Humans have been searching for the fountain of youth for, well, forever.
A mythical spring or other source of water, it restores the youth of anyone who drinks or bathes in its waters.
Fast forward to today, and when longevity, aging and other experts talk about longevity, they’re broadly referring to maintaining cellular energy production and output to ensure cells, and by extension, tissues and organs can preserve their functionality for as long as possible.
And when it comes to energy production, it’s all about your mitochondria. The little structures in virtually all cells that are responsible for burning oxygen, and primarily glucose (carbohydrate) and fat from food to make the universal energy molecule ATP.
Naturally, as you age, your body’s ability to maintain optimal energy production and output declines. Anything that can slow down that decline is a good thing, and is the focus of ‘anti-aging’ or longevity research.
It’s all about NAD
NAD (or nicotinamide adenine dinucleotide), a mouthful I know, is a crucial molecule that is found in all of your cells (1).
All tissues in your body convert vitamin B3 into its main metabolically active form, the coenzyme NAD. More than 400 enzymes require NAD to catalyze (enable) reactions in the body, which is more than for any other vitamin-derived coenzyme (1, 2).
NAD facilitates “metabolism”, a.k.a. as energy production. When you eat food, you eat protein, fat, and carbohydrate. For the most part, carbohydrate and fat (and to a lesser extent, protien) are ‘burned’ to produce energy and that energy is used to make the master energy molecule ATP for your body (3, 4).
All of this happens in your cells and, specifically, it happens within specialized structures within your cells called mitochondrion (mitochondria single) – stay with me. The best way to think of it is using the analogy of a house and furnace. A house is like your cell and the furnace is your mitochondria. Just the the furnace produces energy (in the form of heat), your mitochondria produce energy too (as ATP).
Check out the diagram below to conceptualize the reference; the little red structures are the mitochondria and this is where the action happens in terms of energy production.
To go a little deeper, food energy is broken down via different pathways that occur in different areas of your cell and in the mitochondrion. In simple terms, the byproducts of food energy breakdown (technically electrons) need to be shuttle from one place to another and this is where NAD comes in.
NAD carries these energy units from one reaction to another and that’s why NAD is called a “cofactor”. When NAD is carrying its payload (electrons) it’s abbreviated “NADH”.
So, in short, the products of both carbohydrate and fat breakdown have to be shuttled from one place to another, so they can be metabolized further.
The very simplified diagram below will help to illustrate this. NAD, in the form of NADH, is busy shuttling electrons around.
For a more detailed version below, you can see NAD/NADH (I’ve circled them in blue) through the different biochemical reactions that are involved in energy production without which you wouldn’t be able to read this post and soldier through 🙂
Feel free to skip this part.
Glucose (carb) is ultimately turned into acetyl-CoA (in red), as is fat, via “FAO” or fatty acid oxidation. The fate of both fat and carb is to make their way to the TCA cycle for continued metabolism. The last part of the process is for NAD to bridge the TCA cycle with OXPHOS (oxidative phosphorylation) for the final step of energy (ATP) production. All thanks to NAD/NADH.
NAD is also required for enzymes involved in critical cellular functions, such as the maintenance of genome (DNA) integrity, control of gene expression, and cellular communication (yes, cells cross talk with each other, if that goes south, diseases follows).
Long story short, without NAD, you wouldn’t exist because your cells wouldn’t be able to generate energy. So anything that can help to maintain NAD levels is a good thing because an optimal cell will have a good amount of NAD and a good ratio of NAD to NADH.
If and when NAD levels drop, the ratio will change because there will be a lot less NAD and a lot more NADH. Translation? Both declining energy levels and cellular/organ function; a notable reality of the aging process.
So the question becomes, can maintaining NAD levels and by extension, NAD:NADH ratios help to maintain cellular function? And, is there anyway to slow down the natural decline of NAD we see with aging?
I’ve pointed out the fact that the amount of NAD that your body naturally produces, declines with age (5). It’s estimated that the NAD levels decline up to 50% between the ages of 40 to 60.
Why this is of interest to anti-aging and longevity researchers is because low levels of NAD have been linked with several health concerns (Alzheimer’s, heart disease, diabetes and more) due to the resulting decrease in cellular energy production (and therefore organ function) (2).
Will the real vitamin B3 please stand up?
The building block, or precursor, of NAD includes different forms of what’s generically referred to as “vitamin B3”.
B3 is one of the B vitamins generally referred to as the “B complex”; water soluble vitamins that your body needs on a daily basis because your body doesn’t have any way of storing them (9).
These NAD precursors go by many names depending on their specific structures and include nicotinic acid, niacin, and nicotinamide/niacinamide.
FUN FACT: pellagra is the disease of severe vitamin B3 deficiency. Symptoms are referred to as the three “Ds”: sun-sensitive dermatitis, diarrhea and dementia.
Some of the amino acid tryptophan (which you get from dietary protein) is converted to NAD as well. For this reason, when a person’s vitamin B3 status is estimated, their intake of B3, as well as, the adequacy of their protein intake, is assessed.
Niacin or nicotinic acid
Niacin has become the common term for all derivatives of vitamin B3. Niacin is really the generic name for nicotinic acid. Niacin is naturally present in many foods, added to some food products, and available as a dietary supplement; alone on in combination with other nutrients.
Nicotinamide, also known as niacinamide, is another form of vitamin B3 found in food and supplements. Nicotinamide is generated in two ways; 1] dietary niacin/nicotinic acid is promptly incorporated into your liver cells and is converted into nicotinamide and 2] some of the tryptophan from dietary protein is converted into niacinamide as well.
All commonly known forms of vitamin B3 mentioned above can prevent and reverse vitamin B3 deficiency and can all be converted by your body into NAD.
What is nicotinamide riboside?
Nicotinamide riboside (NR) was discovered in 2004. It is another form of vitamin B3 and like others, NR is converted by your body into NAD.
NR is found in food such as cow’s milk, yeast and beer but only in trace amounts (10).
What’s getting people excited is the growing evidence that NR supplements can easily and effectively increase NAD levels, seemingly better than any other form of vitamin B3 (niacin/nicotinic acid, niacindamide/nicotinamide) (11).
Since 2004, there have been over 150 scientific articles published on NR and the number is rapidly growing. Ultimately, where the evidence for NR lands is unknown because research is in its infancy, but we do have some (exciting) hints.
Benefits of nicotinamide riboside
Converted to NAD
Already mentioned above, NR is easily converted to NAD which is involved in lots of metabolic pathways. Also stated, NAD levels fall as we age and continue to do so throughout life.
While other forms of vitamin B3 are converted to NAD, they can’t prevent declining levels seen in aging. However, as an NAD precursor, NR is different and is effectively used by your body to increase and maintain NAD levels, up to 2.7 times better than other forms of B3 (16).
Activates healthy-aging enzymes
NAD is involved in over 400 different enzyme-based reactions. Enzymes are just specialized proteins that facilitate biochemical pathways; as a simple analogy, they’re the spark plug that keeps things running.
One group of specialized proteins that are activated by NAD are called sirtuins. They’re rockstars in the anti-aging camp because they are involved in influencing lifespan for one.
May be neuroprotective
NAD may help to protect your brain cells as they age by protecting them from damage associated with being alive. Burning oxygen and glucose (or ketones) for energy always has some collateral damage which can impact proteins and fats in the your neurons (23).
NAD also helps to prevent some of the damage in the very thing that is responsible for your cells energy production, your mitochondrion. Energy production will cause damage if left unchecked but NAD (and other antioxidants) helps to protect your mitochondrion from excessive wear and tear which is associated with brain disorders such as Alzheimer’s and Parkinsons to name a couple (24, 25, 26)
Lowers heart disease risk
Blood vessel health is so much more than just the tired trope of LDL “cholesterol”.
The cells of the blood vessels need to expand and contract appropriately (endothelial function), be freed from excessive oxidation (which drives inflammation) and like all cells, need to produce enough energy in order for them to do their best work.
The reality of life is that we age, and aging is known to take its toll on the health of your blood vessels. Overtime, blood vessels can become stiffer for a variety of reasons. Anything that can help your blood vessels be more flexible and less rigid, like they are in younger aged people, is a good thing.
In preliminary animal studies, supplemental NR has been shown to reverse age-related blood vessel changes by increasing NAD levels (R).
Similar benefits have been seen in human studies as well. By raising NAD levels, NR has been shown to reduce aorta stiffness and lower blood pressure in those at risk of, and who have pre-hypertension (high blood pressure)(R).
Any issues with nicotinamide riboside?
To date, safety studies show that NR is very safe and well tolerated. In human research, intakes between 1000-2000 mg per day had no ill effects (R, R). Some have reported side effects with higher doses (500 mg and more per day), such as nausea, fatigue, headache, and indigestion (R).
NR has two fates when consumed. It can be converted into NAD or it can be ‘methylated’ and peed out. In order for NR to be converted to NAD, it needs a reason to, namely, to support energy production. Because energy production (ATP generation) is stimulated by eating, it’s best to take NR with food.
By ramping up the pathways that produce ATP, NAD will be in high demand and with adequate amounts of NR on board, NR will be used.
NAD is also used in the methylation cycle, a pathway integral to overall health. Suffice it to say, to support NAD’s this role, it’s important to ensure you’re getting enough methylation-supporting nutrients such as choline, creatine, and vitamins B12, B6, B2, and folate.
If you’re interested is exploring the possible benefits of NR and increased levels of NAD, supplements are needed.
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Nicotinamide riboside is an alternative form of vitamin B3 that is effective at raising NAD levels within cells. This may help to slow down many of the NAD decline-related issues associated with aging.
Because it may help cells to maintain energy levels and function, NR is commonly marketed as an “anti-aging” product.
Most research on NR and NAD+ is in animals. More high-quality human studies are needed before recommending it as a treatment; at this point, any indication for using it would be seen as “supportive” or “may benefit”.
It has an excellent safety profile with few side effects and taken at doses typically found in common supplements, is unlikely to be an issue for most people and may help to support long term health.