Glucose loading cures everything?

[S.Holmes]

Dr. Stephens' new book:
Restored Hope: A Neuroscience Guide to Optimal Brain and Human Function

slktxt.io/11pKR/11458429

[CrumblingCookie]

I've been looking into vitamin B6, the crucial differences in its vitamers, and their impact on liver.
It looks very worthwhile to what dextrose protocol people, myself included, are struggling with.

First off, for closing in on the topic:
Not only vitamin B1 (Thiamin) is much reduced in alcoholics, but to an equal extent also vitamin B6!
So whenever raising the topic of Thiamin, and high-dose thiamin therapy (HDT), and Costantini, I think we also need to include awareness for B6, especially in its active vitamer of pyridoxal-5-phosphate (PLP, P5P).
Vitamin B6 is also reported to be much reduced in many hospitalized people especially, and in folks over 64years of age.
Especially in the latter group, there's an association between sarcopenia with B6-deficiency, with B6 proving to be an exercise-mimetic!
There appears to be a general association between B6-deficiency and inflammatory responses/diseases, too.
Then, there are mixed and both very tissue and time -specific (sometime opposing) effects of vitamin-B6 deficiency on glycogen stores across the body (heart, skeletal muscles, liver).
As for the liver, the glycogen stores seem to be about equal before exercise, but during and after exercise (or (emotional) stress?) the liver glycogen stores deplete much quicker in B6-deficiency, pointing towards a greater all-body glycogen store and utilization in B6-sufficiency.
That's something in the general direction of what we want to achieve, right?

Then, it's also widely accepted that supplementing PLP even in normal=healthy subjects raises AST and ALT, which are PLP-dependent liver enzymes. Now, raised liver enzymes in the serum are usually a bad sign. But what we are seeing with PLP supplementation is probably more a reversal of falsely low serum liver aminotransferase levels as in: The same amounts of hepatocytes are being damaged and releasing their enzymes into circulation, but the low quantity of those enzymes in this case is reflective of the low cytosolic content of these enzymes within the perishing hepatocytes.
On the other hand, some few long-term PLP users indeed progress into cirrhosis or carcinoma of the liver for which "The cause remains uncertain; possibilities included aldehyde stress from PLP and pyridoxal, or toxicity of PLP photodegradation [especially from liquid PLP suspensions prepared in pediatrics] products" and so the jury's still out.

Now, to the glucose loading, brain restoration, concussions, the impress of trauma, and especially of early-life trauma of nutritional, physical and emotional kinds.
As we all know, early life trauma messes up things for life, especially so with regard to the rate of metabolism and the predominance of serotonin, a high-stress basal state, conditions of literally freezing-up in conditions of stress as the impaired third way of response instead of fight-or-flight, the helplessness etc., as retold by dozens of cited studies and findings by haidut and even mainstream psychology.
There seems to be a helpful connection with PLP:
There are lots of studies titled similar to
Pyrithioxine in the prevention of late consequences of intrauterine and postnatal hypoxia and malnutrition in new-born babies. Act Nerv Super (Praha). 1978 Feb;20(1):85-6.
(that's a Czech one), which unfortunately I cannot source the full texts of. Indeed, there are lots of studies particularly from the former Eastern Block which looked into B6 with regard to autism, epilepsy, learning difficulties, hypoxia, concussion, low protein (LP) or low calorie (LC) malnutrition, e.g.
[Developmental dysphasia: assessment of the drug treatment efficacy],
Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova, 2012, Volume: 112, Issue:7 Pt 2:

    To assess the efficacy of treatment with encephabol, we examined 40 children, 
aged from 3 to 5 years, with developmental dysphasia. All patients were randomized into two equal groups: 
group 1 received encephabol (suspension form, daily dosage 200-250 mg, or 12-15 mg/kg) during 2 months; 
group 2 did not receive this medication. 
In the first group, there was a significant improvement of expressive and impressive speech and speech attention; 
the active vocabulary and a number of phrases in colloquial speech increased by a factor of 3 versus 1.5 in the control group. 
After the treatment with encephabol, the parents reported the decrease in motor disturbances, psychosomatic disorders, 
the improvement of attention and the emotional state of the children.

