For centuries, people tried various remedies to ward off sickness, disease and even death. Today, science is proving that an increase in cellular longevity is not a dream but a reality. Recently, nicotinamide adenine dinucleotide (NAD+) became prized in scientific research due to its central role in biological functions. 

NAD, a coenzyme required to metabolize carbohydrates, fats and amino acids to energy, influences healthy aging. According to Global Market Insights, the NAD+ market exceeded $488 million in 2021. Driven by changing lifestyle choices, the industry is expected to grow 13% CAGR from 2022-2030.

Interest in longevity science is soaring. Anything that promises to help one take control of his health is a hot topic. NAD+ falls into this category as one of the primary targets of longevity research. This column reviews the science of NAD and why it is the fountain of cellular health. 

The Science of NAD+

NAD is found in all living cells. It is comprised of two dynamic energy exchanging forms: NAD+ the oxidized form, and NADH, the reduction form. NAD+ is a critical metabolic intermediate that serves as a universal electron acceptor in hundreds of oxidation/reduction reactions reduced to NADH. Maintaining a healthy ratio of coenzyme NAD+/NADH affects many aspects of cellular health, including the dynamics between metabolism and immune cell functions. 

According to Christine DeWitt, MD, department of dermatology, Georgetown University, NAD+ plays a central role in cell metabolism. It serves as a substrate for sirtuins, which help prevent telomere deterioration, now thought to be critical in aging. Without sufficient NAD+, sirtuins do not work efficiently; they cannot remove acetyl groups from histones, they cannot silence genes nor extend lifespan. NAD+ has a direct and essential relationship with vitamin B3, also commonly known as niacin. This relationship is rooted in the biosynthesis of NAD+ itself, as vitamin B3 serves as a precursor for NAD+ synthesis.

There are three main forms of vitamin B3: niacin (nicotinic acid), nicotinamide (also known as niacinamide) and nicotinamide riboside. Each can be converted into NAD+ through distinct biochemical pathways within the human body, highlighting the critical role of vitamin B3 in cellular energy metabolism and overall health. NAD is such an important molecule in the body that it is made in several different ways.¹ 

Nicotinamide riboside (NR) is a vitamin B3 derivative that serves as an efficient NAD+ precursor. NR is converted into nicotinamide mononucleotide (NMN) by the enzyme NR kinase, and NMN is converted into NAD+.

Intuisse Founder Isabel Greiner incorporates NAD across her entire line. The ingredient transfers electrons from one molecule to another within cells to carry out all sorts of reactions and processes. When NAD is synthesized in the body, it boosts mitochondrial function and repairs damaged cells. This includes the cells that form the elasticity of the skin. As a result, this process reduces wrinkles, dark spots and fine lines caused by aging. NAD is also helpful for people with sun damage to help with skin repair and rejuvenation. If consumer concerns include hyperpigmentation, this ingredient is a must.²  Liposomal delivery systems are a favored method for getting NAD into the skin, as it is a notoriously unstable ingredient. Liposomes help protect the active from degradation and enhance its penetration.

NAD+ IRL

Aramore NAD+ Cell Energizing Lotion was developed by biologists, chemists and experts in longevity science from Harvard and MIT. The moisturizer’s NAD precursor complex includes niacinamide and nicotinamide mononucleotide (NMN). It calms, plumps and firms to give tired skin a new lease on life ($150). 

Invity Youth Activating Overnight Mask ($55) works while you sleep, repairing damage done during the day. It contains a proprietary blend of NAD, ectoin, Immunight and plant extracts. In time, skin looks and feels firmer, and radiance is restored, according to the manufacturer.

Intuisse Active NAD+ Face Serum uses liposomal NAD+ that penetrates the skin barrier. The product should be refrigerated for optimum efficacy or, if stored at room temperature, used within two months ($280). 

