LIFEQODE EDG3​ ​POWDER

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

• Antioxidant support
• Anti-inflammatory effects
• Cardiovascular health
• Improvement of insulin sensitivity
• Support for digestive health
• Potential cancer prevention

Dosage

Children: As with adults, there is no specific dosage for children. Berries can be incorporated into a child's diet in appropriate portion sizes, with suggestions to include them as snacks or in meals several times a week.

Adults: There is no standard dosage for berries, but they are commonly included in the diet as part of a balanced nutrition plan. A general recommendation is to consume a variety of berries several times a week.

Mechanism of action

Berries exert their health benefits primarily through their high content of phytochemicals, including flavonoids, anthocyanins, and other antioxidants. These compounds help to neutralize free radicals, reducing oxidative stress and inflammation in the body. Additionally, berries have been shown to enhance endothelial function and improve insulin sensitivity, contributing to cardiovascular health and metabolic balance.

Pharmacodynamics

The bioactive compounds in berries, particularly anthocyanins, are responsible for many of their pharmacological effects. These compounds can modulate various signaling pathways, influencing inflammation, metabolism, and cell signaling. The antioxidant properties of berries help to reduce oxidative damage to cells, which is linked to chronic diseases such as cancer and heart disease.

Pharmacokinetics

Berries are typically consumed fresh or processed, with their compounds being readily absorbed in the gastrointestinal tract. Once ingested, the antioxidants are transported through the bloodstream to various tissues, where they exert their effects. The half-life and metabolism of specific phytochemicals can vary widely, depending on individual factors such as gut microbiota and overall health status.

Pregnancy

Berries are generally considered safe during pregnancy when consumed in moderation. They are a good source of vitamins and antioxidants, which can benefit both the mother and the developing fetus.

Breast-feeding

Berries are safe to consume while breastfeeding. They provide essential nutrients and antioxidants that may support maternal health and milk production.

Storage

Store berries in a cool, dry place, preferably in the refrigerator to maintain freshness. Consume within a few days of purchase to ensure quality.

Formulations

• Fresh berries
• Frozen berries
• Dried berries
• Berry extracts
• Berry juices

Indications

• Energy source
• Dietary fiber supplement
• Source of vitamins and minerals
• Antioxidant support

Dosage

Children: Corn can be introduced to children as part of a balanced diet. There is no specific paediatric dosage; it should be given according to age-appropriate dietary guidelines.

Adults: Corn can be consumed in various forms as part of a balanced diet. There is no specific adult dosage; intake should be based on dietary preferences and nutritional needs.

Mechanism of action

The primary component of corn is starch, which is a polysaccharide composed of glucose units. Upon ingestion, starch is broken down into glucose by enzymes such as amylase in the digestive system. The glucose is then absorbed into the bloodstream, providing energy to cells throughout the body. Corn also contains antioxidants such as lutein and zeaxanthin, which may help protect against oxidative stress and support eye health.

Pharmacodynamics

Corn is mainly metabolized for energy due to its high carbohydrate content. The dietary fiber in corn aids in digestion and promotes satiety. Additionally, the presence of vitamins and minerals contributes to overall health, supporting various bodily functions including immune response and bone health. The antioxidants in corn may help reduce inflammation and lower the risk of chronic diseases.

Pharmacokinetics

The digestion and absorption of corn depend on its form (whole kernel, cornmeal, corn syrup, etc.). Generally, carbohydrates are digested and absorbed relatively quickly, with glucose appearing in the bloodstream shortly after consumption. The fiber content can slow digestion and help maintain stable blood sugar levels. The bioavailability of nutrients from corn can vary based on processing methods, such as cooking or milling.

Pregnancy

Corn is generally considered safe during pregnancy. It provides essential nutrients such as fiber, vitamins, and minerals, but should be consumed in moderation as part of a balanced diet.

Breast-feeding

Corn is safe for consumption while breastfeeding. It can provide important nutrients, but it's advisable to monitor for any allergic reactions in infants.

Storage

Store corn in a cool, dry place. Fresh corn should be kept in the refrigerator and consumed within a few days for optimal freshness.

