RENERVE PLUS SOFT GELATIN CAPSULES (Each soft gelatin capsule contains Methylcobalamine/Alphalipoic acid/Inositol/Folic acid/Chromium Polynicotinate/Selemethionine/Zinc Monomethionine 1500mcg/200mg/100mg/1.5mg/200mcg/55mcg/25mg)

Indications

• Diabetic neuropathy
• Metabolic syndrome
• Oxidative stress-related conditions
• Potential adjunctive treatment for neurodegenerative diseases

Dosage

Children: Refer to guidelines or literature for specific dosing information, as pediatric dosing must be determined based on the child's age, weight, and clinical condition.

Adults: Refer to guidelines or literature for specific dosing information, as doses may vary based on the condition being treated and individual patient factors.

Mechanism of action

Alpha-lipoic acid acts as a cofactor for several mitochondrial enzymes, including pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase, which are crucial for energy production. It also enhances glucose uptake in peripheral tissues, particularly muscle, by improving insulin sensitivity. Additionally, alpha-lipoic acid exerts potent antioxidant effects by scavenging free radicals and regenerating other antioxidants, contributing to its protective role against oxidative stress.

Pharmacodynamics

The pharmacodynamic effects of alpha-lipoic acid include improved glucose metabolism and insulin sensitivity, as well as a reduction in oxidative stress. It has been shown to decrease markers of inflammation and improve endothelial function. Its dual solubility facilitates its action in both aqueous and lipid environments, allowing it to affect various cellular mechanisms.

Pharmacokinetics

Alpha-lipoic acid is rapidly absorbed after oral administration, with peak plasma concentrations occurring approximately 30 minutes to 2 hours post-dose. It has a bioavailability of about 30% due to extensive first-pass metabolism. The compound is distributed throughout the body, including the brain, where it can exert neuroprotective effects. Alpha-lipoic acid is metabolized in the liver, and its elimination half-life ranges from 30 to 60 minutes. It is primarily excreted in urine as metabolites.

Adverse effects

• Nausea
• Vomiting
• Diarrhea
• Rash
• Headache
• Hypoglycemia

Interactions

• May enhance the effects of antidiabetic medications
• May interact with chemotherapy agents
• May reduce the effectiveness of certain medications due to its antioxidant properties

Precautions

• Use with caution in individuals with diabetes, as it may lower blood sugar levels
• Monitor blood glucose levels closely in patients taking antidiabetic medications
• Caution in patients with allergies to thioctic acid or any component of the formulation

Pregnancy

Limited data on use in pregnancy. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Not well studied during breastfeeding. Use caution and consult a healthcare professional.

Storage

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

Formulations

• Oral tablets
• Capsules
• Intravenous injection

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

• 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

• Polycystic ovary syndrome (PCOS)
• Generalized anxiety disorder
• Depression
• Obsessive-compulsive disorder
• Insulin resistance

Dosage

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

Adults: Refer to the BNF for specific dosing recommendations, as doses may vary based on the condition being treated.

Mechanism of action

Inositol functions primarily as a precursor for the synthesis of phosphoinositides, which are key components of cell membranes. These phosphoinositides are involved in various intracellular signaling pathways, particularly those mediated by G-protein coupled receptors. Inositol also influences the action of neurotransmitters such as serotonin and has been shown to enhance insulin sensitivity and glucose metabolism.

Pharmacodynamics

Inositol has been observed to have mood-stabilizing effects and may improve insulin sensitivity. Its role in cell signaling impacts various physiological processes, including cellular communication and metabolic regulation. The therapeutic effects of inositol in psychiatric conditions may be attributed to its ability to modulate neurotransmitter systems, particularly involving serotonin and dopamine.

Pharmacokinetics

Inositol is well-absorbed from the gastrointestinal tract, with peak plasma levels occurring within 1 to 2 hours after ingestion. It is distributed throughout the body and can cross the blood-brain barrier. Inositol is predominantly excreted in the urine, with a half-life that varies based on dosage and individual metabolism. Metabolism occurs primarily through dephosphorylation to form various inositol phosphates.

Pregnancy

Inositol is generally considered safe during pregnancy but should be used under medical supervision.

