LIBIDUP PE SACHET (Each 10g sachet contains L-Tryptophan/ Myo-Inositol/ D-Chiro-inositol/ Vitamin B6/ L-Arginine/ Grape seed extract/ Safed musli granules 250mg/1.1g/27.6mg/2mg/5mg/120mg/3g)

Indications

• Vitamin B6 deficiency
• Isoniazid-induced neuropathy (prophylaxis and treatment)
• Idiopathic sideroblastic anaemia
• Prevention of penicillamine-induced neuropathy in Wilson's disease
• Metabolic diseases such as cystathioninuria and homocystinuria
• Premenstrual syndrome

Mechanism of action

Pyridoxine hydrochloride is converted in the body to pyridoxal phosphate, which is the active form of vitamin B6. It serves as a cofactor for more than 100 enzymatic reactions, particularly those involved in the metabolism of amino acids, the synthesis of neurotransmitters (such as serotonin, dopamine, and gamma-aminobutyric acid), and the production of hemoglobin. Its role in neurotransmitter synthesis makes it crucial for normal brain function and mood regulation.

Pharmacodynamics

Pyridoxine hydrochloride exerts its effects by facilitating the conversion of amino acids into neurotransmitters and is involved in the synthesis of heme. It impacts the metabolism of tryptophan to serotonin and is essential for the production of norepinephrine and gamma-aminobutyric acid, which are vital for proper neurological function. Deficiency of vitamin B6 can lead to neurological symptoms, including peripheral neuropathy and cognitive disturbances.

Pharmacokinetics

Pyridoxine hydrochloride is readily absorbed from the gastrointestinal tract. It is primarily metabolized in the liver, where it is converted to its active form, pyridoxal phosphate. The elimination half-life of pyridoxine is approximately 15-20 days, and it is excreted primarily through the urine. Renal impairment may affect the metabolism and excretion of pyridoxine, necessitating dose adjustments.

Contra-indications

• Hyperkalaemia
• Severe liver damage

Adverse effects

• Peripheral neuritis
• Hepatitis
• Hypoglycaemia
• Urine discolouration

Interactions

• Potassium aminobenzoate
• Isoniazid

Precautions

• Caution in renal impairment (increased risk of hyperkalaemia)
• Interrupt treatment during periods of low food intake (such as fasting, anorexia, and nausea) to reduce risk of hypoglycaemia
• Monitor liver function tests monthly during high-dose therapy

Pregnancy

Manufacturer advises avoiding use in pregnancy due to potential risk of birth defects; however, no adverse effects have been reported at normal dietary levels.

Breast-feeding

Theoretical risk of toxicity in infants if mothers take large doses.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Formulations

• Pyridoxine hydrochloride 10 mg tablets
• Pyridoxine hydrochloride 20 mg tablets
• Pyridoxine hydrochloride 50 mg tablets
• Pyridoxine hydrochloride oral solution 20 mg per 1 ml

Indications

• Insulin resistance
• Polycystic ovary syndrome (PCOS)
• Metabolic syndrome
• Type 2 diabetes

Dosage

Children: Refer to the BNF for Children for specific dosing guidelines.

Adults: Refer to the BNF for specific dosing guidelines.

Mechanism of action

D-chiro-inositol enhances insulin sensitivity and plays a role in glucose metabolism by acting as a secondary messenger in insulin signaling. It participates in the phosphoinositide signaling pathway, which is crucial for the action of insulin on glucose uptake in muscle and fat tissues. Furthermore, it is involved in the biosynthesis of inositol phosphates, which are important for cellular signaling.

Pharmacodynamics

D-chiro-inositol has been shown to improve insulin sensitivity, reduce insulin resistance, and assist in the regulation of ovarian function in women with PCOS. It is thought to modulate the insulin signaling pathway, thereby improving metabolic parameters associated with insulin resistance. Additionally, it may influence lipid metabolism and reduce triglyceride levels.

Pharmacokinetics

The pharmacokinetics of D-chiro-inositol, including its absorption, distribution, metabolism, and excretion, are not extensively characterized. It is generally considered to be well-absorbed when administered orally. D-chiro-inositol is thought to be metabolized in the liver, and its elimination half-life is not well-established. Further studies are needed to detail its pharmacokinetic profile.

