FOLI-9 TABLETS (Each tablet contains Omega 3 fatty acid EPA/ DHA/ Calcium/ Magnesium/Vitamin C/ Niacinamide/ Iron/ Zinc/ Vit. E /Vit. B6 /Vit. B1/ Vit. B2/ Copper/ Manganese/ Vit. B12/ L Methyl Folate /Iodine/ Selenium/Chromium/ Biotin/ Vit. A/ Vit. D3 / Vit. E 90mg/ 60mg/ 200mg/ 50mg/ 70mg/ 18mg/ 27mg/ 7.5mg/ 6mg/ 1.9mg/ 1.4mg/ 1.4mg/ 1mg/ 1mg/ 1500mcg/ 1000mcg/ 220mcg/ 30mg)

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

• Vitamin C deficiency
• Scurvy
• Adjunct therapy in iron overload conditions

Dosage

Children: Child 1 month–3 years: 125–250 mg daily in 1–2 divided doses; Child 4–11 years: 250–500 mg daily in 1–2 divided doses; Child 12–17 years: 0.5–1 g daily in 1–2 divided doses.

Adults: 500 mg daily, taken in 1-2 divided doses, depending on the clinical condition and dietary needs.

Mechanism of action

Ascorbic acid functions primarily as a reducing agent, facilitating enzymatic reactions in the body, including the hydroxylation of proline and lysine in collagen synthesis. It also plays a role in the absorption of iron from the gastrointestinal tract and enhances the immune response.

Pharmacodynamics

Ascorbic acid is crucial for the maintenance of connective tissue and is involved in the metabolism of several amino acids. Its antioxidant properties help to mitigate oxidative stress and may play a role in reducing the risk of chronic diseases.

Pharmacokinetics

Ascorbic acid is absorbed in the intestines and is widely distributed throughout the body. The renal clearance of ascorbic acid is dose-dependent, with higher doses leading to increased excretion. The half-life varies but is generally around 15 to 30 minutes in healthy individuals, with tissue saturation levels influencing its retention.

Contra-indications

• Hypercalcaemia
• Hyperoxaluria
• Patients with cardiac dysfunction

Adverse effects

• Abdominal pain
• Headache
• Nausea
• Vomiting
• Diarrhoea
• Constipation
• Weight loss
• Polyuria
• Sweating
• Thirst
• Vertigo

Interactions

• Increases risk of cardiovascular adverse effects with iron chelators
• Increases risk of cardiovascular adverse effects with deferiprone
• Increases risk of cardiovascular adverse effects with desferrioxamine

Precautions

• Use with caution in patients with iron overload
• Monitor for symptoms of overdose

Pregnancy

High doses teratogenic in animals but therapeutic doses unlikely to be harmful.

Storage

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

Formulations

• Ascorbic acid 50 mg tablets
• Ascorbic acid 100 mg tablets
• Ascorbic acid 200 mg tablets
• Ascorbic acid 250 mg tablets
• Ascorbic acid 500 mg capsules

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

• Type 2 diabetes mellitus
• Insulin resistance
• Impaired glucose tolerance
• Metabolic syndrome
• Hyperlipidemia

Dosage

Children: Refer to the BNF for Children for specific dosage recommendations suitable for pediatric patients.

Adults: Refer to the BNF for specific dosage recommendations based on the condition being treated.

Mechanism of action

Chromium enhances insulin signaling by upregulating insulin receptor-mediated pathways. It affects downstream effector molecules after insulin binds to its receptor, leading to the activation of phosphatidylinositol 2-kinase (PI3K) and protein kinase B (Akt). This process promotes the translocation of glucose transporter-4 (Glut4) to the cell membrane, facilitating increased glucose uptake. Additionally, chromium can promote GLUT-4 transporter translocation independently of insulin receptor activity under insulin-resistant conditions and aids in cholesterol efflux by increasing membrane fluidity.

Pharmacodynamics

Trivalent chromium is essential for the glucose tolerance factor, which activates insulin-mediated pathways. It enhances insulin binding to cells, increases the density of insulin receptors, and activates insulin receptor kinase, all of which contribute to improved insulin sensitivity. Chromium deficiency can lead to impaired glucose metabolism, and supplementation can normalize glucose tolerance in individuals exhibiting diabetic-like characteristics due to deficiency.

