OVAZOA-RESERVE TABLETS

Adverse effects

• Arthralgia
• Infection
• Dizziness
• Dry mouth
• Gastrointestinal discomfort
• Headaches
• Nausea
• Altered mood
• Night sweats
• Skin reactions
• Aggression
• Depression
• Disorientation
• Weight gain
• Electrolyte imbalance

Interactions

• Fluvoxamine: Severe (increases exposure)
• Givosiran: Moderate (increases exposure)
• Phenytoin: Unknown (decreases exposure)
• Axitinib: Unknown (increases exposure)
• Ritonavir: Unknown (decreases exposure)
• Leflunomide: Unknown (decreases exposure)
• Mexiletine: Unknown (increases exposure)
• Osilodrostat: Unknown (increases exposure)
• Rucaparib: Unknown (increases exposure)
• Teriflunomide: Unknown (decreases exposure)

Precautions

• Use with caution in hepatic impairment
• Use with caution in renal impairment
• Drowsiness may persist into the next day, affecting performance of skilled tasks such as driving

Pregnancy

No information available-avoid.

Breast-feeding

Present in milk-avoid.

Storage

Store in a cool, dry place away from light.

Formulations

• Modified-release tablets (Circadin®, Slenyto®)
• Immediate-release tablets (Adaflex®, Ceyesto®, Syncrodin®)
• Hard capsules
• Oral solution

Indications

• Adrenal insufficiency
• Congenital adrenal hyperplasia
• Polycystic ovary syndrome
• Adrenal tumors
• Hormonal supplementation in aging

Dosage

Children: Refer to the BNF for Children for specific dosing information, as pediatric dosing can vary significantly based on age and condition.

Adults: The usual dose for adults is 25 to 50 mg daily, which may be adjusted based on clinical response and laboratory results.

Mechanism of action

DHEA acts as a prohormone for sex steroids, with DHEAS serving as a reservoir and buffer. It is produced in the adrenal cortex, primarily in the zona reticularis, and is involved in the regulation of adrenal activity. Elevated levels of DHEAS/DHEA can indicate conditions such as adrenal cancer or hyperplasia, and it is linked to polycystic ovary syndrome in women.

Pharmacodynamics

DHEA is synthesized from cholesterol through a series of enzymatic reactions involving cytochrome P450 enzymes. Cholesterol is first converted to pregnenolone by P450 scc, followed by conversion to 17α-hydroxypregnenolone and then to DHEA by CYP17A1. DHEA levels can increase due to factors such as physical exercise and caloric restriction, which some studies suggest may contribute to increased longevity.

Pharmacokinetics

DHEA is absorbed via the gastrointestinal tract and is subject to extensive first-pass metabolism in the liver. It is predominantly bound to serum proteins, primarily albumin and sex hormone-binding globulin. The half-life of DHEA is relatively short, necessitating multiple doses for sustained effects. Metabolism occurs mainly in the liver, with elimination via urine as sulfate and glucuronide conjugates.

Contra-indications

• Pregnancy
• Breastfeeding
• Hormone-sensitive conditions
• Adrenal tumors

Adverse effects

• Acne
• Oily skin
• Mood changes
• Hair loss
• Increased body hair
• Menstrual irregularities
• Headache

Interactions

• Anticoagulants
• Insulin
• Corticosteroids
• Antidepressants

Precautions

• Monitor for hormonal side effects
• Use caution in patients with cardiovascular disease
• Assess for potential effects on mood
• Consider monitoring in patients with liver impairment

Pregnancy

DHEA is contraindicated during pregnancy due to potential hormonal effects on the developing fetus.

Breast-feeding

DHEA is contraindicated during breastfeeding as it may affect milk production and quality.

Storage

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

Formulations

• Tablets
• Capsules

Indications

• Anxiety disorders
• Epilepsy
• Muscle spasms
• Sleep disorders
• Neuropathic pain

Dosage

Children: Refer to specific pediatric dosing guidelines based on clinical indications and formulations available.

Adults: Refer to specific product guidelines or clinical protocols as dosages may vary based on the formulation and intended use.

Mechanism of action

GABA exerts its effects by binding to GABA receptors (specifically GABA-A and GABA-B receptors) in the brain. The binding leads to the opening of ion channels that allow the influx of chloride ions into the neuron, resulting in hyperpolarization of the neuron and decreased likelihood of action potential firing. This mechanism is pivotal in reducing anxiety, seizures, and muscle spasms.