Let me elucidate what "encephabol" is. It's also called pyritinol or pyrithioxine and a semi-synthetic vitamin B6 analog, bonding 2 compounds of pyridoxine together with a disulfide bridge.
Quoting off wikipedia: "It is approved for "symptomatic treatment of chronically impaired brain function in dementia syndromes" and for "supportive treatment of sequelae of craniocerebral trauma" in various European countries".
Craniocerebral trauma. Chronically impaired brain functions regardless of origin. hmm!

According to this study in rats, Pyrithioxine is much more selectively effective yet with its benefits much less extensive than ordinary pyridoxine. And what's really important to know is that pyridoxine is still very crap in comparison to PLP.
This study
The effect of pyrithioxine and pyridoxine on individual behavior, social interactions, and learning in rats malnourished in early postnatal life
Psychopharmacologia. January 1976Volume 46, pages 325–332, (1976)

showed that those early life brain insults of protein or caloric restrictions could be significantly alleviated by a proper form of B6!

The treatment with pyrithioxine reduced significantly behavioral disturbances in adult LP rats
 except the increase of intersignal reactions which was even potentiated. 
Pyridoxine was less effective but normalized the increased number of intersignal reactions both in LP and LC rats. 
The effect of pyridoxine treatment in early life on learning and dyadic interaction of adult LC rats was interesting. 
There was significant improvement in all registered parameters of avoidance learning and a significant increase of sexual acts was recorded.

Also, reading this article
Malnutrition and the Brain: Changing Concepts, Changing Concerns
The Journal of Nutrition Volume 125, Supplement 8, August 1995, Pages 2212S-2220S

just rings all the bells of what Dr. DS is on about as the authors are making it very clear that it's not even the malnutrition per se doing most of the long-lasting harm but the emotional responses concomitant with such stressful events:

"However, recent neuropharmacological research has revealed long-lasting, if not permanent, 
changes in brain neural receptor function resulting from an early episode of malnutrition. 
These more recent findings indicate that the kinds of behaviors and cognitive functions 
impaired by malnutrition may be more related to emotional responses to stressful events 
than to cognitive deficits per se, the age range of vulnerability to 
these long-term effects of malnutrition may be much greater than we had suspected 
and the minimal amount of malnutrition (hunger) necessary 
to produce these long-term alterations is unknown."

Again, this also reminds me of the extensive findings off the Massachusetts Starvation Experiment (MSE) and the very long-lasting aftereffects on its participants from "a meager" 3-4 months of not even full starvation but a caloric cut to about c. 1800 kcal IIRC (The MSE was a trial run for what came to be applied, intensely and extensively for several years, on the population of the defeated German Reich). Remember that lots of folks actually subsist on such caloric intakes nowadays and that metabolism and body overall body temperatures were much higher a hundred years ago.

[Ecstatic_Hamster]

I did take 13mg of ioderal for several years, and selenium, with no good or bad effects. Not noticeable at all. I took thyroid too. And was cold all the time. It did nothing for me.

Anyhow, glucose continues. I’m up to 260 or 300g per day. Given the glucose, I easily gain body fat so I keep trying to cut down on fats. I weighed a lot today but it’s probably from water weight last few days.

No ill effects really. I’m working on specific issues that I want to fix and the jury is out. I’m about 1 month in.

[S.Holmes]

@Ecstatic_Hamster said in Glucose loading cures everything?:

I did take 13mg of ioderal for several years, and selenium, with no good or bad effects. Not noticeable at all. I took thyroid too. And was cold all the time. It did nothing for me.

Anyhow, glucose continues. I’m up to 260 or 300g per day. Given the glucose, I easily gain body fat so I keep trying to cut down on fats. I weighed a lot today but it’s probably from water weight last few days.

No ill effects really. I’m working on specific issues that I want to fix and the jury is out. I’m about 1 month in.

I hope the glucose helps you! Keep us posted!