Breast-feeding

Inositol is likely safe during breastfeeding, but consult a healthcare provider for specific recommendations.

Storage

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

Formulations

• Powder
• Capsules

Indications

• Vitamin B12 deficiency
• Peripheral neuropathy
• Megaloblastic anemia
• Homocystinuria

Dosage

Children: Refer to the BNF for Children for appropriate paediatric dosing information.

Adults: Refer to the BNF for specific dosing recommendations based on the indication.

Mechanism of action

Methylcobalamin functions as a coenzyme in the conversion of homocysteine to methionine, facilitating the synthesis of S-adenosylmethionine (SAMe). SAMe is a critical methyl donor in numerous biochemical reactions, including the methylation of DNA and proteins. Additionally, methylcobalamin is essential for the regeneration of folate, impacting DNA synthesis and repair. It also promotes nerve regeneration and repair, making it beneficial in conditions involving nerve damage.

Pharmacodynamics

Methylcobalamin exhibits neuroprotective properties by enhancing nerve growth factor (NGF) synthesis and supporting neuronal survival. It aids in the reduction of neuropathic pain and may improve neurological function in patients with vitamin B12 deficiency. The compound's role in methylation processes further influences cellular metabolism, contributing to overall health.

Pharmacokinetics

Methylcobalamin is absorbed in the intestines, and its bioavailability can be influenced by the presence of intrinsic factor, which is necessary for vitamin B12 absorption. Once absorbed, it is distributed throughout the body, particularly in the liver, kidneys, and nervous tissue. The elimination half-life of methylcobalamin is variable, and the compound is primarily excreted in the urine as metabolites. Storage and transport within the body are facilitated by transcobalamin II, a specific transport protein.

Adverse effects

• Headache
• Nausea
• Diarrhea
• Dizziness
• Rash
• Itching

Interactions

• Alcohol may decrease the absorption of methylcobalamin
• Certain medications that affect vitamin B12 levels

Precautions

• Patients with Leber's disease should use with caution
• Monitor for signs of hypersensitivity

Pregnancy

Methylcobalamin is generally considered safe during pregnancy as it is a form of vitamin B12, but consult a healthcare provider for personalized advice.

Breast-feeding

Methylcobalamin is excreted in breast milk, but is considered safe for use during breastfeeding; consult a healthcare provider for personalized advice.

Storage

Store in a tightly closed container at room temperature, away from moisture and heat.

Formulations

• Oral tablets
• Sublingual tablets
• Injectable solution

Indications

• Dietary supplementation
• Potential treatment for mood disorders
• Support for liver health
• Antioxidant support

Dosage

Children: Dosage for pediatric populations is not well established and should be

Adults: Dosage is variable and should be determined based on individual needs and clinical response. Refer to specific guidelines or product labeling for detailed dosing information.

Mechanism of action

Monomethionine functions by serving as a precursor to S-adenosylmethionine (SAMe), which is crucial for the methylation of DNA, proteins, and lipids. Through this methylation process, monomethionine can influence various metabolic pathways, including those involved in the synthesis of neurotransmitters and the detoxification of homocysteine. Additionally, it contributes to the reduction of oxidative stress by promoting the synthesis of glutathione, a key antioxidant in the body.

Pharmacodynamics

The pharmacodynamic effects of monomethionine are primarily mediated through its conversion to SAMe. This conversion leads to enhanced methylation reactions, impacting various physiological functions such as mood regulation, liver function, and the metabolism of lipids and neurotransmitters. Monomethionine may also exert neuroprotective effects due to its role in maintaining glutathione levels, thus protecting against oxidative damage in neuronal tissues.

Pharmacokinetics

Monomethionine is absorbed in the gastrointestinal tract after oral administration, although specific absorption rates have not been extensively studied. It is metabolized in the liver, contributing to the synthesis of SAMe. The elimination half-life and specific metabolic pathways of monomethionine are not well-characterized in the literature. Its effects may last longer due to the involvement of SAMe in several biochemical processes.

