content
- introduction
- Therapeutic effects of tryptophan
- influence of tryptophan on the serotonin system in the brain
- tryptophan - more than a non-prescription sleep aid
- influence of tryptophan on mood - treatment of disorders of affectivity
- Under what Tryp doses, a sufficient therapeutic effect can be expected?
- comes under what conditions, the maximum uptake of tryptophan into the brain - or how to optimally stimulate the central serotonin synthesis?
- physical endurance as possible, the central availability increase of tryptophan
- Other drugs with influence on the central availability of tryptophan
- Inhibition of Tryptopan-degrading enzymes increased the central tryptophan availability
- The effects of stress on the tryptophan-serotonin system
- How could a suitable regimen for the tryptophan intake look like?
- Recommended duration of therapy
- tryptophan deprivation
- What are the other, negative side effects of regular tryptophan supplementation? How can I prevent this?
- is to take 5-HTP as an alternative to trypsin supplementation?
- Are there other Ways to increase the intake of non-Tryp tablets Tryp supply and subsequently to stimulate serotonin synthesis?
- interactions between tryptophan and dopamine
- tryptophan - interaction with the analgesic tramadol
- What is happening to long-term tryptophan treatment, taking into account the interactions with the dopamine system?
- Why are the study results for tryptophan in relation to antidepressant effect, so inconsistent?
- refers Why tryptophan in the treatment of depression so little consideration?
tryptophan supplementation - an Update 2010
introduction
In many countries, tryptophan (Tryp) and non-prescription medicines available. Supplementation of Tryp - without prescription - has an important role in the self-medication for the treatment of mood swings, but also to correct personality-related affective disorders, in particular from increased impulsivity (aan het Rot et al 2006)..
Tryp is also used for supportive treatment in addition to selective serotonin reuptake inhibitors (SSRIs) for treatment of depressive disorders (Lowe et al. 2006). Certain personality disorders, but also temporary affective disorders and mood swings can have their origin in dysfunction of the serotonin system (Wilson et al. 2009). This disturbance in turn is often by a relative deficiency due Tryp (Richard et al. 2009). The Tryp supplementation is possible to treat this disorder pathophysiologically causal. Unfortunately, these side effects treatment option for physicians currently has only a minor role. The lack of proof of effectiveness through randomized controlled trials (RCT) can be accepted as a possible explanation. To optimally effective, must be considered in the special revenue Tryp supplementation conditions. The ignorance of these relationships leads to a lack of efficacy and as a consequence to poor acceptance of therapy. The specific conditions appear to revenue side of the patient to reduce further the acceptance of the trypsin treatment.
the amino acid tryptophan is the key precursor for the formation of serotonin. Most of the total body serotonin is located in the gastrointestinal tract (Sanger 2008). Although negligible in terms of volume, the content of serotonin in the brain is of utmost importance to (Richard et al. 2009). Serotonin as a neurotransmitter in the brain takes very much influence on behavior and mood. Serotonin is also on other physiological Functions such as sleep and appetite involved. A lack of serotonin are involved seems essential in the development of certain forms of depression. A prolonged tryptophan deficiency leads inevitably to a reduced formation of serotonin. The vulnerability to serotonin-or tryptophan deficiency is individually very different characteristics (Richard et al. 2009, Janssen et al. 2007). The vulnerability seems to be genetic on the one (Roiser JP et al. 2006, Markus et Firker 2009 b), seems also to develop as a result of chronic stress (Jans et al. 2007 Firker et Markus 2009). Regular treatment with tryptophan as the vulnerable people in accordance with a positive impact on mood and may improve depressive symptoms (Murphy et al. 2006, Markus et al. 2008). This amino acid seems particularly effective in the therapy to be of affective disorders. For example, can be excessive impulsivity (aan het Rot et al. 2006), but also reduce irritability (Steinberg et al. 1999) with tryptophan.
tryptophan (Tryp) is an essential amino acid. A balanced diet with normal protein content ensures an adequate supply of tryptophan. Of the 20 amino acids in the human body has the lowest concentration of tryptophan and apply the fabric store to be minimal (Monographie L-Tryptophan 2006). As a consequence from tryptophan is considered one of the rate-limiting amino acids for protein synthesis. The average daily intake is with 1 to 1.5 g given (Benedict et al 1983, Richard et al 2009..). By increasing the protein content in the daily diet can indeed increase the total supply of tryptophan, this is usually without effect on serotonin metabolism in the brain (Fernstrom et al. 1979). Positive effects such as depressive disorders can not be achieved on these routes. An increase in the relative proportion of tryptophan in the total protein intake seems, however, a possibility to influence the formation of serotonin in the brain. To Tryp-share increase in the total protein intake is, in addition to the Tryp supplementation in particular whey protein, which has a relatively high trypsin content. A high carbohydrate in the diet and particularly the isolated carbohydrate intake also appears to be a positive effect on serotonin synthesis (Lieberman et al. In 1986, Richard et al. 2009).
