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Glucose Ketone Index

Alzheimer's, cardiovascular, and other chronic diseases; biomarkers, lifestyle, supplements, drugs, and health care.
circular
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Glucose Ketone Index

Postby circular » Wed Oct 02, 2019 7:25 pm

Has anyone found anything to suggest the glucose ketone index (GKI) adds any substantiated value to our toolkit? I haven’t found anything in pubmed.

And why is glucose divided by 18 before dividing that by the ketone level?

I’m not feeling sold on the GKI concept but curious what others think. Maybe I just don’t get it and am missing something.
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Re: Glucose Ketone Index

Postby TheresaB » Thu Oct 03, 2019 4:47 am

How I came to know about the GKI was a few years ago through Dr Thomas Seyfried. If he didn't coin the term, I think he was the one who made it popular. He's a cancer researcher from Boston College so his primary focus is as a tool for cancer. Many cancers love glucose and restricting glucose as a source of fuel for growth can be very effective in treatment, tolerating/enhancing standard of care treatments, and prevention. His desire is to have a ratio of glucose less than 1 in comparison to ketones. That GKI of less than 1 is one of the primary objectives I try to reach on my annual multi-day fast as a cancer prevention measure. I also understand it is used to help as a proxy measure for autophagy since there is no direct measure for autophagy.

You divide by 18 to get equal measures, sort of like converting liters to gallons.
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Re: Glucose Ketone Index

Postby Tincup » Thu Oct 03, 2019 5:00 am

circular wrote:
And why is glucose divided by 18 before dividing that by the ketone level?



GKI is glucose/ketones (BHB) with both expressed in mmol/L. Since glucose in the US is normally reported in mg/dL you divide by 18 (18.02 to be exact) to convert.

GKI was developed by Dt Thomas Seyfried as a way to measure ketosis status for cancer patients. He suggested they should try to keep GKI<1 and not with exogenous ketones. It is difficult to do while eating. I know a 7 year brain cancer survivor, Allison Gannett, who does this. Integrative ND oncologist, Nasha Winters, prescribes this.

I meet this standard on extended water fasts, but not whilst eating.

I can’t comment as to the utility for E4s on a daily basis.
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Re: Glucose Ketone Index

Postby aphorist » Thu Oct 03, 2019 7:08 am

It's just a simple ratio that some person can claim they 'invented' or that they are some 'pioneer' in identifying. Assuming you are not in diabetic ketoacidosis or taking exogenous ketones, what matters most is the absolute level of ketones, such that they are available as an energy substrate and your body has undergone a metabolic shift.

I'd personally like to know the difference in flux in muscle/brain at various GKI levels, because why is the magic ratio 1.0 and not 1.1 or 0.9 or whatever? IDK. Seems like it's just some cute simple metric.

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Re: Glucose Ketone Index

Postby Tincup » Thu Oct 03, 2019 8:00 am

aphorist wrote:I'd personally like to know the difference in flux in muscle/brain at various GKI levels, because why is the magic ratio 1.0 and not 1.1 or 0.9 or whatever? IDK. Seems like it's just some cute simple metric.


If you tested the average person their GKI is probably infinite because their BHB is 0. I don't think Seyfried would distinguish between 0.9 and 1.1. There is likely a difference between 1, 5, 50, 500 & infinity. For example, glucose of 80 and ketones of 0.5 would be a GKI of ((80/18)/.05)=8.9 while 80 and 2 would be 2.2. Also in the cancer realm, the concept is to get the glucose low, not just the BHB high. Not saying this is best for cognition. A number close to 1 would be glucose of 60 and BHB of 3 = 1.1.
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Re: Glucose Ketone Index

Postby mike » Fri Oct 04, 2019 5:01 pm

aphorist wrote:It's just a simple ratio that some person can claim they 'invented' or that they are some 'pioneer' in identifying. Assuming you are not in diabetic ketoacidosis or taking exogenous ketones, what matters most is the absolute level of ketones, such that they are available as an energy substrate and your body has undergone a metabolic shift.

I would disagree with this a bit. The value of one is where ketones = glucose. Getting ketones > glucose means GKI < 1. The body will use glucose before ketones if it has a choice (mostly to clear it), so to get to a point where your body is properly using ketones, you want to starve the body of glucose. This is particularly important for diabetics - I constantly run over .5 for ketones, but it is no where near as effective because of my high sugars. One needs to eat mostly fat to keep below 1 while eating. Generally a GKI of 3 is considered the starting range for nutritional ketosis. Getting to under 1 and you start getting increasing autophagy and often see shrinkage of cancer.
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Re: Glucose Ketone Index

Postby aphorist » Tue Oct 08, 2019 7:10 am

mike wrote:I would disagree with this a bit. The value of one is where ketones = glucose. Getting ketones > glucose means GKI < 1. The body will use glucose before ketones if it has a choice (mostly to clear it), so to get to a point where your body is properly using ketones, you want to starve the body of glucose. This is particularly important for diabetics - I constantly run over .5 for ketones, but it is no where near as effective because of my high sugars. One needs to eat mostly fat to keep below 1 while eating Generally a GKI of 3 is considered the starting range for nutritional ketosis. Getting t.o under 1 and you start getting increasing autophagy and often see shrinkage of cancer.