[S.Holmes]

@CrumblingCookie said in Glucose loading cures everything?:

I've been looking into vitamin B6, the crucial differences in its vitamers, and their impact on liver.
It looks very worthwhile to what dextrose protocol people, myself included, are struggling with.

First off, for closing in on the topic:
Not only vitamin B1 (Thiamin) is much reduced in alcoholics, but to an equal extent also vitamin B6!
So whenever raising the topic of Thiamin, and high-dose thiamin therapy (HDT), and Costantini, I think we also need to include awareness for B6, especially in its active vitamer of pyridoxal-6-phosphate (PLP, P5P).
Vitamin B6 is also reported to be much reduced in many hospitalized people especially, and in folks over 64years of age.
Especially in the latter group, there's an association between sarcopenia with B6-deficiency, with B6 proving to be an exercise-mimetic!
There appears to be a general association between B6-deficiency and inflammatory responses/diseases, too.
Then, there are mixed and both very tissue and time -specific (sometime opposing) effects of vitamin-B6 deficiency on glycogen stores across the body (heart, skeletal muscles, liver).
As for the liver, the glycogen stores seem to be about equal before exercise, but during and after exercise (or (emotional) stress?) the liver glycogen stores deplete much quicker in B6-deficiency, pointing towards a greater all-body glycogen store and utilization in B6-sufficiency.
That's something in the general direction of what we want to achieve, right?

Then, it's also widely accepted that supplementing PLP even in normal=healthy subjects raises AST and ALT, which are PLP-dependent liver enzymes. Now, raised liver enzymes in the serum are usually a bad sign. But what we are seeing with PLP supplementation is probably more a reversal of falsely low serum liver aminotransferase levels as in: The same amounts of hepatocytes are being damaged and releasing their enzymes into circulation, but the low quantity of those enzymes in this case is reflective of the low cytosolic content of these enzymes within the perishing hepatocytes.

Now, to the glucose loading, brain restoration, concussions, the impress of trauma, and especially of early-life trauma of nutritional, physical and emotional kinds.
As we all know, early life trauma messes up things for life, especially so with regard to the rate of metabolism and the predominance of serotonin, a high-stress basal state, conditions of literally freezing-up in conditions of stress as the impaired third way of response instead of fight-or-flight, the helplessness etc., as retold by dozens of cited studies and findings by haidut and even mainstream psychology.
There seems to be a helpful connection with PLP:
There are lots of studies titled similar to
Pyrithioxine in the prevention of late consequences of intrauterine and postnatal hypoxia and malnutrition in new-born babies. Act Nerv Super (Praha). 1978 Feb;20(1):85-6.
(that's a Czech one), which unfortunately I cannot source the full texts of. Indeed, there are lots of studies particularly from the former Eastern Block which looked into B6 with regard to autism, epilepsy, learning difficulties, hypoxia, concussion, low protein (LP) or low calorie (LC) malnutrition, e.g.
[Developmental dysphasia: assessment of the drug treatment efficacy],
Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova, 2012, Volume: 112, Issue:7 Pt 2:

    To assess the efficacy of treatment with encephabol, we examined 40 children, 
aged from 3 to 5 years, with developmental dysphasia. All patients were randomized into two equal groups: 
group 1 received encephabol (suspension form, daily dosage 200-250 mg, or 12-15 mg/kg) during 2 months; 
group 2 did not receive this medication. 
In the first group, there was a significant improvement of expressive and impressive speech and speech attention; 
the active vocabulary and a number of phrases in colloquial speech increased by a factor of 3 versus 1.5 in the control group. 
After the treatment with encephabol, the parents reported the decrease in motor disturbances, psychosomatic disorders, 
the improvement of attention and the emotional state of the children.

Let me elucidate what "encephabol" is. It's also called pyritinol or pyrithioxine and a semi-synthetic vitamin B6 analog, bonding 2 compounds of pyridoxine together with a disulfide bridge.
Quoting off wikipedia: "It is approved for "symptomatic treatment of chronically impaired brain function in dementia syndromes" and for "supportive treatment of sequelae of craniocerebral trauma" in various European countries".
Craniocerebral trauma. Chronically impaired brain functions regardless of origin. hmm!