A tryptophan deficiency has a direct impact on short-term serotonin metabolism in the brain and leads to vulnerable people in decreased mood (Jans et al 2007, Moreno et al. 2000) and impairment of learning and memory (Park et al. 1994). The immediate consequences of a generated under study conditions relative Tryptophan deficiency can be very pronounced in some individuals. A tryptophan-free diet is poor or within 5 - 7 h (. Richard et al 2009) has a negative effect on mood and can lead to mood disorders, such as increased impulsivity (Dougherty et al 2007. Walder Haug et al. 2007, Schweighofer et al. 2008) or aggression (Moeller et al. 1996). In addition, early memory performance, such as disrupted the consolidation of acquired knowledge (Park et al. 1994 Sambeth et al. 2007). Moreover there are indications that a trypsin deficiency to be delayed decision making significantly (Rogers et al. 1999). The vulnerability to Stress also appears to be increasing at a Tryp deficiency significantly (Firker et Markus 2008).
Therapeutic effects of tryptophan
tryptophan, among other things approved in Germany as a drug for the treatment of sleep disorders. L-tryptophan is a non-prescription medicine and is offered in a dose of 500 mg per tablet. In the scientific literature that has always stood another application in focus: the treatment of depressive disorders. As an important precursor to the formation of serotonin (5-hydroxytryptamine) may intervene directly in the Tryp this central neurotransmitter metabolism. The influence of the serotonin system to the chemical class of selective serotonin Reuptake inhibitors (SSRIs) has emerged in the past 20 years as the most effective treatment option for the treatment of depression (Petersen et al. 2002). Besides the influence of depressive symptoms has the Tryp administration worked effectively to reduce affective disorders, particularly for the treatment of severe impulsivity (aan het Rot et al. 2006). When seasonal affective disorder (SAD), the so-called winter depression, is deteriorating because of the shortened days with the absence of daylight influence the mood of sensitive people. Besides the well-documented effectiveness in its light therapy (10,000 lux for at least 30 min) also seems to be the Tryp-handed an additional positive effect on (Lam et al. 1997). Moreover there are indications that a Tryp-dose positive effect on cognitive abilities (Haider et al. 2006). A major difference compared to the Tryp is a treatment standard for depressive disorders apply serotonin reuptake inhibitors in the time to onset. While the Tryp-effect detectable on the symptoms is usually after about a week (. Levitan et al 2000), the serotonin reuptake inhibitors require significantly longer (2-3 weeks) report to the patient about an improvement in symptoms. Moreover there are indications that the effect of serotonin reuptake inhibitors by the additional improve administration of Tryp (Lowe et al. 2006, Levitan et al. 2000) leaves.
influence of tryptophan on the serotonin system in the brain
The conversion of tryptophan into 5-Hydroxythryptophan and finally in 5-hydroxytryptamine (serotonin) in the CNS is stimulated by exogenous addition of Tryp. Necessary condition for a sufficient serotonin synthesis in the brain seems to be a steady supply of free Tryp at the blood-brain barrier to be.
After the recording of Tryp across the blood-brain barrier, the first step, the hydroxylation by the enzyme trypsin hydroxylase. This reaction is the rate-determining step on the road to serotonin synthesis. This enzyme is under physiological conditions only half saturated (Young et Gautier 1981) and by a high substrate availability in its activity further stimulated (Fernstrom and Wurtman 1972, Heuthen et al. 1992), ie, a high concentration of free tryptophan in the bra barrier to increased formation of 5-hydroxytryptophan (5-HTP), a precursor of serotonin (5-hydroxytryptamine). Please do
is that both vitamin B6 (Hvas et al 2004) and a magnesium deficiency (Durlach J et al 2002, Korbitz BC 1970.) Inhibits the activity of the enzyme and thus reduces serotonin synthesis . The same is true for caffeine, which also reduced the activity of the enzyme Tryp-hydroxylase (Lim et al 2001). A regular coffee may therefore adversely affect the serotonin synthesis.
tryptophan - more than a non-prescription sleep aid
The effect of initiating sleep Tryp be explained by its inclusion into the brain and metabolism of melatonin (Cubero et al 2006, Heuthen et al 1992..).
Administration of Tryp in doses from 1 to 1.5 g has immediate effect as the effect of initiating a sleep that occurs after about 30 minutes (Hartmann 1982). This effect only occurs when Tryp is administered in the second half of the day and one also is in a physical hibernation. The different effects of Tryp at different times may be related to the endogenous circadian rhythm Tryp of free blood in context. The natural circadian rhythm of plasma levels of free Tryp points to its minimum in the night, while the maximum is observed in the early evening (Eynard et al. 1993). Accompanying the initiating sleep effect of a tryp-specific cognitive disorder, which is described as pleasant. Physical activity after taking Tryp prevents the effect of initiating sleep completely. The mental concentration with other everyday activities is not directly affected by Tryp-taking. Very mild cognitive impairment are rarely observed during exercise, but without significantly affecting the performance or coordination.
