The Cardiometabolic Lens

More than ever, cardiovascular health is being reframed in the context of metabolic health. This has become more pronounced with the rise of GLP-1 receptor agonist drugs. Previously used to treat diabetes, they have become popular for weight loss. “The rise in the use of GLP-1 medications and their benefits has forced researchers and practitioners to rethink how they view heart and vascular health,” says Irfan Qureshi, ND, global head of product development at Metagenics. “There is a greater realization that metabolic diseases are extremely interconnected. Weight gain, insulin resistance, endothelial function, and other conditions are no longer viewed as separate conditions but are key aspects of cardiovascular health.”

Stacy Smith, senior medical affairs liaison for Gnosis by Lesaffre, agrees. “Modern formulations are being increasingly designed to support multiple interconnected pathways, rather than focusing solely on cholesterol or blood pressure,” says Smith, adding that there are other factors at play here as well: the very common use of statins. Statins have long been understood to deplete coenzyme Q10 levels, but there may be broader implications to their use.

“More than 40 million Americans take them, making statins one of the most prescribed drug classes in the world,” she explains. “But emerging research now shows a concerning effect: statins can cause a sharp drop in GLP-1 levels—nearly 50% within just 4 months—through a microbiota-dependent mechanism.¹ This decline in GLP-1 may worsen insulin resistance and raise diabetes risk, highlighting the need for greater awareness and supportive strategies for metabolic and gut health in long-term statin users.”¹

Smith also points to research indicating that statins can deplete vitamin K2 levels, which may have implications for vascular health, as the vitamin inhibits arterial calcification.² Taking all this into account, formulators have begun changing how they design and market dietary supplement products.

“Formulations are also evolving as this realization sets in and as consumers are demanding solutions that address all or many of these related conditions,” says Qureshi. “Whereas products previously may have addressed cholesterol or blood pressure and focused on reducing numbers or stabilizing key indicators, newer products address metabolic health as an integrated system. Thanks to the explosion in the use of GLP-1 agonists, products must now focus on things like insulin sensitivity and blood sugar regulation, endothelial health and function, mitochondrial wellness and energy production, preserving muscle mass during rapid weight loss, and supporting a healthy inflammatory response in metabolic tissue.”

What This Means for Product Innovation

“While the stalwart ingredients in the category remain omega-3s, coenzyme Q10, magnesium, and others, companies need to understand the paradigm shift that is occurring in the minds of customers to steer away from formulas that address legacy heart health factors such as cholesterol, blood pressure, and circulation, to products that address cardiovascular wellbeing as a metabolic condition,” says Qureshi.

From his perspective, this means addressing mechanisms that drive cardiovascular disease—such as endothelial function, mitochondrial health, inflammation, and dysregulated metabolism—in a more integrated fashion. “Including ingredients that address such causal factors and educating consumers on how ingredients in a formulation work together to tackle issues in a complementary fashion can make products more attractive to consumers in this category,” he explains.

“The next generation of heart health innovation lies in pairing legacy ingredients with targeted micronutrients that address under-recognized mechanisms such as vascular calcification, endothelial dysfunction, and methylation imbalance,” posits Stacy. For example, the addition of active folate, such as Quatrefolic from Gnosis by Lesaffre, may offer a powerful point of differentiation because it would allow “formulators to move beyond generic B-vitamin blends and deliver precise support for homocysteine metabolism, nitric oxide signaling, and vascular health, crucial for individuals with MTHFR polymorphisms or impaired folate conversion,” she explains.

Stacy cites research showing that the active form of folate, 5-methyltetrahydrofolate, can significantly reduce homocysteine levels, and that adding vitamin K2 can complement folate’s benefits by supporting vascular health and managing oxidative stress, offering a comprehensive approach to heart health.

A comprehensive approach does not have to be one-size-fits-all, Stacy points out, as formulators can still tailor products to target specific populations such as those with metabolic disorders or high cholesterol. “Innovation increasingly comes from strategic stacking,” says Stacy. This means combining structure-supporting nutrients, metabolic regulators, mitochondrial cofactors, and targeted botanicals in “clinically coherent formulas.”

“This systems-based design approach enables brands to differentiate with science-driven positioning that reflects the evolving complexity of cardiovascular health,” she explains.

Of course, unpacking these nuances is not always easy. “From the standpoint of consumer perception, educating customers on specific reasons for the inclusion of key complementary ingredients can help formulations gain differentiation,” says Qureshi. “This is not only about the science behind an ingredient, but rather how this science is expressed to consumers. Structure-function claims that speak directly to how ingredients work and why that is important for cardiovascular health are crucial ways of communicating differentiated benefits.”

Despite the potential challenges of communicating these benefits, the nuanced interconnected nature of our health, particularly heart health and other metabolic conditions, does offer tangible opportunities for innovation in nutraceutical formulation. Additionally, it is a concept that consumers are becoming increasingly receptive to as their perspectives on how to approach heart health evolve.

References

1. Zhang Y, Li X, Chen J, et al. Statins aggravate insulin resistance through reduced blood glucagon-like peptide-1 levels in a microbiota-dependent manner. Cell Metab. 2024;36(2):408-421.e5. doi: 10.1016/j.cmet.2023.12.027
2. Okuyama H, Langsjoen PH, Hamazaki T, et al. Statins stimulate atherosclerosis and heart failure: pharmacological mechanisms. Expert Rev Clin Pharmacol. 2015;8(2):189-199. doi:10.1586/17512433.2015.1011125