EZORB FEM TABLETS

Indications

• Supplemental support for exercise performance
• Potential aid in reducing fatigue during physical exertion

Dosage

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

Adults: Refer to the BNF for specific dosing recommendations.

Mechanism of action

L-aspartate is hypothesized to enhance performance in prolonged and short intensive exercise by sparing muscle glycogen stores and promoting glycogen resynthesis. It serves as a substrate for energy production in the Krebs cycle and stimulates the purine nucleotide cycle, thus potentially influencing energy metabolism during physical activity.

Pharmacodynamics

As a non-essential amino acid, L-aspartate is produced in sufficient quantities under normal physiological conditions. It is a precursor for protein synthesis and plays a role in various metabolic pathways, including those related to energy production and nucleotide synthesis. It is classified as a glycogenic amino acid, contributing to gluconeogenesis and energy metabolism.

Pharmacokinetics

L-aspartate is readily absorbed and utilized by the body, participating in several metabolic pathways, including the Krebs cycle and amino acid metabolism. The exact pharmacokinetic parameters such as half-life, peak plasma concentration, and elimination route are not well characterized in the literature.

Indications

• Vitamin D deficiency
• Rickets
• Osteomalacia
• Osteoporosis
• Hypoparathyroidism

Dosage

Adults: The usual adult dose for vitamin D deficiency is 800 to 2000 IU daily, depending on the severity of deficiency and clinical condition. Higher doses may be used under medical supervision.

Mechanism of action

Cholecalciferol is converted to its active forms, 25-hydroxyvitamin D in the liver and 1,25-dihydroxyvitamin D in the kidneys. These metabolites enhance the intestinal absorption of calcium and phosphorus, increase serum calcium levels, and mobilize these minerals from bone. This process is regulated by parathyroid hormone, which influences calcium and phosphate metabolism, particularly in the kidneys.

Pharmacodynamics

The pharmacodynamics of cholecalciferol involve its conversion to active metabolites that play a significant role in calcium and phosphorus homeostasis. The metabolites facilitate intestinal absorption of these minerals, promote bone mineralization, and influence renal reabsorption. The onset of action occurs within 10 to 24 hours following administration, as metabolic activation is required for its biological effects.

Pharmacokinetics

Cholecalciferol is absorbed in the gastrointestinal tract, and its absorption is enhanced by the presence of dietary fats. It is transported in the bloodstream bound to vitamin D-binding protein. Once in the liver, it undergoes hydroxylation to form 25-hydroxyvitamin D, which is further converted in the kidneys to the active form, 1,25-dihydroxyvitamin D. The elimination half-life of cholecalciferol varies, typically spanning several days, and it is primarily excreted in bile and urine.

Adverse effects

• Hypercalcemia
• Hypercalciuria
• Nausea
• Vomiting
• Constipation
• Weakness
• Fatigue

Interactions

• May enhance the effects of thiazide diuretics, leading to increased risk of hypercalcemia
• Anticonvulsants may increase metabolism of vitamin D, leading to reduced effectiveness
• Cholestyramine may reduce absorption of vitamin D

Precautions

• Monitor serum calcium levels in patients with renal impairment
• Caution in patients with a history of hypercalcemia or hyperparathyroidism
• Use with caution in patients taking other medications that affect calcium metabolism

Pregnancy

Cholecalciferol can be used during pregnancy if indicated, as vitamin D is essential for fetal bone development.

Breast-feeding

Cholecalciferol is excreted in breast milk, but is generally considered safe during breastfeeding.

Storage

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

Formulations

• Capsules
• Tablets
• Liquid formulations

Indications

• Menopausal symptoms
• Cardiovascular health
• Bone health
• Estrogen-dependent cancers

Dosage

Children: Use in children is not

Adults: Dosage varies based on the specific formulation and indication. Refer to the specific product guidelines or the BNF for detailed dosing recommendations.

