Serotonion plays a part in numerous functions in the human body including modulation of appetite, sleep, mood and emotion (Schloss & Williams 1998). It also plays a role in memory and learning (Sarkisyan & Hedlund 2009) and temperature regulation (Hodges et al 2008).
In addition, a high comorbidity exists between depression and CVD (Halaris 2009). It is well established that serotonin plays an important part in the pathogenesis of CVD via platelet aggregation and regulation of smooth muscle in the CV system (Nigmatullina et al 2009, Jonnakuty & Gragnoli 2008).
Serotonin receptors are also widespread in the gastro-intestinal tract (found on neurones, smooth muscle cells and epithelial cells) where it plays a vital role in intestinal secretion, sensation and peristalsis (Jonnakuty & Gragnoli 2008). It is thought that altered serotonin signaling may contribute to GI conditions such as irritable bowel syndrome (Sikander et al 2009, Camilleri 2009).
Serotonin is synthesised from an amino acid tryptophan via two steps:-
1. Tryptophan to 5-HTP
2. 5-HTP to serotonin
5-HTP is an intermediate in the metabolism of tryptophan to serotonin. It may be more beneficial than tryptophan, as tryptophan can also be metabolized along different pathways (e.g. to niacin), whereas 5-HTP is a direct precursor to serotonin. In addition, 5-HTP easily crosses the blood-brain barrier (BBB) without the need for a transport protein (and therefore does not compete with other amino acids) (Jonnakuty & Gragnoli 2008).
1. Conversion of tryptophan to 5-HTP (5-hydroxytryptophan) is via rate-limiting enzyme tryptophan hydroxylase (Stipanuk & Watford 2000:406), a non-heme iron-dependent enzyme (Windahl et al 2008). Other essential cofactors include folic acid (Bland & Jones 2005:641), vitamin C (Stone & Townsley 1973), calcium (Kuhn et al 1997) and magnesium (Lysz et al 1982). SAMe also functions as a methyl donating co-factor in this rate-limiting step (Mischoulon & Fava 2002)
Indirectly, adequate vitamin B3 levels are also required (if inadequate niacin is present, tryptophan will be preferentially converted to niacin) and low levels of other B vitamins can also have a negative effect on production (Osiecki 2006 :494)
2. Conversion of 5HTP to serotonin by 5-hydroxytryptophan decarboxylase a pyridoxal phosphate (active form of vitamin B6 dependent enzyme (Stipanuk & Watford 2000:406). Zinc is required for the conversion of B6 to its active form (Ebadi et al 1984). Magnesium is also essential for this conversion (Jonnakuty & Gragnoli 2008)
Methyl donors, e.g. TMG and SAMe, must be present for the serotonin pathways to function correctly (Miller 2008).
If you take 5-HTP as a supplement, you must take it with a carbohydrate-rich snack, which triggers the release of insulin. Insulin decreases plasma levels of certain amino acids that compete with tryptophan for transport across the BBB (Takeda et al 2004). This allows more tryptophan into the brain, which is then synthesized into serotonin.
Conventional treatment
Low levels of serotonin have been linked to depression and the main conventional treatment for depression is through the use of SSRIs (selective serotonin reuptake inhibitors), which slow down the process of serotonin reuptake (neurones normally recycle serotonin by absorbing it into the pre-synaptic terminal once it has elicited the desired effect on the post-synaptic neurone). This leads to the chemical remaining in the vicinity of the receptors for longer, making it more likely that enough will build up to trigger an impulse in the next neurone. SSRIs work by allowing the body to make the best use of the reduced amounts of serotonin that it has at the time.
Side effects of SSRIs are an important issue - approximately 15% of patients cannot tolerate certain side effects and may discontinue SSRIs (Khawam et al 2006)
Common side effects include:-
• Sleep disturbances and insomnia
• Sexual dysfunction
• Weight gain
• Nausea and vomiting
Less common symptoms include:-
• Drowsiness
• Headache
• Loss of appetite
• Diarrhoea
It has also been claimed that antidepressants, especially SSRIs, may lead to an increased risk of suicide, particularly among children and adolescents. Although the evidence is inconclusive, the US FDA has warned clinicians of the risk and recommends close monitoring of patients at the start of treatment (Khawam et al 2006)
Refrences:
available on the request
Please email your views, comments, research, etc. to admin@bcnh.co.uk
In addition, a high comorbidity exists between depression and CVD (Halaris 2009). It is well established that serotonin plays an important part in the pathogenesis of CVD via platelet aggregation and regulation of smooth muscle in the CV system (Nigmatullina et al 2009, Jonnakuty & Gragnoli 2008).
