Both supplements of L-tryptophan and 5-HTP have been used in the treatment of depression, but the use of 5-HTP may offer the advantage of bypassing the conversion of L-tryptophan into 5-HTP by the enzyme tryptophan hydroxylase, which is the rate-limiting step in the synthesis of serotonin. Tryptophan hydroxylase can be inhibited by numerous factors, including stress, insulin resistance, vitamin B6 deficiency, and insufficient magnesium... Moreover, 5-HTP easily crosses the blood–brain barrier, and unlike L-tryptophan, does not require a transport molecule to enter the central nervous system (Green et al., 1980; Maes et al., 1990). Besides serotonin, other neurotransmitters and hormones, such as melatonin, dopamine, norepinephrine, and beta-endorphin have also been shown to increase following oral administration of 5-HTP. All of these compounds are thought to be involved in the regulation of mood as well as sleep and may represent mechanistic pathways stimulated by 5-HTP administration.
l-5-HTP has definitely got antidepressant effect in patients of depression. Antidepressant effect was seen within 2weeks of treatment and was apparent in all degrees of depression. The therapeutic efficacy of l-5-HTP was considered as equal to that of fluoxetine.
Mood: 5-HTP is helpful to managing depression and anxiety. SSRIs plug the serotonin leak, while 5-HTP and tryptophan helps fill the tank. While an increase in synaptic serotonin can be achieved with SSRIs, either increasing serotonin synthesis, or identifying postsynaptic serotonin receptor agonist are additional anxiolytic strategies. In this regard, dietary supplementation with tryptophan and 5-HTP, which crosses the blood-brain barrier, increases brain serotonin… and produces anxiolytic effects.
Sleep: Tryptophan administered at night is known increase physiological concentrations of both serotonin and melatonin, which makes it a useful supplement for improving sleep latency in mild insomniacs.
Evidence suggests that stress and/or a dietary lack of tryptophan may make deficiencies of serotonin and melatonin common. In addition, older animals and human beings have a reduced ability to synthesize melatonin. Disorders of melatonin levels and rhythms are suggested to be a cause of affective disease, abnormal sleep, Alzheimer's disease, and some age related disorders. If these ideas prove to be true, then preventive measures are possible.
The effects of 3 g L-tryptophan on sleep, performance, arousal threshold, and brain electrical activity during sleep were assessed in 20 male, chronic sleep-onset insomniacs (mean age 20.3 +/- 2.4 years). Following a sleep laboratory screening night, all subjects received placebo for 3 consecutive nights (single-blind), ten subjects received L-tryptophan, and ten received placebo for 6 nights (double-blind). All subjects received placebo on 2 withdrawal nights (single-blind). There was no effect of L-tryptophan on sleep latency during the first 3 nights of administration. On nights 4-6 of administration, sleep latency was significantly reduced. Unlike benzodiazepine hypnotics, L-tryptophan did not alter sleep stages, impair performance, elevate arousal threshold, or alter brain electrical activity during sleep.
Over the past 20 yr, 40 controlled studies have been described concerning the effects of L-tryptophan on human sleepiness and/or sleep. The weight of evidence indicates that L-tryptophan in doses of 1 g or more produces an increase in rated subjective sleepiness and a decrease in sleep latency (time to sleep). There are less firm data suggesting that L-tryptophan may have additional effects such as decrease in total wakefulness and/or increase in sleep time. Best results (in terms of positive effects on sleep or sleepiness) have been found in subjects with mild insomnia, or in normal subjects reporting a longer-than-average sleep latency. Mixed or negative results occur in entirely normal subjects--who are not appropriate subjects since there is no room for improvement. Mixed results are also reported in severe insomniacs and in patients with serious medical or psychiatric illness.