Adverse effects

• Gastrointestinal upset
• Nausea
• Diarrhea
• Allergic reactions

Interactions

• May interact with medications that affect liver enzymes
• Potential interactions with other amino acids or supplements

Precautions

• Use with caution in patients with liver disease
• Monitor for allergic reactions in sensitive individuals

Pregnancy

Safety during pregnancy has not been established, consult 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.

Formulations

• Capsules
• Powder for oral solution

Indications

• Hyperlipidemia
• Dyslipidemia
• Atherosclerosis
• Peripheral vascular disease

Dosage

Children: Refer to established clinical guidelines or pharmacology references for pediatric dosing, as specific pediatric doses may not be established.

Adults: Refer to established clinical guidelines or pharmacology references for specific dosing information, as dosing can vary based on the specific formulation and indication.

Mechanism of action

Polynicotinate exerts its effects primarily through the activation of nicotinic acid receptors, which leads to increased lipolysis in adipose tissue, resulting in the mobilization of free fatty acids. It also enhances the activity of lipoprotein lipase, aiding in the clearance of triglycerides from the bloodstream. This action contributes to a reduction in total cholesterol and low-density lipoprotein (LDL) levels while potentially increasing high-density lipoprotein (HDL) levels.

Pharmacodynamics

Polynicotinate influences lipid metabolism by modulating the synthesis and breakdown of lipoproteins. Its vasodilatory properties can lead to improved blood flow, which may contribute to its therapeutic effects in conditions related to poor circulation. Additionally, its modulation of lipid levels is beneficial in reducing the risk of cardiovascular diseases.

Pharmacokinetics

Polynicotinate is absorbed from the gastrointestinal tract, with the rate of absorption influenced by the presence of food. It undergoes extensive first-pass metabolism in the liver. The peak plasma concentration is typically reached within a few hours of administration. The elimination half-life is variable but generally ranges around 1 to 2 hours. Excretion primarily occurs via the kidneys, with metabolites being eliminated in urine.

Adverse effects

• Gastrointestinal disturbances
• Headache
• Dizziness
• Flushing
• Nausea

Precautions

• Use with caution in patients with liver or kidney impairment
• Monitor for allergic reactions

Pregnancy

There is limited data on the safety of polynicotinate during pregnancy. It should be used only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Limited information is available on the excretion of polynicotinate in human milk. Caution should be exercised when administering to nursing mothers.

Storage

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

Formulations

• Tablets
• Capsules
• Oral solution

Indications

• Antioxidant therapy
• Cancer prevention
• Metabolic support
• Support for immune function

Dosage

Children: Refer to clinical guidelines for pediatric dosing recommendations, as specific doses can differ significantly based on age and weight.

Adults: Refer to clinical guidelines for specific dosing recommendations as they may vary based on the condition being treated.

Mechanism of action

Selemetionine acts as an antioxidant, reducing oxidative stress by scavenging free radicals and enhancing the body's antioxidant defense systems. It is thought to influence cellular signaling pathways and gene expression related to cell survival and apoptosis. Additionally, it may enhance the activity of selenoenzymes, which are crucial for antioxidant protection and the metabolism of thyroid hormones.

Pharmacodynamics

Selemetionine exhibits protective effects against oxidative damage, which can contribute to various diseases, including cancer and cardiovascular disorders. It influences metabolic pathways involving sulfur and selenium, enhancing the synthesis of glutathione, a key antioxidant. The compound also has immunomodulatory effects, supporting the immune system's response to stress and inflammation.

Pharmacokinetics

After oral administration, selemetionine is absorbed in the gastrointestinal tract and distributed throughout the body. Its metabolism primarily involves conversion to selenocysteine, which is incorporated into selenoproteins. The excretion of selemetionine and its metabolites occurs mainly through urine. The half-life of selemetionine can vary based on the individual's metabolic rate and health status.

Adverse effects

• Nausea
• Diarrhea
• Fatigue
• Headache
• Dizziness

Precautions

• Use with caution in patients with liver impairment
• Monitor for potential allergic reactions

Pregnancy

There is insufficient data on the use of selemethionine in pregnant women, therefore it should be used only if clearly needed.

Breast-feeding

It is not known whether selemethionine is excreted in human milk. Caution should be exercised when administering to a nursing mother.

Storage

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

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.