or protein ingested the more insulin is required.

image004

Hence, it appears that to reduce insulin demand we need to reduce carbs and / or protein!

The figure below shows a similar chart for the glucose score (i.e. the area under the curve of the blood glucose rise over three hours after ingestion of the food).  Again, this indicates that the blood glucose response is lowest for foods that contain a higher proportion of calories from fat (R2 = 0.45, r = 0.68, p < 0.001).

image005

While it appears that insulin demand is triggered by carbohydrates and protein, what is not clear is the relative degree to which carbohydrates and protein contribute to insulin demand.  Are they equivalent or does protein cause a smaller insulin  response?

protein

Another observation from trading is that you can learn a lot by considering outliers.  You have to decide whether the data points that don’t quite fit the trend are garbage or ‘black swans’ need to be accounted for in the system.

In the carbohydrate vs insulin relationship the outliers are the high protein foods that trigger a higher insulin response than can be explained by considering carbohydrates alone.

As shown in this plot, high protein foods are typically lower in carbohydrates which produce the greatest amount of glucose.  Choosing higher protein foods will generally reduce insulin (R2 = 0.10, r = 0.47, p < 0.001).

image006

Increasing protein will also typically lead to a spontaneous reduction in intake due to the thermic and satiety effects of protein. [3] [4]   Protein is critically important for many bodily functions.  It is vital to eat adequate protein.

However protein in excess of the body’s needs for growth and repair can be converted to glucose.  The fact that protein can turn to glucose represents a potential ‘hack’ for diabetics trying to manage their blood glucose as they can get the glucose required for brain function without spiking blood glucose as much as carbohydrates.

Choosing higher protein foods will generally lead to better blood glucose control.  Although high protein foods still raise the blood glucose somewhat, particularly if you are not insulin sensitive, however the blood glucose response is gentler and hence the pancreas can secrete enough insulin to balance blood glucose.

image007

For most people, transitioning to a reduced carbohydrate whole foods diet will give them most of the results they are after.  However for people with Type 1 Diabetes or people trying to design a therapeutic ketogenic diet, consideration of protein may be important to further refine the process to achieve the desired outcomes.

For a healthy bodybuilder the glucogenic and insulinogenic effect of protein might be an anabolic advantage, with the post workout protein shake providing an insulin spike to help build muscle.

However for someone struggling to lose weight on a low carb diet, considering the insulinogenic effect of protein might just be what they need to reduce insulin and normalise blood sugars and thus enable them to reach their goals.

glycaemic index

The glycaemic index is a reasonable predictor of insulin demand in terms of correlation (R2 = 0.54, r = 73, p < 0.01), however the ‘elephant in the room’ again is the high protein low carbohydrate foods (e.g. white fish, low fat cheese, lean beef etc).

image009

The other issue is that the glycaemic index is an empirical measurement that has to be measured in humans “in vivo” and can’t easily be calculated based on commonly available food properties.  And again, the glycaemic index does not deal with the insulin response from high protein foods.

glycaemic load

The same issues apply to glycaemic load.  There is a reasonable correlation between glycaemic load and insulin demand.  However it still does not explain the insulin effect of high protein foods (R2 = 0.57, r = 0.75, p < 0.01).  And you have to run these tests in real people “in vivo”.

image010

glucose score

Like the food insulin index, the glucose score is measured “in vivo” based on the area under the curve of a healthy person’s glucose rise due to a particular food.

Glucose score is interesting in that it actually achieves an excellent correlation with insulin demand (R2 = 0.75, r = 0.87, p < 0.001), however there is still a disconnect when it comes to high protein foods.

image010

It seems that some foods that do not raise blood glucose significantly over three hours still elicit an insulin response.  High protein foods digest slowly although they do still require insulin to metabolise.  In a normal healthy person the body’s insulin response to protein is balanced by release of glycogen from the liver, with blood glucose being kept in balance by insulin and glycogen. [5]

In a normal person the insulin keeps up with this slow blood glucose rise and hence we do not see a pronounced blood glucose spike due to high protein foods.

The interesting outliers here are processed low fat milk products that seem to require more insulin than would be anticipated by the blood glucose response.  On the other side of the trend line we have brown rice, pasta and other less processed whole foods which raises the blood glucose but does not require as much insulin as might be expected.

