19

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In what context can there be a glucose deficiency? Is infection the real cause? (Ridiculously long.)

Answered on September 12, 2014
Created October 06, 2011 at 4:43 PM

Is dietary carbohydrate even necessary at all? In the recent past, this question wouldn't even be asked. Knowing that the body can manufacture its own glucose via gluconeogenesis, dietary carbohydrate has long been considered non-essential. Recently, however, The Jaminets, in The Perfect Health Diet (PHD), and on their website, have advocated getting glucose needs met through direct consumption, and express the view that glucose deficiency is imminent in those who consume fewer than 50g of carbohydrate. The PHD recommends 400-600 calories of carbohydrate per day, or 100-150g.

In contradistinction to this recommendation, Phinney and Volek, in The Art and Science of Low Carbohydrate Living (ASLCL), describe a functional gap in human physiology, at precisely this range of carbohydrate intake. The argument goes that if enough carbohydrate is consumed to suppress ketogenesis -- more than 50g -- then at this range you have barely enough glucose to feed your brain and no alternative source of fuel. The only way to support any extra glucose needs under this condition, such as may be needed by extra activity, is to consciously notice how much glucose you need and supply it at frequent intervals. On the other hand, if one consumes little enough carbohydrate for long enough that ketoadaptation occurs, then the brain's needs can mostly be met by ketones, and moreover, most of the muscle fueling will be provided by fat. Glucose needs drop tremendously in response to not eating any.

At first glance, it may seem intuitive that the best dietary intake of glucose is to predict and match the body's glucose needs. This would "save" the body from having to manufacture any. There are problems with this idea, however. First of all, just because glucose needs to be manufactured, if not provided, and this is obviously not without cost, there is no evidence that the process is difficult or "stressful". (See http://paleohacks.com/questions/25449/why-do-people-consider-ketosis-stressful-to-the-body.) And ingesting glucose for use is not "free" either; to the contrary, the knock on effects of ingesting glucose -- the effects of raised blood glucose, as well as the effects of the raised insulin that is rushed in to cope with the raised glucose, and the extra oxidative stress involved in carbohydrate metabolism -- may be much more "stressful", than the gluconeogenetic process.

Moreover, guessing at precise carbohydrate need seems like an error-prone pursuit. The risks of underestimation have already been mentioned, but overestimating may also be costly. Carbohydrate is a "preferred" fuel, which is an amusing and misleading anthropomorphic way of saying that the body needs to get rid of it right away: when it's available it will always be used first, because to do otherwise would be harmful. Using it may also be harmful, in comparison with using fat or ketones, at least insofar as it creates more oxidative stress and inflammation.

After considering the possible pitfalls of trying to estimate and provide for the precise glucose needs of the body, a questionable evolutionary strategy, it seems more plausible, at least to me, that the best method of getting what glucose you need, is the hands-off approach of letting your liver (and kidneys) make it on an as needed basis, responding directly to internal fuel needs. The remaining question that needs to be answered is whether this is adequate. Can this approach really lead to a so-called "glucose deficiency."

I want to pause here and stress that there is a big difference in saying that it is implausible that the body cannot meet its glucose needs without dietary glucose, and saying that the glucose deficiency symptoms that Jaminet has outlined don't exist. It would be foolish (not to mention disrepectful) to ignore the real experience that some people, including Jaminet himself have reported, just because it doesn't fit a theoretical framework. To quote Namby Pamby (a comment to this answer: http://paleohacks.com/questions/68656/dr-ron-rosedales-recent-posts-about-safe-starches-what-do-you-think/68748#68748), some people get the following symptoms on ketogenic levels of carbohydrate, that disappear with sufficient added starch: "constipation due to mucosal dryness; fungal toes and scaly feet that resembled an alligator's; dry eyes (although for me this may have other causes); fainting spells when getting up from a chair; possible hypothyroidism, as I display subclinical symptoms; and low LIBIDO!" So my question is, what is really going on here? I want to draw an analogy that might be appreciated in the paleosphere. It is indisputable that low carb diets can reverse metabolic syndrome in a large proportion of affected people. Does this mean that carbohydrate consumption is the cause of metabolic syndrome? No, it doesn't imply that. Similarly, it may be the case that Jaminet's Syndrome can be reversed by eating 150 grams of carbohydrate a day. Does this mean that lack of dietary glucose causes Jaminet's Syndrome? No, it doesn't imply that either.

