O Desmethylangolensin

• Mild antioxidant
• Mild anti-inflammatory
• Potential anticancer properties
• Cardiovascular support

• Bone health
• Menopausal symptom relief
• Metabolic regulation
• Gut health

O-Desmethylangolensin (O-DMA) is a metabolite formed during the biotransformation of the soy isoflavone daidzein by gut microbiota. Its biological activities and mechanisms of action are distinct from both its parent compound daidzein and the alternative metabolite equol. The formation of O-DMA represents an alternative metabolic pathway for daidzein, occurring primarily in individuals who do not produce equol (non-equol producers). This transformation involves the cleavage of the C-ring of daidzein by specific gut bacteria, resulting in a non-isoflavonoid structure.

Several bacterial species have been identified as capable of this conversion, including members of the genera Eubacterium, Clostridium, and Bacteroides. The ability to produce O-DMA varies among individuals based on their gut microbiome composition, diet, and other factors, with approximately 80-90% of adults being O-DMA producers. Unlike equol, which maintains an isoflavone structure similar to estradiol, O-DMA has a significantly altered structure that results in different biological activities. The structural changes in O-DMA compared to daidzein include the opening of the heterocyclic C-ring, resulting in a non-isoflavonoid structure with a 2-(4-hydroxyphenyl)propionic acid configuration.

This structural alteration significantly reduces its estrogenic activity compared to daidzein or equol. As a phytoestrogen metabolite, O-DMA demonstrates very weak estrogenic activity, with significantly lower binding affinity for estrogen receptors (ERs) compared to daidzein or equol. Its binding affinity for both ER-α and ER-β is estimated to be less than 1% of that of estradiol. This weak estrogenic activity suggests that O-DMA’s biological effects are primarily mediated through non-estrogenic mechanisms.

O-DMA exhibits mild antioxidant properties, though its antioxidant capacity is generally lower than that of daidzein or equol. It can scavenge some reactive oxygen species (ROS) and free radicals, primarily through its phenolic hydroxyl group. The structural changes resulting from the C-ring cleavage significantly alter its antioxidant capacity compared to daidzein. O-DMA demonstrates mild anti-inflammatory effects through partial inhibition of inflammatory pathways.

It may reduce the production of pro-inflammatory cytokines including tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), though these effects are generally weaker than those of daidzein or equol. It may also inhibit cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression to a limited extent. In cardiovascular health, O-DMA may contribute to modest improvements in lipid profiles and vascular function, though these effects are likely less pronounced than those of daidzein or equol. It may help reduce total cholesterol and low-density lipoprotein (LDL) cholesterol while potentially increasing high-density lipoprotein (HDL) cholesterol, though the clinical significance of these effects remains uncertain.

For bone health, O-DMA may help inhibit osteoclast differentiation and activity to a limited extent, potentially contributing to reduced bone resorption. These effects are likely mediated through non-estrogenic mechanisms, as O-DMA’s estrogenic activity is very weak. The bone-protective effects of O-DMA are generally considered to be less potent than those of equol. In metabolic regulation, O-DMA may contribute to modest improvements in insulin sensitivity and glucose metabolism, though these effects are likely less pronounced than those of daidzein or equol.

It may help activate adenosine monophosphate-activated protein kinase (AMPK) in skeletal muscle and liver to a limited extent, leading to increased glucose uptake and reduced gluconeogenesis. O-DMA has demonstrated potential anticancer properties in preclinical studies, though the mechanisms are not fully understood. It may inhibit cancer cell proliferation, induce apoptosis, and reduce angiogenesis and metastasis to some extent. These effects are likely mediated through multiple pathways, including inhibition of tyrosine kinases, modulation of cell cycle regulators, and reduction of inflammatory mediators.

The anticancer effects of O-DMA are generally considered to be less potent than those of genistein or equol. The pharmacokinetics of O-DMA are complex and influenced by various factors. After formation in the intestine from daidzein, O-DMA can be absorbed into the bloodstream or excreted in the feces. Absorbed O-DMA undergoes phase II metabolism in the liver, primarily through glucuronidation and sulfation, forming conjugates that are more water-soluble and readily excreted in urine.

