Formulators: 13 innovative healthy-aging ingredients

[Editor's note: This article is part of the Natural Products Insider digital magazine on developing and marketing healthy aging supplements. Download it for free here.]

Don’t believe everything you hear. Despite numerous systemic and societal limitations, humanity has accelerated its pace for delivering better health outcomes. Genetic and biomarker testing, telehealth, big data and AI (artificial intelligence) have all grown together at such a rapid pace that anyone anywhere in the country can access tools, medicines and supplements to an extent unimaginable 30 years ago. 

The world of nutrition and anti-aging has matured, too. Pure woo remedies and detox foot baths of the 20th century have been replaced with hardcore science in the new century. That’s real clinical studies, on real ingredients and products. Just ask PubMed. 

Cracking the longevity code 

We’ve broken down longevity into bite-sized pieces — from the Horvath clock for DNA methylation to crazy Venn diagrams to the collective analysis of compounds that may extend life span, including NAC (N-acetyl-L-cysteine), vitamin E, curcumin, quercetin and, yes, even aspirin. 

Just like the hip bone’s connected to the knee bone … longevity’s connected to mitochondrial health, which is connected to inflammatory signaling and immune response, which is connected to the gut. When it comes to anti-aging, the human body’s pathways are mapped in every direction. We know our stuff. Kind of. Almost. 

Related:Cracking the longevity code — digital magazine

We also know that every individual is an island, each with a different complex condition of biochemistry and nutritional status. Advanced supplement companies in the practitioner space have been combining diagnostics with nutrition for years. File it under “things that just make sense.” But are we using our data for the best health outcomes? 

One of my favorite challenges is to try (or mainly, pretend) I’m cracking the code on health with integrative medicine. Between diet, supplements and conventional medicine, may we live to be a hundred, on average, eventually. To this aim, health research begs, borrows and steals from the shoulders of giants. Which is great since we’re more educated now. Better yet, we’ve got years of advance notice on emerging biomarkers and pathways from pharma R&D worth paying attention to. GLP (glucagon-like peptide)-1 is today’s example, yet no pathway is a silver bullet. Tomorrow could bring even more possibilities. 

My own journey 

Here’s a nugget from personal experience: Anti-aging isn’t just about optimizing how we feel or how far we can run. It’s also about understanding and controlling our risk factors and being able to lower them with diet and supplements. 

Related:Formulators: 15 ingredients to build supplements for aging bodies

In cardiovascular health and weight management, a huge gap still exists between oatmeal and Ozempic — and then, the song remains the same for the rest of our lives. For example, in cardio health, a large swath of the U.S. population, perhaps 100 million strong, is sitting in limbo, waiting for advances in preventive, health span-lengthening supplements that can control both LDL (low-density lipoprotein) and “lipoprotein little a” or Lp(a). 

You thought LDL was bad? Lp(a) is much worse — it contains the worst kind of gooey, sticky, artery-clogging LDL that dissolves right into the vascular endothelium. Lp(a) is genetically determined, hard to budge with lifestyle changes and can be elevated from a young age. Yet studies show that lowering Lp(a) from high to normal levels cuts the risk of major cardiac and stroke events in half. Yes, in half. 

The problem is doctors don’t typically test Lp(a) unless a person has other risk factors like high cholesterol. The main reason is because no current cholesterol treatments can reduce it, although some are in phase 3 trials and hopefully will be approved in a few years. As someone with familial high cholesterol, I only recently got my Lp(a) tested. It was pretty high — something my doctor said it would have been nice to know 20 years ago. I agreed. Testing of Lp(a) is available from Quest Diagnostics as part of its CardioIQ panel, and anyone with cardiovascular risk factors should consider requesting it. 

Related:14 ingredients for healthy cognition, stress and sleep supplements

The good news is omega-3 EPA (eicosapentaenoic acid), niacin, CoQ10 and a diet of whole plant foods have each shown to modestly but significantly reduce Lp(a). My doctor recommended high-dose niacin (luckily, I know the good brands!). We’re ahead of the game with knowledge, if only we use it to our advantage. And now I’m finally taking my (proven) supplements religiously. 