I haven't read the PHD (I'd like to!), but based on this blog post, the Jaminets' belief that gluconeogenesis cannot provide all the glucose we need comes from adding to the brain's requirements at least the following: glycosolated proteins, glycoproteins, immune function (to create ROS's), feeding infections, and athletic activity.

I'd like to focus on the point about feeding infections, because it is unique in being not necessarily a normal body function, and therefore it is plausible that the body didn't evolve with this functional requirement. To summarize an idea that I think also comes to me from Jaminet, the character of infectious disease has, in recent decades(?) changed from the type that acutely affects its host, often killing him, to the type that lives like a parasite, crippling the function of the individual to a greater or lesser degree. So it may well be the case that a significant number of modern folk are carrying with them an infection that needs feeding. And it seems plausible to me that such beasts could steal glucose from the system that cannot be replaced quickly enough to avoid problems in the host who is not supplementing with carbohydrates. Moreover, there is a rumour I've been hearing that I haven't verified, that fungal infections are particularly insidious, because they are not weakened by glucose deprivation, being able to survive on ketones as well. If this is true, and a fungal infection is strongly present in an individual, then it could explain why this person's health would worsen, rather than improve, on a ketogenic diet, and specifically that they would have fungal, scaly skin as a telltale symptom.

So what I am proposing is that the preponderance of people who are not faring well on a ketogenic diet, but who thrive on a middling level of carbohydrates, which otherwise, it may be argued, should be the worst possible range, is that there is an infectious epidemic that is impairing many bodies' natural abilities to provide enough glucose. If this is correct, then being constrained to eat starch is a condition similar to the condition of being constrained to eat a ketogenic diet for the "metabolically damaged", i.e. those with metabolic syndrome. A possible test of this hypothesis is that if the infection could be identified and cured, the person would be expected to then tolerate a ketogenic diet without experiencing glucose deficiency.

100fd85230060e754fc13394eee6d6f1

(18696)

on September 07, 2013
at 01:28 AM

You're right. Moreover, it seems to vary from person to person.

543a65b3004bf5a51974fbdd60d666bb

(4493)

on May 14, 2012
at 11:02 PM

I feel your pain. i suggest you post your own new question so you hopefully get some help. your queries will just get missed buried here. You can always just paste all your text from above as a new question and add a link to reference this question http://paleohacks.com/questions/68915/in-what-context-can-there-be-a-glucose-deficiency-is-infection-the-real-cause . I wish i had some answers for you myself.

9d43f6873107e17ca4d1a5055aa7a2ad

on October 07, 2011
at 04:32 AM

Well, I don't know Adrianna and I wasn't talking about people who have seen a doctor, I was talking about the hundreds of people who self-diagnose with candida who have not been tested for it.

Ed71ab1c75c6a9bd217a599db0a3e117

(25477)

on October 07, 2011
at 03:50 AM

Her name is adrianna for those of you wanting confirmation.

Ed71ab1c75c6a9bd217a599db0a3e117

(25477)

on October 07, 2011
at 03:50 AM

One of the posters on the monster mda thread showed up in my office in nashville unannounced and wanted a hack.....she got a work up and guess what we found? Overgrowth of candida. She posted her findings on the thread. So now you know one person. I know hundreds because im a clinician who tests people with problems who want to know WHY instead of arguing about macronutrients and the Kitavans.

100fd85230060e754fc13394eee6d6f1

(18696)

on October 06, 2011
at 09:37 PM

Haha. Thanks, Paul. I may not agree with all of your conclusions, but I've learned a lot from your work, and hope to reconcile our ideas as fairly I can.

