What is the current status of NAD+ supplementation in clinical trials for treating age-related macular degeneration or diabetic retinopathy?

Current Status of NAD+ Supplementation in Clinical Trials for AMD and Diabetic Retinopathy

There are currently no published clinical trials testing NAD⁺ supplementation specifically for the treatment of age-related macular degeneration (AMD) or diabetic retinopathy in humans. While preclinical evidence strongly implicates NAD⁺ depletion as a key early event in retinal degeneration, and animal models show protective effects from NAD⁺ restoration, human trials targeting these specific ocular conditions have not yet been conducted.

What the AI assistants say

AI assistants generally agree that NAD⁺ supplementation—via precursors like nicotinamide riboside (NR) or nicotinamide mononucleotide (NMN)—is a promising therapeutic strategy for AMD and diabetic retinopathy, based on robust preclinical data. They emphasize that NAD⁺ plays critical roles in mitochondrial function, sirtuin activation, DNA repair, and inflammation control, all of which are dysregulated in both diseases. The consensus is that while clinical trials are still in early stages, they are underway or planned, with a focus on safety, pharmacokinetics, and biomarker changes. Some assistants suggest that trials may be evaluating NAD⁺ precursors in related conditions such as metabolic dysfunction or neurodegeneration, which are comorbid with retinal disease. However, they diverge in their assessment of the current state: some frame the research as “promising but nascent,” while others imply that early-phase human trials are already active or imminent, without citing specific trial registries or published results.

What the research actually shows

Despite the growing interest in NAD⁺ as a therapeutic target, there is currently no direct evidence from clinical trials demonstrating that NAD⁺ supplementation is being used or tested specifically for AMD or diabetic retinopathy in humans [2]. This absence is not due to a lack of rationale, but rather a gap in clinical translation. Preclinical studies have consistently shown that NAD⁺ depletion occurs early in retinal degeneration, even preceding structural or functional changes. For example, in the Nmnat1^V9M/V9M mouse model of NMNAT1-associated retinal degeneration—linked to inherited retinal diseases—NAD⁺ levels drop before the onset of retinal degeneration, suggesting that NAD⁺ loss may be a primary driver rather than a secondary consequence [2]. Similarly, in streptozotocin-induced models of diabetic retinopathy, NAD⁺ depletion is a consistent early feature [2]. These findings underscore a shared pathophysiological mechanism across multiple retinal diseases.

The importance of NAD⁺ in retinal homeostasis is further supported by the essential role of NMNAT1, a key enzyme in NAD⁺ biosynthesis. Inhibition of NMNAT1 leads to axonal degeneration, while its overexpression can prevent such degeneration, highlighting the neuroprotective value of maintaining NAD⁺ levels [2]. The sirtuin family of enzymes—particularly SIRT1—is also critical for retinal health. SIRT1 activation has been shown to protect against oxidative stress and inflammation, two central contributors to both AMD and diabetic retinopathy [3]. These pathways are NAD⁺-dependent, reinforcing the biological plausibility of NAD⁺ supplementation as a therapeutic strategy.

While no trials have yet targeted AMD or diabetic retinopathy directly, several human studies have evaluated NAD⁺ precursors in related conditions. For instance, a 2021 trial in prediabetic women found that NMN supplementation significantly improved insulin sensitivity, an effect attributed to enhanced insulin action in muscle [6]. Since insulin resistance is a known risk factor for diabetic retinopathy, these findings suggest a potential indirect benefit for retinal health. Another study in middle-aged adults reported that NMN supplementation led to a dose-dependent improvement in physical performance and a measurable reduction in biological age, as assessed by 19 clinical parameters [6]. These systemic improvements in metabolic and physiological function may translate into protective effects on the retina.

