PROXEED PLUS POWDER (Each sachet contains Vit C/ Folate/ Vit B12/ Zinc/ Selenium/ L-Carnitine fumarate/ Acetyl-L-Carnitine HCL/ Citric Acid/ Coenzyme Q10 90mg/333mcg/1.5mcg/10mg/50mcg/1000mg/500mg/50mg/20mg)

Indications

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

Dosage

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

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

Mechanism of action

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

Pharmacodynamics

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

Pharmacokinetics

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

Adverse effects

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

Precautions

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

Pregnancy

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

Breast-feeding

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

Storage

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

Formulations

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

Indications

• Cognitive disorders
• Neurodegenerative diseases
• Peripheral neuropathy
• Male infertility
• Mental fatigue
• Type 2 diabetes

Dosage

Children: Refer to the BNF for Children for appropriate pediatric dosing guidelines.

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

Mechanism of action

The main mechanism of action of acetylcarnitine involves donating an acetyl group during fatty acid metabolism, facilitating the transport of fatty acids like acetyl CoA into the mitochondrial matrix. It also acts through neuroprotective pathways, decreasing oxidative stress and enhancing neuronal survival. Acetylcarnitine has been shown to improve sperm motility and has antioxidant properties that help reduce free radical production and lipid peroxidation.

Pharmacodynamics

Acetylcarnitine has demonstrated positive effects on mental fatigue, cognitive function, and various neurodegenerative disorders. Clinical studies have indicated benefits in peripheral neuropathy, with improvements in CD4 cell counts and reductions in lymphocyte apoptosis among HIV patients. Additionally, it enhances glucose disposal in type 2 diabetic patients, potentially by increasing glycogen synthase activity.

Pharmacokinetics

Acetylcarnitine is absorbed readily from the gastrointestinal tract, with peak plasma levels occurring within 2 to 4 hours post-administration. It is distributed throughout the body, particularly in tissues where fatty acid metabolism occurs. The drug is metabolized in the liver and other tissues, with excretion primarily occurring through the urine as metabolites. The exact half-life of acetylcarnitine in humans has not been well defined, and its pharmacokinetic profile may vary based on individual metabolic conditions.

Adverse effects

• Nausea
• Vomiting
• Abdominal cramps
• Diarrhea
• Increased appetite
• Headache
• Insomnia
• Agitation

Precautions

• Caution in patients with a history of seizure disorders.
• Use with caution in patients taking anticoagulant medications due to potential interactions.

Pregnancy

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

Breast-feeding

It is unknown whether acetylcarnitine is excreted in human milk. Caution should be exercised when administering to nursing mothers.

Storage

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

Formulations

• Oral capsules
• Oral tablets
• Oral solution

Indications

• Acidulant in food and beverages
• Preservative in pharmaceutical formulations
• pH adjuster in various chemical preparations

Dosage

Children: Refer to product-specific guidelines for appropriate dosing based on formulation and indication.

Adults: Refer to product-specific guidelines for appropriate dosing based on formulation and indication.

Mechanism of action

Citric acid acts by chelating metal ions, which can enhance the solubility of certain compounds and improve their bioavailability. It also contributes to the acidity of the environment, which can influence enzymatic activity and metabolic pathways, particularly in the degradation of citronellol.

Pharmacodynamics

Citric acid exhibits mild pharmacological effects primarily attributed to its role in metabolic processes. It aids in the regulation of pH levels, which can impact enzymatic reactions and biochemical pathways. The acid's chelating properties may help to reduce the toxicity of certain metal ions in biological systems.

Pharmacokinetics

Citric acid is rapidly absorbed after oral administration and is metabolized in the liver. It undergoes conversion to various metabolites in the citric acid cycle, contributing to energy production. The elimination primarily occurs through urine, with minimal accumulation in the body.

Pregnancy

Citric acid is generally regarded as safe during pregnancy when used in food amounts. However, consult a healthcare provider for advice on medicinal use.

