NR Side Effects: What Nobody Tells You Before You Start

So I'm standing in my bathroom at 6:47 AM on a Tuesday in March 2021, staring at this bottle of NR capsules I'd just gotten from Amazon. $43.99 for a month's supply. My hands are shaking slightly—not from excitement, from the three cups of coffee I'd already downed because I'd been up since 4 AM reading Reddit threads about NAD+ precursors.

I'd spent the previous two weeks going down the longevity rabbit hole. Started with a David Sinclair podcast, ended up at 2 AM watching YouTube videos about cellular senescence. And everyone kept saying the same thing: "NR is super safe, basically no side effects, just take it."

That should have been my first red flag. Nothing that actually works has zero side effects.

I unscrewed the cap—it made that satisfying crack sound—and shook out two capsules. 300mg each. The bottle said take one, but I'd read that 600mg was the "optimal dose" in some study. Classic mistake. My wife walked past the bathroom, saw me holding the pills, and said "another one of your experiments?" She wasn't wrong. This was supplement number... I don't know, maybe 15? I'd started keeping a spreadsheet at that point.

What I didn't know then, standing there in my grey hoodie with the coffee stain on the sleeve, was that NR would actually work. And that the side effects—the real ones, not the ones listed on the bottle—would teach me more about my body than I'd learned in six years of biohacking.

TL;DR: NR genuinely raises NAD+ levels and most people tolerate it well, but the real side effects include: nausea (especially on empty stomach), flushing/warmth sensation, mild headaches in week 1-2, digestive weirdness, and occasionally vivid dreams or disrupted sleep. The key is starting low (100-150mg), taking it with food, and timing it right. After 4+ years of use, I've learned these effects are manageable and usually temporary—but nobody warned me about them upfront.

The First Week: When Your Body Realizes Something's Different

Day one, nothing. I took 600mg with breakfast—scrambled eggs and toast, around 7:30 AM—and went about my day. Worked from home, had three Zoom meetings, felt completely normal. Around 2 PM I remember thinking "well, this is a waste of $44."

Day two, I woke up at 5:15 AM. Not because my alarm went off. Just... awake. Fully alert. That's not normal for me—I'm the guy who hits snooze four times. I lay there in the dark, listening to my wife breathe, wondering if this was placebo or real.

Day three is when things got weird.

I took my 600mg around 7 AM again, but this time on a mostly empty stomach. Just coffee. Big mistake. About 45 minutes later, sitting at my desk trying to write code, this wave of nausea hit me. Not like "I'm going to throw up" nausea, more like... a rolling discomfort in my stomach, this mild queasiness that made me stop typing and just sit there.

And then the warmth started. My face felt flushed, like I'd just done a hard workout or had a shot of whiskey. I touched my cheeks—they were actually warm to the touch. My heart rate was normal (I checked my Apple Watch immediately, because I'm paranoid like that), but I felt this strange internal heat spreading from my core outward.

I wasn't sure if I was having some kind of reaction or if this was normal. The bottle didn't mention any of this. The product listing on Amazon definitely didn't mention it. So I did what any rational person does at 8 AM on a Wednesday: I dove back into Reddit.

Turns out, this is completely normal. The nausea happens because NR can be rough on an empty stomach—something about how it's metabolized in the gut. The flushing is related to increased NAD+ metabolism and improved circulation. Some people theorize it's from the methylation demands. Nobody really knows for sure, but it's common enough that there are dozens of threads about it.

I felt like an idiot for not researching the actual experience before starting. I'd read all the studies, understood the biochemistry, knew about the sirtuins and the PARPs and all that... but I hadn't read about what it actually feels like to take this stuff.

The Digestive Situation Nobody Mentions

Around day five, my digestion got... active. That's the polite way to say it. I'll be more specific: I was in the bathroom more frequently, and things were moving faster than usual. Not diarrhea exactly, just accelerated transit time.

This lasted about a week. My buddy Marcus—the guy who actually recommended NR to me in the first place—had warned me about this, but I'd forgotten. He'd said something like "yeah, your gut might get weird for a few days" but I hadn't really processed what that meant.

The theory, as far as I understand it, is that NR affects gut bacteria and intestinal cell metabolism. Your gut lining has a high turnover rate, lots of metabolic activity, so when you suddenly boost NAD+ levels, things shift. Some people get constipated. I got the opposite. Neither is fun.

What helped: taking it with a full meal (not just coffee and toast), staying hydrated, and honestly just waiting it out. By day 12 or 13, my digestion had normalized. But those first ten days? I was working from home for a reason.

I cut my dose to 300mg during this period. One capsule instead of two. That helped a lot. The digestive issues decreased noticeably, and I still felt the energy benefits. This was my first lesson in "more is not always better."

The Sleep Paradox (Week 2-4)

Here's where it got really interesting. Around week two, I started sleeping better—deeper, more restorative, waking up feeling actually refreshed. My Oura ring data backed this up: my REM and deep sleep percentages both increased.

