AJ WELLNESS VITAL WOMAN CAPSULES

Indications

• Isolated carboxylase defects
• Defects of biotin metabolism
• Prevention of deficiency in complete biliary obstruction

Dosage

Children: Neonate: Initially 10 mg once daily, adjusted according to response; maintenance 5–20 mg daily. Child: Initially 10 mg once daily, adjusted according to response; maintenance 5–20 mg daily, higher doses may be required.

Adults: For adults, the dosing may vary based on the condition being treated. General guidance is to refer to the BNF for specific dosing recommendations.

Mechanism of action

Biotin acts as a coenzyme for carboxylase enzymes, facilitating critical metabolic processes including gluconeogenesis, fatty acid synthesis, and amino acid catabolism.

Pharmacodynamics

Biotin is essential for the carboxylation of substrates in metabolic pathways, influencing energy metabolism and the synthesis of important biomolecules. It supports normal growth and development.

Pharmacokinetics

Biotin is absorbed in the intestine and is widely distributed in body tissues. It is not stored in large amounts, with excess being excreted in urine. The half-life and specific pharmacokinetic parameters can vary based on individual metabolism and dietary intake.

Adverse effects

• Rough skin
• Dry hair
• Enlarged liver
• Increases in erythrocyte sedimentation rate
• Increased serum calcium
• Increased serum alkaline phosphatase concentration

Precautions

• Excessive doses may be teratogenic
• High levels of vitamin A may cause birth defects

Pregnancy

No information available.

Breast-feeding

No information available.

Formulations

• Tablet
• Oral suspension
• Oral solution
• Solution for injection

Indications

• Selenium deficiency
• Supportive therapy in conditions requiring antioxidant support
• Potential adjunct in cancer prevention strategies

Dosage

Children: Refer to BNF for Children for specific dosing information.

Adults: Initially 100–500 micrograms daily, adjusted according to response and serum levels.

Mechanism of action

Selenium is metabolized to selenophosphate and selenocysteine, which are essential for the synthesis of selenoproteins. This process involves the incorporation of selenium into proteins through a specialized tRNA that recognizes the RNA sequence UGA, which is facilitated by SECIS structures and SBP-2 proteins. Key selenoproteins, like glutathione peroxidases, help protect cells from oxidative damage, thus playing a significant role in reducing the risk of diseases such as atherosclerosis and certain cancers.

Pharmacodynamics

Selenium is incorporated into various selenoproteins that perform essential functions, including antioxidant activity, redox balance, and regulation of thyroid hormones. Its role in antioxidant defense mechanisms is particularly important for protecting cells against reactive oxygen species (ROS). Selenium supplementation has been linked to improved immune function and potential cancer prevention.

Pharmacokinetics

Selenium is absorbed through the gastrointestinal tract, and its bioavailability can vary based on the source and form of selenium. Once absorbed, it is distributed to various tissues, where it is incorporated into selenoproteins. Selenium is primarily excreted through urine, and its half-life can depend on dietary intake and individual metabolism. Selenium status can be assessed through blood levels of selenoproteins and selenium itself.

Adverse effects

• Nausea
• Anaemia
• Aplastic anaemia
• Skin reactions
• Gastrointestinal disorders

Precautions

• Selenium supplementation should not be given unless there is good evidence of deficiency.
• Use caution in patients with a history of hypersensitivity to selenium or its compounds.

Pregnancy

Limited information is available regarding selenium supplementation during pregnancy. Consult specialist sources for guidance.

Breast-feeding

Limited information is available; the effect of selenium on copper levels in milk is conflicting, and its impact on the infant is unknown.

Storage

After opening, store in a refrigerator (2–8°C).

Formulations

• Tablets (e.g., L-Selenomethionine 200 micrograms, SelenoPrecise 100 micrograms)
• Capsules (e.g., Trientine dihydrochloride 250 mg)
• Injection solutions (e.g., Sodium selenite 50 micrograms per 1 ml)

Indications

• Cognitive impairment
• Dementia
• Memory enhancement
• Anxiety
• Peripheral vascular disease

Dosage

Children: Safety and efficacy in children have not been established. Use is not generally recommended without professional guidance.

Adults: Refer to specific product guidelines, as Ginkgo biloba is available in various forms including tablets, extracts, and teas. Typical doses range from 120 to 240 mg per day, divided into two or three doses.

Mechanism of action

The exact mechanism of action of Ginkgo biloba is not fully understood, but it is believed to enhance cerebral blood flow and improve circulation by inhibiting platelet-activating factor (PAF) and promoting vasodilation through nitric oxide release. Additionally, the antioxidant properties of flavonoids and terpenoids may protect neurons from oxidative stress and free radical damage.

Pharmacodynamics

Ginkgo biloba exhibits several pharmacodynamic effects, including increased blood flow to the brain, improved oxygen utilization, and enhanced glucose metabolism. It may also modulate neurotransmitter systems, including serotonin and dopamine, which could contribute to its effects on mood and cognitive function. The anti-inflammatory properties may further aid in neuroprotection.

