The term “anti-aging” gets a bad reputation. It sounds like we’re trying to stop something that’s already well underway, or like we can’t embrace the parts of ourselves we’re supposed to love. But the reality is there are metabolic changes happening underneath the skin well before we see the effects of aging. Choosing to approach our health from the inside out might be just what we need to improve the way we age. 

In fact, one of the hallmarks of aging is a process known as “mitochondrial dysfunction", a term that refers to our cells' general loss in power and efficiency over time. It may be one of the reasons we age at all. And if the mitochondria are at the heart of why we age, it makes sense to look at every possible way of keeping them functioning for as long as possible.

That’s one of the reasons why some of the world’s leading scientists are turning to nicotinamide riboside. This unique form of vitamin B3 shows the potential to affect mitochondrial health and in turn, many of the age-related problems associated with it.

Understanding the mitochondria.

Inside almost every cell are these tiny, strangely shaped organelles called mitochondria— “the powerhouses of the cell.” These mini-organs are responsible for producing 90% of the energy we need in our bodies. The mitochondria are the reason why we exist as the complex animals we are today, rather than bacteria.

We didn’t always know just how vital the mitochondria were to our health. One key way of keeping mitochondria healthy is a molecule known as NAD+ (nicotinamide adenine dinucleotide). Our cells naturally produce NAD+, and we use it constantly throughout the day.

We also know our NAD+ supply declines as we age. Once researchers realized NAD+ could be the key to keeping our cells healthy, they scrambled for a way to make more of it.

The beginning of the vitamin B3s.

Researchers already knew of two vitamins that began the chemical process to increase NAD+: niacin and nicotinamide. These were discovered in the 1930s and used to treat pellagra, a potentially deadly vitamin B3 deficiency disease.

Niacin would also go on to be a treatment for high cholesterol in the 1950s. However, people found that ingesting niacin in high doses sometimes resulted in an annoying skin flush that was both irritating and unsightly.

Nicotinamide didn’t cause the skin flush and could in theory provide a lot of the same benefits, but it inhibited the activation of important cellular repair promoting proteins known as sirtuins. Neither nicotinamide nor niacin were as effective as researchers were hoping they’d be.

Although these two vitamins were NAD+ precursors, they weren’t ideal solutions. With niacin’s negative side effects, and the relative effectiveness of nicotinamide, researchers still didn’t have a good enough vitamin supplement for increasing NAD+ levels.

The discovery of nicotinamide riboside.

Another vitamin B3 known as nicotinamide riboside was discovered in the 1940s in yeast. But it wasn’t until the early 2000s that scientists began to see the potential of this third form of vitamin B3 to not only increase NAD+ but also improve human health in general. In 2004, a Dartmouth College research team discovered that nicotinamide riboside, like its vitamin B3 brothers, was also a precursor to NAD+.

The team, led by Charles Brenner, PhD, found that nicotinamide riboside could increase NAD+ in mice and that those mice experienced a plethora of health benefits as a result.

The mice showed everything from improved blood sugar levels and cholesterol levels to reduced nerve damage, and resistance to weight gain. Dr. Charles Brenner found these results so inspiring, he took the next step to see what nicotinamide riboside could mean for human health.

In 2014, Dr. Charles Brenner became the first human to consume nicotinamide riboside as a supplement. The results were just as promising. This relatively unknown form of vitamin B3 significantly increased his NAD+ levels safely, quickly, and without any negative side effects. 

A fully vetted supplement.

While Brenner made for a great lab rat and the findings produced from his self-trial were encouraging, clearly more testing was needed to confirm whether nicotinamide riboside was a viable supplement option for humans. As the Dr. Roy J. Carver Chair of Biochemistry at the University of Iowa Carver College of Medicine, Dr. Charles Brenner collaborated with his colleagues at Queen’s University Belfast to perform the first formal human trial of nicotinamide riboside.

In their trial, 12 healthy adults were given a single varying serving of nicotinamide riboside, with seven-day gaps between servings. Blood and urine samples were collected throughout the trial and analyzed. In 2016, they published the promising results, circulated by Nature Communications. Nicotinamide riboside supplementation safely increased NAD+ levels.

The far-reaching scope of nicotinamide riboside.

Nicotinamide riboside uses a unique pathway to produce NAD+ that none of the other vitamin B3s use.

Nicotinamide riboside also activates sirtuins, the cellular repair promoting proteins.These sirtuins then work overtime to help cells stay strong as we age.

