The Gut-Heart Connection

The gut–heart connection is a real and active field of research. It is also one where the honest version of the story is considerably more interesting than the version you usually get sold.

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So here is the honest version. We sell a probiotic, which means you should read what follows with an appropriate amount of suspicion — and it also means we have gone and read the primary literature rather than the summaries of the summaries. Some of what we found supports the popular story. A fair amount of it does not.

What is genuinely established: inflammation matters

Start with the part that is not in dispute. Chronic low-grade inflammation really is causally involved in cardiovascular disease, and we know that because the causal experiment has been run three separate times.

In CANTOS, 10,061 people who had already had a heart attack received an antibody targeting interleukin-1β. The drug did not touch their cholesterol — “canakinumab did not reduce lipid levels from baseline” — and it still reduced recurrent cardiovascular events, “independent of lipid-level lowering”¹. Two later trials of low-dose colchicine, COLCOT (4,745 patients) and LoDoCo2 (5,522 patients), found the same direction of effect^2,3.

That is about as clean a demonstration as cardiology gets: lower the inflammation, change the outcome, without changing the lipids.

Borrowing the biology of a drug trial to imply a benefit for a supplement is the single most common move in this corner of the internet. We are not going to make it.

What the probiotic research actually shows

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There is real research here. It is smaller than the headlines suggest, it is highly strain-specific, and its own authors are careful about it. All three of those things matter.

Blood lipids

The largest synthesis pooled 40 randomized trials and 2,795 people. It found a reduction in LDL cholesterol of about 5 mg/dL and in total cholesterol of about 8 mg/dL — the latter with substantial heterogeneity between studies. The authors’ own summary is worth quoting exactly: the evidence is described as “current preliminary evidence”, and they conclude that “large and well conducted RCTs are required to provide further convincing support for these results”⁴.

Earlier meta-analyses found effects in the same range, and both identified the effect as attaching to particular named strains rather than to probiotics in general^5,6. That is the crux of the whole thing, and we come back to it below.

Blood pressure

A meta-analysis in Hypertension found probiotic consumption changed systolic blood pressure by −3.56 mmHg and diastolic by −2.38 mmHg, concluding that probiotics “may improve BP by a modest degree, with a potentially greater effect when baseline BP is elevated, multiple species of probiotics are consumed, the duration of intervention is ≥8 weeks, or daily consumption dose is ≥10¹¹ colony-forming units”⁷. A later umbrella review of 14 meta-analyses and 15,494 participants found smaller effects again — about −1.96 mmHg systolic and −1.28 diastolic⁸.

Note the conditions in that first quotation. The effect is largest in people whose blood pressure is already elevated — which is to say, in people who have a diagnosed condition and should be under a doctor’s care, not reading a supplement blog.

The TMAO story, told properly

If you have read anything about gut bacteria and heart health in the last decade, you have met TMAO. It is the most-cited mechanism in the field and it makes a wonderfully tidy story: certain gut bacteria turn compounds in red meat and eggs into trimethylamine, your liver converts that to TMAO, and high TMAO tracks with cardiovascular risk.

The tidy story is built on real work. A 2011 Nature paper showed that feeding mice choline or TMAO “promoted atherosclerosis”¹¹, and a 2013 New England Journal of Medicine study of 4,007 patients found that higher plasma TMAO was associated with more major adverse cardiovascular events¹².

Then it gets complicated, in three ways that almost nobody mentions.

One: the fish problem

The largest dietary source of TMAO is not steak. It is fish — which contains it directly, in quantity, and which is about as close to universally accepted as cardioprotective as any food gets. A group of Norwegian researchers put the difficulty about as bluntly as scientists ever do:

That paper is titled, in full, “Microbial trimethylamine-N-oxide as a disease marker: something fishy?” Scientists do not often get to do that.

Two: it may largely be a kidney signal

A 2023 analysis in Nature Communications, drawing on a large European cohort, found that “next to age, kidney function is the primary variable predicting circulating TMAO, with microbiota composition and diet playing minor, albeit significant, roles”¹⁴. Since impaired kidney function is itself a powerful cardiovascular risk factor, a good deal of what looked like TMAO causing heart disease may be TMAO reporting on kidneys.

