NAD+ vs. Spermidine: Which Is Better for Longevity?

Have you been hearing a lot about spermidine and NAD for longevity? We sure have, and we're on top of the facts and myths about both of these cutting-edge supplements, which have been gaining increasing popularity in the "healthy aging" crowd of late.

Spermidine supplements and supplements that boost NAD+ have different, though complementary, effects in the body.

• NAD+ supports cellular energy.

  As a metabolite of vitamin B3, the body uses NAD+ for, well, everything! Its starring role is in your cellular energy pathways, and because of that, it affects all the systems, cells, and organs in your body.
  

• Spermidine helps your body rid itself of old cells.

  Researchers are excited about spermidine because of its effects on autophagy, which is a word for the body's cellular cleanup mechanisms. You need autophagy to keep your body systems in tip-top working order.

It's no wonder people are talking about one or the other as the best supplement for aging cells. Let's get into more detail about how they both work and if you should add either (or both!) to your healthy aging routine.

Some people think of this in terms of spermidine vs. NAD supplement, but we'd say that's not the best way to think about them.

What is NAD+ and what does it do?

NAD+ is a coenzyme that the body absolutely, positively needs for cellular energy but also to properly regulate your genes, maintain a healthy immune and inflammatory response, support healthy aging, and much, much more. In fact, your cells can't function without it.

So, yeah, NAD+ is keeping you and everyone else alive, every day, every second. Hard-working molecule, right?

Here's the catch—actually, there are two catches:

1. Your levels of NAD+ (which stands for nicotinamide adenine dinucleotide) decrease with age. Could this be why people often start to slow down as they age? (Or, is it just that, as we age, we think "sure I'll take a nap! Why not?!") This is actively being studied.
   
2. While our bodies make NAD+ from vitamin B3, also known as niacin, niacinamide, or nicotinamide, you can't really increase the NAD+ levels in your cells very much just by taking vitamin B3 or getting niacin in your diet.

The only way to potentially increase your levels is with NAD+ boosting supplements, which contain precursors that the body turns into NAD+.

Examples of this include nicotinamide riboside (flows right off the tongue doesn't it?!) which is often abbreviated as NR. Some supplements contain a precursor called nicotinamide mononucleotide (another tongue twister!) which is usually abbreviated to NMN.

NR has been widely studied to boost NAD+ levels in the body, which in turn promotes cellular energy. It's also more bioavailable than NMN. This is why NR is getting so much attention as an exciting healthy aging nutrient.

What is spermidine and how does it work in the body?

Spermidine is one of the most exciting healthy aging substances, and supplements, to come along in a very long time. There may be as much excitement about spermidine supplementation as there was about resveratrol back in the day! It belongs to a class of molecules called polyamines and is probably most famous for its effects on autophagy, which means it can help your cells and organs to clean themselves out.

But, like NAD+, spermidine supplementation does a lot more than one thing. It also:

• Promotes a healthy inflammatory response throughout your body.
• It's been shown to help the brain and memory.
• People who consume more spermidine tend to have healthier cardiovascular systems.

Healthy brain, healthy heart…no wonder it's an up-and-coming healthy aging superstar supplement!

NAD+ vs. Spermidine: Compare and Contrast

Does spermidine promote autophagy?

In one word: yes. In fact, spermidine has been studied in laboratories all over the world for exactly this effect.

However, a much more common question is "What is autophagy?" To explain this will take more than one word! Autophagy can be thought of as the way cells keep themselves young and tidy. It's not just our skin, hair and memory that can change with age: components of our cells, as a result of regular metabolism, become less effective over the years (just like your car).

Autophagy is a self-regulating process, going on all the time, that allows cells to clean out cellular elements that are no longer functioning in a healthy manner. And it turns out that our bodies' autophagy mechanisms are a major part of reining in the aging process.

If we don't have a good cellular self-cleanup process in place, things get bogged down. That's why healthy aging enthusiasts look for ways to support autophagy, including:

1. Spermidine supplements
2. Intermittent fasting and caloric restriction
3. The plant extract luteolin, also available in some supplements

Interestingly, some research suggests that NAD supplements may also support autophagy. All the more reason to consider adding both to your routine!

Are NAD+ and spermidine more effective when taken together?

Since these two supplements have never been studied as a combination, there's no way to be absolutely certain about this. However, it's not far-fetched at all to think that there could be NAD and spermidine synergy. Because the two have different, complementary effects, they may well be better together.

We can ask this in another way:

• Do they have different roles and functions in the body? Yes.
• Do the things they do work together—meaning, are they complementary? Yes.
• Do their functions overlap so that, if you take one, you probably don't need the other? Nope.
• Will you benefit by keeping your levels of both up? Yes!

While we can't say it's a completely proven scientific fact that they're more effective when taken together, you probably want both the cellular energetics benefits (and the many other benefits) of NAD+, and surely you also want the cellular housekeeping, cardiovascular, and brain and memory benefits of spermidine. So to increase the chances of getting all the benefits of both, yes by all means, take these supplements together!

We can add this: even though we talk about cardiovascular and healthy aging and memory benefits of spermidine, boosting your NAD+ levels by taking nicotinamide riboside will certainly help keep all those systems humming. NAD+ is involved in pretty much every single function your body has to perform. And not just involved in them, but essential to them. So taking NAD+ precursors is a smart move!

But so is taking spermidine. And by smart we don't just mean the brain benefits, but the fact that spermidine helps all the cells in your body work well—just in a different way than NAD does it.

