Women Who Can’t Convert Soy to ODMA Show Higher Blood Pressure, Study Finds

A compound most people have never heard of may quietly shape cardiovascular risk for millions of women who eat soy. New research published in BMC Cardiovascular Disorders by Childs H and colleagues finds that women whose gut bacteria cannot convert the soy isoflavone daidzein into O-desmethylangolensin (ODMA) show significantly higher systolic blood pressure than women who can make that conversion. The difference, 7.6 mmHg on average, is clinically meaningful and adds to growing evidence that gut microbial function, not just diet, drives cardiovascular outcomes.

ODMA non-producers show 7.6 mmHg higher systolic blood pressure

The central finding is specific: women classified as ODMA non-producers had adjusted mean systolic blood pressure 7.6 mmHg higher than high producers (95% CI: 1.1 to 14.1, p=0.02). A 7 to 8 mmHg difference in systolic pressure is not trivial; that range overlaps with the effect size seen in some antihypertensive medications at modest doses. Non-producers also showed a non-significant trend toward higher fasting serum glucose, with an adjusted mean difference of 6.1 mg/dL (CI: -0.9 to 13.2, p=0.09), suggesting a broader metabolic pattern that will need larger studies to confirm.

ODMA is produced when specific gut bacteria metabolize daidzein, an isoflavone found in soy foods and supplements. As a 2017 review in Advances in Nutrition explains, individuals can be sorted into producers and non-producers based on their gut microbiome composition, and not everyone who eats soy ends up with ODMA in circulation. The current study operationalized this by measuring the ratio of urinary ODMA to urinary daidzein: a ratio of zero meant non-producer, a ratio below 0.5 meant low producer, and above 0.5 meant high producer.

Cardiovascular implications for midlife women eating soy

The study population came from the Study of Women's Health Across the Nation (SWAN), a well-characterized cohort of diverse U.S. women in midlife. The 148 participants included in this analysis all reported consuming isoflavones through diet or supplements, which is an important design choice: it restricted the comparison to women who were actually exposed to daidzein, making metabotype the variable of interest rather than dietary habit.

For midlife women, blood pressure trajectories matter enormously. Systolic pressure tends to rise after menopause, and the women in this study spanned the menopausal transition. If the capacity to produce ODMA is one factor modulating that trajectory, the implications stretch well beyond individual soy intake. Prior animal and ex vivo work supports the plausibility of the mechanism: research on vascular effects of O-DMA found that the metabolite can relax isolated arteries and reduce arterial blood pressure directly, suggesting a genuine physiological pathway rather than a statistical artifact.

How the SWAN subset study isolated metabotype effects

Classifying participants required measuring urinary ODMA and daidzein concentrations using HPLC-MS-MS, a precise mass spectrometry method that distinguishes these structurally similar compounds reliably. The 148-woman sample was drawn from the larger SWAN cohort, and multivariable linear regression models adjusted for age, race, self-reported health, blood pressure medication use, smoking, menopausal status, and anthropometry. Controlling for blood pressure medication use is particularly important here: it ensures the blood pressure difference reflects underlying physiology rather than a disparity in treatment access or adherence.

The three-group metabotype classification (non-producers, n=23; low producers, n=90; high producers, n=35) reflects a realistic distribution. Roughly 15 to 25 percent of soy consumers are thought to be ODMA non-producers, depending on the population, so the 23 non-producers in this sample are proportionally plausible. The comparison that drove the significant blood pressure result was non-producers versus high producers, which represents the two ends of the metabolic spectrum.

Open questions about sample size and population breadth

With 148 participants total and only 23 non-producers, the study is underpowered to detect modest effects on secondary outcomes, which is the most likely explanation for the glucose trend that fell short of significance. The confidence interval on the systolic blood pressure finding (1.1 to 14.1 mmHg) is wide, spanning nearly 13 points, and reflects genuine uncertainty about the true effect size. As broader reviews of gut microbiome cardiovascular research have noted, small observational samples with heterogeneous methods make definitive conclusions difficult, and this study is no exception.

The SWAN cohort, while racially diverse, is still a U.S.-based sample of midlife women, so generalizability to younger women, men, or non-Western populations is unclear. The authors acknowledge that more research is needed to confirm these relationships across other populations. Residual confounding is also possible: women with different gut microbiome compositions may differ in other dietary or lifestyle factors that were not fully captured in the models.

Gut microbiome modulation as a possible next target

The findings point toward a practical question: if the gut microbiome determines whether soy isoflavones produce a cardiovascular benefit, can that microbiome be shifted? Therapeutic strategies targeting the gut microbiota, including probiotics, dietary interventions, and nutraceuticals, represent an active area of investigation for cardiovascular disease prevention. Identifying the specific bacterial taxa responsible for ODMA production would be a necessary first step toward any targeted intervention.

For now, this study adds a concrete data point to the broader picture of how gut microbial function shapes cardiovascular risk in women. The 7.6 mmHg blood pressure difference between ODMA non-producers and high producers, observed in a real-world diverse cohort with careful statistical controls, is the kind of signal that justifies larger replication studies. Soy is not a blood pressure drug, but the bacteria that process it may eventually inform who benefits most from eating it.

Evidence rating

EMERGING — 80/100

Caveats:

• Observational design — shows association, not causation; diet, lifestyle, and unmeasured confounders could explain the blood pressure difference.
• Small sample: only 23 non-producers vs. 35 high-producers among 148 women, limiting statistical power and generalizability.
• Restricted to women who consumed isoflavones; findings may not apply to people with low soy intake or to men.
• Funding was not disclosed by the authors, so potential conflicts of interest cannot be fully assessed.
• Not yet independently replicated; the authors themselves note that more work in other populations is needed.

Cross-sectional observational study drawing on SWAN cohort data (n=148 isoflavone-consuming women). Demonstrates an association between gut microbial ODMA-producer metabotype and lower systolic blood pressure, but cannot establish causation. The non-producer subgroup is small (n=23), and the finding has not yet been independently replicated in a separate population.