Effects of Oral Butyrate on Blood Pressure in Patients with Hypertension:A Randomized, Placebo-Controlled Trial

BACKGROUND: The microbiota-derived short chain fatty acid butyrate has been shown to lower blood pressure (BP) in rodent studies. Nonetheless, the net effect of butyrate on hypertension in humans remains uncovered. In this study, for the first time, we aimed to determine the effect of oral butyrate on BP in patients with hypertension. METHODS: We performed a double-blind randomized placebo-controlled trial including 23 patients with hypertension. Antihypertensive medication was discontinued for the duration of the study with a washout period of 4 weeks before starting the intervention. Participants received daily oral capsules containing either sodium butyrate or placebo with an equivalent dosage of sodium chloride for 4 weeks. The primary outcome was daytime 24-hour systolic BP. Differences between groups over time were assessed using linear mixed models (group-by-time interaction). RESULTS: Study participants (59.0±3.7 years; 56.5% female) had an average baseline office systolic BP of 143.5±14.6 mm Hg and diastolic BP of 93.0±8.3 mm Hg. Daytime 24-hour systolic and diastolic BP significantly increased over the intervention period in the butyrate compared with the placebo group, with an increase of +9.63 (95% CI, 2.02-17.20) mm Hg in daytime 24-hour systolic BP and +5.08 (95% CI, 1.34-8.78) mm Hg in diastolic BP over 4 weeks. Butyrate levels significantly increased in plasma, but not in feces, upon butyrate intake, underscoring its absorption.CONCLUSIONS: Four-week treatment with oral butyrate increased daytime systolic and diastolic BP in subjects with hypertension. Our findings implicate that butyrate does not have beneficial effects on human hypertension, which warrants caution in future butyrate intervention studies. REGISTRATION: URL: https://onderzoekmetmensen.nl/; Unique identifier: NL8924.</p

Gut microbiota in hypertension and atherosclerosis: A review

Gut microbiota and its metabolites such as short chain fatty acids (SCFA), lipopolysaccharides (LPS), and trimethylamine-N-oxide (TMAO) impact cardiovascular health. In this review, we discuss how gut microbiota and gut metabolites can affect hypertension and atherosclerosis. Hypertensive patients were shown to have lower alpha diversity, lower abundance of SCFA-producing microbiota, and higher abundance of gram-negative bacteria, which are a source of LPS. Animal studies point towards a direct role for SCFAs in blood pressure regulation and show that LPS has pro-inflammatory effects. Translocation of LPS into the systemic circulation is a consequence of increased gut permeability. Atherosclerosis, a multifactorial disease, is influenced by the gut microbiota through multiple pathways. Many studies have focused on the pro-atherogenic role of TMAO, however, it is not clear if this is a causal factor. In addition, gut microbiota play a key role in bile acid metabolism and some interventions targeting bile acid receptors tend to decrease atherosclerosis. Concluding, gut microbiota affect hypertension and atherosclerosis through many pathways, providing a wide range of potential therapeutic targets. Challenges ahead include translation of findings and mechanisms to humans and development of therapeutic interventions that target cardiovascular risk by modulation of gut microbes and metabolites

A suboptimal diet is associated with poorer cognition: The NUDAD project

Nutrition is one of the modifiable risk factors for cognitive decline and Alzheimer’s disease (AD) dementia, and is therefore highly relevant in the context of prevention. However, knowledge of dietary quality in clinical populations on the spectrum of AD dementia is lacking, therefore we studied the association between dietary quality and cognitive impairment in Alzheimer’s disease (AD) dementia, mild cognitive impairment (MCI) and controls. We included 357 participants from the NUDAD project (134 AD dementia, 90 MCI, 133 controls). We assessed adherence to dietary guidelines (components: vegetables, fruit, fibers, fish, saturated fat, trans‐fat, salt, and alcohol), and cognitive performance (domains: memory, language, visuospatial functioning, attention, and executive functioning). In the total population, linear regression analyses showed a lower vegetable intake is associated with poorer global cognition, visuospatial functioning, attention and executive functioning. In AD dementia, lower total adherence to dietary guidelines and higher alcohol intake were associated with poorer memory, a lower vegetable intake with poorer global cognition and executive functioning, and a higher trans‐fat intake with poorer executive functioning. In conclusion, a suboptimal diet is associated with more severely impaired cognition—this association is mostly attributable to a lower vegetable intake and is most pronounced in AD dementia.</p