Mechanism of action

Isoflavones are selective estrogen receptor modulators that exert estrogenic-like effects under certain conditions. They bind preferentially to estrogen receptor beta (ERβ) with a binding affinity approximately 20 times higher than that to estrogen receptor alpha (ERα). Isoflavones can exhibit antiestrogenic actions by blocking the binding of endogenous estrogens and their receptor signaling. They may inhibit the proliferation of breast cancer cells by arresting cell cycle progression and inducing apoptosis. Additionally, isoflavones may act on androgen receptors to inhibit tyrosine kinase activity, blocking cancer cell growth.

Pharmacodynamics

Isoflavones, particularly from soy, have been shown to lower LDL cholesterol levels and improve blood pressure in women with hypertension. In postmenopausal women, dietary intake of isoflavones has been associated with reduced bone resorption and increased bone formation markers. Their effects on menopausal symptoms, breast cancer, and prostate cancer remain controversial, though some studies suggest they may decrease cancer development markers in prostate cells.

Pharmacokinetics

Isoflavones are metabolized in the gut and liver, leading to various bioactive metabolites. Their bioavailability can be affected by dietary factors and individual metabolism. Peak plasma concentrations occur about 2 to 4 hours after ingestion, with a half-life that varies depending on the specific isoflavone and individual factors. Isoflavones are primarily excreted via urine.

Adverse effects

• gastrointestinal disturbances
• allergic reactions
• headaches
• fatigue
• dizziness

Interactions

• may interact with anticoagulants, potentially increasing bleeding risk
• may affect the metabolism of certain medications via CYP450 enzymes
• estrogenic drugs may exhibit compounded effects when used with isoflavones

Precautions

• use cautiously in individuals with hormone-sensitive conditions
• monitor patients with a history of breast or prostate cancer
• consider potential interactions with other medications

Pregnancy

Isoflavones should be used with caution during pregnancy due to their estrogen-like effects; consult healthcare professionals for guidance.

Breast-feeding

Limited data is available; consult healthcare professionals before use during breastfeeding.

Storage

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

Formulations

• capsules
• tablets
• powdered supplements
• soy-based food products

Indications

• Nutritional supplementation
• Support in metabolic disorders related to nucleotide synthesis
• Potential use in conditions requiring enhanced cellular proliferation

Dosage

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

Adults: Refer to BNF for specific dosing recommendations.

Mechanism of action

Orotate functions as a substrate in the synthesis of UMP through multiple biosynthetic pathways. It is involved in the UMP biosynthesis pathways, contributing to the formation of pyrimidine nucleotides that are vital for nucleic acid synthesis. Specifically, orotate is converted to UMP by the enzyme orotate phosphoribosyltransferase, which catalyzes the transfer of a ribose-phosphate moiety to orotate.

Pharmacodynamics

Orotate influences the synthesis and regulation of nucleotides, which are fundamental components of RNA and DNA. By facilitating the production of UMP, orotate indirectly affects various cellular processes, including cell proliferation, growth, and metabolism. Adequate levels of pyrimidines, such as those derived from orotate, are essential for maintaining the integrity of genetic material and supporting cellular functions.

Pharmacokinetics

The pharmacokinetics of orotate involves its absorption, distribution, metabolism, and excretion in the body. While specific data on its pharmacokinetic parameters are limited, orotate is generally expected to be absorbed through the gastrointestinal tract when administered. Once in circulation, it may be distributed to tissues where it participates in nucleotide synthesis. The elimination route of orotate and its metabolites is primarily through renal excretion.

Pregnancy

There is limited data on the use of orotate during pregnancy. Consult healthcare professionals for guidance.

Breast-feeding

It is not known whether orotate is excreted in human milk. Caution is advised when administering to nursing mothers.

Storage

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

Formulations

• {'formulation': 'Orotate', 'dosage_form': 'tablet', 'strength': 'various'}

Indications

• Vitamin deficiency syndromes (e.g., scurvy for vitamin C deficiency, rickets for vitamin D deficiency)
• Support for immune function
• Antioxidant support
• Bone health maintenance
• Vision health
• Energy metabolism support

Dosage

Children: Refer to the BNF for Children for specific vitamin dosing guidelines, which depend on age and nutritional requirements.