The plasma half-life of O-DMA is relatively long compared to daidzein or equol, estimated at approximately 20-24 hours based on limited studies. This longer half-life may allow for more sustained biological effects despite its lower potency. The biological effects of O-DMA are thus a combination of its direct actions through both estrogenic and non-estrogenic mechanisms, though its potency is generally lower than that of daidzein or equol. The overall health benefits associated with O-DMA formation (via daidzein intake) may therefore vary significantly between individuals based on their gut microbiome composition and ability to produce O-DMA versus equol.

O-Desmethylangolensin (O-DMA) is not typically available as a direct supplement but is formed in the body as a metabolite of daidzein through gut microbiota activity. Therefore, dosage recommendations focus on daidzein intake to promote O-DMA formation. Based on the available research and typical consumption patterns in Asian populations with high soy intake, the following dosage ranges for daidzein can be considered to promote O-DMA formation: For total soy isoflavones (typically containing 30-40% daidzein), the common dosage range is 40-100 mg daily, corresponding to approximately 12-40 mg of daidzein, which can lead to variable amounts of O-DMA depending on individual gut microbiota. For soy protein isolate (typically containing 1-3 mg daidzein per 100g), typical dosages range from 15-30 g daily, corresponding to approximately 0.15-0.9 mg of daidzein.

For fermented soy products (which may have higher bioavailability), typical dosages would provide approximately 5-20 mg of daidzein daily. It’s important to note that the conversion of daidzein to O-DMA can vary significantly between individuals based on gut microbiome composition, diet, and other factors. Some individuals may convert a higher percentage of daidzein to O-DMA, while others may convert daidzein to equol instead. Approximately 80-90% of adults are O-DMA producers, while only 30-50% are equol producers.

For most health applications, consistent daily intake of daidzein-containing foods or supplements is recommended to maintain steady levels of O-DMA. Divided doses (2-3 times daily) may be preferred due to the relatively long half-life of O-DMA (approximately 20-24 hours based on limited studies), though consistent daily intake is likely more important than specific timing within the day.

O-Desmethylangolensin (O-DMA) is not typically consumed directly but is formed in the intestine as a metabolite of daidzein through gut microbiota activity. The formation and subsequent absorption of O-DMA depend on several factors, including the individual’s gut microbiome composition, diet, and intestinal transit time. The conversion of daidzein to O-DMA represents an alternative metabolic pathway to equol production. This conversion is performed by specific gut bacteria, including members of the genera Eubacterium, Clostridium, and Bacteroides.

The efficiency of this conversion varies significantly among individuals, with approximately 80-90% of adults being O-DMA producers, while only 30-50% are equol producers. Some individuals may produce both O-DMA and equol, while others may produce primarily one or the other. Once formed in the intestine, O-DMA can be absorbed into the bloodstream or excreted in the feces. The absorption of O-DMA from the intestine into the bloodstream is estimated to be moderate to high, with approximately 40-60% of formed O-DMA being absorbed based on limited studies.

The absorption occurs primarily through passive diffusion across the intestinal epithelium, facilitated by O-DMA’s relatively small molecular size and moderate lipophilicity resulting from the C-ring cleavage. After absorption, O-DMA undergoes phase II metabolism in the liver, primarily through glucuronidation and sulfation, forming conjugates that are more water-soluble and readily excreted in urine. These conjugates may be less biologically active than free O-DMA, though some evidence suggests they can be deconjugated in target tissues, releasing the active compound. The plasma half-life of O-DMA is relatively long compared to daidzein or equol, estimated at approximately 20-24 hours based on limited studies.

This longer half-life may allow for more sustained biological effects despite its lower potency. The bioavailability of O-DMA (via daidzein intake) is influenced by various factors, including the food matrix, processing methods, and individual factors such as gut microbiome composition, intestinal transit time, and genetic factors affecting metabolic enzymes. Fermented soy products (like tempeh, miso, and natto) may lead to higher O-DMA formation and absorption compared to non-fermented soy products, as fermentation can convert some of the glycoside forms of isoflavones to more bioavailable aglycone forms and may introduce bacteria that facilitate the conversion of daidzein to O-DMA.

