Ketogenic Diet: Transitioning, Experiences, Reasons, Cautions ...

[circular]

I remember hearing that people in ketosis often have higher morning blood sugar. It was discussed somewhere in our forums long ago. Since you probably had low insulin which triggers the liver to generate ketones, I'm not sure why the sugar was higher. But this page suggests that it may not necessarily be catabolizing muscle to make sugar...

'The Liver & Blood Sugar'

The liver makes sugar when you need it….
When you’re not eating – especially overnight or between meals, the body has to make its own sugar. The liver supplies sugar or glucose by turning glycogen into glucose in a process called glycogenolysis. [I assume your glycogen was already low or depleted?] The liver also can manufacture necessary sugar or glucose by harvesting amino acids, waste products and fat byproducts. This process is called gluconeogenesis.

I'm not sure where other than muscle the liver might get 'harvested' amino acids, but at least it can apparently also used waste products and fat byproducts. So I think it would be hard to know for certain whether it's catabolizing muscle?

Meanwhile, .5 ketones sounds low for you lately (?), but it's showing what's in storage. I'm wondering if you brain, sleeping deeply off the Klonipin, was eating like crazy to make up for some lost time, both ketones and sugar? By 10:30 your ketones were up from a lower low than lately (?), so I'm thinking they just need more time for storage levels to get back to where you had them. I don't think I would be too concerned unless a pattern forms (hear me working on not over-worrying ?). Having gotten a good night's sleep is probably more important for that short-term snapshot. It's good your tracking so you can see. My last four ketone readings were 1.2, 1.6, 1.3 and then .5 after I ate a few more carbs today, but I don't think I'm catabolizing muscle. Sometimes there are just swings.

Hopefully someone who knows more than I do will help. These are just some off the cuff thoughts.

[circular]

Physiological insulin resistance, that was it. See if this page has anything helpful, or you may find a better one on it. My eyes are crossing.

[Tincup]

I'm looking at notes from a Mercola interview from the recent Chronic Lyme Disease Summit. The title of his interview was "Improving Mitochondrial Health." He was talking a lot about the health benefits of a high-fat diet and ketosis. I have notes I took that say if you fast too long and your body isn't ready for it (i.e., sufficiently keto-adapted), your body will use protein from your lean body mass and convert that to glucose. As a result, you will lose lean body mass. That is a catabolic process.

Mercola recommends that when you're fasting, you should measure your blood glucose when you get up and then every 30 minutes thereafter. Your blood glucose should be dropping for a period of time. When it starts rising, that means you are breaking down the protein in your muscles for sugar. That's when you need to eat. (He didn't say this, but I would guess that you can learn over time how long you can safely fast without having to measure every 30 minutes every day.) But he says that fasting too long is a type of fasting that is "fatally flawed."

In my case, for my glucose to rise to 98 from sleeping 7 hours straight without waking up for my usual middle-of-the-night snack, the only explanation that makes sense is gluconeogenesis. I did my weights routine today to try to offset that catabolic process.

In an interview with a similar topic http://podcast.drpompa.com/episodes/115 ... tochondria, Mercola mentions wearing a continuous glucose monitor (CGM) and also talks about the catabolism indicated by the rise in glucose. I'm not sure you're insufficiently keto adapted. One of the other things that can raise glucose is stress. I learned this years ago when I had friends with a young (4 years old) T1 diabetic. They said when she was sick, it was almost impossible to control her blood sugar well.

I don't test every 30 minutes (and I'm not sure home testing - or even Mercola's CGM, which needs to be correlated with prick testing 2x/day - gives the precision he's assuming), however I tend to have modestly high morning fasting blood sugar, say 98. By the end of my 22 hour fast it is typically in the low 70's. Part of of the high fasting blood sugar can be the "dawn effect." The liver starts cranking out glycogen in the morning to get the day going. If you are physiologically insulin resistant, your fasting sugar can be kind of high.

When you are stressed, for whatever reason, your liver will start kicking out glycogen.

In my case, skipping one eating period (2 out of 24 hours) led to a ketone level of 5.6 mmol/L and glucose of 59 mg/dL. This is indicative of being well adapted as somebody who isn't would take many more days of water fasting to get to this level. I've been fasting 22 hours/day for about 50 weeks. I've yet to have noticeable muscle catabalism or loss of strength.

I still think you've got plenty of fuel (glucose & ketones), so investigating other reasons for your hunger is indicated.