Pharmacokinetics

Ginkgo biloba extracts are well-absorbed after oral administration. The bioavailability of its active constituents varies, and peak plasma concentrations occur within 1 to 4 hours post-ingestion. The elimination half-life of ginkgo flavonoids is approximately 4 to 5 hours, and metabolites are primarily excreted in urine. Factors such as age, health status, and concurrent medications can affect its pharmacokinetics.

Adverse effects

• Headache
• Dizziness
• Gastrointestinal upset
• Allergic skin reactions
• Palpitations

Interactions

• Anticoagulants (e.g., warfarin)
• Antiplatelet agents (e.g., aspirin)
• Nonsteroidal anti-inflammatory drugs (NSAIDs)
• Certain antidepressants (e.g., selective serotonin reuptake inhibitors)

Precautions

• Use with caution in patients with bleeding disorders
• Monitor for potential interactions with other medications
• Discontinue use prior to surgery to reduce bleeding risk

Pregnancy

Not recommended due to insufficient safety data.

Breast-feeding

Lack of sufficient data, caution is advised.

Storage

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

Formulations

• Tablets
• Capsules
• Liquid extracts

Indications

• Antioxidant support
• Cardiovascular health
• Anti-inflammatory treatment
• Support for immune function
• Potential anti-cancer effects

Dosage

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

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

Mechanism of action

Bioflavonoids exert their effects primarily through their antioxidant activity, which involves scavenging free radicals and reducing oxidative stress. They modulate various signaling pathways, including those involved in inflammation, cell proliferation, and apoptosis. Some bioflavonoids also influence the activity of enzymes involved in drug metabolism and can affect the bioavailability of other compounds.

Pharmacodynamics

Bioflavonoids demonstrate a wide range of pharmacological activities, including anti-inflammatory, antiviral, and antimicrobial effects. They interact with various cellular targets, including transcription factors and enzymes, to exert protective effects against cellular damage and inflammation. Their ability to enhance endothelial function and promote vasodilation contributes to cardiovascular health.

Pharmacokinetics

Bioflavonoids are generally well-absorbed in the gastrointestinal tract, although their bioavailability can vary significantly depending on the specific flavonoid and its sources. They undergo extensive metabolism in the liver, where they are converted into various metabolites. The elimination half-life of bioflavonoids can vary, and their pharmacokinetic profiles are influenced by factors such as dietary intake and the presence of other substances in the gut.

Adverse effects

• Headache
• Gastrointestinal disturbances
• Skin rashes
• Allergic reactions

Interactions

• May enhance the effects of certain medications, such as anticoagulants and antiplatelet agents
• Potential interaction with certain chemotherapy agents

Precautions

• Use with caution in patients with known allergies to flavonoids
• Monitor for interactions if the patient is on anticoagulant therapy

Pregnancy

Bioflavonoids are generally considered safe during pregnancy, but it is advisable to consult a healthcare provider before use.

Breast-feeding

Bioflavonoids are typically deemed safe during breastfeeding, but consultation with a healthcare professional is recommended.

Storage

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

Formulations

• Capsules
• Tablets
• Powders
• Liquid extracts

Indications

• Eczema
• Rheumatoid arthritis
• Dry skin conditions
• Menstrual pain
• Respiratory conditions

Dosage

Children: Refer to specific product guidelines or professional recommendations, as dosages may differ based on age, weight, and clinical condition.

Adults: Refer to specific product guidelines or professional recommendations, as dosages can vary widely depending on the indication and formulation.

Mechanism of action

Borage oil exerts its effects primarily through the presence of gamma-linolenic acid (GLA), an omega-6 fatty acid. GLA is converted in the body to prostaglandin E1 (PGE1), which is known to have anti-inflammatory properties. This pathway impacts various physiological processes, including inflammation and immune response modulation.

Pharmacodynamics

Borage oil has been shown to possess anti-inflammatory and skin barrier-enhancing effects. The GLA in borage oil can influence the production of eicosanoids, which are signaling molecules that mediate inflammation and other physiological functions. This can result in reduced symptoms in inflammatory conditions and improved skin hydration and elasticity.

Pharmacokinetics

Following oral administration, borage oil is metabolized in the liver, where GLA is released and subsequently incorporated into cell membranes. The bioavailability of GLA can be affected by various factors, including the presence of dietary fats. The half-life of GLA in the body is not well-defined, but its effects can persist due to incorporation into cellular structures. Excretion of metabolites occurs primarily through the urine.

Adverse effects

• Gastrointestinal disturbances
• Allergic skin reactions
• Headaches
• Drowsiness

Interactions

• May interact with anticoagulants or antiplatelet drugs, increasing the risk of bleeding
• Caution with other herbal supplements that have sedative effects

Precautions

• Use with caution in individuals with liver disease
• Should not be used during pregnancy or breastfeeding due to potential toxicity

Pregnancy

Borage should be avoided during pregnancy due to potential toxicity and lack of safety data.

