Hypoglycemia low blood glucose while highly fat adapted with high ketones Research?

[PaulL]

Karim’s story is useful since apparently people can and do survive even with blood glucose in the 30s, but I am still seeking actual research in addition.

Dr. Phinney has a story of some friends of his who used an insulin clamp to drive down the serum glucose of some fat-adapted athletes they were studying. He said that, even though the researchers realized later that they could get into trouble for taking such a risk (and no IRB would ever countenance such shenanigans today), they did publish the results. I’ll try to track down a reference to the paper; I remember coming across it within the last six months.

[MAlvis]

Personally, I have never seen anyone in ketosis and using a CGM (extremely helpful) with CGM glucose concentrations below about 45 mg/dl.

However, does mean they have any problems or symptoms?
No!. Typically report feeling and thinking better than usual.

All the fear about low glucose concentrations comes from insulin and sulfonylurea medications which can drive glucose low enough in people who are not keto adapted, typically below 40 mg/dL and end up symptomatic. The concerns about low are driven by those using they bad tools and concerns that people go low enough they become confused, comatose and die if their glucose continue to go down
far below 40. The lowest I have ever seen, by finger stick, was 0 mg/dL (accuracy unclear) because was in a VA hospital surgical ward and had been given too much insulin. He was, of course, comatose, but awakened, very confused, after being given D50 IV.

There is Zero evidence that I am aware of the low glucose ever becomes a problem for people adapted to nutritional ketosis.

Be aware that many issues which many physicians believe are not true.

Medicine remains more art than science and overwhelmingly about disease, not health: http://goo.gl/Blh6rW

Milton Alvis
https://www.quora.com/profile/Milton-Alvis-1
http://www.healthtap.com/Dr-MiltonAlvis

[PaulL]

Phinney says that when his friends performed that study, they drove the participants’ serum glucose down to levels that normallly cause coma or death, but the guys were fine. I love his line, “But the only people having palpitations were the ones in the white coats.”

Of course, no IRB in its right mind would authorize such a study today.

I believe this is the writeup of the study I have in mind. If not, it’s a very similar study.
“Resistance to Symptomatic Insulin Reactions after Fasting,” Drenick et al., 1972)

[atomicspacebunny]

I am talking about people who feel fine, even wonderful, and who may be on long extended fasts, with glucose down below 55-ish (3.0) and ketones up above 5.0-7.0

My guess is this isn’t well studied and few medical people know the actual effects even if it has been researched.

Phinney & Volek: Starvation Ketosis: During total fasting when there is complete absence of any caloric intake for several days, the resulting increase in ketones is referred to as starvation ketosis. The absence of any dietary carbohydrate and protein over a week or more raises ketone concentrations to between 5 and 10 mmol/L, significantly higher than nutritional ketosis, but lower than concentrations in keto-acidosis. Starvation ketosis is an important physiologic process that evolved millions of years ago, enabling humans to survive for prolonged periods on body fat when food was not available.4 Obviously starvation ketosis is not sustainable long term, nor is it advisable to intentionally induce it for shorter periods (i.e., intermittent fasting) because of essential nutrient deprivation, lean tissue loss, and other potentially dangerous side effects.5 …” …More

Megan Ramos: “…But my blood sugar levels are typically between 3 and 3.9 mmol/L, which translates into 50 to …or sorry 54 to 70 mg/dL. So, that 65 to 99 mg/dL is considered to be normal by government standards here in Canada, the 54 to 70 is considered to be common amongst ketogenic population. A lot of my patients too, who follow ketogenic diet, they’re getting sugars between 3 and 3.9 or between 54 and 70.

Sort of branching off the first question about blood glucose levels, what are optimal blood ketone levels? Good question. We don’t really know what any of these ketone levels mean. It’s crazy. I get asked these questions all the time and there’s a occasional post on the keto page or there’s different doctors making different speculations about what are optimal ketone levels. There’s just not a whole lot of data out there really telling us the significance of certain ketone levels. We do have some research and we can see that nutritional ketosis is between 0.5 and 1.5 mmol/L. When your ketones are between 0.5 and 1.5 mmol/L, then you’re in a good state of nutritional ketosis. Nutritional ketosis does not equate to therapeutic ketosis that you would use to treat metabolic syndrome, neurological conditions such as MS or Parkinson’s or Alzheimer’s disease or various cancers. Nutritional ketosis is just for overall health and well-being.