Accounting for fibre (i.e. net carbs rather than total carbs) goes some way to help anticipate the effect of processing.  However the effect of processed foods is an interesting area for future study that is beyond the capacity of this dataset to address.

I ran a number of correlation analysis and could not find an explanation of why a certain food sat above or below the trend line, whether it be carbohydrates, sugar, fibre or protein.

sugar

The sugar content of a food is not a particularly useful predictor of insulin demand (R2 = 0.10, r = 0.32, p = 0.001) compared with net carbohydrates (R2 = 0.48, r = 0.69, p < 0.05).  Quitting sugar is only part of the solution.  Most people struggling with diabetes or obesity should ideally consider their total carbohydrate intake.

image011

curve fitting

Kirstine Bells’ Clinical Application of the Food Insulin Index to Diabetes Mellitus[6] documents the development of a number of formula to explain the relationship between food properties and the food insulin index response.  The aim of this her thesis was essentially to build an improved glycemic index to predict insulin response rather than only considering changes in blood glucose.

The chart below shows the best relationship developed using a stepwise multiple linear regression analysis of the various parameters to forecast insulin demand documented in Clinical Application of the Food Insulin Index to Diabetes Mellitus. [7]

The correlation is excellent (R2 = 0.78, r = 0.89, p < 0.001).  However this relationship relies heavily on the glucose score (GS) which has to be tested “in vivo”.

image012

If we strip out the glucose score then the best relationship achieved in the thesis is the one shown below using carbohydrates and protein with a correction factor (R2 = 0.46, r = 0.68, p < 0.001).

The problem with this approach is that it assumes that high fat foods have some insulinogenic effect.  However we have seen above that high fat foods have a negligible insulin response.  This formula also does not account for indigestible fibre which should be subtracted from the total carbohydrate count.  And according to this formula a food with zero carbohydrate and zero protein would still have a significant insulin index response of 10.4, which does not make sense.

image013

simple is true

If we take out indigestible fibre (net carbs), assume that fat has a negligible insulin response and refine the protein factor to maximise the correlation with the test data, we end up with this chart which has an improved correlation compared to the model above (R2 = 0.49, r = 0.70, p < 0.001).

image014

This approach also does a good job of predicting blood glucose (R2 = 0.59, r = 0.77, p < 0.001) as shown in the chart below.

image015

practical application

Individual foods can be ranked and prioritised based on their proportion of insulinogenic calories using the following formula:

image016

Foods with the lowest proportion of insulinogenic calories will have the gentlest impact on blood glucose and have the lowest insulin demand, a consideration which will be very useful for people who are insulin resistant (i.e. Type 2 Diabetes or Pre-Diabetes) or not able to produce adequate insulin themselves (i.e. Type 1 Diabetes).

You can find a detailed list of foods ranked by their proportion of insulinogenic calories here and with consideration of nutrients and other factors based on different goals here.

Diabetics and people wanting to reduce the insulin demand of their diet can track the total insulin load (as opposed to carbohydrate counting) using the following formula:

image017

The total insulin load can be reduced by decreasing carbohydrates, increasing fibre, moderating protein to the body’s optimum requirement and increasing fat until target blood glucose are achieved.

can we design a “perfect” system?

There is still quite a degree of in this real life data.  This could be due to measurement error in the macronutrients, food quantity, individual characteristics of the people that the food was tested on, or something else.

This approach considering the insulinogenic effect of protein and carbohydrates does however help to better predict insulin demand than carbohydrate alone.

The fact that there is still a high degree of variability in the data and hence limited ability to accurately predict the insulin response to food can be mitigated by keeping the overall insulin load of the diet reasonably low.

Dr Richard Bernstein talks about the ‘law of small numbers’ whereby the compounding errors in the calculation of insulin requirement and the mismatch of insulin response with the rate of digestion misalign means that it is impossible to accurately calculate insulin dose.

The only way to manage the high level of variability is to reduce insulin demand to manageable levels.  This is especially beneficial for people who are injecting insulin, but also relevant for the rest of us.

summary

Building on the analysis of the food insulin index data, the key assumptions that underpin this system are:

  1. carbohydrates require insulin,
  2. indigestible fibre does not require insulin, and
  3. the glucogenic portion of protein that is not used for growth and repair and not lost in digestion also requires insulin.