Pregnancy

There is insufficient data on the use of d-chiro-inositol in pregnancy. Caution is advised and it should only be used if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Limited data is available on the excretion of d-chiro-inositol in human milk. Caution is recommended when administering to breastfeeding mothers.

Storage

Store in a cool, dry place. Protect from light and moisture.

Indications

• General wellness support
• Anti-inflammatory effects
• Antioxidant activity
• Digestive aid
• Support for immune function

Dosage

Children: Paediatric dosing should be determined based on the specific extract and its intended use. Consultation with a healthcare provider is recommended for accurate dosing.

Adults: Dosage varies widely depending on the specific extract and formulation. It is essential to follow the manufacturer's instructions or consult a healthcare professional for appropriate dosing.

Mechanism of action

The mechanism of action of herbal extracts can vary significantly based on their constituents. Commonly, they exert their effects through multiple pathways including modulation of neurotransmitter systems, interference with inflammatory processes, or direct antioxidant activity. Some extracts may activate certain receptors or inhibit enzymes related to disease processes.

Pharmacodynamics

The pharmacodynamics of extracts is complex due to the presence of multiple active compounds which can have synergistic or antagonistic effects. These compounds may influence cellular signaling pathways, alter gene expression, or modulate immune response. The overall pharmacological profile is determined by the specific composition of the extract, its concentration, and the biological target it interacts with.

Pharmacokinetics

The pharmacokinetics of extracts involves absorption, distribution, metabolism, and excretion of the active compounds. Generally, herbal extracts are absorbed in the gastrointestinal tract, with bioavailability influenced by factors such as formulation, the presence of food, and individual metabolic differences. Compounds may undergo hepatic metabolism, and elimination can occur through urine or feces, depending on their chemical nature.

Pregnancy

Consult a healthcare professional before use, as the safety of the extract during pregnancy has not been established.

Breast-feeding

Consult a healthcare professional before use, as the safety of the extract during breastfeeding has not been established.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Dosage

Children: Refer to specific medication guidelines for dosing adjustments due to grapefruit juice interactions.

Adults: Refer to specific medication guidelines for dosing adjustments due to grapefruit juice interactions.

Mechanism of action

Grapefruit juice contains compounds called furanocoumarins, which inhibit cytochrome P450 3A4 (CYP3A4) enzymes in the liver and intestines. This inhibition can lead to increased plasma concentrations of drugs that are metabolized by CYP3A4, resulting in enhanced pharmacological effects and potential toxicity.

Pharmacodynamics

The pharmacodynamic effects of grape juice are closely related to its antioxidant properties, primarily due to resveratrol and flavonoids. These compounds help in reducing oxidative stress and inflammation. However, the primary clinical concern is the modulation of drug metabolism, particularly affecting drugs with a narrow therapeutic index.

Pharmacokinetics

Grapefruit juice can significantly alter the pharmacokinetics of certain medications by affecting their absorption and metabolism. The inhibition of CYP3A4 can lead to increased bioavailability of drugs that are substrates of this enzyme, resulting in higher plasma concentrations. The effects of grapefruit juice can persist for up to 24 hours post-consumption, complicating timing and dosing of affected medications.

Interactions

• grapefruit juice + abemaciclib: Severe (increases exposure)
• grapefruit juice + aliskiren: Severe (decreases exposure)
• grapefruit juice + amiodarone: Severe (increases exposure)
• grapefruit juice + dronedarone: Severe (increases exposure)
• grapefruit juice + rupatadine: Severe (increases exposure)
• grapefruit juice + piperaquine: Severe (increases concentration)
• grapefruit juice + antipsychotics, second generation: Severe (increases exposure)
• grapefruit juice + lurasidone: Severe (increases exposure)
• grapefruit juice + quetiapine: Severe (increases exposure)
• grapefruit juice + cariprazine: Severe (increases exposure)

Pregnancy

Consult healthcare provider for guidance on use during pregnancy.

Breast-feeding

Consult healthcare provider for guidance on use during breastfeeding.

Storage

Store in a cool, dry place away from direct sunlight.

Indications

• Cardiovascular diseases
• Erectile dysfunction
• Peripheral arterial disease
• Wound healing
• Muscle growth and recovery
• Immune system support

Dosage

Children: For paediatric dosing, it is important to refer to the BNF for Children for appropriate guidelines based on the child's age, weight, and clinical condition.