The late-night recording of Tryp should take place well behind the last meal. Under these conditions, good bioavailability for the central serotonin synthesis and conversion to melatonin is given.
influence of tryptophan on mood - treatment of disorders of affectivity
requires the mood effects of Tryp targeted Supplemtation. The first signs of improved mood already after 3 to 4 days - significantly (1.5 3 g / day) intake. After 2 to 3 weeks should be a clear subjective improvement may be detected. After resolution of the Board of symptoms a weaning is appropriate. In Depending on the cause of serotonin deficiency may experience the symptoms again within weeks. needed in these cases after the treatment phase, it is usually a maintenance therapy Tryp. A Tryp-day dose of 1.5 - 3 g for 3 to 4 days of the week seems to be sufficient to maintain the positive effects.
Affective disorders are often accompanied by an influence of the subjective state and experience and have a negative effect on imagination and thought content. Typical symptoms include negative affect with disapproving facial expression, avoidance behavior accompanied with negative mood. Many of these symptoms also speak well to trypsin treatment. Also a
affect incontinence with a lack of control of emotions and expressions of feeling which are at low exaggerated and uncontrollable events, can be positively influenced by the stimulation of serotonin synthesis. These people are prone to impulsivity, is reduced under these Tryp supplementation (at least 2 to 4 weeks, dose is 1.5 - 3 g / day).
also a general, non-specific increased excitability, irritability or imbalance to assign the causes are not clear, can respond to trypsin supplementation.
Under what Tryp doses, a sufficient therapeutic effect can be expected?
The safe and effective evaluated doses of tryptophan with 0.4 to 4 g daily given (Monographie L-tryptophan). In numerous studies on the treatment of depression with tryptophan doses were administered daily 6 g (Herrington et al. In 1974, D'Elia et al. 1977, Steinberg et al. 1999). As a complementary therapy Tryp was also used in doses of 3 g daily successful (Lam et al. 1997). As a sleep aid, however, are already doses of ≥ 1 g sufficiently effective. Repeated daily administration of 1,5 - 3 g Tryp about 2 to 3 weeks seems sufficient to offset a relative lack of central serotonin and make positive changes happen (aan het Rot et al 2006).. A daily Dose of 1.5 g Tryp is only sufficient when the conditions for admission are designed so that high concentrations of free Tryp effect at the blood-brain barrier for a sufficiently long period. The intake of eg 1.5 g Tryp together with a normal meal are not likely to increase the supply of free at the Tryp BH barrier crucial. In principle the introduction of Tryp together with protein-rich food is unfit to affect the central serotonin synthesis significantly. Accordingly, 1.5 are - 3 g daily dose Tryp-sufficient only if the administration in the fasting state, ie,> 3 hours after the last and at least 2 hours before the next Meal takes place. Further optimized the concentration of free Tryp if the Tryp-taking after a long fasting period (the morning before the first meal) takes place. Under a long-lasting endurance exercise (eg running or cycling), without intermediate energy supply to be achieved almost perfect conditions to stimulate the inclusion of the CNS and the central serotonin synthesis (Chaouloff 1997).
comes under what conditions, the maximum uptake of tryptophan into the brain - or how to optimally stimulate the central serotonin synthesis?
Tryp competes with other amino acids such as phenylalanine, tyrosine, valine, leucine and isoleucine by the same transporter at the blood-brain barrier (BH-barrier). These amino acids are among the group of large neutral (LNAA) and branched-chain amino acids (BCAA). A low ratio of the competing Tryp AS was repeatedly observed in depressed patients (Moller, 1985, Kaneko et al. 1992). Only the free, not protein-bound form of the Tryp can happen to the BH bound. Conditions for a maximum Tryp recording are therefore a high proportion of free to total Tryp-tryptophan in the blood and a low concentration of competing amino acids (LNAA, BCAA). Pharmacokinetic studies indicate that sufficiently high doses of Tryp (at least 1 - 1.5 g per single dose) must be given to to achieve the required high concentrations of free Tryp to the BH bound (Green et al. 1980). These studies have also shown that the concentration is high enough to free Tryp only within the first 2 to 3 hours after oral intake in order to ensure effective uptake into the brain. To stimulate the central serotonin synthesis, it seems also necessary that a threshold in the ratio of Tryp to competing amino acids in plasma (Tryp / LNAA ratio) is exceeded. Accordingly, an increase of Tryp / LNAA ratio in plasma of 40 would be - 70% compared to baseline is required (Markus et al 2008)..
Physical to increase endurance as possible, the central availability of tryptophan
under prolonged physical endurance it comes to metabolic changes, which have a beneficial effect on the central availability of Tryp (Chaouloff 1997). Animal studies also indicate that endurance exercises lead to a stimulation of endogenous serotonin synthesis. (. Meeusen et al 1996) Administration of Tryp before an endurance exercise leads to a further increase in serotonin synthesis in the brain
Numerous studies with beta-2 agonists (eg salbutamol, clenbuterol) is well known that these drugs - probably an activation of central beta-2 receptors - the listing of Tryp in the CNS to promote (Lenard et al 2003.). Under intense endurance exercise, it is physiologically of the increased noradrenaline / adrenaline secretion also for the activation of beta-2 receptors and this mechanism probably leads to an increased central availability of Tryp.