Pharmacodynamics

The primary pharmacodynamic effect of GABA is its ability to inhibit neurotransmission, leading to sedation, relaxation, and anticonvulsant effects. GABA is also involved in various physiological processes, including the regulation of muscle tone and the modulation of mood.

Pharmacokinetics

GABA has a limited ability to cross the blood-brain barrier when administered orally, which may affect its bioavailability and efficacy as a therapeutic agent. It is primarily metabolized in the brain and liver, with its effects being influenced by the overall balance of excitatory and inhibitory neurotransmitters in the central nervous system. The half-life of GABA varies based on the route of administration and individual patient factors.

Contra-indications

• Hypersensitivity to gamma-aminobutyric acid or any component of the formulation
• Severe respiratory depression
• Acute or severe liver disease
• Myasthenia gravis
• Pregnancy (unless under specific medical advice)

Adverse effects

• Drowsiness
• Dizziness
• Ataxia
• Nausea
• Vomiting
• Hypotension
• Respiratory depression
• Dependence potential
• Withdrawal symptoms upon discontinuation

Interactions

• CNS depressants (e.g., alcohol, benzodiazepines) may enhance sedative effects
• Antidepressants may have additive effects leading to increased sedation
• Medications that affect liver enzymes may alter gamma metabolism

Precautions

• Use with caution in patients with a history of substance abuse
• Monitor for signs of respiratory depression, especially in the elderly or those with pre-existing respiratory conditions
• Gradual dose reduction is recommended to minimize withdrawal symptoms

Pregnancy

Not recommended unless the potential benefit justifies the potential risk to the fetus. Consult healthcare provider.

Breast-feeding

Use with caution. Gamma may be excreted in breast milk. Monitor infant for sedation.

Storage

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

Formulations

• Oral tablets
• Oral solutions
• Injectable forms

Indications

• Protein supplementation in athletes
• Muscle recovery post-injury
• Support in conditions causing muscle wasting
• Management of metabolic disorders such as phenylketonuria

Dosage

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

Adults: Refer to the BNF for specific adult dosing guidelines.

Mechanism of action

Leucine undergoes catabolism primarily in muscle tissue, where it is transaminated by branched-chain amino acid aminotransferase, resulting in the formation of various keto acids. These products are further oxidized by branched-chain alpha-keto acid dehydrogenase, leading to the production of acetyl-CoA and acetoacetyl-CoA, classifying leucine as a strictly ketogenic amino acid. The metabolic pathways diverge thereafter, producing multiple intermediates necessary for various physiological functions.

Pharmacodynamics

As an essential amino acid, leucine aids in the regulation of blood sugar levels, supports muscle tissue growth and repair, enhances growth hormone production, and promotes wound healing. It is also known to help prevent muscle protein breakdown that can occur after physical trauma or stress. Leucine may have therapeutic potential for individuals with metabolic disorders such as phenylketonuria, where amino acid metabolism is impaired.

Pharmacokinetics

Leucine is absorbed in the intestines after dietary intake and is transported to tissues where it is utilized. Its bioavailability is influenced by dietary composition and the presence of other amino acids. Once in the muscle tissue, leucine is readily catabolized to produce energy substrates, contributing to muscle metabolism and repair processes. The half-life and excretion routes of leucine are not extensively documented but are primarily through urine in the form of metabolites.

Pregnancy

Leucine is considered safe during pregnancy when consumed in normal dietary amounts. However, high doses should be avoided unless prescribed by a healthcare professional.

Breast-feeding

Leucine is also considered safe during breastfeeding when taken in dietary amounts. High doses should be approached with caution and discussed with a healthcare provider.

Storage

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

Formulations

• Capsule
• Tablet
• Powder

Indications

• Folate deficiency
• Hyperhomocysteinemia
• Supporting treatment in certain neurological disorders
• Prevention of neural tube defects during pregnancy

Dosage

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

Adults: Refer to the BNF for specific dosing recommendations.

Mechanism of action

Levomefolic acid acts as a methyl donor in the conversion of homocysteine to methionine, a reaction that is catalyzed by vitamin B12-dependent methionine synthase. This process is essential for reducing homocysteine levels and facilitating the production of S-adenosylmethionine (SAMe), which participates in various methylation reactions, including neurotransmitter synthesis.

Pharmacodynamics

Levomefolate serves as an active metabolite in one-carbon metabolism, regulating key cellular functions such as DNA synthesis, gene expression, and amino acid metabolism. By acting as a cofactor in the synthesis of neurotransmitters like dopamine, serotonin, and norepinephrine, it plays a vital role in maintaining mental health and cognitive function. Additionally, it contributes to red blood cell formation and myelin synthesis.