10 other ingredients for formulators 

Living longer and healthier is not just about the amount of fat in a person’s blood. Smart consumers (and smart product developers) looking to extend health span know we often need to address multiple risk factors — sometimes hidden or undiagnosed — with multiple supplements. A product mix, if you will. For instance, while high Lp(a) doubles cardio risk, lowering Lp(a) alone may not make a difference in cardiac outcomes if inflammation is not controlled. Because while Lp(a) is associated with inflammation, it likely isn’t the sole source. Armed with my Lp(a) levels, I’m going hardcore on foods and supplements for silent inflammation — another big white space for increasing health span. 

Plenty of “joint health” studies have been done for outcomes like osteoarthritis (OA), but the worst inflammation is the kind we don’t feel … the one that courses through cells and arteries, untested for and often unnoticed for decades. Perhaps it is expressed as high c-reactive protein (CRP) — but perhaps not, for many people like me. One area modern medicine falls short is the lack of reliable universal diagnostic testing for inflammation, let alone that very few drugs can reduce it. So, we’re still searching for solutions, but supplements may be able to help. 

Emerging ingredients like palmitoylethanolamide (PEA), indigenous to animal biochemistry, are promising. First discovered and described by Nobel Prize winner Rita Levi-Montalcini, PEA is dubbed “the body’s own anti-inflammatory.” It’s an essential ligand for fatty acid amide hydrolase (FAAH) in the arachidonic acid/endocannabinoid pathway, which appears to dynamically respond based on an individual’s inflammation levels. Large-scale human studies have shown pain reduction; and recently, a formula of PEA, curcumin and quercetin improved physical activity and gait force in older companion dogs experiencing knee inflammation. 

Traditional plants and fungi commonly known about for eons are now being scientifically investigated. Turmeric (curcumin or Curcuma longa specifically), reishi (Ganoderma lingzhi) mushroom fruiting body, ginseng root (Panax ginseng) and astragalus (Astragalus membranaceus) are being studied in humans for anti-inflammatory and anti-aging effects: DNA damage, heart disease risk and immune status. A veritable catalog of various plant sources of polyphenols and flavonoids is available, each class with perhaps hundreds of natural compounds that have been studied for anti-inflammatory and anti-aging effects, each no slouch in its own right. 

When it comes to polyphenol sources, the more diverse the better. If I had to choose one, muscadine grape (Vitis rotundifolia) is a fruit source of polyphenols and flavonoids purported to be among the most diverse from a single plant. Amounts of resveratrol, catechins like EGCG (epigallocatechin gallate), anthocyanins, quercetin and its family of flavonoids, along with ellagitannins, proanthocyanidins and numerous phenolic isomers make muscadine grape a rich source of well-studied antioxidants. As a result, muscadine has a range of potential applications related to quenching molecular fires and increasing health span. Recent studies have shown that muscadine grape extract works as a postbiotic by improving the gut microbiome, extending its effects to the cardiovascular system, brain and other organs. 

3 body problems 

Again, there’s no silver bullet, and we need to gravitate to where the science is reliable and repeatable. The Mediterranean diet with a daily protein supplement makes sense, for example. I envision a future where we have validated the body’s own ways to extend health span across the spectrum of age groups. I expect ingredients like HMB (hydroxymethylbutyrate), exogenous nucleotides, spermidine and NMN (nicotinamide mononucleotide) to continue to show, in the vein of CoQ10 and PEA, nutrients innate to our biochemistry and found in our diet can have real life-giving properties as supplements. Another thing that just makes sense. 

By looking both inside and out — and to the past, present and future — we can leverage the tools at our disposal for reducing health risk and increasing health span as we age. Hopefully we continue to borrow from the giants and make good product decisions for the health and lifelong happiness of our consumers.