Breast-feeding

Citric acid is considered safe during breastfeeding when consumed in food amounts. For medicinal use, consult a healthcare provider.

Storage

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

Indications

• Metabolic disorders
• Nutritional deficiencies
• Energy production enhancement
• Support for enzyme activity

Dosage

Children: Refer to specific coenzyme formulations for dosing information, as dosages can vary widely based on intended use and formulation.

Adults: Refer to specific coenzyme formulations for dosing information, as dosages can vary widely based on intended use and formulation.

Mechanism of action

Coenzymes function by binding to enzymes and assisting in the catalytic activity. They may serve as carriers for specific chemical groups or facilitate the transfer of electrons, thereby enhancing the enzyme's ability to convert substrates into products. The specific mechanism can vary depending on the type of coenzyme and the enzyme it interacts with.

Pharmacodynamics

Coenzymes enhance the activity of enzymes by stabilizing transition states, reducing activation energy, and enabling the conversion of substrates into their respective products. They are essential for numerous biological processes, including energy metabolism, amino acid synthesis, and nucleic acid synthesis. The functional impact of coenzymes is largely dependent on their concentration and the presence of specific enzymes.

Pharmacokinetics

The pharmacokinetics of coenzymes can vary widely depending on the specific coenzyme and its role in metabolic pathways. Generally, coenzymes are synthesized in the body from vitamins and other precursor molecules. They are utilized in enzymatic reactions and may be recycled or degraded after use. The absorption, distribution, metabolism, and excretion of coenzymes are influenced by dietary intake and physiological needs.

Pregnancy

Coenzyme Q10 is generally considered safe during pregnancy, but it is advisable to consult a healthcare provider before use.

Breast-feeding

Coenzyme Q10 is likely safe during breastfeeding, but it is recommended to consult a healthcare professional prior to use.

Storage

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

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

Mechanism of action

Levocarnitine acts as a carrier molecule for long-chain fatty acids, transporting them into mitochondria for beta-oxidation, which is critical for energy production. It also exports acyl groups from subcellular organelles and cells to urine, preventing toxic accumulation. The mechanism of action includes interactions with carnitine transporters, translocases, and acetyltransferases. Additionally, it normalizes the brain's redox state and enhances urea synthesis in the liver, potentially activating the glucocorticoid receptor. L-carnitine's antagonistic effects on thyroid hormone action, including inhibiting its nuclear entry, contribute to its therapeutic applications.

Pharmacodynamics

Levocarnitine plays a significant role in lipid metabolism and energy production through its involvement in the transport of fatty acids into the mitochondria. A deficiency in carnitine can lead to various metabolic issues, including liver, heart, and muscle dysfunction. The therapeutic use of levocarnitine includes its ability to stimulate gastric and pancreatic secretions and treat hyperlipoproteinemias. The L-isomer of carnitine is specifically active in lipid metabolism, and its deficiency can be identified through biochemical markers such as low plasma concentrations of free carnitine and elevated acylcarnitine levels.

Pharmacokinetics

Levocarnitine is absorbed in the intestines and distributed throughout the body tissues. It is primarily metabolized in the liver, with excretion occurring via urine. The pharmacokinetics of levocarnitine can vary based on dietary intake, physiological status, and specific health conditions that may affect its metabolism and clearance. The bioavailability of levocarnitine may also be

Adverse effects

• Nausea
• Vomiting
• Abdominal cramps
• Diarrhea
• Fishy body odor
• Rash
• Seizures (rare)

Interactions

• Anticoagulants may have altered effects.
• Thyroid hormones may have altered action due to L-carnitine's peripheral antagonism.

Precautions

• Use with caution in patients with renal impairment.
• Monitor for potential interactions with other medications.

Pregnancy

Limited data is available on the use of levocarnitine during pregnancy. Use only if clearly needed and after assessing benefits versus risks.

Breast-feeding

Levocarnitine is excreted in human milk. Caution is advised when administered to nursing mothers.

