Hypertension researchers finds hypertension treatment that mimics effect of exercise

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Saroj Chakraborty, a fourth-year Ph.D. student at the University of Toledo, left, and Dr. Bina Joe, Distinguished University Professor and chair of UT's Department of Physiology and Pharmacology. Credit: Dan Miller, University of Toledo

Couch potatoes rejoice—there might be a way to get the blood pressure lowering benefits of exercise in pill form.

Hypertension researchers at The University of Toledo have shown that by increasing the body’s supply of beta hydroxybutyrate, a chemical produced predominantly by the liver, it is possible to regulate high blood pressure without reducing sodium intake or increasing exercise.

“Our team found that high salt consumption lowered levels of circulating beta hydroxybutyrate.

When we put beta hydroxybutyrate back in the system, normal blood pressure is restored,” said Dr. Bina Joe, Distinguished University Professor and chair of UT’s Department of Physiology and Pharmacology and director of the Center for Hypertension and Precision Medicine.

“We have an opportunity to control salt-sensitive hypertension without exercising.”

The team’s findings were published Tuesday in the Oct. 16 issue of the life sciences journal Cell Reports.

Beta hydroxybutyrate is a ketone body produced in the liver from the metabolism of fatty acids.

It had not been previously explored as a method for controlling blood pressure, but the UT researchers noted a number of intriguing connections between how the body produces beta hydroxybutyrate and environmental factors known to raise or lower blood pressure.

“As we searched through the literature we saw beta hydroxybutyrate has been observed increasing with exercise or calorie restriction.

Both of those activities also reduce blood pressure.

The key piece of our discovery is we now know that beta hydroxybutyrate decreases with salt consumption.

This is a novel mechanism by which salt is tied to an increase in blood pressure,” said Saroj Chakraborty, a fourth-year Ph.D. student in the UT Department of Physiology and Pharmacology and the paper’s lead author.

To test its hypothesis, the team led by Chakraborty and Joe developed a study in which they fed lab rats a chemical called 1,3-butanediol.

When that supplement reaches the liver, enzymes convert it to beta hydroxybutyrate.

From there, it goes to the kidney where it was shown to reduce inflammation commonly associated with hypertension—and significantly decrease blood pressure in the process.

“By fixing the kidney it is indirectly contributing to the lowering of blood pressure. There could be many other organs that it is impacting,” Joe said. “We are studying the heart, blood vessels, brain and other organ systems.

But this paper says that this molecule, predominately made in the liver, goes to the kidney, fixes kidney damage and controls your blood pressure.”

Joe noted that controlling function of the liver to regulate blood pressure is a new concept for researchers.

UT has received a provisional patent on the concept.

Researchers in Joe’s lab next want to compare the level of beta hydroxybutyrate in hypertensive patients against those without high blood pressure. Further studies also will determine how much 1,3-butanediol is needed to modulate blood pressure and whether it might cause any potential damage to other organs.

Once the team collects that data, the researchers hope to secure funding for a clinical trial.

While lowering blood pressure without hitting the gym might sound appealing to those averse to breaking a sweat, it also could prove beneficial to those who aren’t able to exercise.

“There are certain patients who are not able to exercise for various reasons. This could prove to be a legitimate alternative for those individuals,” Chakraborty said.

More information: Cell Reports (2018). DOI: 10.1016/j.celrep.2018.09.058
Journal reference: Cell Reports search and more info website

Provided by: University of Toledo

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What is Beta-Hydroxybutyrate (BHB) & How Does it Work?

Beta-Hydroxybutyric Acid, also commonly referred to as beta-hydroxybutyrate or just BHB, is technically not a ketone body in terms of structure, but it has ketone-like actions in humans and is thus classified as one.

BHB is the most efficient ketone body in terms of either being utilized directly by tissues or being oxidized to acetoacetate and then utilized.

The mitochondria of cells can use ketones to generate energy as an alternative when carbohydrate/calorie intake is low.

In humans, there are three main types of ketones (referred to as ketone bodies) synthesized by mitochondria in the liver: acetone, acetoacetic acid (AcAc), and beta-hydroxybutyric acid (BHB).

On a molecular level, ketones are natural molecules made as byproducts of fatty acid metabolism. These molecules have a rather simple structure, containing a primary carbonyl group (i.e. carbon bonded to oxygen)  and two carbon-based groups (chemical structures shown below).

