The NAD+ side effects question has a strange answer in the medical literature. In the randomized trials that exist, oral NAD+ precursors produced side effects at about the same rate as placebo. The intravenous drips sold at clinics rest on one retrospective chart review and one randomized trial that reports no adverse events. One eight-week trial of 140 adults found at least one adverse event in 40.0 percent of the group taking 1,000 milligrams of nicotinamide riboside daily, against 48.6 percent of the placebo group (Conze, Brenner and Kruger, Scientific Reports, July 5, 2019). That is the pattern across the oral trials.
We read the primary papers, the FDA compounding records and each registered trial of the injectable form we could locate.
NAD+ Side Effects in the Oral Trials: Headache, Nausea, Dyspepsia
Nicotinamide riboside and nicotinamide mononucleotide are the two precursors in most capsules. Both have randomized trials that report adverse events in enough detail to read.
The Conze trial randomized 140 adults with a body mass index between 25 and 30 to placebo or to 100, 300 or 1,000 milligrams of nicotinamide riboside daily for eight weeks, 35 people per arm. Ninety-five adverse events occurred across 61 participants. Two findings matter: no serious adverse events and no reports of flushing. And the gastrointestinal category, the one people ask about, ran 5 of 35 participants on placebo (14.3 percent), 7 of 35 at 100 milligrams (20.0 percent), 5 of 35 at 300 milligrams (14.3 percent) and 4 of 35 at 1,000 milligrams (11.4 percent). The three events the investigators judged possibly related at the highest dose were sore back, muscle soreness and nausea, all mild.
One disclosure belongs beside those numbers: ChromaDex funded the trial, two authors worked for the company, and the third was the inventor of intellectual property licensed by ChromaDex. A reader deserves to know who paid.
The higher-dose test came from Norway. Berven and colleagues randomized 20 people with Parkinson’s disease to 1,500 milligrams of nicotinamide riboside twice daily or placebo for four weeks, a total of 3,000 milligrams daily (Nature Communications, November 2023). Forty-two adverse events occurred, 25 in the treatment arm and 17 in the placebo arm. Nine of ten people on the supplement and eight of ten on placebo reported at least one event, and all events graded as mild. The common ones in the treatment arm were headache in three people, then dyspepsia, nausea, fatigue, tremor and muscle cramp in two each. Nausea and dyspepsia resolved by the end of follow-up. No painful flushing appeared, which the authors noted as a contrast to high-dose nicotinic acid, a different form of vitamin B3.
The one laboratory signal worth naming is homocysteine. The Norwegian team reported a slight initial rise in serum homocysteine, then described the methyl donor pool as intact. A prescriber would want that monitored.
The mononucleotide has a smaller file of the same shape. Pencina and colleagues gave 30 overweight or obese adults 1,000 milligrams twice daily for 28 days and reported adverse events similar between groups (Journal of Clinical Endocrinology and Metabolism, July 2023). Yi and colleagues randomized 80 healthy middle-aged adults to 300, 600 or 900 milligrams daily for 60 days, found no safety issues, and had all 80 complete the trial (GeroScience, February 2023).
NAD+ Side Effects at One Year: The Parkinson’s Trial That Went the Wrong Way
The largest and longest test of a NAD+ precursor published so far also separates two questions that get blended together: does it harm people, and does it help them.
Brakedal and colleagues screened 537 people and randomized 410 with early Parkinson’s disease across 11 centers in Norway, then analyzed 393. Participants took 500 milligrams of nicotinamide riboside twice daily or placebo for 52 weeks (JAMA, October 2026). On the movement score, the supplement arm worsened by 2.45 points while the placebo arm improved by 0.27, an adjusted difference of 2.72 points favoring placebo. Nonmotor symptom burden also worsened more on the supplement.
Serious adverse events went the other direction. They occurred in 17 of 205 participants on nicotinamide riboside (8.3 percent) and 29 of 205 on placebo (14.1 percent). That is a supplement that failed its efficacy test across a year without a harm signal.
NAD+ Side Effects From a Needle: One Trial and Two Unfinished Records
The injectable form is where the marketing lives and where the evidence thins out. The mechanics of the shot are a separate subject, covered in our guide to peptide injection sites; what the trials recorded is here.