Adults: The typical dosage for adults varies based on the condition being treated, but common oral doses range from 2 to 30 grams per day, divided into multiple doses. For specific dosing recommendations, please refer to the BNF.

Mechanism of action

L-arginine is converted to nitric oxide by nitric oxide synthase (NOS), which is crucial for vascular function and blood flow regulation. NO activates guanylate cyclase, leading to increased levels of cyclic GMP, a secondary messenger that mediates vasodilation and other cellular responses. This pathway is vital in both the cardiovascular and immune systems, with different isoforms of NOS (eNOS, nNOS, iNOS) contributing to various physiological effects.

Pharmacodynamics

L-arginine has been shown to enhance immune responses, improve wound healing, stimulate growth hormone release, and support muscle hypertrophy and tissue repair. Its role in nitric oxide production aids in vasodilation, improving blood circulation and oxygen delivery to tissues, which is essential for recovery and regeneration.

Pharmacokinetics

L-arginine is absorbed from the gastrointestinal tract, with peak plasma concentrations occurring within 1-2 hours after oral administration. It is metabolized primarily in the liver and kidneys, with a half-life of approximately 1-2 hours. The bioavailability of L-arginine can be influenced by dietary intake and metabolic conditions.

Adverse effects

• Gastrointestinal disturbances
• Nausea
• Diarrhea
• Abdominal pain
• Hypotension
• Allergic reactions

Interactions

• Antihypertensive agents may have additive effects leading to increased hypotension
• Sildenafil and other medications for erectile dysfunction may have enhanced effects when used with L-arginine

Precautions

• Caution in patients with a history of asthma or allergies
• Use with caution in patients with hypotension
• Monitor blood pressure in patients taking antihypertensive medications

Pregnancy

The safety of L-arginine in pregnancy has not been established. Consult a healthcare provider before use.

Breast-feeding

L-arginine is excreted in breast milk, and its safety during breastfeeding is not well established. Consult a healthcare provider.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Formulations

• Oral tablets
• Powder for oral solution
• Capsules

Indications

• Insomnia
• Anxiety
• Depression
• Migraine headaches
• Chronic pain
• Obsessive-compulsive disorder
• Seasonal affective disorder
• Nutritional supplementation in infant formulas

Dosage

Adults: Refer to the BNF for specific dosing guidelines.

Mechanism of action

During the catabolism of tryptophan, several important side reactions occur, starting with the action of an iron porphyrin oxygenase that opens the indole ring. Kynurenine, a key intermediate, can be converted into kynurenic acid, which exhibits antiexcitotoxic and anticonvulsant properties. Furthermore, tryptophan is involved in producing nicotinic acid, contributing to NAD+ and NADP+ synthesis, and influencing serotonin turnover, which affects thyroid-stimulating hormone and prolactin release.

Pharmacodynamics

Tryptophan is crucial for synthesizing proteins, enzymes, and neurotransmitters, particularly serotonin and melatonin. It can act as a natural relaxant, alleviating insomnia, reducing anxiety and depression, and potentially alleviating migraine headaches. Additionally, it may help in chronic pain management, decrease impulsivity, and treat obsessive-compulsive disorders. Deficiencies in tryptophan can lead to adverse cardiovascular effects, including coronary artery spasms.

Pharmacokinetics

L-Tryptophan is absorbed in the gastrointestinal tract, with its bioavailability influenced by factors such as dietary composition and the presence of competing amino acids. It is metabolized primarily in the liver, with metabolites entering various metabolic pathways, including kynurenine and serotonin synthesis. The pharmacokinetics of tryptophan are affected by transport mechanisms across cell membranes, particularly within the context of tRNA charging and metabolic pathways related to amino acid catabolism.

Adverse effects

• Nausea
• Dizziness
• Drowsiness
• Dry mouth
• Abdominal pain
• Diarrhea

Precautions

• Use with caution in patients with a history of liver disease
• May interact with other medications that affect serotonin levels

Pregnancy

Safety during pregnancy has not been established; use only if clearly needed.

Breast-feeding

It is unknown if tryptophan is excreted in human milk; caution is advised.

Storage

Store in a cool, dry place away from direct sunlight.

Formulations

• Capsules
• Tablets
• Powder for oral solution

Indications

• Aphrodisiac
• Enhancement of sexual performance
• Support for male reproductive health
• Stress management

Dosage

Children: Refer to specific product guidelines or consult a healthcare professional, as there is limited data on the safety and efficacy of Musli in children.

