Isofem
Isofem Uses, Dosage, Side Effects, Food Interaction and all others data.
Isoflavone is a soy phytoestrogen and a biologically active component of several agriculturally important legumes such as soy, peanut, green peas, chick peas and alfalfa . Soybean is an exceptionally rich source of dietary isoflavones, where the average isoflavone content is 1-2 mg/gram . The main soy isoflavones are mostly present in glycosylated forms and include Genistein, Daidzein, and glycitein, which accounts for approximately 50%, 40%, and 10%, respectively, of the total soybean isoflavone content . The clinical benefits of soy proteins have been studied and demonstrated for many years, with some evidence of soy products associated with a reduced incidences of coronary heart disease, atherosclerosis, type II diabetes mellitus, and breast and prostate cancer . While existing data are consistent or inadequate in supporting most of the suggested health benefits of consuming soy proteins and isoflavones , the trials investigating isoflavone as a potential treatment for atrophy, menopause, and postmenopausal symptoms are ongoing. Isoflavone is found as one of constituents in oral over-the-counter dietary supplements indicated for improved bone mass density and body fat regulation.
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 Genistein and Daidzein) 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 .
Vitamin D ultimately comprises a group of lipid-soluble secosteroids responsible for a variety of biological effects, some of which include increasing the intestinal absorption of calcium, magnesium, and phosphate. With reference to human use, there are 2 main forms of vitamin D - vitamin D3 (cholecalciferol) and vitamin D2 (ergocalciferol). When non-specific references are made about 'vitamin d', the references are usually about the use of vitamin D3 and/or D2.
Vitamin D3 and D2 require hydroxylation in order to become biologically active in the human body. Since vitamin D can be endogenously synthesized in adequate amounts by most mammals exposed to sufficient quantities of sunlight, vitamin D functions like a hormone on vitamin D receptors to regulate calcium in opposition to parathyroid hormone. Vitamin D plays an essential physiological role in maintaining calcium homeostasis and metabolism. There are several different vitamin D supplements that are given to treat or to prevent osteomalacia and rickets, or to meet the daily criteria of vitamin D consumption.
The in vivo synthesis of the predominant two biologically active metabolites of vitamin D occurs in two steps. The first hydroxylation of vitamin D3 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 vitamin D 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 .
| Trade Name | Isofem |
| Generic | Isoflavone + Vitamin C + Vitamin D + Vitamin E natural + Ca + dan Zn |
| Weight | 60mg, 100mg, 400iu, 10mg, 200mg, 15mg |
| Type | Tablet |
| Therapeutic Class | |
| Manufacturer | Meprofarm |
| Available Country | Indonesia |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Isoflavone is a biologically active phytoestrogen found in high concentrations in soy and other legumes.
Indicated for over-the-counter use as a dietary supplement for increasing bone density and regulating blood fat.
Vitamin D is an ingredient found in a variety of supplements and vitamins.
Vitamin D is indicated for use in the treatment of hypoparathyroidism, refractory rickets (also known as vitamin D resistant rickets), and familial hypophosphatemia .
Isofem is also used to associated treatment for these conditions: Nutrient supplementationDeficiency, Vitamin D
How Isofem works
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, Genistein 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 .
Genistein 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 .
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 stimulates 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 .
Toxicity
No toxicokinetic data available.
The use of pharmacological or nutraceutical vitamin d and/or even excessive dietary intake of vitamin d is contraindicated in patients with hypercalcemia, malabsorption syndrome, abnormal sensitivity to the toxic effects of vitamin d, and hypervitaminosis D .
Hypersensitivity to vitamin d is one plausible etiologic factor in infants with idiopathic hypercalcemia - a case in which vitamin d use must be strictly restricted .
As vitamin d intake is available via fortified foods, dietary supplements, and clinical drug sources, serum concentrations and therapeutic dosages should be reviewed regularly and readjusted as soon as there is clinical improvement . Dosage levels are required to be individualized on an individual patient by patient basis as caution must be exercised to prevent the presence of too much vitamin d in the body and the various potentially serious toxic effects associated with such circumstances .
In particular, the range between therapeutic and toxic doses is quite narrow in vitamin d resistant rickets . When high therapeutic doses are used, progress should be followed with frequent blood calcium determinations .
When treating hypoparathyroidism, intravenous calcium, parathyroid hormone, and/or dihydrotachysterol may be required .
Maintenance of normal serum phosphorus levels by dietary phosphate restriction and/or administration of aluminum gels as intestinal phosphate binders in those patients with hyperphosphatemia as frequently seen in renal osteodystrophy is essential to prevent metastatic calcification .
