Joseph Keenan, MD
Professor Emeritus, University of Minnesota Department of Family Practice and Community Health
Associate Professor, University of Minnesota Department of Food Science and Nutrition
Former Director of the Family Practice Residency Program and the University of Minnesota Geriatrics Fellowship Program.
Dr. Joe Keenan has been doing research, focusing primarily on preventive cardiology, for more than 35 years. He has also done research on geriatrics and nutritional health. Over this time, he has published 58 papers in peer-reviewed scientific journals, published 17 books and chapters in books, and has made presentations at more than 150 national and international conferences and conventions. During his career he has received awards and recognition for his professional work including: “Excellence in Primary Care Research” 1993, Minn. Academy of Family Physicians; “Outstanding Service Award” 1995, American Geriatrics Society; “Best Doctors in America” 1998-2009; “Who’s Who, National Registry of Best Professionals in America” 2003-2011; “Who’s Who in America-Marquis Lifetime Achievement Award” 2018.
He recently published the book, The Niacin Breakthrough, which is a summary of much of his research in preventive cardiology and concludes with four chapters on healthy aging.
Q: What inspired you to write The Niacin Breakthrough?
A: Over the years of my research in preventive cardiology I have been impressed with the many unique benefits of nicotinic acid, both in managing dyslipidemia and its additional benefits beyond lipid management. These additional benefits include 1) prevention of oxidation of LDL cholesterol making it less pathogenic, 2) reduction of small dense particles of LDL, which are the most pathogenic, 3) reduction in the molecule called chemoattractant protein 1, which is the initiator of much vascular disease (plaques and thrombi), 4) prevention of incidence and severity of strokes, 5) reduction in the intimal thickness of arteries, 6) improvement, when used with bicarbonate, in kidney function in persons with severe kidney failure. I added the last four chapters on healthy aging to include some additional important findings from my research, my clinical experience and the research of others.
Q: How has niacin evolved over the decades?
A: Nicotinic acid became very popular in the late 1970s when the results from the Coronary Drug Project (conducted from 1966-1975) showed that nicotinic acid not only improved dyslipidemia in every way, but also reduced heart attacks, strokes, cardiovascular hospitalizations and surgery. A 15-year post hoc analysis also showed nicotinic acid improved life expectancy by 1.6 years.
Unfortunately, many physicians did not prescribe immediate release nicotinic acid with the proper instructions on how to avoid flushing side effects and many persons had to discontinue use because of flushing and upset stomach. Then development of formulations of controlled release nicotinic acid greatly reduced the incidence of side effects and new clinical trials in the 80s and 90s again showed lipid benefits, reduction of cardiac events and reduction of intimal thickness of arteries.
This led to two very large clinical trials: AIM HIGH study 2006-2009 and HPS-2 THRIVE study 2007-2011 that were intended to show the benefits of combining a controlled release form of nicotinic acid with a statin drug. Both studies failed to show a benefit of adding nicotinic acid to statins and instead reported possible harm with adding nicotinic acid. They reported these findings as final results of the studies which devastated the providers use of nicotinic acid worldwide. Further analysis of the results of both of the studies showed they were seriously flawed, and the poor results were inappropriately attributed to the use of nicotinic acid.
The retraction of the wrong interpretation of the study results did not have the degree of worldwide reporting that the initial negative results had, so most physicians continued to discard nicotinic acid as not a safe and useful medication to use for managing dyslipidemia. Nicotinic acid, (specifically wax matrix controlled-release nicotinic acid) remains underutilized despite its many lipid and non-lipid benefits and better safety with fewer and less serious side effects than statins. More recent studies are showing that statins are associated with increased risk of dementia in older persons and even though they reduce LDL cholesterol, they don’t reduce the most pathogenic small dense particles of LDL as well as nicotinic acid does. These issues are part of the reason I wrote the book The Niacin Breakthrough, and quite frankly naturopathic physicians (NPs) seem much more interested in nicotinic acid benefits than medical doctors (MDs).
Q: What are the key risk factors linked to cardiovascular disease and how important are dietary and lifestyle changes?
A: There are quite a few risk factors linked to cardiovascular disease, some of which are impossible to eliminate (genetics, sex, age) but dietary and lifestyle changes remain the most important ways that we can manage these risk factors. Dietary factors include both what you eat and how much you eat. It’s important for cardiovascular health to not be overweight, so best to not eat more calories than you burn.