Adults: Refer to specific vitamin guidelines as dosage varies significantly depending on the type of vitamin and individual needs.

Mechanism of action

Vitamins function primarily as coenzymes or precursors for coenzymes in enzymatic reactions. For instance, B vitamins are involved in energy metabolism, while vitamins A, C, D, E, and K support various physiological functions including vision, antioxidant activity, calcium regulation, and blood clotting. Each vitamin has a unique mechanism of action based on its structure and role in the body.

Pharmacodynamics

Vitamins exert their effects at the cellular level, influencing metabolic pathways, gene expression, and immune responses. For example, vitamin D regulates calcium and phosphate homeostasis, while vitamin A is crucial for vision and immune function. Deficiencies in vitamins can lead to a range of disorders, highlighting their importance in maintaining health.

Pharmacokinetics

The pharmacokinetics of vitamins vary widely. Fat-soluble vitamins (A, D, E, and K) are stored in liver and adipose tissues and can be released into circulation as needed. Water-soluble vitamins (B-complex and C) are not stored and must be consumed regularly, with excess amounts excreted in urine. Absorption rates, half-lives, and distribution can also differ based on the specific vitamin and individual metabolic factors.

Interactions

• tretinoin+vitamin: Severe (increases risk of vitamin toxicity)
• retinoids+vitamin: Severe (increases risk of vitamin toxicity)
• retinoids+vitamin: Moderate (increases risk of toxicity)
• carbamazepine+vitamin: Unknown (decreases effects)
• cobicistat+vitamin: Unknown (increases exposure)
• vitamin D substances+digoxin: Unknown (increases risk of toxicity)
• idelalisib+vitamin: Unknown (increases exposure)
• clarithromycin+vitamin: Unknown (increases exposure)

Pregnancy

Consult healthcare professional before use. Vitamin supplementation during pregnancy should be carefully managed to avoid hypervitaminosis.

Breast-feeding

Consult healthcare professional before use. Some vitamins can pass into breast milk and may affect the infant.

Storage

Store in a cool, dry place, away from direct sunlight. Ensure it is kept out of reach of children.

Formulations

• {'name': 'Vitamin A', 'form': 'Capsule', 'strength': '10000 IU'}
• {'name': 'Vitamin D', 'form': 'Tablet', 'strength': '1000 IU'}
• {'name': 'Vitamin E', 'form': 'Softgel', 'strength': '400 IU'}

Mechanism of action

There are also claims that L-aspartate has ergogenic effects, that it enhances performance in both prolonged exercise and short intensive exercise. It is hypothesized that L-aspartate, especially the potassium magnesium aspartate salt, spares stores of muscle glycogen and/or promotes a faster rate of glycogen resynthesis during exercise. It has also been hypothesized that L-aspartate can enhance short intensive exercise by serving as a substrate for energy production in the Krebs cycle and for stimulating the purine nucleotide cycle.

Pharmacodynamics

L-aspartate is considered a non-essential amino acid, meaning that, under normal physiological conditions, sufficient amounts of the amino acid are synthesized in the body to meet the body's requirements. L-aspartate is formed by the transamination of the Krebs cycle intermediate oxaloacetate. The amino acid serves as a precursor for synthesis of proteins, oligopeptides, purines, pyrimidines, nucleic acids and L-arginine. L-aspartate is a glycogenic amino acid, and it can also promote energy production via its metabolism in the Krebs cycle. These latter activities were the rationale for the claim that supplemental aspartate has an anti-fatigue effect on skeletal muscle, a claim that was never confirmed.

