For decades, clinicians have focused on which nutrients to recommend and at what dose. But a growing body of research suggests another variable may be just as important: how those nutrients are delivered to the body over time.
Most supplements on the market—whether powders, capsules, liquids, or standard tablets—release their active ingredients quickly after ingestion. While that may seem efficient, rapid release can create sharp spikes in nutrient levels followed by rapid decline. In clinical settings, this pattern can lead to inconsistent therapeutic exposure, the need for multiple daily doses, and sometimes an increase in side effects.
A useful way to think about supplement delivery is to imagine a city bus transporting commuters across town.
With many conventional supplements, the bus pulls up to the first stop and everyone gets off immediately. The active ingredients are released all at once, leaving little sustained delivery for the rest of the journey through the digestive tract.
Some delayed-release or enteric-coated capsules perform slightly better. They may drop off most passengers at the first stop, a few at the second, and perhaps a handful at the third. But the release pattern can still be uneven and unpredictable.
An innovative technology known as SmartMatrix™ wax-matrix tableting is attempting to change that model.
A Different Kind of Delivery System
The SmartMatrix™ tableting technology results in a homogeneous structure of vegetable waxes that form a stable matrix throughout the tablet. Active ingredients are secured inside this structure and released gradually as the wax matrix dissolves during digestion. (It’s why the finished tablet is known as a Secure Release™ tablet.)
The structure has been compared to a natural honeycomb.
Just as bees construct combs to hold and protect honey, the wax lattice in a Secure Release™ tablet creates microscopic compartments that hold active ingredients in place. As digestion progresses, the matrix slowly releases those ingredients over a controlled period of time.
This approach differs from common sustained-release delivery technologies that rely on porous fillers or sponge-like materials designed to trap nutrients. Those tablets or capsules can sometimes adhere to stomach tissues or dissolve unpredictably depending on gastric conditions, potentially increasing gastrointestinal irritation or causing inconsistent release of the active compounds.
The wax-matrix design aims to produce a more predictable release profile that more closely resembles the way nutrients are absorbed from food.
Evidence from Niacin Research
One of the best examples of how delivery technology can influence tolerability comes from studies involving nicotinic acid (niacin). Niacin has long been used to support healthy cholesterol and lipid metabolism, but traditional forms are often limited by flushing and digestive discomfort when high doses are required.
By contrast, extended-release wax-matrix niacin (1–2 g/day) is well tolerated.
Clinical trials consistently show remarkably low dropout rates (averaging around 4 percent), predominantly due to flushing, itching, or digestive upset.
For example:
| Dropout Rate | Clinical Trial |
| 2.4% | Keenan JM. J Clin Lipidol. 2013;7(1):14-23. |
| 3.4% | Keenan JM, et al. J Am Geriatr Soc. 1992;40(1):12-18. |
| 3.4% | Keenan JM, et al. Arch Intern Med. 1991;151(7):1424-32. |
| 4.0% | Alderman JD, et al. Am J Cardiol. 1989;64(12):725-9. |
| 4.5% | Aronov DM, et al. Arch Fam Med. 1996;5(10):567-75. |
| 8.0% | Keenan JM, et al. J Fam Pract. 1992;34(3):313-9. |
| 4.3% | Average |
For clinicians familiar with the tolerability challenges associated with immediate-release niacin, these findings suggest that delivery technology can significantly influence patient experience.
Extending the Technology to Other Nutrients
Researchers and manufacturers are now exploring how similar delivery systems might benefit other nutrients and bioactive ingredients that are rapidly absorbed and quickly cleared from circulation.
One example is L-theanine, a highly water-soluble amino acid known for supporting relaxation and cognitive calm. Standard formulations are absorbed quickly, often leading to short-lived effects.
A sustained-release version using the SmartMatrix™ approach has been designed to release approximately 50 percent of the dose within the first hour, followed by a controlled release of roughly 10 percent per hour over the next six to eight hours.
The goal is to extend the functional window of the compound while reducing the need for repeated dosing.
Other compounds with this delivery system include nicotinamide (niacinamide), 5-HTP, and dihydroberberine, where controlled release helps maintain steadier metabolic or neurological support throughout the day.
In some cases, sustained delivery may also reduce dosing frequency, improving patient adherence. For example, dihydroberberine formulations using controlled release may allow twice-daily dosing, compared with the three-times-daily schedules often required for conventional berberine hydrochloride. With 5 times better absorption, dihydroberberine also allows for a lower dose that further promotes digestive comfort.
A Question of Transparency
One issue that continues to concern many healthcare providers is the widespread use of the term “sustained release” in supplement marketing without clear evidence of how those products actually dissolve.
With wax-matrix systems, dissolution is verified using validated methods, including the Tumble Wheel Dissolution Method (National Formulary XIV), the preferred test for modified-release tablets with water-soluble nutrients, as it mimics digestion by changing the pH during testing.
For practitioners, these dissolution curves provide objective data on release kinetics, allowing clinicians to evaluate whether a product’s delivery claims are supported by measurable evidence. You don’t have to take my word for it, check out the EndurPro website for our Certificates of Analysis for our most popular products; including the highly water soluble ingredient L-Theanine.
Rethinking the Role of Delivery in Clinical Nutrition
The growing interest in delivery technology reflects a broader shift in how clinicians think about nutrient therapy.
While ingredient selection remains critical, the timing and consistency of exposure may be equally important. Controlled delivery systems aim to move nutrient supplementation closer to the body’s natural pattern of digestion—where nutrients are absorbed gradually rather than all at once.
If the city bus analogy holds true, the goal is simple: instead of unloading every passenger at the first stop, deliver them steadily across the entire route.
For clinicians seeking more predictable nutrient exposure and improved patient compliance, delivery systems like SmartMatrix™ may represent an emerging area worth watching.
References
Alderman JD, Pasternak RC, Sacks FM, Smith HS, Monrad ES, Grossman W. Effect of a modified, well-tolerated niacin regimen on serum total cholesterol, high density lipoprotein cholesterol and the cholesterol to high density lipoprotein ratio. Am J Cardiol. 1989;64(12):725-729. doi:10.1016/0002-9149(89)90754-6
Aronov DM, Keenan JM, Akhmedzhanov NM, Perova NV, Oganov RY, Kiseleva NY. Clinical trial of wax-matrix sustained-release niacin in a Russian population with hypercholesterolemia. Arch Fam Med. 1996;5(10):567-575. doi:10.1001/archfami.5.10.567 doi:10.1001/archfami.5.10.567
Keenan JM. Wax-matrix extended-release niacin vs inositol hexanicotinate: a comparison of wax-matrix, extended-release niacin to inositol hexanicotinate “no-flush” niacin in persons with mild to moderate dyslipidemia. J Clin Lipidol. 2013;7(1):14-23. doi:10.1016/j.jacl.2012.10.004
Keenan JM, Bae CY, Fontaine PL, et al. Treatment of hypercholesterolemia: comparison of younger versus older patients using wax-matrix sustained-release niacin. J Am Geriatr Soc. 1992;40(1):12-18. doi:10.1111/j.1532-5415.1992.tb01822.x
Keenan JM, Fontaine PL, Wenz JB, Myers S, Huang ZQ, Ripsin CM. Niacin revisited. A randomized, controlled trial of wax-matrix sustained-release niacin in hypercholesterolemia. Arch Intern Med. 1991;151(7):1424-1432. doi:10.1001/archinte.151.7.1424
Keenan JM, Wenz JB, Ripsin CM, Huang Z, McCaffrey DJ. A clinical trial of oat bran and niacin in the treatment of hyperlipidemia. J Fam Pract. 1992;34(3):313-319. PMID: 1541958
