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Tuesday, March 30, 2010

Stuttering and plasma copper levels

Folia Phoniatr Logop. 2005 Jul-Aug;57(4):216-22.


Copper in developmental stuttering.



Alm PA.



Department of Clinical Neurosciences, Lund University, Lund, Sweden. Per.Alm@psykiatr.lu.se



Erratum in:



* Folia Phoniatr Logop. 2007;59(3):154.



It has previously been reported that men with developmental stuttering showed reduced concentration of copper in the blood, and a negative correlation between the copper level and the severity of stuttering. Disorders of copper metabolism may result in dysfunction of the basal ganglia system and dystonia, a motor disorder sharing some traits of stuttering. It has been shown that copper ions affect the dopamine and the GABA systems. With this background we investigated the plasma level of copper, the copper binding protein ceruloplasmin, and the estimated level of free copper in stuttering adults. Sixteen men with developmental stuttering were compared with 16 men without speech problems. The samples were assayed in one batch in a pseudorandom and counterbalanced order. No significant differences were found between stuttering men and the control group in any of the biological variables, and no negative correlation between copper and the general severity of stuttering was shown. On the contrary, an explorative analysis resulted in a positive correlation between high plasma copper and superfluous muscular activity during stuttering (r=0.51, p=0.04). This result indicates that there is no relation between developmental stuttering and low plasma copper in the main population of stuttering adults. Copyright (c) 2005 S. Karger AG, Basel.

Friday, March 26, 2010

Corticosteroids, anxiety and depression

Effect of Prednisolone

Today I took corticosteroid prednisolone 5 mg in the morning (only prednisolone, no other supplements). I just wanted to compare the effects of prednisolone to that of geriforte. As I expected, prednisolone produced similar effect like geriforte.

Positive effects:
  1. Improved sense of general well being
  2. No unsteadiness while walking and no vertigo
  3. Decreased perception of heat and hot spicy food (chillies) -  due to anti-inflammatory effects
Negative effects:

  1. No improvement on stuttering
  2. My voice is not louder with lack of deep bass notes. My voice sounds like a voice of a person who gave lecture for many hours continuously.
So, from these observation of the symptoms, I could make out that geriforte may contain a chemical which could act on the corticosteroid receptors in the CNS. It could be an low dose synthetic corticosteroid or could be a natural steroid resembling compound glycyrrhizin from Glycyrrhiza glabra (licorice, liquorice, yastimadhu, athimathuram) or could be phytosterols.

In the evening, I got mild headache, resembling low serotonin-induced headache. So, I could feel that after taking geriforte for about 10 days and prednisolone for 1 day, the cumulative effects of steroids (increased steroid levels) would have suppressed my serotonin levels and due to that I might have got headache.

So, this observation indicates that increased cortisol level during stress would decrease the serotonin levels. It may
  • decrease the serotonin release or 
  • decrease the serotonin receptor 5-HT1A or 
  • decrease the serotonin transporter or 
  • increase the metabolism of serotonin
Update on 06 October 2015

Effect of Betamethasone valerate:

Composition of Betnovate-N cream:

The main active ingredient - betamethasone (as valerate) 0.1%
an antibacterial agent - neomycin sulphate 3%
a preservative - chlorocresol
in a base containing cetomacrogol 1000, white soft paraffin, and liquid paraffin.
The cream does not contain any lanolin, parabens or colouring agents. 


I applied betnovate-N cream on my face and neck for some red eruptions in the night around 1.30 am before going to sleep. The next morning, I could get up around 8 am without any lethargy and I could do more work with sustained focus and concentration. This focus and concentration was enhanced by taking vitamin C 500 mg in the morning after breakfast. This enhanced focus and concentration sustained even until late night.

When I applied the cream in the morning after I get up around 8 am, it produced unpleasant effects. I could not have sustained focus and concentration. It increased stuttering with reduced volume while speaking.

When I applied the cream at 9 pm in night, I could sleep without much disturbance. But while getting up next morning, I felt lethargic and tired. But after arriving at office, I could sustain focus and concentration in my work until evening.

While I applied this cream during night, I experienced vivid dreams. Some are frightening. In some dreams, I used to get angry. Even though the sleep appeared to be full of dreams, I used to get the well-slept feeling after waking up.

I am planning to try this strategy for next 3 weeks to regulate my cortisol levels. It appears that I have either low cortisol level or hypoactive HPA axis.   



Thursday, March 25, 2010

Tea and stress

I am a tea taker always and I prefer tea instead of coffee always. I don't know why. Sometimes I used to find that some brands of tea worsened my stuttering and some improved my stuttering.

References:


Psychopharmacology (Berl). 2007 Jan;190(1):81-9. Epub 2006 Sep 30.

The effects of tea on psychophysiological stress responsivity and post-stress recovery: a randomised double-blind trial.