Staying healthy as we age will never be as simple as one vitamin, even with one as promising as nicotinamide riboside. There are over 100 studies looking into nicotinamide riboside, with many showing that increased NAD+ levels are tied to metabolic and muscular health in mice. There are even more studies underway understanding the role of NAD+ in the support of other age-related health challenges including declining liver function, weight gain, insulin levels, and brain function in mice.

With eight completed human trials and many more underway, it’s only a matter of time before we know whether the benefits of this one simple vitamin could reach far beyond those of an average "anti-aging" supplement.

By Dr. Michael Roizen, Emeritus Chief Wellness Officer at the Cleveland Clinic and Chair of the Persona Nutrition Medical Advisory Board.

Walking into a store to purchase daily minimums of vitamins and supplements that you are lacking in your diet can be extremely confusing. There are oodles of bottles stacked next to each other on multiple shelves that span one end of the store to the other. No one in that store is analyzing your diet to find out what, if anything is missing.

In my expert opinion, I was excited to see personalized nutrition that analyzes what is missing in a person’s actual diet hit mainstream interest as it provides clarity about and access to essential vitamins, minerals and nutraceuticals that optimize health throughout the lifespan. From prenatal vitamins and minerals needed to optimize your and your baby’s health to nutrients scientifically researched that facilitate healthy aging, like NAD+.

There are five top reasons why personalized nutrition can support your overall wellness.

1. Digging deep to find what your body really needs – no more, no less.

By using a personalized approach to your nutrition, you’re able to zero in to address the nutritional gaps that you may experience based on your daily habits, dietary preferences, allergies, health conditions and prescription medication use. By answering online nutritional assessments – like Persona Nutrition’s comprehensive online questionnaire – (which I helped to develop) you will curate a morning and an evening pack of vitamins and supplements that are specific to your body’s needs.

2. Identifying drug-nutrient interactions.

I implied that prescription medications can provide nutrients as a part of the composition or they can deplete nutrients. This is an important consideration that many people miss. Most consumers don’t realize that their prescription medications may interact with supplements and vitamins and even nutrients in their diet. Persona Nutrition’s online nutritional assessment cross-references more than 2,000 prescription medications to ensure you are avoiding possible interactions. Persona is scanning more prescription medications than any other personalized nutrition company.

If it doesn’t feel like your prescription medication is working, speak to your doctor immediately. There could be an underlying interaction you are experiencing.

3. Connecting you to registered dietitians and nutritionists.

Life is always changing and sometimes we experience trigger moments – like injury, illness, dietary changes, etc. – and need to pivot or adjust our nutrition program. Before I started working with Persona Nutrition as a member of its Medical Advisory Board, I explored other personalized nutrition companies and found that Persona was the only company that built a customer care team entirely of educated nutritionists and registered dietitians to guide its customers. It really is a game-changer for those who want to have the flexibility of adjusting their regimen when needed.

4. Timing for true optimization.

Personalization extends beyond being able to curate a pack of vitamins and supplements based on what the body truly needs. It includes knowing the best times of day to take which supplement. This is another way personalized nutrition can support your overall wellness. Personalized packs of vitamins can be organized by morning or evening to ensure your body is optimizing each and every nutrient.

5. Delivering directly to your doorstep.

While this may seem like a trivial benefit of personalized nutrition, using a nutrition company that delivers dietary vitamins, minerals and supplements directly to your doorstep every 28 days can help ensure you are taking your vitamins every day. Unlike prescription medications that are designed to start working immediately, vitamins, minerals and nutraceuticals take time to build up in the body and muscles.

If you’re considering a personalized nutrition option to increase your NAD+, the way I do, Persona Nutrition now offers Tru Niagen® as one of its 86 plus high-quality vitamins and supplements – delivered directly to your front door!

Michael Roizen, MD, Emeritus Chief Wellness Officer, the Cleveland Clinic; Chair, Persona Nutrition Medical Advisory Board; and author of “What to Eat When: A Strategic Plan to Improve Your Health and Life Through Food”, with nine NY Times Bestsellers including four #1’s, including #1 in five other countries, and author of over 190 peer-reviewed publications.

NAD+ is an acronym for nicotinamide adenine dinucleotide, an essential coenzyme required by every living cell in your body to help generate energy. 