Pharmacokinetics

Chromium absorption occurs primarily in the intestines, but its bioavailability is influenced by various dietary factors, such as the presence of other minerals and vitamins. The mineral is transported in the bloodstream bound to transferrin and is predominantly stored in the liver, spleen, and bone. The elimination of chromium occurs mainly through urine, with small amounts excreted in feces. The half-life and exact metabolic pathways for chromium can vary based on its form and the individual's nutritional status.

Pregnancy

Chromium is generally considered safe during pregnancy when taken in appropriate amounts, but it is advisable to consult a healthcare provider.

Breast-feeding

Chromium is excreted in breast milk, and while it is deemed safe in moderate amounts, consultation with a healthcare provider is recommended.

Storage

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

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

• Nutritional support
• Management of dyslipidemia
• Support for cardiovascular health
• Anti-inflammatory therapies

Dosage

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

Adults: Dosage varies widely depending on the specific type of fatty acid and the condition being treated. Refer to specific guidelines for dietary or therapeutic doses.

Mechanism of action

Fatty acids exert their effects through several mechanisms, including serving as energy sources, components of cell membrane phospholipids, and precursors for signaling molecules such as eicosanoids. They can modulate gene expression and influence metabolic pathways by activating nuclear receptors, such as peroxisome proliferator-activated receptors (PPARs).

Pharmacodynamics

Fatty acids influence lipid metabolism, inflammation, and insulin sensitivity. They can alter membrane fluidity and receptor function, impacting cellular signaling. Saturated fatty acids may promote inflammatory processes, while unsaturated fatty acids, particularly omega-3 and omega-6 fatty acids, can exert anti-inflammatory effects and promote cardiovascular health.

Pharmacokinetics

Fatty acids are absorbed in the intestine via passive diffusion and are transported in the blood bound to albumin or as part of lipoproteins. They are metabolized in the liver, where they can undergo beta-oxidation to generate energy or be converted into ketone bodies. The half-life varies depending on the type of fatty acid and its incorporation into various tissues.

Pregnancy

Consult with a healthcare provider before use, as the effects of fatty acids during pregnancy can vary.

Breast-feeding

Consult with a healthcare provider before use, as some fatty acids may be excreted in breast milk.

Storage

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

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

• Iodine deficiency
• Goiter
• Hypothyroidism
• Thyroiditis
• Fibrocystic breast disease

Dosage

Children: Refer to the BNF for Children for appropriate dosing guidelines based on age and weight.

Adults: Refer to the BNF for appropriate dosing guidelines based on condition and clinical judgment.

Mechanism of action

Molecular iodine inhibits the induction and promotion of carcinogenesis in mammary tissues and has shown beneficial effects in fibrocystic breast disease. It temporarily decreases thyroid hormone production through the acute Wolff-Chaikoff effect, followed by a return to normal hormone synthesis due to down regulation of the sodium-iodide symport. This mechanism can lead to a transient hypothyroid state in some individuals with underlying thyroid conditions.

Pharmacodynamics

Iodine is vital for the synthesis of thyroid hormones thyroxine (T4) and triiodothyronine (T3). It affects the metabolism of amine-derived hormones and plays a role in amino acid metabolism. The acute excess of iodide can lead to decreased circulating levels of T4 and T3 in susceptible individuals, while most people can escape this effect and maintain normal thyroid function.

Pharmacokinetics

Iodine is absorbed primarily in the gastrointestinal tract and is distributed throughout the body, particularly in the thyroid gland, where it is concentrated for hormone synthesis. The kidney plays a significant role in the excretion of excess iodine. The half-life of iodine in the body varies and can be influenced by dietary intake and underlying health conditions.

Adverse effects

• Hypothyroidism
• Hyperthyroidism
• Iodine allergy
• Gastrointestinal disturbances

Interactions

• Thyroid hormones
• Antithyroid drugs
• Lithium
• Diuretics

Precautions

• Use with caution in patients with thyroid dysfunction
• Monitor thyroid function periodically during treatment
• Pregnant or breastfeeding women should consult a healthcare provider before use

Pregnancy

Iodine is essential for fetal thyroid hormone synthesis, but excessive iodine intake should be avoided.

Breast-feeding

Iodine is excreted in breast milk; consult a healthcare provider regarding supplementation.