Do I get NAD+ and spermidine in my food?

Not really, at least not enough to make a huge difference. Scientists are studying the healthy aging and cell benefits of NAD+ precursors like nicotinamide riboside, as well as the polyamine spermidine in dosages we can only get from supplements. So to follow the research, you'll want to take advantage of spermidine supplementation and nicotinamide riboside (and eat a healthy diet)!

Yes, you can get some spermidine from foods, including wheat germ, but usually only in small amounts. Wheat germ is the best-known source of it, but it's unlikely you're consuming enough of it that way.

And NAD+ you don't get from diet at all, though your body can make some from vitamin B3 (which is in nuts and many animal-based foods like meat, fish and eggs). In the case of NAD+, unfortunately, there's less and less in our cells and in our bodies as we age, and many researchers who study aging believe that one of the effects of the decline in NAD+ is more rapid aging.

This is why there's so much excitement about boosting these two powerhouses using dietary supplements. If you really want to get the most out of the healthy aging benefits of spermidine and NAD+, you're going to need to look beyond diet alone.

Of course, this isn't to say that what you eat doesn't matter! A healthy diet is one of the most important factors in healthy aging. And a diet rich in veggies, whole grains, legumes, nuts and seeds, fruits, and healthy fats and proteins is certainly one of the best strategies for staying (or even getting) healthy.

Frequently Asked Questions

What's the best form of NAD+ to take with spermidine?

Many people who combine an NAD precursor with spermidine choose to take NR. This is one of the better-known and well-researched options. Another precursor is NMN.

Which is better for healthy aging: spermidine or NAD+?

There really is no "better" in this choice when it comes to supplements. Spermidine and NAD+ have different roles in the body and work in different ways. Also, science is still discovering all the many ways they can keep you healthy and support healthy aging.

Ideally, you wouldn't have to choose, and you could reap the advantages of both. If you must choose just one, we suggest you learn as much as you can about both of them and then decide which most appeals to you.

Another possibility if you're going to take just one is to take one of them one month (or three months), and then switch to the other, and repeat.

How to take NAD and spermidine together?

They can be taken at the same time, so no concerns here. Simply follow the dosage directions on the label. Always speak with your healthcare provider when adding a supplement to your regimen.

What's the bottom line on spermidine vs. NAD supplementation?

They're both healthy aging superstars. While turmeric and curcumin and resveratrol and mushroom coffee may get a lot of headlines, it's time to welcome a couple of "new kids" on the block!

The NAD+ precursor nicotinamide riboside, and spermidine, are in the supplement stacks of cutting-edge healthy-aging enthusiasts for good reason, and can help you, too. Spermidine is best known for inducing autophagy and supporting cardiovascular and brain and memory health. NAD+ is essential for every cell and function in your body and is best known for being absolutely essential to cellular energetics. (A fancy way of saying it's needed for life itself.)

Adding these two well-regarded supplements is a good complement to a healthy lifestyle. We all want to age gracefully, after all! So why not pull out all the stops?

References

• Eisenberg T, et al. "Cardioprotection and lifespan extension by the natural polyamine spermidine." Nature. November 2016. https://www.nature.com/articles/nm.4222
• Freeberg KA, et al. "Dietary Supplementation With NAD+-Boosting Compounds in Humans: Current Knowledge and Future Directions." J Gerontol A Biol Sci Med Sci. December 2023. https://pmc.ncbi.nlm.nih.gov/articles/PMC10692436/
• Halling JF, Pilegaard H. "Autophagy-Dependent Beneficial Effects of Exercise." Cold Spring Harb Perspect Med. August 2017. https://pmc.ncbi.nlm.nih.gov/articles/PMC5538402/
• Kiechl S, et al. "Higher spermidine intake is linked to lower mortality: a prospective population-based study." Am J Clin Nutr. August 2018. https://pubmed.ncbi.nlm.nih.gov/29955838/
• Madeo F, et al. "Nutritional Aspects of Spermidine." Annual Review of Nutrition. July 2020. https://www.annualreviews.org/content/journals/10.1146/annurev-nutr-120419-015419
• Ni YQ, Liu YS. "New Insights into the Roles and Mechanisms of Spermidine in Aging and Age-Related Diseases." Aging Dis. December 2021. https://pmc.ncbi.nlm.nih.gov/articles/PMC8612618/
• Pekar T, et al. "The positive effect of spermidine in older adults suffering from dementia : First results of a 3-month trial." Wien Klin Wochenschr. May 2021. https://pmc.ncbi.nlm.nih.gov/articles/PMC8116233/
• Shabkhizan R, et al. "The Beneficial and Adverse Effects of Autophagic Response to Caloric Restriction and Fasting." Adv Nutr. September 2023. https://pmc.ncbi.nlm.nih.gov/articles/PMC10509423/
• Wilson N, et al. "The autophagy-NAD axis in longevity and disease." Trends Cell Biol. September 2023. https://pubmed.ncbi.nlm.nih.gov/36878731/
• Wu H, et al. "The association of dietary spermidine with all-cause mortality and CVD mortality: The U.S. National Health and Nutrition Examination Survey, 2003 to 2014." Front Public Health. September 2022. https://pubmed.ncbi.nlm.nih.gov/36249217/
• Xie N, et al. "NAD+ metabolism: pathophysiologic mechanisms and therapeutic potential." Nature. October 2020. https://www.nature.com/articles/s41392-020-00311-7
• "Autophagy." National Cancer Institute.