NAD+ Benefits

The conversion of vitamin B3 into NAD+ is vital for numerous cellular processes, including energy production, DNA repair and cell signaling. NAD+ acts as a co-enzyme in redox reactions, crucial for mitochondrial functions and ATP production. In human skin, increasing NAD+ levels help slow the aging process, reduce age-related skin conditions, and improve skin health and appearance. NAD repairs DNA mutations, makes collagen, proteins and new cells, regulates the immune system, reduces inflammation and heals wounds. 

Unfortunately, the body does not have an endless supply of NAD+. Levels and NAD+/NADH ratios decline with age. Lower levels are associated with many of the aging symptoms that were previously considered unavoidable. Many recognize the relationship between NAD+ and insulin sensitivity, stress management, circadian rhythm and neurodegeneration. This contributes to the visible signs of aging such as wrinkles, loss of elasticity and dullness. Furthermore, there are several physical and cognitive issues such as lower cellular energy production, reduced capacity for DNA repair and collagen synthesis, decreased autophagy and diminished skin cell renewal. 

Studies show boosting NAD+ levels can extend the lifespan of yeast, worms and mice by improving mitochondrial function and increasing resistance to stress. NAD+ is primarily responsible for the energy conversion process inside the cell. A balanced dose of NAD+ reverses age-induced issues and help you look and feel younger. NAD+ plays a pivotal role in maintaining skin health by fueling cellular processes that repair DNA, generate energy and fortify skin cells against stress and damage. NAD+ is believed to stimulate collagen production essential for maintaining skin’s elasticity and firmness.³ When applied topically, NAD+ can penetrate the outer layers of the skin and provide targeted benefits. The problem is, that NAD is such a large molecule that it cannot penetrate into the skin. For this reason, in topical skincare, NAD precursors must be used. Oral supplements and injections of NAD are more effective than topical products. 

Although NAD+ can penetrate the skin when correctly formulated, it quickly converts to niacinamide, a popular ingredient already incorporated into many skincare formulas. Niacinamide is the precursor for the coenzyme NAD, and even helps enhance cell longevity. Some studies suggest that it may increase NAD+ levels in the skin, boosting cellular energy, promoting repair mechanics, improving skin texture and reducing the appearance of fine lines and wrinkles. 

Applying NAD precursors directly to the skin may reduce the causes of skin aging and protect against environmental stressors. Delivery systems such as encapsulation and liposomal delivery systems help protect NAD+ from degradation and improve its penetration into the deeper layers of the skin making it more effective in promoting healthy and youthful-looking skin. The combination of NAD+ with other antioxidants such as vitamin C, resveratrol and co-enzyme Q10 in skincare formulations provides comprehensive protection against environmental damage and boosts cellular energy. These antioxidants protect skin cells from the harmful effects of UV rays, pollution and other environmental stressors that can cause damage and accelerate the aging processes. 

Boosting Brands

Acaderma Better with Age Revival Light Cream ($80) is formulated to suit oily and eczema-prone skin types. This formulation contains ceramides, peptides and patented Sehaw extract from kinkeliba tea. It also has NAD+ booster, which helps regulate stressors that contribute to fine lines and wrinkles. 

Dr. Sam’s Flawless Moisturizer Intense is formulated for consumers with sensitive skin. It is clinically proven to repair the skin barrier after one use. It uses a breakthrough ingredient, sunflower shoot extract (SSE), to boost depleted levels of NAD+. 

Code Age Eternal Plat NAD+ Face Serum contains NAD+, resveratrol, niacinamide, collagen and vitamins C and E. This firming serum offers around-the-clock hydration while boosting skin cell renewal.

Supplements & Injections

Due to its efficiency in raising NAD+ levels, nicotinamide riboside (NR) has garnered significant interest as a dietary supplement aimed at boosting NAD+ for health and longevity. NAD+ precursors increase NAD+ levels in the body. Human clinical trials demonstrate that NAD+ precursors, NR and nicotinamide mono nucleotide (NMN), safely and effectively increase NAD+ levels in the body. These supplements are included in the Basis and Signal brands. 

