Sugar Was Working Great For A Few Weeks, But Then Caused Muscle Stiffness

[brigadierbarty]

and pain.

I was having 5 cups OJ with starchy meals and this was working great for me. See my recent thread where I saw temps of 100 and was able to stop taking thyroid hormone. I was seeing other benefits too, like lower blood sugars, and old injuries started healing. Basically everything was going great.

The problem is that around week 3 I developed pretty severe back/neck muscle pain and stiffness. It's definitely the orange juice because I've actually experienced this before. A few years ago I got sick and couldn't keep most food down, so I was drinking a lot of V8 and OJ (didn't know anything about Peat, I was just doing this instinctively). I developed the exact same problem back then, and it resolved after I stopped drinking OJ. Similarly, I've been off OJ for a few days now and the pain and stiffness are resolving.

I thought maybe it was too much potassium but I checked electrolytes and they're all well within normal range. Liver enzymes and other standard bloodwork are all normal too. According to cronometer I'm hitting all nutrient targets except vitamin E (strict no PUFA). I was getting about 6 cups dairy. Also of note, supplementing with ribose a few months back caused the exact same problem.

Anyone experienced this before? Doing a search, it looks like sugar causes muscle stiffness in a lot of people, eg people who drink a lot of soda. I don't know if Peat has addressed this.

Should I just cut back on sugar? Maybe 2-3 cups OJ daily is enough.

 

[Diokine]

I think that this is related to transient hyperinsulinemia leading to moderate insulin resistance, particularly in the basal ganglia. This disrupts cholinergic/dopaminergic signalling and can lead to stiffness. The insulin resistance can be caused by several things, viral factors, gut inflammation, circadian disruption, etc. Additionally if you are just slamming OJ and not allowing your mental processes to integrate it into your physiology (ie. tasting it fully,) it can contribute to increased levels of insulin.

Any pain or strange sensations in your ears or jaw, or a heaviness or "stickyness" in the eyes?

 

[Dan W]

Might be interesting to compare another type of juice in case it's something specific to the OJ (ripeness issues, citrus, enzymes, etc.).

 

[brigadierbarty]

I think that this is related to transient hyperinsulinemia leading to moderate insulin resistance, particularly in the basal ganglia. This disrupts cholinergic/dopaminergic signalling and can lead to stiffness. The insulin resistance can be caused by several things, viral factors, gut inflammation, circadian disruption, etc. Additionally if you are just slamming OJ and not allowing your mental processes to integrate it into your physiology (ie. tasting it fully,) it can contribute to increased levels of insulin.

Any pain or strange sensations in your ears or jaw, or a heaviness or "stickyness" in the eyes?

Negative on those symptoms. I will say I'm chugging it to protect my teeth. But see my comment on bananas below.

Might be interesting to compare another type of juice in case it's something specific to the OJ (ripeness issues, citrus, enzymes, etc.).

Actually now that I think about it I had a very mild version of this back when I was eating lot of bananas. I was doing a lot of weightlifting and trying to eat sugar peri-workout. So my guess is most sugar will do this to me, or at least fruit sugar. I was eating about 8 bananas per day at that time, so the amount of sugar was comparable, about 120g daily. OTOH maybe it really was the potassium, and my muscles were taking up the excess potassium to keep blood levels normal?

 

[Dan W]

Any chance the muscle pain / stiffness matches the behavior of trigger points?
Trigger points: diagnosis and management. - PubMed - NCBI

Not that I have any great insight if it does, but I vaguely suspect my trigger point pain is related to serotonin, low CO2, electrolyte changes, and something-something prostaglandins. So that might give you some things to observe when trying different fruits or different levels of sugar intake.

 

[brigadierbarty]

BTW @Diokine, I have a fasting insulin pending, to use as a measure of insulin resistance, that we can compare with my baseline. It'll be interesting to see how it changed. Based on how my blood sugars have been I think it will be lower.

 

[HDD]

Do you still have good temperatures and pulse @brigadierbarty ?

 

[brigadierbarty]

Do you still have good temperatures and pulse @brigadierbarty ?

My temps seem to be coming down, hands are colder. I've had to modify my diet so I'm not sure if it's due to lower caloric intake, but I don't think so.

