As we age, it’s natural for us to feel less energetic. Age does that to people. It’s not that we’re running out of energy. After all, we fill our bellies several times a day with enough food to power us through the day. Problem is, as we age our bodies don’t burn that fuel as efficiently as they once did.

It’s similar to what happens with a car over time. The air filter gets dirty, fuel injectors get clogged, spark plugs wear out, carbon builds up on the pistons and cylinders, and suddenly a car that had great pickup and was getting 30 miles a gallon is sluggish and getting only about 20 mpg.

When it comes to our bodies, we have other factors working against us, including   contaminants in our air, food, and water; stress; poor sleep; infections; chronic illnesses too numerous to mention; and even alcohol, caffeine, and medications. When we’re young, our bodies can compensate for this daily wear and tear. As we age, we become less resilient.

The mitochondria (the energy plants within cells) don’t produce energy as efficiently as they once did. The telomers, which keep the strands of our DNA from unraveling, become shorter. And the various systems of the body (i.e., digestive, respiratory, circulatory, and so on) function less efficiently.

To restore proper function, we need a tune-up, and one of the primary objectives of such a tune-up is to increase our Nicotinamide adenine dinucleotide (NAD+) levels.

What Is NAD+?

Nicotinamide adenine dinucleotide (NAD) is a chemical compound present in every cell of the body. It serves as an essential cofactor — a substance that enzymes rely on to perform various fundamental physiological processes. NAD+ is the oxidized version of the compound that’s more biologically available in the body.

Numerous scientific reviews and peer reviewed studies have associated low levels of NAD+ with aging and chronic disease. Scientific evidence now demonstrates that a decline in cellular nicotinamide adenine dinucleotide (NAD+) is a feature of aging and may play a role in the process. In other words, low NAD+ isn’t merely a symptom of aging; it actually causes aging.

Low NAD+ has been linked to numerous age-related diseases, including:

  • Metabolic and cardiovascular disease
  • Cancer
  • Cognitive decline (including Alzheimer’s disease)
  • Sarcopenia (loss of skeletal muscle mass and strength)
  • Frailty

“The coenzyme NAD+ is critical in cellular bioenergetics and adaptive stress responses. Its depletion has emerged as a fundamental feature of aging that may predispose to a wide range of chronic diseases. Maintenance of NAD+ levels is important for cells with high energy demands and for proficient neuronal function. NAD+ depletion is detected in major neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases, cardiovascular disease and muscle atrophy.

Emerging evidence suggests that NAD+ decrements occur in various tissues during aging, and that physiological and pharmacological interventions bolstering cellular NAD+ levels might retard aspects of aging and forestall some age-related diseases.”

~ 2017, Trends in Molecular Medicine, “NAD+ in Aging: Molecular Mechanisms and Translational Implication,” Evandro F Fang, et al.

NAD+ in My Functional Medicine Practice

I have been using NAD+ supplementation in my practice for several years to treat patients who suffer from fatigue. Their symptoms range from difficulty getting out of bed to feeling wiped out after a one-mile walk, or finding themselves exhausted after vigorous exercise and having difficulty recovering. If you suffer from fatigue, you know just how exhausted and depleted you can feel and how that impacts your quality of life.

When a patient’s chief complaint is fatigue, I focus on one primary objective —identifying and addressing the root cause, which often results in providing immediate relief. First, we identify and address the root causes of the patient’s fatigue (which are unique to each patient but can often be linked, at least in part, to mitochondrial dysfunction). At this point, I may recommend NAD+ injections. Soon after receiving an injection, most of my patients report improvement in their energy levels and stamina.

Restoring Mitochondrial Function

NAD+ has multiple benefits and mechanisms of action, which I delve into later in this blog post. But I firmly believe that the increased energy and stamina my patients say they experience after receiving NAD+ injections is primarily the result of improved mitochondrial function.

Mitochondria are the powerhouses inside cells. They manufacture most of the adenosine triphosphate (ATP) your body needs. ATP is an organic compound that provides energy to drive and support many processes in living cells, including muscle contractions, nerve impulses, and chemical synthesis. In healthy conditions, mitochondria account for about 90 percent of ATP produced in a cell. Mitochondria also perform a vital role in the activation of immune cells.

