FOREVER ACTIVE BOOST ENERGY DRINK

Mechanism of action

Cyanocobalamin serves as a cofactor for methionine synthase and L-methylmalonyl-CoA mutase enzymes. Methionine synthase is essential for the synthesis of purines and pyrimidines that form DNA. L-methylmalonyl-CoA mutase is involved in the degradation of propionate, crucial for fat and protein metabolism. The lack of vitamin B12 results in the accumulation of methylmalonyl CoA, contributing to neurological manifestations. Additionally, it is vital for the synthesis of methionine from homocysteine, and its deficiency can lead to functional folate deficiency, which impacts red blood cell formation.

Pharmacodynamics

Cyanocobalamin corrects vitamin B12 deficiency and alleviates symptoms and laboratory abnormalities associated with pernicious anemia, such as megaloblastic indices, gastrointestinal lesions, and neurological damage. It is essential for growth, cell reproduction, hematopoiesis, nucleoprotein, and myelin synthesis. The drug significantly impacts fat and carbohydrate metabolism, as well as protein synthesis. Rapidly dividing cells, such as those in the bone marrow, have a high demand for vitamin B12. Parenteral administration of cyanocobalamin can quickly reverse the anemia and gastrointestinal symptoms of vitamin B12 deficiency, while also preventing the progression of related neurological damage.

Pharmacokinetics

Cyanocobalamin is absorbed in the intestine, primarily in the ileum, via specific transport mechanisms that may be impaired in individuals with intrinsic factor deficiency (as seen in pernicious anemia). Once absorbed, it is widely distributed in body tissues, with significant concentrations found in the liver, kidneys, and heart. The vitamin is stored in the liver, where it can be released into circulation as needed. Cyanocobalamin undergoes conversion to its active forms, methylcobalamin and adenosylcobalamin, which are utilized in various metabolic processes. The elimination half-life is variable, but it is generally excreted via urine as metabolites

Adverse effects

• Abdominal distension
• Decreased appetite
• Flatulence
• Nausea

Interactions

• Folic acid may interact with cyanocobalamin, especially in cases of megaloblastic anemia caused by folate deficiency.

Precautions

• Should not be given alone for pernicious anemia.
• Use caution in patients with Leber's disease, as it may worsen optic atrophy.

Pregnancy

Cyanocobalamin is essential during pregnancy as it helps prevent neural tube defects. It is advised that females of childbearing potential take 5 mg of folic acid daily before conception and throughout pregnancy.

Breast-feeding

Cyanocobalamin is generally considered safe during breastfeeding, but it is advised to monitor the infant for any adverse effects.

Storage

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

Formulations

• Tablet: 1000 micrograms
• Tablet: 500 micrograms
• Tablet: 100 micrograms
• Oral solution: 50 micrograms per ml
• Solution for injection: 1000 micrograms per ml

Indications

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

Mechanism of action

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

Pharmacodynamics

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

Pharmacokinetics

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

Contra-indications

• Hyperkalaemia
• Severe liver damage

Adverse effects

• Peripheral neuritis
• Hepatitis
• Hypoglycaemia
• Urine discolouration

Interactions

• Potassium aminobenzoate
• Isoniazid

Precautions

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

Pregnancy

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

Breast-feeding

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

Storage

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

Formulations

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

Indications

• Vitamin B2 deficiency
• Isoniazid-induced neuropathy (prophylaxis and treatment)
• Metabolic diseases
• Cystathioninuria
• Homocystinuria
• Wilson's disease
• Prevention of penicillamine-induced neuropathy

Mechanism of action

Riboflavin acts as a precursor to flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), which are essential coenzymes in various enzymatic reactions. It binds to riboflavin hydrogenase, riboflavin kinase, and riboflavin synthase, facilitating the production of FMN and FAD. These coenzymes are critical for normal tissue respiration and energy metabolism, influencing hydrogen transport in oxidative enzyme systems such as cytochrome C reductase and succinic dehydrogenase. Moreover, riboflavin contributes to the antioxidant activity by aiding in the production of reduced glutathione, a key antioxidant in the body.

Pharmacodynamics

Riboflavin is an easily absorbed, water-soluble micronutrient that supports energy production by assisting in the metabolism of fats, carbohydrates, and proteins. It is vital for red blood cell formation, antibody production, and regulating growth and reproduction. The vitamin plays a significant role in maintaining healthy skin, nails, and hair, as well as supporting thyroid activity. Riboflavin also has therapeutic implications in preventing or treating various eye disorders, including cataracts.

