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NAD+ May Be The Health-Boosting Antioxidant Of Your Dreams

Meet the molecule tied to muscle performance, weight loss, and healthy aging.

Fast Facts

  • NAD+ is a coenzyme involved in hundreds of metabolic processes. NAD+ levels decline naturally with age. 
  • Declining NAD+ levels have been linked to a number of health issues including diabetes, heart disease, neurodegenerative diseases, cancer, and premature aging.
  • Some studies suggest that supplementing with NAD+ may improve muscle performance, boost immunity, help with weight loss, and support heathy aging.

The internet is buzzing with products and treatments that claim to help you look and feel younger. While there’s no magic bullet that can give you the muscles, stamina, or skin of your 20s, some treatments have some promising science behind them, including nicotinamide adenine dinucleotide (NAD). Emerging research suggests that NAD+ (a form of NAD) might help fight the ravages of aging and delay the progression of age-related diseases.

NAD+ isn’t the fountain of youth. But it is one of your body’s most important molecules due to its key role in almost all major biological processes, says Jack Jeng, M.D., Chief Medical Officer at Hone Health. 

“NAD+ remains one of the most promising and exciting molecules in the field of aging and longevity today,” says Jeng.

NAD+ is a coenzyme found in every cell of your body that’s involved in hundreds of metabolic processes. It’s critical for converting nutrients into energy and regulating other cellular functions. 

But levels of NAD+ drop as you age. Brain imaging studies suggest (1, 2) that NAD+ levels in the brain drop by as much as 25 percent between young adulthood and old age. Stress, alcohol use, and diet can speed up that decline (3).

Why that’s worrying: Declining NAD+ levels have been linked to a number of health issues including diabetes, heart disease, neurodegenerative diseases, cancer, and even premature aging (4).

Fortunately, some early research suggests that NAD+ therapy may slow or even reverse some aspects of aging and delay the progression of these age-related diseases.

“Many of the published studies utilized animal models so we are still awaiting confirmatory results in humans,” says Jeng. “But the data is overwhelmingly positive and there appear to be no serious adverse effects with NAD+ supplementation.”

More studies are needed, Jeng notes, but NAD injections, supplements, and IV therapy “have the potential to reduce disease and suffering while helping us live healthier and longer lives.”

NAD+ Basics

  • NAD+ is a coenzyme found in every cell of your body that’s involved in hundreds of metabolic processes.
  • Declining levels of NAD+ have been linked to diseases like diabetes, heart disease, neurodegenerative disease, cancer, and premature aging.
  • Research on NAD+ is still young, but animal studies and a few clinical trials in humans have shown promising results.

What Is NAD+?

There’s a lot to unpack about NAD+ but before diving too deeply into the potential benefits of NAD+ therapy and NAD+ injections, it’s helpful to understand how coenzymes work in the body.

Coenzymes help other enzymes function properly, so they’re often referred to as “helper molecules,” because they support many cellular processes (5). NAD+ is involved in hundreds of reactions in the body, including:

  • Helping cells produce energy from food. NAD works closely with other molecules like AMP (adenosine monophosphate) and ADP (adenosine diphosphate) to create energy (6).
  • Repairing DNA (7)
  • Cell signaling
  • Electron transport, which is important for creating energy
  • Maintaining healthy mitochondria. Most aging-related diseases, particularly, neurodegenerative diseases, have mitochondrial involvement (8), so maintaining their health as you age is critical.
  • Regulating gene expression
  • Immune function

What Are The Differences Between NAD, NAD+, and NADH?

NAD+ is sometimes referred to as just NAD, but they’re not exactly the same thing. There are actually two forms of NAD: NAD+ (the oxidized form) and NADH (the reduced form).

The two forms of NAD are what is called a redox couple. In redox reactions, one substance loses electrons (oxidation) while another gains them (reduction). These reactions play a central role in energy creation.

For example: in cellular respiration—the process by which food is transformed into energy within cells through the transfer of electrons—NAD switches back and forth between the oxidized form in which it loses an electron (NAD+) and the reduced form in which it gains one (NADH) from glucose.

NADH shuttles its gained electron to the mitochondria to generate adenosine triphosphate (ATP), the energy-carrying molecule found in your cells. Your mitochondria utilize ATP in order to store, release, and use energy.

Once NADH drops off its electron, it is converted back to NAD+, ready to start the process again.

