NAD+ in a Pill:
Challenges, Bioavailability and Formula
Taking an effective intravenous therapy and replicating that in a pill – that was the challenge.
How do you formulate an oral supplement that consists of delicate compounds that can help deliver NAD+ and other therapeutic agents to the brain? It’s a tricky subject and tough question to answer. The ratios, feasability and stability of ingredients had to be perfected, and the quality of each raw ingredient must be meticulously tested to ensure a final product that gets the job done. Learn how we did it.
NAD+ (nicotinamide adenine dinucleotide) has received a lot of recent attention in the press and among certain scientific communities such as the addiction and integrative medical fields. A growing number of medical clinics are utilizing NAD+ intravenous infusions for numerous chronic diseases and neurological cases with positive results. We wrote about the multitude of benefits from this therapy in another article (“A Closer Look at NAD Brain Restoration Therapy“), and also highlighted the importance of NAD+ as we age. Now we take things a step further and see how we can take the therapeutic effects of a medical procedure, and package that into a pill available for anyone to benefit from.
But first, let’s quickly go over the background and importance of NAD+, and show the significance as it relates to a number of modern health issues.
What is NAD+?
As we grow older, certain genes can be triggered that accelerate degenerative aging processes. This can result in symptoms such as chronic fatigue, loss of mental clarity, depression, stress, anxiety, and various other chronic illnesses. A critical factor in this process is a coenzyme by the name of nicotinamide adenine dinucleotide (NAD+) that enables the transfer of energy from the foods we eat to vital cell functions, especially in the brain. Every cell in the body needs it. This compound is required to “turn off” those genes that accelerate aging, and it’s also involved in a host of other functions from helping to regulate our circadian rhythms (sleep cycles) to lowering cholesterol and blood sugar. The problem as we’ll see comes when NAD+ levels begin to decline (something known as NAD Energy Deficiency, or NED), either due to lifestyle, diet, use of drugs or alcohol, stress, toxins, or a host of other factors.
“NAD+ is the closest we’ve gotten to a fountain of youth. It’s one of the most important molecules for life to exist, and without it, you’re dead in 30 seconds.”
DAVID SINCLAIR
CO-DIRECTOR OF THE PAUL F. GLENN CENTER FOR THE BIOLOGY OF AGING AT HARVARD MEDICAL SCHOOL
Modern Life and the Impact on NAD+ Production
The rigors of modern life have taken a toll on the levels of NAD+ in our bodies. Three main factors are to blame for NAD+ deficiencies:
- Stress: We simply can’t seem to escape it in today’s rat race environment. Stress has become common place, with the American Psychological Association linking chronic stress to the six leading causes of death: heart disease, cancer, lung ailments, accidents, cirrhosis of the liver and suicide. Add in oxidative stress, where an imbalance between the production of free radicals and the ability of the body to counteract with antioxidants occurs, and you create an environment where NAD+ is being depleted quite quickly. One such biomarker of oxidative stress is 8-Isoprostane. This prostaglandin-like compound is produced by free radical-catalyzed peroxidation, and has been suggested to be the most reliable approach to monitor oxidative stress. High levels of 8-isoprostane is an indication of oxidative damage and a reduction in available NAD+.
- Diet / Alcohol / Drugs: Part of the reason for NAD+ deficiency is that diet and what you put in your body is critical. The modern day diet for most has resulted in the abandoning of traditional, whole foods in favor of modern processed foods high in sugar, refined flour and unhealthy fats.In addition, the use of alcohol and drugs are contributors of NAD+ depletion. Studies have demonstrated the efficacy and safety of IV NAD in detoxifying patients from alcohol, opiates, tranquilizers and stimulants. Clinical experience has shown benefits in greatly reducing withdrawal symptoms, as well as reducing, and often eliminating associated cravings.