Serotonin receptors are also widespread in the gastro-intestinal tract (found on neurones, smooth muscle cells and epithelial cells) where it plays a vital role in intestinal secretion, sensation and peristalsis (Jonnakuty & Gragnoli 2008). It is thought that altered serotonin signaling may contribute to GI conditions such as irritable bowel syndrome (Sikander et al 2009, Camilleri 2009).
Serotonin is synthesised from an amino acid tryptophan via two steps:-
1. Tryptophan to 5-HTP
2. 5-HTP to serotonin
5-HTP is an intermediate in the metabolism of tryptophan to serotonin. It may be more beneficial than tryptophan, as tryptophan can also be metabolized along different pathways (e.g. to niacin), whereas 5-HTP is a direct precursor to serotonin. In addition, 5-HTP easily crosses the blood-brain barrier (BBB) without the need for a transport protein (and therefore does not compete with other amino acids) (Jonnakuty & Gragnoli 2008).
1. Conversion of tryptophan to 5-HTP (5-hydroxytryptophan) is via rate-limiting enzyme tryptophan hydroxylase (Stipanuk & Watford 2000:406), a non-heme iron-dependent enzyme (Windahl et al 2008). Other essential cofactors include folic acid (Bland & Jones 2005:641), vitamin C (Stone & Townsley 1973), calcium (Kuhn et al 1997) and magnesium (Lysz et al 1982). SAMe also functions as a methyl donating co-factor in this rate-limiting step (Mischoulon & Fava 2002)
Indirectly, adequate vitamin B3 levels are also required (if inadequate niacin is present, tryptophan will be preferentially converted to niacin) and low levels of other B vitamins can also have a negative effect on production (Osiecki 2006 :494)
2. Conversion of 5HTP to serotonin by 5-hydroxytryptophan decarboxylase a pyridoxal phosphate (active form of vitamin B6 dependent enzyme (Stipanuk & Watford 2000:406). Zinc is required for the conversion of B6 to its active form (Ebadi et al 1984). Magnesium is also essential for this conversion (Jonnakuty & Gragnoli 2008)
Methyl donors, e.g. TMG and SAMe, must be present for the serotonin pathways to function correctly (Miller 2008).
If you take 5-HTP as a supplement, you must take it with a carbohydrate-rich snack, which triggers the release of insulin. Insulin decreases plasma levels of certain amino acids that compete with tryptophan for transport across the BBB (Takeda et al 2004). This allows more tryptophan into the brain, which is then synthesized into serotonin.
Conventional treatment
Low levels of serotonin have been linked to depression and the main conventional treatment for depression is through the use of SSRIs (selective serotonin reuptake inhibitors), which slow down the process of serotonin reuptake (neurones normally recycle serotonin by absorbing it into the pre-synaptic terminal once it has elicited the desired effect on the post-synaptic neurone). This leads to the chemical remaining in the vicinity of the receptors for longer, making it more likely that enough will build up to trigger an impulse in the next neurone. SSRIs work by allowing the body to make the best use of the reduced amounts of serotonin that it has at the time.
Side effects of SSRIs are an important issue - approximately 15% of patients cannot tolerate certain side effects and may discontinue SSRIs (Khawam et al 2006)
Common side effects include:-
• Sleep disturbances and insomnia
• Sexual dysfunction
• Weight gain
• Nausea and vomiting
Less common symptoms include:-
• Drowsiness
• Headache
• Loss of appetite
• Diarrhoea
It has also been claimed that antidepressants, especially SSRIs, may lead to an increased risk of suicide, particularly among children and adolescents. Although the evidence is inconclusive, the US FDA has warned clinicians of the risk and recommends close monitoring of patients at the start of treatment (Khawam et al 2006)
Refrences:
available on the request
Please email your views, comments, research, etc. to admin@bcnh.co.uk