In order to reduce our insulin load we should do the following, in order of priority:

  1. Reduce insulin load until you normalise blood glucose levels (i.e. reduce digestible carbohydrates and moderate protein if necessary),
  2. Increase nutrient density as much as you can while still maintaining good blood glucose levels (note: this will likely also include fibre from non-starchy veggies which will also increase fibre which reduces insulin and slows digestion),
  3. Reduce dietary fat if you still need to reduce body fat levels, and
  4. Implement an intermittent fasting routine to improve your insulin sensitivity and to kick-start ketosis.

references

[1] http://ses.library.usyd.edu.au/handle/2123/11945

[2] http://www.amazon.com/Brain-Maker-Power-Microbes-Protect/dp/0316380105

[3] http://wholehealthsource.blogspot.com.au/2013/04/glucagon-dietary-protein-and-low.html

[4] http://www.ncbi.nlm.nih.gov/pubmed/16002798

[5] http://wholehealthsource.blogspot.com.au/2013/04/glucagon-dietary-protein-and-low.html

[6] http://ses.library.usyd.edu.au/handle/2123/11945

[7] http://ses.library.usyd.edu.au/handle/2123/11945

[8] http://www.amazon.com/Brain-Maker-Power-Microbes-Protect-ebook/dp/B00MEMMS9I

what is a ‘well formulated ketogenic diet’?

While everyone uses fat for fuel to some degree, a ketogenic diet aims to reduce insulin levels to a point where ketone levels are high enough to be measured in the blood, breath or urine. [1]

In starvation, insulin levels plummet with glucose levels coming down and ketone levels increase progressively.

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According to Dr Steve Phinney’s chart below, a “well formulated ketogenic diet” contains between 3 and 20% carbohydrates and between 10 and 30% protein.

image016

Other dietary templates such as the Mediterranean or Paleo diets typically contain more carbohydrates and less fat.

The concern typically expressed about restricted carbohydrate diets is that they will not provide adequate nutrition (i.e. vitamins, minerals and amino acids).

Diabetics, along with the general population, are advised to eat in line with the USDA Food Pyramid / My Plate guidelines which emphasise “healthy whole grains” while discouraging saturated fat and cholesterol.

Diabetics are told that they should not deprive themselves of any foods or not to risk getting inadequate nutrition, but rather to “cover” any carbohydrates they eat with insulin (or treat with medications such as Metformin for type 2 diabetics).

Even in health circles ketosis is sometimes considered to be extreme and not worth the effort for most people, but is it really that hard to achieve?

When we look at the relationship between ketones, blood sugar and HbA1c we see that someone with excellent blood glucose levels will have a moderate amount of blood ketones.

The chart and table below are based on my tracking of blood sugars and ketone values.  Optimal blood (i.e. 4.6mmol/L) glucose corresponds to a ketone value of about 1.3mmol/L.

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HbA1c average blood sugar ketones
 (%)  (mmol/L)  (mg/dL)  (mmol/L)
low normal 4.1 3.9 70 2.1
optimal 4.5 4.6 83 1.3
excellent < 5.0 < 5.4 < 97 > 0.4
good < 5.4 < 6.0 < 108 < 0.3
danger > 6.5 > 7.8 > 140 < 0.3

In view of this it’s hard to see why ketosis is extreme.  It’s just what happens when someone has reduced their dietary insulin load to a point where they are achieving excellent blood sugars!

Ketosis is a sliding scale.  Some people will want to push their ketone levels to therapeutic levels though fasting and a higher fat diet, but this may not be necessary for general health.

Most people would benefit from reducing their dietary insulin load to a point where their blood sugars are close to excellent.

See Diabetes 102 for more info on what your blood sugars should be and the Goldilocks Glucose Zone for more thoughts on how to manipulate your diet to get excellent blood glucose levels.

I am a big fan of Steve Phinney (I attended a masterclass with him when he was in Brisbane last year), but I think he potentially alienates people when he starts off talking about the Inuit and Steffanson living off all meat diets.

I also understand why the people generally might baulk at the idea of mainlining butter and MCT oil to drive up ketones.  “How can eating all that extra fat really be healthy?” they ask.

