NAD+ Supplementation: No Current Clinical Practice Guideline Recommendations
There are currently no established clinical practice guidelines recommending NAD+ (nicotinamide adenine dinucleotide) or its precursors (nicotinamide riboside, nicotinamide mononucleotide) for routine use in adults with diabetes, cardiovascular disease, or chronic kidney disease.
Critical Evidence Gap
The provided major clinical practice guidelines—including KDIGO guidelines for CKD management 1, KDOQI nutrition guidelines 1, KDIGO blood pressure guidelines 1, and diabetes nutrition guidelines 1—do not mention NAD+ supplementation at any point. This absence is striking given these are the most authoritative and recent guidelines governing management of the exact conditions where NAD+ has been studied.
Why NAD+ Is Not Guideline-Recommended
Safety Concerns in CKD Patients
Patients with advanced CKD accumulate toxic NAD+ metabolites (2PY and 4PY) at several-fold higher concentrations than healthy individuals, and these metabolites are independently associated with increased cardiovascular disease risk 2. This creates a dangerous scenario where NAD+ supplementation could theoretically worsen cardiovascular outcomes in the very population (CKD patients) who already face markedly elevated CVD risk as their primary cause of death 2.
Problematic Metabolism in Diabetes
Diabetic patients have fundamentally impaired NAD+ salvage pathways due to decreased nicotinamide phosphoribosyl transferase expression and compromised phosphoribosyl pyrophosphate synthesis 3. This means:
- NAD+ precursors may not efficiently convert to active NAD+ in diabetic tissues 3
- Nicotinamide catabolites accumulate and cause oxidative stress 3
- The risk-benefit ratio becomes unfavorable without co-administration of insulin sensitizers, polyphenols, benfotiamine, and aldose reductase inhibitors 3
Insufficient Clinical Evidence
While preclinical studies show promise, human clinical trials remain small, heterogeneous in dosing and duration, and lack definitive evidence that raising NAD+ improves physiological function 4. The 2023 systematic review identified only 10 studies with 489 total participants across disparate conditions, with common side effects including muscle pain, nervous disorders, fatigue, and headaches 5.
What Guidelines Actually Recommend Instead
For CKD Patients
- SGLT2 inhibitors for adults with CKD and eGFR ≥20 mL/min/1.73 m² with albuminuria ≥200 mg/g or heart failure (1A recommendation) 1
- RAS inhibitors (ACE-I or ARB) at maximum tolerated doses for those with albuminuria 1
- Nonsteroidal mineralocorticoid receptor antagonists for type 2 diabetes with eGFR >25 and persistent albuminuria despite RASi (2A recommendation) 1
- Protein intake of 0.8 g/kg/day for CKD stages 3-5 not on dialysis 1, 6
For Diabetes with CKD
- SGLT2 inhibitors for type 2 diabetes with CKD and eGFR ≥20 (1A recommendation) 1
- HbA1c targets individualized between <6.5% to <8% depending on hypoglycemia risk 1
- Sodium intake <2 g/day 1
- Moderate-intensity physical activity ≥150 minutes/week 1
For Cardiovascular Disease
- Blood pressure targets of <130/80 mmHg for those with albuminuria 1
- Mediterranean-style diet rich in MUFAs 1
- Fatty fish consumption at least twice weekly for omega-3 fatty acids 1
Clinical Bottom Line
Do not prescribe NAD+ precursors for diabetes, cardiovascular disease, or kidney disease outside of research protocols. The evidence base remains insufficient, metabolism is impaired in these conditions, and potentially harmful metabolites accumulate—particularly in CKD patients 2, 3. Instead, implement the proven guideline-directed medical therapies listed above that have robust evidence for reducing morbidity and mortality 1.
If patients inquire about NAD+ supplements they've purchased over-the-counter, counsel them on the lack of clinical evidence, potential risks in kidney disease, and superior alternatives with established benefit 4, 5, 2.