Storage

Store in a cool, dry place away from light.

Formulations

• Iodine solution
• Iodine tincture
• Potassium iodide tablets

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

• Allergic conditions
• Autoimmune diseases
• Asthma and chronic obstructive pulmonary disease (COPD)
• Certain cancers (e.g., leukemia, lymphoma)
• Skin conditions (e.g., dermatitis)
• Inflammatory bowel disease
• Multiple sclerosis exacerbations
• Severe infections requiring immunosuppression

Dosage

Children: Refer to BNF for Children for specific dosing; doses vary significantly based on the child's age, weight, and condition being treated.

Adults: Refer to BNF for specific dosing; typically, initial doses range from 4 to 48 mg depending on the severity of the condition.

Mechanism of action

Methylprednisolone exerts its effects by binding to glucocorticoid receptors, leading to the modulation of gene expression. This interaction influences the transcription of anti-inflammatory proteins while suppressing the expression of pro-inflammatory genes, ultimately resulting in reduced inflammation and immune response.

Pharmacodynamics

The pharmacodynamic effects of methylprednisolone are characterized by its ability to decrease inflammation, suppress the immune response, and affect carbohydrate metabolism. Therapeutic doses lead to various systemic effects, including modification of leukocyte distribution and inhibition of cytokine production.

Pharmacokinetics

Methylprednisolone is well absorbed after oral administration, with a bioavailability of approximately 50%. It has a volume of distribution that reflects extensive tissue binding. The drug is metabolized primarily in the liver through conjugation and reduction, and its metabolites are excreted in urine. The half-life varies based on the route of administration but is generally around 18 to 36 hours.

Adverse effects

• Increased blood pressure
• Hyperglycemia
• Weight gain
• Mood changes
• Insomnia
• Gastrointestinal disturbances
• Increased susceptibility to infections

Interactions

• methylphenidate+apraclonidine: Severe (decreases effects)
• methylthioninium chloride+bupropion: Severe (increases risk of severe hypertension)
• methylphenidate+linezolid: Severe (increases risk of elevated blood pressure)
• rasagiline+methylphenidate: Severe (increases risk of a hypertensive crisis)
• mao-inhibitors+methylphenidate: Severe (increases risk of a hypertensive crisis)
• dronedarone+methylprednisolone: Moderate (increases exposure)
• miconazole+methylprednisolone: Moderate (increases concentration)
• antifungals, azoles+methylprednisolone: Moderate (increases exposure)
• crizotinib+methylprednisolone: Moderate (increases exposure)

Precautions

• Use with caution in patients with hypertension
• Monitor blood glucose levels in diabetic patients
• Consider potential for infection risk due to immunosuppression
• Evaluate for psychiatric effects in susceptible individuals

Pregnancy

Corticosteroids may be used during pregnancy if the potential benefit justifies the risk to the fetus. Careful monitoring is advised.

Breast-feeding

Corticosteroids are excreted in breast milk; caution is advised. Monitor the infant for potential effects.

Storage

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

Formulations

• Tablets
• Injectable solutions
• Topical preparations

Mechanism of action

Methylsulphate functions as a methylating agent, transferring a methyl group to nucleophiles. This process involves the formation of a sulfonium ion, which is highly reactive and can readily react with nucleophilic sites on various substrates, leading to methylation reactions.

Pharmacodynamics

The pharmacodynamics of methylsulphate is primarily related to its role as a methylating agent in biochemical reactions. It can alter the structure and function of biological molecules, potentially affecting cellular processes and signaling pathways. However, detailed pharmacodynamic studies specific to therapeutic use are limited.

Pharmacokinetics

There is limited information on the pharmacokinetics of methylsulphate, given its typical use as a reagent in laboratory settings rather than a clinical drug. When used in chemical reactions, its reactivity and transformation into other compounds would dictate its pharmacokinetic profile, which could vary significantly based on the specific context of use.

Pregnancy

There is limited data on the use of methylsulphate in pregnancy. Consult relevant guidelines.

Breast-feeding

Data on the excretion of methylsulphate in human milk is not available. Caution is advised.

Storage

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

Indications

• Dermatitis
• Acne
• Rosacea
• Hyperpigmentation
• Skin aging

Dosage

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

Adults: Refer to the BNF for specific dosing guidelines based on the condition being treated.