Pharmacokinetics

Riboflavin is rapidly absorbed in the gastrointestinal tract, with its bioavailability influenced by dietary intake. It is primarily excreted through urine, with excess intake leading to bright yellow urine, which is a harmless side effect. The vitamin does not accumulate in the body, necessitating regular dietary intake to maintain adequate levels.

Adverse effects

• Urine discolouration
• Peripheral neuritis

Precautions

• With intravenous use, risk of cardiovascular collapse; resuscitation facilities must be available and monitor closely.

Pregnancy

Crosses the placenta but no adverse effects reported; information at high doses limited.

Breast-feeding

Present in breast milk but no adverse effects reported; information at high doses limited.

Storage

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

Formulations

• 100 mg modified-release tablets
• 50 mg capsules
• 100 mg capsules
• 100 mg tablets
• Oral solution

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

• Fatigue
• Cognitive enhancement
• Weight loss
• Increased physical performance
• Energy boost

Dosage

Children: Safety and efficacy in children have not been established. Consult a healthcare provider for guidance.

Adults: Dosage can vary widely based on the formulation and intended use. It is important to refer to specific product guidelines for dosing information, as recommendations can differ.

Mechanism of action

The primary mechanism of action of guarana is through the stimulation of the central nervous system via its caffeine content. Caffeine acts as an antagonist of adenosine receptors, leading to increased neuronal firing and the release of neurotransmitters such as dopamine and norepinephrine. This results in heightened alertness, improved mood, and enhanced cognitive function. Theobromine, another component, can improve blood flow and has mild diuretic effects.

Pharmacodynamics

The pharmacodynamic effects of guarana are largely attributed to its caffeine content, which can enhance alertness, reduce perception of effort during physical activity, and improve cognitive performance. Additionally, guarana may exert antioxidant effects due to its high levels of polyphenols. The synergistic action of its various compounds can lead to increased energy expenditure and fat oxidation, which may aid in weight management.

Pharmacokinetics

After ingestion, caffeine is rapidly absorbed and reaches peak plasma concentrations within 1-2 hours. It has a half-life of approximately 3-7 hours, which can vary based on individual factors such as age, liver function, and concurrent medications. Guarana's effects can last longer than caffeine alone due to the gradual release of caffeine and other active compounds, resulting in prolonged stimulation.

Contra-indications

• Hypersensitivity to guarana or any of its components
• Severe cardiovascular disorders
• Severe anxiety disorders

Adverse effects

• Insomnia
• Nervousness
• Headache
• Gastrointestinal disturbance
• Increased heart rate
• Hypertension

Interactions

• Caffeine-containing products may enhance stimulant effects
• Anticoagulants may have an increased risk of bleeding
• MAO inhibitors can lead to hypertensive crisis

Precautions

• Use caution in individuals with a history of heart disease
• Monitor for increased anxiety or agitation
• Consider dose adjustments in individuals with liver impairment

Pregnancy

Limited data on safety during pregnancy. Use only if clearly needed and prescribed by a healthcare provider.

Breast-feeding

Limited data available; consult a healthcare provider before use.

Storage

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

Formulations

• Powder
• Capsules
• Liquid extract

Indications

• Digestive disorders
• Anxiety and stress relief
• Anti-inflammatory purposes
• Immune system support
• Cough and cold relief
• Skin conditions

Dosage

Children: Dosage for paediatric patients should be approached with caution and is dependent on the specific herb, preparation, and clinical condition. Refer to established herbal guidelines or consult a healthcare provider for appropriate dosing.

Adults: Dosage for herbs varies widely depending on the specific herb and its preparation. Consult specific guidelines or herbal compendia for detailed dosing information.

Mechanism of action

The mechanism of action of herbs varies significantly among different types. Generally, they may exert their effects through various pathways, including modulation of enzymatic activity, interaction with neurotransmitter systems, and alteration of immune responses. For instance, flavonoids in certain herbs can have antioxidant effects, while alkaloids may influence neurotransmitter receptors.

Pharmacodynamics

The pharmacodynamics of herbs involves their interaction with biological systems, which can lead to therapeutic effects or adverse reactions. Factors such as dosage, preparation, and individual patient characteristics can influence the efficacy and safety of herbal remedies. Many herbs contain active compounds that can exert effects similar to those of conventional drugs, such as anti-inflammatory, analgesic, or antimicrobial properties.

Pharmacokinetics

The pharmacokinetics of herbs includes absorption, distribution, metabolism, and excretion of their active constituents. Many herbal compounds are rapidly absorbed in the gastrointestinal tract, but their bioavailability can be affected by factors such as formulation and presence of food. Metabolism often occurs in the liver, and elimination can vary widely among different compounds. The pharmacokinetics of a specific herb may be influenced by the method of preparation, such as infusion or tincture.