- Inflammation: Inflammation has become a major issue and contributing factor in a majority of common chronic conditions. Simply put, inflammation is your body’s response to stress – whether it be from diet, emotions, lifestyle, or environment. One particular component of inflammation that is associated with NAD+ depletion is a glycoprotein called CD38. Found on the surface of many immune cells, CD38 plays an important role in inflammation. CD38 causes migration of neutrophils and monocytes toward sites of inflammation, signals maturation of dendritic cells during inflammatory cytokine activation, and generates Ca2+mobilizing metabolites. To do this though, it must consume large amounts of NAD+.
NAD+ and Aging
Compelling research shows that NAD+ has a unique ability to protect tissues, induce DNA repair, and increase life span. To understand how NAD+ can prevent aging, we have to look at an increasing subject of aging – telomeres. Telomeres form the ends of human chromosomes. Without them, DNA strands become damaged and our cells can’t do their job. They basically act as the aging clock in every cell. The issue arises because telomeres shorten with each round of cell division, and shortening can be exacerbated by a number of other influences. Shorter telomeres are linked to an increased incidence of disease and premature cellular aging. Other studies have associated short telomeres with a decrease in bone mineral density in women and immune functioning.
Research has shown the correlation of NAD+ and telomere length. Increased NAD+ availability can increase tankyrase removal of Telomeric Repeat Factor 1 (TRF1). TRF1 is a protein that binds at telomere ends and is known to protect telomeres from DNA mechanisms that are used for repair purposes and at the same time regulate the activity carried out by telomerase. This action, in turn, improves telomerase access and elongation of the telomere, which is important in a slowing of the aging process.
NAD+ and the Brain
One of the most impacted organs from NAD+ deficiency is the brain. NAD+ plays a vital role in the brain, with a 2007 study stating, “NAD+ and NADH (the reduced form of NAD+) may also mediate brain aging and the tissue damage in various brain illnesses. Our latest studies have suggested that NADH can be transported across the plasma membranes of astrocytes, and that NAD+ administration can markedly decrease ischemic brain injury. Based on this information, it is proposed that NAD+ and NADH are fundamental mediators of brain functions, brain senescence and multiple brain diseases.”
NAD+ helps to replenish the supply of neurotransmitters, improve cognitive functioning, withdraw from addictive substances, overcome anxiety, depression, chronic or acute stress, post-traumatic stress, CTE, and other conditions by giving the brain what it needs to return to proper functioning. NAD+ has been shown to be effective with cases of brain fog, cognitive impairment, and “chemo brain”. It has a powerful capacity to “reset” the brain to its original set point.
“I felt great….there was a definite improvement in energy levels, focus, and mindset.”
NAD+ in a Pill
We know that intravenous infusions of specific stable forms of NAD+ have an impact on NAD+ levels, and some supplements are utilizing the precursor, Nicotinamide Riboside (NR), which has shown promise in raising NAD+ levels in plasma, but how can we introduce NAD+ in a pill format and get it to where it needs to go – in this case the brain. That’s the challenge Innovative Medicine along with Thomas K. Szulc, MD and a team in pharmaceutical and nutraceutical development accepted.
Absorption & Bioavailability
One of the greatest concerns of ingesting NAD+ versus intravenous or intranasal application is the absorption of NAD+ through the digestive system. It has long been known that taking any supplement orally (by mouth) is a fairly complex and sometimes inefficient process where compounds in the supplement must cross from the small intestine into the bloodstream. This also means that all the compounds in any supplement must first survive the stomach acid that can destroy many ingredients.
NAD+ is considered a delicate molecule, and thus many believe that orally consuming the coenzyme may destroy it. This line of thought stems from a 1983 bioavailability study that indicated that ingested NAD+ was primarily hydrolyzed in the small intestine by brush border cells (Baum et al., 1982; Gross and Henderson, 1983). But other studies since that time seem to show a different story.
One study in 2006 entitled “Comparison of metabolic fates of nicotinamide, NAD+ and NADH administered orally and intraperitoneally; characterization of oral NADH” (J Nutr Sci Vitaminol (Tokyo). 2006 Apr;52(2):142-8.) researched the outcome of mice who were administered nicotinamide (Nam), NAD+ (the oxidized version of nicotinamide adenine dinucleotide) and NADH (the reduced version of nicotinamide adenine dinucleotide) both intraperitoneally (injection to the abdomen) and orally. The results showed “intraperitoneal injection of Nam, NAD+ and NADH produced significant increases in urinary excretion of Nam and its metabolites. Similar results were obtained when Nam and NAD+ were given orally.”