But I also started having vivid dreams. Like, movie-quality, remember-every-detail-when-you-wake-up vivid. Some were cool. Some were unsettling. One night I dreamed I was back in my college dorm room, trying to find my computer science textbook, and I could read the actual text on the book spines. I woke up at 3:47 AM (I remember checking my phone) and couldn't fall back asleep for an hour.

This happened maybe 3-4 times during weeks 2-4. Just these random nights of incredibly vivid dreams followed by middle-of-the-night wakefulness. It wasn't every night, but it was often enough to be noticeable.

I posted about this in a longevity-focused Discord server I'm in, and about half the people said they'd experienced the same thing. The other half thought we were crazy. No studies mention this. It's not in any of the side effect profiles. But it's real.

My theory—totally unscientific—is that NAD+ affects brain metabolism during sleep, particularly during REM when your brain is highly active. More NAD+ means more energy available for dream generation? I have no idea. But I wasn't imagining it.

What helped: I moved my NR dose earlier in the day. Started taking it with breakfast around 7 AM instead of with my second meal around 11 AM. The vivid dreams decreased significantly. Still happened occasionally, but not as intensely.

The Headaches (And How I Fixed Them)

Week three, I got headaches. Not migraines—I've had those, and these weren't that bad—but this dull, persistent pressure behind my eyes. Usually started mid-afternoon, around 2-3 PM, and lasted until evening.

I almost quit NR entirely. I remember sitting on my couch on a Friday night, my wife watching some home renovation show, me pressing my fingers into my temples thinking "is raising my NAD+ levels really worth feeling like this?"

But I'd already spent $44, and I'm stubborn. So I did more research.

Turns out, NR increases methylation demands. Your body uses methyl groups (from B vitamins, particularly B12 and folate) to metabolize nicotinamide. If you're not getting enough B vitamins, you can develop relative deficiencies. The headaches were likely from increased methylation stress.

I started taking a B-complex supplement. Nothing fancy, just a standard methylated B-complex from Thorne. $22 on Amazon. Within three days, the headaches stopped. Completely gone.

This was around day 23. I noted it in my tracking spreadsheet: "Added B-complex, headaches resolved." I still take B vitamins with my NR. Every single day. Non-negotiable.

What Actually Stuck Around (The Long-Term Reality)

I'm now four years into taking NR. Not continuously—I've cycled off a few times, tried DHEA and other supplements instead—but I always come back to it. It's one of the few things I've kept in my routine this long.

Here's what the side effect profile actually looks like after the initial adjustment period:

What completely went away:

What still happens occasionally:

What I've learned to avoid:

My current protocol: 300mg NR with breakfast, taken alongside a B-complex and some BPC-157 during my recovery phases. Simple, consistent, no issues.

The Side Effects That Aren't Really Side Effects

There's this phenomenon with NR where some of the "side effects" are actually the mechanism working. Let me explain.

The flushing? That's improved circulation and metabolic activity. That's literally what you want. It feels weird, but it's not harmful.

The initial fatigue some people report (I didn't get this, but others do)? That's likely your body reallocating energy toward cellular repair processes instead of just keeping you artificially alert. It usually resolves within a week.

The increased urination? NR can have a mild diuretic effect. You're not dehydrated, your kidneys are just working more efficiently. Drink more water, problem solved.

I think a lot of people quit NR in the first week because they interpret these normal metabolic shifts as "bad reactions." They're not. They're signs that something is actually happening at a cellular level.

But—and this is important—actual bad reactions do happen. If you experience severe nausea, persistent headaches that don't resolve with B vitamins, racing heart rate, or any kind of chest discomfort, stop taking it and talk to a doctor. I'm not a medical professional. This is just my experience with mild, manageable side effects.

The Interactions Nobody Warns You About

Around month six, I started taking GHRP-2 for recovery. I'd read they worked through completely different mechanisms—NR for NAD+, GHRP-2 for growth hormone—so I figured they'd stack well.

The first week combining them, I felt amazing. Too amazing. Like, artificially alert, slightly jittery, hard to sit still. My resting heart rate went from its usual 58-60 BPM to around 68-70 BPM. Nothing dangerous, but noticeable.

I'm not saying NR and peptides don't mix—plenty of people combine them successfully. But adding multiple metabolically active compounds at once amplifies the effects. Both the good ones and the uncomfortable ones.

I dropped the GHRP-2 dose by 30% and the weird overstimulated feeling went away. Lesson learned: when stacking supplements or peptides, start each one individually, establish your baseline response, then combine them at lower doses than you'd use solo.

Same thing happened when I tried combining NR with HCG during a testosterone optimization phase. The HCG alone was fine. The NR alone was fine. Together? I felt wired and anxious for about three days until I adjusted the timing (NR in morning, HCG before bed).

How to Actually Minimize Side Effects (What Works)

After four years and probably 30+ adjustments to my protocol, here's what actually works for minimizing NR side effects:

Start stupidly low: Don't do what I did and jump straight to 600mg. Start with 100-150mg for the first week. I know the studies use 300-1000mg, but those are researching efficacy, not comfort. Your body needs time to adjust.