Probiotic supplementation – certain probiotic strains (Eubacterium, Clostridium, Bacteroides) can enhance the conversion of daidzein to O-DMA, potentially increasing its formation by 1.5-3 fold, Fermented soy products – fermentation processes can enhance the conversion of daidzein to O-DMA, potentially increasing its formation by 2-4 fold compared to non-fermented soy products, Prebiotic fiber – certain prebiotic fibers can promote the growth of bacteria capable of converting daidzein to O-DMA, potentially enhancing its formation, Consistent daily intake – regular consumption of daidzein-containing foods or supplements can help maintain the gut microbiota capable of converting daidzein to O-DMA, Dietary polyphenols – certain polyphenols may enhance the activity of gut bacteria involved in daidzein metabolism, potentially increasing O-DMA formation, Reduced intestinal transit time – factors that reduce intestinal transit time may allow more time for gut bacteria to convert daidzein to O-DMA, Avoiding broad-spectrum antibiotics – antibiotics can disrupt the gut microbiota capable of converting daidzein to O-DMA, reducing its formation, Avoiding high-fat meals – high-fat meals may reduce the conversion of daidzein to O-DMA by altering gut microbiota activity, Avoiding excessive alcohol consumption – excessive alcohol can disrupt the gut microbiota capable of converting daidzein to O-DMA, Maintaining a diverse, plant-rich diet – a diverse diet rich in plant foods can promote a healthy gut microbiome capable of efficiently converting daidzein to O-DMA

Since O-DMA is not typically consumed directly but is formed in the body from daidzein, timing recommendations focus on daidzein intake to optimize O-DMA formation and absorption. Consistent daily intake of daidzein-containing foods or supplements is recommended to maintain the gut microbiota capable of converting daidzein to O-DMA and to ensure steady levels of O-DMA. Due to the relatively long half-life of O-DMA (estimated at 20-24 hours based on limited studies), once-daily dosing of daidzein-containing foods or supplements may be sufficient for maintaining steady levels, though divided doses may still be beneficial for optimizing daidzein absorption. Consuming daidzein-containing foods or supplements with meals containing some fat may enhance the absorption of daidzein and subsequently the formation of O-DMA, though excessive fat should be avoided as it may negatively impact gut microbiota activity.

For cardiovascular support, consistent daily intake of daidzein-containing foods or supplements is recommended, with some evidence suggesting that morning intake may be particularly beneficial for blood pressure regulation, though more research is needed. For menopausal symptom relief, consistent daily intake of daidzein-containing foods or supplements is recommended, with some women reporting better results when consuming isoflavones in the morning for hot flashes that occur during the day, or in the evening for night sweats. For bone health, consistent daily intake of daidzein-containing foods or supplements is important, as these effects develop gradually over time with regular use. For metabolic regulation, consistent daily intake of daidzein-containing foods or supplements is recommended, with some evidence suggesting that consuming isoflavones with meals may help reduce postprandial glucose spikes, though more research is needed.

The timing of daidzein intake relative to other medications should be considered, as isoflavones may interact with certain drugs, particularly those affecting hormone levels or those metabolized by the same enzymes. In general, separating daidzein intake from other medications by at least 2 hours is recommended to minimize potential interactions.