Adults: Refer to specific product guidelines or consult a healthcare professional, as doses can vary widely based on the formulation and intended use.

Mechanism of action

Musli is thought to exert its effects through the modulation of hormonal levels and the enhancement of nitric oxide production, which may improve blood flow and support sexual function. It may also influence the expression of various genes related to reproductive health and stress response pathways.

Pharmacodynamics

The active compounds in Musli, including saponins, alkaloids, and glycosides, are believed to contribute to its aphrodisiac effects. These compounds may positively influence testosterone levels, enhance spermatogenesis, and improve libido. Additionally, Musli may have antioxidant properties, protecting cells from oxidative stress.

Pharmacokinetics

Limited data is available on the pharmacokinetics of Musli. However, like many herbal extracts, it is expected to be absorbed in the gastrointestinal tract, with bioavailability dependent on the formulation and method of administration. Metabolism may occur in the liver, and elimination is likely via urinary and fecal pathways.

Pregnancy

Insufficient data is available regarding the safety of musli during pregnancy. Consult a healthcare provider before use.

Breast-feeding

There is limited information on the excretion of musli in breast milk. Consult a healthcare provider before use.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Indications

• Polycystic ovary syndrome (PCOS)
• Insulin resistance
• Metabolic syndrome
• Mood disorders
• Neurodegenerative diseases

Dosage

Children: Dosage for paediatric patients is not established; refer to BNF for Children for specific guidance.

Adults: The typical adult dose of myo-inositol is 2 to 4 grams daily, usually divided into two doses.

Mechanism of action

Myo-inositol functions primarily as a precursor in the biosynthesis of inositol phosphates, which are critical for cell signaling. It contributes to the synthesis of 1D-myo-inositol hexakisphosphate and other inositol phosphates, facilitating the regulation of cellular functions such as insulin signaling and lipid metabolism. Myo-inositol also plays a role in the modulation of neurotransmitter signaling, particularly in the central nervous system.

Pharmacodynamics

Myo-inositol has been shown to influence insulin sensitivity and may help in restoring ovarian function in women with PCOS. It acts as a second messenger in various hormonal signaling pathways, particularly those involving insulin and follicle-stimulating hormone (FSH). The drug's action can lead to improved ovarian response and metabolic profiles in affected individuals.

Pharmacokinetics

Myo-inositol is well-absorbed when administered orally, with a bioavailability that may vary based on the formulation. It is distributed throughout the body and has a half-life that supports multiple dosing regimens. Myo-inositol is eliminated primarily through renal excretion, and its metabolism is closely linked to the pathways of inositol phosphate metabolism.

Pregnancy

The safety of myoinositol during pregnancy has not been established. Consultation with a healthcare professional is advised.

Breast-feeding

Myoinositol is generally considered safe during breastfeeding, but it is recommended to consult a healthcare provider for personalized advice.

Storage

Store at room temperature, away from moisture and direct sunlight. Keep out of reach of children.

Formulations

• Powder
• Tablet
• Capsule

Indications

• Vitamin B6 deficiency
• Peripheral neuropathy associated with isoniazid therapy
• Supplementation in specific dietary deficiencies

Dosage

Children: Refer to the BNF for Children for specific paediatric dosing guidance.

Adults: Refer to the BNF for specific dosing details, typically 10-50 mg daily for deficiency.

Mechanism of action

Pyridoxine, mainly in its active form pyridoxal 5'-phosphate, is involved in numerous biochemical reactions, including amino acid metabolism, glycogen breakdown, nucleic acid synthesis, and the production of key neurotransmitters. It aids in the synthesis of hemoglobin and sphingolipids, and its deficiency can impair several physiological processes, including immune response and vascular health.

Pharmacodynamics

Pyridoxine is utilized for the prevention and treatment of vitamin B6 deficiency, particularly in individuals undergoing treatment with isoniazid, which can deplete vitamin B6 levels. It may also have beneficial effects on blood pressure and lipid profiles, as studies have shown it can lower both systolic and diastolic blood pressure, inhibit platelet aggregation, and improve cholesterol levels. Additionally, it plays a role in enhancing immune function and protecting endothelial cells from injury.