Three — and this is the one that matters most to us

Set aside the causality question entirely. Suppose TMAO does drive cardiovascular risk. There is still the small matter of whether taking a probiotic does anything to it.

A meta-analysis of 8 randomized controlled trials in 270 participants found that “probiotic supplementation has no significant effect on TMAO levels compared to the control group (WMD −0.08 µmol/L; 95% CI −0.76 to 0.60, P = 0.813)”, with subgroup analysis showing no significant effect in healthy or unhealthy participants either¹⁵.

The most scientific-sounding paragraph in most gut–heart articles is the one with the least behind it.

We are including all of this rather than quietly dropping the section, because a version of this article that kept the TMAO paragraph and cut the inconvenient parts would have been easier to write and worse to read.

Short-chain fatty acids and blood vessels: mind the species gap

The other mechanism you will see everywhere is short-chain fatty acids — the compounds your gut bacteria make when they ferment fiber. The vascular research on them is genuinely interesting and almost entirely in rodents.

The landmark study gave mice propionate in their drinking water at 200 mmol/L and found reduced cardiac hypertrophy, fibrosis and vascular dysfunction. Its authors were careful: the data “suggest that lifestyle modifications leading to augmented SCFA production could be a beneficial nonpharmacological preventive strategy”¹⁶. Suggest. Could be. Mice.

Two further things are worth being precise about. First, the human data is thin, and the one study that measured arterial stiffness and endothelial function directly found no change in either. Second — and this one applies to every fermented product on the shelf, including ours — the SCFAs in the vascular literature are produced in your colon from fiber, at concentrations orders of magnitude above anything a spoonful of liquid contains. The organic acids in a ferment are a real part of what a ferment is. They are not the same thing as colonic fermentation, and we are not going to pretend otherwise.

The problem underneath all of it

Every positive finding above attaches to specific named strains at specific doses. In the lipid literature the effects trace to organisms like L. reuteri NCIMB 30242 and particular L. plantarum strains^5,6. A strain is the designation after the species name, and it matters because two strains of the same species can behave completely differently.

Flourish declares its eleven organisms at species level — spanning nine genera under current taxonomy¹⁷ — with no strain designations. Which means, stated plainly: none of the published strain-level evidence transfers to our bottle, and there is no published clinical trial of Flourish. That is true of most multi-species products on the market, and it is a fair question to put to any of them, including us.

What actually helps, which is boring and well established

None of the above changes the genuinely useful advice, and the useful advice has never depended on a supplement.

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• Eat more plants and more fiber. Vegetables, legumes, whole grains, fruit. This is the intervention with by far the strongest evidence behind it, and it happens to feed your gut bacteria as a side effect rather than as a marketing angle.
• Eat fermented foods if you enjoy them. Yogurt, kefir, kimchi, sauerkraut, miso. Pleasant, traditional, and part of a normal diet.
• Move most days. Not heroically. Walking counts. Gardening counts.
• Manage stress and sleep. Both affect the gut and the cardiovascular system, and both are easier to say than to do.
• Do the medical basics. Know your numbers, take prescribed medication as prescribed, and do not stop anything because a website told you a supplement would cover it.

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Where Flourish fits

Flourish is a fermented living liquid — a probiotic and, under the fermentation definition of the term, a postbiotic¹⁸ — that some people like taking every day. It is not a cardiovascular product, we have not run a trial on it, and this article has not argued that it does anything for your heart.

What we will say is what FDA’s own rules allow us to say and what we can stand behind: it is a simple daily habit, it is easy to take because it is a liquid rather than a capsule, and the honest reason to drink it is that you want live cultures in your diet — not because a blog told you it would protect your arteries.

If that is a less exciting pitch than the one you were expecting from an article with this title, we would rather be the company that tells you that.

