Viridian 5-HTP 100mg 60 capsules
What is 5-HYDROXYTRYPTOPHAN (5-HTP)?
5-Hydroxytryptophan (5-HTP) is the direct precursor to serotonin and has been used clinically for over 30 years.
5-HTP was highly investigated in clinical research during the 1960s and 1970s. Mechanistically, it showed favourable results in mood, dietary regulation and raising both serotonin and serotonin metabolite levels.
5-HTP is normally present in the central nervous system at low levels. A rich, sustainable 5-HTP source is the seeds of Griffonia Simplicifolia an abundant African shrub.
In normal physiology dietary tryptophan can access two pathways of metabolism; the kynurenine pathway or the synthesis of 5-HTP, serotonin and melatonin. These pathways are tightly regulated by physiological requirements.
5-HTP, it is synthesized from tryptophan, by the enzyme tryptophan hydroxylase in the gastrointestinal tract. Subsequently, 5-HTP is converted to serotonin either in the gut or once 5-HTP has crossed the blood brain barrier. In the gut, serotonin is involved in gastric emptying and motility, however in the brain it functions within mood as a neurotransmitter. Interestingly, neither tryptophan nor serotonin can cross the blood brain barrier, therefore it is essential that the brain has an adequate supply of 5-HTP to synthesize serotonin. A lack of circulating 5-HTP can arise when insufficient tryptophan is provided from the diet, however it has been shown that inflammation and stress can divert tryptophan to the kynurenine pathway and away from 5-HTP and the subsequent serotonin production3. Furthermore, the kynurenine pathway stimulates the production of inflammatory mediators and a cycle of insufficient serotoninergic activity, thus, contributing to low mood.
Serotonin is a monoamine neurotransmitter in the mammalian central nervous system, where it plays an important part in regulating mood and memory. Sub-optimal levels of serotonin are thought to contribute to mood and mental health disorders4. Therefore 5-HTP is directed for mood, anxiety, depression and binge eating disorders when associated with sub-optimal levels of serotonin.
What is 5-HTP used for?
MOOD - Depression is characterised by persistent depressed mood and/or anhedonia with further mood symptoms. The main antidepressant therapy is based on the theory that depression results from a lack of serotoninergic activity. Thus, it is treated using serotonin transporter (SERT) inhibitors, such as; selective serotonin reuptake inhibitors (SSRI) and dual serotonin and noradrenaline reuptake inhibitors. However, such medications only achieve remission in one-third of patients.
Consequently, those that experience a lack of improvement may seek alternative therapies. A review of mechanistic literature evaluated the use of 5-HTP as an adjunct to SERTs for treatment resistant depression (TRD). It was reported that the therapies improved the available serotonin and in theory could be a possible resolution for individuals with treatment-resistant depression. Currently, 5-HTP is contraindicated with SERTs and so such an intervention should be overseen by a medical professional.
Five studies evaluated the administration of 5-HTP on various types of depression; of which 2 had a crossover design. The studies evaluated 6-26 subjects, who were administrated 200-3250mg daily 5- HTP for 5-365 days. The results showed 34-67% reduction in the Hamilton Depression Scale, while improvements ranged from 33-76% of total subjects.
Two additional studies evaluated the use of 5-HTP compared to antidepressant medication. The studies evaluated 30 and 69 subjects over 20+ and 40 days administered either 200-1200mg daily 5-HTP or imipramine or fluvoxamine. Both studies reported that 5-HTP had equally effective results to both imipramine and fluvoxamine.
A similar random controlled trial assessed 5-HTP compared to fluoxetine for 8 weeks, the subjects were diagnosed first episode depression and used the Hamilton Depression Scale by means of assessment. The 5-HTP group received 150mg over 3 doses daily for the first 2 weeks, then increased to 300mg over 3 doses for weeks 3 and 4. For weeks 5-8 400mg was administered over 3 daily doses. While the fluoxetine group were administered 20mg, 30mg and 40mg daily that increased in time with the 5-HTP regimen. After the first 2 weeks both groups showed equal improvements in the Hamilton Depression Scale, however by the end of the study 73.33% of the 5-HTP group and 80% of the fluoxetine group showed positive response. Therefore, the authors concluded that in this population, 5-HTP performed equally to fluoxetine in reducing depressive symptoms.
5-HTP and panic disorders.
PANIC DISORDERS - It has been shown that panic disorder patients have a greater risk of lowered serotonin and tryptophan depletion that subsequently increases the vulnerability to panic episodes. A study proposed to assess the effect of 200mg 5-HTP or placebo on 24 panic disorder patients and 24 healthy volunteers to a 35% CO2 panic challenge. The randomised controlled trial observed a significantly reduced reaction to the panic challenge in the 5-HTP subjects, regarding subjective anxiety, panic symptom score and number of panic attacks, as opposed to placebo, confirming the hypothesis that reduced serotonin is involved in the aetiology of panic disorder.