• Not typically consumed directly but formed as a metabolite of daidzein; side effects are generally associated with daidzein or soy isoflavone intake
• Gastrointestinal discomfort (mild to moderate, common with high soy isoflavone intake)
• Nausea (uncommon with moderate soy isoflavone intake)
• Menstrual changes in women (rare, due to very weak phytoestrogenic effects of O-DMA)
• Allergic reactions (rare, particularly in individuals with soy allergies)
• Mild headache (uncommon with moderate soy isoflavone intake)
• Skin rash (rare with moderate soy isoflavone intake)
• Mild insomnia (rare with moderate soy isoflavone intake)
• Constipation or diarrhea (uncommon with moderate soy isoflavone intake)

• Pregnancy and breastfeeding (due to insufficient safety data on isoflavone metabolites)
• Hormone-sensitive conditions including hormone-dependent cancers (breast, uterine, ovarian) due to potential phytoestrogenic effects, though O-DMA has very weak estrogenic activity
• Individuals with soy allergies (for soy-derived daidzein that leads to O-DMA formation)
• Individuals with severe liver disease (due to potential effects on liver enzymes involved in isoflavone metabolism)
• Individuals scheduled for surgery (discontinue soy isoflavone supplements 2 weeks before due to potential effects on blood clotting)
• Children and adolescents (high-dose isoflavone supplementation due to potential hormonal effects during development)
• Individuals with thyroid disorders (isoflavones may affect thyroid function in susceptible individuals)
• Individuals with estrogen receptor-positive breast cancer or a history of such cancer (due to potential estrogenic effects of isoflavones, though O-DMA has very weak estrogenic activity)
• Individuals with endometriosis or uterine fibroids (conditions that may be estrogen-sensitive)
• Individuals with a history of kidney stones (some studies suggest isoflavones may increase risk in susceptible individuals)

• Hormone replacement therapy and hormonal contraceptives (isoflavones and their metabolites may interfere with or enhance effects due to phytoestrogenic activity, though O-DMA has very weak estrogenic activity)
• Tamoxifen and other selective estrogen receptor modulators (SERMs) (potential competitive binding to estrogen receptors by isoflavones and their metabolites, though O-DMA has very weak binding affinity)
• Anticoagulant and antiplatelet medications (isoflavones and their metabolites may enhance antiplatelet effects, potentially increasing bleeding risk)
• Cytochrome P450 substrates (isoflavones may affect the metabolism of drugs that are substrates for CYP1A2, CYP2C9, and CYP3A4)
• Thyroid medications (isoflavones may affect thyroid function in susceptible individuals)
• Antidiabetic medications (isoflavones and their metabolites may enhance blood glucose-lowering effects)
• Drugs metabolized by UDP-glucuronosyltransferases (UGTs) (potential competition for these enzymes involved in isoflavone metabolism)
• Drugs with narrow therapeutic indices (warfarin, digoxin, etc.) require careful monitoring due to potential interactions with isoflavones
• Aromatase inhibitors (isoflavones may counteract the effects of these drugs used in breast cancer treatment, though O-DMA has very weak estrogenic activity)
• Antibiotics (may disrupt gut microbiota capable of converting daidzein to O-DMA)

O-DMA is not typically consumed directly but is formed in the body as a metabolite of daidzein through gut microbiota activity. Therefore, upper limits focus on daidzein or total soy isoflavone intake. Based on available research and safety data, the upper limit for total soy isoflavone intake is generally considered to be 100-150 mg daily for most adults, corresponding to approximately 30-60 mg of daidzein. This level of intake is unlikely to cause significant adverse effects in most healthy adults.

The Japanese Ministry of Health, Labour and Welfare has established an upper limit for soy isoflavone consumption at 70-75 mg/day (as aglycone equivalents) for food supplements, which would correspond to approximately 21-30 mg of daidzein. Higher doses may increase the risk of hormonal effects and drug interactions, particularly in sensitive individuals. For general health maintenance, doses exceeding these levels are not recommended without medical supervision. The safety profile of O-DMA (via daidzein intake) is generally favorable at recommended doses, with most side effects being mild and transient.

The very weak estrogenic activity of O-DMA compared to daidzein or equol may actually contribute to its favorable safety profile, particularly in hormone-sensitive conditions. However, the potential for drug interactions necessitates caution, particularly with long-term use or in vulnerable populations. Individuals with hormone-sensitive conditions, thyroid disorders, or those taking medications with potential interactions should consult healthcare providers before using soy isoflavone supplements. The long-term safety of high-dose isoflavone supplementation has not been fully established, though the weak estrogenic activity of O-DMA suggests lower risk compared to more potent phytoestrogens.