Mechanism of action

Most individuals naturally generate adequate amounts of vitamin D through ordinary dietary intake of vitamin D (in some foods like eggs, fish, and cheese) and natural photochemical conversion of the vitamin D3 precursor 7-dehydrocholesterol in the skin via exposure to sunlight. Conversely, vitamin D deficiency can often occur from a combination of insufficient exposure to sunlight, inadequate dietary intake of vitamin D, genetic defects with endogenous vitamin D receptor, or even severe liver or kidney disease. Such deficiency is known for resulting in conditions like rickets or osteomalacia, all of which reflect inadequate mineralization of bone, enhanced compensatory skeletal demineralization, resultant decreased calcium ion blood concentrations, and increases in the production and secretion of parathyroid hormone. Increases in parathyroid hormone stimulate the mobilization of skeletal calcium and the renal excretion of phosphorus. This enhanced mobilization of skeletal calcium leads towards porotic bone conditions. Ordinarily, while vitamin D3 is made naturally via photochemical processes in the skin, both itself and vitamin D2 can be found in various food and pharmaceutical sources as dietary supplements. The principal biological function of vitamin D is the maintenance of normal levels of serum calcium and phosphorus in the bloodstream by enhancing the efficacy of the small intestine to absorb these minerals from the diet. At the liver, vitamin D3 or D2 is hydroxylated to 25-hydroxyvitamin D and then finally to the primary active metabolite 1,25-dihydroxyvitamin D in the kidney via further hydroxylation. This final metabolite binds to endogenous vitamin d receptors, which results in a variety of regulatory roles - including maintaining calcium balance, the regulation of parathyroid hormone, the promotion of the renal reabsorption of calcium, increased intestinal absorption of calcium and phosphorus, and increased calcium and phosphorus mobilization of calcium and phosphorus from bone to plasma to maintain balanced levels of each in bone and the plasma. In particular, calcitriol interacts with vitamin D receptors in the small intestine to enhance the efficiency of intestinal calcium and phosphorous absorption from about 10-15% to 30-40% and 60% increased to 80%, respectively. Furthermore, calcitriol binds with vitamin D receptors in osteoblasts to stimulate a receptor activator of nuclear factor kB ligand (or RANKL) which subsequently interacts with receptor activator of nuclear factor kB (NFkB) on immature preosteoclasts, causing them to become mature bone-resorbing osteoclasts. Such mature osteoclasts ultimately function in removing calcium and phosphorus from bone to maintain blood calcium and phosphorus levels. Moreover, calcitriol also stimulates calcium reabsorption from the glomerular filtrate in the kidneys. Additionally, it is believed that when calcitriol binds with nuclear vitamin D receptors, that this bound complex itself binds to retinoic acid X receptor (RXR) to generate a heterodimeric complex that consequently binds to specific nucleotide sequences in the DNA called vitamin D response elements. When bound, various transcription factors attach to this complex, resulting in either up or down-regulation of the associated gene's activity. It is thought that there may be as much as 200 to 2000 genes that possess vitamin D response elements or that are influenced indirectly to control a multitude of genes across the genome. It is in this way that cholecalciferol is believed to function in regulating gene transcription associated with cancer risk, autoimmune disorders, and cardiovascular disease linked to vitamin D deficiency. In fact, there has been some research to suggest calcitriol may also be able to prevent malignancies by inducing cellular maturation and inducing apoptosis and inhibiting angiogenesis, exhibit anti-inflammatory effects by inhibiting foam cell formation and promoting angiogenesis in en

Pharmacodynamics

The in vivo synthesis of the predominant two biologically active metabolites of vitamin D occurs in two steps. The first hydroxylation of vitamin D3 cholecalciferol (or D2) occurs in the liver to yield 25-hydroxyvitamin D while the second hydroxylation happens in the kidneys to give 1, 25-dihydroxyvitamin D. These vitamin D metabolites subsequently facilitate the active absorption of calcium and phosphorus in the small intestine, serving to increase serum calcium and phosphate levels sufficiently to allow bone mineralization. Conversely, these vitamin D metabolites also assist in mobilizing calcium and phosphate from bone and likely increase the reabsorption of calcium and perhaps also of phosphate via the renal tubules. There exists a period of 10 to 24 hours between the administration of cholecalciferol and the initiation of its action in the body due to the necessity of synthesis of the active vitamin D metabolites in the liver and kidneys. It is parathyroid hormone that is responsible for the regulation of such metabolism at the level of the kidneys.