Pregnancy

Herbs can have varying effects during pregnancy, and it is essential to consult a healthcare professional before use, as some may be unsafe.

Breast-feeding

Caution is advised when using herbs during breastfeeding, as some components may be excreted in breast milk and affect the infant.

Storage

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

Indications

• Vitamin B3 deficiency
• Hyperlipidemia
• Dyslipidemia

Mechanism of action

Niacin decreases lipids and apolipoprotein B (apo B)-containing lipoproteins by modulating triglyceride synthesis in the liver and inhibiting lipolysis in adipose tissue. It inhibits hepatocyte diacylglycerol acyltransferase-2, preventing the final step of triglyceride synthesis, leading to reduced VLDL production. Additionally, niacin inhibits HDL catabolism receptors, increasing HDL levels and half-life. Acute effects include inhibition of nonesterified fatty acid release from adipocytes and stimulation of prostaglandin release from skin Langerhans cells, although these acute effects diminish over time.

Pharmacodynamics

Niacin is used therapeutically to treat vitamin deficiencies and to manage conditions like hyperlipidemia and dyslipidemia. It effectively reduces levels of VLDL and LDL while increasing HDL levels. Niacin has a wide therapeutic window, with typical oral doses ranging from 500 mg to 2000 mg. Caution is advised in patients with diabetes, renal failure, uncontrolled hypothyroidism, and in elderly patients, particularly when combined with simvastatin or lovastatin, due to an increased risk of myopathy and rhabdomyolysis.

Pharmacokinetics

Niacin is absorbed from the gastrointestinal tract and undergoes hepatic metabolism. It is excreted primarily in the urine. The pharmacokinetics can be affected by factors such as age, renal function, and concomitant medications. Peak plasma concentrations are typically reached within 30 minutes to 2 hours after oral administration, depending on the formulation used.

Contra-indications

• Hypersensitivity to niacin or any of its components
• Active liver disease
• Peptic ulcer disease

Adverse effects

• Flushing
• Itching
• Nausea
• Vomiting
• Diarrhea
• Abdominal pain
• Hepatotoxicity
• Hyperglycemia
• Gout exacerbation

Interactions

• Increased risk of myopathy and rhabdomyolysis with statins such as simvastatin or lovastatin
• May enhance the effects of antihypertensive medications
• Potential interaction with anticoagulants

Precautions

• Caution in patients with diabetes due to potential for hyperglycemia
• Monitor liver function tests periodically during prolonged therapy
• Use with caution in patients with renal impairment
• Elderly patients may be more susceptible to adverse effects

Pregnancy

Niacin should only be used during pregnancy if clearly needed and the benefits outweigh the risks. Consult with a healthcare provider for individual assessment.

Breast-feeding

Niacin is excreted in breast milk. Caution is advised when administering to nursing mothers, and a decision should be made whether to discontinue breastfeeding or the drug.

Storage

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

Formulations

• Immediate-release tablets
• Extended-release tablets
• Sustained-release tablets

Indications

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

Dosage

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

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

Mechanism of action

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

Pharmacodynamics

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

Pharmacokinetics

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

Pregnancy

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

Breast-feeding

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

Storage

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

Formulations

• Tablets
• Oral solution
• Injectable form

Mechanism of action

Vitamin B12 serves as a cofactor for _methionine synthase_ and _L-methylmalonyl-CoA mutase_ enzymes. Methionine synthase is essential for the synthesis of purines and pyrimidines that form DNA. L-methylmalonyl-CoA mutase converts L-methylmalonyl-CoA to _succinyl-CoA_ in the degradation of propionate, an important reaction required for both fat and protein metabolism. It is a lack of vitamin B12 cofactor in the above reaction and the resulting accumulation of methylmalonyl CoA that is believed to be responsible for the neurological manifestations of B12 deficiency. Succinyl-CoA is also necessary for the synthesis of hemoglobin. In tissues, vitamin B12 is required for the synthesis of _methionine_ from homocysteine. Methionine is required for the formation of S-adenosylmethionine, a methyl donor for nearly 100 substrates, comprised of DNA, RNA, hormones, proteins, as well as lipids. Without vitamin B12, tetrahydrofolate cannot be regenerated from 5-methyltetrahydrofolate, and this can lead to functional folate deficiency,. This reaction is dependent on methylcobalamin (vitamin B12) as a co-factor and is also dependent on folate, in which the methyl group of methyltetrahydrofolate is transferred to homocysteine to form _methionine_ and _tetrahydrofolate_. Vitamin B12 incorporates into circulating folic acid into growing red blood cells; retaining the folate in these cells. A deficiency of vitamin B12 and the interruption of this reaction leads to the development of megaloblastic anemia.