Formulations

• Fresh corn
• Canned corn
• Frozen corn
• Cornmeal
• Corn syrup
• Corn oil

Indications

• Constipation
• Irritable bowel syndrome (IBS)
• Diverticulitis
• Hyperlipidemia
• Type 2 diabetes management
• Weight management

Dosage

Children: For children, the recommended daily intake of fiber varies by age and is approximately 14 grams per 1,000 calories consumed. It is advisable to refer to specific pediatric guidelines for more detailed dosing.

Adults: The general recommendation for adults is to consume 25 to 30 grams of dietary fiber daily from food sources, rather than supplements, to promote optimal health.

Mechanism of action

Fiber works primarily by adding bulk to the stool and facilitating regular bowel movements. Soluble fiber dissolves in water to form a gel-like substance, which can help to slow digestion and regulate blood sugar levels by slowing the absorption of sugar. Insoluble fiber does not dissolve in water and helps food pass more quickly through the stomach and intestines.

Pharmacodynamics

The pharmacodynamics of fiber involve its ability to enhance gastrointestinal health. Soluble fiber can lower cholesterol levels, improve glycemic control, and promote satiety, which may assist in weight management. Insoluble fiber contributes to increased stool bulk and can help prevent constipation. The fermentation of soluble fiber in the colon produces short-chain fatty acids, which have various health benefits, including anti-inflammatory effects.

Pharmacokinetics

Fiber is not absorbed in the gastrointestinal tract; thus, it has no bioavailability. It passes through the stomach and small intestine largely intact, reaching the colon where it can be fermented by gut microbiota. The rate of fermentation and the production of short-chain fatty acids can vary based on the type of fiber consumed and the individual's gut microbiome.

Adverse effects

• Bloating
• Gas
• Abdominal cramps
• Diarrhea
• Constipation

Precautions

• Increase fiber intake gradually to avoid gastrointestinal discomfort.
• Adequate fluid intake is necessary to prevent constipation.
• Caution is advised in patients with gastrointestinal disorders.

Pregnancy

Fiber is generally considered safe during pregnancy. It supports digestive health and can help alleviate constipation common in this population.

Breast-feeding

Fiber is safe during breastfeeding and can aid in postpartum digestive health.

Storage

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

Formulations

• Powder
• Capsules
• Tablets
• Granules
• Natural food sources (fruits, vegetables, whole grains)

Indications

• Acetaminophen overdose
• Wound healing
• Burn treatment
• Management of cystic fibrosis
• Support in bronchitis

Dosage

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

Adults: Refer to the BNF for specific dosing recommendations.

Mechanism of action

L-Cystine acts as a precursor for glutathione synthesis, which is essential for cellular protection against oxidative stress. By increasing glutathione levels, it helps to restore cellular integrity and mitigate damage caused by reactive oxygen species.

Pharmacodynamics

L-Cystine is a dimeric amino acid formed from two cysteine molecules, which are linked by a disulfide bond. This compound plays a vital role in the body's antioxidant defense system, particularly by enhancing glutathione levels, which is crucial for various metabolic processes. L-Cystine is also involved in metabolic pathways associated with the utilization of vitamin B6 and supporting pancreatic insulin supply. Its properties aid in the healing process of wounds and burns and assist in clearing mucus in respiratory conditions, thus contributing to improved respiratory health.

Pharmacokinetics

L-Cystine is absorbed in the gastrointestinal tract and is metabolized in the liver. Following its absorption, it participates in the synthesis of glutathione, which is distributed throughout the body, including the lungs, liver, kidneys, and bone marrow. The half-life and elimination profiles of L-Cystine are not extensively documented but are influenced by factors such as dietary intake and the body's demand for glutathione.

Pregnancy

L-Cystine should be used during pregnancy only if clearly needed, as safety in pregnancy has not been established.

Breast-feeding

L-Cystine is excreted in breast milk, and caution should be exercised when administering to nursing mothers.