Department of Epidemiology and Public Health, University College London, 1-19 Torrington Place, London, UK. a.steptoe@ucl.ac.uk
RATIONALE: Tea has anecdotally been associated with stress relief, but this has seldom been tested scientifically. OBJECTIVES: To investigate the effects of 6 weeks of black tea consumption, compared with matched placebo, on subjective, cardiovascular, cortisol and platelet responses to acute stress, in a parallel group double-blind randomised design. MATERIALS AND METHODS: Seventy-five healthy nonsmoking men were withdrawn from tea, coffee and caffeinated beverages for a 4-week wash-out phase during which they drank four cups per day of a caffeinated placebo. A pretreatment laboratory test session was carried out, followed by either placebo (n = 38) or active tea treatment (n = 37) for 6 weeks, then, a final test session. Cardiovascular measures were obtained before, during and after two challenging behavioural tasks, while cortisol, platelet and subjective measures were assessed before and after tasks. RESULTS: The tasks induced substantial increases in blood pressure, heart rate and subjective stress ratings, but responses did not differ between tea and placebo treatments. Platelet activation (assessed using flow cytometry) was lower following tea than placebo treatment in both baseline and post-stress samples (P < 0.005). The active tea group also showed lower post-task cortisol levels compared with placebo (P = 0.032), and a relative increase in subjective relaxation during the post-task recovery period (P = 0.036). CONCLUSIONS: Compared with placebo, 6 weeks of tea consumption leads to lower post-stress cortisol and greater subjective relaxation, together with reduced platelet activation. Black tea may have health benefits in part by aiding stress recovery.

Wednesday, March 24, 2010

My vertigo

I used to have the feelings of movement when sitting in front of the computer or about to faint feelings when sitting in front of the computer. It started in 2005. Later it used to occur frequently. If I take multivitamin tablets or 2 eggs/day, it used to disappear. If I stop taking multivitamin or eggs, then it used to appear again.

Later I learned that it is vertigo. Check the references below for vertigo.

My vertigo used to disappear when I was taking 5-HTP, multivitamin, DL-phenylalanine, magnesium, taurine, glycine, vitamin C + bioflavonoids, omega-3.

So, the possibility for my vertigo could be chronic depression induced peripheral neuropathy. My left hand weakness and tingling sensation in ring finger of left hand could also be due to peripheral neuropathy.

References:
  1. http://www.merck.com/mmhe/sec06/ch080/ch080c.html
  2. http://en.wikipedia.org/wiki/Vertigo#Signs_and_symptoms

Tuesday, March 23, 2010

Effect of high dose vitamin C

High dose (800 mg/day) vitamin C (controlled release) had produced good effects in me before starting 5-HTP and DL-phenylalanine supplementation.

Positive effects:

  1. Increased focus and concentration - can stick to the chair until I finish the work
  2. Increased mental energy - sustained mental energy until I finish the work 3-4 hours at a stretch.
  3. Increased my music listening - made me to hear deep bass beats and sharp notes clearly. I could enjoy music (I observed this effect, when I am taking geriforte, magnesium, glycine, taurine and bioflavanoids along with vitamin c 500mg 2 times daily)
Negative effects:

  1. Little worsening of my stuttering sometimes when I started taking 5-HTP and DL-phenylalanine supplementation.
  2. Unsteadiness while walking (I observed this effect, when I am taking geriforte, magnesium, glycine, taurine and bioflavanoids along with vitamin C 500mg 2 times daily). This unsteadiness could be due to vertigo. I remember when I was taking 800 mg/day controlled release tablets of vitamin C buffered tablets, my unsteadiness worsened gradually and after some time it stopped completely (I could sense some fluid coming out of my left ear and after that my unsteadiness went away).
The research literature indicates that high doses of ascorbic acid may act as a neuromodulator in the brain. It may increase the biosynthesis of norepinephrine. It may act as a dopamine antagonist (block amphetamine induced effects and potentiate haloperidol induced effects). It may potentiate the dopamine's ability to inhibit prolactin release. Also, it may increase glutamate transmission.

References:
  1. J Neurochem. 1986 Mar;46(3):939-45.
    Stimulatory effect of ascorbic acid on norepinephrine biosynthesis in digitonin-permeabilized adrenal medullary chromaffin cells.
    Morita K, Levine M, Pollard HB.
  2. Proc Natl Acad Sci U S A. 2000 Feb 15;97(4):1891-6.
    Ascorbic acid acts as an inhibitory transmitter in the hypothalamus to inhibit stimulated luteinizing hormone-releasing hormone release by scavenging nitric oxide.
    Karanth S, Yu WH, Walczewska A, Mastronardi C, McCann SM.
  3. Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11783-8. Epub 2001 Sep 18.
    Ascorbic acid stimulates gonadotropin release by autocrine action by means of NO.
    Karanth S, Yu WH, Walczewska A, Mastronardi CA, McCann SM.
  4. Psychopharmacology (Berl). 2002 Jan;159(3):319-24. Epub 2001 Nov 20.