Since the inclusion of Tryp at the blood-brain barrier is dependent on Others, on the concentration of the same transport system-using branched-chain amino acids (BCAA), which during exercise increases occurring inclusion of BCAA (leucine, isoleucine, valine) in the muscles of cheap labor Effect on the Tryp-uptake into the brain (Blomstrand et al. 1991). BCAA are in prolonged endurance exercise under the influence of insulin and insulin-independent added to energy supply in the muscle cells. The Tryp / BCAA ratio is in the blood during an endurance exercise shifted increasingly in favor of tryptophan and thus increases the probability of Tryp-uptake into the brain.
addition Tryp competes with free fatty acids (FFA) for binding to albumin in the blood. Only the albumin-bound not to pass through the Tryp BH barrier. All conditions that increase the proportion of FFA in the blood, increase the concentration of free Tryp (STRUDER et al. 1996). From these observations would be to derive that charges to be absorbed with very low intensity to increase the central absorption of tryptophan and serotonin synthesis. Various studies indicate, however, that increase serotonin synthesis pressures are particularly intense (Caperuto et al. 2009). A compromise would therefore be a high stress intensity at which but still is an essential part of the energy supply of the fat metabolism (70% - 75% VO2max), also increases at this intensity during the exposure, the concentration of free fatty acids continuously (Strüder et al. 1997). From a loading period of 40 - 60 min increases parallel to FFA concentration and the fraction of free to Tryp. the endurance exercise is also started in a fasting state (laid back last food intake> 4 hours), the FFA levels are already high in the beginning of exercise. under these conditions for 30 minutes before the beginning of exercise Tryp in a dose of 1.5 g is applied to be an early high levels of free Tryp in the blood reaches. The Tryp recording should be at least 100 ml of water (not fruit juice, as the subsequent release of insulin reduces FFA levels). To pass to the systemic availability of Tryp about 30 minutes over the entire pollination period exist then optimal conditions for tryptophan uptake in the CNS. Since even after the exposure period, the concentration of FFA at least increased for one hour stay (Henderson et al. 2007), the next meal should be taken only after some delay, so as to maintain an overall long term optimum conditions for the Tryp-uptake into the brain. Prolonged endurance exercise only lead to increased uptake into the CNS Tryp when fed during exercise no carbohydrates (Blomstrand et al. 2005).
Other agents with influence on the central availability of tryptophan
The following substances having an effect on the concentration of FFA may therefore indirectly influence the Tryp uptake into the CNS. Administration of chromium (chromium picolinate-) leads acutely and chronically to an increase in free Tryp, probably on the increase of FFA (Franklin and Odontiadis 2004).
for heparin administration, as an anticoagulant (to prevent blood clotting) is an increase in the concentration of free Tryp documents that can be attributed to an increase in FFA levels in heparin (STRUDER et al. 1996).
The ingestion of caffeine does lead to an increase in FFA and increases and the free, not protein-bound part of the Tryp, but an inhibitory effect is on serotonin synthesis (inhibition of the enzyme Tryp-hydroxylase, Lim et al. 2001) and can therefore as adjuvant therapy for non-depressive symptoms and affective disorders recommended be.
Moreover there are indications that during treatment with acetylsalicylic acid (ASA, aspirin), an increase of free tryptophan in the blood comes. This ASS tryptophan displaced from its plasma protein binding on albumin (Maharaj et al. 2004). This effect is the therapeutic dose of 500 mg in the ASA analgesic and antipyretic effects, documented, and seems therefore of clinical relevance. Other drugs that increase the proportion of free Tryp by displacement from albumin binding are Clofibrate (lipid lowering agents) and probenecid (reduction of elevated uric acid levels) (Badawy 2009).
for niacin is known to be acutely to a reduction in FFA concentration leads (dosage 500 mg). Less well known is that there are about 3 hours after ingestion of a rebound phenomenon with a significant increase in FFA is (Peireira 1967 Kamanna 2007). The capture of Tryp about 3 hours after niacin administration should also result in an increased concentration of free Tryp, creating good conditions for an optimized Tryp-bioavailability.
Administration of physiological doses of niacin (vitamin B3) has an always beneficial effect on serotonin synthesis, when a relative of vitamin B3 deficiency. An inadequate supply of vitamin B3 will cause the body to a substantial part of the recorded Tryp for endogenous synthesis of vitamin B3 used. The concomitant administration of niacin (vitamin B3) in low doses together with Tryp to compensate for deficiencies does not make sense, since niacin that in the liver for degradation of Tryp competent enzyme (TDO) is activated (Sainio et al. 1990). Consequently, the balance of an insufficient vitamin B3 status before the start of trypsin treatment to be completed.