NAD+ and NADH

  • NAD+ is a coenzyme. Coenzymes help other enzymes function properly, they’re often referred to as “helper molecules.”
  • There are two forms of NAD: NAD+ (the oxidized form) and NADH (the reduced form). NAD switches between NAD+ and NADH
  • Redox couples play a central role in energy creation.
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How Does NAD+ Work in the Body?

Your body synthesizes NAD+ when you eat foods containing tryptophan (an amino acid your body uses to create niacin) or forms of vitamin B3. We don’t make most of our body’s NAD+, we actually recycle the molecules and reuse them (9).

The two main NAD+-responsive signaling pathways requiring NAD+ involve sirtuins and PARPs. Sirtuins regulate a wide variety of proteins involved in mitochondrial function, metabolism, inflammation, cell division, circadian rhythms, and cell creation and death. PARPs are required for important cellular processes like DNA repair. “Once we discovered the role of NAD+ with sirtuins and PARPs, we realized how critical the molecule really is,” says Jeng.

What Causes NAD+ Levels to Decline?

Beyond aging, other issues that can cause NAD+ levels to decline include:

Excessive Alcohol Consumption

NAD+ is used by the body to convert alcohol to acetaldehyde, a toxic compound responsible for hangovers and alcohol-related cancers (10). Excessive alcohol consumption has many negative effects, such as liver damage, and it has also been shown to decrease NAD+ levels (11).

Liver Disease

NAD+ is primarily synthesized in your liver (12). Forms of liver disease, including nonalcoholic fatty liver disease, primary sclerosing cholangitis, and primary biliary cholangitis, depress NAD+ levels, with alcohol-related liver disease having the greatest negative effect (13).

Diabetes

Both type 1 and type 2 diabetes have been shown to decrease NAD+ levels. While the mechanism is complex, the primary cause for the decrease appears to be due to increased NAD+ utilization for DNA repair (14).

Obesity

Several studies have found that obesity decreases NAD+ levels. Giving mice NAD-boosting molecules has been found to stop obesity-related NAD+ decline—and even suppresses weight gain (15).

NAD+ In The Body

  • Your body synthesizes NAD+ when you eat foods containing tryptophan (an amino acid your body uses to create niacin) or forms of vitamin B3.
  • Aging, alcohol misuse, illness, and obesity can cause NAD+ levels to decline.

How Can You Increase NAD+ Levels?

There are several ways to increase NAD+ in your body.

Diet

Eating foods rich in certain B vitamins can increase NAD+ levels, says Reda Elmardi, R.D., C.S.C.S., a dietitian and strength and conditioning trainer.

Two types of B vitamins to focus on:

  • Niacin (Vitamin B3)
    Niacin is a water-soluble vitamin that helps maintain good health. It is often referred to as Vitamin B3. In addition to its role in energy production, niacin has been shown to improve memory and cognitive function (16).
  • Riboflavin (Vitamin B2)
    Riboflavin is a water-soluble vitamin that is involved in many metabolic processes. It is responsible for helping the body produce red blood cells and other compounds.
 

Foods high in niacin and riboflavin include vegetables, fruits, nuts, legumes, whole grains, fish, meat, dairy products, and eggs.

Oral and Topical Supplementation

Oral supplements typically contain nicotinamide riboside or nicotinamide mononucleotide, which is converted into NAD+ in the body. But oral supplementation may not be as effective as NAD+ injections or NAD+ infusions because rather than going straight into your bloodstream, it has to pass through your digestive system, where it is metabolized (17).

Topical supplements contain nicotinamide mononucleotide or nicotinamide adenine dinucleotide phosphate, which are both converted into NAD+ after they are absorbed through the skin.

NAD+ Injections

NAD+ injections are given subcutaneously into fatty tissue—usually in the back of the arm, the abdomen, or the flank/lower back, which is then absorbed into the bloodstream. Injections may lead to better absorption when compared to oral administration because it bypasses the gastrointestinal system.

You can work with Hone to see if NAD+ injections are right for you. Simply create an account, then describe your symptoms and goals using Hone’s online form. A board-certified physician will review your answers, and prescribe NAD+ if appropriate. If your prescription is approved, NAD+ will be sent straight to your door.

NAD+ IV infusion

IV infusions of NAD+ are the most direct delivery method and have been used for decades, spanning back to a 1961 report describing its use for the treatment of addiction. While this mode of administration appears to be safe and well-tolerated, it has to be given slowly over hours as faster drip rates can cause headaches and shortness of breath (18).