Pharmacodynamics

**General effects** Cyanocobalamin corrects vitamin B12 deficiency and improves the symptoms and laboratory abnormalities associated with pernicious anemia (megaloblastic indices, gastrointestinal lesions, and neurologic damage). This drug aids in growth, cell reproduction, hematopoiesis, nucleoprotein, and myelin synthesis. It also plays an important role in fat metabolism, carbohydrate metabolism, as well as protein synthesis. Cells that undergo rapid division (for example, epithelial cells, bone marrow, and myeloid cells) have a high demand for vitamin B12. **Parenteral cyanocobalamin effects** The parenteral administration of vitamin B12 rapidly and completely reverses the megaloblastic anemia and gastrointestinal symptoms of vitamin B12 deficiency. Rapid parenteral administration of vitamin B12 in deficiency related neurological damage prevents the progression of this condition. **Nasal spray effects** In 24 vitamin B12 deficient patients who were already stabilized on intramuscular (IM) vitamin B12 therapy, single daily doses of intranasal cyanocobalamin for 8 weeks lead to serum vitamin B12 concentrations that were within the target therapeutic range (>200 ng/L).

Mechanism of action

Binds to riboflavin hydrogenase, riboflavin kinase, and riboflavin synthase. Riboflavin is the precursor of flavin mononucleotide (FMN, riboflavin monophosphate) and flavin adenine dinucleotide (FAD). The antioxidant activity of riboflavin is principally derived from its role as a precursor of FAD and the role of this cofactor in the production of the antioxidant reduced glutathione. Reduced glutathione is the cofactor of the selenium-containing glutathione peroxidases among other things. The glutathione peroxidases are major antioxidant enzymes. Reduced glutathione is generated by the FAD-containing enzyme glutathione reductase. Riboflavin is converted to 2 coenzymes, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), which are necessary for normal tissue respiration. Riboflavin is also required for activation of pyridoxine, conversion of tryptophan to niacin, and may be involved in maintaining erythrocyte integrity. Riboflavin functions as the coenzyme for flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN), which primarily influence hydrogen transport in oxidative enzyme systems (eg, cytochrome C reductase, succinic dehydrogenase, xanthine oxidase). Two active forms of riboflavin exist ... coenzyme flavin mononucleotide (FMN) and coenzyme flavin adenine dinucleotide (FAD). They are formed by reaction of riboflavin with 1 and 2 molecules of ATP as follow: riboflavin + ATP = riboflavin-P (FMN) + ADP; FMN + ATP = riboflavin-ADP (FAD) + PP. Riboflavin is a water-soluble, yellow, fluorescent compound. The primary form of the vitamin is as an integral component of the coenzymes flavin mononucleotide (FMN) and flavin-adenine dinucleotide (FAD). It is in these bound coenzyme forms that riboflavin functions as a catalyst for redox reactions in numerous metabolic pathways and in energy production. ... The redox reactions in which flavocoenzymes participate include flavoprotein-catalyzed dehydrogenations that are both pyridine nucleotide (niacin) dependent and independent, reactions with sulfur-containing compounds, hydroxylations, oxidative decarboxylations (involving thiamin as its pyrophosphate), dioxygenations, and reduction of oxygen to hydrogen peroxide. There are obligatory roles of flavocoenzymes in the formation of some vitamins and their coenzymes. For example, the biosynthesis of two niacin-containing coenzymes from tryptophan occurs via FAD-dependent kynurenine hydroxylase, an FMN-dependent oxidase catalyzes the conversion of the 5'-phosphates of vitamin B6 to coenzymic pyridoxal 5'-phosphate, and an FAD-dependent dehydrogenase reduces 5,10-methylene-tetrahydrofolate to the 5'-methyl product that interfaces with the B12-dependent formation of methionine from homocysteine and thus with sulfur amino acid metabolism. For more Mechanism of Action (Complete) data for Riboflavin (7 total), please visit the HSDB record page.

Pharmacodynamics

Riboflavin or vitamin B2 is an easily absorbed, water-soluble micronutrient with a key role in maintaining human health. Like the other B vitamins, it supports energy production by aiding in the metabolising of fats, carbohydrates, and proteins. Vitamin B2 is also required for red blood cell formation and respiration, antibody production, and for regulating human growth and reproduction. It is essential for healthy skin, nails, hair growth and general good health, including regulating thyroid activity. Riboflavin also helps in the prevention or treatment of many types of eye disorders, including some cases of cataracts.