Numerous factors can damage the mitochondria, including:

  • Aging: Mitochondrial function diminishes over time.
  • Genomic susceptibility: Some patients are genetically susceptible to mitochondrial damage, particularly those with the APOE4 gene, which increases the risk of developing Alzheimer’s and cardiovascular disease.
  • Toxic metals: Exposure to heavy metals including mercury from fish and dental amalgams and lead can damage the mitochondria or negatively impact their function.
  • Pollution: Pesticides, herbicides, and other pollutants can negatively impact the health and function of mitochondria.
  • Alcohol
  • Medications/drugs, including the following:
    • Acetaminophen
    • Antibiotics
    • Aspirin
    • Azidothymidine (AZT), which is used to delay the development of acquired immune deficiency syndrome (AIDS) in patients infected with the human immunodeficiency virus (HIV)
    • Cocaine
    • Grisepfulvin, which is an antifungal medication used to treat infections such as ringworm, athlete’s foot, jock itch, and toenail fungus
    • Methamphetamine
    • L-dopa, which is commonly used to treat Parkinson’s disease
    • Non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin, ibuprofen, naproxen, and indomethacin
    • Statins (cholesterol-lowering medications)

How NAD+ Helps to Restore Mitochondrial Health and Function

NAD+ is central to energy metabolism. It directly and indirectly influences many key cellular functions, including DNA repair, chromatin remodeling, cellular aging, and immune cell function. Because cells are the building blocks of the body, all these cellular processes have an impact on your overall health and how you feel.

Restoring NAD+ levels restore mitochondrial function, essentially giving cells a tune-up and positively impacting your health in the following ways:

  • Supports healthy inflammatory response and alleviates age-related inflammation
  • Supports insulin control and energy production within cells
  • Improves the body’s ability to repair its DNA — the body’s genetic programming code for development, function, growth, and reproduction
  • Helps regulate circadian rhythm to enhance sleep

After receiving NAD+ injections, many of my patients have reported increased energy, decreased inflammation, and a better sense of well-being.

Side effects of NAD+ injections are uncommon but include the following:

  • Nausea
  • Redness, tenderness, or swelling at the injection site
  • Infection at the injection site (rare)
  • Headaches
  • Agitation

I don’t recommend NAD+ injections for patients who are pregnant, breastfeeding, prone to seizures, or allergic to NAD+ supplements (injectable or oral NAD+).

Steps You Can Take to Increase Your NAD+ Levels Naturally

Receiving NAD+ via injection is the fastest way to increase NAD+ levels and start feeling relief, but you can also increase NAD+ levels with a few changes to your diet and lifestyle:

  • Practice intermittent fasting — not eating for an extended period; for example, from 7 p.m. to 11 a.m. or eating one high-quality meal a day. Intermittent fasting isn’t for everyone, and I don’t recommend it if you’re hypoglycemic. But it offers several health benefits, including improved weight management and blood-sugar regulation, healthy blood pressure, and lower cholesterol. It also enhances sirtuin activity (sirtuins are signaling proteins that play a role in regulating metabolism).
  • Exercise regularly, alternating aerobic exercise and strength training. Excessive aerobic exercise without strength training may actually deplete NAD+.
  • Avoid excessive exposure to the sun. I’m all for getting outdoors, but excessive exposure to the sun damages DNA, and your body uses NAD+ to repair it.
  • Avoid alcohol. Alcohol consumption is linked to a notable drop in NAD+ levels.
  • Take a quality oral Nicotinamide Mononucleotide (NMN) supplement. NMN is a key ingredient your body uses to replenish NAD+. NMN doesn’t work as quickly as NAD+ injections, but it is still helpful.

Keep in mind that low NAD+ isn’t the root cause of your fatigue. Something is causing it to be low, so don’t look at supplementation or even exercising as a quick fix. Work with your healthcare provider to develop a personalized treatment plan for identifying and addressing the root causes of your low NAD+. You may have a hidden infection, ongoing exposure to an environmental toxin (such as toxic mold), a chronic illness, or some other health condition that’s depleting NAD+. Until the root cause or causes are successfully addressed, you’re likely to continue to struggle with low NAD+ and the resulting fatigue.

About the Author: Dr. Matt Lewis, D.C., DACBN, CFMP®, specializes in diagnosing and treating the underlying causes of the symptoms related to chronic and unexplained illness through nutrition, lifestyle, chiropractic, and other natural approaches to whole-health healing in Tampa, Fla. Dr. Lewis has 20 years of experience practicing nutritional and holistic medicine. He earned his B.S. in Biology from Shenandoah University, his Doctorate in Chiropractic from Life University, his Diplomate status in Clinical Nutrition from the American Clinical Board of Nutrition, his CFMP® from Functional Medicine University, and his certification as a Digestive Health Specialist (DHS) through the Food Enzyme Institute. Dr. Lewis’ passion for health and wellness stems from his own personal experience. With a family history of autoimmune conditions and diabetes, and his own lab tests showing his genetic susceptibility to Hashimoto’s thyroiditis (autoimmune thyroid), Dr. Lewis has learned how to restore his own health and vigor to prevent the onset of these and other illnesses and live an incredibly active life. Through this process, he acquired a deeper understanding of health and wellness, which he now offers his patients in Tampa and elsewhere.