Essentially, by incorporating BHB into your supplement regimen, your body receives a fast-acting source of ketones to utilize; thus, even if you consume a carbohydrate-rich diet, exogenous BHB can provide many of the benefits of nutritional ketosis.

There’s also a handful of scientific studies that suggest BHB regulates appetite, enhances cognition, fights inflammation, reduces the risk of cancer, and impedes age-related neurodegeneration. [1,2,3]

WHERE DOES BHB COME FROM?

BHB comes from two sources, within your body (endogenous) and outside of your body (exogenous).

Endogenous BHB is made in the liver as a byproduct of fatty acid metabolism when fasting and/or when carbohydrates are restricted in your diet. Since the body needs energy to subsist, synthesis of BHB is a crucial process for creating fuel from fatty acids, and without it, fasting would be a deadly condition even in the short term.

On the other hand, exogenous BHB is BHB that derives from a source outside of your body (i.e. dietary supplement).

For example, consuming a BHB supplement is one way to rapidly increase blood BHB levels in your body without the need for a ketogenic diet.

This confers many of the same benefits as ketosis and happens rather rapidly.

Most exogenous BHB comes bound to a salt, like magnesium or calcium, which is more absorbable by your body.

Thus, you’ll most likely see that exogenous ketones supplementshave BHB salts listed on the ingredient panel. If they’re not, you should be wary of the product’s efficacy.

Now that you have a clear grasp of where BHB comes from, it’s pertinent to understand what the heck it does and why you should care. Read on as the next section details the roles of BHB and its benefits.

WHAT DOES BETA HYDROXYBUTYRATE DO?

Ultimately, BHB is the primary substrate the initiates nutritional ketosis in your body. Once BHB is synthesized, it can be broken down to both acetoacetic acid and acetate (meaning BHB has the most energetic potential of all three ketone bodies). This applies to both endogenous and exogenous BHB.

What’s particularly important about BHB is that it readily diffuses across the blood-brain barrier (BBB), which is a strictly regulated juncture to prevent unwanted substances from crossing into the brain.

It was thought for years that glucose was the brain’s primary source of energy, but due to BHB’s water-attracting nature, it crosses into the brain and positively affects cognitive function and mental acuity. In other words, BHB has nootropic properties.

In terms of producing energy for your body, BHB enters mitochondria of cells and breaks down to acetoacetic acid and eventually acetone.

During each stage of these molecular changes, a compound called acetyl-CoA is produced which is fed into the Kreb’s cycle so your body can synthesize ATP – the energy currency of cells.

Normally glucose would serve as the main substrate for producing ATP, but when carbohydrates are low in the diet, your body resorts to BHB to take care of energy production.

So you can see why BHB is so critical for maintaining energy levels and cognitive function. Naturally, you might be wondering whether or not BHB is safe? In most cases, yes; read on to learn more about the safety of BHB.

BETA-HYDROXYBUTYRATE SAFETY

Frankly speaking, beta-hydroxybutyrate is about as safe as water. It is a natural compound that your body thrives on during times of energy deprivation. Just like water, though, extremely high levels of BHB in the body can create a metabolic state known as diabetic ketoacidosis.

However, if you have a healthy pancreas and aren’t diabetic, it is extremely unlikely you will ever reach diabetic ketoacidosis.

In the event you were to consume exorbitant amounts of exogenous BHB, your body would work rapidly to excrete the excess and keep blood ketones in a healthy range.

BETA-HYDROXYBUTYRATE SIDE EFFECTS

If you are just starting out on a ketogenic diet, chances are you will experience some side effects in the initial week as your body shifts from carbohydrate metabolism and becomes ‘fat adapted’.

The side effects during this period may include things like lethargy, mood swings, irritability, and brain fog which is noted as the keto flu.  T

o bypass these ramifications, it is best to supplement with exogenous BHB while you transition to a keto diet.

Be wary, though, that taking too much exogenous BHB can also cause unwanted side effects. Typical side effects of large BHB doses include gastrointestinal distress, flatulence, and dry mouth.

BENEFITS OF BETA-HYDROXYBUTYRATE BHB SALTS SUPPLEMENTATION

The main benefit of consuming exogenous BHB is that you will quickly transition into ketosis and avoid many of the side effects from starting a ketogenic diet. Moreover, BHB provides a lasting source of energy that will drive your physical and cognitive performance for hours.

If you’re curious what exactly the benefits of ketosis are, and how to set up a ketogenic diet, we highly recommend reading our guides:

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