Pharmacokinetics

Levomefolate is absorbed efficiently from the gastrointestinal tract and is known to cross the blood-brain barrier, which is significant for its role in neurological functions. It is metabolized in the liver and excreted through urine. Its pharmacokinetic profile is influenced by individual variations in folate metabolism and transport pathways.

Pregnancy

Levomefolic acid is generally considered safe during pregnancy as it is a natural form of folate.

Breast-feeding

Levomefolic acid is compatible with breastfeeding, as it is a natural metabolite of folate.

Storage

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

Indications

• Antioxidant support
• Cardiovascular health
• Neuroprotection
• Potential cancer prevention

Dosage

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

Adults: Refer to specific product guidelines and clinical studies for dosing. Doses may vary based on the intended use and formulation.

Mechanism of action

Tocotrienols exert their effects primarily through their antioxidant activity, which helps to neutralize free radicals and reduce oxidative stress. They also influence various signaling pathways, including the inhibition of cholesterol synthesis and modulation of gene expression related to inflammation and apoptosis.

Pharmacodynamics

The pharmacodynamics of tocotrienols involve their ability to inhibit the proliferation of cancer cells and reduce lipid peroxidation. They may also enhance nitric oxide production and improve endothelial function, contributing to cardiovascular health. Tocotrienols have been shown to possess neuroprotective effects, potentially benefiting neurodegenerative conditions.

Pharmacokinetics

Tocotrienols are absorbed in the intestinal tract, and their bioavailability can be influenced by dietary fat. They are metabolized in the liver and are excreted primarily via the bile. The half-life of tocotrienols in the plasma is relatively short, necessitating regular intake for sustained effects.

Pregnancy

Safety during pregnancy has not been established. Use with caution and only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known whether tocotrienol is excreted in human milk. Caution should be exercised when administering to nursing women.

Storage

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

Formulations

• Capsules
• Softgels
• Powder

Indications

• Supplementation in individuals with coenzyme Q10 deficiency
• Support for cardiovascular health
• Management of certain neurodegenerative diseases
• Enhancement of energy levels and exercise performance

Dosage

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

Adults: Refer to the BNF for specific dosing recommendations.

Mechanism of action

Ubiquinol participates in the mitochondrial electron transport chain, where it acts as an electron carrier, transferring electrons between complexes I and III. This process is essential for the generation of ATP through oxidative phosphorylation. Additionally, as an antioxidant, ubiquinol helps to neutralize free radicals, thereby protecting cellular components from oxidative damage. It is involved in several metabolic pathways, including the TCA cycle and aerobic respiration.

Pharmacodynamics

Ubiquinol enhances mitochondrial energy production and improves cellular bioenergetics. Its antioxidant properties contribute to the stabilization of cellular membranes and the protection of lipids, proteins, and DNA from oxidative damage. The effect of ubiquinol on mitochondrial function can lead to improved exercise capacity, enhanced cardiovascular function, and potential neuroprotective benefits.

Pharmacokinetics

Ubiquinol is absorbed from the gastrointestinal tract and is distributed throughout the body, particularly in organs with high energy demands, such as the heart, liver, and kidneys. Its bioavailability can be influenced by factors such as formulation, food intake, and individual metabolic variations. The half-life of ubiquinol is variable, but it is generally estimated to be several hours. It is metabolized in the liver and excreted primarily through the bile.

Pregnancy

There is insufficient data on the safety of ubiquinol during pregnancy. Consult healthcare professionals before use.

Breast-feeding

Limited data available. Caution is advised when using ubiquinol while breastfeeding.

