The ingredient was discovered via the work of Dr Naji Abumrad, MD, a surgeon at Vanderbilt University. The ingredient’s development was until recently housed within a company called Metabolic Technologies, which is a spinoff of Iowa State University.
Now the ingredient is being pushed by a company called Big Bold Health, which is the brainchild of Jeffrey Bland, PhD, who is also the president of the Personalized Medicine Institute. Metabolic Technologies itself was recently acquired by branded ingredient manufacturing and marketing firm TSI Health, which Bland said is cooperating in the new ingredient’s development.
The molecule, 2-HOBA, or 2-hydroxybenzylamine, is found is a number of plant sources. But Bland said this particular phytochemical is found in high concentrations in a particular heirloom food crop called tartary buckwheat.
Bland said the ingredient came out of Dr Abumrad’s work early work on HMB, or beta-hydroxy beta-methylbutyric acid. Dr Abumrad’s early interest in this ingredient had to do with his specialty in obesity and bariatric surgery and the ability of HMB to ameliorate muscle loss post surgery. This ingredient came to be branded as myHMB, and was the focus of TSI’s recent acquisition of Metabolic Technologies. Dr Abumrad also started looking for other bioactive molecules from natural sources that could help his patients.
“Dr Abumrad had occasion to look at some of the ingredients that had been found in traditional ancient food crops and in particular buckwheat stood out. Buckwheat had a history of helping to lower people’s blood pressure. Was that just because people changed their diets, or was there something special in the buckwheat?” Bland said.
(As a side note, Dr Abumrad has been in the news lately for his friendship with the singer Dolly Parton, who because of her connection to him made a $1 million donation to Vanderbilt in April to support its coronavirus research efforts.)
Bland said TSI is driving the development of 2-HOBA as an alternative blood pressure drug. He said the company has filed an IND and is beginning its clinical trial development. But Bland said he was much more interested in the nutritional aspects of the substance.
“We are much more interested in the food related effects at a much lower dose,” Bland said.
“My interest in 2-HOBA wasn’t specially around blood pressure. Rather I saw it as one of the few substances that could be seen as an immune system rejuvenating substance,” he said.
Working on the levuglandins
Bland the mechanism at work has to do with 2-HOBA’s effect on a family of reactive aldehydes in the body called levuglandins. 2-HOBA, which is technically described as a “selective dicarbonyl electrophile scavenger,” is able to surround and neutralize these potentially damaging molecules, or ‘quench’ them, to use Bland’s characterization. He said the mechanism was different from what is commonly associated with the class of phytochemicals known as antioxidants.
The levuglandins arise from the oxidation of fatty acids in the body. In a situation of systemic, low level inflammation which is component of many lifestyle-based diseases that plague Western society, an overabundance of these levuglandins can affect immune system performance via a complex interaction that involves the blood vessels, Bland said.
“You wouldn’t necessarily think that the compliance of our blood vessels is tied to our immune system state. When the immune system is aroused it communicates that situation to the endothelial cells,” Bland said.
In the presence of a pathogenic attack, the blood vessels constrict, raising blood pressure to help more of the specialized immune system cells to circulate faster and arrive where they’re needed in greater numbers. But the loop can work in reverse, too, leaving the immune system primed for an attack which hasn’t come.
“The you get what we call sterile inflammation, or inflammation that arises without an infection,” Bland said.
Bland said 2-HOBA has shown promise in breaking this cycle, allowing blood pressure to recede naturally and the immune system to return to resting, healthful state, rather than being overly stimulated or ‘worn out,’ to use an oversimplification.
“You have to break the loop of the dog chasing its tail, so to speak, so the dog can rest,” Bland said.
So, with good news on the mechanism of action and safety and tolerability fronts, where can one get commercial quantities of this ingredient? Bland said it is found at small levels in many varieties of buckwheat, but is found at much higher levels in a particular strain known as tartary buckwheat.
Rediscovering a crop
Tartary buckwheat, like other varieties of the plant, originated in Central Asia and had been a small part of the human agricultural picture for thousands of years. It was a popular food crop in Colonial times because it was prolific and easy to grow on many different soil types and didn’t require much in the way of inputs.
But it grew in a willowy fashion and so was harder to harvest. Over the years it had lost out to more mainstream crops like wheat and oats which had been bred for shorter, stouter and even length stems that stood up straight for the combine to neatly nip off the seed heads.
“Also, it is a very phytochemical right plant and as a result it has a lot of bitter, off flavor notes that don’t match the tastes of modern palates,” Bland said.
“Over the years it had virtually disappeared,” he added.
The botanical might have vanished from the scene altogether were it not for the efforts aficionado Sam Beer, a retired Cornell University professor turned farmer in upstate New York.
Beer has been growing tartary buckwheat for a number of years on his farm and has enough capacity for Big Bold Health to get a start on commercial scale extraction. Bland’s plan is to build on Beer’s start and the knowledge he has acquired with the goal of creating a cooperative of farmers that can grow the crop.
“Sam was the only person that we could find who was growing organic traditional tartary buckwheat,” Bland said.
There’s a learning curve, which includes how to best harvest the plants that in early times were cut by hand. Beer’s early attempts at mechanical harvesting were frustrating because the plant, which grew tall, had a tendency to be lying down by the time it was ready to harvest. So running a conventionally set up combine over the field tended to knock many of the seeds off onto the ground.
Direct to consumer brand
Bland said Beer has expanded his acreage and several other area farmers are on board. The plan is to offer the finished products direct to consumer under the Big Bold Health name. Bland said that effort is being supported by a clinical trial that is underway in the Seattle area which is using Big Bold Health’s finished dietary supplement, which supplies a dose of 2-HOBA and the other phytochemicals found in the plant that he said corresponds to eating a 1/4 lb serving of tartary buckwheat.
Big Bold Health is selling the supplement branded as HTB Rejuvenate on its website. The supplement also includes a dose of myHTB and supplies all of the phytochemicals found in tartarty buckwheat, which along with 2-HOBA include rutin, quercetin, hesperidin, luteolin and diosmin. The company is also selling Dutch Harbor Omega fish oil capsules, made via a dedicated supply chain from the Aleutian Islands. And a shake mix version of the HTB Rejuvenate product is in the works.
“I have always wanted to try to find a way to redefine health away from disease. I thought I would give it one more shot with a direct to consumer opportunity,” Bland said.