​A lot of research shows that fat burning occurs between 1.5 and 3.O mmol/L. There are some research that indicates that once you’re above 3, it doesn’t increase your rate of fat loss. But there’s a difference between 1.5 and 3.O. Yes, 3.O indicates more body fat burning or more fat burning in general than 1.5 mmol/L. The researches done doesn’t really show much more of a significant impact of having ketones of 4, 5 or 6 as compared to 3 for weight loss and fat burning. What should your numbers be? What if your ketones are 6? What if they’re 5? What if they’re 4? Is that a bad thing? We don’t really know. I’ll tell you a little bit about my numbers. My morning ketone numbers are usually between 3 and 6. What gauge is my blood ketone number is in the morning, determines on how late in the evening I eat. I try to eat no later than 7:00 or 7:30 come hell or high water. Most days, my husband and I finish eating at 2:00 PM if we intend to eat at all that day if we’re not fasting. But the weekends, Friday nights, it doesn’t always pan out that way. I really, really try except for the odd time, which ends up being about once or twice month where I end up eating a little bit past 7:30. Rarely, rarely, do I ever eat past 8:00 or 8:30 in the evening. Usually, those are very late nights too where I’m up until 1:00 or 2:00 in the morning at a social event. Those are my morning numbers, between 3 and 6. I feel good and my blood sugar levels are low.

​Now, having these high ketone levels can be a problem if the blood sugar levels are going up. I usually tell people that if their ketones hit 4 and their blood sugar levels are trending up and not down, they need to stop and they need to eat. They don’t need to eat carbohydrates but you need to eat a well-balanced ketogenic or low carbohydrate meal. Get in plenty of non-starchy vegetables, get in some good fats, a variety of good fats, eat some good hearty protein and then just hold off on fasting for a little bit. It becomes very dangerous when the blood glucose levels and ketone levels are both going up. Now, my ketone levels can be 6 and my blood glucose levels can be around 3 mmol/L, which is around 65. That’s not a word for concern and I feel fantastic. We are learning more and more what these numbers mean. What is really optimal, we don’t really know. Also, for patients that are fasting, when you’re in a fasting state and you start to get ketones of 0.5 and 1.5, that does actually indicate some body fat burning. If you’re in a fasted state and you see ketones of 1, don’t beat yourself up. You are burning fat. We know that that 1 is not coming from nutritional ketosis because you haven’t eaten. You’re fasting.

​All these numbers are a little funky. We still need to learn a lot. We need to learn what they mean on their own on a high fat diet, on a ketogenic diet. We need to learn what fasting means for these numbers too, a little bit more. If you are fasting, don’t get discouraged when you see ketones over 0.5. That’s usually when I start to be able to correlate patients ketones with weight loss. As soon as my patients start getting ketones of 0.5, I notice weight loss on the scale and body fat loss in terms of taking their measurements. That’s when you’re in a fasted state. That’s really good. Even though that’s considered nutritional ketosis if you’re eating, for weight loss, you’re still losing weight at those numbers if you’re fasting. Don’t go crazy trying to get high numbers. Be very cautious if your ketones go up and your blood sugar levels are also going up. If it looks like that’s a trend, it’s always better to be safe than sorry and stop and have something to eat. There’s never any pain in eating some bacon and eggs and you can always jump back into your fast after that.

​I know many of you are going to now write in asking about diabetic keto acidosis but I’m going to talk about that in another few Q & A’s from now. We’re going to cover a little bit more on the ketogenic diet and what is diabetic keto acidosis. …” - Megan Ramos

[Herb_Martin]

PaulLOld BaconianAdmin
atomicspacebunnyBunny
Karim_Wassef
carolTAdmin
JanieJaneRegular

I need to read and study much of the above but wanted to at least say some kind of thank you now to everyone who is offering help.

This is much more of what I was seeking, and there may even be more in these references and links than I suspect.

I think the main thing we are still missing (it probably doesn’t exist or we’d have found it by now) is:

What is a dangerous (or what’s safe) LOW blood glucose level for a fully fat adapted person who is on a ketogenic diet or fast with ketones at a high level and who is experiencing NO SYMPTOMS?

Apparently Karim (and others) have been into the 30s, I’ve been in the 50’s (which isn’t that low).

I trust Karim’s report but it would be nice to have some non-anecdotal guidelines rather than “below 70 etc is hypoglycemia” and requires possible medical intervention.

MAlvisMilton Alvis, MD
What would you do if someone like Karim walked in with a BG of 33 and felt wonderful while his ketones were 5+?

Wendysue1960Wendy
Thank you Wendy though I am not looking for problems with hypoglycemia unless you were highly ketogenic (>2.0->5.0) AND likely if you had NO SYMPTOMS before it became a serious problem.