Mechanism of action

Niacinamide functions primarily as a precursor to NAD and NADP, which are crucial for numerous enzymatic reactions in the body. It is involved in the NAD salvage pathway, which recycles nicotinamide for NAD synthesis. This process is vital for cellular energy production and metabolic processes. Niacinamide also has anti-inflammatory properties, which may contribute to its effects in skin health.

Pharmacodynamics

Niacinamide exhibits various pharmacological effects, including enhancing skin barrier function, reducing inflammation, and improving skin pigmentation. It has been shown to modulate keratinocyte function, improve collagen synthesis, and decrease the synthesis of sebum, thereby providing beneficial effects in conditions like acne and rosacea.

Pharmacokinetics

Niacinamide is readily absorbed from the gastrointestinal tract. It is distributed widely throughout the body and can cross biological membranes. The metabolism of niacinamide primarily occurs in the liver through methylation and conjugation, and it is excreted in urine as metabolites. The half-life of niacinamide is approximately 1-2 hours, and its effects can be prolonged due to its role in NAD synthesis.

Pregnancy

No evidence of harm, but use only if clearly needed.

Breast-feeding

Considered safe to use while breastfeeding.

Storage

Store in a cool, dry place away from light.

Formulations

• {'type': 'Topical cream', 'concentration': 'Various concentrations available'}
• {'type': 'Oral tablets', 'concentration': '100 mg, 250 mg, 500 mg'}

Indications

• Cardiovascular disease prevention
• Hypertriglyceridemia
• Rheumatoid arthritis
• Inflammatory bowel disease
• Cognitive decline and dementia
• Mood disorders

Dosage

Adults: Dosage varies based on the condition being treated. For general health, a common recommendation is 250-500 mg of combined EPA and DHA

Mechanism of action

Omega fatty acids exert their effects through various mechanisms, including the modulation of inflammatory pathways and the synthesis of specialized pro-resolving mediators. They are incorporated into cell membranes, affecting membrane fluidity and receptor function. Omega-3 fatty acids can also decrease the production of pro-inflammatory eicosanoids and increase anti-inflammatory mediators, promoting a balanced inflammatory response.

Pharmacodynamics

The pharmacodynamics of omega fatty acids involve their role in cellular signaling, gene expression, and lipid metabolism. Omega-3 fatty acids, particularly EPA and DHA, have been shown to influence the resolution of inflammation and enhance endothelial function. They also play a role in neuroprotection and cognitive function, with evidence suggesting that adequate omega-3 intake is associated with reduced risk of neurodegenerative diseases.

Pharmacokinetics

Omega fatty acids are absorbed in the intestine through the action of bile salts and pancreatic enzymes. Once absorbed, they are transported via chylomicrons into the lymphatic system and then into the bloodstream. They are distributed throughout the body, particularly in the brain and heart. The half-life of omega fatty acids can vary, with some studies suggesting an elimination half-life of several days to weeks, depending on the specific fatty acid and individual metabolism. They undergo beta-oxidation for energy production and can be converted into eicosanoids, which mediate various physiological functions.

Adverse effects

• Nausea
• Diarrhea
• Fishy aftertaste
• Allergic reactions
• Increased bleeding risk

Interactions

• Anticoagulants may increase the risk of bleeding when combined with omega-3 fatty acids
• Antihypertensive medications may have additive effects on blood pressure

Precautions

• Use cautiously in patients with bleeding disorders
• Monitor patients on anticoagulants for signs of increased bleeding
• Consider the source of omega-3 fatty acids, as some may contain contaminants

Pregnancy

Generally considered safe when used in recommended amounts, but high doses should be avoided due to potential bleeding risk.

Breast-feeding

Considered safe; omega-3 fatty acids can be beneficial for both mother and infant.

Storage

Store in a cool, dry place, away from light. Refrigeration may be required for some formulations to maintain stability.