Breast-feeding

Not recommended during breastfeeding as safety has not been established.

Storage

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

Formulations

• Borage oil (capsules, liquid)
• Dried borage leaves (for herbal teas)

Indications

• Nutritional supplementation for chromium deficiency
• Management of insulin resistance
• Support for glucose metabolism in type 2 diabetes
• Potential adjunct therapy for weight management

Dosage

Children: Refer to specific formulations and guidelines for dosing; pediatric doses should be determined based on age, weight, and clinical indication.

Adults: Refer to specific formulations and guidelines for dosing; general recommendations for chromium supplementation vary widely based on health status and dietary needs.

Mechanism of action

Chromium enhances the action of insulin by increasing the sensitivity of insulin receptors. It is thought to facilitate the transport of glucose across cell membranes by activating insulin receptors, thus promoting glucose uptake in tissues. Chromium may also influence lipid metabolism and improve the response to insulin in individuals with insulin resistance.

Pharmacodynamics

Chromium is known to improve glucose tolerance and reduce insulin resistance in individuals with type 2 diabetes. It may also have a role in reducing serum lipid levels, including total cholesterol and triglycerides. The pharmacodynamic effects of chromium can vary based on the form administered and individual metabolic responses.

Pharmacokinetics

Chromium is absorbed in the gastrointestinal tract, with absorption rates varying based on dietary factors and the form of chromium ingested. It is distributed throughout the body, with significant accumulation in the liver, spleen, and bone. Chromium is excreted primarily through urine, and its half-life can vary based on the individual's metabolic state and the form of chromium used.

Adverse effects

• Gastrointestinal disturbances
• Nausea
• Diarrhea
• Skin reactions
• Headaches

Interactions

• May interact with certain medications that affect blood sugar levels
• Potential interactions with antacids and other medications that affect metal absorption

Precautions

• Use with caution in individuals with diabetes
• Monitor blood glucose levels in diabetics taking chromium supplements
• Potential for allergic reactions in sensitive individuals

Pregnancy

Safety during pregnancy is not established; consult a healthcare provider before use.

Breast-feeding

Safety during breastfeeding is not established; consult a healthcare provider before use.

Storage

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

Formulations

• Chromium picolinate
• Chromium chloride
• Chromium nicotinate

Indications

• Antioxidant support
• Immune system support
• Anti-inflammatory effects
• Culinary uses

Dosage

Children: Refer to the BNF for Children for specific dosing recommendations based on age and condition.

Adults: Refer to specific product guidelines or clinical recommendations, as dosages may vary based on the form of citrus used (e.g., juice, supplements).

Mechanism of action

Citrus fruits contain a variety of bioactive compounds, including ascorbic acid (vitamin C), flavonoids, and limonoids. These compounds exert their effects through antioxidant activity, modulating cellular signaling pathways, and enhancing immune function. The flavonoids in citrus may inhibit oxidative stress and inflammation, contributing to their health-promoting effects.

Pharmacodynamics

The pharmacodynamic properties of citrus components are largely attributed to their antioxidant capacity and ability to scavenge free radicals. The bioactive compounds interact with various cellular pathways, potentially reducing the risk of chronic diseases such as cardiovascular disease and certain cancers. The vitamin C content also plays a crucial role in collagen synthesis and immune support.

Pharmacokinetics

Citrus bioactive compounds are absorbed in the gastrointestinal tract, with vitamin C being readily absorbed. The metabolism of flavonoids occurs primarily in the liver through phase I and II metabolic processes, resulting in various metabolites that can exert biological effects. The elimination half-lives of these compounds vary, and they are primarily excreted via the urine.

Pregnancy

Citrus fruits are generally considered safe during pregnancy. However, excessive consumption may lead to gastrointestinal discomfort, and pregnant individuals should consult with healthcare providers regarding their diet.

Breast-feeding

Citrus fruits are safe during breastfeeding, but it is advisable to consume them in moderation as they may cause gastrointestinal discomfort in some infants.

Storage

Citrus fruits should be stored in a cool, dry place. They can also be refrigerated to extend freshness, but should be kept in a breathable bag to avoid moisture accumulation.

Formulations

• fresh fruit
• juice
• essential oil

Indications

• Copper deficiency
• Occipital Horn Syndrome
• Menke's disease
• Contraception (via copper IUD)

Dosage

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

Adults: Refer to the relevant clinical guidelines and BNF for specific dosing information.

Mechanism of action

Copper is absorbed from the gastrointestinal tract via high affinity copper uptake proteins and low affinity copper uptake proteins, likely being reduced to the Cu1+ form prior to transport. Inside enterocytes, it binds to the copper transport protein ATOX1, which facilitates its transport to copper transporting ATPase-1 on the Golgi membrane for incorporation into the Golgi apparatus. Once in systemic circulation, copper binds primarily to ceruloplasmin, albumin, and alpha 2-macroglobulin. It acts as a cofactor in a variety of oxidase enzymes and also influences sperm motility when released from copper IUDs, contributing to its contraceptive effect.