How to Increase NAD+

  • Eating foods rich in certain B vitamins can increase NAD+ levels.
  • Oral supplementation may not be as effective as NAD+ injections or NAD+ infusions
  • IV infusions of NAD+ are the most direct delivery method.

Declining NAD+ levels have been linked to diabetes, heart disease, neurodegenerative diseases, cancer, and even premature aging

What Are the Benefits of NAD+ Supplementation?

While human data is limited and studies are ongoing, these are the benefits of boosting NAD+ levels that seem to be the most promising:

Improving muscle performance

A recent clinical study (19) with healthy older men comparing daily NAD+ supplementation with placebo showed improved muscle performance (measured by gait speed and grip strength).

Protecting the liver and kidneys

Studies involving mice show that boosting NAD+ levels improves the health of the liver, increases its ability to regenerate, and protects it from toxicity. Data from mice also showed NAD+ supplementation protects the kidneys from damage seen in diabetes and chemotherapy (9).

Improving blood vessel function

Cardiovascular and cerebrovascular diseases such as hypertension, coronary heart disease, and strokes cause immense suffering and are a leading cause of death in the United States. While human data is still being generated, animal models demonstrate that boosting NAD+ levels improves blood vessel function and blood flow while reducing elastic artery stiffness (9).

Delaying neurological diseases

Earlier studies have shown that diets rich in niacin, an NAD+ precursor, may reduce the risk of Parkinson’s disease (20, 21). More recently, neuroscientists have become interested in the effects of NAD+, and studies in animal models have shown promise in delaying the effects of Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis (ALS) (9).

Boosting immunity

NAD+ helps maintain healthy cells through DNA repair and may boost the immune system. Animal studies show that NAD+ supplementation has anti-inflammatory properties, which may offer additional immunity benefits (9).

Helping with weight loss

When you eat, your body breaks down carbohydrates into glucose and oxygen. The glucose enters your cells where it gets converted into ATP, and this conversion requires NAD+. 

Obesity and the subsequent metabolic disorders impair glucose uptake through insulin resistance and have been shown to decrease NAD+ levels in a range of tissues. Administration of NAD-boosting molecules in mice prevented the reduction of NAD+ levels, improved insulin sensitivity, and suppressed weight gain (9).

Aging and longevity:

Age-related NAD+ declines don’t just happen in humans; they’re seen across many organisms. Boosting NAD+ levels has been shown to increase lifespan in yeast and mice (9). While human studies will take a lifetime (literally), there are multiple studies in progress.

NAD+ Supplementation

Supplementing with NAD+ may:

  • Improve muscle performance
  • Protect the liver and kidneys
  • Improve blood vessel function
  • Delay neurological diseases
  • Boost immunity
  • Help with weight loss

Who Shouldn’t Try NAD+?

If you’re thinking of taking the leap into trying NAD+, Jeng suggests making sure you keep these aspects in mind:

  • While no serious adverse effects have been seen with NAD+ supplementation in animal or human studies, robust safety data in humans remain limited. It is possible that raising NAD+ levels may promote DNA repair and angiogenesis (the formation of new blood vessels), which could theoretically help cancer cells grow. But long-term studies in mice did not demonstrate this; in fact, they showed prevention of cancer growth and spread (9).
  • NAD+ is considered a supplement, so it is not regulated as a medication by the FDA and there’s no established dose. Human studies over a period of days to weeks have shown oral nicotinamide riboside (an NAD+ precursor) up to 2 grams daily is well tolerated and safe (22, 23, 24, 25).
  • No drug or food interactions have yet to be determined, but always consult your doctor before starting any supplements.
  • NAD+ supplements alone are not a miracle cure. As with all supplements, it should be taken in combination with a healthy lifestyle and diet.

The Bottom Line

Studies on NAD+ suggest that supplementing with the coenzyme could help prevent some age-related diseases and slow the aging process. More research is needed, however, especially with human clinical trials. If you are interested in boosting your NAD+ levels through NAD+ supplements, injections, or IV therapy, speak to your doctor.
References:
1. Bagga P, et al (2020). Single-Voxel 1 H MR spectroscopy of cerebral nicotinamide adenine dinucleotide (NAD+ ) in humans at 7T using a 32-channel volume coil. https://pubmed.ncbi.nlm.nih.gov/31502710/

2. Zhu, Xiao-Hong et al (2015). In vivo NAD assay reveals the intracellular NAD contents and redox state in healthy human brain and their age dependences. https://www.pnas.org/doi/abs/10.1073/pnas.1417921112