21fd060d0796fdb8a4a990441e08eae7

(24543)

on October 06, 2011
at 08:19 PM

You love that analysis at the margin, huh Paul :) There's no keeping a good economist down.

9e20abb05f3f6e3cc4bb107f8980aecd

(5939)

on October 06, 2011
at 08:06 PM

Great question Ambimorph. I agree that in some people infections are a significant marginal contributor to glucose needs, and make zero-carb diets intolerable.

77877f762c40637911396daa19b53094

(78467)

on October 06, 2011
at 08:05 PM

Not only that, but also it depends on how fast you swallow :D :P If you swallow good, you will have lower sugar surges. Its all in the paper, read it :)

77877f762c40637911396daa19b53094

(78467)

on October 06, 2011
at 08:01 PM

In experiments with phagocytic index starch was indeed pretty well toelrated, it reduced immunity only by around 10% comparing to 50% of refined stuff. I guess it then depends on how well u digest starch. Copy number variation is big and this also depends on the time of the day. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2377015/

100fd85230060e754fc13394eee6d6f1

(18696)

on October 06, 2011
at 07:38 PM

And damage is not necessarily bad, either, as in exercise, as you mention. What doesn't kill you makes you stronger, at least sometimes.

100fd85230060e754fc13394eee6d6f1

(18696)

on October 06, 2011
at 07:37 PM

True. Inflammation itself is necessary. It's a response to damage. What's not good is lingering inflammation.

100fd85230060e754fc13394eee6d6f1

(18696)

on October 06, 2011
at 07:34 PM

Thanks! You know the points you make about alcohol being "preferred", and also alcohol being health-promoting in small doses, reminds me of a related idea I was thinking about. Just as KGH suggests that ketosis might be hormetic. It might be the other way around. Maybe carbohydrate intake is hormetic. Or maybe they both are. Maybe the best diet is like Melissa's and alternates.

77877f762c40637911396daa19b53094

(78467)

on October 06, 2011
at 07:33 PM

@Ambimorph: Not all cells use OP. What is necessary is fermentation. OFC, you would not exist without OP, but some cells do not have mitos, and sometimes mitos can't deliver (i.e. exercise, again) and sometimes cells can happen to get into hypoxic conditions.

77877f762c40637911396daa19b53094

(78467)

on October 06, 2011
at 07:31 PM

@Ambimorph: Oxidative phosporilation is not necessary. What is necessary is fermentation. OFC, you would die without OP, but some cells do not have mitos, and sometimes mitos can't deliver (i.e. exercise, again).

77877f762c40637911396daa19b53094

(78467)

on October 06, 2011
at 07:29 PM

@Ambimorph: That ROS production that inspired you may very well be physiological. ROS are not necessarily evil (i.e. exercise)

100fd85230060e754fc13394eee6d6f1

(18696)

on October 06, 2011
at 07:29 PM

Re: infections, maybe the nature of infections has changed.

100fd85230060e754fc13394eee6d6f1

(18696)

on October 06, 2011
at 07:28 PM

True. I meant that at higher intensity, the change to a dependence on glucose is mitigated.

77877f762c40637911396daa19b53094

(78467)

on October 06, 2011
at 07:28 PM

@Ambimorph: Its well established that dietary sugar, not glucose metabolism damages immune function. That is not controversial at all.

100fd85230060e754fc13394eee6d6f1

(18696)

on October 06, 2011
at 07:25 PM

Good point. Except for the fungal infection symptom itself, those do sound like deficiencies!