Pharmacodynamics

Copper is essential for the activity of many enzymes and plays a vital role in processes such as iron metabolism, neurotransmitter synthesis, and antioxidant defense. Copper ions, particularly when released from intrauterine devices, have been shown to decrease sperm viability, thereby impacting fertility.

Pharmacokinetics

Copper is absorbed from the gut and is predominantly transported in the plasma bound to proteins such as ceruloplasmin and albumin. The absorption efficiency can vary; however, a significant portion of dietary copper is usually absorbed. The body regulates copper levels through hepatic excretion and storage mechanisms, ensuring homeostasis. Excess copper can lead to toxicity, while deficiency results in various health issues.

Pregnancy

Copper is considered essential during pregnancy, but excessive intake should be avoided due to potential toxicity.

Breast-feeding

Copper is excreted in breast milk, and adequate maternal intake is important for infant development.

Storage

Store in a cool, dry place, away from moisture and heat.

Indications

• Premenstrual syndrome (PMS)
• Eczema (atopic dermatitis)
• Rheumatoid arthritis
• Breast pain (mastalgia)
• Menopausal symptoms

Dosage

Children: Refer to established guidelines or consult a healthcare professional for appropriate dosing in children. Specific dosing recommendations are not well established.

Adults: Refer to established guidelines or consult a healthcare professional for appropriate dosing. Typical doses range from 500 mg to 3000 mg of evening primrose oil per day, depending on the condition being treated.

Mechanism of action

Evening primrose oil exerts its effects primarily through the presence of gamma-linolenic acid (GLA). GLA is converted in the body into prostaglandins, which are compounds that help regulate inflammation and other physiological processes. By increasing the levels of prostaglandins, GLA may help to alleviate symptoms associated with inflammation and hormonal imbalances.

Pharmacodynamics

The pharmacodynamic effects of evening primrose oil are attributed to its fatty acid composition, particularly GLA. It has been shown to modulate inflammatory responses, enhance skin barrier function, and may influence hormonal regulation, providing symptomatic relief in conditions like PMS and eczema. The anti-inflammatory effect may also contribute to its use in managing conditions like rheumatoid arthritis.

Pharmacokinetics

Evening primrose oil is absorbed in the gastrointestinal tract and metabolized by the liver. The bioavailability of GLA may vary among individuals and can be influenced by dietary factors. The half-life of GLA is not well-defined in the literature. The oil is generally well-tolerated, but gastrointestinal side effects may occur in some users.

Pregnancy

Limited data is available on the use of evening primrose oil during pregnancy. Caution is advised.

Breast-feeding

Evening primrose oil is generally considered safe during breastfeeding, but consult a healthcare provider for personalized advice.

Storage

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

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.

Indications

• Folate deficiency
• Megaloblastic anemia
• Prevention of neural tube defects in pregnancy
• Supplementation in patients on certain medications (e.g., methotrexate)

Dosage

Children: Refer to the BNF for Children for appropriate pa

Adults: Refer to specific guidelines or the BNF for appropriate adult dosing based on the indication.

Mechanism of action

Folate functions as a coenzyme in the conversion of homocysteine to methionine, a process that is vital for DNA synthesis and repair. It is involved in the one-carbon metabolism pathway, where it acts as a carrier of one-carbon units necessary for the synthesis of purines and thymidylate, thus supporting the production of nucleotides and DNA. This mechanism is particularly important in rapidly dividing cells.

Pharmacodynamics

Folate is critical for the formation of red blood cells and the proper functioning of the nervous system. It aids in the production of nucleic acids, which are essential for cell proliferation. Folate deficiency can lead to impaired DNA synthesis, resulting in megaloblastic anemia characterized by the presence of large, immature red blood cells in the bloodstream. Adequate folate levels are also associated with reduced risk of neural tube defects in developing fetuses.

Pharmacokinetics

Folate is absorbed in the proximal part of the small intestine, primarily in the jejunum, and is transported in the bloodstream bound to plasma proteins. It undergoes hepatic metabolism and is stored mainly in the liver. The elimination half-life varies, but dietary folate can be retained in the body for several weeks. Excess folate is excreted through the urine. The bioavailability of folate from food sources is lower compared to synthetic folic acid found in supplements.

Interactions

• folates+fluorouracil: Severe (increases risk of toxicity)
• folates+antiepileptics: Moderate (decreases concentration)
• folates+fosphenytoin: Moderate (decreases concentration)
• folates+phenobarbital: Moderate (decreases concentration)
• folates+phenytoin: Moderate (decreases concentration)
• folates+primidone: Moderate (decreases concentration)
• sulfasalazine+folates: Unknown (decreases absorption)

Pregnancy

Folate is essential for fetal development and is often recommended to prevent neural tube defects.

Breast-feeding

Folate is generally safe during breastfeeding, as it is important for both maternal and infant health.