I propose an alternative sales pitch for ketosis:

  1. ketosis occurs when your blood sugars are close to optimal,
  2. blood sugars can be optimised by reducing the insulin load of your diet, and
  3. once you optimise your blood sugars you will reduce your hunger, access your body fat for fuel and a whole host of other health markers will improve.

What’s not to like?

What do you think?

[this post is part of the insulin index series]

[Like what you’re reading?  Skip to the full story here.]

[1] http://www.dietdoctor.com/lose-weight-by-achieving-optimal-ketosis

[2] https://www.youtube.com/watch?v=2KYYnEAYCGk

the carbohydrate debate

On the low carbohydrate end of this debate you have people like Dr David Perlmutter, Nora Gedgaudas, Ron Rosedale and Dr William Davis arguing that you should restrict carbohydrate for metabolic and brain health as well as the prevention and cure of a range of diseases.

Below is one of the more confronting charts from Dr Perlmutter’s Grain Brain showing that the rate of brain shrinkage with age increases dramatically once we get an HbA1c of more than 5.2%.

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Increasing HbA1c is correlated with an increased risk of cancer, particularly once we get an HbA1c over about 6% (i.e. average blood sugar of 7.0mmol/L or 126mg/dL).

image002

The risk of cardiovascular disease, coronary heart disease and stroke all increase once an HbA1c greater than 5.0%, and especially over 5.4% is reached.

It is also worth noting that being on antidiabetic medication, even if it reduces your blood sugar, does not reduce your risk of heart disease.

image003

Perhaps keeping your blood sugar under control is the most important thing you can do to manage your health and slow the aging process, regardless of whether you have been formally diagnosed with diabetes.

If you are not getting HbA1c checked regularly you can use the average blood glucose results from your home blood sugar meter (i.e. fasting, before meals and after meals).

The conversion between HbA1c and average blood sugar are shown below.  I have also added risk level values based on the cardiovascular disease data above, and ketone values based on my data as discussed in this article.

HbA1c average blood sugar ketones
 (%)  (mmol/L)  (mg/dL)  (mmol/L)
low normal 4.1 3.9 70 2.1
optimal 4.5 4.6 83 1.3
excellent < 5.0 < 5.4 < 97 > 0.5
good < 5.4 < 6.0 < 108 < 0.3
danger > 6.5 > 7.8 > 140 < 0.3

One of the most extreme proponents of the restricted carbohydrate dietary approach is Dr Ron Rosedale who says that carbohydrates cause oxidation in the body, and that we should do everything we can to minimise oxidation by minimising carbohydrates ingested.

While the body does need glucose, it is preferable to have the body make it via gluconeogenesis (from protein) rather than directly feeding the body carbohydrates which will lead to oxidation. [3]

mainstream recommendations

On the other extreme you have dieticians recommending the USDA food pyramid telling us that we can’t survive without our healthy whole gains and that our brains run on glucose and hence we need to eat carbs or else.

The generally accepted diagnosis levels for type 2 diabetes are shown below.  Currently one in twelve adults worldwide are classified as diabetic based on this criteria.  This number is forecast to grow by more than half over the next two decades to 592 million people by 2035. [4]

  Fasting After meal
  (mg/dL) (mmol/L) (mg/dL) (mmol/L)
“normal” < 100 < 5.6 < 140 < 7.8
Pre-diabetic 100 – 126 5.6 – 7.0 140 – 200 7.8 – 11.1
Type 2 diabetic > 126 > 7.0 > 200 > 11.1

Comparing these diabetes diagnosis criteria with the optimal levels it is clear that blood glucose levels that are considered “normal” are far from optimal.  By the time you are “pre-diabetic” you are well into the danger zone!

the middle ground?

Somewhere between the dieticians and the low carb zealot you have people such as Paul Jaminet, Chris Kresser and Robb Wolf who advocate for some carbohydrates for the majority of the population.

When you listen to the argument a little closer though, it is interesting to find that even these respected health experts are all talking about a level of carbohydrates much lower than the typical western dietary intake and the typical mainstream recommendation.