Supplements containing NAD+ precursors, such nicotinamide riboside or nicotinamide mononucleotide, increase the body’s NAD+ levels supporting skin health from within. These precursors are converted into NAD+, bolstering skin’s ability to repair and regenerate. These supplements are generally safe with minimal side effects. Promising research suggests NAD+ supplementation has several health benefits such as increased alertness and energy, improved sleep, enhanced muscle recovery post exercise, hair and nail growth, and collagen regeneration. Short term benefits include boosts to mental and physical energy. Long-term benefits occur because NAD is so integral to energy sensing pathways. When NAD levels are optimized, blood sugar levels improve. 

Successful Supplements

Great skin starts from within, so it makes sense that NAD+ supplements are big business right now. Basis (Elysium) is clinically proven to safely increase NAD+ by 40% in humans. It boosts cellular energy and maintains healthy DNA. 

Signal is a novel mitochondria-centric product formulated to counter aging-dependent declines in metabolism by promoting youthful energy and metabolic efficiency. 

NAD+ Direct Optima Max, by NAD Clinic, is an oral supplement that helps increase NAD+ levels and activates critical sirtuins. It fortifies the immune system. Direct administration of NAD via intravenous drip bypasses the digestive system, potentially offering a more immediate and potent way to elevate NAD+ levels in the body compared to oral supplements. By injecting NAD+ directly into the bloodstream, it is theorized that this co-enzyme can more efficiently reach cells throughout the body, enhancing cellular functions almost immediately. 

NAD+ plays a pivotal role in metabolic processes, including the conversion of nutrients into energy, DNA repair and supporting cellular health. NAD injections offer various health benefits including enhanced energy production, anti-aging effects, improved cognitive function and addiction recovery support. NAD injections are increasingly popular, and more clinics offer the service. These injections can be expensive and are usually not widely available in the traditional medical setting, but they are more commonly found in specialized clinics and wellness centers. The procedure should be performed under medical supervision. 

NAD+ via IV is often used for general wellness and potential antiaging benefits, but its direct impact on the skin is not yet fully established. Topical application of NAD+ is still an area of ongoing research and the efficacy of it compared to IV remains unclear, however NAD+ offers five pillars of wellness and longevity: human performance (endurance, strength and cognitive clarity), longevity (supports cellular repair and DNA protection and slows the aging process), sexual health (enhances libido and vascular health), metabolic syndrome (manages conditions like diabetes, obesity and heart disease), and hair and skin (promotes a youthful appearance through enhanced cell regeneration). 

In summary, NAD+ can help us live longer and better.

References:

1. Dr. David Sinclair, Professor of Genetics, Harvard Medical School “Why We Age”.
2. New Beauty, Summer/Fall 2024, “Skin Longevity.”
3. Dr. Leslie Baumann, Professor of Cosmetic Dermatology, Miller School of Medicine, Florida.

Navin Geria

Chief Scientific Officer

Ayurderm Technologies, LLC
navin@ayurderm.com

Navin Geria, former Pfizer Research Fellow is a cosmetic and pharmaceutical product development chemist and the chief scientific officer of AyurDerm Technologies LLC, which provides Ayurvedic, natural and cosmeceutical custom formulation development and consulting services to the spa-wellness-dermatology industries. He has launched dozens of cosmeceutical and ayurvedic anti-aging products. Geria has more than 30 years of experience in the personal care industry and was previously with Clairol, Warner-Lambert, Schick-Energizer, Bristol-Myers and Spa Dermaceuticals. He has nearly 20 US patents and has been published extensively. Geria edited the Handbook of Skin-Aging Theories for Cosmetic Formulation Development focus book published in April 2016 by Harry’s Cosmeticology. He is a speaker, moderator and chairman at cosmetic industry events.