 

[HDD]

My temps seem to be coming down, hands colder. I've had to modify my diet so I'm not sure if it's due to lower caloric intake, but I don't think so.

Your pain/stiffness could be hypo symptoms. Do you get adequate protein?

 

[brigadierbarty]

Your pain/stiffness could be hypo symptoms. Do you get adequate protein?

Well the pain/stiffness are resolving as my temps are coming down. I get about 100g protein and I'm pretty sedentary.

 

[brigadierbarty]

A bit OT but just saw this @Diokine.

It may be possible to stop the progression of Parkinson's disease with a drug normally used in type 2 diabetes, a clinical trial suggests.

First hints Parkinson's can be stopped - BBC News

 

[Diokine]

@brigadierbarty

Thanks for the link, fascinating stuff. Aspirin in combination with glycine is probably nearly as effective and safer.

Regulation of Glucose Homeostasis by GLP-1
Thus, GLP-1 released from L cells activates vagal sensory neurons that project to the brainstem in order to initiate efferent vagal reflexes via the parasympathetic branch of the autonomic nervous system. Parasympathetic neurons release acetylcholine (ACh) in the islets in order to activate muscarinic cholinergic receptors that stimulate Ca2+ mobilization in β-cells, and these neurons also release PACAP to stimulate cAMP production in β-cells. The net effect is an indirect and neurally mediated action of GLP-1 to potentiate GSIS.84

GSIS - glucose stimulated insulin response

Modulation by the hypothalamus of glucagon and insulin secretion in rabbits: studies with electrical and chemical stimulations.
It is concluded that the actions of acetylcholine in the VMH, probably though activation of nicotinic receptor, and of epinephrine in the LHN are important for hypothalamic modulation of the selective releases of glucagon and insulin, respectively. (Endocrinology 108: 605, 1981)

VMH - ventromedial hypolthalamic nucleus

The metabolic response to ingested glycine
Overall, the data suggest that oral glycine stimulates the secretion, either directly or indirectly, of a gut hormone that potentiates or is additive with the effect of insulin in stimulating the removal of glucose from the circulation. It also inhibits the effect of glucagon on endogenous glucose production. Nevertheless, this remains only a speculation at present.

Aspirin stimulates insulin and glucagon secretion and increases glucose tolerance in normal and diabetic subjects.


Edit:

This is probably the best primer I have found on the subject

Minireview: The Role of the Autonomic Nervous System in Mediating the Glucagon Response to Hypoglycemia

 

[Xisca]

Just my 2c about mixing OJ and starch... I think they do not get along well for digestion. That would be the same for bananas if they are mixed with other types of fruits that are acidic by nature.

I have my fruits with dairies, goat cheese for me, or even they go well with liver! Today I had liver with tomatoes and then I added honey in the plate.

I think starches mix well only with fat and vegetables. The last 2 and especially some fiber, if not a harsh one IMO, prevent the sharp rise in glucose, thus insuline problems.

 

[lampofred]

Are you making sure to eat plenty of protein whenever you eat starch/drink sugar? This happened to me too and it was because too many carbs relative to protein was increasing my serotonin/lactic acid/ammonia. B vitamins especially B1 will help a lot in clearing out the lactic acid and ammonia in the short term, and shifting away from serotonin dominance will help in the long term.

 

[brigadierbarty]

Ok I think I know what was going on - it was probably the vitamin C. Doing a search, it seems that some people develop muscle pain after taking vitamin C.

Vitamin C causes pain

Interestingly, based on those posts it seems that people who have this kind of reaction to vitamin C usually have some pre-existing problem, like fibromyalgia, "chronic Lyme", or fluoroquinolone toxicity. For example, one guy says that he used to be able to handle high doses of vitamin C, but ever since taking Levaquin even smaller doses cause problems. I have no history of fibromyalgia or those other conditions, but a while back I was entertaining the idea that I might have mild chronic fatigue syndrome (which is why I was taking ribose). What most of these conditions (fibromyalgia, fluoroquinolone toxicity, CFS) have in common is that they supposedly all involve mitochondrial dysfunction. Here's a study showing vitamin C can inhibit mitochondrial biogenesis. It's probably not a coincidence that ribose gave me the same symptoms.

Oral administration of vitamin C decreases muscle mitochondrial biogenesis and hampers training-induced adaptations in endurance performance

Results: The administration of vitamin C significantly (P = 0.014) hampered endurance capacity. The adverse effects of vitamin C may result from its capacity to reduce the exercise-induced expression of key transcription factors involved in mitochondrial biogenesis. These factors are peroxisome proliferator–activated receptor co-activator 1, nuclear respiratory factor 1, and mitochondrial transcription factor A. Vitamin C also prevented the exercise-induced expression of cytochrome C (a marker of mitochondrial content) and of the antioxidant enzymes superoxide dismutase and glutathione peroxidase.

Conclusion: Vitamin C supplementation decreases training efficiency because it prevents some cellular adaptations to exercise.

Oral administration of vitamin C decreases muscle mitochondrial biogenesis and hampers training-induced adaptations in endurance performance

Another theory is that oxalate can cause fibromyalgia symptoms, and since vitamin C is metabolized into oxalate, it can cause the same problems. Eg

The GP who gave up fruit and veg to cure her aches and pains | Daily Mail Online

So @Dan Wich you were probably right. What juices do people usually recommend besides OJ?

@Diokine, my fasting insulin went down, and so did my HOMA-IR score, from ~1 to .8, so it looks like I'm less insulin resistant if anything.

 

[Diokine]

@brigadierbarty

This was an interesting one to think about. My first thought is that vitamin C shouldn't cause an increase in muscle pain of this type, and in fact I would think it would helpful therapy. It does seem possible there is a mechanism where something like that could be possible, though I still think it's quite a stretch. I'm working under the hypothesis that muscle pain of this type (tight muscles in neck, shoulders, trigger points and painful joints) is essentially caused by disruptions in acetylcholine/dopamine metabolism.

@Dan Wich

You brought up a very good point with trigger points, my view is that they are in the same class of pathology and share a common foundation in acetylcholine/dopamine.

Mechanisms of Myofascial Pain
The persistence of myofascial trigger points requires a self-sustaining positive feed-forward process. Simons presented the integrated hypothesis for myofascial trigger points to offer an explanation [4]. The integrated hypothesis is a six-link chain that starts with step (1): the abnormal release of acetylcholine. This triggers step (2): increased muscle fiber tension which is seen as the taut band found in a myofascial trigger point. The taut band is thought to constrict blood flow that leads to step (3): local hypoxia. The reduced oxygen disrupts mitochondrial energy metabolism reducing ATP and leads to step (4): tissue distress and step (5): the release of sensitizing substances. These sensitizing substances lead to pain by activation of nociceptors (pain receptors) and also lead to step (6): autonomic modulation that then potentiates step (1): abnormal acetylcholine release.

Etiology of Myofascial Trigger Points
The integrated TrP hypothesis postulates that in myofascial pain motor endplates release excessive acetylcholine, which is evidenced histopathologically by the presence of sarcomere shortening [1]. These areas of intense focal sarcomere contraction have been described in animals and humans.

And so disruptions in parts of the brain that control movement (I focus particularly on the basal ganglia) can drastically alter the sympathetic nervous tone and cause over excitation and contraction, and lack of relaxation in the entire body. Postural muscles of the neck and spine are especially effected. I think what generally initiates this process is a functional insulin resistance in the brain, resulting in fatigue and loss in sensitivity of neural tissue. This functional insulin resistance can be caused by many things - viral factors, gut issues, circadian disruption, inflammation, etc. The point I am trying to make is that it is possible to have reduced glucose uptake in the brain with physiological levels of insulin in the blood.

Vitamin C and glucose utilize some of the same transport mechanisms, so it's conceivable that a lot of it could transiently decrease uptake of glucose. I tend to think that even if that were a possible mechanism the effects would be so minimal as to be irrelevant. Ascorbic acid is found throughout the brain and nervous system, and is generally critically protective. You mentioned something about floroquinolone toxicity, CFS, causing issues with vitamin C, which is interesting. Those problems typically involve glutamate-type toxicity especially involving NMDA receptors. Insulin response in the brain and NMDA/GABA activity is closely related, and so in general over-excitation and neural-cell stress will contribute to functional insulin resistance.


Insulin in Central Nervous System: More than Just a Peripheral Hormone

More recently, some authors reported that insulin modulated the expression of NMDA receptors, increasing neuronal Ca2+ influx and reinforcing synaptic communication between neurons [153], and also modulated long-term potentiation, a molecular model of learning [126, 154]. This was further supported by insulin-mediated control of cell surface glutamate and GABA receptor density (via the modulation of receptor targeting to the membrane and endocytic internalization), thus affecting synaptic plasticity [31]. Additionally, we showed that insulin prevented the decrease in GABA and glutamate uptake and their increased extrasynaptosomal levels in rat synaptosomes after oxidative stress and/or type 2 diabetes [155, 156]. Apparently, such neuromodulatory role of insulin could arise from its direct effect on neurotransmitter transport or from decreased ATP levels and subsequent reversal of the amino acid transporters [155, 156], thus protecting neurons against damaging effects of excitotoxicity or oxidative stress.

Insulin Action in Brain Regulates Systemic Metabolism and Brain Function

There is a big connection between ascorbic acid and acetycholine, especially so when there is a lot of excitation via NMDA. Is it possible to think of cases where ascorbic acid could cause issues, in the context of altered NMDA and glutamatergic activity? Definitely. I still think the foundation of the problem is functional insulin resistance.


A vitamin as neuromodulator: ascorbate release into the extracellular fluid of the brain regulates dopaminergic and glutamatergic transmission.
In fact, by facilitating glutamate release, ascorbate may indirectly oppose the action of dopamine, though the nature of the neostriatal dopaminergic-glutamatergic interaction is far from settled. Ascorbate also may alter the redox state of the NMDA glutamate receptor thus block NMDA-gated channel function.

Ascorbic Acid and the Brain: Rationale for the Use against Cognitive Decline
Evidence of altered glutamate transport (e.g., changes in EAAT2 and EAAT3 transporters) is seen in human AD postmortem samples, particularly in patients with hippocampal sclerosis [16]. AA is released from astrocytes as glutamate is taken up, and this relationship is termed a hetero-exchange although this does not fully represent how the two processes are tethered [17,18]. It is presumed that AA moderates the oxidative stress induced by glutamate [19] and so is protective against overstimulation and cell death. This relationship has been more closely investigated in relation to Huntington’s disease [20,21,22], which also involves cell death. GLT-1 is a high affinity transporter that relies on Na-dependent transport across an electrochemical gradient for rapid removal of glutamate from the synapse. It is sensitive to oxidative stress, and disruption of the transporter leads to glutamate accumulation and hyperstimulation of receptors. Memantine is the first of a new class of drugs for AD that blocks NMDA receptors and its efficacy suggests that further research into glutamatergic signaling and AD is warranted. Therefore, as the role of glutamate transport and NMDA receptors in AD becomes clearer, this may be revealed as another key area where high intracellular AA levels are critical for brain health.

Vitamin C Function in the Brain: Vital Role of the Ascorbate Transporter (SVCT2)
Ascorbate has been proposed to function as a neuromodulator of both dopamine- and glutamate-mediated neurotransmission (reviewed in [15,104]). More recent studies relating ascorbate modulation of glutamate dynamics with changes in rat behavior show that such modulation is complex, since it depends on the site in the brain studied, level of behavioral activity, and level of extracellular ascorbate [102,130,131]. The mechanism(s) by which ascorbate affects neuronal transmission have not been established, but could relate in part to redox changes in the N-methyl-D-aspartate (NMDA) receptor. For example, ascorbate has been shown to protect neurons from excitotoxicity induced by activation of the NMDA receptor and it prevented glutamate-induced cell damage and death in cultured cerebellar granule cells [132,133]. This could be due to redox modulation of the receptor itself by ascorbate [134,135], or to direct scavenging of ROS generated by receptor activation. A more severe stress of ischemia releases large amounts of ascorbate from brain cells [136], which is associated with glutamate uptake by neurons and glia [99,137]. Removal of extracellular glutamate by such a process, would also decrease excitotoxicity caused by activation of cell surface and synaptic glutamate receptors [15,104,138].

Safety of fluoroquinolones: An update
A possible reconciliation of these discrepancies is that fluoroquinolones can also induce excitatory effects through direct activation of N-methyl-D-aspartate (NMDA) and adenosine-receptor mechanisms. Thus, it may be that only under specific conditions of sufficient CNS penetration, coupled with threshold antagonism of inhibitory pathways (GABA) and stimulation of excitatory pathways (NMDA, adenosine), that observable CNS symptoms are manifested.

 

[Dan W]

@Diokine, I've only begun to dig into your references and I'm already learning things I've been wondering about for years. Thank you!

 

[Texon]

@Diokine So how about Oolong tea (for gaba and some caffeine) with milk and honey/sugar? BTW the low oxalate diet from the British gp particularly resonates with me, and I'm a 65 yo male.

 

[Texon]

@brigadierbarty

This was an interesting one to think about. My first thought is that vitamin C shouldn't cause an increase in muscle pain of this type, and in fact I would think it would helpful therapy. It does seem possible there is a mechanism where something like that could be possible, though I still think it's quite a stretch. I'm working under the hypothesis that muscle pain of this type (tight muscles in neck, shoulders, trigger points and painful joints) is essentially caused by disruptions in acetylcholine/dopamine metabolism.

@Dan Wich

You brought up a very good point with trigger points, my view is that they are in the same class of pathology and share a common foundation in acetylcholine/dopamine.

Mechanisms of Myofascial Pain
The persistence of myofascial trigger points requires a self-sustaining positive feed-forward process. Simons presented the integrated hypothesis for myofascial trigger points to offer an explanation [4]. The integrated hypothesis is a six-link chain that starts with step (1): the abnormal release of acetylcholine. This triggers step (2): increased muscle fiber tension which is seen as the taut band found in a myofascial trigger point. The taut band is thought to constrict blood flow that leads to step (3): local hypoxia. The reduced oxygen disrupts mitochondrial energy metabolism reducing ATP and leads to step (4): tissue distress and step (5): the release of sensitizing substances. These sensitizing substances lead to pain by activation of nociceptors (pain receptors) and also lead to step (6): autonomic modulation that then potentiates step (1): abnormal acetylcholine release.

Etiology of Myofascial Trigger Points
The integrated TrP hypothesis postulates that in myofascial pain motor endplates release excessive acetylcholine, which is evidenced histopathologically by the presence of sarcomere shortening [1]. These areas of intense focal sarcomere contraction have been described in animals and humans.

And so disruptions in parts of the brain that control movement (I focus particularly on the basal ganglia) can drastically alter the sympathetic nervous tone and cause over excitation and contraction, and lack of relaxation in the entire body. Postural muscles of the neck and spine are especially effected. I think what generally initiates this process is a functional insulin resistance in the brain, resulting in fatigue and loss in sensitivity of neural tissue. This functional insulin resistance can be caused by many things - viral factors, gut issues, circadian disruption, inflammation, etc. The point I am trying to make is that it is possible to have reduced glucose uptake in the brain with physiological levels of insulin in the blood.

Vitamin C and glucose utilize some of the same transport mechanisms, so it's conceivable that a lot of it could transiently decrease uptake of glucose. I tend to think that even if that were a possible mechanism the effects would be so minimal as to be irrelevant. Ascorbic acid is found throughout the brain and nervous system, and is generally critically protective. You mentioned something about floroquinolone toxicity, CFS, causing issues with vitamin C, which is interesting. Those problems typically involve glutamate-type toxicity especially involving NMDA receptors. Insulin response in the brain and NMDA/GABA activity is closely related, and so in general over-excitation and neural-cell stress will contribute to functional insulin resistance.


Insulin in Central Nervous System: More than Just a Peripheral Hormone

More recently, some authors reported that insulin modulated the expression of NMDA receptors, increasing neuronal Ca2+ influx and reinforcing synaptic communication between neurons [153], and also modulated long-term potentiation, a molecular model of learning [126, 154]. This was further supported by insulin-mediated control of cell surface glutamate and GABA receptor density (via the modulation of receptor targeting to the membrane and endocytic internalization), thus affecting synaptic plasticity [31]. Additionally, we showed that insulin prevented the decrease in GABA and glutamate uptake and their increased extrasynaptosomal levels in rat synaptosomes after oxidative stress and/or type 2 diabetes [155, 156]. Apparently, such neuromodulatory role of insulin could arise from its direct effect on neurotransmitter transport or from decreased ATP levels and subsequent reversal of the amino acid transporters [155, 156], thus protecting neurons against damaging effects of excitotoxicity or oxidative stress.

Insulin Action in Brain Regulates Systemic Metabolism and Brain Function

There is a big connection between ascorbic acid and acetycholine, especially so when there is a lot of excitation via NMDA. Is it possible to think of cases where ascorbic acid could cause issues, in the context of altered NMDA and glutamatergic activity? Definitely. I still think the foundation of the problem is functional insulin resistance.


A vitamin as neuromodulator: ascorbate release into the extracellular fluid of the brain regulates dopaminergic and glutamatergic transmission.
In fact, by facilitating glutamate release, ascorbate may indirectly oppose the action of dopamine, though the nature of the neostriatal dopaminergic-glutamatergic interaction is far from settled. Ascorbate also may alter the redox state of the NMDA glutamate receptor thus block NMDA-gated channel function.

Ascorbic Acid and the Brain: Rationale for the Use against Cognitive Decline
Evidence of altered glutamate transport (e.g., changes in EAAT2 and EAAT3 transporters) is seen in human AD postmortem samples, particularly in patients with hippocampal sclerosis [16]. AA is released from astrocytes as glutamate is taken up, and this relationship is termed a hetero-exchange although this does not fully represent how the two processes are tethered [17,18]. It is presumed that AA moderates the oxidative stress induced by glutamate [19] and so is protective against overstimulation and cell death. This relationship has been more closely investigated in relation to Huntington’s disease [20,21,22], which also involves cell death. GLT-1 is a high affinity transporter that relies on Na-dependent transport across an electrochemical gradient for rapid removal of glutamate from the synapse. It is sensitive to oxidative stress, and disruption of the transporter leads to glutamate accumulation and hyperstimulation of receptors. Memantine is the first of a new class of drugs for AD that blocks NMDA receptors and its efficacy suggests that further research into glutamatergic signaling and AD is warranted. Therefore, as the role of glutamate transport and NMDA receptors in AD becomes clearer, this may be revealed as another key area where high intracellular AA levels are critical for brain health.

Vitamin C Function in the Brain: Vital Role of the Ascorbate Transporter (SVCT2)
Ascorbate has been proposed to function as a neuromodulator of both dopamine- and glutamate-mediated neurotransmission (reviewed in [15,104]). More recent studies relating ascorbate modulation of glutamate dynamics with changes in rat behavior show that such modulation is complex, since it depends on the site in the brain studied, level of behavioral activity, and level of extracellular ascorbate [102,130,131]. The mechanism(s) by which ascorbate affects neuronal transmission have not been established, but could relate in part to redox changes in the N-methyl-D-aspartate (NMDA) receptor. For example, ascorbate has been shown to protect neurons from excitotoxicity induced by activation of the NMDA receptor and it prevented glutamate-induced cell damage and death in cultured cerebellar granule cells [132,133]. This could be due to redox modulation of the receptor itself by ascorbate [134,135], or to direct scavenging of ROS generated by receptor activation. A more severe stress of ischemia releases large amounts of ascorbate from brain cells [136], which is associated with glutamate uptake by neurons and glia [99,137]. Removal of extracellular glutamate by such a process, would also decrease excitotoxicity caused by activation of cell surface and synaptic glutamate receptors [15,104,138].

Safety of fluoroquinolones: An update
A possible reconciliation of these discrepancies is that fluoroquinolones can also induce excitatory effects through direct activation of N-methyl-D-aspartate (NMDA) and adenosine-receptor mechanisms. Thus, it may be that only under specific conditions of sufficient CNS penetration, coupled with threshold antagonism of inhibitory pathways (GABA) and stimulation of excitatory pathways (NMDA, adenosine), that observable CNS symptoms are manifested.

I should add that if one lives in the U.S. we are being exposed to so many glutamate analogs at every level of the food chain, it would be ridiculous to try to list all of them here. What do you think are the best antidotes to this short of avoidance?

 

[Quaid]

Wondering if the increase in sugar consumption is causing fatty sluggish liver and contributing to your muscle stiffness?