We found one randomized human trial of intravenous NAD+ itself. Yu, Xu and Cao enrolled 180 adults with heart failure from ischemic cardiomyopathy, all with a left ventricular ejection fraction of 45 percent or less and NYHA class II or III, and randomized them to intravenous NAD+ at 10 milligrams per day for seven days or to a placebo of glucose solution or normal saline, on top of guideline-directed medical therapy (American Journal of Cardiovascular Drugs, January 2026). At one month, ejection fraction rose to 45.44 percent on NAD+ against 42.44 percent on placebo, a difference the authors reported as significant at p = 0.024. The combined cardiac and cerebrovascular event rate at six months was 14.6 percent against 24.7 percent, which the authors reported as a trend at p = 0.089 rather than a result.
That paper gives no adverse-event accounting. Its stated outcomes were ejection fraction, natriuretic peptide, the event composite and functional class. Injection-site reactions, blood pressure during infusion, infusion speed and how the infusion felt do not appear among them. A reader who wants to know whether a NAD+ drip causes chest tightness or a pounding heart gets no answer from the randomized trial, only from the chart review.
The rest of the intravenous record is small and observational. Reyna, Heinzen and Patel reviewed electronic medical records from a commercial wellness setting where clients received four consecutive days of 500 milligrams of intravenous NAD+ or intravenous nicotinamide riboside (Frontiers in Aging, February 2026). The NAD+ clients reported moderate to severe gastrointestinal symptoms, a faster heart rate and chest pressure during the infusion, and their infusions ran about 97 minutes against 37 minutes in the riboside group. Symptoms resolved when the infusion stopped, and liver and inflammation markers showed no significant change.
The registry records show the field knows this. A study of intravenous nicotinamide riboside against intravenous NAD+ in 53 participants listed blood pressure, heart rate and dried blood spot NAD as its primary outcomes, with no results posted since an update on April 24, 2024 (NCT06382688). A second study, recruiting with an estimated 70 participants, lists the McGill Pain Questionnaire and subjective discomfort as its primary outcomes, so the open question is how much the injection hurts (NCT06919328). Neither study has published results.
A review published in March 2026 reached the same place. Godic and Townsend examined intravenous longevity therapy, NAD+ included, and concluded that until adequately powered randomized trials show reproducible long-term safety, the practice “should be regarded as an experimental intervention rather than an evidence-based dermatological or anti-aging practice” (Acta Dermatovenerologica Alpina, Pannonica, et Adriatica, March 2026).
NAD+ Side Effects and the Regulatory Gap
No FDA-approved NAD+ drug exists, and that fact explains the missing side-effect table better than any clinic page does.
A label search of DailyMed, the National Library of Medicine database of drug labeling, returns no product label for nicotinamide adenine dinucleotide (searched November 6, 2026). No label means no approved indication, no approved dose and no standardized adverse-reaction section.
Compounding fills part of that space without filling the evidence gap. On January 20, 2026, the FDA sent a warning letter to GenoGenix LLC stating that the company compounded drug products using bulk substances that included “nicotinamide adenine dinucleotide (NAD+)” and that those products “are not eligible for the exemptions provided by section 503B, because 5-Amino-1MQ and NAD+ do not appear on the 503B bulks list.” Separately, NAD appears on the FDA’s 503A list of bulk drug substances under Category 1, the category for substances FDA is still evaluating for compounding eligibility, in a list updated May 14, 2026. Under evaluation is the operative phrase.
The injected product sits between two regulatory stools: not an approved drug with a label, and not a settled compounding ingredient. What that means for the vial a reader is handed is the subject of our review Are Peptides Safe? The Answer Depends on the Vial.
The Questions the Trials Do Not Answer
Four gaps deserve stating plainly, because silence in a trial is not evidence of safety. Use beyond 52 weeks has no randomized data. Pregnancy and breastfeeding have no trial data. Interactions with prescription medicines have not been tested. Kidney and liver impairment have no safety data.
Doses vary by product, route and clinic, and none of the numbers above translate into a dose for a reader. That decision belongs to a prescriber who knows the patient. A directory of clinics by city is a starting point for that conversation, not a substitute for it. Readers who want the compound overview can start at our compounds library, and readers comparing local providers can use find a clinic.
How to Judge a NAD+ Side Effect Claim
Four questions separate a claim from a finding: route, since a pill trial cannot vouch for a drip; dose and duration, since a four-week study answers a different question than a year; size, since a 20-person trial detects large problems and misses small ones; and funding, since a reader deserves to know who paid.