Jimmy Moore had planned to water fast all of January. He fasted something like 28 or 29 days out of 31. He told me he broke it because the stress of traveling caused an insulin spike and created hunger he couldn't deal with, so he broke the fast.

[TheBrain]

I'm wondering if you brain, sleeping deeply off the Klonipin, was eating like crazy to make up for some lost time, both ketones and sugar? By 10:30 your ketones were up from a lower low than lately (?), so I'm thinking they just need more time for storage levels to get back to where you had them. I don't think I would be too concerned unless a pattern forms (hear me working on not over-worrying ?). Having gotten a good night's sleep is probably more important for that short-term snapshot. It's good your tracking so you can see. My last four ketone readings were 1.2, 1.6, 1.3 and then .5 after I ate a few more carbs today, but I don't think I'm catabolizing muscle. Sometimes there are just swings.

Circ, thanks for your thoughts about this matter. I love to think that my brain was eating like crazy with all the deep sleep I got that night from not waking up to eat.

And your reply reminded me that George said it's hard to correlate ketone levels with specific actions.

I'm still not sure what was going on, but I'm no longer getting the higher blood glucose readings in the morning. I'm back in the 80s.

Physiological insulin resistance, that was it. See if this page has anything helpful, or you may find a better one on it. My eyes are crossing.

Thanks for this link. In that article, the first possible reason listed states: "Think of palmitic as a signal molecule to tell the muscles that inhibition of glucose uptake is needed and to tell the liver that increased gluconeogenesis is required because there is no food coming in. Chris Kresser also supports this view."

This makes sense to me. My body is used to food coming in during the middle of the night, but that one night when I slept 7 hours straight, it didn't get that food. Hence, increased gluconeogenesis.

Still, I'm not certain of anything.

[TheBrain]

In an interview with a similar topic http://podcast.drpompa.com/episodes/115 ... tochondria, Mercola mentions wearing a continuous glucose monitor (CGM) and also talks about the catabolism indicated by the rise in glucose. I'm not sure you're insufficiently keto adapted. One of the other things that can raise glucose is stress. I learned this years ago when I had friends with a young (4 years old) T1 diabetic. They said when she was sick, it was almost impossible to control her blood sugar well.

I don't test every 30 minutes (and I'm not sure home testing - or even Mercola's CGM, which needs to be correlated with prick testing 2x/day - gives the precision he's assuming), however I tend to have modestly high morning fasting blood sugar, say 98. By the end of my 22 hour fast it is typically in the low 70's. Part of of the high fasting blood sugar can be the "dawn effect." The liver starts cranking out glycogen in the morning to get the day going. If you are physiologically insulin resistant, your fasting sugar can be kind of high.

When you are stressed, for whatever reason, your liver will start kicking out glycogen.

In my case, skipping one eating period (2 out of 24 hours) led to a ketone level of 5.6 mmol/L and glucose of 59 mg/dL. This is indicative of being well adapted as somebody who isn't would take many more days of water fasting to get to this level. I've been fasting 22 hours/day for about 50 weeks. I've yet to have noticeable muscle catabalism or loss of strength.

I still think you've got plenty of fuel (glucose & ketones), so investigating other reasons for your hunger is indicated.

Jimmy Moore had planned to water fast all of January. He fasted something like 28 or 29 days out of 31. He told me he broke it because the stress of traveling caused an insulin spike and created hunger he couldn't deal with, so he broke the fast.

George, thanks for your thoughts on this matter. I do know I was stressed. The dog issue was weighing on me, and I had my first appointment with a functional medicine MD coming up on 5/31. I was excited about the appointment but worried about having to wake up at 5 am in order to arrive in time for my 9 am appointment. (It was as minimum 2 1/4-hour drive, but rush-hour traffic in Raleigh can be bad.) I hate intentionally getting up that early, but he had a last-minute cancellation, so I grabbed the slot.

However, I suspect my glycogen stores are typically low and become depleted while I'm sleeping. So if stress makes the liver kick out glycogen, I'd guess this wouldn't apply in my case.

My new MD would like for me to have two-week continuous glucose monitoring to see what's going on in the area "under the curve." Because I see an endocrinologist, he recommended I ask for that through him. I have since made my request and am waiting for a response. My new MD made a lot of other recommendations, which I can get into later. But he is concerned about my sleep issues and waking up hungry, along with other issues. I'm hoping he can help me get to the bottom of this hunger issue and resolve it.