Some regulatory authorities have expressed caution about long-term, high-dose isoflavone supplementation in certain populations, such as women with a history or family history of breast cancer. It’s worth noting that traditional soy food consumption, which provides moderate amounts of isoflavones (typically 25-50 mg/day in Asian populations with high soy intake), has a long history of safe use and is associated with various health benefits in epidemiological studies. Moderate consumption of traditional soy foods as part of a balanced diet is generally considered safe for most individuals.

O-Desmethylangolensin (O-DMA) is not directly regulated by the FDA as it is not typically available as a supplement but is formed in the body as a metabolite of daidzein through gut microbiota activity. The regulatory status primarily pertains to daidzein and soy isoflavones. In the United States, soy isoflavone extracts containing daidzein are regulated as dietary supplements under the Dietary Supplement Health and Education Act (DSHEA) of 1994. Manufacturers cannot make specific disease treatment claims but may make general structure/function claims with appropriate disclaimers.

The FDA has not evaluated the safety or efficacy of O-DMA specifically. In 1999, the FDA authorized a health claim for soy protein and coronary heart disease, stating that ’25 grams of soy protein a day, as part of a diet low in saturated fat and cholesterol, may reduce the risk of heart disease.’ However, in 2017, the FDA proposed to revoke this health claim based on inconsistent findings from recent studies. This proposed revocation is still under review. Soy foods are generally recognized as safe (GRAS) when consumed in traditional amounts.

Eu: O-DMA is not specifically regulated in the European Union. Soy isoflavone extracts containing daidzein (which can be converted to O-DMA in the body) are primarily regulated as food supplements under the Food Supplements Directive (2002/46/EC). The European Food Safety Authority (EFSA) has evaluated several health claims related to soy isoflavones and has generally not found sufficient evidence to approve specific claims, particularly for menopausal symptoms and bone health. EFSA has expressed some caution regarding long-term, high-dose isoflavone supplementation in certain populations, such as women with a history or family history of breast cancer. In 2012, EFSA concluded that soy isoflavones do not adversely affect the breast, thyroid, or uterus in postmenopausal women when taken at doses of 35-150 mg/day for up to 30 months.

Uk: O-DMA is not specifically regulated in the United Kingdom. Soy isoflavone extracts containing daidzein are regulated as food supplements. They are not licensed as medicines and cannot be marketed with medicinal claims. The Medicines and Healthcare products Regulatory Agency (MHRA) has not issued specific guidance on O-DMA or soy isoflavones.

Canada: O-DMA is not specifically regulated in Canada. Health Canada regulates soy isoflavone extracts containing daidzein as Natural Health Products (NHPs). Several products containing soy isoflavones have been issued Natural Product Numbers (NPNs), allowing them to be sold with specific health claims, primarily related to menopausal symptom relief and bone health.

Australia: O-DMA is not specifically regulated in Australia. The Therapeutic Goods Administration (TGA) regulates soy isoflavone extracts containing daidzein as complementary medicines. Several products containing soy isoflavones are listed on the Australian Register of Therapeutic Goods (ARTG). Traditional use claims are permitted with appropriate evidence of traditional use.

Japan: O-DMA is not specifically regulated in Japan. Soy foods are recognized as part of the traditional diet and are widely consumed. Soy isoflavone extracts containing daidzein are available as Foods for Specified Health Uses (FOSHU) with approved health claims related to cholesterol reduction and bone health. The Ministry of Health, Labour and Welfare has established an upper limit for soy isoflavone consumption at 70-75 mg/day (as aglycone equivalents) for food supplements.

China: O-DMA is not specifically regulated in China. Soy foods are recognized as part of the traditional diet and are widely consumed. Soy isoflavone extracts containing daidzein are regulated as health foods and can be marketed with approved health claims after evaluation by the China Food and Drug Administration (CFDA).

Korea: O-DMA is not specifically regulated in South Korea. Soy foods are recognized as part of the traditional diet and are widely consumed. Soy isoflavone extracts containing daidzein are regulated as health functional foods and can be marketed with approved health claims after evaluation by the Ministry of Food and Drug Safety (MFDS).