Storage

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

Formulations

• L-Cystine 500 mg tablets
• L-Cystine oral solution

Indications

• Support in recovery from surgery or trauma
• Management of catabolic states in critically ill patients
• Treatment of gastrointestinal disorders
• Support for immune function in immunocompromised patients

Dosage

Adults: Refer to the BNF for specific dosing guidelines, taking into account the patient's clinical

Mechanism of action

Supplemental L-glutamine's possible immunomodulatory role may be accounted for in a number of ways. L-glutamine appears to play a major role in protecting the integrity of the gastrointestinal tract, especially the large intestine. During catabolic states, the demand for L-glutamine by the intestine and lymphocytes exceeds that supplied by skeletal muscle. L-glutamine is the preferred respiratory fuel for enterocytes, colonocytes, and lymphocytes. Supplementing L-glutamine may reverse catabolic states by sparing skeletal muscle, inhibit translocation of Gram-negative bacteria from the large intestine, maintain secretory IgA, support lymphocyte proliferation, and enhance phagocytosis by immune cells.

Pharmacodynamics

L-glutamine is biochemically important as a constituent of proteins and plays a crucial role in nitrogen metabolism. It is involved in the assimilation of ammonia into organic compounds, primarily through conversion from glutamic acid via the enzyme glutamine synthetase. L-glutamine serves as a nitrogen donor in the biosynthesis of various compounds, including other amino acids, purines, and pyrimidines. Additionally, it improves the redox potential of nicotinamide adenine dinucleotide (NAD).

Pharmacokinetics

L-glutamine is absorbed in the gastrointestinal tract and is distributed throughout the body, with a major storage site in skeletal muscle. It has a relatively short half-life and is utilized rapidly in metabolic processes, particularly in states of stress or injury where the demand for glutamine increases significantly. Renal function plays a role in its metabolism and clearance.

Adverse effects

• Gastrointestinal disturbances
• Nausea
• Vomiting
• Abdominal pain
• Headache
• Dizziness

Precautions

• Caution in patients with renal impairment
• Monitor for potential effects on ammonia levels

Pregnancy

L-glutamine should only be used in pregnancy if the potential benefit justifies the potential risk to the fetus. Consultation with a healthcare provider is advised.

Breast-feeding

L-glutamine is considered safe during breastfeeding; however, it is recommended to consult a healthcare professional before use.

Storage

Store at room temperature, protect from moisture and light. Keep out of reach of children.

Formulations

• Oral powder
• Capsules

Indications

• Lysine deficiency
• Support in muscle development
• Post-surgical recovery
• Malnutrition
• Herpes simplex virus management

Dosage

Children: Refer to the BNF for Children for dosing information tailored to paediatric patients.

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

Mechanism of action

Lysine functions as a precursor for the synthesis of various proteins and hormones. It is involved in the production of carnitine, which is necessary for the transport of fatty acids into mitochondria for energy production. Additionally, lysine enhances the absorption of calcium and aids in the formation of collagen, which is essential for the structural integrity of connective tissues.

Pharmacodynamics

Lysine has been shown to reduce anxiety and stress by modulating serotonin levels in the brain. It also helps in preventing the replication of the herpes simplex virus, suggesting antiviral properties. Clinical studies indicate that lysine supplementation may lead to improved outcomes in conditions associated with lysine deficiency, such as impaired growth and muscle loss.

Pharmacokinetics

Lysine is absorbed in the gastrointestinal tract through active transport mechanisms. It has a bioavailability of approximately 80% when ingested in food. The metabolism of lysine primarily occurs in the liver, where it is converted into various metabolites. The elimination half-life of lysine is relatively short, necessitating regular intake through diet or supplementation to maintain adequate levels in the body.

Pregnancy

There is limited data on the safety of betaine during pregnancy. Consult healthcare professionals for guidance.

Breast-feeding

Betaine is generally considered safe during breastfeeding, but consult a healthcare provider before use.

Storage

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

Formulations

• tablets
• powder

Dosage

Children: Refer to specific drug guidelines as paediatric dosing must be determined based on the individual drug and condition being treated.

Adults: Refer to specific drug guidelines as dosing can vary widely based on the exact medication and its intended use.

Mechanism of action

The mechanism of action of mixed drugs can vary widely, often involving multiple pathways. For example, some may act as agonists or antagonists at certain receptors, while others may inhibit enzymes or modulate neurotransmitter levels. This complexity allows mixed drugs to have a broad spectrum of effects, which can be beneficial in treating conditions that require multifaceted approaches.

Pharmacodynamics

Pharmacodynamics of mixed drugs also varies significantly. Their effects can be dose-dependent, with lower doses potentially providing different therapeutic effects than higher doses. The interactions with various receptors and pathways can lead to synergistic or antagonistic effects, influencing the overall therapeutic outcome. Side effects and therapeutic efficacy must be carefully monitored.

Pharmacokinetics

Pharmacokinetics of mixed drugs includes absorption, distribution, metabolism, and excretion, which are influenced by the drug's chemical structure and route of administration. Many mixed drugs are absorbed rapidly and have wide distribution in body tissues. Metabolism can occur in the liver, often involving cytochrome P450 enzymes, and excretion may be renal or hepatic, depending on the drug's properties. The half-life can vary, affecting dosing schedules and potential for drug interactions.

Pregnancy

Consult with a healthcare provider regarding use during pregnancy, as the safety profile may vary depending on the specific components involved in the mixed formulation.

Breast-feeding

Consult with a healthcare provider regarding use during breastfeeding, as the safety profile may vary depending on the specific components involved in the mixed formulation.

Storage

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

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

Certain conditions, e.g. an acetaminophen overdose, deplete hepatic glutathione and subject the tissues to oxidative stress resulting in loss of cellular integrity. L-Cystine serves as a major precursor for synthesis of glutathione.

Pharmacodynamics

L-Cystine is a covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. Cystine is a chemical substance which naturally occurs as a deposit in the urine, and can form a calculus (hard mineral formation) when deposited in the kidney. The compound produced when two cysteine molecules linked by a disulfide (S-S) bond. Cystine is required for proper vitamin B6 utilization and is also helpful in the healing of burns and wounds, breaking down mucus deposits in illnesses such as bronchitis as well as cystic fibrosis. Cysteine also assists in the supply of insulin to the pancreas, which is needed for the assimilation of sugars and starches. It increases the level of glutathione in the lungs, liver, kidneys and bone marrow, and this may have an anti-aging effect on the body by reducing age-spots etc.

Mechanism of action

Supplemental L-glutamine's possible immunomodulatory role may be accounted for in a number of ways. L-glutamine appears to play a major role in protecting the integrity of the gastrointestinal tract and, in particular, the large intestine. During catabolic states, the integrity of the intestinal mucosa may be compromised with consequent increased intestinal permeability and translocation of Gram-negative bacteria from the large intestine into the body. The demand for L-glutamine by the intestine, as well as by cells such as lymphocytes, appears to be much greater than that supplied by skeletal muscle, the major storage tissue for L-glutamine. L-glutamine is the preferred respiratory fuel for enterocytes, colonocytes and lymphocytes. Therefore, supplying supplemental L-glutamine under these conditions may do a number of things. For one, it may reverse the catabolic state by sparing skeletal muscle L-glutamine. It also may inhibit translocation of Gram-negative bacteria from the large intestine. L-glutamine helps maintain secretory IgA, which functions primarily by preventing the attachment of bacteria to mucosal cells. L-glutamine appears to be required to support the proliferation of mitogen-stimulated lymphocytes, as well as the production of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma). It is also required for the maintenance of lymphokine-activated killer cells (LAK). L-glutamine can enhance phagocytosis by neutrophils and monocytes. It can lead to an increased synthesis of glutathione in the intestine, which may also play a role in maintaining the integrity of the intestinal mucosa by ameliorating oxidative stress. The exact mechanism of the possible immunomodulatory action of supplemental L-glutamine, however, remains unclear. It is conceivable that the major effect of L-glutamine occurs at the level of the intestine. Perhaps enteral L-glutamine acts directly on intestine-associated lymphoid tissue and stimulates overall immune function by that mechanism, without passing beyond the splanchnic bed. The exact mechanism of L-glutamine's effect on NAD redox potential is unknown but is thought to involve increased amounts of reduced glutathione made available by glutamine supplementation. This improvement in redox potential reduces the amount of oxidative damage which sickle red blood cells are more susceptible to. The reduction in cellular damage is thought to reduce chronic hemolysis and vaso-occlusive events. L-glutamine has important functions in regulation of gastrointestinal cell growth, function, and regeneration. Under normal conditions, glutamine concentration is maintained in the body by dietary intake and synthesis from endogenous glutamate. Data from clinical studies indicate that the role of and nutritional requirements for glutamine during catabolic illness, trauma, and infection may differ significantly from the role of and nutritional requirements for glutamine in healthy individuals. Glutamine concentrations decrease and tissue glutamine metabolism increases during many catabolic disease states, and thus glutamine is often considered a "conditionally essential" amino acid.