Mechanism of action

Isoflavones are selective estrogen receptor modulators that exert estrogenic-like effects under certain experimental conditions, as they are structurally similar to mammalian 17β-estradiol. They may bind to both α and β isoforms of estrogen receptor (ER), but with binding affinities to ERβ approximately 20 times higher than that to ERα. The role of isoflavones on estrogen-dependent cancer has been studied, since they may mediate antiestrogenic actions by blocking the binding of endogenous estrogens and their receptor signalling. In cell culture, [DB01645] inhibited the proliferation of MDA-MB-231 human breast cancer cells, probably by arresting the cell cycle progression at the G2–M transition. In addition, genistein was shown to induce apoptosis, modify eicosanoid metabolism, and inhibit angiogenesis. There is an evidence that soy isoflavones may act on androgen receptors to inhibit tyrosine kinase activity, thereby blocking the growth and proliferation of cancer cells. Isoflavones may not significantly contribute to the hypolipidemic effects of soy protein, but may exert coronary benefits by improving endothelial function; in clinical trials of postmenopausal women, isoflavones improved flow-mediated dilation in women with impaired endothelial function. Some observational data suggests that isoflavones improve endothelial function by increasing the number of circulating endothelial progenitor cells, which replace damaged endothelial cells. Isoflavone may modulate the key transcription factors involved in the regulation of lipid metabolism by acting on the peroxisome proliferator-activated receptors (PPAR) alpha and gamma, which are receptors that regulate the transcription of genes involved in lipid and glucose homeostasis and lipid metabolism. Multiple biological actions of isoflavones, such as favorable effect on the blood lipid profile and inhibition of LDL cholesterol oxidation, may lead to cardio protective effects. [DB01645] has been shown to have antioxidant properties on hydrogen peroxide production _in vitro_ and blocks the formation of oxygen free radicals. Studies also suggest that at micromolar concentrations, genistein increases glucose-stimulated insulin secretion in cell lines and mouse pancreatic islets via a cAMP-dependent protein kinase mechanism. Based on the findings of experimental studies, genistein may exert a positive effect on bone formation by decreasing osteoclastic resorption factor, such as collagen C-telopeptide, and increasing osteoblastic formation markers, such as bone-alkaline phosphatase. _In vitro_, it antagonized the catabolic effects of parathyroid hormone (PTH) in osteoblasts by reversing the PTH-induced increase in soluble receptor activator of nuclear factor-xB ligand and decrease in osteoprotegerin expression.

Pharmacodynamics

Isolated soy protein with isoflavones was shown to decrease LDL cholesterol levels in randomized trials assessed by the American Heart Association. In a study of postmenopausal women, daily dietary intake of 101 mg of aglycone isoflavones (indicating [DB01645] and [DB13182]) was associated with lowered LDL cholesterol and apolipoprotein B levels by 8% and reduced systolic and diastolic blood pressure by 6.8% in hypertensive women. In a meta-analysis of randomized controlled trials of menopausal women, soy isoflavones attenuated bone loss of the spine and decreased the levels of deoxypyridinoline, a bone resorption marker, while increasing serum bone-specific alkaline phosphatase, a bone formation marker. The findings from studies investigating the effects of soy consumption on menopausal symptoms, breast cancer, and prostate cancer remain somewhat controversial and inconclusive. Consumption of soy isoflavones may decrease the markers of cancer development and progression in prostate cells, including prostate-specific antigen (PSA), testosterone, and androgen receptor in patients with prostate cancer but not in normal subjects. Although epidemiologic data in Asian women demonstrate that high soy food intake is associated with protection against breast cancer, soy foods have little effect on intermediary markers of breast cancer risk and postmenopausal soy intake may not reduce the risk of developing breast cancer. However, preliminary studies show that soy food intake reduces tumor recurrence in breast cancer patients. Soy isoflavones reported to interfere with thyroid peroxidase, which are involved in the production of thyroid hormones.