NAD Injection, Capsules or IVs: What's the best way to boost NAD+ levels?

Sublingual delivery involves placing the NAD⁺ supplement under the tongue. By absorbing through the mucous membranes, it potentially bypasses the digestive system and may enhance bioavailability. While studies are quite limited, new research suggests that sublingual NAD⁺ can boost NAD ⁺ levels [6]. There was a 2-fold increase in plasma NAD⁺ levels after just 10 minutes of dosing. Sublingual delivery has also been shown to increase NAD ⁺ availability in mammalian cells, supporting cellular metabolism. The findings also suggest a bioavailability of sublingual NAD⁺ at 22% compared to IV administration.

IV administration delivers NAD⁺ directly into the bloodstream for rapid availability. While understudied, clinical studies have been published that have evaluated the efficacy of IV NAD⁺ therapy.

In one study, repeated NAD⁺ infusions over six days significantly increased the blood NAD⁺ metabolome (which includes NAD⁺ and its related metabolites) in elderly adults aged 70–80 [7]. However, another study found that a single IV NAD⁺ infusion did not significantly raise whole blood NAD⁺ levels within 24 hours [8]. Although NAD⁺ levels trended upward at seven and 14 days post-infusion, the increases were not statistically significant compared to baseline or other treatment groups. Some clinical trials also assess metabolic health markers such as blood pressure and cardiovascular disease risk when evaluating the outcomes of NAD⁺ interventions. IV NAD⁺ therapy is also being explored for its potential role in addiction treatment, particularly in supporting recovery from substance use disorders.

Intramuscular (IM) injections deliver NAD⁺ directly into muscle tissue. While these injections are commonly offered by wellness clinics and marketed for benefits like accelerated recovery, reduced pain, healthy aging support, improved mental clarity, and relief from chronic fatigue, there is a lack of peer-reviewed clinical trials evaluating their safety and efficacy. The potential adverse effects and adverse consequences of IM NAD⁺ injections, including their impact on muscle function, remain unclear due to limited research. Although rapid absorption is often cited as an advantage, these claims remain largely anecdotal. Until more rigorous research is available, other NAD⁺-boosting strategies may offer a more evidence-based approach.

This method delivers NAD⁺ or its precursors through the skin. Preliminary studies using microneedle patches for nicotinamide mononucleotide delivery found that lower concentrations (like 2.9%) offered a more efficient balance of stability and absorption. Higher concentrations were associated with greater compound breakdown prior to absorption, making lower doses the more effective option in this context [9]. While these findings are promising for transdermal delivery, additional research is needed to assess the efficacy of other NAD⁺ precursors, including niacinamide. Nicotinamide mononucleotide supplements are also available in oral and transdermal forms, and are being studied for their potential benefits in anti-aging and NAD⁺ replenishment strategies. Extended release niacin is another formulation developed to reduce side effects associated with traditional niacin supplements, such as flushing.

Combining NAD⁺ supplementation with a healthy diet may further support metabolic health and help maintain optimal NAD⁺ levels.

Animal studies have shown that brain NAD⁺ levels begin to decline by young adulthood and decline further by middle age [10]. Intranasal administration may offer a way to bypass the blood-brain barrier and deliver NAD⁺ directly to the brain. In rodent models, this method significantly reduced brain damage following a transient ischemic attack; such animal models are crucial for preclinical research on NAD⁺ delivery. A dose given intravenously did not yield comparable results [11]. Another study found that intranasal NAD⁺ given 2 to 5 hours after brain injury reduced neuronal cell death by 60–90% [12]. Intranasal NAD⁺ delivery is also being explored for its potential to support mitochondrial function and promote mitochondrial biogenesis in the brain, which may be particularly relevant for neurodegenerative diseases and cognitive decline.

While more research is needed, particularly in humans, these findings suggest intranasal delivery may be a promising, targeted approach for brain-specific support. However, current evidence does not indicate that it increases NAD⁺ levels systemically, so its benefits may be limited to neurological applications.