Mechanism of action

Niacin performs a number of functions in the body and so has many mechanisms, not all of which have been fully described. Niacin can decrease lipids and apolipoprotein B (apo B)-containing lipoproteins by modulating triglyceride synthesis in the liver, which degrades apo B, or by modulating lipolysis in adipose tissue. Niacin inhibits hepatocyte diacylglycerol acyltransferase-2. This action prevents the final step of triglyceride synthesis in hepatocytes, limiting available triglycerides for very low density lipoproteins (VLDL). This activity also leads to intracellular degradation of apo B and decreased production of low density lipoproteins, the catabolic product of VLDL. Niacin also inhibits a high density lipoprotein (HDL) catabolism receptor, which increases the levels and half life of HDL. Prolonged niacin treatment elicits beneficial effects on the plasma lipid and lipoprotein profile that is associated with a protective CVD risk profile. Acute niacin treatment inhibits nonesterified fatty acid release from adipocytes and stimulates prostaglandin release from skin Langerhans cells, but the acute effects diminish upon prolonged treatment, while the beneficial effects remain. To gain insight in the prolonged effects of niacin on lipid metabolism in adipocytes, we used a mouse model with a human-like lipoprotein metabolism and drug response [female APOE*3-Leiden.CETP (apoE3 Leiden cholesteryl ester transfer protein) mice] treated with and without niacin for 15 weeks. The gene expression profile of gonadal white adipose tissue (gWAT) from niacin-treated mice showed an upregulation of the "biosynthesis of unsaturated fatty acids" pathway, which was corroborated by quantitative PCR and analysis of the FA ratios in gWAT. Also, adipocytes from niacin-treated mice secreted more of the PUFA DHA ex vivo. This resulted in an increased DHA/arachidonic acid (AA) ratio in the adipocyte FA secretion profile and in plasma of niacin-treated mice. Interestingly, the DHA metabolite 19,20-dihydroxy docosapentaenoic acid (19,20-diHDPA) was increased in plasma of niacin-treated mice. Both an increased DHA/AA ratio and increased 19,20-diHDPA are indicative for an anti-inflammatory profile and may indirectly contribute to the atheroprotective lipid and lipoprotein profile associated with prolonged niacin treatment. /The study objective was/ to determine the effects of niacin on adiponectin and markers of adipose tissue inflammation in a mouse model of obesity. Male C57BL/6 mice were placed on a control or high-fat diet (HFD) and were maintained on such diets for the duration of the study. After 6 weeks on the control or high fat diets, vehicle or niacin treatments were initiated and maintained for 5 weeks. Identical studies were conducted concurrently in HCA2 (-/-) (niacin receptor(-/-)) mice. Niacin increased serum concentrations of the anti-inflammatory adipokine, adiponectin by 21% in HFD-fed wild-type mice, but had no effect on lean wild-type or lean or HFD-fed HCA2 (-/-) mice. Niacin increased adiponectin gene and protein expression in the HFD-fed wild-type mice only. The increases in adiponectin serum concentrations, gene and protein expression occurred independently of changes in expression of PPARgamma C/EBPalpha or SREBP-1c (key transcription factors known to positively regulate adiponectin gene transcription) in the adipose tissue. Further, niacin had no effect on adipose tissue expression of ERp44, Ero1-Lalpha, or DsbA-L (key ER chaperones involved in adiponectin production and secretion). However, niacin treatment attenuated HFD-induced increases in adipose tissue gene expression of MCP-1 and IL-1beta in the wild-type HFD-fed mice. Niacin also reduced the expression of the pro-inflammatory M1 macrophage marker CD11c in HFD-fed wild-type mice. Niacin treatment attenuates obesity-induced adipose tissue inflammation through increased adiponectin and anti-inflammatory cytokine expression and reduced pro-inflammatory cytokine expressio

Pharmacodynamics

Niacin is a B vitamin used to treat vitamin deficiencies as well as hyperlipidemia, dyslipidemia, hypertriglyceridemia, and to reduce the risk of myocardial infarctions. Niacin acts to decrease levels of very low density lipoproteins and low density lipoproteins, while increasing levels of high density lipoproteins. Niacin has a wide therapeutic window with usual oral doses between 500mg and 2000mg. Patients with diabetes, renal failure, uncontrolled hypothyroidism, and elderly patients taking niacin with simvastatin or lovastatin are at increased risk of myopathy and rhabdomyolysis.

Mechanism of action

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

Pharmacodynamics

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