Pharmacodynamics

Like other amino acids, glutamine is biochemically important as a constituent of proteins. Glutamine is also crucial in nitrogen metabolism. Ammonia (formed by nitrogen fixation) is assimilated into organic compounds by converting glutamic acid to glutamine. The enzyme which accomplishes this is called glutamine synthetase. Glutamine can then be used as a nitrogen donor in the biosynthesis of many compounds, including other amino acids, purines, and pyrimidines. L-glutamine improves nicotinamide adenine dinucleotide (NAD) redox potential.

Mechanism of action

Homocystinuria is a hereditary disorder characterized by high levels of the amino acid homocysteine. This condition can be caused by deficiencies or defects in cystathionine beta-synthase (CBS), 5,10-methylenetetrahydrofolate reductase (MTHFR), and cobalamin cofactor metabolism (cbl). CBS converts homocysteine to cystathionine, and a deficiency in this enzyme can lead to an accumulation of homocysteine. MTHFR is responsible for producing 5-methyltetrahydrofolate, a methyl donor that participates in the conversion of homocysteine back to methionine; therefore, an MTHFR deficiency can also lead to homocystinuria. Additionally, a defect in cobalamin (vitamin B12) cofactor metabolism can lead to homocystinuria, since a metabolite of cobalamin (methylcobalamin) promotes the conversion of homocysteine to methionine. Betaine transfers a methyl group via the enzyme betaine homocysteine methyl transferase (BHMT), converting homocysteine back into methionine and dimethylglycine (DMG). In patients with homocystinuria, betaine reduces homocysteine levels and improves health outcomes. Betaine acts as metabolic intermediate in transmethylating processes (creatine and methionine synthesis). Betaine acts as a methyl group donor in the remethylation of homocysteine to methionine in patients with homocystinuria. This reduces toxic concentrations of homocysteine, usually to 20 to 30% or less of pretreatment concentrations. Betaine or trimethylglycine is a quarternary ammonium compound that was first discovered in the juice of sugar beets (Beta vulgaris). Betaine is a metabolite of choline ... and is a substrate in one of the two recycling pathways that convert homocysteine to L-methionine. The other and principal recycling reaction is catalyzed by the enzyme methionine synthase and uses methylcobalamin as a cofactor and 5-methyltetrahydrofolate as a cosubstrate. Betaine-homocysteine methyltransferase (BHMT) is a zinc metalloenzyme which catalyzes the transfer of a methyl group from betaine to homocysteine in the formation of methionine. BHMT is found in the liver and kidneys and may also exist in brain tissue. Betaine acts to lower homocysteine levels in some with primary hyperhomocysteinemia/homocystinuria via this enzyme.

Pharmacodynamics

Betaine decreases plasma homocysteine concentrations in homocystinuria cases caused by deficiencies or defects in cystathionine beta-synthase (CBS), 5,10-methylenetetrahydrofolate reductase (MTHFR), and cobalamin cofactor metabolism (cbl). The decrease of homocysteine is estimated to be 20-30% of pre-treatment levels. Betaine supplementation in patients with homocystinuria also improves metabolic abnormalities in cerebrospinal fluid. Reports have shown that depending on the type of homocystinuria, the therapeutic effectiveness of betaine alone may be limited, insufficient to decrease total homocysteine levels and prevent clinical symptoms. In patients with homocystinuria due to cystathionine beta-synthase (CBS) deficiency, betaine should be used when serum total homocysteine levels remain high despite dietary therapy. Patients taking betaine for several years do not show evidence of tolerance. Also, betaine concentrations are not correlated with homocysteine concentrations. In patients with MTHFR deficiency and cbl defects, betaine may increase methionine and S-adenosyl methionine (SAM) plasma levels. Patients with CBS deficiency without a dietary restriction of methionine may accumulate excessive amounts of methionine. Clinical data shows that in patients with CBS deficiency, increased plasma methionine levels were associated with cerebral edema.