People who get overweight, especially with abdominal fat tend to develop metabolic syndrome (also called prediabetes or insulin resistant syndrome). Metabolic syndrome is an equivalent risk for heart attack or stroke as having had a prior heart attack and it tends to progress to type 2 diabetes with all those additional health risks if not managed properly. While appropriate diet is important for managing or preventing metabolic syndrome, regular aerobic exercise (30 minutes 3-5x/week) is also an important lifestyle practice for weight management that also improves insulin sensitivity and increases the level of HDL “good” cholesterol.
There is quite a long list of dos and don’ts when it comes to dietary changes for cardiovascular health. Salt intake should be limited to less that 3,000 mg/d to avoid high blood pressure and less than 1,000 mg/d if managing high blood pressure. It is generally recommended to limit to a moderate intake of saturated fats and cholesterol containing foods, but it is more important to avoid trans-fatty acids which are present in fried foods, and some nuts and seeds. Trans-fatty acids can both increase LDL and lower HDL cholesterol. Foods that contain fiber (fruits, vegetables) are generally good for cardiovascular health especially foods that have soluble fiber (oats, barley, beans). Soluble fiber binds the cholesterol that the liver produces in bile and the cholesterol that may have been ingested with your meal and carries it to the colon where it is metabolized by the normal flora of the colon. That not only prevents the cholesterol from being absorbed, it provides prebiotic nutrition for colon flora, and those metabolic by-products are the main source of nutrition for the endothelial cells of the colon.
Q: Please name the different types of niacin. Which forms are beneficial for cardiovascular health?
A: Niacin is another name for vitamin B3 and it comes in two forms: nicotinic acid and nicotinamide (also known as niacinamide). Both niacin forms can produce the active metabolic form of vitamin B3 called nicotinamide adenine dinucleotide (NAD+), which is critical for the intracellular chemistry of every cell in the body. Only nicotinic acid has the cardiovascular benefits that I previously listed.
Q: What is the BaleDoneen Method and how is it beneficial?
A: The BaleDoneen Method is a recent discovery of the role that pathogenic bacteria in the oral flora can play by producing inflammatory lesions in the arteries of the body. These arterial inflammations can progress to an obstructing thrombus causing a heart attack or stroke. People with poor oral hygiene, especially gingivitis, can create a pathogenic bacteremia by simply brushing their teeth. Just a slight tear or scratch in a surface capillary in the gum area can open that blood vessel to entry by bacteria in the mouth. The pathogenic bacteria (five different strains identified) can then go throughout the body looking for a place to attach to an arterial wall and start an inflammation. The benefit of nicotinic acid in reducing the risk of this bacteria induced inflammation and thrombus is nicotinic acid’s ability to reduce chemoattractant protein 1, which is a molecule that helps the bacteria attach to the intimal lining of the artery. The other very important piece of the BaleDoneen method of reducing cardiovascular disease is maintaining good oral hygiene and make yearly dental checkups a regular part of our preventive health care.
Q: Please explain the “Supplement Superfecta” for healthy aging.
A: The “Supplement Superfecta” for healthy aging is a name I coined to describe four supplements (Niacin, Dihydroberberine SR, Taxifolin Complex SR and Mixed Tocotrienols) that I consider uniquely beneficial to not only help prevent many health issues associated with aging, but also to deliver many positive benefits that can make our older years more functional and enjoyable. I must explain that I am a horse racing enthusiast, and I breed, raise and race thoroughbred racehorses. A “Superfecta” is the most profitable horse racing bet that you can make on a single race. It requires choosing the top four horses in a race and their order of finish (1st, 2nd, 3rd and 4th). So, it was quite natural for me, when I had identified these four uniquely beneficial supplements for healthy aging, to call them my “Superfecta for Healthy Aging.” They are beneficial for everyone’s health, but I consider them invaluable for those approaching their last lap and want to do their best in finishing their run in the human race.
Niacin
I have already listed the many cardiovascular benefits of nicotinic acid, which also can reduce the microvascular disease in the brain (ministrokes) which is one cause of dementia. The other goal I recommend for persons taking statins is to try to reduce or eliminate statins with optimal dosing of nicotinic acid since statins are associated with an increased risk of dementia.
Recent research on the other form of niacin (niacinamide) has shown that it has a unique ability to improve glaucoma, the most common cause of blindness in the elderly. It takes a high dose of 1,500 mg twice daily. It doesn’t work like traditional symptom-relief glaucoma eye drops to reduce pressure in the eye, but rather improves the function of retinal vision cells, the cause of the vision impairment. Both nicotinic acid and nicotinamide produce the important NAD+ nutrient that is important for all the body’s intracellular chemistry and NAD+ is also important for mitochondrial function and prevention of dementia. As we age we need more NAD+ for good cell function and our bodies are less able to recycle and maintain proper levels of NAD+.
