49 replies to this topic

[stablemind]

I'm testing out 500 mg Piracetam with 1 scoop of whey protein which contains ~3g Glutamic acid + Glutamine + 250 mg of a calcium blend including citrate, malate, and carbonate. So far it seems pretty effective at reducing the amount of Piracetam I normally need, and the effects seem stronger.

Edited by stablemind, 24 January 2013 - 07:11 PM.

[LBGSHI]

Interestingly, all three mornings after taking 400mg magnesium glycinate before sleep the night before, I've awoken feeling energetic, perhaps even hyper. Two of the three mornings (the first and third), I awoke feeling refreshed, but the second morning I got only a few hours of sleep, so that's to be expected. Given the strange, energetic feeling on waking (which I don't mind and rather like), I wonder if magnesium is indeed acting synergistically with those remnants of my stack still present in my system from the day before. If that's the case, I may experience significant effects from adding magnesium to my daytime stack...but since it's an NMDA inhibitor, I wonder how low the threshold would be before it became detrimental to nootropic use. I may try it out in the next few days, but I'd like to continue using it in my pre-sleep stack for a few more days to form a proper judgment of its effects.

[dirdir207]

Interestingly, all three mornings after taking 400mg magnesium glycinate before sleep the night before, I've awoken feeling energetic, perhaps even hyper. Two of the three mornings (the first and third), I awoke feeling refreshed, but the second morning I got only a few hours of sleep, so that's to be expected. Given the strange, energetic feeling on waking (which I don't mind and rather like), I wonder if magnesium is indeed acting synergistically with those remnants of my stack still present in my system from the day before. If that's the case, I may experience significant effects from adding magnesium to my daytime stack...but since it's an NMDA inhibitor, I wonder how low the threshold would be before it became detrimental to nootropic use. I may try it out in the next few days, but I'd like to continue using it in my pre-sleep stack for a few more days to form a proper judgment of its effects.

A lot of NMDA antagonists have a rebound effect of increased glutamergic activity. You may be having a similar effect from taking your magnesium prior to bed. It also probably doesn't hurt that the magnesium is also of the glycinate variety in addition to the glycine you take at night, ensuring that during the day, whilst supplementing glutamic acid and calcium you have all the necessary ingredients to activate those receptors.

Keep us informed as to what effects you experience should you decide to try the magnesium during the day.

[dirdir207]

So I researched a lot into neuronal excitability, homeostatic synaptic plasticity, calcium ions, and the potassium/sodiums pumps the last two days. I think in terms of calcium supplementation we may actually be going completely in the wrong direction for what we are trying to achieve. Piracetam being an allosteric modulator of the NMDA and AMPA receptors increases glutamate release and facilitates the opening of voltage gated ion channels. In general the point is to increase neuronal excitability NMDA activation and long term potentiation.

The problem is greater concentrations of calcium actually decrease neuronal excitability, in contrast hypocalcaemia increases neuronal excitability by reducing the amount that the threshold must change to initiate a full depolarization of the axon while leaving the resting potential unchanged. To put it another way, the resting potential stays the same but as calcium levels drop the amount of partial depolarization needed to allow sodium influx to be self-perpetuating is reduced. Symptoms of hypocalcaemia are as follows:

"CATS go numb"- Convulsions, Arrythmias, Tetany and numbness/parasthesias in hands, feet, around mouth and lips.
Petechiae which appear as on-off spots, then later become confluent, and appear as purpura (larger bruised areas, usually in dependent regions of the body).
Oral, perioral and acral paresthesias, tingling or 'pins and needles' sensation in and around the mouth and lips, and in the extremities of the hands and feet. This is often the earliest symptom of hypocalcaemia.
Carpopedal and generalized tetany (unrelieved and strong contractions of the hands, and in the large muscles of the rest of the body) are seen.
Latent tetany
Trousseau sign of latent tetany (eliciting carpal spasm by inflating the blood pressure cuff and maintaining the cuff pressure above systolic)
Chvostek's sign (tapping of the inferior portion of the zygoma will produce facial spasms)[1]
Tendon reflexes are hyperactive
Life threatening complications
Laryngospasm
Cardiac arrhythmias
ECG changes include:
Intermittent QT prolongation, or intermittent prolongation of the QTc (corrected QT interval) on the EKG (electrocardiogram) is noted. The implications of intermittent QTc prolongation predisposes to life-threatening cardiac electrical instability (and this is therefore a more critical condition than constant QTc prolongation). This type of electrical instability puts the patient at high risk of torsades de pointes, a specific type of ventricular fibrillation which appears on an EKG (or ECG) as something which looks a bit like a sine wave with a regularly increasing and decreasing amplitude. (Torsades de pointes, as with any type of ventricular tachycardia, causes death, unless the patient can be electrically cardioverted, and returned to a normal cardiac rhythm.)

Hypercalcaemia being the opposite, mainly drowsiness, confusion, hallucinations, stupor and / or coma, fatigue and sluggish reflexes.

I think what we really should be supplementing is potassium, as the symptoms of hyperkalemia pretty much mimic hypocalcaemia. In fact the treatment for hyperkalemia is usually calcium. Supplementing potassium should have a much greater impact on general excitability then supplementing calcium.

At least it seems to make sense to me.

Edited by dirdir207, 28 January 2013 - 06:49 AM.

[stablemind]

I went ahead and tested Mg Glycinate before bed and during Piracetam use and I've found that 200 mg before bed is just right. It seems to calm my mind and reduce the excitation that Piracetam causes, which would often prevent me from falling asleep. Taking 400 mg would make it too difficult to wake up the next morning. When I took Mg at the same time I took Piracetam, I did not really notice anything significant, so I think I'm going to continue taking it at night as it seems to prevent the hypomanic effects I would often get at night after using Piracetam.

[LBGSHI]

So I researched a lot into neuronal excitability, homeostatic synaptic plasticity, calcium ions, and the potassium/sodiums pumps the last two days. I think in terms of calcium supplementation we may actually be going completely in the wrong direction for what we are trying to achieve. Piracetam being an allosteric modulator of the NMDA and AMPA receptors increases glutamate release and facilitates the opening of voltage gated ion channels. In general the point is to increase neuronal excitability NMDA activation and long term potentiation.

The problem is greater concentrations of calcium actually decrease neuronal excitability, in contrast hypocalcaemia increases neuronal excitability by reducing the amount that the threshold must change to initiate a full depolarization of the axon while leaving the resting potential unchanged. To put it another way, the resting potential stays the same but as calcium levels drop the amount of partial depolarization needed to allow sodium influx to be self-perpetuating is reduced. Symptoms of hypocalcaemia are as follows:

"CATS go numb"- Convulsions, Arrythmias, Tetany and numbness/parasthesias in hands, feet, around mouth and lips.
Petechiae which appear as on-off spots, then later become confluent, and appear as purpura (larger bruised areas, usually in dependent regions of the body).
Oral, perioral and acral paresthesias, tingling or 'pins and needles' sensation in and around the mouth and lips, and in the extremities of the hands and feet. This is often the earliest symptom of hypocalcaemia.
Carpopedal and generalized tetany (unrelieved and strong contractions of the hands, and in the large muscles of the rest of the body) are seen.
Latent tetany
Trousseau sign of latent tetany (eliciting carpal spasm by inflating the blood pressure cuff and maintaining the cuff pressure above systolic)
Chvostek's sign (tapping of the inferior portion of the zygoma will produce facial spasms)[1]
Tendon reflexes are hyperactive
Life threatening complications
Laryngospasm
Cardiac arrhythmias
ECG changes include:
Intermittent QT prolongation, or intermittent prolongation of the QTc (corrected QT interval) on the EKG (electrocardiogram) is noted. The implications of intermittent QTc prolongation predisposes to life-threatening cardiac electrical instability (and this is therefore a more critical condition than constant QTc prolongation). This type of electrical instability puts the patient at high risk of torsades de pointes, a specific type of ventricular fibrillation which appears on an EKG (or ECG) as something which looks a bit like a sine wave with a regularly increasing and decreasing amplitude. (Torsades de pointes, as with any type of ventricular tachycardia, causes death, unless the patient can be electrically cardioverted, and returned to a normal cardiac rhythm.)

Hypercalcaemia being the opposite, mainly drowsiness, confusion, hallucinations, stupor and / or coma, fatigue and sluggish reflexes.

I think what we really should be supplementing is potassium, as the symptoms of hyperkalemia pretty much mimic hypocalcaemia. In fact the treatment for hyperkalemia is usually calcium. Supplementing potassium should have a much greater impact on general excitability then supplementing calcium.

At least it seems to make sense to me.

The above is correct, but not very applicable - it refers only to extremes.

In this thread, we're discussing only a minor increase in calcium, most probably that required to achieve normal, recommended calcium levels (the majority of people being calcium deficient, per http://ods.od.nih.go...thProfessional/). If one drinks a significant amount of milk or eats calcium-rich foods already, this course of action is probably not required (as I mentioned earlier in this thread, "there are likely many nootropic users exceeding my calcium intake just by drinking a few glasses of milk per day.").

In emphasizing the importance of calcium in synaptic activity and specifically excitatory synaptic activity, I refer back to the subject of the excitatory synapse, as described on Wikipedia: http://en.wikipedia....ic_transmission - "This influx of calcium into the presynaptic terminal is necessary for neurotransmitter release."


Also of interest, among others, are the following studies on LTP (Long Term Potentiation) and calcium:

http://www.ncbi.nlm....pubmed/10195125 - "Long-term potentiation (LTP) of synaptic strength can be induced by synchronous pre- and postsynaptic activation, and a rise in postsynaptic calcium is essential for induction of LTP."

http://www.ncbi.nlm..../pubmed/1972782 - "In the CA1 hippocampal region, intracellular calcium is a putative second messenger for the induction of long-term potentiation (LTP), a persistent increase of synaptic transmission produced by high frequency afferent fibre stimulation." - "The results directly confirm the calcium rise predicted by NMDA receptor models of LTP induction."


...and this study concerning low-threshold calcium spikes in synaptic transmission:

http://www.ncbi.nlm....pubmed/10792445 - "These results demonstrate that in cortical pyramidal neurons the activation of low-threshold calcium spikes results in the amplification of synaptic responses"


While grossly excessive calcium supplementation would very likely decrease excitatory synaptic activity, normal and even nominally super-normal calcium levels are essential for neuronal excitation, synaptic neurotransmission, and long-term potentiation, which are the cornerstone intentions of nootropic supplementation. This is especially relevant in the context of nootropic supplementation, which causes increased demands for calcium influx into neurons. Per ods.od.nih.gov (http://ods.od.nih.go...thProfessional/), the recommended minimum dietary calcium intake is 1000mg per day (in contrast, I'm currently supplementing 250mg x3 for a total of 750mg per day, and I generally don't drink milk or eat anything significantly rich in calcium, as I never get around to it), and the tolerable upper intake level (the level below which no adverse health effects are noted) is 2500mg per day.

This is not to say that you're incorrect concerning potassium supplementation. By all means, do the legwork and create a new thread if it looks promising; I'll be all ears (or eyes)

I went ahead and tested Mg Glycinate before bed and during Piracetam use and I've found that 200 mg before bed is just right. It seems to calm my mind and reduce the excitation that Piracetam causes, which would often prevent me from falling asleep. Taking 400 mg would make it too difficult to wake up the next morning. When I took Mg at the same time I took Piracetam, I did not really notice anything significant, so I think I'm going to continue taking it at night as it seems to prevent the hypomanic effects I would often get at night after using Piracetam.

Cool; thanks for the update. I haven't tried magnesium with my daytime stack yet, but I've consistently gotten positive results with it in my pre-sleep stack.

Edited by LBGSHI, 29 January 2013 - 08:13 PM.

[dirdir207]

I appreciate the thorough and informative reply! I of course was not implying that anyone should induce any of those extremes or shoot up potassium chloride in the name of neuronal excitability, I instead simply meant to imply raising ones potassium levels would have a similar yet not quite as profound effect somewhere along the scale. I figured if it increases excitability at that extreme, that there must be a steady increase in excitability relative to a steady increase in potassium. Which although i'm sure is true, you have nonetheless dismantled my tentative view on calcium supplementation after my reading, it is indeed paramount. It's always good to get a good discussion going, and I always try to remind myself of my fallibility on these matters, as well as trying to view things from all angles.

[LBGSHI]

I appreciate the thorough and informative reply! I of course was not implying that anyone should induce any of those extremes or shoot up potassium chloride in the name of neuronal excitability, I instead simply meant to imply raising ones potassium levels would have a similar yet not quite as profound effect somewhere along the scale. I figured if it increases excitability at that extreme, that there must be a steady increase in excitability relative to a steady increase in potassium. Which although i'm sure is true, you have nonetheless dismantled my tentative view on calcium supplementation after my reading, it is indeed paramount. It's always good to get a good discussion going, and I always try to remind myself of my fallibility on these matters, as well as trying to view things from all angles.

Agreed; I'm always interested in input. And I am also fallible, which is why I started this thread concerning "questions and comments"

[dirdir207]

Just as an update, I have been supplementing calcium for about a week now and have had thus far only a mediocre increase in piracetams efficacy. I like you consume very little calcium in my diet and am likely fairly deficient. On a whim I doubled my calcium dose today and am currently experiencing the most profound piracetam effects I have experienced in a long time. Focus, clarity, music appreciation and color saturation are VERY noticeably above baseline, and noticeably enhanced above the typical effects I receive from piracetam on a daily basis. I'm going to keep at this dosage for the next couple of days and see if I continue to have these effects. Thus far calcium has been the most impressive adjunct supplementation for piracetam since its effects started to wain.

[stablemind]

Just as an update, I have been supplementing calcium for about a week now and have had thus far only a mediocre increase in piracetams efficacy. I like you consume very little calcium in my diet and am likely fairly deficient. On a whim I doubled my calcium dose today and am currently experiencing the most profound piracetam effects I have experienced in a long time. Focus, clarity, music appreciation and color saturation are VERY noticeably above baseline, and noticeably enhanced above the typical effects I receive from piracetam on a daily basis. I'm going to keep at this dosage for the next couple of days and see if I continue to have these effects. Thus far calcium has been the most impressive adjunct supplementation for piracetam since its effects started to wain.

What kind of dose did you take?

[dirdir207]

I had been taking a gram of calcium citrate daily and noted only slightly increased effects. Today I took two grams and altered nothing else about my routine so I assume my results are attributable to the calcium increase.

[OpaqueMind]

On the 2nd day of a cerebrolysin cycle I supplemented calcium for the first time. The difference is night and day, so I'm thinking I may have been severely deficient in the first place.Thoughts became clearer, colours more saturated and fatigue lifted. All in all a great addition, thank you for bringing this to our attention!

[LBGSHI]

Just as an update, I have been supplementing calcium for about a week now and have had thus far only a mediocre increase in piracetams efficacy. I like you consume very little calcium in my diet and am likely fairly deficient. On a whim I doubled my calcium dose today and am currently experiencing the most profound piracetam effects I have experienced in a long time. Focus, clarity, music appreciation and color saturation are VERY noticeably above baseline, and noticeably enhanced above the typical effects I receive from piracetam on a daily basis. I'm going to keep at this dosage for the next couple of days and see if I continue to have these effects. Thus far calcium has been the most impressive adjunct supplementation for piracetam since its effects started to wain.

I had been taking a gram of calcium citrate daily and noted only slightly increased effects. Today I took two grams and altered nothing else about my routine so I assume my results are attributable to the calcium increase.

Nice; glad it helped. I've gotten consistently improved effects from oxiracetam when supplementing calcium citrate, which I've been doing for over two weeks now with no ill effects and no decrease in positive effects. It certainly seems that I was depleting calcium or not getting enough in the first place (or both), and that supplementation has corrected for that.

On the 2nd day of a cerebrolysin cycle I supplemented calcium for the first time. The difference is night and day, so I'm thinking I may have been severely deficient in the first place.Thoughts became clearer, colours more saturated and fatigue lifted. All in all a great addition, thank you for bringing this to our attention!

Cool. How much calcium are you taking, and in what form (calcium citrate, etc)?

[dirdir207]

Quick update, piracetams effects continued to intensify today and whilst looking in the mirror I noted the return of the "shiny eye" effect which I have not encountered in quite some time.

[Heh]

Just as an update, I have been supplementing calcium for about a week now and have had thus far only a mediocre increase in piracetams efficacy. I like you consume very little calcium in my diet and am likely fairly deficient. On a whim I doubled my calcium dose today and am currently experiencing the most profound piracetam effects I have experienced in a long time. Focus, clarity, music appreciation and color saturation are VERY noticeably above baseline, and noticeably enhanced above the typical effects I receive from piracetam on a daily basis. I'm going to keep at this dosage for the next couple of days and see if I continue to have these effects. Thus far calcium has been the most impressive adjunct supplementation for piracetam since its effects started to wain.

When did you take calcium? With Piracetam on an empty stomach, after Piracetam with a meal, some other time? I'm wondering if there's a need to take the two at exactly the same time, or if simply raising calcium levels is sufficient.

[LBGSHI]

Quick update, piracetams effects continued to intensify today and whilst looking in the mirror I noted the return of the "shiny eye" effect which I have not encountered in quite some time.

Wow, nice.

When did you take calcium? With Piracetam on an empty stomach, after Piracetam with a meal, some other time? I'm wondering if there's a need to take the two at exactly the same time, or if simply raising calcium levels is sufficient.

I can't speak for dirdir207, but I've been taking mine on an empty stomach with oxiracetam, glutamic acid, and either alpha-GPC or centrophenoxine, alternately.

[OpaqueMind]

On the 2nd day of a cerebrolysin cycle I supplemented calcium for the first time. The difference is night and day, so I'm thinking I may have been severely deficient in the first place.Thoughts became clearer, colours more saturated and fatigue lifted. All in all a great addition, thank you for bringing this to our attention!

Cool. How much calcium are you taking, and in what form (calcium citrate, etc)?

I'm taking 800mg of simple calcium, at least that what the bottle says. Just 'calcium'. Pretty much every other mineral supplement I've seen there's a binding mechanism. Strange...

[LBGSHI]

I'm taking 800mg of simple calcium, at least that what the bottle says. Just 'calcium'. Pretty much every other mineral supplement I've seen there's a binding mechanism. Strange...

Ah. The problem with calcium by itself is its low absorption rate (which is why you're taking 800mg rather than 400 or less). If pure calcium works for you, stick to it. However, you may find that calcium citrate is more potent due to more calcium actually entering your bloodstream via your GI tract.

[dirdir207]

I would also suggest supplementing d3 as well as it is essential for the absorption of calcium.

[dirdir207]

Also to answer the earlier question I generally try to take anything that is synergistic with piracetam 40 minutes to an hour prior to piracetam ingestion to ensure I have the necessary ingredients in place for maximum efficacy. After some time though it shouldnt make much of a difference when you take it since you will have built up sufficient reserves, then its just maitenance.