Take it with a real meal: Not coffee and toast. Actual food with protein and fat. I take mine with eggs, avocado, maybe some oatmeal. The fat seems to help with absorption and reduces nausea significantly.

Add B vitamins from day one: Don't wait for headaches like I did. Get a methylated B-complex (methylfolate and methylcobalamin, not folic acid and cyanocobalamin) and take it alongside your NR. This prevents methylation stress before it starts.

Time it early: Morning dose, ideally with breakfast. Some people can take it at lunch and be fine, but if you have any sleep sensitivity, earlier is better.

Stay hydrated: NR can increase metabolic water demands. I aim for at least 80oz of water on days I take it. Dehydration amplifies every side effect.

Give it three weeks: Most side effects resolve in 2-3 weeks as your body adjusts. If you're still having issues after week three, that's when you should reconsider the dose or the supplement entirely.

Don't combine with stimulants initially: If you're a heavy coffee drinker like me, consider reducing caffeine for the first week or two. NR has a subtle stimulant-like effect in some people, and stacking it with 400mg of caffeine can feel uncomfortable.

When to Actually Worry (Red Flags)

Most NR side effects are mild and temporary. But there are a few situations where you should stop and consult a healthcare provider:

I've been lucky—I've never experienced any of these. But I'm in a Discord server with about 200 other biohackers, and I've seen maybe 3-4 people report genuine adverse reactions that required stopping NR. It's rare, but it happens.

Also, if you have any pre-existing conditions—especially anything involving methylation issues (MTHFR mutations), liver conditions, or cardiovascular issues—talk to a doctor before starting NR. I'm not a medical professional. This is just what worked for me. Your biology might be completely different.

Frequently Asked Questions

Does NR cause cancer by overactivating cellular processes?

This is the fear I had around month two. I'd read some paper suggesting that boosting NAD+ could theoretically fuel cancer cells. Here's what I learned: there's no evidence in humans that NR promotes cancer. In fact, some research suggests adequate NAD+ levels might be protective. Cancer cells have dysregulated metabolism regardless of NAD+ availability. That said, if you have active cancer or a history of cancer, discuss this with your oncologist. Don't make this decision based on my blog post.

Can you build tolerance to NR and need higher doses over time?

I've been taking 300mg for four years. Same dose. Same effects. No tolerance that I can detect. My energy levels, sleep quality, and recovery remain consistent. Some people cycle it (4 weeks on, 1 week off) but I haven't found that necessary. The research doesn't show tolerance development, and my experience matches that.

Is the flushing/warmth sensation dangerous?

No. It's just vasodilation and increased metabolic activity. It feels weird, especially the first few times, but it's not harmful. It usually decreases in intensity after the first 2-3 weeks. If it's really uncomfortable, split your dose (150mg morning, 150mg lunch) or take it with a larger meal. The flushing is actually a sign that something is happening metabolically.

Should I take NR if I'm under 30?

NAD+ levels don't decline significantly until your 30s and 40s. If you're 22 with optimal health, you probably don't need NR. Your natural NAD+ production is likely fine. That said, some younger people take it for athletic performance or recovery. I didn't start until 34, after my bloodwork showed early metabolic dysfunction. If you're young and healthy, focus on sleep, nutrition, and exercise first. Save NR for when you actually need it.

What I Know Now That I Wish I'd Known Then

It's 6:30 AM in April 2025. I'm in the same bathroom, four years older, holding the same bottle of NR. Different brand now—I switched to a liposomal version that seems to work better—but same morning ritual.

My hands aren't shaking this time. I know exactly what to expect. 300mg with breakfast. B-complex alongside it. Water. The faint warmth will start around 45 minutes later, barely noticeable now. No nausea. No headaches. No digestive drama.

My testosterone is at 680 ng/dL now. Sleep averages 7.5 hours. I ran a half marathon last year at 37. I can't attribute all of that to NR—I've changed a lot of variables—but it's been a consistent part of the stack that got me here.

If I could go back to that Tuesday morning in March 2021, here's what I'd tell myself: The side effects are real, but they're manageable and mostly temporary. Start lower than you think you need to. Add B vitamins from day one. Take it with actual food. Give it three weeks before judging whether it works.

And maybe most importantly: the fact that it has side effects doesn't mean it's dangerous. It means it's actually doing something. Your cells are adjusting to having more energy available. That adjustment period is uncomfortable, but it's not harmful.

The bottle says "take one capsule daily." It doesn't say "you might feel weird for two weeks." It doesn't mention the flushing or the vivid dreams or the increased bathroom trips. But now you know. Now you won't be standing in your bathroom at 8 AM on day three, wondering if you're having some kind of reaction, feeling like an idiot for not researching this better.

You'll know it's normal. You'll know it passes. You'll know what actually works to minimize the discomfort.

And maybe, four years from now, you'll still be taking it too.