Dihydroberberine SR
Berberine is an ancient Chinese herbal remedy for prevention of cancer, but it is poorly absorbed in its natural state. Hydrating berberine makes it water soluble and very easily absorbed, but also very quickly metabolized giving it a short-term therapeutic blood level. That required increasing the dose to maintain therapeutic blood levels which had side effects of gastritis or giving it multiple times per day. So the solution for optimal blood levels with lower dosing was to create a wax matrix controlled-release formulation which has amazingly improved its benefits. A very large amount of solid research has shown that dihydroberberine, 150 mg twice a day, can improve metabolic syndrome and hypertension as well as many prescription drugs. Metabolic syndrome has increased significantly in the elderly with the COVID-19 pandemic by reducing their activity and giving the tendency to eat more when there is nothing else to do. Dihydroberberine can also lower cholesterol and it has benefits in immune support and preventing viral infections. It has also helped manage the brain cancer called glioblastoma, and it is helpful in reducing alcoholic and non-alcoholic liver disease.
Taxifolin Complex SR
Taxifolin Complex SR is an incredibly effective supplement for immune support and prevention of serious complications of pneumonia which have been so devastating to many older persons who have had COVID-19 infections. It is comprised of vitamin C 500 mg, zinc 15 mg and dihydroquercitin 50 mg in a wax matrix formulation for controlled release and is taken twice a day. The main ingredient for improving immune support is the dihydroquercitin, which is a hydrated form of quercitin, an ancient Chinese herbal remedy to prevent infections. The natural herbal source is poorly absorbed so hydration made it easily absorbed, but like dihydroberberine it requires wax matrix controlled-release formulation to maintain therapeutic levels with twice daily dosing. It is a potent antioxidant and anti-inflammatory agent that has been shown to have cardio protection, hepatoprotection, cancer prevention, Alzheimer’s prevention, and it prevents oxidation of LDL cholesterol.
Mixed Tocotrienols
Tocotrienols are related supplement to vitamin E (alpha tocopherol), which has similar chemical structure but has three added double bonds. There are four forms of tocotrienols depending on where the double bonds are located (alpha, beta, gamma and delta) and all four forms are included in the mixed tocotrienols supplement. Like vitamin E, tocotrienols are a fat soluble supplement so they would have to be taken with a fatty meal if they weren’t emulsified in a gel capsule in a fatty solution. This emulsification formulation allows good absorption even if not taken with a fatty meal. This is another one of the Superfecta supplements with an amazing list of benefits for everyone’s health, especially the elderly. It too, like taxifolin, is a very potent antioxidant that has unique benefits for brain health. It reduces neurotoxicity and prevents brain mitochondrial dysfunction which is one of the main causes of dementia. Population studies have shown that low blood levels of tocotrienols are associated with increased risk of cognitive impairment and dementia.
An impressive two-year study done in Malaysia showed persons on 200 mg twice daily had no increase in brain white matter lesions (mini-scars seen on brain MRI scans) which are associated with dementia compared to control group who had an increase in these lesions. The tocotrienol group also had fewer stokes and less stroke severity and related complications. Tocotrienols also have a potent immune system support with their antioxidant and anti-inflammatory actions that also can improve arthritis. They also can not only reduce oxidation of LDL, but 300 mg/day can also reduce cholesterol. Last, but not least, tocotrienols have benefit in preventing and improving cancer including this list: brain, breast, colorectal, stomach, leukemia, liver, pancreatic, prostate and skin cancers. I personally can attest to the cancer benefits. I was diagnosed with metastatic Non-Hodgkins lymphoma in 2013 and my oncologist was about to start me on a very potent and very toxic form of chemotherapy. I had just learned about the potential cancer benefits of tocotrienols, so I asked my oncologist to allow me to take a four-month trial before starting chemotherapy. We were both amazed four months later when the repeat CT scans showed complete resolution of the primary and metastatic cancer. I have remained on tocotrienols 200 mg twice daily and have stayed in complete remission.
Q: Is there anything else you would like to add?
A: What I would like to emphasize in promoting my “Superfecta Supplements” is that their unique and complementary benefits would not be possible without the proper formulation of each supplement to assure optimal therapeutic results and minimal side effects and toxicity. My research, including bioavailability studies, has shown that wax matrix formulation is ideal for controlling otherwise quickly releasing water soluble supplements. The polygel capsules with tocotrienols emulsified is also ideal for eliminating the requirement of taking them with a fatty meal. I feel it is important for providers to know and inform their patients, not only what unique benefits these supplements offer, but what formulations are needed to get these benefits.