Modulating central serotonergic function by acute tryptophan depletion (ATD) has provided the fundamental insights into which cognitive functions are influenced by serotonin. It may be expected that serotonergic stimulation by tryptophan (Trp) loading could evoke beneficial behavioural changes that mirror those of ATD. The current review examines the evidence for such effects, notably those on cognition, mood and sleep. Reports vary considerably across different cognitive domains, study designs, and populations. It is hypothesised that the effects of Trp loading on performance may be dependent on the initial state of the serotonergic system of the subject. Memory improvements following Trp loading have generally been shown in clinical and sub-clinical populations where initial serotonergic disturbances are known. Similarly, Trp loading appears to be most effective for improving mood in vulnerable subjects, and improves sleep in adults with some sleep disturbances. Research has consistently shown Trp loading impairs psychomotor and reaction time performance, however, this is likely to be attributed to its mild sedative effects. (c) 2009 Elsevier Ltd. All rights reserved.
5-HTP (Hydroxytryptophan) and tryptophan have been examined to see whether these treatments are effective, safe and acceptable in treating unipolar depression in adults. The researchers reported that the symptoms of depression decreased when 5-HTP and tryptophan were compared to a placebo (non-drug). However, side effects had occurred (dizziness, nausea and diarrhoea). They also reported that tryptophan has been associated with the development of a fatal condition. More evidence is needed to assess efficacy and safety, before any strong and meaningful conclusions can be made. Until then, the reviewers propose that the use of antidepressants which have no known life threatening side effects remain more attractive. The review sets out the required methodology for effectively studying these substances in proper controlled studies.
Mood: Consuming tryptophan increases the concentration of tryptophan in the brain and synthesis of serotonin. “The neurotransmitter, serotonin (5-HT), synthesized in the brain, plays an important role in mood alleviation, satiety, and sleep regulation. Although certain fruits and vegetables are rich in 5-HT, it is not easily accessible to the CNS due to blood brain barrier. However the serotonin precursor, tryptophan, can readily pass through the blood brain barrier. Tryptophan is converted to 5-HT by tryptophan hydroxylase and 5-HTP decarboxylase, respectively, in the presence of pyridoxal phosphate, derived from vitamin B6. Hence diets poor in tryptophan may induce depression as this essential amino acid is not naturally abundant even in protein-rich foods.”
Light suppresses melatonin while darkness stimulates its synthesis. Many people have trouble falling asleep. Delayed sleep phase syndrome results in late sleep onset, despite normal sleep architecture and total sleep duration. Melatonin has been shown to improve sleep latency (the time it takes to fall asleep) in several randomized controlled studies. Rather than immediately prior to sleeping, melatonin works best when given two hours before sleeping. Melatonin is also useful for jet lag, irregular sleep-wake rhythms, and shift work sleep disorder. Exogenously administered melatonin has phase shifting properties, and the effect follows a phase- response curve (PRC) that is about 12 h out of phase with the PRC [phase response curve] of light Melatonin administered in the afternoon or early evening will phase advance the circadian rhythm, whereas melatonin administered in the morning will phase delay the circadian rhythm (Fig. 2). The magnitude of phase shifts is time-dependent, and the maximal phase shifts result when melatonin is scheduled around dusk or dawn. The effect of exogenous melatonin is minimal when administered during the night, at least during the first-half of the night.
Nonapnea sleep disorders: Nonapnea sleep disorder In humans, melatonin secretion increases soon after the onset of darkness, peaks in the middle of the night (between 2 and 4 a.m.), and gradually falls during the second half of the night
Taurine has a variety of actions in the body such as cardiotonic, host-defensive, radioprotective and glucose-regulatory effects. However, its action in the central nervous system remains to be characterized. In the present study, we tested to see whether taurine exerts anti-anxiety effects and to explore its mechanism of anti-anxiety activity in vivo. The staircase test and elevated plus maze test were performed to test the anti-anxiety action of taurine. Convulsions induced by strychnine, picrotoxin, yohimbine and isoniazid were tested to explore the mechanism of anti-anxiety activity of taurine. The Rotarod test was performed to test muscle relaxant activity and the passive avoidance test was carried out to test memory activity in response to taurine. Taurine (200 mg/kg, p.o.) significantly reduced rearing numbers in the staircase test while it increased the time spent in the open arms as well as the number of entries to the open arms in the elevated plus maze test, suggesting that it has a significant anti-anxiety activity. Taurine's action could be due to its binding to and activating of strychnine-sensitive glycine receptor in vivo as it inhibited convulsion caused by strychnine; however, it has little effect on picrotoxin-induced convulsion, suggesting its anti-anxiety activity may not be linked to GABA receptor. It did not alter memory function and muscle activity. Taken together, these results suggest that taurine could be beneficial for the control of anxiety in the clinical situations. Copyright (c) 2007 S. Karger AG, Basel.
Excitatory amino acid stimulation of phosphatidylinositol (PI) hydrolysis has been associated with development of the CNS. Normally minimally ineffective in stimulating PI hydrolysis in the neonatal rat cerebellum, N-methyl-D-aspartate (NMDA) increased levels of PI hydrolysis 82.3 +/- 5.5% above basal values in the presence of 1 microM baclofen, a gamma-aminobutyric acidB (GABAB) receptor agonist. This effect was observed at day 7 but not in adult cerebellum. The effect of baclofen could be mimicked by low dose GABA and taurine, actions which were blocked by prior application of a specific GABAB antagonist. Therefore, the ability of NMDA to stimulate PI hydrolysis in neonatal cerebellar tissue may be regulated by the degree of GABAB receptor stimulation.
The interactions of taurine with GABAB receptors were studied in membranes from the brain of the mouse by measuring the binding of [3H]baclofen and that of [3H]GABA in the presence of isoguvacine. Taurine displaced ligand binding to GABAB receptors concentration-dependently with an IC50 in the micromolar range. The effects of baclofen on the release of taurine and GABA from slices of cerebral cortex of the mouse were assessed using a superfusion system. Potassium-stimulated release of both [3H]taurine and [3H]GABA was unaffected by baclofen but potentiated by delta-aminovalerate. The enhancement of release of [3H]taurine by delta-aminovalerate was partially antagonized by baclofen, suggesting that baclofen-sensitive receptors could modify the release.
Taurine, an inhibitory amino acid, potently acts on a subclass of gamma-aminobutyric acid type A (GABAA) receptors. Taurine competitively inhibits [3H]muscimol binding to purified GABAA receptors with an average IC50 value of 50 microM, and enhances [3H]flunitrazepam binding to GABAA-linked benzodiazepine receptors with an EC50 of about 10 microM and with maximal extent lower than that for GABA. Taurine shows variable affinities (low micromolar to near millimolar) for muscimol binding sites in different brain regions as measured by autoradiography. The taurine-sensitive GABA sites are enriched in dentate gyrus, substantia nigra, cerebellum molecular layer, median thalamic nuclei, and hippocampal field CA3; these areas are also enriched in mRNA for the GABA-binding beta 2 subunit subtype. Taurine shows differential affinities for the multiple muscimol-GABA binding polypeptides present in purified GABAA receptors, notably a higher affinity for a beta 55 than a beta 58 polypeptide; these probably represent beta 2 and beta 3 clones, respectively. This work defines a significant target of taurine's inhibitory activity as some GABAA receptor GABA sites, lending support to the hypothesis that this endogenous substance may have a physiological action.
Anxiety & Sleep: Taurine helps with both sleep and anxiety through reducing excitatory neurotransmission. It increases GABA in the brain, can bind to GABA receptors, and indirectly suppresses NMDA signaling. It also acts on glycine receptors, which contributes to its anti-anxiety effects.
Anxiety: Phenibut is used reduce tension, alleviate anxiety, and diminish fear. PB was classified as an atypical tranquilizer, or day-tranquilizer. It has antistress, thymoleptic (activating), and nootropic (cognition enhancing) components of action.
Memory: Studies indicated that PS provides metabolic support for memory, learning, concentration, and behavior. This exploratory study demonstrates that SB-PS may have favorable effects on cognitive function in elderly with memory complaints.
In young adults, with neuroticism scores above rather than below the median, the taking of 300mg PS each day for a month was associated with feeling less stressed and having a better mood. The study for the first time reports an improvement in mood following PS supplementation in a sub-group of young healthy adults.
While the placebo group showed the expected increase in distress after the test, the group treated with 400 mg PAS showed decreased distress. These data provide initial evidence for a selective stress dampening effect of PAS on the pituitary-adrenal axis, suggesting the potential of PAS in the treatment of stress related disorders.
Stress - PS may increase the availability of cortisol in chronically stressed men and may attenuate stress-induced memory impairments. Results of the present study are discussed within the context of previous research and current state of knowledge.
Adrenal Fatigue / Hypoadrenalism - Low CoQ10 has been shown to lead to hypoadrenalism. The role of adrenal steroids in antioxidant regulation is not known. Previously, we demonstrated some Coenzyme Q(10) (CoQ(10)) alterations in pituitary diseases, which can induce complex pictures due to alterations of different endocrine axes. Therefore we determined CoQ(10) and Total Antioxidant Capacity (TAC) in pituitary-dependent adrenal diseases: 6 subjects with ACTH-dependent adrenal hyperplasia (AH); 19 with secondary isolated hypoadrenalism (IH), 19 with associated hypothyroidism (multiple pituitary deficiencies, MPH). CoQ(10) was assayed by HPLC; TAC by the system metmyoglobin-H(2)O(2), which, interacting with the chromogenous 2,2(I)-azinobis-(3-ethylbenzothiazoline-6-sulphonate), generates a spectroscopically revealed radical compound after a latency time (Lag) proportional to the antioxidant content. CoQ(10) levels were significantly lower in IH than AH and MPH, with a similar trend when adjusted for cholesterol. Also TAC was lower in IH than in AH and MPH, suggesting that adrenal hormones can influence antioxidants. However, since thyroid hormones modulate CoQ(10) levels and metabolism, when thyroid deficiency coexists it seems to play a prevalent influence.
Coenzyme Q10 supplements at a dose of 150 mg can decrease oxidative stress and increase antioxidant enzyme activity in patients with CAD. A higher dose of coenzyme Q10 supplements (>150 mg/d) might promote rapid and sustainable antioxidation in patients with CAD.
B12 Deficiency: Homocysteine - “Vitamin B12 (mean 0.5 mg) produced an additional reduction in blood homocysteine of 7%, whereas vitamin B6 (mean 16.5 mg) did not have any significant effect. Hence, in typical populations, daily supplementation with both 0.5 to 5 mg folic acid and about 0.5 mg vitamin B12 would be expected to reduce homocysteine levels by one quarter to one third (from about 12 micromol/L to about 8 to 9 micromol/L).”
Pyridoxine (B6) nutritional status has a significant and selective modulatory impact on central production of both serotonin and GABA - neurotransmitters which control depression, pain perception, and anxiety.
In the present study, the role of vitamin D in the regulation of estrogen synthesis in gonads was investigated. Vitamin D receptor null mutant mice showed gonadal insufficiencies. Uterine hypoplasia and impaired folliculogenesis were observed in the female, and decreased sperm count and decreased motility with histological abnormality of the testis were observed in the male. The aromatase activities in these mice were low in the ovary, testis, and epididymis at 24%, 58%, and 35% of the wild-type values, respectively. The gene expression of aromatase was also reduced in these organs. Elevated serum levels of LH and FSH revealed hypergonadotropic hypogonadism in these mice. The gene expressions of estrogen receptor α and β were normal in gonads in these mice. Supplementation of estradiol normalized histological abnormality in the male gonads as well as in the female. Calcium supplementation increased aromatase activity and partially corrected the hypogonadism. When the serum calcium concentration was kept in the normal range by supplementation, the aromatase activity in the ovary increased to 60% of the wild-type level, but LH and FSH levels were still elevated. These results indicated that vitamin D is essential for full gonadal function in both sexes. The action of vitamin D on estrogen biosynthesis was partially explained by maintaining calcium homeostasis; however, direct regulation of the expression of the aromatase gene should not be neglected.
Vitamin D is a fat-soluble nutrient. It is one of the 24 micronutrients critical for human survival. The sun is the major natural source of the nutrient, but vitamin D is also found naturally in fish and eggs. It is also added to dairy products. Supplemental vitamin D is associated with a wide range of benefits, including increased Cognition, immune health, bone health and well-being. Supplementation can also reduce the risks of cancer, heart disease, diabetes and multiple sclerosis. People deficient in vitamin D may also experience increased Testosterone levels after supplementation. The body produces vitamin D from cholesterol, provided there is an adequate amount of UV light from sun exposure. There is only a sufficient amount of UV light coming from the sun when the UV index is 3 or higher, which only occurs year-round near the equator, between the 37th parallels. Most people are not deficient in vitamin D, but they do not have an optimal level of vitamin D either. Due to the many health benefits of vitamin D, supplementation is encouraged if optimal levels are not present in the body.