5-HTP for weight loss.
WEIGHT LOSS - Often mood can be linked to changes in body composition; therefore, this has led to researchers to investigate the effect on body composition from mood improvement interventions. A double blind crossover study evaluated the effects of 8mg/kg daily of 5-HTP compared to placebo on female patients with a Body Mass Index between 30-40 for a 5-week period. It was reported that food intake reduced with a confirmed weight loss during the period of observation.
To investigate dietary changes related to 5-HTP treatment an intervention study explored the effect of 900mg daily of 5-HTP compared to placebo in 20 diagnosed obese subjects over two 6-week periods. The first 6- week period was completed without dietary recommendations, however, during the second period the participants were recommended to achieve a 5040-kJ/1204 calorie daily intake. A significant weight loss was observed in the 5-HTP group during both periods, furthermore upon dietary analysis a reduction in carbohydrate intake and a consistent presence of early satiety were also reported. These findings led the authors to conclude that the good tolerance of 5-HTP suggested it may be a safe treatment for obesity. The authors further investigated the effects of 5-HTP administration in 25 overweight non-insulin dependent diabetic subjects in a double-blind, placebo-controlled study. The subjects received either 750mg daily 5-HTP or placebo for two consecutive weeks, during which no dietary restriction was prescribed. At baseline, brain tryptophan availability in diabetic patients was significantly reduced when compared to a group of healthy controls. The 5-HTP group significantly decreased their daily energy intake, by reducing carbohydrate and fat intake, which resulted in reduced body weight. These outcomes confirm the role of the serotonergic system in reducing energy intake, by predominantly inhibiting carbohydrate intake, and suggest that 5-HTP may be safely used to improve the compliance to dietary prescriptions in non-insulin dependent diabetes mellitus.
5-HTP and Sleep.
SLEEP - Normal metabolism of serotonin leads to melatonin production, the ‘sleep hormone’. Melatonin naturally occurs in the evening in preparation for the onset of sleep. A small study investigated the effect on sleep through the increased brain serotonin using 5-HTP, on 12 healthy subjects. It was found that rapid eye movement (REM) sleep increased from 5% to 53% when compared to the placebo baseline, furthermore, total rapid eye movement activity increased. However, non-REM sleep decreased slightly, this was suggested to be compensatory for the increased amount of REM sleep. This confirms the theory that reduced brain serotonin contributes to total insomnia.
Normal serotonin metabolism has been shown to be critical for REM sleep and so, it is suggested that impaired serotonin metabolism is a contributing factor to sleep terrors. An open trial on 45 children, aged 3-10 years with sleep terrors compared the use of 5-HTP to placebo. 5-HTP was administrated at 2mg/kg of bodyweight daily at bedtime for 20 days. After the treatment it was reported that 93.5% of patients showed a positive response.
5-HTP and gut health.
GASTROINTESTINAL HEALTH - Poor gastrointestinal integrity is often referred to as ‘leaky gut’ and arises when tight junction proteins signal for the opening of the tight junctions between the cells that line the gastrointestinal tract. Thought as an alarm response; the opening of tight junctions can be triggered by food allergens, food sensitivity, stress or infection. The amino acid tryptophan is converted to 5-HTP in the gastrointestinal tract, of which some is converted to serotonin at the same point and is known to be involved with gastric emptying and motility, and the rest crosses the blood brain barrier. Subsequently, it was thought that 5-HTP is involved in the gastrointestinal tract function and so a randomized double-blind placebo controlled crossover study investigated the effect of 5-HTP in comparison to placebo on intestinal barrier function and mucosal serotonin metabolism. 15 healthy volunteers were given 100mg 5-HTP and plasma samples were taken; before, at 60, 90 and 120 minutes after the 5-HTP administration to assess for markers of gastrointestinal integrity, furthermore, a gastroduodenoscopy was performed to obtain mucosal samples from the duodenum. Measures for intestinal permeability were significantly reduced in the 5-HTP group compared to placebo. While some of the zonulin-1 markers of gut integrity was increased, others remained unaffected, interestingly, the integrity regulating proteins were located significantly closer to each other after 5-HTP administration. These findings led the authors to conclude that oral administration of 5-HTP reinforces small intestinal barrier function by lowering intestinal permeability, inducing the expression of the tight junction protein zonulin-1 and rearranging tight junction proteins.