Formulations

• Capsules
• Softgels
• Liquid oil
• Fortified foods

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

Chromium is an essential nutrient involved in the metabolism of glucose, insulin and blood lipids. Its role in potentiating insulin signalling cascades has been implicated in several studies. Chromium upregulates insulin-stimulated insulin signal transduction via affecting effector molecules downstream of the insulin receptor (IR). IR-mediated signalling pathway involves phoshorylation of multiple intracellular domains and protein kinases, and downstream effector molecules. Upon activation by ligands, intracellular β-subunit of IR autophosphorylates and activates tyrosine kinase domain of the IR, followed by activation and phosphorylation of regulatory proteins and downstream signalling effectors including phosphatidylinositol 2-kinase (PI3K). PI3K activates further downstream reaction cascades to activate protein kinase B (Akt) to ultimately promote translocation of glucose transporter-4 (Glut4)-vesicles from the cytoplasm to the cell surface and regulate glucose uptake. Chromium enhances the kinase activity of insulin receptor β and increases the activity of downstream effectors, pI3-kinase and Akt. Under insulin-resistant conditions, chromium also promotes GLUT-4 transporter translocation that is independent of activity of IR, IRS-1, PI3-kinase, or Akt; chromium mediates cholesterol efflux from the membranes via increasing fluidity of the membrane by decreasing the membrane cholesterol and upregulation of sterol regulatory element-binding protein. As a result, intracellular GLUT-4 transporters are stimulated to translocate from intracellular to the plasma membrane, leading to enhanced glucose uptake in muscle cells. Chromium attenuates the activity of PTP-1B _in vitro,_ which is a negative regulator of insulin signaling. It also alleviates ER stress that is observed to be elevated the suppression of insulin signaling. ER stress is thought to activate c-Jun N-terminal kinase (JNK), which subsequently induces serine phosphorylation of IRS and aberration of insulin signalling. Transient upregulation of AMPK by chromium also leads to increased glucose uptake. While the toxicity of metals and metalloids, like arsenic, cadmium, mercury, lead and chromium, is undisputed, the underlying molecular mechanisms are not entirely clear. General consensus holds that proteins are the prime targets; heavy metals interfere with the physiological activity of specific, particularly susceptible proteins, either by forming a complex with functional side chain groups or by displacing essential metal ions in metalloproteins. Recent studies have revealed an additional mode of metal action targeted at proteins in a non-native state; certain heavy metals and metalloids have been found to inhibit the in vitro refolding of chemically denatured proteins, to interfere with protein folding in vivo and to cause aggregation of nascent proteins in living cells. Apparently, unfolded proteins with motile backbone and side chains are considerably more prone to engage in stable, pluridentate metal complexes than native proteins with their well-defined 3D structure. By interfering with the folding process, heavy metal ions and metalloids profoundly affect protein homeostasis and cell viability. This review describes how heavy metals impede protein folding and promote protein aggregation, how cells regulate quality control systems to protect themselves from metal toxicity and how metals might contribute to protein misfolding disorders.

Pharmacodynamics

Trivalent chromium is part of glucose tolerance factor, an essential activator of insulin-mediated reactions. Chromium helps to maintain normal glucose metabolism and peripheral nerve function. Chromium increases insulin binding to cells, increases insulin receptor density and activates insulin receptor kinase leading to enhanced insulin sensitivity. In chromium deficiency, intravenous administration of chromium resulted in normalization of the glucose tolerance curve from the diabetic-like curve typical of chromium deficiency.

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

Molecular iodine is known to inhibit the induction and promotion of N-methyl-n-nitrosourea-induced mammary carcinogenesis, to regress 7,12-dimethylbenz(a)anthracene-induced breast tumors in rats.It has also been shown to have beneficial effects in fibrocystic human breast disease. An acute iodide excess (above the preexisting dietary intake) transiently decreases the production of thyroid hormones in the thyroid gland; this is referred to as the acute Wolff-Chaikoff effect. In normal people, this is followed by a return to normal levels of hormone synthesis, referred to as escape from the acute Wolff-Chaikoff effect, without a significant change in circulating hormone levels. Escape is thought to be the result of down regulation of the sodium-iodide symport (NIS), the iodide transporter in the thyroid gland, resulting in a decrease in the intrathyroidal iodine and the resumption of normal hormone synthesis. An acute or chronic excess of iodide can also decrease circulating T4 and T3 levels and induce a hypothyroid state in some people who have underlying thyroid disorders. These effects are the result of a failure to escape from the acute Wolff-Chaikoff effect. Most people who experience iodine-induced hypothyroidism recover when the excess iodine intake is discontinued.