Allostasis differs from homeostasis Vis-a` -Vis its emphasis on dynamic rather than static biological set-points, considerations of the brain’s role in feedback regulation, and view of health as a whole-body adaptation to contexts (Schulkin, 2003b). These insights have encouraged new ways of conceptualizing complex, multi-systemic biological activities where, as Heraclitus wrote, ‘‘the only constant is change’’. The allostatic load model expands the theory of allostasis by applying it to the cause and effects of chronic stress… Allostatic load (AL) represents the ‘wear and tear’ the body experiences when repeated allostatic responses are activated during stressful situations (McEwen and Stellar, 1993). Real or interpreted threats to homeostasis initiate the sympathetic– adrenal–medullary (SAM) axis release of catecholamines and the hypothalamic–pituitary–adrenal (HPA) axis secretion of glucocorti- coids that mobilize energy necessary for fight-or-flight responses (Sapolsky et al., 2000)… While adaptive acutely, chronic over-activation of SAM- and HPA-axis products induce a ‘domino effect’ on interconnected biological systems that overcompensate and eventually collapse themselves, leaving the organism susceptible to stress-related diseases (Korte et al., 2005; Lupien et al., 2006; McEwen, 1998b)… A key feature of allostasis, AL, and ultimately allostatic overload is that multiple mediators of adaptation are involved and interconnected in a non-linear network… At first, prolonged secretion of the stress hormones epinephrine, norepinephrine, and cortisol (antagonized by dehydroepiandosterone) can falter in their ability to protect the distressed individual and instead begin to damage the brain and body (McEwen, 2006a)… Over time, subsidiary biological systems compensate for the over and/or under production of primary mediators and in turn shift their own operating ranges to maintain abated chemical, tissue, and organ functions. This prodromal stage is referred to as the secondary outcomes, whereby metabolic (e.g., insulin, glucose, total cholesterol, high density lipoprotein cholesterol, triglycerides, visceral fat depositing), cardiovascular (e.g., systolic and diastolic blood pressure), and immune (e.g., fibrinogen, c-reactive protein (CRP)) parameters reach sub-clinical levels. The final stage of AL progression is allostatic overload, whereby the culmination of physiological dysregulations leads to disordered, diseased, and deceased endpoints referred to as tertiary outcomes.
When the SAM- and HPA-axes are repeatedly activated during stressful situations — at work and/or at home — they exert a pathophysiological strain on the individual. This maladaptive process is referred to as allostatic load (McEwen and Stellar, 1993). Because burnout remains an ill understood condition that is often treated like depression, evidence-based approaches and technologies that disentangle them are needed. We believe that the development of AL algorithms might be extremely beneficial for healthcare providers that are not currently equipped to prevent, detect, or even accurately diagnose burnout. As chronic stress at work contributes to both depression and burnout, it follows that measuring AL along with stress hormone dynamics might help differentiate these and other diseases. In addition to being an integral product of stress responses and a key mediator leading to AL, cortisol follows a normal diurnal rhythm necessary for proper functioning. A normal circadian profile consists of an acute increase during the first hour after awakening (Federenko et al., 2004; Pruessner et al., 1997), followed by gradual decreases throughout the day. The awakening cortisol response (ACR) is used as a robust marker of HPA-axis integrity and is very sensitive to psychological stress (Schulz et al., 1998). In a recent meta-analysis of 62 articles, it was found that the magnitude of the ACR is positively associated with job stress and general life stress, but negatively associated with fatigue, burnout, and exhaustion (Chida and Steptoe, 2009). Indeed, hypocortisolism is a phenomenon that occurs in approximately 20—25% of patients suffering from stress-related diseases like chronic fatigue syndrome, fibromyalgia, PTSD, burnout, and atypical depression to name a few (for a review, see Fries et al., 2005).