While NAD+ precursors and therapies are generally well-tolerated by most individuals, potential downsides include mild side effects such as fatigue, headaches, gastrointestinal discomfort, nausea, or localized flushing and irritation at injection sites. Additionally, direct intravenous infusions or high-dose precursor supplementation can be quite expensive, lack comprehensive long-term safety data across diverse populations, and require careful medical supervision to avoid potential adverse biological interactions.