100fd85230060e754fc13394eee6d6f1

(18696)

on October 06, 2011
at 06:59 PM

And I temporarily completely forgot my main source of this idea: http://www.lucastafur.com/2011/05/bioenergetics_08.html "glucose's complete oxidation involves more complex I activity, ultimately promoting more ROS production by the mitochondria"

100fd85230060e754fc13394eee6d6f1

(18696)

on October 06, 2011
at 06:55 PM

This page seems to imply that oxidative phosphorylation is a necessary step of carbohydrate metabolism: http://www.angelfire.com/ak2/chemists/metabolism.html

100fd85230060e754fc13394eee6d6f1

(18696)

on October 06, 2011
at 06:54 PM

Okay. Here's something more concrete, but I don't have the background to fully appreciate. Please help! If it's true that oxidative phosphorylation is a normal part of glucose metabolism, then that implies that glucose metabolism results in oxidative stress. See http://en.wikipedia.org/wiki/Oxidative_phosphorylation

100fd85230060e754fc13394eee6d6f1

(18696)

on October 06, 2011
at 06:34 PM

The idea that glucose metabolism is pro-inflammatory, and not just non-anti-inflammatory, is less established. It might be that it mostly happens in "susceptible" people. Suggestive evidence here: http://circ.ahajournals.org/content/106/16/2067.abstract , http://care.diabetesjournals.org/content/26/5/1589.short , http://www.ajcn.org/content/92/3/634.full http://www.fasebj.org/content/19/6/638.full.pdf , http://www.jbc.org/content/279/13/12126.abstract So, I'll edit to reflect the uncertainty better. Thanks!

6670b38baf0aae7f4d8ac2463ddc37c0

(3946)

on October 06, 2011
at 06:31 PM

Waiting for the mind numbing answers you are sure to receive from this brilliant question.

100fd85230060e754fc13394eee6d6f1

(18696)

on October 06, 2011
at 06:02 PM

Also see http://www.ncbi.nlm.nih.gov/pubmed/18339375 , http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2367001/?tool=pubmed , http://onlinelibrary.wiley.com/doi/10.1002/ana.20062/abstract .

100fd85230060e754fc13394eee6d6f1

(18696)

on October 06, 2011
at 05:58 PM

Well, the less controversial evidence is that ketones are anti-inflammatory. E.g. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2649682/ , http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1940242/?tool=pubmed , http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1865572/?tool=pubmed . But this presupposes existing inflammation. I.e. if you have inflammation, then ketones will reduce it.

Ef4c5b09fdccf73be575d3a0c267fdd9

(2539)

on October 06, 2011
at 05:18 PM

Good luck to anyone attempting to cure it. I am on Fluconazole now to rid mine and while massive improvements have been made, there is still much work to be done. I do believe that Paul is still working on his too, from our discussions. They do seem to be quite insidious, unfortunately. Also, if one does not have sufficient gut flora or establish it during anti-fungal treatment, it seems likely the problem will return very quickly. There is so little research in this area I think we will be in the dark for a while.

Ce41c230e8c2a4295db31aec3ef4b2ab

(32556)

on October 06, 2011
at 05:15 PM

Wow...interesting hypothesis!

9d43f6873107e17ca4d1a5055aa7a2ad

on October 06, 2011
at 05:15 PM

"Using it may also be harmful, in comparison with using fat or ketones, at least insofar as it creates more oxidative stress and inflammation." Where is this from?

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5 Answers

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8
9d43f6873107e17ca4d1a5055aa7a2ad

on October 06, 2011
at 06:47 PM

I think a huge issue here is that many of these people who are saying that glucose deficiency contributed to a fungal infection are self-diagnosing their fungal infections. I'm not saying they do not have fungal infections, but I'm concerned that it could be something else at play like a mineral/vitamin deficiency, particularly considering the number of VLC-ers that consume nothing but muscle meat.

Because there aren't many (I don't know any) people confirming their fungal infections with tests, then we don't know what species are the issue and we can't discuss what these species are metabolizing and whether they can consume ketones. People have told me that these fungal infections don't show up on tests because they are subclinical...but then how do they really know they have fungal infections?

Ed71ab1c75c6a9bd217a599db0a3e117

(25477)

on October 07, 2011
at 03:50 AM

One of the posters on the monster mda thread showed up in my office in nashville unannounced and wanted a hack.....she got a work up and guess what we found? Overgrowth of candida. She posted her findings on the thread. So now you know one person. I know hundreds because im a clinician who tests people with problems who want to know WHY instead of arguing about macronutrients and the Kitavans.

100fd85230060e754fc13394eee6d6f1

(18696)

on October 06, 2011
at 07:25 PM

Good point. Except for the fungal infection symptom itself, those do sound like deficiencies!

Ed71ab1c75c6a9bd217a599db0a3e117

(25477)

on October 07, 2011
at 03:50 AM

Her name is adrianna for those of you wanting confirmation.

9d43f6873107e17ca4d1a5055aa7a2ad

on October 07, 2011
at 04:32 AM

Well, I don't know Adrianna and I wasn't talking about people who have seen a doctor, I was talking about the hundreds of people who self-diagnose with candida who have not been tested for it.

3
21fd060d0796fdb8a4a990441e08eae7

(24543)

on October 06, 2011
at 06:46 PM

This might be an issue: you say that ketogenesis is suppressed at 50g of glucose, and a "middle range" of carbs is a problematic gap for humans.

But what about this, which is lifted from ketotic.org...

"The effect on the blood ketone body concentration of a 100 g oral dose of either alanine, glucose or starch was studied in forty-four healthy men...Starch ingestion caused the blood ketone body concentrations to fall, but to a lesser extent than after alanine or glucose ingestion. After starch ingestion, as after glucose, the mean blood ketone body concentration was rising again at 16.00 (Fig. 1), thus reaffirming the evanescence of the antiketogenic effects of carbohydrate administration."

In other words, given this type of evidence, is there still a weakness in eating 50g of carbs a day? Ketogenesis, if I recall correctly, can't be measured accurately by keto-stix because that is just excess ketones. You can still make ketones though as long as you don't have enough oxaloacetate, or if you have enough MCTs.

100fd85230060e754fc13394eee6d6f1

(18696)

on September 07, 2013
at 01:28 AM

You're right. Moreover, it seems to vary from person to person.

77877f762c40637911396daa19b53094

(78467)

on October 06, 2011
at 08:05 PM

Not only that, but also it depends on how fast you swallow :D :P If you swallow good, you will have lower sugar surges. Its all in the paper, read it :)

77877f762c40637911396daa19b53094

(78467)

on October 06, 2011
at 08:01 PM

In experiments with phagocytic index starch was indeed pretty well toelrated, it reduced immunity only by around 10% comparing to 50% of refined stuff. I guess it then depends on how well u digest starch. Copy number variation is big and this also depends on the time of the day. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2377015/

2
77877f762c40637911396daa19b53094

(78467)

on October 06, 2011
at 07:14 PM

The PHD recommends 400-600 calories of carbohydrate per day, or 100-150g.

I beleive its more like 400-600 calories CHO + PROTEIN

Carbohydrate is a "preferred" fuel, which is an amusing and misleading anthropomorphic way of saying that the body needs to get rid of it right away: when it's available it will always be used first, because to do otherwise would be harmful.

As elaboration, let me post here as appropriate what M. Frantz said:

there appears to be a hierarchy for the autoregulation of substrate utilization and storage that is determined by storage capacity and specific fuel needs of certain tissues.44 For example, alcohol has the highest priority for oxidation because there is no body storage pool for it, and conversion of alcohol to fat is energetically expensive. Amino acids and carbohydrates are next in the oxidative hierarchy. Body proteins are functional, and there are not storage depots for amino acids. There is a limited capacity to store carbohydrate as glycogen, and conversion of carbohydrate to fat is energetically expensive as well. In contrast, there is virtually unlimited storage capacity for fat, largely in adipose tissue, and the storage efficiency of fat is high. Because of the oxidative priority of alcohol and protein, the body has an exceptional ability to maintain their balance across a wide range of intake of each. Carbohydrate oxidation closely matches carbohydrate intake.45,46 Therefore, the amount of fat oxidized or stored is the difference between total energy needs and the oxidation of the other priority fuels???alcohol, protein, and carbohydrate.

So, if carbs are preffered, then alcohol is ultimate fuel. We know a lot about alcohol and know that it can even be healthy in very small doses. The same may very well be true for sugar.

I haven't read the PHD (I'd like to!), but based on this blog post, the Jaminets' belief that gluconeogenesis cannot provide all the glucose we need comes from adding to the brain's requirements at least the following: glycosolated proteins, glycoproteins, immune function (to create ROS's), feeding infections, and athletic activity

He also speaks about theoretical limit because liver can use limited amount of oxygen. See http://goo.gl/8OAC7 topic What limits the liver???s capacity to convert amino acids to glucose?

"Using it may also be harmful, in comparison with using fat or ketones, at least insofar as it creates more oxidative stress and inflammation." Where is this from? ??? Melissa- Hunt Gather Love

Here it goes, for start

http://www.second-opinions.co.uk/leukocytic_index.html http://orthomolecular.org/library/jom/2005/pdf/2005-v20n03-p179.pdf


Amazing post by the way, you are one great lady Ambimorph. Jaminet is very cool dude too, and his place is somehow relaxing.

Since he likes to post music videos on his forum, here is something to listen for everybody while reading this great post.

http://www.youtube.com/watch?v=XHPjpflNssY

100fd85230060e754fc13394eee6d6f1

(18696)

on October 06, 2011
at 07:34 PM

Thanks! You know the points you make about alcohol being "preferred", and also alcohol being health-promoting in small doses, reminds me of a related idea I was thinking about. Just as KGH suggests that ketosis might be hormetic. It might be the other way around. Maybe carbohydrate intake is hormetic. Or maybe they both are. Maybe the best diet is like Melissa's and alternates.

1
Dc12c10d21f8db4d79f40e99bd9ad6a3

on September 07, 2013
at 12:44 AM

Sorry to resurrect, but this was really interesting. I lost a helluva lotta weight on a keto diet. Then I went abroad, caught a bug, took antibiotics- and bam: symptoms of hypothyroid (cold hands, constipation, dark circles under the eyes, weight stalled, went up, down, all around).

Having read Jaminet's article I have upped my carb intake on the understanding that this is caused by glucose deficiency. No idea what (if any) effect this will have on my weight loss. But if the issue is being exacerbated by some fungal infection, which is plausible given the antibiotic use, what then?

I mean, it all fits- long term hypocaloric keto diet, gut dysbiosis, symptoms of low thyroid...so what now? If the thyroid issue is caused by glucose deficiency, do I need to visit a doc or is this something I can fix with diet? What about the possible dysbiosis? How'm I going to explain all this to my doc, who doesn't know I was keto (he offered me pills for weight loss, for goodness sake). I'm in the UK, so really I have a choice of Mainsteam Doc or switch to Another Mainstream Doc, it's not a case of "find a sympathetic one".

Any advice?

543a65b3004bf5a51974fbdd60d666bb

(4493)

on May 14, 2012
at 11:02 PM

I feel your pain. i suggest you post your own new question so you hopefully get some help. your queries will just get missed buried here. You can always just paste all your text from above as a new question and add a link to reference this question http://paleohacks.com/questions/68915/in-what-context-can-there-be-a-glucose-deficiency-is-infection-the-real-cause . I wish i had some answers for you myself.

0
E5c7f14800c5992831f5c70fa746dc5c

(12857)

on October 06, 2011
at 06:42 PM

"most of the muscle fueling will be provided by fat"

Everyones muscles are mostly fueled by fat. The intensity of exercise determines fuel use not what you eat.

Paleo and pre-paleo man probably had more infections than modern day humans.

100fd85230060e754fc13394eee6d6f1

(18696)

on October 06, 2011
at 07:28 PM

True. I meant that at higher intensity, the change to a dependence on glucose is mitigated.

100fd85230060e754fc13394eee6d6f1

(18696)

on October 06, 2011
at 07:29 PM

Re: infections, maybe the nature of infections has changed.

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