According to this study in rats, Pyrithioxine is much more selectively effective yet with its benefits much less extensive than ordinary pyridoxine. And what's really important to know is that pyridoxine is still very crap in comparison to PLP.
This study
The effect of pyrithioxine and pyridoxine on individual behavior, social interactions, and learning in rats malnourished in early postnatal life
Psychopharmacologia. January 1976Volume 46, pages 325–332, (1976)

showed that those early life brain insults of protein or caloric restrictions could be significantly alleviated by a proper form of B6!

The treatment with pyrithioxine reduced significantly behavioral disturbances in adult LP rats
 except the increase of intersignal reactions which was even potentiated. 
Pyridoxine was less effective but normalized the increased number of intersignal reactions both in LP and LC rats. 
The effect of pyridoxine treatment in early life on learning and dyadic interaction of adult LC rats was interesting. 
There was significant improvement in all registered parameters of avoidance learning and a significant increase of sexual acts was recorded.

Also, reading this article
Malnutrition and the Brain: Changing Concepts, Changing Concerns
The Journal of Nutrition Volume 125, Supplement 8, August 1995, Pages 2212S-2220S

just rings all the bells of what Dr. DS is on about as the authors are making it very clear that it's not even the malnutrition per se doing most of the long-lasting harm but the emotional responses concomitant with such stressful events:

"However, recent neuropharmacological research has revealed long-lasting, if not permanent, 
changes in brain neural receptor function resulting from an early episode of malnutrition. 
These more recent findings indicate that the kinds of behaviors and cognitive functions 
impaired by malnutrition may be more related to emotional responses to stressful events 
than to cognitive deficits per se, the age range of vulnerability to 
these long-term effects of malnutrition may be much greater than we had suspected 
and the minimal amount of malnutrition (hunger) necessary 
to produce these long-term alterations is unknown."

Again, this also reminds me of the extensive findings off the Massachusetts Starvation Experiment (MSE) and the very long-lasting aftereffects on its participants from "a meager" 3-4 months of not even full starvation but a caloric cut to about c. 1800 kcal IIRC (The MSE was a trial run for what came to be applied, intensely and extensively for several years, on the population of the defeated German Reich). Remember that lots of folks actually subsist on such caloric intakes nowadays and that metabolism and body overall body temperatures were much higher a hundred years ago.

Do you know the range of dose required to heal the body from these stresses? I had many traumas as a child: emotional abuse, sexual abuse (incident), malnutrition/starvation from birth to age 20, and others. (My father punished my mother for minor offenses by withholding the meager sum he gave her to buy groceries. She had to feed a family of 6 on a pittance.)

I just restocked my pyridoxine today. Do you think P5P is safer than pyridoxine in high or adequate doses?

[Ecstatic_Hamster]

@S-Holmes I have always thought so. P5P is all I recommend.

[CrumblingCookie]

@Ecstatic_Hamster said:

P5P is all I recommend.

I'm also scrapping all supplement products with pyridoxine, which I had used or bookmarked, from future use to replace them with products which contain only P5P=PLP.

@S-Holmes said:

Do you know the range of dose required to heal the body from these stresses?

I'm sorry you had to live through such experiences. It really hurts just from reading about it.
In that pyrithioxine in Developmental dysphasia study above they used an enormous 12-15mg/kg or 200-250mg in 3-5 year old kids. A scaringly high dose.

I've looked into treatments of inborn vitamin B6-dependent epilepsies because they go most in-depth with the clinical practicalities of vitamer B6 dosing.
Clinicians for those recommend equally high doses of between 10-50(at the very most!)mg/kg of either PLP or pyridoxine (PN).
Which is wild, as that would come to >840mg PLP daily for an 70kg adult. On the other hand they use to set an upper threshold of 200-300mg/daily for all - be they adults or lightweight infants.
That essentially breaks down the dosage question to empiric observation of the individual. It's being stressed to use as low a dose as needed for clearance of symptoms.
Given the absence of clearly distinguishable acute fits as a marker in non-epileptics, I suppose dosing PLP comes down to subjective intuition and feeling over the short and long term, as well as meeting recognition of possible adverse effects with an ensuing dose-reduction.