Most people opt for oral supplementation to support NAD⁺ levels and mitochondrial function as it’s convenient, non-invasive, and often the most cost-effective method. Optimizing NAD⁺ supplementation can help support energy homeostasis, cellular repair, and cellular homeostasis, as well as promote a healthy immune system. These strategies can improve metabolic health, support metabolic homeostasis, and enhance overall well-being. These strategies can have beneficial effects on overall health by enhancing cellular function, metabolism, cognitive function, and resilience. But here are a few science-backed tips to help you get the most out of your NAD⁺ routine:

Niacinamide is water-soluble and doesn’t require fat for absorption, but taking it with food, especially meals containing tryptophan-rich foods such as nuts, seeds, beans, and chicken, may further support NAD⁺ levels. That’s because tryptophan feeds into the de novo NAD⁺ pathway, which may enhance the salvage pathway used by niacinamide [13]. Both tryptophan and niacinamide support metabolic pathways and activate genes involved in NAD⁺ biosynthesis.

Exercise has been shown to upregulate NAMPT, a rate-limiting enzyme in the NAD⁺ salvage pathway, thereby enhancing NAD⁺ biosynthesis. Research shows that combining NAD ⁺ precursor supplementation with regular physical activity may synergistically boost NAD⁺ levels [14]. Regular exercise and NAD⁺ supplementation may help improve muscle insulin sensitivity and overall insulin sensitivity, which are important for improving insulin sensitivity and metabolic health. These effects can contribute to improved physical performance.

Some studies suggest that combining NAD⁺ precursors with polyphenols like quercetin or resveratrol, found in our foundational longevity supplement Vitality, may enhance cellular protection and support NAD⁺ metabolism [15]. Apigenin, found in our sleep supplement Restore, also reduces the NAD⁺-consuming CD38, an enzyme that increases with inflammation [16]. By lowering CD38 activity, apigenin helps ensure your NAD⁺ booster supports healthy aging rather than further fueling inflammaging.

Poly(ADP-ribose) is produced by poly(ADP-ribose) polymerases (PARPs) during NAD⁺ consumption, and plays a key role in DNA repair and cellular stress responses.

NAD⁺ metabolism also plays a key role in regulating immune cells and immune cell function, which is important for controlling systemic inflammation and may be particularly relevant in inflammatory conditions such as rheumatoid arthritis.

NAD⁺ levels and the activity of NAD⁺-dependent enzymes like sirtuins exhibit circadian oscillations [17]. Taking our NAD⁺ booster in the morning may align with these natural rhythms, potentially enhancing its effectiveness. Research on mice found that administering NAD⁺ precursors in the morning improved metabolic markers compared to supplementation in the evening, which was less effective and, in some cases, disrupted circadian gene expression in the liver [18]. Aligning NAD⁺ supplementation with circadian rhythms may help mitigate the aging process and reduce the risk of age related disorders and age related diseases.

One day, it hits you: less stamina, more sluggishness.

That’s because NAD⁺ — a vital coenzyme your cells need to produce energy, repair DNA, and combat oxidative stress — declines with age. This age-associated decline is linked to age-related declines in cellular function, contributing to the onset of various age-related diseases. Declining NAD⁺ levels impact a wide range of cellular processes, including DNA repair, redox reactions, and mitochondrial NADH production. Disruptions in anabolic processes and glucose metabolism further contribute to metabolic dysfunction and metabolic disorders as we age. NAD⁺ is also essential for maintaining genomic stability, helping to prevent DNA damage and preserve proper genetic information transfer.

Our solution? NAD⁺, our latest science-backed supplement with niacinamide, a powerful precursor that helps replenish and sustain NAD⁺ levels to support cellular health, healthy aging, and longevity — no NAD+ injection required. Supporting NAD⁺ levels can benefit human health by influencing molecular mechanisms involved in cancer progression, metabolic health, and body weight regulation, and by reducing chronic inflammation, a known risk factor for age-related diseases. NAD⁺ also supports mitochondrial homeostasis, aids in the clearance of defective mitochondria, and helps slow cellular aging.

NAD⁺ is central to molecular cell biology, the electron transport chain, and the formation of derivatives like nicotinic acid adenine dinucleotide, all of which are vital for healthy aging, disease prevention, and maintaining optimal cellular processes.