Even for high doses of niacin (> 500 mg) are the unfavorable effects on the availability of the serotonin synthesis Tryp described (Penberthy 2007). High doses of niacin another important Tryp stimulate the degradation of responsible enzyme system (indoleamine-2 ,3-Dihydroxyoxigenase).
more Tryp is substituted more Tryp is the synthesis of serotonin available. This statement is incorrect! The repeated administration of high doses of Tryp does not lead to the expected high trypsin levels in the blood. Responsible for this are two enzymes break down, the Tryp. The activity of both enzymes is induced by a high Tryp recording. The enzyme tryptophan dioxygenase (TDO) is mainly localized in the liver. Since stimulate repeated high doses of the enzyme Tryp, it makes sense to distribute the Tryp-taking on several low doses and schedule regular days without Tryp administration. This approach is supported by studies on pharmacokinetics of Tryp, the latest 4 - 6 hours after taking back a normalization Tryp plasma levels of documentation (Green et al. In 1980, Moller 1981). It should be noted that the single dose should be chosen such that sufficiently high concentrations are generated at free Tryp (≥ 1.5 g Tryp) (Green et al. 1980). In summary, it seems like good, Tryp not to give a permanent treatment, but as an interval therapy with breaks, and to consistently achieve the normalization of the TDO enzyme activity.
Another option to increase the supply of Tryp to the bra-barrier would be the administration of substances that inhibit the TDO enzyme.
The second key enzyme for the degradation of Tryp is indoleamine-2 ,3-Dihydrooxygenase (IDO). This enzyme is in contrast to the TDO in many tissues before and has a special significance for the development of tolerance to foreign antigens. The IDO activity is increased by a high offer of Tryp Tryp and thus reduces the availability of serotonin synthesis.
Inhibition of Tryptopan-degrading enzymes increased the central tryptophan availability
The enzyme tryptophan dioxygenase (TDO), which is located mainly in the liver, prevents high tryptophan intake through its decomposition, that the offer of free Tryp for inclusion in the central nervous system proportional to the absorbed dose increases (Salter et al. 1995). It also seems an inverse relationship between the levels of serotonin in the brain and consist of TDO activity in the liver (Daya et al. 1989).
There are indications that the administration of paracetamol to inhibit TDO activity and thus the amount of Tryp, which stands for the synthesis of serotonin available increased (Daya et al. 2000, Maharaj et al. 2004). The same effect on the TDO activity was described for acetylsalicylic acid (ASA, aspirin) in an animal study (Maharaj et al. 2004).
Also for the administration of melatonin, an inhibitory effect on TDO activity is documented (Walsh et al. 1997). In particular, since high doses of melatonin can affect the sleep-wake rhythm, sleep, a combination with the adjoining Tryp to be unsuitable as a long-term medication.
There is evidence that alcohol consumption also increases the TDO activity. Within 2 hours after alcohol consumption is a waste of Tryp plasma levels and an increase of kynurenine metabolites was measured (Badawy et al. 2009). As described above, also stimulate physiological doses of vitamin B3, the enzyme and thereby reduce the TDO Tryp levels in the blood (Sainio et al. 1990).
The second important enzyme for the degradation of Tryp is indoleamine-2 ,3-Dihydrooxygenase (IDO).
For a number of natural substances, inhibition of IDO is described. For example, rosmarinic acid inhibits the IDO activity and thus the degradation of Tryp (Lee et al 2007). It is possible that some of the positive effects of lemon balm extract (containing a high content of rosmarinic acid, for example Gastrovegetalin ®) due to its influence on the serotonin system.
Also for the Curcurmin (turmeric) has an inhibitory effect on IDO activity documented (Jeong et al. 2009). Curcurmin in the literature for an antidepressant effect is described, the effect is mediated only partly via serotonin receptors (Wang et al. 2008).
A recent study provides the first evidence that cocoa also exerts an inhibitory effect on IDO activity (Jenny et al. 2009). Further studies must show whether Cocoa in the usually distorted quantities is positive for the Tryp availability.
resveratrol, a substance that occurs naturally in grapes (especially high concentrations have been documented for red wine), also inhibits the enzyme IDO (Banerjee et al. 2008).
Even the butyrate appears to be a very significant effect on the IDO activity to have. Initial studies have shown that sodium butyrate down-regulated the IDO enzyme activity (GM Jiang et al. 2010). For the butyrate has long been known that in the area of the mucosa develops a tumorprotektive effect. On the way dietary butyrate concentration in the gut can, for example by increased Range of resistant starch increased in the diet. If in vivo confirm that improve nutritionally induced high butyrate concentrations, the central tryptophan availability, so would be an easier way available to counter such a high stress-induced IDO activity. This high level of IDO activity may be instrumental in the development of depression as a result of chronic stress.
aspirin appears to have different mechanisms of the central availability of tryptophan to influence positively. Besides the increase of the free Tryp by displacement from plasma protein binding and inhibition of TDO activity, is another mechanism discussed: ASS thus reduced the interferon-γ-mediated increased activity of IDO as a result of immune stimulation (Schroecksnadel et al 2005.).