Storage

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

Formulations

• Tablets
• Injection

Indications

• Cognitive enhancement
• Memory disorders
• Tinnitus
• Peripheral vascular disease
• Anxiety
• Age-related macular degeneration

Dosage

Children: Safety and efficacy have not been established in children, so refer to specific guidelines if considering use in paediatric populations.

Adults: Refer to specific product guidelines, typically ranging from 120 to 240 mg of standardized ginkgo extract per day, divided into two or three doses.

Mechanism of action

The exact mechanism of action of ginkgo is not fully understood, but it is thought to involve several pathways. Ginkgo extracts contain flavonoids and terpenoids, which are believed to contribute to its pharmacological effects. These compounds may enhance cerebral blood flow by dilating blood vessels and reducing blood viscosity. Ginkgo also has antioxidant properties that help protect against oxidative stress, and it may modulate neurotransmitter systems, particularly those involving serotonin and dopamine.

Pharmacodynamics

Ginkgo exhibits various pharmacodynamic effects, including vasodilation, increased blood flow, and improved neurotransmission. It is noted for its ability to enhance cognitive function, particularly in older adults with mild cognitive impairment. The antioxidant properties of ginkgo help mitigate damage caused by free radicals, potentially reducing the risk of neurodegenerative diseases. Its effects on blood circulation can also alleviate symptoms associated with peripheral vascular disease.

Pharmacokinetics

Ginkgo is rapidly absorbed after oral administration, with peak plasma concentrations typically occurring within 1-3 hours. It undergoes extensive metabolism in the liver, primarily via cytochrome P450 enzymes. The elimination half-life of ginkgo components can vary, generally ranging from 4 to 12 hours. The bioavailability of ginkgo extracts can be influenced by formulation and individual patient factors, including age and health status.

Contra-indications

• Hypersensitivity to ginkgo or any of its components
• Active bleeding disorders
• Concurrent use with anticoagulants or antiplatelet agents

Adverse effects

• Gastrointestinal upset
• Headache
• Dizziness
• Allergic skin reactions
• Palpitations

Interactions

• Increased risk of bleeding when used with warfarin, aspirin, or other anticoagulants
• Potential interaction with selective serotonin reuptake inhibitors (SSRIs) and other antidepressants
• May affect the metabolism of certain drugs metabolized by cytochrome P450 enzymes

Precautions

• Use with caution in patients with a history of seizures
• Monitor for bleeding complications in patients with bleeding disorders
• Discontinue use prior to surgical procedures to reduce bleeding risk

Pregnancy

Limited data available, caution advised; consult healthcare provider.

Breast-feeding

Insufficient reliable information available regarding safety; consult healthcare provider.

Storage

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

Formulations

• Ginkgo biloba extract (standardized)
• Ginkgo leaf tablets
• Ginkgo capsules
• Ginkgo tinctures

Indications

• Wound healing
• Skin ulceration
• Burns
• Psoriasis
• Dermatitis

Dosage

Children: Refer to the BNF for Children for appropriate dosing information based on the child's age and condition.

Adults: Refer to the BNF for specific formulations and dosing guidelines, as dosages may vary based on the condition being treated and the formulation used.

Mechanism of action

While there is no well-controlled data to formally substantiate the method of action, ongoing studies suggest that allantoin may induce a histological wound healing profile in animal models, leading to improved reestablishment of normal skin. This includes increased vasodilation, inflammatory cell presence, angiogenesis, fibroblast proliferation, and collagen deposition in treated wounds compared to untreated ones.

Pharmacodynamics

There is limited controlled data regarding the pharmacodynamic properties of allantoin. However, studies indicate that allantoin may possess moisturizing and keratolytic effects, increasing the extracellular matrix's water content and enhancing the desquamation of dead skin cells. These activities can promote cell proliferation and facilitate wound healing.

Pharmacokinetics

Specific pharmacokinetic data for allantoin in humans is limited. However, it is known to be applied topically, which suggests local absorption at the site of application. Systemic absorption is considered minimal due to its low molecular weight and hydrophilicity.

Pregnancy

There is limited data on the safety of allantoin in pregnancy. It is advisable to consult a healthcare professional before use.

Breast-feeding

Allantoin is generally considered safe during breastfeeding, but caution is recommended. Consult a healthcare professional before use.

Storage

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

Formulations

• Topical cream
• Gel
• Ointment

Indications

• Manganese deficiency
• Bone health and development
• Antioxidant support
• Enzyme cofactor in metabolic processes

Dosage

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

Adults: Refer to specific clinical guidelines or the BNF for appropriate dosing recommendations.

Mechanism of action

Manganese serves as a cofactor for several enzymes, including manganese superoxide dismutase (MnSOD), which protects cells from oxidative stress by catalyzing the dismutation of superoxide radicals into oxygen and hydrogen peroxide. It also participates in the activation of enzymes involved in carbohydrate, fat, and protein metabolism.