Mineral oil interferes with the absorption of lipid-soluble vitamins, including vitamin d preparations .
The administration of thiazide diuretics to hypoparathyroid patients who are concurrently being treated with vitamin d can result in hypercalcemia .
At this time, no long term animal studies have been performed to evaluate vitamin potential for carcinogens, mutagenesis, or fertility .
As various animal reproduction studies have demonstrated fetal abnormalities in several species associated with hypervitaminosis D, the use of vitamin d in excess of the recommended dietary allowance during normal pregnancy should be avoided . The safety in excess of 400 USP units of vitamin d daily during pregnancy has not been established . The abnormalities observed are similar to the supravalvular aortic stenosis syndrome described in infants that is characterized by supravalvular aortic stenosis, elfin facies, and mental retardation .
In a nursing mother given large doses of vitamin D, 25-hydroxycholecalciferol appeared in the milk and caused hypercalcemia in her child. Caution is subsequently required when contemplating the use of vitamin d in a nursing woman, and the necessity of monitoring infants' serum calcium concentration if vitamin d is administered to a breastfeeding woman .
Adverse reactions associated with the use of vitamin d are primarily linked to having hypervitaminosis D occurring [FDA Lanel]. In particular, hypervitaminosis D is characterized by effects specific effects on specific organ systems. At the renal system, hypervitaminosis D can cause impairment of renal function with polyuria, nocturne, polydipsia, hypercalciuria, reversible asotemia, hypertension, nephrocalcinosis, generalized vascular calcification, or even irreversible renal insufficiency which may result in death . Elsewhere, hypervitaminosis D can also cause CNS mental retardation . At the level of soft tissues, it can widespread calcification of the soft tissues, including the heart, blood vessels, renal tubules, and lungs . In the skeletal system, bone demineralization (osteoporosis) in adults can occur while a decline in the average rate of linear growth and increased mineralization of bones, dwarfism, vague aches, stiffness, and weakness can occur in infants and children . Finally, hypervitaminosis D can also lead to nausea, anorexia, and constipation at the gastrointestinal level as well as mild acidosis, anemia, or weight loss via metabolic processes .
The LD(50) in animals is unknown .
Volume of Distribution
Isoflavones are readily distributed to all tissues, and they are known to cross the placental barrier and blood brain barrier . They are also distributed to the extra-vascular compartments. In a human study, the volume of distribution of daidzein and genistein were 336.25 L and 258.76 L, respectively .
Elimination Route
Following oral ingestion, serum isoflavone concentrations increase in a dose-dependent manner . Isoflavones are metabolized by gut microflora, where they need to undergo deglycosylation in order to be absorbed in the intestine . After oral ingestion, glycosylated isoflavones are rapidly deglycosylated, absorbed and metabolized in intestinal enterocytes and liver, entering the systemic circulation predominantly as conjugates with limited bioavailability . In humans, the mean time to reach peak plasma concentrations (Tmax) for conjugated and unconjugated genistein and daidzein are approximately 5-6 and 6-8 hours, respectively .
Vitamin D3 and D2 are readily absorbed from the small intestine (proximal or distal) .
Half Life
The half-life of isoflavones is between 4 and 8 h . Daidzein has a longer intestinal half-life than genistein due to more rapid degradation of genistein . Individual half-life of daidzein and genistein in a human pharmacokinetic study were 7.75 h and 7.77 h, respectively .
Although certain studies suggest the half-life of 1,25-hydroxyvitamin D3 may be approximately 15 hours, the half-life of 25-hydroxyvitamin D3 appears to have a half-life of about 15 days . Intriguingly however, the half-lives of any particular administration of vitamin d can vary and in general the half-lives of vitamin D2 metabolites have been demonstrated to be shorter overall than vitamin D3 half-lives with this being affected by vitamin d binding protein concentrations and genotype in particular individuals .
Clearance
In a human study, the clearance rate for daidzein and genistein were 30.09 L/h and 21.85 L/h, respectively .
Some studies propose an estimated clearance rate for 1,25-dihydroxyvitamin D as 31 +/- 4 ml/min in healthy adults .
Elimination Route
Renal excretion is the predominant route of elimination for dietary isoflavones, where approximately 10-60% of total administered dose is excreted in urine . Glucuronide conjugates account for the majority (70-90%) of the isoflavone content in urine, followed by sulphate conjugates (10-25%) and aglycone forms (1-10%) . Fecal excretion is minimal, which accounts for 1-4% of the dietary isoflavone ingested .
The primary excretion route of vitamin D is via the bile into the feces .
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