Storage

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

Formulations

• Capsules
• Softgels
• Tablets

Mechanism of action

Melatonin is a derivative of tryptophan. It binds to melatonin receptor type 1A, which then acts on adenylate cylcase and the inhibition of a cAMP signal transduction pathway. Melatonin not only inhibits adenylate cyclase, but it also activates phosphilpase C. This potentiates the release of arachidonate. By binding to melatonin receptors 1 and 2, the downstream signallling cascades have various effects in the body. The melatonin receptors are G protein-coupled receptors and are expressed in various tissues of the body. There are two subtypes of the receptor in humans, melatonin receptor 1 (MT1) and melatonin receptor 2 (MT2). Melatonin and melatonin receptor agonists, on market or in clinical trials, all bind to and activate both receptor types.The binding of the agonists to the receptors has been investigated for over two decades or since 1986. It is somewhat known, but still not fully understood. When melatonin receptor agonists bind to and activate their receptors it causes numerous physiological processes. MT1 receptors are expressed in many regions of the central nervous system (CNS): suprachiasmatic nucleus of the hypothalamus (SNC), hippocampus, substantia nigra, cerebellum, central dopaminergic pathways, ventral tegmental area and nucleus accumbens. MT1 is also expressed in the retina, ovary, testis, mammary gland, coronary circulation and aorta, gallbladder, liver, kidney, skin and the immune system. MT2 receptors are expressed mainly in the CNS, also in the lung, cardiac, coronary and aortic tissue, myometrium and granulosa cells, immune cells, duodenum and adipocytes. The binding of melatonin to melatonin receptors activates a few signaling pathways. MT1 receptor activation inhibits the adenylyl cyclase and its inhibition causes a rippling effect of non activation; starting with decreasing formation of cyclic adenosine monophosphate (cAMP), and then progressing to less protein kinase A (PKA) activity, which in turn hinders the phosphorilation of cAMP responsive element-binding protein (CREB binding protein) into P-CREB. MT1 receptors also activate phospholipase C (PLC), affect ion channels and regulate ion flux inside the cell. The binding of melatonin to MT2 receptors inhibits adenylyl cyclase which decreases the formation of cAMP.[4] As well it hinders guanylyl cyclase and therefore the forming of cyclic guanosine monophosphate (cGMP). Binding to MT2 receptors probably affects PLC which increases protein kinase C (PKC) activity. Activation of the receptor can lead to ion flux inside the cell. Melatonin is implicated in numerous physiological processes, including circadian rhythms, stress, and reproduction, many of which are mediated by the hypothalamus and pituitary. The physiological actions of melatonin are mainly mediated by melatonin receptors. /The authors/ describe the distribution of the melatonin receptor MT1 in the human hypothalamus and pituitary by immunocytochemistry. MT1 immunoreactivity showed a widespread pattern in the hypothalamus. In addition to the area of the suprachiasmatic nucleus (SCN), a number of novel sites, including the paraventricular nucleus (PVN), periventricular nucleus, supraoptic nucleus (SON), sexually dimorphic nucleus, the diagonal band of Broca, the nucleus basalis of Meynert, infundibular nucleus, ventromedial and dorsomedial nucleus, tuberomamillary nucleus, mamillary body, and paraventricular thalamic nucleus were observed to have neuronal MT1 receptor expression. No staining was observed in the nucleus tuberalis lateralis and bed nucleus of the stria terminalis. The MT1 receptor was colocalized with some vasopressin (AVP) neurons in the SCN, colocalized with some parvocellular and magnocellular AVP and oxytocine (OXT) neurons in the PVN and SON, and colocalized with some parvocellular corticotropin-releasing hormone (CRH) neurons in the PVN. In the pituitary, strong MT1 expression was observed in the pars tuberalis, while a weak staining was found in the posterior and ant

Pharmacodynamics

Melatonin is a hormone normally produced in the pineal gland and released into the blood. The essential amino acid L-tryptophan is a precursor in the synthesis of melatonin. It helps regulate sleep-wake cycles or the circadian rhythm. Production of melatonin is stimulated by darkness and inhibited by light. High levels of melatonin induce sleep and so consumption of the drug can be used to combat insomnia and jet lag. MT1 and MT2 receptors may be a target for the treatment of circadian and non circadian sleep disorders because of their differences in pharmacology and function within the SCN. SCN is responsible for maintaining the 24 hour cycle which regulates many different body functions ranging from sleep to immune functions

Mechanism of action

DHEA can be understood as a prohormone for the sex steroids. DHEAS may be viewed as buffer and reservoir. As most DHEA is produced by the zona reticularis of the adrenal cortex, it is argued that there is a role in the immune and stress response. DHEAS/DHEA are useful to detect excess adrenal activity as seen in adrenal cancer or hyperplasia, including certain forms of congenital adrenal hyperplasia as it is produced nearly entirely by the adrenal glands. Women with polycystic ovary syndrome tend to have elevated levels of DHEAS.

Pharmacodynamics

DHEA is naturally produced from cholesterol through two cytochrome P450 enzymes. Cholesterol is converted to pregnenolone by the enzyme P450 scc (side chain cleavage); then another enzyme, CYP17A1, converts pregnenolone to 17α-Hydroxypregnenolone and then to DHEA. DHEA is increased by exercise and calorie restriction. Some theorize that the increase in endogenous DHEA brought about by calorie restriction is partially responsible for the longer life expectancy known to be associated with calorie restriction.