It's great that you've had no noticeable muscle catabalism or loss of strength with your ketogenic diet. However, you are very active, much more so than I am. In fact, it sounds to me like you are an athlete. Might you be building muscle every day with your active lifestyle?

On the doggie matter, my husband and I are doing a two-week trial with Layla! If it doesn't work out (but I'm confidant it will), we will foster her until a permanent home can be found. She is such a sweetie. She's a German Shepherd who doesn't bark or shed! How unusual is that?! Oddly enough, her former owner developed Alzheimer's and could no longer care for her. His wife didn't pick up the slack (I'm sure she was overwhelmed), and Layla was left outside and would only get food occasionally. Her healthcare needs were completely ignored, and she got very sick. And who knows how well the husband was able to care for Layla prior to his diagnosis. She's five years old now but has been under the care of the rescue for nine months or so.

[circular]

This is the part above I found most interesting:

The liver also can manufacture necessary sugar or glucose by harvesting amino acids, waste products and fat byproducts. This process is called gluconeogenesis.

I think it would be hard to know if one's liver needed to catabolize muscle or whether there were enough raw ingredients already floating around.

I'm not sure if this is the same, but Dr. Gundry tests 'free fatty acids'. Mine were .73 which HDLabs said was 'high risk', but which didn't bother Dr. Gundry at all, who said it just means you're burning fat for fuel. He likes it in HDLabs 'high risk' zone. This was before I was consciously ketogenic, but would have been on the lower carb end of carb eating. I don't know how quickly these fluctuate, or whether the liver harvests these if they are 'fat byproducts' (?) for gluconeogenesis. I'd be interested in knowing more about this. It appears free fatty acids are another paradoxical marker and probably worth their own post which I'll start and come back and link to here … viewtopic.php?f=29&t=2310&p=26699#p26699

[TheBrain]

Circ, one thing that isn't clear to me is whether "amino acids, waste products, and fat byproducts" would be used in gluconeogenesis all together or separately. My limited understanding is that amino acids need to be a raw material for gluconeogenesis to occur. But I am not certain of that. I'm basing what I know on what I've heard Dan Kalish and Mercola say about gluconeogenesis.

[Tincup]

From Dom D'Agostino,
Interesting article in Journal of Biological Chemistry: "Acetoacetate accelerates muscle regeneration and ameliorates muscular dystrophy in mice" http://www.jbc.org/content/early/2015/1 ... 0.full.pdf

ABSTRACT
Acetoacetate (AA) is a ketone body and acts as a fuel to supply energy for cellular activity of various tissues. Here, we uncovered a novel function of AA in promoting muscle cell proliferation. Notably, the functional role of AA in regulating muscle cell function is further evidenced by its capability to accelerate muscle regeneration in normal mice and ameliorates muscular dystrophy in mdx mice. Mechanistically, our data from multi-parameter analyses consistently support the notion that AA plays a non-metabolic role in regulating muscle cell function. Finally, we show that AA exerts its function through activation of the Mek1-Erk1/2-cyclin D1 pathway, revealing a novel mechanism in which AA serves as a signaling metabolite in mediating muscle cell function. Our findings highlight profound functions of a small metabolite as signaling molecule in mammalian cells.

Moreover, the efficiency of AA in promoting cell proliferation was similar to that of IGF1 (insulin-like growth factor 1), a cytokine well known for its ability to stimulate C2C12 cell proliferation. Notably, we observed that AA potentiated the stimulatory effect of IGF1 on C2C12 cell proliferation and partially antagonized the inhibitory effect of myostatin (MSTN) (Fig. 1d).

Acetoacetate is made in the liver from fat when in ketosis. Betahydroxybuterate is the storage form and what is measured in serum ketones. AA is converted to this for storage.

[circular]

I suspect this June 2016 article is a bit of a red herring, but maybe not? The title and abstract raise concerns about elevated ketones stemming from ketogenic diets (and other sources), but I wonder if the full text ends up just showing the issues are only in the context of higher blood sugar and insulin in diabetics, ie the long known about ketoacidosis. Just wonder what the paper actually says and it's behind a paywall.

Hyperketonemia and ketosis increase the risk of complications in type 1 diabetes.