Pharmacodynamics

Manganese plays a role in various biochemical pathways, particularly in the metabolism of amino acids, cholesterol, glucose, and carbohydrates. It is crucial for bone formation and the maintenance of cartilage. Manganese also aids in the synthesis of glycosyltransferases, which are important for the formation of glycoproteins and proteoglycans.

Pharmacokinetics

Manganese is absorbed primarily in the small intestine, with absorption efficiency influenced by dietary factors and the presence of competing minerals. It is transported in the bloodstream bound to proteins such as alpha-2-macroglobulin and transferrin. Manganese is stored in the liver, pancreas, and bones, and is excreted primarily through bile and to a lesser extent in urine. Its half-life in the human body is not well defined due to its trace nature and variable absorption.

Pregnancy

Manganese is classified as a dietary mineral that is essential for human health, but excessive intake should be avoided during pregnancy as it may affect fetal development.

Breast-feeding

Manganese is present in breast milk, and normal dietary intake is considered safe during breastfeeding. However, excessive supplementation should be avoided.

Storage

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

Indications

• Eczema
• Premenstrual syndrome (PMS)
• Rheumatoid arthritis
• Menopausal symptoms
• Skin disorders

Dosage

Children: Refer to specific product guidelines, as dosages can vary based on formulation and indication.

Adults: Refer to specific product guidelines, as dosages can vary based on formulation and indication.

Mechanism of action

Gamma-linolenic acid (GLA) is metabolized to prostaglandin E1, which exerts anti-inflammatory effects. This pathway involves the conversion of GLA to dihomo-gamma-linolenic acid (DGLA), which is a precursor for the synthesis of anti-inflammatory prostaglandins, helping to modulate inflammatory responses in the body.

Pharmacodynamics

GLA is thought to alter the metabolism of arachidonic acid, leading to decreased production of pro-inflammatory eicosanoids. This can help alleviate symptoms associated with inflammatory conditions, and the fatty acids present in primrose may also contribute to skin barrier function and hydration, making it beneficial for skin-related disorders.

Pharmacokinetics

After oral administration, GLA is absorbed in the gastrointestinal tract, with peak plasma concentrations typically occurring within a few hours. It is then distributed throughout the body, where it can be incorporated into cell membranes. The metabolism of GLA involves conversion into various metabolites, including DGLA, and it is excreted mainly through urine and feces. The half-life of GLA can vary based on individual metabolism and dietary factors.

Adverse effects

• Gastrointestinal upset
• Nausea
• Diarrhea
• Headache
• Allergic skin reactions

Interactions

• May enhance the effects of anticoagulants
• May interact with antipsychotic medications

Precautions

• Use with caution in individuals with bleeding disorders
• Monitor for potential allergic reactions

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. Keep out of reach of children.

Formulations

• Oil
• Capsules
• Tablets

Mechanism of action

Biotin is necessary for the proper functioning of enzymes that transport carboxyl units and fix carbon dioxide, and is required for various metabolic functions, including gluconeogenesis, lipogenesis, fatty acid biosynthesis, propionate metabolism, and catabolism of branched-chain amino acids. In human tissues biotin is a cofactor for the enzymatic carboxylation of four substrates: pyruvate, acetyl coenzyme A (CoA), propionyl CoA, and beta-methylcrotonyl CoA. As such, it plays an important role in both carbohydrate and fat metabolism. Carbon dioxide fixation occurs in a two-step reaction, the first involving binding of carbon dioxide to the biotin moiety of the holoenzyme, and the second involving transfer of the biotin-bound carbon dioxide to an appropriate acceptor. Biotin functions in carbon dioxide fixation reactions in intermediate metabolism, transferring the carboxyl group to acceptor molecules. It acts similarly in decarboxylation reactions. Biotin is essential in human metabolism for its part in the previously described enzymatic steps, in catalyzing deamination of amino acids, and in oleic acid synthesis. Biotin is a cofactor for the enzymatic carboxylation of pyruvate, acetyl coenzyme A (CoA), propionyl CoA, and beta-methylcrotonyl CoA, and, therefore, plays an important role in carbohydrate and fat metabolism. Protein folding in the endoplasmic reticulum (ER) depends on Ca2+; uptake of Ca2+ into the ER is mediated by sarco/endoplasmic reticulum Ca2+-ATPase 3 (SERCA3). The 5'-flanking region of the SERCA3 gene (ATP2A3) contains numerous binding sites for the transcription factors Sp1 and Sp3. Biotin affects the nuclear abundance of Sp1 and Sp3, which may act as transcriptional activators or repressors. Here we determined whether biotin affects the expression of the SERCA3 gene and, thus, protein folding in human lymphoid cells. Jurkat cells were cultured in media containing 0.025 nmol/L biotin (denoted "deficient") or 10 nmol/L biotin ("supplemented"). The transcriptional activity of the full-length human SERCA3 promoter was 50% lower in biotin-supplemented cells compared to biotin-deficient cells. Biotin-dependent repressors bind to elements located 731 to 1312 bp upstream from the transcription start site in the SERCA3 gene. The following suggest that low expression of SERCA3 in biotin-supplemented cells impaired folding of secretory proteins in the ER, triggering unfolded protein response: (i) sequestration of Ca2+ in the ER decreased by 14 to 24% in response to biotin supplementation; (ii) secretion of interleukin-2 into the extracellular space decreased by 75% in response to biotin supplementation; (iii) the nuclear abundance of stress-induced transcription factors increased in response to biotin supplementation; and (iv) the abundance of stress-related proteins such ubiquitin activating enzyme 1, growth arrest and DNA damage 153 gene, X-box binding protein 1 and phosphorylated eukaryotic translation initiation factor 2alpha increased in response to biotin supplementation. Collectively, this study suggests that supplements containing pharmacological doses of biotin may cause cell stress by impairing protein folding in the ER. Evidence is emerging that biotin participates in processes other than classical carboxylation reactions. Specifically, novel roles for biotin in cell signaling, gene expression, and chromatin structure have been identified in recent years. Human cells accumulate biotin by using both the sodium-dependent multivitamin transporter and monocarboxylate transporter 1. These transporters and other biotin-binding proteins partition biotin to compartments involved in biotin signaling: cytoplasm, mitochondria, and nuclei. The activity of cell signals such as biotinyl-AMP, Sp1 and Sp3, nuclear factor (NF)-kappaB, and receptor tyrosine kinases depends on biotin supply. Consistent with a role for biotin and its catabolites in modulating these cell signals, greater than 2000 biotin-dependent genes have