    A randomized controlled trial of high dose ascorbic acid for reduction of blood pressure, cortisol, and subjective responses to psychological stress.

    Center for psychomatic and Psychobiological Research, University of Trier, Trier, Germany. stuartbrody@hotmail.com
    RATIONALE: Physiological responses to stress are considered disruptive to health. High-dose ascorbic acid has reduced indices of stress in laboratory animals. METHODS: We conducted a randomized double-blind, placebo-controlled 14-day trial of sustained-release ascorbic acid (60 healthy young adults; 3 x1000 mg/day Cetebe) and placebo (60 healthy young adults) for reduction of blood pressure, cortisol, and subjective response to acute psychological stress (Trier Social Stress Test, TSST, consisting of public speaking and mental arithmetic). Six subjects from each group were excluded. RESULTS: Compared to the placebo group, the ascorbic acid group had less systolic blood pressure (an increase of 23 versus 31 mmHg), diastolic blood pressure, and subjective stress responses to the TSST; and also had faster salivary cortisol recovery (but not smaller overall cortisol response). Cortisol response to 1 microg ACTH, and reported side-effects during the trial did not differ between groups. Plasma ascorbic acid level at the end of the trial but not pre-trial was associated with reduced stress reactivity of systolic blood pressure, diastolic blood pressure, and subjective stress, and with greater salivary cortisol recovery. CONCLUSIONS: Treatment with high-dose sustained-release ascorbic acid palliates blood pressure, cortisol, and subjective response to acute psychological stress. These effects are not attributable to modification of adrenal responsiveness.


    Psychopharmacology (Berl). 2005 Aug;181(1):71-9. Epub 2005 Oct 15. 


     

Effect of phenylalanine

Positive effects:
  1. Slightly increased energy
  2. Good erections, increased sensation of penis while penetrating and ejaculating
  3. Reduction of anxiety
  4. Less rigidity in the muscles
Negative effects:
  1. Unsteadiness while walking - It could be due to worsening of existing vertigo also.
  2. Increased BP (145/100) - this normalized to 130/90 - 120/84 after few months
  3. Presyncope (feeling like about to faint) - This also could be due to existing vertigo
  4. Bass tone of voice increased - earlier my voice used to be softer without much bass.
  5. Worsened stuttering - I experienced a new form of stuttering which i never experienced before in my lifetime. When I am talking for few minutes continuously, suddenly a blank pause appears in my speech. At that time I am not able to initiate any sound from my throat. After 5 seconds of unusual pause only I could make any other sound. It does not occur in the starting of the speech. It always occurs after 10-20 minutes of speech. Very embarrassing condition.
The side effects indicate that phenylalanine is affecting my basal ganglia especially my striatum which controls the motor coordination of speech. It may not be the effect of phenylalanine in other depressed individuals. My dopamine system may be heavily damaged due to my stuttering. So, it now responds differently to phenylalanine.

Genetic Control of Phenylalanine and Tyrosine Biosynthesis in Neurospora Crassa. Offprint from: Genetics, vol. 62, 1969.Dietary Phenylalanine and Brain Function

Effect of 5-HTP

I took 5-HTP for 9 months for my dperession and I found that it is having both positive and negative effects. I took 5-HTP along with other nutrients like DL-phenylalanine, magnesium, taurine, glycine, omega 3 (EPA + DHA), vitamin C + Bioflavanoids and multivitamins. However, to the best of my knowledge and experience, I could identify the effects of 5-HTP.

Positive effects:
  1. Reduction of anxiety (possibly through suppression of adrenergic system through NE-beta receptors) - The maximal reduction of anxiety occurred when I took DL-phenylalanine.
  2. The tingling sensation and heaviness feeling in my left hand ring finger went away. I could type with left hand fingers without any conscious awareness of this problem.
  3. My obsessive and compulsive behaviours like circling with fingers, looking for symmetry in the objects I see, massaging my hands, massaging my stomach and chest, silent pronouncing of eating sounds while eating etc.,
  4. My stuttering becomes less and fluency and diction improved.
Negative effects:
  1. Excessive fatigue (more with more dosage and after taking for 1 month)
  2. Excessive sleepiness (Used to sleep for 8+ hours/day)
  3. Decrease in libido (No spontaneous sex drive, Weak erections. But, I could get strong erections and increased sensation of the penis while having sex after supplementation with DL-phenylalanine. No change in libido even after supplementation with DL-Phenylalanine). However, I noticed a strange thing. After taking the 5-HTP for 1 month and if I stop it suddenly for 1 full day, then my libido increased.
  4. Decreased movements (I could not walk faster or do things faster)
  5. Decreased motivation to do any new things or risk taking
  6. Mental clouding - less clarity in thinking, can't think deeply
  7. Less caring for the spouse and children - less familial bonding and attachment
  8. Increased tendency to pick up fights with wife

The reason for the side effects could be due to the suppression of dopamine in CNS.