Without NAD+, your heart wouldn’t pump blood through your veins. Your lungs wouldn’t pull in any air. And the neurons in your brain wouldn’t fire. None of the vital organs in your body would work at all without this key molecule. NAD+ is like the oil in your car; it keeps your engine running smoothly.

Now, early human clinical trials show the role NAD+ plays with aging cells. Hassina Massudi and a team of researchers from the University of New South Wales uncovered age-associated changes in relation to low NAD+ levels. Their research shows us that NAD+ levels decline as much as 50% between the ages of 40-60 and that low levels of NAD+ are linked to many age-related health issues. 

But there’s good news. A paper published in the Translational Medicine of Aging shows positive therapeutic potential of boosting NAD+ as we age. The paper states, “NAD+ replenishment may serve as a potential therapeutic strategy for aging and multiple conditions to improve the quality of life of the increasing aged population.”

Luckily, there are several supplements on the market to help support your NAD+ production. We’ll take the time to go through each and highlight the pros and cons.

A straight NAD+ supplement.

The most obvious way to supplement your NAD+ is with more NAD+. As a dietary supplement, NAD comes in two forms: NAD+ and NADH. 

Why does it come in two forms? Think of a molecule of NAD as a delivery guy, picking up electrons from one house and delivering them to another. Before the NAD molecule picks up the electrons, it’s called NAD+. When it grabs the electrons, it’s called NADH. Regardless, there are no clinical studies to show a biological advantage of supplementing NAD+ vs NADH and vice versa so the difference is negligible. 

The biggest caveat of a straight NAD+ supplement is its potency. Unfortunately, NAD+ as a straight supplement is very difficult to maintain in capsule form. In both forms, the molecule degrades quickly when exposed to light and heat, and deteriorates when exposed to water. In fact, an FDA briefing document says NAD+ is unlikely to remain stable in capsule form under ordinary storage conditions.

Even if the pill is able to maintain its integrity, NAD+ as a straight supplement is largely ineffective in the body. A paper in the Journal of Nutritional Science and Vitaminology shows that the digestive process breaks down orally-administered NAD+ into common NAD+ precursors before the cells get a chance to absorb it. Likewise, the paper reveals orally-administered NADH breaks down into unidentified mystery metabolites, making it unclear if metabolized NADH increases NAD+ in the body at all.

Also, if NAD+ were to remain intact, its ability to permeate cellular walls remains problematic. NAD+ is a large phosphorylated molecule that can only enter a cell through special doorways known as transporters. While some specialized cells may contain these transporters, a published study from the Journal of Biological Chemistry shows that NAD+ biosynthesis in human cells is not so clear. The study shows that NAD+ must be broken down into smaller building blocks before being passed into the cell and converted back to NAD+. 

What’s more, a single molecule of NAD+ is more than twice the weight of one molecule of most NAD+ precursors, such as nicotinamide riboside. That means a capsule of nicotinamide riboside contains more than twice as many molecules as the same size capsule of NAD+. 

On a more tangible level, effective NAD+ capsules are literally too big to swallow. During a clinical study with schizophrenic patients published by the British Journal of Psychiatry, scientists discovered that a 250-milligram capsule of NAD+ is too big to swallow, forcing them to split the NAD+ into two smaller 125-milligram capsules.

Fortunately, your cells excel at using NAD+ precursors to make more NAD+ naturally. So, if you want to crank up the amount of NAD+ in your body, supplementing your diet with an NAD+ building block is a much more fruitful way to go.

Niacin (NA) as an NAD+ boosting supplement.

Nicotinic acid, commonly known as niacin, is a form of vitamin B3 that can elevate NAD+ levels. This was the earliest form of B3, discovered in the 1930s to treat pellagra—a deadly vitamin B3 deficiency disease. 

Unlike a straight NAD+ supplement, niacin is an NAD+ precursor. An NAD+ precursor is a building block molecule that eventually becomes NAD+ through a series of chemical conversions. 

Niacin takes a three-step process (known as the Preiss-Handler pathway) through the cell to convert into NAD+. However, it is not an ideal NAD+ booster. People found that ingesting niacin in high doses sometimes resulted in a flushing of the skin that was both irritating and unsightly. 

Nicotinamide (NAM) as an NAD+ boosting supplement.

Nicotinamide, also known as niacinamide or NAM, is a second form of vitamin B3 and is also a precursor to NAD+. Unlike niacin, it does not cause the skin to flush, making it a more ideal NAD+ booster. However, the vitamin inhibits sirtuins, an important class of proteins that promotes cellular repair. 