Storage

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

Formulations

• Oral solution
• Tablets
• Capsules

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

The mechanisms of action of acetylcarnitine have not been fully elucidated, but it seems that the main role of acetylcarnitine is to donate an acetyl group during fatty acid metabolism to help transport fatty acids, such as acetyl CoA, into the mitochondrial matrix where fatty acid metabolism occurs. Additionally several studies have found that separate from its metabolic role, acetylcarnitine has neuromodulatory, neurotrophic, and neuroprotective effects that most likely are involved in its positive effects in neurological diseases. In its role in treating male infertility, acetylcarnitine increases the active movement of sperm cells. One study has also mentioned a role for acetylcarnitine as an antioxidant. The study found that through the receptor, tyrosine kinase A, acetylcarnitine was able to decrease the production of free radicals, peroxidation of lipids, and oxidation of proteins as well as decrease glutathione levels and increase thioredoxin. Three primary mechanisms of action are supported by neurochemical outcome measures performed with these models and with in vitro models of acute neuronal cell death. The metabolic hypothesis is based on the oxidative metabolism of the acetyl component of acetyl-L-carnitine and is a simple explanation for the reduction in postischemic brain lactate levels and elevation of ATP seen with drug administration. The antioxidant mechanism is supported by reduction of oxidative stress markers, for example, protein oxidation, in both brain tissue and cerebrospinal fluid. The relatively uncharacterized mechanism of inhibiting excitotoxicity could be extremely important in both acute brain injury and chronic neurodegenerative disorders. New experiments performed with primary cultures of rat cortical neurons indicate that the presence of acetyl-L-carnitine significantly inhibits both acute and delayed cell death following exposure to NMDA, an excitotoxic glutamate antagonist. Finally, several other mechanisms of action are possible, including a neurotrophic effect of acetyl-L-carnitine and inhibition of mitochondrial permeability transition. While the multiple potential mechanisms of neuroprotection by acetyl-L-carnitine limit an accurate designation of the most important mode of action, they are compatible with the concept that several brain injury pathways must be inhibited to optimize therapeutic efficacy. L-Acetylcarnitine (LAC, 100 mg/kg, sc), a drug commonly used for the treatment of painful neuropathies, substantially reduced mechanical allodynia in rats subjected to monolateral chronic constriction injury (CCI) of the sciatic nerve and also attenuated acute thermal pain in intact rats. In both cases, induction of analgesia required repeated injections of LAC, suggesting that the drug induces plastic changes within the nociceptive pathway. In both CCI- and sham-operated rats, a 24-day treatment with LAC increased the expression of metabotropic glutamate (mGlu) receptors 2 and 3 in the lumbar segment of the spinal cord, without changing the expression of mGlu1a or -5 receptors. A similar up-regulation of mGlu2/3 receptors was detected in the dorsal horns and dorsal root ganglia of intact rats treated with LAC for 5-7 days, a time sufficient for the induction of thermal analgesia. Immunohistochemical analysis showed that LAC treatment enhanced mGlu2/3 immunoreactivity in the inner part of lamina II and in laminae III and IV of the spinal cord. An increased mGlu2/3 receptor expression was also observed in the cerebral cortex but not in the hippocampus or cerebellum of LAC-treated animals. Reverse transcription-polymerase chain reaction combined with Northern blot analysis showed that repeated LAC injections selectively induced mGlu2 mRNA in the dorsal horns and cerebral cortex (but not in the hippocampus). mGlu3 mRNA levels did not change in any brain region of LAC-treated animals. To examine whether the selective up-regulation of mGlu2 receptors had any role in LAC-induced analgesia, ...

Pharmacodynamics

The complete physiological effects of acetycarnitine are still being studied. What has been discovered so far is that acetylcarinitine has positive effects on mental fatigue, neurodegenerative disorders, cognitive functions, peripheral neuropathy, and sperm motility. Specifically, in one study involving patients with HIV, patients on acetylcarnitine supplementation had increased CD4 cells, decreased lymphocyte apoptosis, improved polyneuropathy and cardiovascular damage, and decreased triglyceride and TNF alpha levels in the blood. Another study showed that acetylcarnitine increased glucose disposal in type 2 diabetic patients through possibly increasing the activity of glycogen synthase.

