Center for Clinical and Translational Science

Hypertension is a disease of the westernized world, as it stems from lifestyle habits: salt and alcohol consumption, lack of physical activity, smoking, and obesity. Since publication of the original Dietary Approach to Stop Hypertension (DASH) diet study in 1997 many additional controlled studies have demonstrated the clinical efficacy of the DASH diet to meaningfully lower blood pressure.

The DASH diet emphasizes fruits, vegetables, and low-fat dairy products and is reduced in fat and cholesterol. It is exceedingly unlikely that a “magic nutrient” can explain its additive effect over simply a low salt diet. Rather the impressive BP reductions reported are best interpreted as a combined effect from multiple dietary factors rather than the effects of a single factor. Lower salt consumption reduces blood pressure, but the DASH diet is much more effective, lowering blood pressure as efficiently as one anti-hypertensive drug.

Certain dietary patterns have been associated with low BP. Observational studies and clinical trials have associated vegetarian diets with lower BP, yet the nutrients responsible for the BP-lowering effects of these diets have remained uncertain. Attention has focused on macronutrients (particularly the type and amount of fat), micronutrients (potassium, magnesium, and calcium), and fiber. However, data from observational studies and small-scale trials have been extremely inconsistent.

The precise mechanism through which DASH achieves its effect is not understood. The overall goal of my project is to learn more about its mechanism. One hypothesis is that the additive affect is attributed to the increasing the consumption of potassium.
Observational studies highlight the role of potassium in preventing stroke, reducing blood pressure and cardiovascular morbidity, and protecting the kidneys from damage caused by hypertension. But how does potassium exert its beneficial effect? Potassium is the trigger for release of aldosterone, a hormone, from the adrenal glands that results in excretion of the additional potassium. Potassium excretion obligates sodium excretion, so, potassium acts like a diuretic drug, but without drug side effects. To assess whether the DASH diet results in aldosterone-induced changes in ion channel composition in the kidneys’ epithelium, we will monitor urine exosomes, which contain epithelial cell membranes.

Traditionally, adherence to the DASH diet has been evaluated using questionnaires, but we have learned that patients commonly underreport the amount of sodium they consume. One of the great strengths of the Rockefeller University Hospital staff’s extensive experience in conducting long-term, in-hospital nutritional studies with research volunteers, is that we can monitor carefully food intake and collect biologic samples to independently assess dietary adherence, outcomes, and mechanisms.
We hypothesize that exposing stage 1 hypertensive volunteers to a high potassium and low sodium DASH diet will change the composition of renal ion channel in an aldosterone-dependent manner, leading to excretion of both sodium and potassium and a reduction in blood pressure.

The aims of the study are to 1) characterize urinary exosomes before and during the DASH diet, and 2) validate the urinary sodium/potassium ratio as a measure of DASH adherence. We are recruiting ten healthy volunteers with relatively mild (stage 1) hypertension and they will consume the DASH diet as inpatients at the Rockefeller University Hospital for two weeks. Participants will undergo daily blood pressure measurements, daily blood and urine sample collection, 24-h urine collection, and 24-h ambulatory blood pressure monitoring (ABPM).

The menu was planned based upon the guidelines of the National Heart Blood and Lung Institute (NHBLI) of the National Institute of Health (NIH).

 

In designing the study, our challenges were to meet the diet requirements while making the menu palatable and appealing. The main differences from the American style diet are the low salt (2.3 grams of sodium recommended compared to more than 4.5 grams in a typical American diet) and the high potassium. To achieve these goals, the DASH diet has an abundance of fruits and vegetables. To avoiding the potential confounding effect of weight reduction on blood pressure, we also had to calculate caloric intake to maintain weight stability throughout the study.

The clinical protocol was developed with assistance from many Rockefeller Center for Clinical and Translational Science (CCTS) and Hospital staff under the Translational Research Navigation process. Under the ongoing threat of COVID-19, the protocol was interrupted just as it began, and to resume, had to be re-Navigated to incorporate the new rules and challenges related to risk assessment, social distancing, SARS-CoV-2 testing, and staff and patient safety. These include asking participants to complete a symptom survey prior to arrival on campus and testing for the virus before admission.

 

The first participant was enrolled on June 14th, 2020. Below is an example of the impact the diet had on the participant’s 24-hour ambulatory blood pressure. The most dramatic change is during sleep where the participant’s blood pressure decreased from 120/74 to 109/67 mmHg. This enhanced “nocturnal dipping” is associated with improved cardiovascular health and reduced all-cause mortality.

 

Understanding the mechanism underlying the DASH diet may shed light on the physiologic process by which nutrition influences blood pressure and potentially lead the way to new therapeutics that target ion channels.
We also hope that by introducing our participants to better nutritional choices we will be able to not only reduce their blood pressure during the intervention, but help them to carry the lessons home, modify their lifestyle, continuing eating a healthier diet after the study, and sustaining the lower blood pressure without requiring medication.

 

This article affords me a great opportunity to thank the great staff of the Rockefeller University Hospital, the Navigation team, and the Clinical Research Support Office headed by Dr Rhonda Kost, who made this trial come to life with the reopening of the University.