3. Poljsak B, et al (2020) Healthy Lifestyle Recommendations: Do the Beneficial Effects Originate from NAD+ Amount at the Cellular Level?. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752291/

4. Yahyah Aman, et al (2018). Therapeutic potential of boosting NAD+ in aging and age-related diseases. https://www.sciencedirect.com/science/article/pii/S2468501118300063

5. Coenzymes, an overview [Fact Sheet] https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/coenzymes

6. Covarrubias AJ, et a; (2021) NAD+ metabolism and its roles in cellular processes during ageing. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7963035/

7. Nady Braidy, et al (2020). NAD+ therapy in age-related degenerative disorders: A benefit/risk analysis. https://www.sciencedirect.com/science/article/abs/pii/S0531556519307582?via%3Dihub

8. Haas RH (2019). Mitochondrial Dysfunction in Aging and Diseases of Aging. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627182/

9. Rajman L, et al (2018) Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence. Cell Metab. https://pubmed.ncbi.nlm.nih.gov/29514064/

10. Guo R, Ren J (2010). Alcohol and acetaldehyde in public health: from marvel to menace.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2872347/

11. Samuel W. French (2016). Chronic alcohol binging injures the liver and other organs by reducing NAD+ levels required for sirtuin’s deacetylase activity. https://www.sciencedirect.com/science/article/abs/pii/S0014480016300107?via%3Dihub

12. Zhou CC, et al.(2016). Hepatic NAD(+) deficiency as a therapeutic target for non-alcoholic fatty liver disease in ageing. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4945761/

13. Fan L, Cacicedo JM, Ido Y. (2020). Impaired nicotinamide adenine dinucleotide (NAD+ ) metabolism in diabetes and diabetic tissues: Implications for nicotinamide-related compound treatment. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610120/

14. Fan L, Cacicedo JM, Ido Y (2020). Impaired nicotinamide adenine dinucleotide (NAD+ ) metabolism in diabetes and diabetic tissues: Implications for nicotinamide-related compound treatment. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610120/

15. Okabe K, Yaku K, Tobe K, Nakagawa T (2019). Implications of altered NAD metabolism in metabolic disorders. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6511662/

16. Kennedy DO. (2016) B Vitamins and the Brain: Mechanisms, Dose and Efficacy–A Review. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4772032/

17. Liu L, Set al (2018) Quantitative Analysis of NAD Synthesis-Breakdown Fluxes. https://pubmed.ncbi.nlm.nih.gov/29685734/

18. O’Hollaren P (1961) Diphosphopyridine nucleotide in the prevention, diagnosis and treatment of drug addiction. A preliminary report. https://pubmed.ncbi.nlm.nih.gov/13730082/

19. Igarashi, M., et al (2022). Chronic nicotinamide mononucleotide supplementation elevates blood nicotinamide adenine dinucleotide levels and alters muscle function in healthy older men. https://www.nature.com/articles/s41514-022-00084-z

20. Hellenbrand W, et al (1996). Diet and Parkinson’s disease. II: A possible role for the past intake of specific nutrients. Results from a self-administered food-frequency questionnaire in a case-control study. https://pubmed.ncbi.nlm.nih.gov/8797457/

21. Fall PA, et al (1999). Nutritional and occupational factors influencing the risk of Parkinson’s disease: a case-control study in southeastern Sweden. https://pubmed.ncbi.nlm.nih.gov/9918341/
22. Airhart SE, et al (2017). An open-label, non-randomized study of the pharmacokinetics of the nutritional supplement nicotinamide riboside (NR) and its effects on blood NAD+ levels in healthy volunteers. https://pubmed.ncbi.nlm.nih.gov/29211728/

23. Dollerup OL, et al (2018). A randomized placebo-controlled clinical trial of nicotinamide riboside in obese men: safety, insulin-sensitivity, and lipid-mobilizing effects. https://pubmed.ncbi.nlm.nih.gov/29992272/

24. Simic P, et al (2020). Nicotinamide riboside with pterostilbene (NRPT) increases NAD+ in patients with acute kidney injury (AKI): a randomized, double-blind, placebo-controlled, stepwise safety study of escalating doses of NRPT in patients with AKI. https://pubmed.ncbi.nlm.nih.gov/32791973/

25. Dollerup OL, et al (2020). Nicotinamide riboside does not alter mitochondrial respiration, content or morphology in skeletal muscle from obese and insulin-resistant men. https://pubmed.ncbi.nlm.nih.gov/31710095/

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