Chris Kresser recommends 20 to 30% carbs for healthy people and says that a lower carb ketogenic approach will likely be beneficial for people with Alzheimer’s, dementia or neuro-degenerative disorders. [5]

Paul Jaminet’s definition of “low-carbohydrate” means eating less than the body’s glucose utilisation which forces the body to make up the deficit via gluconeogenesis. [6]  Jaminet says that the body’s preferred source of fuel is fat.  However the body typically runs on a mix of around 30% glucose for fuel (or about 600 calories per day).

Jaminet notes that if we eat more than around 30% carbohydrates the liver will end up with more glucose than it can store and we will end up with excess glucose in the blood.  The pancreas will secrete insulin to remove this excess sugar and store it as body fat.

If we eat less than 30% carbohydrates the body will convert protein to glucose through gluconeogenesis, and the risk of excess sugar in the blood is reduced.  This balance is represented graphically in the figure below.

image014

the big picture

When you stand back and look at the big picture, most recommendations are that that the general population should be consuming significantly less carbohydrates than are consumed in the typical western diet.

There is no perfect diet or level of carbohydrates that suits everyone.  Active people or those who are not metabolically broken will be able to tolerate more carbohydrates because they will be burning them quickly rather than storing them.

People who are sedentary or obese (i.e. 70% of the western population these days) or those with blood sugar dysregulation should opt for a carbohydrate restricted approach.

Jaminet also points out that there is an ideal range for blood sugar.  While people operating in ketosis can tolerate lower blood glucose levels while being asymptomatic, extremely low levels of blood sugar will lead to decreased health and eventually death.  That is, there is a lower limit for blood sugar, however your body will do everything it can to stop you from getting there.  So in the absence of injecting too much insulin it is probably not going to be an issue for most people.

image015

Similarly, at high levels of blood sugar we will get the numerous complications of high blood glucose and diabetes.  Somewhere between these two extremes is an optimal blood sugar level which Dr Richard Bernstein puts at about 83mg/dL or 4.6mmol/L. [8]

so just tell me what to do!

In view of the fact that the various health markers shown above start to go pear shaped beyond a HbA1c value of about 5.0mmol/L and then really start to fall apart above a HbA1c of 5.4mmol/L, I think it makes sense to reduce your insulin load until you get your blood sugar into the ‘good’, if not ‘excellent’ or ‘optimal’ ranges as shown in the table below.

HbA1c average blood sugar ketones
 (%)  (mmol/L)  (mg/dL)  (mmol/L)
low normal 4.1 3.9 70 2.1
optimal 4.5 4.6 83 1.3
excellent < 5.0 < 5.4 < 97 > 0.5
good < 5.4 < 6.0 < 108 < 0.3
danger > 6.5 7.8 > 140 < 0.3

If you’re a Kitavin eating fruit in the jungles of Papua New Guinea or Rich Froning living off peanut butter and sweet potato, that might mean you should keep on doing what you’re doing.

If you look in the mirror and see a bit more body fat than you’d like, it probably means you might benefit from actively managing the glucose levels and insulin load of your diet.

Once you get them into the excellent range you will automatically tap into ketosis which will mean that you will be burning fat for fuel and losing weight without feeling like you are starving yourself!

If you are looking for more inspiration on what to do at this point check out the list of optimal foods here and optimal meals here.

Learn more about how to bring your blood sugars in line here, how to lose weight here, and what to eat if you’re lucky enough to be a metabolically healthy and fit athlete here.

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[1] http://www.drperlmutter.com/important-blood-test/

[2] http://www.cardiab.com/content/12/1/164

[3] https://vimeo.com/52872503

[4] http://www.dailymail.co.uk/health/article-2997882/Diabetes-epidemic-400-million-sufferers-worldwide-Number-condition-set-soar-55-20-years-unless-humans-change-way-eat-exercise.html

[5] http://chriskresser.com/how-to-feed-your-brain from 9:25

[6] http://perfecthealthdiet.com/2011/10/jimmy-moore%E2%80%99s-seminar-on-%E2%80%9Csafe-starches%E2%80%9D-my-reply/

[7] http://perfecthealthdiet.com/2011/11/safe-starches-symposium-dr-ron-rosedale

[8] https://www.youtube.com/watch?v=zJGAbZIvRh8

[9] http://www.dietdoctor.com/lose-weight-by-achieving-optimal-ketosis