Other’s seem to share in the idea that NAD+ can be orally administered without destroying the molecule as it passes through the digestive system. In the clinical research and experience with various patients by Thomas K. Szulc, MD, he found that NAD+ in specific formulas with other ingredients taken orally had a positive effect relative to NAD+ administered intravenously in small doses. It was this research and compatibility analysis into a formula that would be readily absorbed, bioavailable, and create a synergistic cognitive enhancing effect that led him to formulate an oral nutraceutical supplement with NAD+ as the main ingredient (more on that below).
Formulation
As mentioned earlier, NAD+ is a delicate oxidizing agent. To simply put any ingredient into a pill and expect positive results would be foolish. In addition, simply raising NAD+ levels in plasma without having that NAD+ enter the brain would prove to be an ineffective supplement. The challenge here is to formulate a oral supplement that consists of compounds that can both provide a synergistic effect (thus requiring less quantity of any ingredient for maximal impact) and help deliver the therapeutic agents to the brain. The ratios, feasability and stability of combining certain ingredients, and quality of each raw ingredient must be meticulously tested to ensure a final product that has a potent therapeutic effect on the brain. This again, was a challenge that took a team consisting of physicians, medical professionals, and experts in compatibility analysis as well as pharmaceutical and nutraceutical development and encapsulation to figure out. The result is a nutraceutical brain formula unlike any other.
NADOVIM®:
A Special NAD+ Formula
Nadovim is the first daily nutraceutical whole brain health supplement with NAD+ as the primary ingredient. Formulated exclusively for Innovative Medicine by Dr. Thomas K. Szulc and utilizing a state-of-the art FDA-registered and inspected manufacturer, Nadovim combines a stable, high quality form of nicotinamide adenine dinucleotide along with seven other natural ingredients proven to boost cognitive functioning. This bioenergetically selected and enhanced supplement helps to fuel the brain, increasing clarity, memory, focus, mood and general well-being.
The advanced formula contains high quality (energetically tested by Dr. Szulc and our medical team) nootropic agents such as Bacopa monierri, Cat’s claw, and coenzyme Q10 alongside other vitamins, amino acids and nutrients to help support proper brain function and raise levels of NAD+. NAD+ depletion (also called a NAD Energy Deficiency, or NED) is one of the main contributors to symptoms such as brain fatigue, brain fog, loss of concentration, poor memory, and a host of other brain-related symptoms we sometimes attribute to aging. Better understanding the depletion of this incredibly important coenzyme and how mitochondrial function becomes impaired, we see as a result of this there are fewer mitochondria surviving. Mitochondria are the “powerhouses” that help ensure cellular processes. This vicious cycle of mitochondrial depletion results in many of the physical symptoms of aging and degenerative processes, such as chronic fatigue, chronic fatigue syndrome, substance abuse, depression, stress, anxiety, and various other chronic illnesses.
Nadovim has the ability to provide the brain and body with NAD+ and a proprietary formula of botanicals, amino acids, vitamins and minerals that reverses NED and improve cognitive functioning. Only two capsules a day is sufficient in producing the following benefits:
- Supports overall brain health
- Improves cognitive function (kinase activity, neuronal synthesis, restoration of synaptic activity and nerve impulse transmission)
- Increases focus, concentration, and clarity of mind
- Stimulates production of dopamine, serotonin, and noradrenaline, thereby improving mood
- Reduces stress and cortisol / acts as an anti-stress agent against acute and chronic stress
- Improves memory acquisition and retention as well as problem-solving abilities
- Enhances mitochondrial function and reduces oxidative stress in the brain
- Boosts attention, cognition and impulse control
- Acts as a neuro-protectant
Discover more about Nadovim
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