The effects of stress on the tryptophan-serotonin system
The relationship between prolonged high stress levels and the incidence of depression is described in the literature repeatedly. The mechanism, through the stress on depressive symptoms is, however, still insufficiently understood. A possible explanation is that stress, increased cortisol release, the TDO-stimulated activity and thus contributes to the degradation of Tryp (Hirota T. et al. 1985). This mechanism of action explains only partly the occurrence of depression as an expression of relative serotonin deficiency (Miura et al. 2008). A recent study by Kiank et al. 2010 is coming to the conclusion that repeated stress situations lead regardless of cortisone to a relative lack of tryptophan with a subsequently reduced formation of serotonin. The cause of the diminished supply is the tryptophan studies show that the activation of the enzyme indoleamine-2 ,3-dioxygenase (IDO) by certain cytokines (TNFalpha, IFNgamma). Prolonged stress affects therefore the activation of both tryptophan-degrading enzyme (TDO, IDO), a maximum inhibitory effect on the formation of serotonin. This observation provides a satisfactory explanation for the frequent occurrence of depressive symptoms due to high stress.
might look like an appropriate treatment regimen for the tryptophan dose?
For persons engaged in any regular endurance sports, the gift would be recommended by 2x daily 1.5 g of Tryp in a fasting state with the largest possible distance to your next meal. Individually, higher doses than 1.5 g Tryp be necessary.
order not used to the effect of Tryp initiating sleep, should a late-evening ingestion should be avoided. Would be likely in the morning music directly after getting up, at least one hour before the breakfast. The second dose may be in the early afternoon with at least 2 - 3 hours distance made for lunch.
for persons who participate regularly in endurance sports, the intake of 1.5 g offers Tryp 30 minutes to load before beginning. Because of the ready availability of Tryp under these conditions, a single dose per day is sufficient (endurance exercise ≥ 1 hours).
Recommended duration of therapy
After two treatment cycles every 4 weeks, possibly with a dose adjustment after the first cycle, should demonstrate a clear treatment effect, otherwise you have this treatment approach for affecting the serotonin system critically. Several controlled studies show that individual patients respond to influence the serotonin system by Tryp administration not (Jans et al. 2007). Based
on a 4-week treatment cycle in the first week, the Tryp-taking with a daily 1.5 - started 3 g over 3 days, followed by a rest day. On 5 and 6 Day of the week again 1.5 - 3 g Tryp taken daily. End of the week again there is a taking a break.
therapy Weeks 1 - 3
1 - 3 Day: 1.5 - 3 g daily Tryp
4th Tag: Taking break
5th + 6. Day: 1.5 - 3 g daily Tryp
7th Tag: Taking break
is the second and third week of treatment identical to the first week. The fourth week of therapy is characterized by a maintenance therapy
two days without treatment followed by a day of 1,5 - 3 g Tryp. The 4th and 5 Treatment-free day, again, on 6 Tag is again 1.5 - 3 g taken Tryp, the 7th Day without treatment.
maintenance therapy: first
and 2 Tag: treatment interruption
third Day: 1.5 - 3 g Tryp
4th and 5 Tag: treatment interruption
6th Day: 1.5 - 3 g Tryp
7th Tag: To avoid treatment interruption
disturbances in the serotonin synthesis, which are due to the lack of necessary co-factors, it seems appropriate at regular intervals, vitamin B6, to supplement with magnesium, folic acid and, if omega-3 fatty acids.
tryptophan deprivation
disturbances of serotonin synthesis, which are due to a trypsin deficiency, which requires constant supplementation necessary, may lead to undesirable side effects. After long-term supplementation of Tryp (> 3 months), it may already after 3 to 5 days without Tryp-taking to a kind of rebound phenomenon will occur at the existing symptoms before starting treatment again with clearer expression. Typical symptoms can, for example, increased agitation (restlessness, drivenness), increased irritability or a general his discontent. In addition, a kind of restlessness and an inability to concentrate, is observed. It is possible that this acute serotonin deficiency can be enhanced by exposure to sunlight or by means of preventive light therapy (10,000 lux for at least 30 minutes per day) prevent (aan het Rot et al. 2008).
What are the other, negative side effects of regular tryptophan supplementation? How can I prevent this?
The metabolism and the degradation of Tryp leads only to the formation of neuroprotective compounds (kynurenic acid) and the emergence of neuotoxischen substances (quinolinic acid) (Costantino 2009). Moreover there are indications that a non-physiologically high supply of Tryp (> 5 g) to an increased production of free radicals leads (Forrest et al. 2004, Coskun et al. 2006). An additional antioxidant protection would be recommended for long-term therapy. One way of increasing the endogenous antioxidant capacity exists in the supplementation of N-acetylcysteine (NAC). This can stimulate the formation of endogenous glutathione (Vats et al. 2008).
An important side effect of the application, the Tryp Tryp-associated eosinophilia-myalgia syndrome. The increased incidence of eosinophilia-myalgia syndrome in the early 90s led to a temporary Application Ban Tryp. The cause of this frequently at higher doses and longer duration of use common side effect was never fully understood. Perhaps this incident cases were caused by production impurities (Blackburn 1997). After reviewing the literature, there are still hints (Blackburn 1997) for the occurrence of eosinophilia-myalgia syndrome (EM syndrome) after long-term treatment with high Tryp doses (Kamb et al. 1992:> 4 g / day). Possible signs may include elevated eosinophil count, muscle aches or muscle pain, skin lesions are also sklerodermieähnliche (Szeimies, Meurer 1993). As a beginning EM syndrome of unknown origin can be seen in endurance athletes, muscle pain (Penberthy 2007), making the impossible a training over several weeks. Due to the combination of Tryp resource and endurance training may be sufficient under these conditions probably lower cumulative doses in order to trigger these symptoms.
is to take 5-HTP as an alternative to trypsin supplementation?