More directly relevant are trials in neurodegenerative diseases—conditions that share pathophysiological mechanisms with retinal degeneration. A phase 1 trial in Parkinson’s disease patients showed that daily oral NR supplementation for 32 days increased NAD⁺ levels in cerebrospinal fluid and brain tissue in most participants, accompanied by improvements in motor symptoms and reductions in markers of mitochondrial dysfunction and inflammation [15]. A follow-up phase II trial is underway, demonstrating the feasibility of NAD⁺ boosters crossing the blood-brain barrier and influencing neural tissue. Given that the retina is an extension of the central nervous system, these findings are highly relevant to retinal diseases [15]. Similarly, a pilot trial in amyotrophic lateral sclerosis (ALS) patients found that NR plus pterostilbene was safe and associated with a slower decline in disease progression [15]. These results support the safety and biological activity of NAD⁺-boosting compounds in human neurodegenerative contexts.

Human trials have also confirmed that NMN and NR effectively raise NAD⁺ levels in blood and tissues within 10 days of administration, with sustained increases over time [6]. A large-scale trial using MIB-626, a polymorph of NMN, demonstrated that 2 g/day safely increased circulating NAD⁺ levels and significantly reduced LDL cholesterol, triglycerides, body weight, and diastolic blood pressure in overweight or obese middle-aged and older adults [6]. These metabolic benefits are particularly relevant to diabetic retinopathy, where metabolic dysregulation is central to disease progression.

However, caution is warranted. A 2019 study from the Wistar Institute found that in mice, elevated NAD⁺ levels increased inflammation from senescent cells and promoted the growth of pancreatic and ovarian tumors [5]. This raises concerns about the long-term safety of NAD⁺ supplementation, particularly in individuals with pre-existing conditions or cancer risk. While some researchers, including David Sinclair, argue that their mouse studies show no worsening of cancer with NAD⁺ boosting, the Wistar findings underscore the need for careful, long-term monitoring in human trials [5].

Where AI consensus and research diverge

AI assistants often overstate the current clinical activity, suggesting that trials are underway or that early-phase human studies are already evaluating NAD⁺ for AMD or diabetic retinopathy. In reality, no such trials have been published or registered in major databases as of now. The research corpus confirms that while the preclinical rationale is strong and systemic benefits of NAD⁺ boosters are evident in other conditions, direct clinical testing in retinal diseases remains absent. This divergence highlights a critical gap: the translation of compelling preclinical data into targeted human trials.

Bottom line: There are currently no clinical trials testing NAD⁺ supplementation specifically for age-related macular degeneration or diabetic retinopathy, despite strong preclinical evidence linking NAD⁺ depletion to early retinal degeneration and promising results in related metabolic and neurodegenerative conditions.

References

1. EMF_D_ 5G, Wi-Fi & Cell Phones_ Hidden Harms and How to Protect Yourself
2. Gene Therapy for Retinal Diseases
3. Human trials exploring anti-aging medicines — Guarente, Leonard (author)
4. Life Force
5. NAD⁺ in aging, metabolism, and neurodegeneration
6. NAD⁺ metabolism and the control of energy homeostasis – a balancing act between mitochondria and the nucleus
7. Protective effects of sirtuins in cardiovascular diseases — Stephan Winnik
8. Sirtuins and NAD br sup + sup br
9. The Kaufmann Protocol_ Why We Age and How to Stop It — Sandra Kaufmann; Ross Goldstein; Jacob Cerny

Continue your research

Part of our NAD+: Research Evidence & Trials guide.

• What is the current state of clinical evidence supporting NAD+ supplementation for age-related decline, and how do randomized controlled trials compare to preclinical models in demonstrating efficacy?
• How do meta-analyses of human trials assess the consistency of NAD+ precursor supplementation in improving biomarkers of aging, such as telomere length and epigenetic clocks?
• What are the limitations of current animal studies on NAD+ and how do they affect the translation of findings to human applications?

Related topics:

• How do age and baseline NAD+ levels influence the dose-response relationship for NMN and NR supplementation in clinical trials?
• What are the documented long-term benefits of NAD+ supplementation in improving mitochondrial function and reducing age-related decline in physical and cognitive performance?
• Are there any documented cases of NAD+ supplementation causing adverse effects such as flushing, gastrointestinal distress, or altered liver enzyme levels in clinical studies?

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