Nicotinamide Riboside (NR) as an NAD+ boosting supplement.

Nicotinamide riboside is the third and most recently discovered form of vitamin B3, also an NAD+ precursor. A study by Wendell Gingrich and Fritz Schlenk published in the Journal of Bacteriology shows that nicotinamide riboside was originally discovered during a 1940’s study on yeast. But it wasn’t until the early 2000s that scientists began to see the potential of this third form of vitamin B3. 

A clinical trial published in Scientific Reports, where nicotinamide riboside was administered to healthy adults, reveals nicotinamide riboside both safely and effectively increases NAD+ levels. 

Unlike nicotinamide, nicotinamide riboside does not inhibit sirtuins. In fact, a study published in Nature Communications reveals that nicotinamide riboside significantly increases levels of both NAD+ and adenine diphosphate ribose (ADPR)—a byproduct of healthy sirtuin activity—demonstrating that it stimulates more NAD+ consuming activities. That means nicotinamide riboside increases NAD+, which then activates your sirtuins to regulate a variety of fundamental biological processes throughout your body.

Also, unlike niacin, nicotinamide riboside does not cause flushing. In fact, high doses of nicotinamide riboside have been administered to humans without any attributable reports of flushing.

Nicotinamide riboside is converted to NAD+ by traveling along the shortest and most direct pathway inside your cells compared to niacin or nicotinamide, saving your cells time and energy. 

Nicotinamide Mononucleotide (NMN) as an NAD+ boosting supplement.

Nicotinamide mononucleotide, or NMN, is another NAD+ precursor that is relatively new to the scene. NMN is not a form of vitamin B3 but rather a molecule derived from riboside and nicotinamide. NMN has been used in many preclinical studies; a study published in Biomolecules shows the therapeutic applications of NMN. However, NMN has been minimally tested in one clinical study that did not report any effects of NMN on NAD+ levels. In other words, no one knows for sure if daily supplementation with NMN is safe for human consumption or if it actually increases NAD+ in humans. 

Also, a study published in Nature Communications, on NMN’s metabolism in mammalian cells suggests NMN is too big to enter your cells. The research shows that your body must first convert supplemental NMN into nicotinamide riboside before it can enter your cells. In short, it’s a cumbersome and inefficient process.

Tryptophan as an NAD+ boosting supplement.

Tryptophan is an amino acid used by the body to synthesize proteins and can only be obtained through diet. It is found in foods like turkey, chicken, meat, cheese, yogurt, and eggs.

A study published in the Annual Review of Nutrition evaluated all the NAD+ precursor vitamins, revealing tryptophan as the least efficient. The study shows that tryptophan takes a six-step pathway through the cell to convert into NAD+. Along the six-step pathway (technically called de novo biosynthesis), tryptophan converts into several other chemical compounds that can get sidetracked down other pathways, making the tryptophan pathway the longest and most inefficient pathway for synthesizing NAD+. 

In the end, the payout is quite minimal. A review of niacin, provided by Oregon State University, shows that the tryptophan pathway requires at least 60 milligrams of tryptophan to produce the same amount of NAD+ generated by 1 milligram of niacin. 

The best supplement to replenish your NAD+.

Although there are several ways of boosting your NAD+, it’s clear that not all methods are equally viable. Here’s an overview of all the points we’ve covered pertaining to NAD+ supplementation:

1. Straight NAD+ and NMN are too big. Size matters. Straight NAD+ and NMN cannot be directly absorbed by your cells. Your body has to break them down into smaller precursors before they can pass through your cellular walls. The three B3 vitamins, niacin, nicotinamide, and nicotinamide riboside, are the smallest precursors of NAD+ that can enter your cells intact.

2. Some have annoying side effects. Niacin, when activated, can cause reddened skin, a burning sensation, and itching. However, no other NAD+ boosting supplement reports these symptoms.

3. Some boost NAD+ but suppress other positive cellular functions. Although nicotinamide does not cause flushing like niacin, it affects sirtuin activity in your cells. Sirtuins are an important class of proteins responsible for cellular maintenance. 

4. Pathways are important. There’s more than one path that leads to boosting NAD+ in your cells. Some are quicker than others. Out of all the options, nicotinamide riboside travels along the fastest and most efficient pathway to produce NAD+.