Low to Medium (for daidzein sources)

O-Desmethylangolensin (O-DMA) is not typically available as a direct supplement but is formed in the body as a metabolite of daidzein through gut microbiota activity. Therefore, cost considerations focus on daidzein sources. Standardized soy isoflavone extracts (containing 30-40% daidzein) typically cost $0.30-$1.00 per day for basic extracts (40-100 mg daily, corresponding to approximately 12-40 mg of daidzein) and $1.00-$2.00 per day for premium, highly standardized formulations. Soy protein isolate (containing daidzein) typically costs $0.20-$0.50 per day for basic products (15-30 g daily) and $0.50-$1.00 per day for premium formulations.

Fermented soy products (tempeh, miso, natto) typically cost $0.50-$2.00 per serving, providing variable amounts of daidzein with enhanced bioavailability. Whole soy foods (tofu, edamame, soy milk) typically cost $0.30-$1.00 per serving, providing variable amounts of daidzein. Probiotic supplements that may enhance the conversion of daidzein to O-DMA typically cost $0.50-$2.00 per day for basic products and $2.00-$4.00 per day for premium formulations. For research purposes, high-purity isolated O-DMA (>95%) is available from specialized chemical suppliers at costs ranging from $200-$500 per gram, though these are not intended for supplementation.

The value of O-DMA (via daidzein intake) varies significantly between individuals based on their gut microbiome composition and ability to convert daidzein to O-DMA versus equol. For cardiovascular support, O-DMA (via daidzein intake) offers moderate value. Epidemiological studies have associated high soy consumption with reduced cardiovascular risk, though the specific contribution of O-DMA to these effects is unclear. The conversion of daidzein to O-DMA may contribute to the cardiovascular benefits of soy isoflavones, particularly in non-equol producers.

When compared to other cardiovascular supplements, soy isoflavones are inexpensive and offer a reasonable option for general cardiovascular support. For menopausal symptom relief, O-DMA (via daidzein intake) offers limited to moderate value. Clinical studies on soy isoflavones have shown modest benefits for vasomotor symptoms, though results have been inconsistent. The very weak estrogenic activity of O-DMA suggests that it may contribute less to these benefits than equol in equol producers.

When compared to other natural approaches for menopausal symptoms, soy isoflavone extracts are inexpensive but may be less effective for individuals who produce O-DMA but not equol. For bone health, O-DMA (via daidzein intake) offers limited to moderate value. Epidemiological studies have associated high soy consumption with better bone health, particularly in Asian populations. The limited bone-protective effects of O-DMA suggest that it may contribute less to these benefits than equol in equol producers.

When compared to other bone health supplements, soy isoflavones are inexpensive but may be less effective for individuals who produce O-DMA but not equol. For anti-inflammatory support, O-DMA (via daidzein intake) offers moderate value. Preclinical studies have demonstrated mild anti-inflammatory effects of O-DMA, though these effects are generally weaker than those of daidzein or equol. When compared to other anti-inflammatory supplements, soy isoflavones are inexpensive and offer a reasonable option for general anti-inflammatory support.

For metabolic regulation, O-DMA (via daidzein intake) offers moderate value. Some studies have associated soy consumption with improved insulin sensitivity and glucose metabolism, though the specific contribution of O-DMA to these effects is not well-established. When compared to other supplements for metabolic health, soy isoflavones are inexpensive and offer a reasonable option for general metabolic support. When comparing the cost-effectiveness of different sources of daidzein (which can be converted to O-DMA): Whole soy foods (tofu, edamame, soy milk) offer the best value for general health maintenance, providing daidzein along with protein, fiber, and other beneficial nutrients.