Blurred vision

Blurred vision occurred to me at the age of 7-8 years. I still remember it happened to me when I played cricket in the hot sun between 11.00AM to 12.30PM. My eyes squinted and could not see the objects properly, especially the near ones. But, still I could recognise everything and I could continue to play. The symptoms worsened when I run more. Still it happens whenever I walk for more than 1 hour at a stretch or strenous play outdoors. If I do exercise indoors, it does not occur. It also increases with stress building activities like driving to a new location to meet an appointment.

So far the possible reasons I could identify to my knowledge are,

1. Increased acetylcholine levels
2. Increased adrenaline levels

2nd May 2010
Blurred vision occurred to me in the recent days while driving for more than 30 minutes. Along with multivitamins, 5-HTP, DL-phenylalanine, magesium, taurine, glycine, vitamin C, I was taking geriforte and blurred vision occurred to me worse enough to impair my driving. However, I remembered that it did not occur while I was going for driving classes. The single driving class lasted more than 3 hours sometimes and it was stressful. But no blurred vision occurred at that time. I remembered that I was taking omega 3 supplement (DHA + EPA = 780 mg) at that time. For the past two days night, I took the same omega -3 supplement and today I drove to 20 km up and 20 km down for a wedding ceremony. No sensible blurring and squinting occurred. So, it is clear now that either omega -3 deficiency or improper omega3/omega 6 ratio could be the reason for my blurred vision and squint. Also I was taking mentat for the past few weeks. It is a dopamine agonist. So may be a dopaminergic neurotransmission also may play a role in this. More literature search is required in this.    

Lysine and arginine for high trait anxiety

Recently I read few research articles claiming reduction of high trait anxiety after administration of lysine and arginine. I have to try these combination to see the effect on my stuttering and the effect on my social anxiety.

Effects of Himalaya's geriforte

I am taking himalaya's geriforte for the past few days. And as usually, I found my anxiety is low and my stuttering is very minimal. Fluency of speech is excellent with good diction. From the literature, I found that geriforte may work through steroid receptors in the body.

I assume that my cortisol levels are low than the normal. (Even though the laboratory test results indicate the normal results. 1. I tested at Malar hospital, Chennai at 10 am after a coconut oil full body massage and steam bath at a naturopath's clinic (No breakfast, had only tea), tested in blood 2. Test done by neurogistics, US with saliva samples.) Since I experience everyday social anxiety stress due to my stuttering, I expect my cortisol levels to be higher than normal.

Also, based on the research literature, my LC-NE (locus ceroleus-norepinephrine) circuit seems to be high. Due to that, I used to have slightly elevated BP always (130/90). My cortisol levels should be lower than normal due to the continuous increased LC-NE activity. Due to everyday stress, my cortisol may appear to be normal (It could be actually an increase from the lower level).

After taking geriforte for few days, I tested my BP. Surprisingly, my BP was lower around 120/80 on repeated readings. Also, it increased my fluency to a greater level. From these things, I can assume that geriforte may work on corticosteroid receptors. Because glucocorticoids are known to reduce the LC-NE firing. Also, I experienced reduction of anxiety and stress.

Also I am taking a baby milk formula which contains tryptophan and tyrosine along with omega 6 and omega 3. I use this milk powder for making my milk tea. After taking this I don't find any greater influence of serotonergic effects like intense nausea. Also, the phenylalanine or tyrosine related effects like increased BP or increased stuttering or presyncope (about to faint feelings) or increased limb movements while walking. I assume that geriforte may normalize the HPA axis by reducing the LC-NE activity and decrease the impaired negative feedback of cortisol at the HPA axis.

Also, I experienced side effects after taking this medicine. gasping for breath while talking (bronchoconstriction), bloated stomach, blurred vision and some unusual irritating feeling inside my head (I don't know how to express this symptom and this symptom is completely stopped after I took magnesium with glycine and taurine, so it could be increased glutamate activity) which produced restlessness. The bronchoconstriction effect subsided slowly after few doses. Blurred vision is worsened with stress (when I was driving to a new place, blurred vision occurred and it didn't subside even after resting for few hours and eating lunch, after sleeping only it subsided). So, the blurred vision could be also due to increased epinephrine release during the stress.

So based on the adverse effects of this drug, the mechanism of action could be through cholinergic system. I read one literature that ashwagandha acts through inhibition of acetylcholine esterase. This could be the possible reason for blurred vision.

Also, I found that my fecal incontinence is much better now. So, it could have been caused by the weaker sphincter muscle which is again caused by a low acetylcholine level.