Sources

1. Ridker, P. M., Everett, B. M., Thuren, T., MacFadyen, J. G., Chang, W. H., Ballantyne, C., et al. (2017). Antiinflammatory therapy with canakinumab for atherosclerotic disease. New England Journal of Medicine, 377(12), 1119–1131 — 10,061 patients with previous myocardial infarction; “canakinumab did not reduce lipid levels from baseline”; anti-inflammatory therapy “led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering”; canakinumab “was associated with a higher incidence of fatal infection than was placebo” with no significant difference in all-cause mortality. Source
2. Tardif, J. C., Kouz, S., Waters, D. D., Bertrand, O. F., Diaz, R., Maggioni, A. P., et al. (2019). Efficacy and safety of low-dose colchicine after myocardial infarction. New England Journal of Medicine, 381(26), 2497–2505 — COLCOT; 4,745 patients; primary endpoint 5.5% versus 7.1% (hazard ratio 0.77; 95% CI 0.61–0.96). Source
3. Nidorf, S. M., Fiolet, A. T. L., Mosterd, A., Eikelboom, J. W., Schut, A., Opstal, T. S. J., et al. (2020). Colchicine in patients with chronic coronary disease. New England Journal of Medicine, 383(19), 1838–1847 — LoDoCo2; 5,522 patients; primary endpoint 6.8% versus 9.6% (hazard ratio 0.69; 95% CI 0.57–0.83). Source
4. Ghorbani, Z., Kazemi, A., U P Bartolomaeus, T., Martami, F., Noormohammadi, M., Salari, A., et al. (2023). The effect of probiotic and synbiotic supplementation on lipid parameters among patients with cardiometabolic risk factors: a systematic review and meta-analysis of clinical trials. Cardiovascular Research, 119(4), 933–956 — 40 randomized controlled trials, n = 2,795; LDL-C weighted mean difference −5.08 mg/dL (95% CI −7.61 to −2.56); total cholesterol −8.43 mg/dL with I² = 56.8%; “the current preliminary evidence… large and well conducted RCTs are required to provide further convincing support for these results.” Source
5. Wu, Y., Zhang, Q., Ren, Y., & Ruan, Z. (2017). Effect of probiotic Lactobacillus on lipid profile: a systematic review and meta-analysis of randomized, controlled trials. PLoS ONE, 12(6), e0178868 — 15 trials, 976 subjects; total cholesterol −0.26 mmol/L and LDL-C −0.23 mmol/L; effects identified with specific species, “significantly reduction of TC using L. plantarum and reduction of LDL-C using L. plantarum or L. reuteri.” Source
6. Kriaa, A., Bourgin, M., Potiron, A., Mkaouar, H., Jablaoui, A., Gérard, P., et al. (2019). Microbial impact on cholesterol and bile acid metabolism: current status and future prospects. Journal of Lipid Research, 60(2), 323–332 — a narrative review, largely rodent and in vitro; notes that studies focusing on bile salt hydrolase activity alone are “insufficient to justify a cholesterol-lowering effect of these strains,” and that the field “remains poorly studied.” The human data it cites is strain-specific — a yogurt containing Lactobacillus reuteri NCIMB 30242. Source
7. Khalesi, S., Sun, J., Buys, N., & Jayasinghe, R. (2014). Effect of probiotics on blood pressure: a systematic review and meta-analysis of randomized, controlled trials. Hypertension, 64(4), 897–903 — systolic blood pressure −3.56 mmHg (95% CI −6.46 to −0.66) and diastolic −2.38 mmHg; probiotics “may improve BP by a modest degree, with a potentially greater effect when baseline BP is elevated, multiple species of probiotics are consumed, the duration of intervention is ≥8 weeks, or daily consumption dose is ≥10(11) colony-forming units.” Source
8. Zarezadeh, M., Musazadeh, V., Ghalichi, F., Kavyani, Z., Nasernia, R., Parang, M., et al. (2023). Effects of probiotics supplementation on blood pressure: an umbrella meta-analysis of randomized controlled trials. Nutrition, Metabolism and Cardiovascular Diseases, 33(2), 275–286 — 14 meta-analyses, 15,494 participants; systolic weighted mean difference −1.96 mmHg and diastolic −1.28 mmHg. Source
9. US Food and Drug Administration (2000). Regulations on statements made for dietary supplements concerning the effect of the product on the structure or function of the body, 65 FR 999–1050 (6 January 2000) — “an appropriate structure/function claim for maintaining cholesterol would be ‘helps to maintain cholesterol levels that are already within the normal range’” and “FDA continues to believe that ‘lowers cholesterol,’ however qualified, is an implied disease claim… lowering cholesterol is inextricably linked in the public mind with treating elevated cholesterol and preventing heart disease” (65 FR 1019); “a claim that a product promotes low blood pressure would be considered a disease claim” (65 FR 1006); “elevated blood pressure (hypertension) and elevated cholesterol (hypercholesterolemia) are diseases themselves” (65 FR 1017). Source