Fermented soy products (tempeh, miso, natto) offer good value, providing daidzein in a more bioavailable form due to fermentation, along with beneficial bacteria that may enhance its conversion to O-DMA. Standardized soy isoflavone extracts offer a convenient option for those seeking specific dosages of daidzein, though they lack the additional nutritional benefits of whole soy foods. Soy protein isolate offers a good balance of protein and isoflavones, though the isoflavone content can vary significantly between products. Combining daidzein sources with probiotics that enhance its conversion to O-DMA may offer the best value for those seeking the specific benefits associated with O-DMA, though this approach is more expensive than daidzein sources alone.

Individual variation in daidzein metabolism significantly affects the value proposition of daidzein supplementation. O-DMA producers who are not equol producers (approximately 50-60% of adults) may derive different benefits from daidzein intake compared to equol producers (approximately 30-50% of adults) or individuals who produce both O-DMA and equol.

O-Desmethylangolensin (O-DMA) is not typically available as a direct supplement but is formed in the body as a metabolite of daidzein through gut microbiota activity. Therefore, stability information focuses on daidzein sources and O-DMA stability in research settings. Pure O-DMA (for research purposes) has moderate stability, with a typical shelf life of 1-2 years when properly stored at -20°C under inert gas. At room temperature, its stability is significantly reduced, with a shelf life of approximately 3-6 months when protected from light, heat, and moisture.

The non-isoflavonoid structure of O-DMA, resulting from the C-ring cleavage of daidzein, may make it less susceptible to certain degradation pathways compared to daidzein, though it may be more susceptible to oxidation at certain positions. Standardized soy isoflavone extracts containing daidzein (the precursor to O-DMA) typically have a shelf life of 1-2 years from the date of manufacture when properly stored. Soy protein isolates and other processed soy products containing daidzein typically have a shelf life of 1-2 years when properly stored. Fermented soy products (tempeh, miso, natto) have varying shelf lives depending on the specific product and storage conditions, ranging from a few days for fresh tempeh to several months or years for properly stored miso and natto.

In biological samples (plasma, urine, feces), O-DMA has moderate stability, with significant degradation occurring within 48-72 hours at room temperature or 7-10 days when refrigerated. For research purposes, biological samples containing O-DMA should be stored at -80°C for long-term stability.

For research-grade pure O-DMA, storage under inert gas (nitrogen or argon) at -20°C is recommended for maximum stability. Protect from light, heat, oxygen, and moisture, which can accelerate degradation. For soy isoflavone supplements containing daidzein (the precursor to O-DMA), store in a cool, dry place away from direct sunlight in airtight, opaque containers. Refrigeration can extend shelf life of extracts containing daidzein.

For fermented soy products, follow specific storage recommendations for each product (e.g., refrigeration for tempeh, cool and dry storage for miso). For biological samples containing O-DMA (for research purposes), storage at -80°C is recommended for long-term stability. For short-term storage (up to 10 days), refrigeration at 4°C may be acceptable. The addition of antioxidants such as ascorbic acid or butylated hydroxytoluene (BHT) to research samples can help prevent oxidation and extend stability of O-DMA.

Avoid repeated freeze-thaw cycles for research samples containing O-DMA, as this can accelerate degradation. For long-term storage of research samples, aliquoting before freezing is recommended to minimize freeze-thaw cycles.

Exposure to oxygen – leads to oxidation, particularly at the phenolic hydroxyl group, Exposure to UV light and sunlight – causes photodegradation of the phenolic structure, High temperatures (above 30°C) – accelerates decomposition and oxidation, Moisture – promotes hydrolysis and microbial growth, particularly in liquid formulations and fermented soy products, pH extremes – O-DMA is most stable at slightly acidic to neutral pH (5-7), with increased degradation in strongly acidic or alkaline conditions, Metal ions (particularly iron and copper) – can catalyze oxidation reactions, Enzymatic activity – certain enzymes can further metabolize O-DMA to other compounds, Microbial contamination – particularly relevant for fermented soy products and research samples, can lead to further metabolism or degradation of O-DMA, Repeated freeze-thaw cycles – can accelerate degradation in research samples, Long-term storage at room temperature – leads to gradual degradation even when protected from other degradation factors

Synthesis Methods

Natural Sources

Quality Considerations

O-Desmethylangolensin (O-DMA) itself was not identified or isolated until the modern era and has no direct historical usage as a supplement or medicine. It is a metabolite formed during the biotransformation of the soy isoflavone daidzein by gut microbiota. Therefore, its historical context is primarily related to the traditional consumption of soy and fermented soy products, which contain daidzein that can be converted to O-DMA in the body. Soybeans (Glycine max) have been cultivated in China for over 5,000 years, with the earliest documented use dating back to around 2838 BCE during the reign of Emperor Shennong, who is credited with introducing various agricultural practices and herbal medicines to ancient China.