Pharmacodynamics

Biotin is a water-soluble B-complex vitamin which is composed of an ureido ring fused with a tetrahydrothiophene ring, which attaches a valeric acid substituent at one of its carbon atoms. Biotin is used in cell growth, the production of fatty acids, metabolism of fats, and amino acids. It plays a role in the Kreb cycle, which is the process in which energy is released from food. Biotin not only assists in various metabolic chemical conversions, but also helps with the transfer of carbon dioxide. Biotin is also helpful in maintaining a steady blood sugar level. Biotin is often recommended for strengthening hair and nails. Consequenty, it is found in many cosmetic and health products for the hair and skin. Biotin deficiency is a rare nutritional disorder caused by a deficiency of biotin. Initial symptoms of biotin deficiency include: Dry skin, Seborrheic dermatitis, Fungal infections, rashes including erythematous periorofacial macular rash, fine and brittle hair, and hair loss or total alopecia. If left untreated, neurological symptoms can develop, including mild depression, which may progress to profound lassitude and, eventually, to somnolence; changes in mental status, generalized muscular pains (myalgias), hyperesthesias and paresthesias. The treatment for biotin deficiency is to simply start taking some biotin supplements. A lack of biotin in infants will lead to a condition called seborrheic dermatitis or "cradle cap". Biotin deficiencies are extremely rare in adults but if it does occur, it will lead to anemia, depression, hair loss, high blood sugar levels, muscle pain, nausea, loss of appetite and inflamed mucous membranes.

Mechanism of action

Selenium is first metabolized to selenophosphate and selenocysteine. Selenium incorporation is genetically encoded through the RNA sequence UGA. This sequence is recognized by RNA ste loop structures called selenocysteine inserting sequences (SECIS). These structures require the binding of SECIS binding proteins (SBP-2) to recognize selenocystiene. The specialized tRNA is first bound to a serine residue which is then enzymatically processed to a selylcysteyl-tRNA by selenocystiene sythase using selenophosphate as a selenium donor. Other unidentified proteins are required as part of the binding of this tRNA to the ribosome. Selenoproteins appear to be necessary for life as mice with the specialized tRNA gene knocked out exhibited early embryonic lethality. The most important selenoproteins seem to be the glutathione peroxidases and thioredoxin reductases which are part of the body's defenses againts reactive oxygen species (ROS). The importance of selenium in these anti-oxidant proteins has been implicated in the reduction of atherosclerosis by preventing the oxidation of low density lipoprotein. Selenium supplementation is also being investigated in the prevention of cancer and has been suggested to be beneficial to immune function. Converging data from epidemiological, ecological, and clinical studies have shown that selenium (Se) can decrease the risk for some types of human cancers. Induction of apoptosis is considered an important cellular event that can account for the cancer preventive effects of Se. Prior to occurrence of apoptosis, Se compounds alter the expression and/or activities of signaling molecules, mitochondria-associated factors, transcriptional factors, tumor suppressor genes, and cellular reduced glutathione. Mechanistic studies have demonstrated that the methylselenol metabolite pool has many desirable attributes of chemoprevention, whereas the hydrogen selenide pool with excess of selenoprotein synthesis can lead to DNA single-strand breaks. To elucidate the effects of Se on cytotoxic events, it should be remembered that the chemical forms and the dose of Se, and the experimental system used, are determinants of its biological activities. This mini-review focuses on elucidation of the molecular mechanisms of cancer prevention by Se with the apoptotic approach. /Selenium/ Selenium status can also influence thyroid hormone function via the deiodinase enzymes. Selenium is a critical component of the deiodinase enzymes, including iodothyronine 5'-deiodinases, which convert the prohormone thyroxine (T4) to the active circulating form, triiodothyronine (T3). Selenium is also a component of GPX, the main enzyme responsible for protecting thyroid cells against oxidative damage. GPX is involved in the detoxification of hydrogen peroxide, which is produced in the thyroid during the conversion of T4 to T3. /Selenium/ Selenium readily substitutes for sulfur in biomolecules and in many biochemical reactions, especially when the concentration of selenium is high and the concentration of sulfur is low in the organism. Inactivation of the sulfhydryl enzymes necessary for oxidative reactions in cellular respiration, through effects on mitochondrial and microsomal electron transport, might contribute to acute selenium toxicity. Selenium may have a role in hepatic heme metabolism that is related to GPX or lipid peroxidation. Selenocysteine is specifically found in some proteins (e.g., glutathione peroxidase); selenomethionine appears to randomly substitute for methionine in protein synthesis. This appears to be an additional mechanism for intermediate- or chronic-duration toxicity. Skin, hair, and nail damage are significant indicators of chronic selenium overexposure. The mechanism causing these integumentary effects is unclear, but could be related to the high selenium concentrations in these tissues as a consequence of the substitution of selenium for sulfur in certain amino acids, including the disulfide bridges that pr