Pharmacokinetics

Pyridoxine is rapidly absorbed from the gastrointestinal tract. It is transported to tissues where it is phosphorylated to its active form, pyridoxal 5'-phosphate. The vitamin is primarily excreted in urine as pyridoxine and its metabolites. Its half-life varies depending on the individual’s nutritional status and other factors. Adequate dietary intake is essential for maintaining optimal levels in the body.

Pregnancy

Pyridoxine is generally considered safe during pregnancy. However, high doses should be avoided unless specifically prescribed.

Breast-feeding

Pyridoxine is excreted in breast milk, but at normal dietary levels it is considered safe for breastfeeding mothers.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Formulations

• Tablets
• Oral solution
• Injectable form

Indications

• Aphrodisiac
• Enhancement of sexual health
• Improvement of stamina and energy levels
• Stress management
• General vitality support

Dosage

Children: Refer to specific product guidelines or consult a healthcare professional for appropriate dosing.

Adults: Refer to specific product guidelines or consult a healthcare professional for appropriate dosing.

Mechanism of action

The exact mechanism of action of Safed Musli is not fully understood. However, it is believed to act as an adaptogen, enhancing the body's resistance to stress and fatigue. It may influence the hormonal balance by affecting levels of testosterone and other hormones, which could contribute to its aphrodisiac effects. Additionally, it contains various bioactive compounds, including saponins, alkaloids, and flavonoids, which may exhibit antioxidant properties, contributing to its health benefits.

Pharmacodynamics

Safed Musli is thought to enhance physical performance and sexual function by improving blood circulation, increasing energy levels, and promoting hormonal balance. The saponins present in Safed Musli may also play a role in its anti-inflammatory and antioxidant activities, supporting overall health and well-being.

Pharmacokinetics

The pharmacokinetics of Safed Musli has not been extensively studied. However, it is believed that the active compounds are absorbed in the gastrointestinal tract after ingestion. The onset of action may vary depending on the dosage and individual metabolism. The duration of effect is also not well defined, as it may depend on the specific formulation and preparation of the herb.

Pregnancy

Safety during pregnancy has not been established. Consult a healthcare provider before use.

Breast-feeding

Safety during breastfeeding has not been established. Consult a healthcare provider before use.

Storage

Store in a cool, dry place away from direct sunlight.

Indications

• Dietary supplement for heart health
• Source of essential fatty acids
• Antioxidant support
• Promotion of digestive health
• Management of cholesterol levels

Dosage

Children: Refer to specific seed type and formulation for dosing information, as it can vary widely based on type and intended use.

Adults: Refer to specific seed type and formulation for dosing information, as it can vary widely based on type and intended use.

Mechanism of action

The bioactive compounds in seeds, such as polyunsaturated fatty acids, phytosterols, and antioxidants, exert various effects in the body. For example, omega-3 fatty acids found in flaxseeds can influence lipid metabolism and reduce inflammation by modulating the production of eicosanoids. Antioxidants such as tocopherols and phenolic compounds can scavenge free radicals, reducing oxidative stress.

Pharmacodynamics

Seeds have shown potential benefits, including the modulation of lipid profiles, reduction in inflammatory markers, and improvement in glycemic control. The consumption of seeds may lead to decreased low-density lipoprotein (LDL) cholesterol levels and increased high-density lipoprotein (HDL) cholesterol levels, contributing to cardiovascular health. The dietary fiber in seeds can also aid in digestive health and promote satiety.

Pharmacokinetics

The pharmacokinetics of seeds can vary widely depending on the type of seed and the specific compounds being analyzed. Generally, the bioactive components are digested and absorbed in the gastrointestinal tract, with fatty acids being incorporated into chylomicrons and transported via the lymphatic system. Antioxidants are absorbed in the small intestine and may have systemic effects, while fiber can influence gastrointestinal motility and fermentation in the colon.

Pregnancy

Consult a healthcare provider before use, as safety during pregnancy is not well established.

Breast-feeding

Consult a healthcare provider before use, as safety during breastfeeding is not well established.

Storage

Store in a cool, dry place, away from direct sunlight.