If your ketone level is 0.5 mM, then your absolute level isn't very high and you have not undergone a metabolic shift by definition. Therefore, my point remains unchanged -- the absolute level is probably more important regardless of what the GKI ratio is, although implicitly the absolute ketone level is partially dictated by the level of glucose available. I respect the fact that you are a T1D, but that constitutes 0.3% of the population and is a bit of a unique situation.

No idea how you measure autophagy or determine why below 1.0 is a key threshold. I'd love to see data that explained rates of autophagy at various GKI, but I'm not aware of any idea or any reason to think that it's some kind of key inflection point. Whether or not glucose is 3.0 mM or 4.0 mM, I think matters less than ketone availability because it acts as a signaling molecule. This would make the ratio less important, than the actual metabolic shift itself of ketogenesis in a pronounced way. That's my personal viewpoint, but I'd obviously like to see data that has a more granular view.

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Re: Glucose Ketone Index

Postby aphorist » Tue Oct 08, 2019 7:13 am

Tincup wrote:
If you tested the average person their GKI is probably infinite because their BHB is 0. I don't think Seyfried would distinguish between 0.9 and 1.1. There is likely a difference between 1, 5, 50, 500 & infinity. For example, glucose of 80 and ketones of 0.5 would be a GKI of ((80/18)/.05)=8.9 while 80 and 2 would be 2.2.


I agree with this. But by definition if ketones are 0.5, the person hasn't really undergone a metabolic shift. I'm just rather suspect of getting overly excited about this ratio, because I don't know of any data that dictates why GKI of 1.0 is substantially better than 1.5, etc. I think ketones (BHB, etc.) are effectively signaling molecule and as long as they are elevated, the absolute level of glucose (and subsequent ratio GKI) is not as critical.

I wish I had better data and a more detailed understanding of the gradient.

Tincup wrote:Also in the cancer realm, the concept is to get the glucose low, not just the BHB high. Not saying this is best for cognition. A number close to 1 would be glucose of 60 and BHB of 3 = 1.1.


I wasn't taking cancer into consideration, as that is obviously a pretty unique situation.

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Re: Glucose Ketone Index

Postby Tincup » Tue Oct 08, 2019 7:39 am

[quote="aphorist"I agree with this. But by definition if ketones are 0.5, the person hasn't really undergone a metabolic shift.[/quote]

I've been "keto adapted" for 10 years. I can run my ketones between 0.2 and >8.0 (max on my meter - the later on extended fasts). If I want more serum ketones, I just change my macros or do extended water fasting. By day 3 of a water fast, my ketones are >5.0 mmol/L and glucose is in the 50's md/dL (3's in mmol/L). My personal objective is to be able to generate ketones and use beta hydroxybuterate when my body needs them. Several years ago, I did a two week Cronometer.com study where I measured all my food with a gram or milligram scale. My carb intake was a mean of 122 g/day with fiber 50g and the range was 80 to 180g. My serum ketones ranged from 0.7 to 1.9 mmol/L during the study. More recently I've been adding more resistant starches such as sorghum, millet and fermented legumes into my diet for gut biome reasons. My ketones generally run around 0.5 - 0.7 with this program. However an extended fast will follow my past pattern (glucose in the 50's and ketones >5) as before. Hence, at least for me, I would suggest that I've maintained metabolic adaptation. I've only once experienced "keto flu" during the last 10 years (when I first adapted).

My understanding is that the longer you are adapted, the more efficient the body becomes in ketone utilization, hence the amount of the ketones in "storage" as betahydroxybuterate is not indicative of production. I've not bothered to recently check breath acetone, which is a better indicator of ketone production, because my meter also registers on methane. My large intake of leaves and other fiber creates a lot of methane confounding the interpretation.

{edit} I also did nineteen consecutive cycles of water fasting for five consecutive days (120 hours) out of every 14 days a couple of year ago (weight stable from the start of one cycle to the next), so am very familiar with significant ketosis. My lowest GKI was when I had a glucose of 31 mg/dL (1.7 mmol/L) and ketones of 6.9 - GKI = 0.25. I then went to the gym and set PR's on my lifts.
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Re: Glucose Ketone Index

Postby aphorist » Tue Oct 08, 2019 8:50 am

Tincup wrote:stuff


I meant a shift in terms of current utilization of metabolic substrates at that very moment. Not adaptation. You are clearly well adapted. Presumably if a person is not in diabetic ketoacidosis and their ketones are anything north of 2 mM, their metabolism has undergone this metabolic shift and metabolic substrate utilization has changed -- regardless of whether or not glucose is 82 mg/dL or 62 mg/dL.

I think to really understand granularity of GKI at 2.0 vs. 1.0, etc. we would need to measure flux. There would have to be some kind of radio-labeled measurement of the rate of ketones, glucose being utilized by muscle, brain, etc. in order to really understand substrate utilization at various levels.


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