Have you been frustrated by the mixed health information circulating on the Internet and social media? Me too, and I’m ready to speak up about it. I’ll share what the science shows, and reflect on what I have experienced with patients during my 28 years of practice to support your personal wellness goals.
Today’s Hot Topic: NAD+
If you have scrolled social media recently, you’ve probably heard the buzz about NAD+, the “miracle molecule” that influencers claim will reverse aging, boost energy, and extend your lifespan overnight. I have seen so much mixed information on its benefits and proper usage, it makes even my medically trained brain spin. Some claim daily NAD+ drips are essential for energy and to treat addiction. Others say it’s best absorbed when injected daily or every other day. Then you have some promoting NR (nicotinamide riboside), while voices like Harvard trained David Sinclair champion the oral peptide NMN (nicotinamide mononucleotide).
With all this buzz, it’s important we pause and really understand the role of NAD+ in our bodies — and answer the critical question: is more actually better?
I hope to clear up this debate and share why NAD matters, what the science actually says, and how too much of it might not be the answer. Most importantly, I’ll share how NAD can be used thoughtfully and effectively to support long-term health and the goal of Longevity Medicine.
Why is NAD+ so important?
The answer lies in our mighty mitochondria cells. These organelles are responsible for generating the energy that fuels virtually every function in our body. However, we now know that mitochondria even play a role in turning on or off genes (field of epigenetics), influencing how our bodies respond to aging, stress, and disease. When our mitochondria are not functioning properly, we can feel lifeless, age rapidly, and become susceptible to developing neurodegenerative diseases like Alzheimer’s and Parkinson’s.
That is where NAD+ comes in. It is a coenzyme that helps these amazing mitochondrial cells produce energy from our food. But everyday life takes a toll — oxidative stress and inflammation from things like poor diet, sedentary lifestyles, alcohol, environmental toxins, mold exposure, emotional stress, surgeries, over drinking, and even over exercising can damage our mitochondria and NAD+ supply. As life goes on, we continue to deplete this essential coenzyme. Luckily, we are able to rejuvenate our NAD+ supply so our mitochondria can once again do their jobs. In fact, numerous studies have shown that good levels of NAD+ can improve body composition, better skin, brain, heart and just an overall better sense of well-being. So, as you see, supporting the mitochondria with NAD+ is crucial to a happy healthier life.
How much is too much?
While NAD+ is praised for its potential benefits, emerging research suggests that “excessive” supplementation may do more harm than good. Overloading our bodies with NAD+ can upregulate enzymes that degrade it, potentially tipping the scales towards unintended consequences that can predispose us to cancer and cardiovascular issues instead of doing the good we intended to take it for.
Let me break this down from a scientific perspective. NAD+ is not directly obtained from the diet. Rather, it is synthesized in the body from forms of vitamin B3, such as niacin, nicotinamide, and nicotinamide riboside. It plays a vital role in cellular energy production, which is more specifically called the electron transport chain that occurs in the mitochondrial cell’s membrane. This electron transport chain generates our cell’s energy (known as ATP).
Think of it like a car battery: without enough charge, nothing runs.
Our bodies are in a constant equilibrium known as redox balance, which can be disrupted in disease states. While most of us have heard of oxidative stress (often described as “rusting from within”), fewer are aware of its counterpart: reductive stress. Overloading on NAD+ can throw us into this state, increasing levels of its end products NADH, NADPH and glutathione. Ironically, we then end up undoing our intended benefit from NAD+, leading to mitochondrial disruption, more free radicals instead of less, increased risk of heart disease, neurodegeneration, and even cancer.
Instead of overloading our bodies with NAD+, it is essential to address the root cause of NAD+ depletion.
One key enzyme, NNMT (nicotinamide N Methyltransferase), becomes overactive when excess NAD+ is introduced. This enzyme plays a role in recycling NAD+ but also reduces our methylation reserves, which are critical for detoxification, hormone balance, cardiovascular health, and longevity. This is why it is essential to assess your methylation status before or during NAD+ supplementation. One indirect way to check is by measuring your homocysteine level through a simple blood test. If found to be high (optimal is around 6), then adding nutrients that support methylation can be helpful while you are supplementing NAD+.
Dosing methods… what really works?
Despite the buzz, there actually is limited data on the benefits of high dose IV NAD+ outside of addiction treatment. If used, it must be dripped very slowly – over several hours – to avoid side effects like stomach cramps, headaches, and heart palpitations. NAD+ is a large molecule; therefore, it cannot be absorbed in the skin or taken orally. If you hear someone saying something different, please shut that down!
Subcutaneous injections (into the fat under the skin) are widely shown online, but injecting right near the belly button is a fast track to a large, black bruise from hitting the vessels. Low dose (less than 100 mg) subcutaneous injections, 2-3 days a week can be helpful, though some of my patients report a jittery, adrenaline rush-like response.
My preferred method of NAD+ replacement is through the precursors, nicotinamide riboside (NR, marketed as NIAGEN+) and nicotinamide mononucleotide (NMN). NMN is a nucleotide, while NR is a form of vitamin B3. Both are integral to the biosynthesis of NAD+ and tend to produce fewer side effects than direct NAD+ administration. NR is often praised for its excellent bioavailability, meaning it is readily absorbed and used throughout the body. The difference between them is in the way they are taken up by the cell: NMN’s conversion happens “outside” the cell before being taken up by the cell and NR is “directly” taken up by the cells. While no strong evidence favors one over the other, emerging studies have shown that they can potentially improve hormone balance, fertility, and relieve symptoms of other inflammatory states like long Covid or mold toxicity.
When our body responds to increased NAD+ supplementation in our system, it can lead to a increase in enzymes (CD38and PARP) and harmful byproducts like 4 pyridone-3 carboxamide-1-Beta-D-ribonoside (4PYR) which is linked to cardiovascular damage. So, to combat this, combining NAD+ or its precursors with an antioxidant like apigenin is a smart strategy. Apigenin is a flavonoid that has numerous beneficial effects on our body’s metabolism – mitigating inflammation, supporting brain health, and aiding cellular repair. If used together, you can address the root cause of the issue and can prevent buildup of other metabolites that can cause more damage than benefit.
As you can see, supporting our mitochondria is not something to take lightly — especially with all the buzz around NAD+ supplementation and the real possibility of doing more harm than good if it’s not approached thoughtfully.
When done correctly, enhancing mitochondrial function can lead to healthier aging, better skin, improved body composition, and a greater sense of vitality and well-being.
Simply put, mitochondria power how we look, feel, and function. Therefore, whatever we can do to support our mighty mitochondria is crucial to a happier, healthier life. Healthy habits like better sleep, good gut health, hormone balance, good nutrition, exercise, and less stress all do this. Still, in certain situations, we may need some extra support, and carefully increasing NAD+ through its precursors can help us get there.
More is not always better.
I hope my message now is clear: Overloading the system can backfire, triggering unwanted side effects and disrupting your body’s natural balance. If you choose to supplement, consider cycling it with your NAD+ precursors, and pairing them with supportive antioxidants like apigenin and methylation aids such as SAMe (S-adenosyl-L-methionine) or methylated B vitamins. This balanced approach honors the body’s built-in feedback systems while giving your cells the support they need to thrive.
Supporting your mitochondria isn’t just about energy — it’s about vitality, resilience, and aging well. Do it wisely!
Wishing you wellness,
Dr. Anjali Noble