Mechanism of action

Many of supplemental L-arginine's activities, including its possible anti-atherogenic actions, may be accounted for by its role as the precursor to nitric oxide or NO. NO is produced by all tissues of the body and plays very important roles in the cardiovascular system, immune system and nervous system. NO is formed from L-arginine via the enzyme nitric oxide synthase or synthetase (NOS), and the effects of NO are mainly mediated by 3,'5' -cyclic guanylate or cyclic GMP. NO activates the enzyme guanylate cyclase, which catalyzes the synthesis of cyclic GMP from guanosine triphosphate or GTP. Cyclic GMP is converted to guanylic acid via the enzyme cyclic GMP phosphodiesterase. NOS is a heme-containing enzyme with some sequences similar to cytochrome P-450 reductase. Several isoforms of NOS exist, two of which are constitutive and one of which is inducible by immunological stimuli. The constitutive NOS found in the vascular endothelium is designated eNOS and that present in the brain, spinal cord and peripheral nervous system is designated nNOS. The form of NOS induced by immunological or inflammatory stimuli is known as iNOS. iNOS may be expressed constitutively in select tissues such as lung epithelium. All the nitric oxide synthases use NADPH (reduced nicotinamide adenine dinucleotide phosphate) and oxygen (O2) as cosubstrates, as well as the cofactors FAD (flavin adenine dinucleotide), FMN (flavin mononucleotide), tetrahydrobiopterin and heme. Interestingly, ascorbic acid appears to enhance NOS activity by increasing intracellular tetrahydrobiopterin. eNOS and nNOS synthesize NO in response to an increased concentration of calcium ions or in some cases in response to calcium-independent stimuli, such as shear stress. In vitro studies of NOS indicate that the Km of the enzyme for L-arginine is in the micromolar range. The concentration of L-arginine in endothelial cells, as well as in other cells, and in plasma is in the millimolar range. What this means is that, under physiological conditions, NOS is saturated with its L-arginine substrate. In other words, L-arginine would not be expected to be rate-limiting for the enzyme, and it would not appear that supraphysiological levels of L-arginine which could occur with oral supplementation of the amino acid^would make any difference with regard to NO production. The reaction would appear to have reached its maximum level. However, in vivo studies have demonstrated that, under certain conditions, e.g. hypercholesterolemia, supplemental L-arginine could enhance endothelial-dependent vasodilation and NO production.

Pharmacodynamics

Studies have shown that is has improved immune responses to bacteria, viruses and tumor cells; promotes wound healing and regeneration of the liver; causes the release of growth hormones; considered crucial for optimal muscle growth and tissue repair.

Mechanism of action

A number of important side reactions occur during the catabolism of tryptophan on the pathway to acetoacetate. The first enzyme of the catabolic pathway is an iron porphyrin oxygenase that opens the indole ring. The latter enzyme is highly inducible, its concentration rising almost 10-fold on a diet high in tryptophan. Kynurenine is the first key branch point intermediate in the pathway. Kynurenine undergoes deamniation in a standard transamination reaction yielding kynurenic acid. Kynurenic acid and metabolites have been shown to act as antiexcitotoxics and anticonvulsives. A second side branch reaction produces anthranilic acid plus alanine. Another equivalent of alanine is produced further along the main catabolic pathway, and it is the production of these alanine residues that allows tryptophan to be classified among the glucogenic and ketogenic amino acids. The second important branch point converts kynurenine into 2-amino-3-carboxymuconic semialdehyde, which has two fates. The main flow of carbon elements from this intermediate is to glutarate. An important side reaction in liver is a transamination and several rearrangements to produce limited amounts of nicotinic acid, which leads to production of a small amount of NAD⁺ and NADP⁺. Findings indicate that enhanced rates of serotonin turnover produced by (L)-tryptophan and physical restraint are associated with inhibition of thyroid-stimulating hormone (TSH) and stimulation of prolactin release from anterior pituitary in rats. L-Tryptophan, an indispensable amino acid, serves as a precursor for several small molecules of functional significance including the vitamin niacin, the neurotransmitter serotonin, the metabolite tryptamine, and the pineal hormone melatonin. Increases in tryptophan have been shown to increase synthesis of the neurotransmitters in brain, blood, and other body organs. Amino acids are selected for protein synthesis by binding with transfer RNA (tRNA) in the cell cytoplasm. The information on the amino acid sequence of each individual protein is contained in the sequence of nucleotides in the messenger RNA (mRNA) molecules, which are synthesized in the nucleus from regions of DNA by the process of transcription. The mRNA molecules then interact with various tRNA molecules attached to specific amino acids in the cytoplasm to synthesize the specific protein by linking together individual amino acids; this process, known as translation, is regulated by amino acids (e.g., leucine), and hormones. Which specific proteins are expressed in any particular cell and the relative rates at which the different cellular proteins are synthesized, are determined by the relative abundances of the different mRNAs and the availability of specific tRNA-amino acid combinations, and hence by the rate of transcription and the stability of the messages. From a nutritional and metabolic point of view, it is important to recognize that protein synthesis is a continuing process that takes place in most cells of the body. In a steady state, when neither net growth nor protein loss is occurring, protein synthesis is balanced by an equal amount of protein degradation. The major consequence of inadequate protein intakes, or diets low or lacking in specific indispensable amino acids relative to other amino acids (often termed limiting amino acids), is a shift in this balance so that rates of synthesis of some body proteins decrease while protein degradation continues, thus providing an endogenous source of those amino acids most in need. /Amino acids/ The mechanism of intracellular protein degradation, by which protein is hydrolyzed to free amino acids, is more complex and is not as well characterized at the mechanistic level as that of synthesis. A wide variety of different enzymes that are capable of splitting peptide bonds are present in cells. However, the bulk of cellular proteolysis seems to be shared between two multienzyme systems: the lysosomal and prote