After absorption of free Tryp across the blood-brain barrier is described for enzymatic formation of 5-Hydroxythryptophan (5-HTP). 5-HTP is the direct precursor of serotonin. The benefit of therapy with 5-HTP is a good intake of the substance across the blood-brain barrier. In contrast to the Tryp requires 5-HTP no amino acid transporter to enter the brain. increase all measures aiming at reducing the concentration of free Tryp omitted in the application of 5-HTP. The efficacy of 5-HTP for the treatment of depressive disorders is controversial for many years (van Vliet et al. 1996, Birdsall 1998). So far, no convincing data from controlled studies (van Hiele, 1980). A major drawback to the use of 5-HTP is the fact that there is also outside the brain, in the periphery, the enzymatic conversion of 5-HTP to serotonin. Therefore, in general only part of the administered dose is central to the action. This problem of premature peripheral conversion also exists in the treatment with the precursor of dopamine (L-dopa). The treatment of Parkinson's disease with L-dopa has only a minor impact as long as the peripheral conversion to dopamine is not prevented. By co-administration of the decarboxylase inhibitor carbidopa with L-dopa is the peripheral dopamine formation is prevented and it is more L-dopa for the central dopamine synthesis are available. It is therefore natural to improve the combined administration of L-Tryp with a decarboxylase inhibitor carbidopa as the central availability of 5-HTP. This treatment approach has proved effective in studies to be effective (Smarius et al. 2008). However, no drug is a fixed combination of 5-HTP and carbidopa are available. Another treatment-limiting factor in the administration of 5-HTP is the compatibility. For 1.5 g of Tryp tolerated (Young 1986), it comes after the capture of 50 without noticeable side effects - 100 mg 5-HTP regularly to the occurrence of nausea. For higher doses of 5-HTP trials in a high discontinuation rate due to this incompatibility is documented (Smarius et al. 2008).
Are there other ways to increase the intake of non-Tryp tablets Tryp supply and subsequently to stimulate serotonin synthesis?
alpha-lactalbumin, a protein fraction from the whey protein has a high proportion of Tryp-Tryp, while a favorable / LNAA ratio. Research confirms that a diet enriched with alpha-lactalbumin results in a significant increase in the Tryp / LNAA ratio. The previously conducted clinical trials showed only a slight response in terms of affective and cognitive disorders (Marcus et al 2002, Markus et al. 2008). A treatment recommendation is not based on these data is justified.
Recent studies document that intestinal bacteria are able to form acid tryptophan from China and secrete into the intestinal lumen (Pero et al. 2009). Preliminary data suggest that after the consumption of fruits with a high content of quinic acid (such as wild blueberries, kiwi, cranberry, cranberries, plums and peaches) in the gastrointestinal tract is an increased formation of Tryp. As a result of increased supply from China Tryp acid blood levels were measured, which were above the documented by Tryp-supplementation levels (Pero et al. 2009). This observation provides another building block for the yet insufficient scientific forecasts so that a high proportion of fruit is in the daily diet has a positive influence on health. So far, however, a lack of investigation, a high consumption china acid-containing fruits with a lower incidence of depressive or affective Interference in which to bring.
Link: antidepressant effect of Kiwi and Cranberry?
The Tryp deficiency induced by a mood of waste can be achieved by the same light therapy (10,000 lux for at least 30 minutes per day) prevent (ann het Rot et al. 2008). These observations suggest that the positive effect of light therapy is mediated at least in part on the serotonin system. Study data also suggest that the Tryp administration and light therapy exert an additive effect on the serotonin system (Lam et al. 1997).
Depressive symptoms may be caused by nutritional deficiencies can significantly with. If a lack of serotonin not responsive to the administration of Tryp, should be given to whether a folic acid deficiency (Simon et Young 2007, Astorg et al. 2008) or the insufficient supply of omega-3 fatty acids present (Su 2008). The biochemical relationships suggest that the addition of folic acid and omega-3 fatty acids in patients with suboptimal care may also improve the effect of Tryp on serotonin synthesis (Sarris et al. 2009).
interactions between tryptophan and dopamine
Does the long-term administration of tryptophan to a disturbance in dopamine metabolism?
As a result of a long-term use of Tryp with stimulation of central serotonin synthesis can there may be a relative dopamine deficiency (Andrews et al. 1978 Hashiguti et al. 1993). The expression of this interaction is different, is often observed only after several months to years Tryp resource. Several studies suggest that serotonin and dopamine synthesis is regulated in dependence on each other (Trouvin et al. 1991). An increased synthesis of serotonin has an inhibitory effect on dopamine synthesis and vice versa (Hashiguti et al. 1993). The permanent stimulation of serotonin synthesis by administration of tryptophan seems long to a reduced central dopamine activity result. The probatory administration of L-dopa can with positive response as an indication of the existence of a relative lack of dopamine will be counted. To prevent this imbalance of dopamine and serotonin, it seems necessary at times to stimulate the central dopamine synthesis. Further evidence for the close interaction of serotonin and dopamine activity comes from the observation that reduced under heat stress increased dopamine activity mediated by serotonin central fatigue (Bailey et Dawis 1997, Watson et al. 2005).