What I am trying to discover is SAFE LIMITS for those of us who are monitoring ourselves carefully and what is safe to advise others who are FEELING REALLY GOOD and taking reasonable precautions.

Preferably as citable research papers, but case studies and other reports are also useful both in lieu of peer review hard science and as an adjunct.

Going to re-read and study all of the above but keep it coming please.

[Karim_Wassef]

glucose alone is not a meaningful threshold. It’s all about energy and there are other key sources of energy: ketones, free fatty acids, and even creatine for sudden bursts of energy.

glucose of 30 with ketones of 0 = comatose
glucose of 30 with ketones of 7 = feeling awesome!

I always measure both because one without the other isn’t so meaningful.

[Herb_Martin]

4m

glucose alone is not a meaningful threshold. It’s all about energy and there are other key sources of energy: ketones, free fatty acids, and even creatine for sudden bursts of energy.

glucose of 30 with ketones of 0 = comatose
glucose of 30 with ketones of 7 = feeling awesome!

Ok, I get that, but at least a small part of the motivation of this request is to deal with semi-knowledgable (medical) people who freak out at the sight of 30 or even 50 but have no knowledge of nutritional ketosis.

The other half involves ensuring we don’t give poor advice to someone (including especially ourselves) to ignore a real problem.

So while I agree with you I am still looking for [more] citable science.

[atomicspacebunny]

Do you know of links to any real science or even case studies and reports on people with (technical) hypoglycemia while highly fat adapted with high ketones?

Megan Ramos: ​Now, the problem with these glucose levels is that they’ve sort of been determined based on people who are following the standard North America diet, which we know is high in carbohydrates, starches or fine carbohydrates. All these really opposite foods of the low carbohydrate, high fat diet that a lot of us are trying to follow or the ketogenic diet. Now, I, myself, am keto adapted and I follow a very strict ketogenic diet 95% of the time. I’m still human, guys, so cut me some slack for the 5% of the time that I’m off my game. ​But my blood sugar levels are typically between 3 and 3.9 mmol/L, which translates into 50 to … or sorry 54 to 70 mg/dL. So, that 65 to 99 mg/dL is considered to be normal by government standards here in Canada, the 54 to 70 is considered to be common amongst ketogenic population. A lot of my patients too, who follow ketogenic diet, they’re getting sugars between 3 and 3.9 or between 54 and 70. What does it mean? What is normal? What is acceptable for someone who’s keto adapted? We’re still learning. I usually gauge how my body’s feeling at a certain blood sugar level. I let that determine whether or not it’s normal for me. Hypoglycemia is not defined as a set of numbers. It’s defined as a set of symptoms, so dizziness, mental fatigue, shaking, palms sweaty, hands. That defines hypoglycemia. It’s a list of symptoms.

​I have so many patients in clinic, who are so used to their blood sugar levels being super high, like somewhere around 360, which is about 20 mmol/L for our Canadian friends, and once they drop down to half of that, 180 or 10, they start to feel hypoglycemic because they’re so used to running higher. Sometimes, it takes a body a little while to adapt. This happened to me when I first went on a keto diet. My blood sugar levels dropped and I didn’t feel so great, so I had to cut back on my fasting a little bit. My body adapted to having these lower blood sugar levels. It started fueling on fat more efficiently at the same time and I started feeling fantastic. Now, I feel really great when my blood sugar level’s 3 or 54, I feel fantastic. I feel on top of the world and my body’s fueling nicely on fat. …More

[atomicspacebunny]

What I am trying to discover is SAFE LIMITS for those of us who are monitoring ourselves carefully and what is safe to advise others who are FEELING REALLY GOOD and taking reasonable precautions.

Preferably as citable research papers, but case studies and other reports are also useful both in lieu of peer review hard science and as an adjunct.

Megan Ramos was the very first one (a guinea pig as she humorously calls it) in Dr. Jason Fung’s practice to combine therapeutic fasting with the ketogenic diet (to find out its affects on the human body) as she describes it here in this video:

Megan Ramos - 'Practical Fasting: The Use of Therapeutic Fasting in a Clinical Setting’

Research:

[1] Therapeutic use of intermittent fasting for people with type 2 diabetes as an alternative to insulin

[Karim_Wassef]

we are ketone consumers from birth

watch 6:45 minutes in…

glucose is only necessary for a small % of overall cells. The liver regulates down to the minimum needed.

[Herb_Martin]

Phinney says that when his friends performed that study, they drove the participants’ serum glucose down to levels that normally cause coma or death, but the guys were fine. I love his line, “But the only people having palpitations were the ones in the white coats.”