Soybeans were considered one of the five sacred grains (along with rice, wheat, barley, and millet) essential for sustaining Chinese civilization. The traditional processing of soybeans into various food products, including tofu, tempeh, miso, natto, and soy milk, developed over centuries as methods to improve palatability, digestibility, and shelf life. These processing methods, particularly fermentation, inadvertently enhanced the bioavailability of isoflavones like daidzein by converting their glycoside forms to more bioavailable aglycone forms. Fermentation may also have led to the formation of small amounts of O-DMA and other metabolites directly in the food products.

In traditional Chinese medicine (TCM), soybeans were classified as a ‘neutral’ food with properties that could balance the body’s energy. They were recommended for strengthening the spleen and stomach, promoting fluid production, and detoxifying the body. Soy foods were also traditionally used to support lactation in nursing mothers and to promote overall health and longevity. Fermented soy products like tempeh, miso, and natto have been staples in East Asian diets for centuries.

Tempeh originated in Indonesia, with the earliest known reference dating back to the early 19th century, though it likely existed much earlier. Miso has been produced in Japan since at least the 8th century, evolving from earlier fermented soybean pastes introduced from China. Natto has been consumed in Japan since at least the 11th century and was traditionally valued for its unique flavor and health benefits. The introduction of soybeans to the Western world occurred relatively recently, with significant cultivation in the United States beginning only in the early 20th century.

Initially grown primarily for animal feed and industrial uses, soybeans gradually gained acceptance as a human food source in Western diets, particularly with the rise of vegetarianism and interest in Asian cuisines. The scientific discovery and characterization of O-DMA as a metabolite of daidzein occurred in the late 20th century, with significant advances in the 1980s and 1990s as analytical techniques improved. Researchers identified O-DMA as a major metabolite of daidzein produced by gut microbiota, particularly in individuals who do not produce equol. The identification of O-DMA and other isoflavone metabolites helped explain the significant inter-individual variation in responses to soy isoflavone consumption observed in clinical studies.

This led to the concept of ‘metabolic phenotypes’ as an important factor in determining the health benefits of soy consumption. In recent decades, research on O-DMA has expanded to include its potential biological activities and role in the overall health effects of soy isoflavones. While most research has focused on equol as the more bioactive metabolite of daidzein, there is growing interest in O-DMA itself as a bioactive compound with potential health benefits, particularly given that a higher percentage of individuals produce O-DMA compared to equol. Today, O-DMA is recognized primarily as a metabolic intermediate and biomarker of daidzein metabolism, rather than as a direct supplement or medicine.

Its presence in the body after soy consumption is used in research settings to assess isoflavone metabolism and may be related to the health benefits associated with soy consumption, particularly in individuals who do not produce equol.

Research on the gut microbiota involved in the conversion of daidzein to O-DMA, including the identification of specific bacterial species and enzymes, Studies on factors affecting the conversion of daidzein to O-DMA versus equol, including diet, antibiotics, and probiotics, Investigations into the biological activities of O-DMA compared to daidzein and equol, including its estrogenic, antioxidant, and anti-inflammatory effects, Research on the potential health benefits of O-DMA and its role in the overall health effects of soy isoflavones, Studies on the pharmacokinetics and metabolism of O-DMA in humans, including its absorption, distribution, metabolism, and excretion, Investigations into the potential use of O-DMA as a biomarker for gut microbiota composition and function, Research on the relationship between O-DMA producer status and various health outcomes, including cancer risk, cardiovascular disease, and bone health