Pharmacodynamics

Tryptophan is critical for the production of the body's proteins, enzymes and muscle tissue. It is also essential for the production of niacin, the synthesis of the neurotransmitter serotonin and melatonin. Tryptophan supplements can be used as natural relaxants to help relieve insomnia. Tryptophan can also reduce anxiety and depression and has been shown to reduce the intensity of migraine headaches. Other promising indications include the relief of chronic pain, reduction of impulsivity or mania and the treatment of obsessive or compulsive disorders. Tryptophan also appears to help the immune system and can reduce the risk of cardiac spasms. Tryptophan deficiencies may lead to coronary artery spasms. Tryptophan is used as an essential nutrient in infant formulas and intravenous feeding. Tryptophan is marketed as a prescription drug (Tryptan) for those who do not seem to respond well to conventional antidepressants. It may also be used to treat those afflicted with seasonal affective disorder (a winter-onset depression). Tryptopan serves as the precursor for the synthesis of serotonin (5-hydroxytryptamine, 5-HT) and melatonin (N-acetyl-5-methoxytryptamine).

Mechanism of action

Vitamin B6 is the collective term for a group of three related compounds, pyridoxine (PN), pyridoxal (PL) and pyridoxamine (PM), and their phosphorylated derivatives, pyridoxine 5'-phosphate (PNP), pyridoxal 5'-phosphate (PLP) and pyridoxamine 5'-phosphate (PMP). Although all six of these compounds should technically be referred to as vitamin B6, the term vitamin B6 is commonly used interchangeably with just one of them, pyridoxine. Vitamin B6, principally in its biologically active coenzyme form pyridoxal 5'-phosphate, is involved in a wide range of biochemical reactions, including the metabolism of amino acids and glycogen, the synthesis of nucleic acids, hemogloblin, sphingomyelin and other sphingolipids, and the synthesis of the neurotransmitters serotonin, dopamine, norepinephrine and gamma-aminobutyric acid (GABA).

Pharmacodynamics

Vitamin B6 (pyridoxine) is a water-soluble vitamin used in the prophylaxis and treatment of vitamin B6 deficiency and peripheral neuropathy in those receiving isoniazid (isonicotinic acid hydrazide, INH). Vitamin B6 has been found to lower systolic and diastolic blood pressure in a small group of subjects with essential hypertension. Hypertension is another risk factor for atherosclerosis and coronary heart disease. Another study showed pyridoxine hydrochloride to inhibit ADP- or epinephrine-induced platelet aggregation and to lower total cholesterol levels and increase HDL-cholesterol levels, again in a small group of subjects. Vitamin B6, in the form of pyridoxal 5'-phosphate, was found to protect vascular endothelial cells in culture from injury by activated platelets. Endothelial injury and dysfunction are critical initiating events in the pathogenesis of atherosclerosis. Human studies have demonstrated that vitamin B6 deficiency affects cellular and humoral responses of the immune system. Vitamin B6 deficiency results in altered lymphocyte differentiation and maturation, reduced delayed-type hypersensitivity (DTH) responses, impaired antibody production, decreased lymphocyte proliferation and decreased interleukin (IL)-2 production, among other immunologic activities.