Of course, no IRB in its right mind would authorize such a study today.

I believe this is the writeup of the study I have in mind. If not, it’s a very similar study.
“Resistance to Symptomatic Insulin Reactions after Fasting,” Drenick et al., 1972)

This one is excellent with blood glucose as low a 9 (not just 30), and ketones in the range of 3.8 to 12.6

These subjects were in a metabolic ward and being closely monitored so “don’t try this at home kids” is perhaps good advice but it does indicate that if there is significant fat adaptation with ketones sufficiently present that technical hypoglycemia is not likely to be a health issue in subjects that remain symptom-free.

Still working my way through all that is above. Thanks again everyone.

[PaulL]

What is a dangerous (or what’s safe) LOW blood glucose level for a fully fat adapted person who is on a ketogenic diet or fast with ketones at a high level and who is experiencing NO SYMPTOMS?

The study by Drenick et al. to which I linked earlier claims that “Glucose concentrations as low as 0.5 mmoles/liter (9 mg/100 ml) failed to precipitate hypoglycemic reactions.”

[Karim_Wassef]

Herb - I finally got around to Paul’s post about glucagon…

Turning diabetes upside down

I really recommend reading it since it changes the paradigm to a glucagon dominant model and insulin as the co-pilot.

Basically (my interpretation) - the first function of metabolism is to provide critical energy to critical organs … brain, red blood cells, kidneys. To do that, there is a minimum threshold of glucose needed since those cells don’t have mitochondria. So… if glucose drops below that threshold, glucagon steps in to “liberate” glucose from glycogen, amino acids or fat.

He draws the line at 2mmol/l (36 mg/dL) but I’ve gone below that.

More interestingly - he says that without glucagon, the glucose excisions stop. Likewise, not having insulin doesn’t seem to cause a problem and glucose will naturally get depleted.

I would LOVE to hear Dr Bikman’s response to this. I’m not sure what the alternative mechanisms that regulate blood glucose would be.

Then he goes on to say that very low blood glucose (through drug use) was positively correlated with higher mortality!! This is where I just need someone else to read the article and confirm my reading.

[PaulL]

I’m not sure I fully agree with Dr. Kendrick’s picture of glucagon and its role in diabetes, though I’m not sure he’s wrong, either. I definitely respect him, however, and it occurs to me that I never watched the lecture by Professor Unger that he mentions early in his post, so I think I’d better do that and reserve judgement in the meantime.

However, I also know of no reason to doubt Drenick’s study, either, which would seem to contradict Kendrick. Something to bear in mind, on the other hand, is that Drenick’s subjects were all in ketosis, whereas the normal understanding of what levels of glucose are safe is based on people eating the standard Western diet, and the rules often do appear to change when we eat ketogenically.

To add to the confusion, Professor Bikman has challenged the notion that the brain requires glucose, saying that he has been unable to find any data to support it. Whereas George Cahill, the seminal researcher on fasting, is pretty clear that the brain needs glucose, and I can’t imagine that Bikman is unaware of his work.

Sorry to sound to back-and-forth. More study is called for, obviously. Damn you, keto! Am I really going to have to get a graduate degree in biochemistry? Really?

[Fasti]

I have same issue with high ketones. Constantly above 4+ mmol if I’m ~keto carb (10-20g). Also they just go off the measuring range (8mmol) after 2 days of fasting or prolonged very low carb. I see my hypoglycemia symptoms appear BG values between 2.3-2.7 mmol (41.4 - 48.6).

I haven’t measured it from the blood with ~high carb tactic, but at least Ketonix plummets down when eating more carbs, more quickly if it’s more juicy carbs. So I guess my insulin production is somewhat still working.

I also have weird values from the moment I started keto (3 years ago). I wish I would have measured before the day when I started as I was on ~0% added fat, the only fat coming from meat, with just about half fruits and half green leafy vegetables for about a year. This also showed up on first yearly control (fasting BG at 7.0mmol). No one had any clue how to direct me, because “I was eating healthy”, so I found about keto and started on it. After first day of keto: BG 3.7 mmol (67) and ketones 5.9 mmol. And the values haven’t really changed. Joint pains (especially in fingers) vanished within a week (was a problem for a ~decade), so never going back to constant high processed carbs.

No idea if I’m fat adapted, but the more ketones are in my blood, the worse I feel. I tried multi day water + electrolyte fasting and had to stop after 4 days because of internal chills started appearing. Maybe because even thou I have ~25% fat, my absolute fat weight is very low and those fat cells can’t churn out energy fast enough. Although why are my blood ketones sky-high then? Not able to being used?