There is evidence that can stimulate the synthesis of the neurotransmitter dopamine in a similar manner to serotonin by the administration of the precursor tyrosine (Acworth et al. 1988, Rasmussen et al. 1983, Benedict et al. In 1983, During et al. 1989, Fernstrom et al. 2007). One way to compensate for this imbalance between serotonin and dopamine is, therefore in the gift of the amino acid tyrosine in the revenue from the Tryp breaks in a dose of 20 mg / kg (Badawy et Williams 1982). This early functional dopamine deficiency may manifest in healthy individuals under long-term administration Tryp particular coordinative disturbances during exercise. The normal gait in humans is very different from a balanced serotonin and dopamine-dependent activity (Mann et al. 2008). Decreased dopamine activity can upset this delicate balance and manifests itself in an impairment of the normal movement pattern. For example, showed the benefit of running an obstacle course of coordination, which is subjectively perceived as a kind of rigidity, as "tough running motion" in analogy to the "wächsenden" resistance in the context of Parkinson's disease. The movement does not seem so fluid, the rotor requires much more drive to get the same performance level. Under L-dopa administration (daily 100 mg + 25 mg carbidopa), this deficit improved within 5 to 7 days. It is striking that when corrected for the relative lack of dopamine observed increased strain readiness, improved motivation and a generally increased drive. Because the dopamine and Serotonin synthesis affect each other, should neither tyrosine nor L-dopa are administered with Tryp. Sequential administration, however, permits the correction of relative dopamine deficiency.
tryptophan - interaction with the analgesic tramadol
The serotonin syndrome may occur as a result of the simultaneous administration of L-tryptophan and tramadol. Concomitant treatment with the centrally acting analgesic tramadol and L-tryptophan can cause serious side effects. For example, patients who have taken because of strong pain tramadol, may lead to the taking of 1 g L-tryptophan in a distance of several hours to a serotonin syndrome. The serotonin syndrome is usually the result of a greatly increased serotonin activity. In this case, symptoms, such as changes in mental state, restlessness, rapid involuntary muscle twitching, increased reflex readiness, sweating, chills and tremors on. In many cases, these symptoms resolve within a few hours back in full.
What is happening to long-term tryptophan treatment, taking into account the interactions with the dopamine system? Based
on a 4-week treatment cycle in the first week would be the Tryp-administered with daily output of 1.5 - 3 g could be recommended for 3 days, then for a Date of change to tyrosine (dosage: 0.5 - 1 g) made. The 5th and 6 Day of the week would be back from the supplementation of 1,5 - 3 g Tryp. End of the week taking the product would be wise.
treatment weeks 1 - 3:
1 - 3 Day: 1.5 - 3 g daily Tryp
4th Tag: tyrosine (0.5 - 1 g)
5th - 6 Day: 1.5 - 3 g daily Tryp
7th Tag: Taking break
The second and third week of treatment would be identical to the first week. The fourth week of therapy would be marked again by a maintenance therapy
two days without treatment followed by a day of 1,5 - 3 g Tryp. The 4th and 5 Day would be in turn, treatment-free, 6 Days would 1,5 - 3 g Tryp used, the 7th Day would be without treatment.
Treatment with L-dopa (with carbidopa) should be reserved for the situation, at which the adjusted basis of a long-term unilateral stimulation of serotonin synthesis with Tryp a clinically apparent, relative lack of dopamine.
Why are the study results for tryptophan in relation to antidepressant effect, so inconsistent?
are presently available, convincing data from controlled studies on antidepressant action of trypsin supplementation before (Thomson et al. 1982, Steinberg et al. 1999). In many studies on the effect of tryptophan the necessary conditions for an increase in trypsin concentration of the blood brain barrier is not sufficiently taken into account. When taking Tryp with food it must be assumed that no relevant additional amounts of free tryptophan for serotonin synthesis are available. To achieve an optimum effect by the Tryp, supplementation in the fasting state is necessary. It is therefore not surprising that research reveals the effects of oral tryptophan administration on symptoms of depression and no consistent results.
refers Why tryptophan in the treatment of depression so little consideration?
These special requirements explain to the rhythm of income, why is the acceptance of this treatment option was low. Really good recording conditions are also achieved under athletic endurance. But it is precisely the group of highly endurance-trained individuals has a relatively low incidence of depressive disorders. The antidepressant effect of endurance training is often described in the literature (Martinsen et Nord 2008, Ströhle 2008, Blumenthal 2007, Knubben et al. 2007 Nabkasorn et al. 2006).
Dr. Detlef Nachtigall;
Email: nachtigall.detlef @ googlemail.com
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