Insights from a Case Series Using a Novel Supplement Regimen
Jen Palmer, ND; Joseph M. Keenan, MD
Dietary supplements can provide older adults a therapeutic option for maintaining optimal health without relying on prescription drugs. This article summarizes key findings from a recent case series1 demonstrating the ability of one novel supplement regimen to promote healthy aging in older adults. The regimen can treat dyslipidemia, promote physical and mental well-being, and eliminate the burden of statin drugs and their associated adverse effects.
Study Protocol
This case series, conducted from September 2022 to August 2024, included a convenience sample of 10 adults (7 men and 3 women) living in the United States. The average age of the participants was 80, ranging from 62 to 91. Notably, the majority of the participants (7 out of 10) were taking a statin drug at the start of the study.
Each participant was required to share the study protocol with their personal doctor and request blood tests at baseline, 6 weeks, 12 weeks, and quarterly thereafter to monitor benefits and potential side effects, with closer monitoring as needed. The routine blood test protocol included a blood lipid profile, including lipoprotein (a) (Lp[a]), a comprehensive metabolic profile, and uric acid, homocysteine, and glycated hemoglobin (HbA1c) levels.
Quarterly in-person home visits were also conducted. The first meeting aimed to provide a detailed study protocol, obtain informed consent, and assess each participant’s health history, lifestyle and dietary habits, and support system. Subsequent visits focused on delivering the supplement supply for the next quarter, reviewing diet and lifestyle goals and lab results, and adjusting supplement dosages as needed to minimize side effects or enhance benefits.
Participants also completed the Self-Administered Gerocognitive Exam 2 (SAGE 2) cognitive assessment tool, an early diagnostic tool for cognitive impairment, and a self-reported assessment of physical/mental well-being at baseline and at the final home visit.
Supplement Selection
The supplement regimen included four research-backed dietary ingredients (niacin, dihydro berberine, taxifolin, and mixed tocotrienols) that have the potential to support key health concerns of older adults, including cardiovascular health, metabolic function, immune defense, and cognitive health.
Niacin was included primarily as nicotinic acid (NA) or niacinamide to support cardiovascular health and cellular metabolism. Extensive clinical research2 supports using NA, including wax-matrix NA, for treating dyslipidemia and cardiovascular disease despite skepticism from a recent meta-analysis3 based on two high-profile, flawed clinical trials.4,5
NA has also been reported to help reverse chronic kidney disease6 and offer therapeutic potential for certain neurological disorders and early stroke recovery.7 Both types of niacin (NA and niacinamide) serve as precursors for the body’s production of nicotinamide adenine dinucleotide (NAD+), essential for cellular metabolism and stem cell production.8 Finally, niacinamide may help prevent or delay the progression of glaucoma, the leading cause of age-related blindness.9,10
Dihydroberberine was included primarily to support metabolic health. Dihydroberberine is a highly bioavailable form of berberine,11 requiring a lower therapeutic dosage that eliminates the digestive upset commonly associated with berberine use. Clinical research supports the therapeutic use of berberine for common age-related diseases such as type 2 diabetes, dyslipidemia, hypertension, stroke, metabolic syndrome, polycystic ovarian syndrome, and nonalcoholic liver disease.12,13
Taxifolin (dihydroquercetin) was included primarily to support immune health, an action primarily attributed to its ability to reduce oxidative stress.14 Interestingly, taxifolin has been shown to improve pneumonia recovery in otherwise healthy men when used as an adjuvant to standard therapy.15
Mixed tocotrienols were included primarily for their neuroprotective properties. Mixed tocotrienols are reported to help reduce neurotoxicity and protect against mitochondrial dysfunction,16 delay progression of white matter lesions and reduce the incidence and severity of stroke,17 reduce elevated total and LDL cholesterol,18 and protect LDL cholesterol from oxidation.19
Supplement Delivery Forms and Dosing Schedule
Wax-matrix controlled-release tablets manufactured by Endurance Products Company, Inc. (Sherwood, Oregon) were chosen for the supplements providing water-soluble ingredients (niacin, dihydroberberine, and taxifolin). A proprietary tableting process is used to overcome the “dose dumping” challenge of typical modified-release tablets and provide a steady nutrient release over 4 to 8 hours, depending on the supplement. This delivery form serves two important functions. First, it helps maintain effective therapeutic blood levels without requiring higher or more frequent doses. Second, it reduces the risk of side effects from rapid nutrient absorption. For the mixed tocotrienols supplement, an immediate-release softgel with a fat-soluble suspension (“bio-enhanced”) was chosen to help ensure optimal absorption even if not taken with fat in a meal.
The participants’ medical background and current medication use dictated the supplement choice and dosing schedule (see Table 1). Participants were informed that supplementing with niacin in the form of NA may initially cause mild skin flushing that typically improves within a few weeks. To help prevent flushing, participants were advised to use aspirin or a non-steroidal anti-inflammatory drug (NSAID), if needed, and to increase their intake of methyl donor foods to support liver metabolism of NA.
| Table 1. Supplement Regimen for Healthy Aging: Dosing Schedule | |||
| Key Nutrient | Supplement | Delivery | Dosage |
| Niacin* | Nicotinic Acid (250mg to 750mg per tablet) | WM ER tablet (6-8 hours) | Week 1, 250mg bid; week 2, 500mg bid; week 3, 750mg bid maintained for 3 more weeks |
| Nicotinic Acid/Pantethine (500mg/200mg per tablet) | WM ER tablet (5-7 hours) | For participants taking a statin at baseline: 1 tablet bid increased to 2 tablets bid after week 6; tapered down/off statin use if blood lipids as good as or better than baseline | |
| Nicotinamide (750mg per tablet) | WM SR tablet (5-7 hours) | 2 tablets bid | |
| Dihydroberberine | Dihydroberberine (150mg/tablet) | WM SR tablet (5-7 hours) | 2 tablets bid for participants with metabolic syndrome or type 2 diabetes, otherwise 1 tablet bid |
| Taxifolin | Taxifolin Complex (150mg taxifolin, 500mg vitamin C, 15mg zinc per tablet) | WM SR tablet (5-7 hours) | 1 tablet bid |
| Mixed Tocotrienols | Mixed Tocotrienols (Bio-enhanced) (50mg per softgel) | IR softgel | 4 softgels bid |
| WM indicates wax-matrix; ER, extended-release, SR, sustained-release; IR, immediate-release; bid, twice daily (taken with meals).*Form of niacin dictated by a participant’s medical background and current medication use. | |||
Key Findings
The supplement intervention lasted 16 months, on average, resulting in significant improvements in blood lipid profiles, enhanced physical and mental well-being, and a reduced reliance on statin drugs. Key findings include the following:
- Reduction in Lp(a) levels. Three participants had elevated Lp(a) levels at baseline (85, 125, 256 mg/dl) and were able to achieve normal levels (<30 mg/dl) after 6 weeks of supplementation with wax-matrix NA/pantetheine and wax-matrix dihydroberberine. This is an important outcome given Lp(a) is significantly more atherogenic than LDL cholesterol.20 The participant with the highest baseline Lp(a) level initially improved to 148 mg/dl, but then appeared to develop liver hypersensitivity to NA. NA therapy was temporarily stopped to allow the side effect to resolve, then resumed at a lower dose.
- Statin withdrawal with comparable blood lipid benefits. Of the participants (7 out of 10) taking a statin at baseline, all achieved comparable lipid benefits post-statin withdrawal with a 25% decrease in total cholesterol, 35% decrease in LDL cholesterol, 52% increase in HDL cholesterol, and 46% decrease in triglycerides, on average, compared to baseline. One participant discontinued his supplement regimen and resumed statin therapy due to digestive upset that his doctor attributed to the supplement regimen.
- Improved mental and physical well-being. All 10 participants completed the cognitive and well-being assessments, reporting generally stable or positive physical and mental functions compared to baseline, including improved balance, energy level, and alertness.
Occurrence and Management of Side Effects
Side effects were successfully managed by adjusting supplement regimens. Four participants experienced skin flushing, which was managed by instructing them to avoid chewing tablets; take tablets with meals without hot foods or beverages (which can accelerate tablet dissolution); or take aspirin or an NSAID if needed. Three participants experienced elevated blood homocysteine and were instructed to add a vitamin B12/folate supplement until the homocysteine level returned to normal. Four participants experienced an upset stomach, which was managed by ruling out abnormal liver enzymes and recommending antacids or acid-blocking agents for relief.
Finally, two participants experienced liver hypersensitivity. NA was temporarily withdrawn until liver enzymes (AST, ALT) returned to normal, then gradually resumed at a lower maintenance dose (usually 500 mg twice daily). These participants were also reminded to consume more methyl-donor foods to support NA metabolism.
Discussion and Conclusion
This case series demonstrates the therapeutic potential of a novel dietary supplement regimen to promote healthy aging by addressing dyslipidemia, enhancing physical and mental well-being, and reducing the reliance on prescription drugs such as statins. Importantly, it offers valuable insight for designing a larger controlled clinical trial to address the growing healthcare needs of the aging population.
Notably, all participants taking a statin drug at the start of the study could discontinue use while maintaining blood lipid levels that were equal to or often better than their initial levels. The clinical value of discontinuing statins is profound as it also eliminates their associated adverse side effects, which can be especially troubling for older adults. For example, statins are known to deplete intracellular levels of coenzyme Q10 (CoQ10),21 which is crucial for muscle health and function. Up to 20% of cases of statin intolerance are attributed to statin-induced CoQ10 depletion.22 Additionally, statins are reported to increase atherogenic Lp(a) by up to 20%,23 and statins with high lipophilicity (atorvastatin, simvastatin) are associated with an increased risk of dementia in older people.24 Finally, results from one systematic review25 provide compelling evidence statins are significantly associated with a decrease in insulin sensitivity, regardless of the type of statin used.
The supplement regimen also enhanced physical and mental functions such as balance, energy, and alertness, which are important considerations for older individuals who want to stay active and independent. The fact that all participants maintained or improved their SAGE 2 cognitive assessment scores is encouraging and suggests that supplementation may directly support the preservation of cognitive function.
It is promising to effectively manage the transient side effects through supplement dose adjustment, dietary modifications, or other relatively simple solutions. However, this underscores the need for routine care so that doctors can monitor progress and tailor the protocol to each patient’s specific needs.
Finally, it’s interesting to note that, although the case series included two severe winter seasons, no deaths, strokes, heart attacks, cancer, or serious infections occurred in this group of older adults.
Jen Palmer, ND, is a recognized leader in the dietary supplement industry, with expertise in driving growth for professional supplement brands through strategic educational marketing. Her past roles have included serving as a subject matter expert, educator, and managing continuing medical educational conferences for healthcare professionals.
Joseph Keenan, MD, is a physician, researcher, and Professor Emeritus, University of Minnesota, Department of Family Medicine & Community Health. Dr. Keenan is a leading expert on the use of niacin therapy in the treatment of cardiovascular disease and dyslipidemia and author of The Niacin Breakthrough, The Keenan Protocol for Heart Health and Healthy Aging.
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