So far on this modified 5:2 (what Mercola is talking about in KetoFast) my gut feels way better as I can finally fast periodically without symptoms (out side of gut symptoms, gut always felt good while fasting). So for me it might be that I need to cycle the macros. Also I’m pretty sure I have been destroying my gut for a ~decade before going keto.

Sadly I have never seen any mentions about this issue on any source. Also this is my first time ever discovering someone else having this “problem”!

[carolT]

More interestingly - he says that without glucagon, the glucose excisions stop. Likewise, not having insulin doesn’t seem to cause a problem and glucose will naturally get depleted.

If we’re going to the mouse experiments he mentioned, they started with Type-1 diabetic mice, so no insulin at all. Then they wiped out their pancreatic alpha cells to kill glucagon production. I guess someone could try doing this in a human T1D model but… no way that’s getting approved soon.
The mechanisms of natural depletion may involve physical activity? I’d also not try to overload the system with exogenous glucose as us humans are likely to do.
On the other hand, it does tell us useful information about how an excess of FFA released from adipose can drive glucose higher. Which brings me back to my pet theory that an individual’s I:G ratio says a lot about what their GKI will look like.

Then he goes on to say that very low blood glucose (through drug use) was positively correlated with higher mortality!! This is where I just need someone else to read the article and confirm my reading.

As to this part, I believe he’s talking about increasing the insulin to “solve” the high glucose problem of diabetes by getting glucose in a normal range, not having naturally low glucose due to ketones in the system. The problem is that insulin is the cause of many other issues that lead to all cause mortality so increasing it is counter-productive.

researchers, doctors and every medical professional has believed for decades that if people with diabetes lowered their blood sugars to normal levels, they could not only prevent the complications from diabetes, but also reduce the risk of dying from heart disease.

[Karim_Wassef]

researchers, doctors and every medical professional has believed for decades that if people with diabetes lowered their blood sugars to normal levels, they could not only prevent the complications from diabetes, but also reduce the risk of dying from heart disease.

He’s going against this though… arguing that too low blood glucose increases risk of all cause mortality.

‘Until last week, researchers, doctors and every medical professional has believed for decades that if people with diabetes lowered their blood sugars to normal levels, they could not only prevent the complications from diabetes, but also reduce the risk of dying from heart disease. But the Accord Study, (for Action to Control Cardiovascular Risk in Diabetes), a major NIH study of more than 10,000 older and middle-aged people with type 2 diabetes has found that lowering blood sugar actually increased their risk of death.2’

[carolT]

Yes, he’s against using insulin to lower a T2D glucose into normal range. Doctors never prescribe an amount of insulin that gets you to subnormal. They’re happy if they can reduce A1C to 6 or 7. They typically leave you a good margin above normal so you don’t have unintended hypoglycemic episodes. It’s the added insulin, not low glucose, that’s bad for mortality.

[keep in mind, most T2s can see 300 glucose easily]

Here’s the linked article: http://www.diabetes-book.com/normal-blood-sugars-questioned/

Due to the surprising results of the ACCORD study, they abruptly halted that part of the study which aggressively tried to manage blood sugars to normal levels, which calls into question just how patients with type 2 diabetes should be managed.

[carolT]

You might enjoy reading about how insulin relates to heart disease here: https://cholesterolcode.com/beyond-the-lipid-hypothesis-insulin/

[Fasti]

Think I have found the cause for my constant high ketone values. Way too much oxalates (everyday spinach, cacao snips, many more) keeping my body in some “sick”-state that is causing liver to make ketones. Assuming this as when I have had clear fever and sickness, my ketones skyrocket even if I have had some carbs like yogurt, which in less sick-state would lower the ketone production. My CRP values (ESR and Ferritin too) were also elevated for at least last 5 years (10-60) and doctor couldn’t link it to anything because no other values were out of range (even CT scan provided a healthy person). I linked some of the CRP fluctuations to eating too much cacao nips year ago.

Haven’t measured my ketone blood levels, but my ketone breath meter results have plummeted down to “normal to low”-range (tells how much liver is producing ketones). BG at 4.5mmol (81), which is my average before this discovery too.

So far 2 weeks on ~0 oxalates (spoon of sauerkraut + slice of lemon), rest sensible animal products and oxalate related mitigation. As an added bonus, hunger gone instantly.

So in summary: I think being “sick” might make body to produce lots of ketones to at least expect elevated energy needs.