Mechanism of action

This group of essential amino acids are identified as the branched-chain amino acids, BCAAs. Because this arrangement of carbon atoms cannot be made by humans, these amino acids are an essential element in the diet. The catabolism of all three compounds initiates in muscle and yields NADH and FADH2 which can be utilized for ATP generation. The catabolism of all three of these amino acids uses the same enzymes in the first two steps. The first step in each case is a transamination using a single BCAA aminotransferase, with a-ketoglutarate as amine acceptor. As a result, three different a-keto acids are produced and are oxidized using a common branched-chain a-keto acid dehydrogenase, yielding the three different CoA derivatives. Subsequently the metabolic pathways diverge, producing many intermediates. The principal product from valine is propionylCoA, the glucogenic precursor of succinyl-CoA. Isoleucine catabolism terminates with production of acetylCoA and propionylCoA; thus isoleucine is both glucogenic and ketogenic. Leucine gives rise to acetylCoA and acetoacetylCoA, and is thus classified as strictly ketogenic. There are a number of genetic diseases associated with faulty catabolism of the BCAAs. The most common defect is in the branched-chain a-keto acid dehydrogenase. Since there is only one dehydrogenase enzyme for all three amino acids, all three a-keto acids accumulate and are excreted in the urine. The disease is known as Maple syrup urine disease because of the characteristic odor of the urine in afflicted individuals. Mental retardation in these cases is extensive. Unfortunately, since these are essential amino acids, they cannot be heavily restricted in the diet; ultimately, the life of afflicted individuals is short and development is abnormal The main neurological problems are due to poor formation of myelin in the CNS. 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 proteasomal systems. The lysosome is a membrane-enclosed vesicle inside the cell that contains a variety of proteolytic enzymes and operates mostly at acid pH. Volumes of the cytoplasm are engulfed (autophagy) and are then subjected to the action of the protease enzymes at high concentration. This system is thought to be relatively unselective in most cases, although it can also degrade specific intracellular proteins. The system is highly regulated by hormones such as insulin and glucocorticoids, and by amino acids. The second system is the ATP-dependent ubiquitin-proteasome system, which is present in the cytoplasm. The first step is to join molecules of ubiquitin, a basic 76-amino acid peptide, to lysine residues in the target protein. Several enzymes are involved in this process, which selectively targets proteins for degradation by a second component, the proteasome. Dietary leucine transported into the brain parenchyma serves several functions. Most prominent is the role of leucine as a metabolic precursor of fuel molecules, alpha-ketoisocaproate and ketone bodies. As alternatives to glucose, these compounds are forwarded by the producing astrocytes to the adjacent neural cells. Leucine furthermore participates in the maintenance of the nitrogen balance in the glutamate/glutamine cycle pertinent to the neurotransmitter glutamate. Leucine also serves as a regulator of the activity of some enzymes important for brain energy metabolism. Another role of leucine as an informational molecule is in mTOR signaling that participates in the regulation of food ingestion. The importance of leucine for brain function is stressed by the fact that inborn errors in its metabolism cause metabolic dis

Pharmacodynamics

An essential amino acid. (Claim) Leucine helps with the regulation of blood-sugar levels, the growth and repair of muscle tissue (such as bones, skin and muscles), growth hormone production, wound healing as well as energy regulation. It can assist to prevent the breakdown of muscle proteins that sometimes occur after trauma or severe stress. It may also be beneficial for individuals with phenylketonuria - a condition in which the body cannot metabolize the amino acid phenylalanine

Mechanism of action

Levomefolic acid plays a critical role in methylating homocysteines into methionine by acting as a methyl donor in a reaction catalyzed by vitamine B12-dependent methionine synthase. Homocysteine must either be further metabolized via transulfuration to become cysteine, taurine, and glutathione via a B6-dependent process, or re-methylated to become methionine again. Methionine formed from remethylation of homocysteine by levomefolic acid forms the downstream metabolite S-adenosylmethionine (SAMe), which is involved in numerous biochemical methyl donation reactions, including reactions forming monoamine neurotransmitters. Studies suggest that high plasma levels of homocysteine is associated with increased incidences of arterial plaque formation.

Pharmacodynamics

Levomefolic acid is an active metabolite of folic acid and a methyl group donor in one-carbon metabolism reactions. It regulates important cellular functions such as DNA biosynthesis, gene expression regulation, amino acid synthesis and metabolism, and myelin synthesis and repair. As a only form of folate that can cross the blood-brain barrier, it acts as a cofactor in the production of monoamine neurotransmitters such as dopamine, serotonin and norepinephrine. Levomefolic acid is also involved in red blood cell formation.