I reckon that, ultimately, it's most important to go with steady, regular PLP supplementation. Similarly as with dextrose. Similarly as with oral thiamin.
Those epilepsy clinicians recommend 4-6x daily dosing. I.e. every 4-6 hours.
I think this seems very sensible. That matches up with what I saw in graphs of serum-concentration over time for PN, PL, PLP. It matches up with my own experiences of needing B6 several times daily irrespective of how high the single dose.

To summarize my own experiences with pyridoxine are btw the following:
PN quickly shows initial benefits during the first 1-2 days. Then everything turns sour and even though some things like twitchings gradually improved over the course of months, in general PN feels like an uncomfortable trade-off and overall burden for me. Empirically, I agree with saying anything above c. 10mg PN per single dose becomes intolerable and reverses most benefits.

What those clinicians for inborn B6 conditions also clearly stress is that PLP should preferably always be used, from the start and in general, because PLP is about equally inexpensive as PN and - irrespective of the different pharmacokinetics which apply to everyone "normal" - because of those genetic epilepsy conditions with inhibited conversion of PN->PLP.
They further acknowledge that there's no "pharmaceutical grade"/"pharmacopeia"/"USP" PLP, so "non-drug" chemical supplies or nutraceuticals must be used even for those patients with clearly diagnosed genetic causes. Which I'm finding strange and wrong, but unsurprising.

I'm planning to take 25mg PLP 3-5x per day along with the dextrose. Which translates to 1-2mg PLP/kg. I'll need to find out which single dose feels good and then take that as regularly as possible.

[gentlepotato]

Has anyone read the new book? Wondering what it's about.

[CrumblingCookie]

@S-Holmes
Please try the P5P if you can and share your practical findings.
I've only been taking it for a couple of days. In the mornings I've now twice woken up almost kind of rested, stirring long-lost memories of how sleep and waking up should be and used to be in times over 20 years ago.
It's shows completely different effects than pyridoxine for me. I reckon 15-20mgs every 2-4 hours would be both enough and ideal.

(From taking P5P, prepare for more regular/frequent glucose cravings and increased protein cravings and a maybe acute tension headaches from a new need for and tolerance of magnesium.)
(I feel it's important to strictly avoid any supplemental pyridoxine.)

[S.Holmes]

@CrumblingCookie said in Glucose loading cures everything?:

@S-Holmes
Please try the P5P if you can and share your practical findings.
I've only been taking it for a couple of days. In the mornings I've now twice woken up almost kind of rested, stirring long-lost memories of how sleep and waking up should be and used to be in times over 20 years ago.
It's shows completely different effects than pyridoxine for me. I reckon 15-20mgs every 2-4 hours would be both enough and ideal.

(From taking P5P, prepare for more regular/frequent glucose cravings and increased protein cravings and a maybe acute tension headaches from a new need for and tolerance of magnesium.)
(I feel it's important to strictly avoid any supplemental pyridoxine.)

I just took a second dose. Nothing to report yet.

[sharko]

It seems that you are mainly relying here on beautiful stories of a doctor who has no idea how the body works and mostly he was a little lucky to discover the wonders of sugar.

You went too far with the theories in my opinion.

I think it is nothing more than the difference between the combination with fructose can burden the liver and sucrose which is not sure what its breakdown can be in everyone's intestine.

Instead of trying to complete the logic of Ray Peat's research, you are dealing with a doctor who does not understand anything and looking for answers in irrelevant places.

Most of the answers to all your problems already exist in Ray Peat's research

You searched for a miracle cure and found yourself exerting yourself to the same extent as you would if you had invested in understanding bioenergetics in depth.

Experimenting and collecting evidence, cases and reactions is extremely important, but I would recommend continuing to try to build the logic according to the bioenergetic approach and not try to reinvent the wheel. It won't go well for sure...