Pharmacodynamics

Selenium is incorporated into many different selenoproteins which serve various functions throughout the body.

Mechanism of action

Copper is absorbed from the gut via high affinity copper uptake protein and likely through low affinity copper uptake protein and natural resistance-associated macrophage protein-2. It is believed that copper is reduced to the Cu1+ form prior to transport. Once inside the enterocyte, it is bound to copper transport protein ATOX1 which shuttles the ion to copper transporting ATPase-1 on the golgi membrane which take up copper into the golgi apparatus. Once copper has been secreted by enterocytes into the systemic circulation it remain largely bound by ceruloplasmin (65-90%), albumin (18%), and alpha 2-macroglobulin (12%). Copper is an essential element in the body and is incorporated into many oxidase enzymes as a cofactor. It is also a component of zinc/copper super oxide dismutase, giving it an anti-oxidant role. Copper defiency occurs in Occipital Horn Syndrome and Menke's disease both of which are associated with impaired development of connective tissue due to the lack of copper to act as a cofactor in protein-lysine-6-oxidase. Menke's disease is also associated with progressive neurological impairment leading to death in infancy. The precise mechanisms of the effects of copper deficiency are vague due to the wide range of enzymes which use the ion as a cofactor. Copper appears to reduce the viabilty and motility of spermatozoa. This reduces the likelihood of fertilization with a copper IUD, producing copper's contraceptive effect. The exact mechanism of copper's effect on sperm are unknown. The reason for the less severe reaction when the foreign body is at a distance from the retina has been proposed to be ... that near the retina & its blood vessels there is greater oxygen tension than at a distance, which causes metallic copper to oxidize to toxic copper compounds more rapidly close to or in contact with the retina than at a distance. Furthermore, the abscess formation that is characteristic of copper undergoing oxidation close to the retina & choroiod can be attributed to attraction of polymorphonuclear leukocytes from these nearby vascular tissues, which become heavily infiltrated. Liquefaction & disorganization of the vitreous body has been explained on the basis of copper catalysis of oxidation of ascorbic acid, leading to depolymerization of the hyaluronic acid of the vitreous humor. Changes in protein & hexosamine content have also been related to decrease in viscosity of the vitreous humor. Increased content of amino acids in the vitreous humor has been consistent with proteolysis of the vitreous body, but decreased concentration in the aqueous humor has suggested suppression of secretion of amino acids by the ciliary body under the influence of copper.

Pharmacodynamics

Copper is incorporated into many enzymes throughout the body as an essential part of their function. Copper ions are known to reduce fertility when released from copper-containing IUDs.

Mechanism of action

There is no well controlled data that can formally substantiate the method of action. However, ongoing studies suggest that there may exist a histological wound healing profile induced by allantoin in rats that leads to the amelioration and fastening of the reestablishment of normal skin. This facilitation of wound healing is supported by observations that wounds inflicted to rat subjects to which topical allantoin preparations were applied histologically demonstrated increased vasodilation, presence of inflammatory exudates, number of inflammatory cells, angiogenesis, fibroblast proliferation, and increased collagen deposition when compared to rat subjects with wounds that did not receive any allantoin administration.

Pharmacodynamics

There is no well controlled and appropriate data that can formally substantiate the pharmacodynamic properties of allantoin. Nevertheless, ongoing studies suggest that allantoin possesses moisturizing and keratolytic effects, as well as abilities to increase the water content of the extracellular matrix and enhance the desquamation of upper layers of dead skin cells, all of which are activities that can promote cell proliferation and facilitate wound healing.