Our earlier review of the peptide side-effect record and the FDA safety list applies the same test to 17 withdrawn substances.
Frequently asked questions
What are the side effects of NAD+?
In randomized trials of oral NAD+ precursors, the reported events were mild and matched placebo: headache, nausea, dyspepsia, fatigue and muscle cramp in the treatment arms, at rates the placebo arms often matched. No randomized trial of intravenous NAD+ has published an adverse-event table.
Does NAD+ cause flushing?
The oral trials reported no flushing, and the Norwegian team specifically noted the absence of the painful flushing seen with high-dose nicotinic acid, a different form of vitamin B3.
Is injected NAD+ safer than the pills?
No. The oral trials report adverse events in detail and found rates near placebo. The intravenous record is one randomized trial whose reported outcomes omit adverse events, plus a retrospective review in which NAD+ recipients reported moderate to severe gastrointestinal symptoms, chest pressure and a faster heart rate during infusion.
How much NAD+ did the trials use?
Doses differed by route and by substance. Oral nicotinamide riboside appeared at 100 to 3,000 milligrams daily across the trials cited here, oral nicotinamide mononucleotide at 600 to 2,000 milligrams daily, and intravenous NAD+ at 10 milligrams daily. Each figure belongs to its own study design and none of them is a recommendation.
Is NAD+ FDA approved?
No. DailyMed returns no product label for nicotinamide adenine dinucleotide, and the FDA’s January 20, 2026 warning letter to GenoGenix LLC states that NAD+ does not appear on the 503B bulks list. NAD sits in Category 1 of the FDA’s 503A bulk substances list, the under-evaluation category.
Can NAD+ make a condition worse?
In the largest trial published so far, 410 people with early Parkinson’s disease were randomized and 393 analyzed, and the supplement arm did worse on the movement score and on nonmotor symptoms than placebo over 52 weeks. That is one condition and one trial, and it does not establish harm in other groups.
Sources:
- Conze, Brenner and Kruger, Safety and Metabolism of Long-term Administration of NIAGEN (Nicotinamide Riboside Chloride), Scientific Reports, July 5, 2019.
- Berven and colleagues, NR-SAFE: a randomized, double-blind safety trial of high dose nicotinamide riboside in Parkinson’s disease, Nature Communications, November 2023.
- Brakedal and colleagues, Nicotinamide Riboside for Patients With Early-Stage Parkinson Disease: The NOPARK Randomized Clinical Trial, JAMA, October 2026.
- Yu, Xu and Cao, Effect of Nicotinamide Adenine Dinucleotide on Heart Failure Caused by Ischemic Cardiomyopathy, American Journal of Cardiovascular Drugs, January 2026.
- Pencina and colleagues, Nicotinamide Adenine Dinucleotide Augmentation in Overweight or Obese Middle-Aged and Older Adults, Journal of Clinical Endocrinology and Metabolism, July 2023.
- Yi and colleagues, The efficacy and safety of beta-nicotinamide mononucleotide supplementation in healthy middle-aged adults, GeroScience, February 2023.
- Godic and Townsend, Intravenous longevity therapy: a critical review of evidence, mechanisms, and clinical utility, Acta Dermatovenerologica Alpina, Pannonica, et Adriatica, March 2026.
- Reyna, Heinzen and Patel, Intravenous infusion of nicotinamide adenine dinucleotide versus nicotinamide riboside: a retrospective tolerability pilot study, Frontiers in Aging, February 2026.
- ClinicalTrials.gov, IV Administration of ChromaDex’s Niagen as Compared to NAD+ (NCT06382688), record last updated April 24, 2024.
- ClinicalTrials.gov, Absorption and Tolerability of Injectable Administration of Niagen+, as Compared to NAD+ (NCT06919328), record last updated April 9, 2025.
- FDA, Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act, updated May 14, 2026.
- FDA, Warning Letter to GenoGenix LLC, 718739, January 20, 2026.
- DailyMed, National Library of Medicine drug label search for nicotinamide adenine dinucleotide, searched November 6, 2026.
This article is for information only and is not medical advice. NAD+ products sold online or infused at clinics are not FDA-approved drugs, and doses, purity and sterility vary by source. Talk to a licensed prescriber about your own risks, medicines and conditions before starting or stopping anything described here.