10. 21 CFR 101.93(g)(1) — “a ‘disease’ is damage to an organ, part, structure, or system of the body such that it does not function properly (e.g., cardiovascular disease), or a state of health leading to such dysfunctioning (e.g., hypertension).” See also 21 CFR 101.14, under which any statement characterizing the relationship of a substance to a disease or health-related condition is a health claim requiring prior FDA authorization. Source
11. Wang, Z., Klipfell, E., Bennett, B. J., Koeth, R., Levison, B. S., Dugar, B., et al. (2011). Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature, 472(7341), 57–63 — in mice, “supplementation with choline or TMAO promoted atherosclerosis.” Source
12. Tang, W. H., Wang, Z., Levison, B. S., Koeth, R. A., Britt, E. B., Fu, X., et al. (2013). Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. New England Journal of Medicine, 368(17), 1575–1584 — 4,007 patients; increased plasma TMAO was “associated with an increased risk of a major adverse cardiovascular event” (hazard ratio highest versus lowest quartile 2.54; 95% CI 1.96–3.28). Source
13. Landfald, B., Valeur, J., Berstad, A., & Raa, J. (2017). Microbial trimethylamine-N-oxide as a disease marker: something fishy? Microbial Ecology in Health and Disease, 28(1), 1327309 — “However, fish and seafood contain considerable amounts of TMAO and are generally accepted as cardioprotective: a puzzling paradox that seems to have been neglected. We suspect that the TMAO story may be a red herring.” Source
14. Andrikopoulos, P., Aron-Wisnewsky, J., Chakaroun, R., Myridakis, A., Forslund, S. K., Nielsen, T., et al.; MetaCardis Consortium (2023). Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide. Nature Communications, 14(1), 5843 — “next to age, kidney function is the primary variable predicting circulating TMAO, with microbiota composition and diet playing minor, albeit significant, roles… Our analyses uncover a bidirectional relationship between kidney function and TMAO.” Source
15. Sohouli, M. H., Ozovanu, O. D., Fatahi, S., & Hekmatdoost, A. (2022). Impact of probiotic supplementation on trimethylamine N-oxide (TMAO) levels: a systematic review and meta-analysis of randomized controlled trials. Clinical Nutrition ESPEN, 50, 56–62 — “8 RCT studies with 270 participants were included… probiotic supplementation has no significant effect on TMAO levels compared to the control group (WMD −0.08 µmol/L; 95% CI −0.76 to 0.60, P = 0.813). Furthermore, the results of the analysis of the subgroups did not show a significant effect on this metabolite in both groups of healthy and unhealthy individuals.” Source
16. Bartolomaeus, H., Balogh, A., Yakoub, M., Homann, S., Markó, L., Höges, S., et al. (2019). Short-chain fatty acid propionate protects from hypertensive cardiovascular damage. Circulation, 139(11), 1407–1421 — wild-type and apolipoprotein E knockout-deficient mice receiving propionate at 200 mmol/L in drinking water; the authors conclude the data “suggest that lifestyle modifications leading to augmented SCFA production could be a beneficial nonpharmacological preventive strategy.” Source
17. Zheng, J., Wittouck, S., Salvetti, E., Franz, C. M. A. P., Harris, H. M. B., Mattarelli, P., et al. (2020). A taxonomic note on the genus Lactobacillus: description of 23 novel genera, emended description of the genus Lactobacillus Beijerinck 1901, and union of Lactobacillaceae and Leuconostocaceae. International Journal of Systematic and Evolutionary Microbiology, 70(4), 2782–2858. Source
18. Wegh, C. A. M., Geerlings, S. Y., Knol, J., Roeselers, G., & Belzer, C. (2019). Postbiotics and their potential applications in early life nutrition and beyond. International Journal of Molecular Sciences, 20(19), 4673 — “Postbiotics are functional bioactive compounds, generated in a matrix during fermentation, which may be used to promote health.” Source