Found naturally in buckwheat seeds, particularly in Himalayan Tartary buckwheat, 2-HOBA was investigated as a standalone ingredient by 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. Metabolic Technologies was acquired by TSI in 2020.
Hobamine is garnering attention in the emerging cellular health and healthspan markets, but there are also opportunities in the endurance sports space. Several commercial products are already available formulated with Hobamine.
“We feel this is going to be very new and very special for our market,” Shawn Baier, VP of Business Development, Innovative Products Division, TSI Group, told NutraIngredients-USA.
ROS and IsoLGs
The science of 2-HOBA is linked to the formation of reactive oxygen species (ROS). For some consumers, the term ROS entered their collective knowledge during the “antioxidant bubble” of the mid to late 2000’s, when ingredient suppliers competed to come up with the most powerful antioxidants, measured by their ORAC value. The thinking was that the ever-higher ORAC values indicated to consumers that the antioxidant in question would quench any and all ROS the body produced.
Citing an over-use and misuse of the term and a lack of scientific substantiation that a higher ORAC value provide greater health benefits, the United States Department of Agriculture shuttered its ORAC value database in 2012.
“ROS are formed during basic cellular metabolism,” said Baier. “Moderate ROS levels play a critical role in cellular signaling.”
But excessive ROS formation can then lead to lipid oxidation-derived compounds, such as isolevuglandins (IsoLGs). These IsoLGs are very reactive, and they are reported to form adducts with lysine residues, which can lead to detrimental changes in protein function, immunogenicity, and epigenetic alterations that may contribute to inflammatory diseases.
Rather than trying to attack the process of ROS formation, 2-HOBA targets these IsoLGs. 2-HOBA reportedly has 1,000 times the affinity for IsoLGs as IsoLGs have for their targets, said Baier, if 2-HOBA is present in the blood stream. “2-HOBA could be a scavenger and be a solution,” he added.
TSI is positioning its Hobamine-branded 2-HOBA for foods and dietary supplements and therefore the focus is on a proactive approach to health, minimizing the formation of these IsoLGs and the downstream impacts of that, said Baier.
“In this process, we should be able to see biomarker responses. Are we able to make a healthier immuno-inflammatory system?”
New study
And that brings us to a new study, recently published in Inflammation, and conducted by scientists from Metabolic Technologies (TSI), Iowa State University, and Vanderbilt University.
The new study, which included 17 healthy younger participants (average age of 34) and 16 healthy older participants (average age of 66). The participants were randomly assigned to receive placebo, or 336 or 504 mg 2-HOBA for two weeks.
The data indicated that 2-HOBA supplementation produced significant changes in 15 immune proteins, including significant increases in levels of CCL19, IL-12B, IL-10, and TNF-beta. In addition, levels of TWEAK significantly decreased.
Expanding on some of these, Baier explained that CCL19 (Chemokine (C-C motif) ligand 19) is an anti-inflammatory protein that was found to increase almost 20-fold following ingestion of 2-HOBA in normal. It plays a very important role in the health and maintenance of T- and B-lymphocytes and supports healthy immune function.
IL-10 (Interleukin 10) is a cytokine with potent anti-inflammatory properties, while IL-12B (Subunit beta of interleukin 12) has been identified as an immune cell stimulator that promotes differentiation and proliferation of T cells and enhances the production of interferon gamma supporting healthy immune function.
TNF-beta is reported to influence the maintenance of the immune system and is involved in the regulation of cell survival, proliferation, differentiation, and apoptosis, while TWEAK (TNF-related weak inducer of apoptosis) can promote the proliferation and migration of endothelial cells and induce apoptosis. “When activated chronically after injury, TWEAK promotes inflammation, fibrosis, and angiogenesis,” said Baier, “so improvements are seen by reducing it, which is what we saw in this study.”
The study authors concluded: “Given that 2-HOBA has a proven high safety margin, then its use as a nutritional supplement in healthy individuals has a high likelihood of favorably changing the biofunctions related to the recruitment, attraction, and movement of different immune cell types.”
“The biomarker changes – altogether it shows an improved function of the immune system in healthy people,” Baier told us.
Discussing the doses, Baier notes that the study used relatively high doses, which was linked to showing the safety as well as the efficacy of the ingredient. The company currently has self-affirmed GRAS status for use in foods at a level of 50 mg per serving, while they also recommend a dose for use in dietary supplements of 100 mg per day. “We believe this is sufficient to deal with IsoLGs as they appear,” he said.
Commercial growth
While endurance athletes like marathon runners are known to produce a lot of ROS and experience a suppression of their immune systems, making them more susceptible to upper-respiratory tract infections, for example, TSI is not positioning the ingredient for sports nutrition. However, the opportunities in that category are clear.
The ingredient is already used in commercial products, including BigBoldHealth’s HTB Rejuvenate, SRW’s Cel1, and Healthgevity’s Telomere Prime.
“What’s very exciting is we’re talking to between 12 and two dozen companies about opportunities,” said Baier.
Source: Inflammation
Published online ahead of print, doi: 10.1007/s10753-023-01801-w
“Inflammation Biomarker Response to Oral 2-Hydroxybenzylamine (2-HOBA) Acetate in Healthy Humans. Inflammation”
Authors: J.A. Rathmacher, et al.