Abstract

Diets that boost ketone production are increasingly used for treating several neurological disorders. Elevation in ketones in most cases is considered favorable, as they provide energy and are efficient in fueling the body's energy needs. Despite all the benefits from ketones, the above normal elevation in the concentration of ketones in the circulation tend to illicit various pathological complications by activating injurious pathways leading to cellular damage. Recent literature demonstrates a plausible link between elevated levels of circulating ketones and oxidative stress, linking hyperketonemia to innumerable morbid conditions. Ketone bodies are produced by the oxidation of fatty acids in the liver as a source of alternative energy that generally occurs in glucose limiting conditions. Regulation of ketogenesis and ketolysis plays an important role in dictating ketone concentrations in the blood. Hyperketonemia is a condition with elevated blood levels of acetoacetate, 3-β-hydroxybutyrate, and acetone. Several physiological and pathological triggers, such as fasting, ketogenic diet, and diabetes cause an accumulation and elevation of circulating ketones. Complications of the brain, kidney, liver, and microvasculature were found to be elevated in diabetic patients who had elevated ketones compared to those diabetics with normal ketone levels. This review summarizes the mechanisms by which hyperketonemia and ketoacidosis cause an increase in redox imbalance and thereby increase the risk of morbidity and mortality in patients [ie, diabetic ones only?].

It sounds like the abstract is poorly written and conflates ketoacidosis with ketogenic diets, but it's hard to say without seeing the paper.

[apod]

I suspect this June 2016 article is a bit of a red herring, but maybe not? The title and abstract raise concerns about elevated ketones stemming from ketogenic diets (and other sources), but I wonder if the full text ends up just showing the issues are only in the context of higher blood sugar and insulin in diabetics, ie the long known about ketoacidosis. Just wonder what the paper actually says and it's behind a paywall.

Hyperketonemia and ketosis increase the risk of complications in type 1 diabetes.

Abstract

Diets that boost ketone production are increasingly used for treating several neurological disorders. Elevation in ketones in most cases is considered favorable, as they provide energy and are efficient in fueling the body's energy needs. Despite all the benefits from ketones, the above normal elevation in the concentration of ketones in the circulation tend to illicit various pathological complications by activating injurious pathways leading to cellular damage. Recent literature demonstrates a plausible link between elevated levels of circulating ketones and oxidative stress, linking hyperketonemia to innumerable morbid conditions. Ketone bodies are produced by the oxidation of fatty acids in the liver as a source of alternative energy that generally occurs in glucose limiting conditions. Regulation of ketogenesis and ketolysis plays an important role in dictating ketone concentrations in the blood. Hyperketonemia is a condition with elevated blood levels of acetoacetate, 3-β-hydroxybutyrate, and acetone. Several physiological and pathological triggers, such as fasting, ketogenic diet, and diabetes cause an accumulation and elevation of circulating ketones. Complications of the brain, kidney, liver, and microvasculature were found to be elevated in diabetic patients who had elevated ketones compared to those diabetics with normal ketone levels. This review summarizes the mechanisms by which hyperketonemia and ketoacidosis cause an increase in redox imbalance and thereby increase the risk of morbidity and mortality in patients [ie, diabetic ones only?].

It sounds like the abstract is poorly written and conflates ketoacidosis with ketogenic diets, but it's hard to say without seeing the paper.

I came across these the other day:
https://www.quora.com/How-is-methylglyo ... in-ketosis
http://www.ncbi.nlm.nih.gov/pubmed/16037240

In Aubrey De Gray's book:


There's a paragraph:

one established effect of very low-carbohydrate diets of the Atkins type is to bring down both triglyceride levels and the body’s total exposure to carbohydrates, so some advocates have hypothesized that these diets world reduce a person’s AGE burden. Unfortunately, it turns out that the metabolic state that these diets induce (the notorious “ketosis”) has the unfortunate side effect of causing a jump in the production of the oxoaldehyde methylglyoxal, a major precursor of AGEs that is also, ironically, produced within cells of diabetic patients when they are forced to take in more glucose than they can immediately process … methylglyoxal is far more chemically reactive than blood sugar (up to 40,000 times more reactive, in fact), and is known to cause wide-ranging damage in the body, of which AGE cross-links are but one example. This potentially makes the Atkins diet a recipe for accelerated AGEing

(And here I am, cycling between high levels of ketones and high amounts of post-workout carbohydrates in a small eating window.) Tricky.

This one comes to mind: