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Wednesday, April 21, 2010

My best condition of mood and stuttering - The ideal one

I have experienced ideal conditions also. I mean to say, I had experienced good mood, no depression, no anxiety and no stuttering. I had such incidents under the following conditions. If I could understand the possible underlying mechanisms and if I could reproduce these effects daily by using nutraceutical or pharmacological means, I could be a happy person.

Conditions:
  1. I was taking Zincovit multivitamin tablets (Pls find the composition below). After taking it for few days, I felt some what uneasy feelings of tiredness and low mood. Then I stopped the tablet for one day. On the day of stopping, my energy level was up and almost no stuttering. My voice was louder. During this time, I was with my family. So, social support also play a role in this.
  2. I was taking neurogistics multivitamin caps, 5-HTP, magnesium, glycine, taurine, vitamin C and bioflavonoids. I went to to my relative's house where I didn't take these supplements. I applied coconut oil on my head hair. After 1 hour, my voice was louder, no stuttering. If no coconut oil is applied, the effect was not there. This time also, I was with my close relatives.
  3. Yesterday night (20 may 2010), I slept with a new cotton pillow which is quite fluffy. So it is big. No pillow cover. Today morning I could get up easily without laziness and my mind was full of energy. I felt energetic physically also. My stuttering is also very much reduced today (It is not completely absent). I suspect some anamoly in my neck area which would prevent proper drainage of blood, CSF and other fluids from head to main body. When I sleep with raised head, the drainage seems to occur properly. Other than this, I could not think of any other reason for this.  

Unusual and non stutterable pause in stuttering

I experienced an unusual and unstutterable pause during my speech when I was taking certain supplements.


In 2008, I took Renerve capsules http://www.grandix.in/products_neuro.html

The composition is given below. After taking this caps, I experienced this kind of stuttering for the first time. I speak faster and after 5-15 minutes, the unusual pause of 3- 7 seconds comes in. It is like an epilepsy attack (may be an absence seizure). During that pause, I was not able to make any sound from my throat. But, no loss of consciousness, no loss of memory and no impairment of other functions. And, no other symptoms also. I used to feel like paralysis of my vocal cord. I assume that this could be due to dopamine (either increased or decreased levels) or some minerals.


Products
  Packing
        Composition
ReNerveSoft
Gel
Caps
10x10'sMethyl Cobalamin
Alpha Lipoic Acid
Vitamin E Acetate
Vitamin B1 HCl
Vitamin B6
Vitamin A Concentrate
Calcium Pantothenate
Selenium Dioxide
Folic Acid
Chromium polynicotinate
Inositol
500 mcg
100 mg
25 mg
10 mg
1.5 mg
2500 IU
10 mg
163.6mcg
5 mg
200 mcg
100 mg    


The same effect was observed when I was taking neurogistics multivitamin capsules also. The composition is given below. Here, Vitamin B12 is present as methylcobalamin. So, it could be due to methylcobalamin. when I switched over to other vitamin tablets with Vitamin B12 as cyanocobalamin, this effect was not there. However, this effect could be due to some other component/mechanism also.


This effect was more observed during the time when I was taking DL-phenylalanine 1000 mg (500 mg X 2) daily in mornings. When I was taking this neurogistics multivitamin caps together with 5-HTP along with magnesium, taurine and glycine, this effect was not there. So, I assume the culprits as dopamine and methyl cobalamin. The clear mechanism is unknown. It could be a form of vocal cord dystonia induced by excess dopamine also.

I was taking zincovit multivitamin tablets in 2008. That also caused this effect. But it was less severe. The worst was with neurogistics multivitamin + vitamin C + DL-phenylalanine.

Composition of zincovit tablets:

Vitamins
Ascorbic acid as coated75 mg
Niacinamide50 mg
Alphatocopheryl Acetate concentrate (Powder form)15 mg
Thiamine mononitrate10 mg
Riboflavine10 mg
Calcium Pantothenate2 mg
Pyridoxine Hydrochloride2 mg
Folic aicd1 mg
Vitamin A con. Powder form (as acetate)5000 I.U.
VitaminD3 (Cholecalciferol)400 I.U.
Minerals
Zinc sulphate monohydrate63 mg
Magnesium oxide30 mg
Manganese sulpahte monohydrate2.8 mg
Copper sulphate2 mg
Colloidal Sillicon Dioxide (equ. To Sillica)1 mg
Pottassium Idodie (Eq. to Iodine)150 mcg
Sodium Borate (Equ. Boron)150 mcg
Selenium di oxide monohydrate70 mcg
Chromium picolinate (equ to Chromium)25 mcg
Sodium molybdate Dihydrate (equ to molybdenum)25 mcg
 (Source: http://www.apexlab.com/html/zincovit.html)

Today, I had this effect when I was talking to my landlord (luckily she was counting the rental money I gave to her, So I had some time to observe my pause). Oh my God! What a horrible disturbances in this life? I took Vitamin C (500 mg NOT slow release) + bioflavonoids and DL-phenylalanine 500 mg in the lunch time. Around 7 pm I had this effect.

Possible mechanism:
  1. Vitamin C increases noradrenaline synthesis and DL-phenylalanine increases noradrenaline, dopamine and adrenaline.
  2. I feel this increase may be an excess or there may not be a matching increase in serotonin and GABA. So I should try increasing serotonin (5-HTP) and GABA (Mentat)
Reduced effect of unstutterable stuttering - Update on 12 may 2010:

For the past few days, I am taking the supplements as follows:

Morning: 1 capsule of 5-HTP - 50 mg; 1 capsule of DL-phenylalanine - 500 mg, 2 capsules of neurogistics multivitamin; 1 tablet of l-lysine - 600 mg

Lunch/evening: 1 capsule of DL-phenylalanine 500 mg

Evening/night: 1 capsule of neurogistics multivitamin; 1 capsule of omega -3 (EPA + DHA = 780 mg)

Diet:

Morning - oats or noodles (not much of protein)

Lunch - rice, vegetables and 1 piece of fish

Dinner - rice or dosa with chicken drum stick 1 piece

This condition has reduced my unstutterable stuttering to greater level. Not much of longer pauses like before. I am not taking vitamin C and magnesium. They are said to have antidepressant properties but they may interact with noradrenergic and dopaminergic systems. I suspect the magneisum very much for this effect. Need to explore more on this area.

Ascorbic acid administration produces an antidepressant-like effect: Evidence for the involvement of monoaminergic neurotransmission
Progress in Neuro-Psychopharmacology and Biological Psychiatry, Volume 33, Issue 3, 30 April 2009, Pages 530-540.

Abstract


Ascorbic acid is highly concentrated in the brain, being considered as a neuromodulator. This study investigated the effect of ascorbic acid in the tail suspension test (TST) and in the forced swimming test (FST) in mice and the contribution of the monoaminergic system to its antidepressant-like effect. Moreover, the effects of fluoxetine, imipramine and bupropion in combination with ascorbic acid in the TST were investigated. Ascorbic acid (0.1-10 mg/kg, i.p., 1-10 mg/kg p.o. or 0.1 nmol/mice i.c.v.) produced an antidepressant-like effect in the TST, but not in the FST, without altering the locomotor activity. The effect of ascorbic acid (0.1 mg/kg, i.p.) in the TST was prevented by i.p. pre-treatment with NAN-190 (0.5 mg/kg), ketanserin (5 mg/kg), MDL72222 (0.1 mg/kg), prazosin (62.5 microg/kg), yohimbine (1 mg/kg), propranolol (2 mg/kg), haloperidol (0.2 mg/kg), sulpiride (50 mg/kg), but not with SCH23390 (0.05 mg/kg, s.c.). Additionally, ascorbic acid (1 mg/kg, p.o.) potentiated the effect of subeffective doses (p.o. route) of fluoxetine (1 mg/kg), imipramine (0.1 mg/kg), or bupropion (1 mg/kg) in the TST. The combined treatment of ascorbic acid with antidepressants produced no alteration in the locomotion in the open-field test. In conclusion, our results show that administration of ascorbic acid produces an antidepressant-like effect in TST, which is dependent on its interaction with the monoaminergic system. Moreover, ascorbic acid caused a synergistic antidepressant-like effect with conventional antidepressants. Therefore, the present findings warrant further studies to evaluate the therapeutical relevance of ascorbic acid for the treatment of depression and as a co-adjuvant treatment with antidepressants.
 
   
Evidence for the involvement of the monoaminergic system in the antidepressant-like effect of magnesium. Prog Neuropsychopharmacol Biol Psychiatry. 2009 Mar 17;33(2):235-42. Epub 2008 Nov 27.


Abstract


Literature data has shown that acute administration of magnesium reduces immobility time in the mouse forced swimming test (FST), which suggests potential antidepressant activity in humans. However, its mechanism of action is not completely understood. Thus, this study is aimed at investigating the antidepressant-like action of magnesium and the possible involvement of the monoaminergic system in its effect in the FST. The immobility time in the FST was significantly reduced by magnesium chloride administration (30-100 mg/kg, i.p.) without accompanying changes in ambulation when assessed in an open-field test. The pre-treatment of mice with NAN-190 (0.5 mg/kg, i.p. a 5-HT(1A) receptor antagonist), WAY100635 (0.1 mg/kg, s.c., a selective 5-HT(1A) receptor antagonist), ritanserin (4 mg/kg, i.p., a 5-HT(2A/2C) receptor antagonist), ketanserin (5 mg/kg, a preferential 5-HT(2A) receptor antagonist), prazosin (1 mg/kg, i.p., an alpha(1)-adrenoceptor antagonist), yohimbine (1 mg/kg, i.p., an alpha(2)-adrenoceptor antagonist), haloperidol (0.2 mg/kg, i.p., a non selective dopaminergic receptor antagonist), SCH23390 (0.05 mg/kg, s.c., a dopamine D(1) receptor antagonist) or sulpiride (50 mg/kg, i.p., a dopamine D(2) receptor antagonist) 30 min before the administration of magnesium chloride (30 mg/kg, i.p.) significantly prevented its anti-immobility effect in the FST. Moreover, the administration of sub-effective doses of fluoxetine (10 mg/kg, i.p., serotonin reuptake inhibitor), imipramine (5 mg/kg, i.p., a mixed serotonergic noradrenergic reuptake inhibitor), bupropion (1 mg/kg, i.p., dopamine reuptake inhibitor) was able to potentiate the action of sub-effective doses of magnesium chloride. In conclusion, the present study provides evidence indicating that the antidepressant-like effect of magnesium in the FST is dependent on its interaction with the serotonergic (5-HT(1A) and 5-HT(2A/2C) receptors), noradrenergic (alpha(1)- and alpha(2)- receptors) and dopaminergic (dopamine D(1) and D(2) receptors) systems.


Update on 8 may 2015:

For the past 3 months, I was taking zinc in order to improve my testosterone and dopamine levels. I took zinc 15 mg + vitamin C 250 mg daily in mornings after food. During February 2015, I took proviton capsules + zinc 15 mg + vitamin C 250 mg combination. This produced good energy and mood. However, it produced mild non-stutterable pause also. Also, it increased blood pressure to 156/100 mmHg during the lunch time. The blood pressure dropped to normal levels during the evening hours. So, I had to change the multivitamin from proviton to Supradyn recharge. I continued the zinc but without vitamin C since supradyn recharge has enough vitamin C. This combination also produced non-stutterable pause and caused big embarrassment when I was speaking with my boss. What a pity life I live! Also, it caused poor concentration, unable to focus and less motivation to start doing things. Then, I reduced the dose of zinc to 7.5 mg by taking half tablet. Still the effects persisted with reduced intensity. I stopped zinc one day. On that day of no zinc, I felt great energy, mood and no non-stutterable pause. After that, I stopped taking zinc. That non-stutterable pause is not coming again. However, this non-stutterable pause may be caused by other minerals/vitamins also. I need to explore further and confirm.

In my research with my stuttering and interventions, I suspect the following for the non-stutterable pause. The mechanism could be lack of dopamine in the speech circuit.

1. Zinc
2. Folic acid
3. Methyl cobalamin
4. Methylfolate
5. Selenium

Effects of Mentat

I am taking Mentat tablets (Himalaya drug company) for the past one week (2 tablets in morning and 2 tabs in night). I am also taking multivitamin tablets (Appeton teen grow) and slow release vitamin C tablets (500 mg) + bioflavonoids.

Positive effects:
  1. Reduced anxiety - may be by increased GABA levels
  2. Reduced stuttering - even though the stuttering is somewhat reduced, no feelings of comfortable and enjoyable fluent speaking. Reduced stuttering was observed for the first 1-2 weeks. After that stuttering was present and sometimes worse.
  3. When I took mutton, it increased my libido and affection.
  4. During 2008, I took mentat for about 1 month. It has increased the libido and affection and love feelings very much especially after I take ground nuts (but did not give rise to strong erections) . So the involvement of omega -6 could be a possible mechanism.
  5. No excessive sleep. I could finish sleeping without much difficulty. I could get up after 7-8 hrs easily. This effect was observed after 1 week of taking mentat. Sleeping was much more difficult with 5-HTP, With 5-HTP, I could not finish my sleeping and my sleeping never seemed to end. I felt like I was unable to motivate myself to get up. So, it indicates serotonin reduces dopamine probably in the mesolimbic region of the brain for motivation. 
  6. Increased mobility, increased flexibility of muscles, faster movements without any gait problems, better coordination of muscles while driving were observed after 2 weeks of taking mentat.
  7. I was able to sleep for less time per day, and I was able to motivate myself to do certain things. Example, I had meeting on last week which extended beyond the scheduled time. So I had to rush for the prayer. I could rush for the prayer and I could motivate myself to do such risky operation without any difficulty. I enjoyed such intense stressful rushing. I could drive the car faster and I could reach the prayer place just on time. Even a 2 minute delay would forfeit me from joining the prayers. So it is like "can do" or "cannot do" situation. I could do that. Thats it.
  8. I took less time in getting ready in the morning. usually I take 1 hour 30 minutes (from getting up from bed to start my car; This includes brushing (10 minutes), making and drinking tea (10 minutes) and making breakfast (10 minutes) going to latrine (10-15 minutes), taking bath (20 minutes), eating breakfast (5 minutes), dressing up (15 minutes)  to get ready. After taking mentat, I could get ready by 1 hour by doing all these things faster without having the anxiety of rushing.     
Negative effects:
  1. Muscle weakness - decreased flexibility of muscles (This is minimized by taking vitamin C which may increase noradrenaline levels). But this is not disturbing my driving. This effect was there for first 1-2 weeks. After that, I experienced increased flexibility and mobility. See the positive effects above.
  2. When I started adding DL-phenylalanine 500mg in the morning or in the lunch, it produced headache. Mild headache which lasted for 3 days. This headache did not go away even after taking 5-HTP (50 mg OD). This headache got reduced after taking magnesium + glycine + taurine. I need to explore the mechanism behind this.
  3. After 2 weeks of taking mentat, I got severe headache which is not going even after taking paracetamol 650 mg dose. The headache got reduced after taking magnesium, taurine and glycine and 5-HTP. The headache completely went away after skipping a night's dose of mentat only.
  4. Update on 6 May 2010: I got severe headache yesterday on my right side of head. Due to some purchasing work, I could not take lunch and DL-phenylalanine on day before yesterday. Night also I did not take DL-phenylalanine. Yesterday, I got headache which started around lunch time and worsened in the evening. In the evening, I smoked a cigarette in order to boost serotonin, dopamine and noradrenaline and adrenaline. It gave me a little relief. Then along with dinner, I took DL-phenylalanine 500 mg. Then I applied tiger balm on my side head. Around 12 am headache reduced much and I could sleep better. Today morning, I felt better. So, it looks to me that the headache is probably because of dopamine depletion. Even though I had headache yesterday, my mood was OK and my sociability was also ok. If I get a headache which is aching on left side of my head, then at those times, my mood used to be low. So it could be due to serotonin depletion. yesterday's headache was aching on right side of my head. So, it was different.  
Possible mechanisms: (First written on 21 April 2010)

ObservationPossible mechanism
Less sleep, increased flexibility , less global bradykinesiaIncreased straital and mesolimbic dopamine neurotransmission (Dopamine receptor agonism)
Severe headacheDecrease in serotonin (blockade of 5HT1A autoreceptor)

Possible mechanism (First written on 30 April 2010)

After reading several research papers on anxiety and its animal models, I read about buspirone. The effects of buspirone and mentat seem to be matching perfectly. Since I have not taken buspirone anytime before, I cannot really compare the effects of buspirone and mentat.

See the links below for research articles on buspirone's effects.

Effects of Acute and Chronic Administration of the Serotonin1A Agonist Buspirone on Serotonin Synthesis in the Rat Brain

Alterations of central serotonin and dopamine turnover in rats treated with ipsapirone and other 5-hydroxytryptamine1A agonists with potential anxiolytic properties.


Update on 12 may 2010:

Mentat consumption along with 5-HTP, DL-phenylalanine and multivitamin capsules produced severe headache which usually lasted for one full day. I had few headache attacks like that in the past week. The headache was mostly on the left side of my head. It was associated with irritation, and psychomotor retardation. So, I decided to discontinue mentat.

Composition of Mentat tablets



Each tablet contains:

EXTRACTS OF
QUANTITY
Bacopa monnieri
136 mg
Centella asiatica
70 mg
Withania somnifera
52 mg
Evolvulus alsinoides
52 mg
Nardostachys jatamansi
52 mg
Valeriana wallichii
50 mg
Embelia ribes
50 mg
Prunus amygdalus
50 mg
Acorus calamus
42 mg
Tinospora cordifolia
36 mg
Terminalia chebula
36 mg
Emblica officinalis
36 mg
Celastrus paniculatus
32 mg
Oroxylum indicum
32 mg
POWDERS OF

Bacopa monnieri
80 mg
Orchis mascula
18 mg
Mucuna pruriens
18 mg
Elettaria cardamomum
18 mg
Terminalia arjuna
18 mg
Foeniculum vulgare
18 mg
Ipomoea digitata
18 mg
Zingiber officinale
14 mg
Temninalia belerica
14 mg
Myristica fragrans
14 mg
Syzygium aromaticum
10 mg
Mukta pishti
3 mg


Source: http://www.tetrada-az.com/eng/wp-content/uploads/2012/06/Mentat-tablets-eng.pdf

According to above source, Mentat has the following pharmacological action.


Mentat regulates cholinergic and GABAergic systems of neurotransmission and thus improves brain functions. It restores activity of muscarine and cholinergic receptors of frontal cortex and thus improves I.Q., memory capacity, concentration, and raises stress resistibility level. Mentat contributes to reduction of tribulin level, an endogenous inhibitor of monoamine oxidase which is increased at anxious conditions of different degree. Preparation stimulates improvement in case of concentration instability and behavioral disturbances. Mentat protects against parkinsonism by raising activity of post-synaptic dopamine receptor. Its sedative and tranquilizing action protects from convulsions and is helpful in insomnia. Mentat improves articulation and corrects speech defects.