Mechanism of action

Levocarnitine can be synthesised within the body from the amino acids lysine or methionine. Vitamin C (ascorbic acid) is essential to the synthesis of carnitine. Levocarnitine is a carrier molecule in the transport of long chain fatty acids across the inner mitochondrial membrane. It also exports acyl groups from subcellular organelles and from cells to urine before they accumulate to toxic concentrations. Only the L isomer of carnitine (sometimes called vitamin BT) affects lipid metabolism. Levocarnitine is handled by several proteins in different pathways including carnitine transporters, carnitine translocases, carnitine acetyltransferases and carnitine palmitoyltransferases. L-Carnitine is a peripheral antagonist of thyroid hormone action in some tissues. It inhibits thyroid hormone entry into cell nuclei. In a controlled clinical trial, L-carnitine was shown to reverse or prevent some symptoms of hyperthyroidism. ... Mortality and metabolic consequences of acute ammonium intoxication in mice are reduced by pharmacologic admin of L-carnitine. The mechanism for this effect may have 2 components. L-Carnitine admin normalizes the redox state of the brain (perhaps by incr the avail of beta-hydroxybutyrate and/or acetyl-L-carnitine to the brain), and it incr the rate of urea synth in the liver, perhaps in part by activation of the glucocorticoid receptor. At least part of the protective effect is associated with flux through the carnitine acyltransferases, as analogs of L-carnitine that are competitive inhibitors of carnitine acyltransferases enhance the toxicity of acute ammonium admin. Thus, it has been proposed that L-carnitine incr urea synth in the liver by facilitating fatty acid entry into mitochondria, leading to incr flux through the beta-oxidation pathway, an incr of intramitochondrial reducing equivalents, and enhancement of ATP production. ... Levocarnitine is necessary for normal mammalian fat utilization and energy metabolism. It facilitates entry of long-chain fatty acids into cellular mitochondria, where they are used during oxidation and energy production. It also exports acyl groups from subcellular organelles and from cells to urine before they accumulate to toxic concentrations. Carnitine's primary mechanism of action is apparently attributable to its role as a cofactor in the transformation of free long-chain fatty acids into acylcarnitines for subsequent transport into the mitochondrial matrix. Carnitine is involved in the metabolism of ketones for energy and the conversion of branched-chain amino acids - valine, leucine, and isoleucine - into energy. /Carnitine/ L-Carnitine participates in a reversible transesterification reaction, in which an acyl group is transferred from coenzyme A to the hydroxyl group of L-carnitine ... /This reaction facilitates the/ transfer of long-chain fatty acids from cytoplasm ... /and/ chain-shortened /very-long-chain/ fatty acids from peroxisomes to mitochondria /and the/ modulation of the acyl-CoA/CoA ratio in cellular compartments.

Pharmacodynamics

Levocarnitine is a carrier molecule in the transport of long chain fatty acids across the inner mitochondrial membrane. It also exports acyl groups from subcellular organelles and from cells to urine before they accumulate to toxic concentrations. Lack of carnitine can lead to liver, heart, and muscle problems. Carnitine deficiency is defined biochemically as abnormally low plasma concentrations of free carnitine, less than 20 µmol/L at one week post term and may be associated with low tissue and/or urine concentrations. Further, this condition may be associated with a plasma concentration ratio of acylcarnitine/levocarnitine greater than 0.4 or abnormally elevated concentrations of acylcarnitine in the urine. Only the L isomer of carnitine (sometimes called vitamin BT) affects lipid metabolism. The "vitamin BT" form actually contains D,L-carnitine, which competitively inhibits levocarnitine and can cause deficiency. Levocarnitine can be used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias.