NAC vs NAD vs NR vs Niacin vs NMN: What Are the Differences?

NAC vs NAD vs NR vs Niacin? Due to the small alphabetical differences, these supplements are often mixed up and confused by most consumers. We will cover the essentials and explain about each of these supplements below.

NAD vs NAD+ vs NR

NAD

NAD is derived from Nicotinamide Riboside (NR) and various other precursors. NR is one of the 3 main forms of Niacin (vitamin B3).

NR, nicotinamide mononucleotide (NMN), Niacin (NA) and Niacinamide (NAM) are all NAD precursors, meaning all these precursors will be transformed into NAD. That said, each precursor has it's own different pathway that will lead to NAD.


NAD+ is a substrate for a number of important enzymes, including poly(ADP-ribose) polymerase (PARP) and sirtuin 1 (SIRT1), which is known as a classic longevity protein. NAD+ is also essential in metabolic processes such as creating ATP in your mitochondria. It accepts and donates electrons and is used in oxidation-reduction reactions in the mitochondrial electron transport chain.

The levels of NAD in our body determine the speed of aging process. In younger cells and tissues, the levels of NAD are higher. As a result, younger people tend to have better physical activity, cognitive function and potential for cell repair and regeneration. As we grow, the levels of NAD in our body start to decline. This is reflected in the form of slowed cognitive response, loss of memory and reduced agility.

Research suggests it may be possible to reverse mitochondrial decay with dietary supplements that increase cellular levels of a molecule called NAD (nicotinamide adenine dinucleotide).

NAD is a linchpin of energy metabolism, among other roles, and its diminishing level with age has been implicated in mitochondrial deterioration. Supplements containing nicotinamide riboside, or NR, a precursor to NAD that's found in trace amounts in milk, might be able to boost NAD levels. In support of that idea, half a dozen Nobel laureates and other prominent scientists are working with two small companies offering NR supplements.

The NAD story took off toward the end of 2013 with a high-profile paper by Harvard's David Sinclair and colleagues. Sinclair, recall, achieved fame in the mid-2000s for research on yeast and mice that suggested the red wine ingredient resveratrol mimics anti-aging effects of calorie restriction. This time his lab made headlines by reporting that the mitochondria in muscles of elderly mice were restored to a youthful state after just a week of injections with NMN (nicotinamide mononucleotide), a molecule that naturally occurs in cells and, like NR, boosts levels of NAD.

NAD boosters might work synergistically with supplements like resveratrol to help reinvigorate mitochondria and ward off diseases of aging. Elysium is banking on this potential synergy—its NR-containing supplement includes a resveratrol-like substance called pterostilbene (pronounced tero-STILL-bean), which is found in blueberries and grapes.

While resveratrol has hogged the anti-aging spotlight over the past decade, unsung researchers in places like Oxford, Miss., have quietly shown that pterostilbene is a kind of extra-potent version of resveratrol. The pterostilbene molecule is nearly identical to resveratrol's except for a couple of differences that make it more "bioavailable" (animal studies indicate that about four times as much ingested pterostilbene gets into the bloodstream as resveratrol). Test-tube and rodent studies also suggest that pterostilbene is more potent than resveratrol when it comes to improving brain function, warding off various kinds of cancer and preventing heart disease.

How excited should we be about all this? If I were a middle-aged mouse, I'd be ready to spend some of the nickels and dimes I'd dragged off the sidewalk to try NR supplements. Even before Sinclair's paper, researchers had shown in 2012 that when given doses of NR, mice on high-fat diets gained 60 percent less weight than they did on the same diets without NR. Further, none of the mice on NR showed signs of diabetes, and their energy levels improved. The scientists reportedly characterized NR's effects on metabolism as "nothing short of astonishing."

But the paucity of human data gives me pause. Nobel laureates notwithstanding, I plan to wait until more is known before jumping up from the supper table to run out for some NR. Besides, it probably won’t be long before more data come out given the growing buzz about NAD.

Read more: https://blogs.scientificamerican.com/guest-blog/beyond-resveratrol-the-anti-aging-nad-fad/

NAC (N-Acetyl Cysteine)

N-acetyl L-cysteine (NAC) is a precursor of glutathione, helps to replenish intracellular glutathione, a vital cellular antioxidant. NAC has a low molecular weight and is well absorbed via oral administration. 

2017 paper found NAC has potent thrombolytic effects, meaning it breaks down blood clots once they've formed.

Importantly, NAC may also protect against other problems associated with COVID-19, including the hypercoagulation that can result in stroke and/or blood clots that impair the ability to exchange oxygen in the lungs.

Many COVID-19 patients experience serious blood clots, and NAC counteracts hypercoagulation, as it has both anticoagulant and platelet-inhibiting properties.

NAC also inhibits cellular entry and replication of some respiratory viruses, assists in clearing thickened mucous from the airways, suppresses inflammatory signalling, and may help mitigate viral infection-induced cytokine storm (Ref).


NAC vs NAD

The similarity in terms of spelling with the only difference in one character, these two popular nutrients are often mixed up and confused by most consumers. However, scientifically these two molecules are related to two distinctively different nutrients. NAC is related to glutathione, an antioxidant whereas NAD is related to vitamin B complex. 

NADPH (also often confused with NAD) is responsible for generating free radicals in immune cells by NADPH oxidase. These radicals are used to destroy pathogens.

Hyperglycemia increases reactive oxygen species (ROS) and the resulting oxidative stress plays a key role in the pathogenesis of diabetic complications. Nicotinamide dinucleotide phosphate (NADPH) oxidase is one of the major sources of ROS production in diabetes. In this study, NAC inhibits NADPH oxidase activation in diabetes and reduces tissue oxidative damage in all organs.

Glutathione vs NAC

Taking glutathione by mouth does not appear to be an effective way to get it into your body. Its bioavailability is low and is also thought that glutathione may be broken down by enzymes in the stomach.

NAC has a low molecular weight and is well absorbed via oral administration.

NAD+ Helps Restore Age-Related Muscle Deterioration

As reported by Science Daily, scientists recently discovered that Alzheimer's-like protein aggregates underlie the muscle deterioration commonly seen in aging, and that nicotinamide adenine dinucleotide (NAD+) is essential for combating this condition.

Their study, published in the journal Cell Reports, showed that protein aggregates (amyloid) could be blocked by boosting the levels of NAD+, a biomolecule that is also essential for maintaining mitochondrial function.

NAD+ boosting molecules such as nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), nicotinamide (a form of vitamin B3 or niacin) and nicotinic acid (niacin) have all been shown to protect against age-related muscle disease.

Related: The Crucial Role of NAD+ in Optimal Health

NAD vs NAD+: What's the Difference?

If you have done any research on aging and health recently, you have likely stumbled across the so-called anti-aging molecule, NAD. You have probably also seen it called NAD+ and maybe even as NADH. So, what is the difference, if there is any?

The short answer is that there is a difference, at least between NAD and NADH. Generally speaking, when NAD is used, NAD is being talked about generally. And often when using “NAD” it is referring to the specific chemical forms of NAD, NAD+ and NADH, interchangeably.

NAD exists in two forms: NAD+ and NADH. Its ability to switch between these two forms is what allows NAD to carry out its main function—carrying electrons from one reaction to another in the process of metabolism and energy production.

As an electron carrier, NAD+ and NADH help to convert the nutrients in your food into a form of energy your cells can use.

Niacin (NA)

Niacin or the original vitamin B3 is another precursor to nicotinamide adenine dinucleotide (NAD+). There are three main forms of vitamin B3, which are dietary precursors to nicotinamide adenine dinucleotide (NAD). These are nicotinamide riboside (NR), nicotinic acid and nicotinamide; collectively referred to as vitamin B3.

Is NAC different from Niacin? Yes, they are very different. Although both of these molecules belong to different categories, we get this question often. Niacin is part of the vitamin B complex whereas NAC is a precursor of glutathione.

Related: Niacin and Melatonin: Metabolic Health and COVID-19

NR vs NMN

While most anti-aging products try to reverse signs of aging on your skin, nicotinamide riboside — also called niagen — aims to reverse signs of aging from inside your body.

There are multiple precursors to NAD+, each with its own physiologic effects. Nicotinamide riboside (NR) is a popular one with several notable benefits over other precursors like niacin (NA) and niacinamide (NAM). NA, for instance, may induce uncomfortable flushing, while NAM may inhibit sirtuin at high doses, both undesirable effects.

Because of its unique profile of benefits and low risks, NR has emerged as a popular choice, especially by its discoverer, biochemist Charles Brenner, among the NAD+ precursors. In Scientific Reports, researchers noted:

“Because NR does not cause flushing or inhibit sirtuins and the genes (NRK1 and NRK2) required for the metabolism of NR to NAD+ are upregulated in conditions of metabolic stress, NR has a particularly strong potential as a distinct vitamin B3 to support human wellness during metabolic stress and aging.”

“Therefore, administration of niacin or niacinamide is unlikely to be widely adopted for maintaining health and function with aging,” researchers wrote in Nature Communications.

Within your body, nicotinamide riboside is converted into NAD+, a helper molecule that exists inside each of your cells and supports many aspects of healthy aging.

Nicotinamide riboside supplements — such as niagen — have quickly become popular because they appear to be especially effective at raising NAD+ levels (Trusted Source). Nicotinamide riboside is also found in trace amounts in cows’ milk, yeast and beer (Trusted Source).

NR used to be considered superior because no NMN transporter — required to get it into cells — had been detected. We now know there is such a transporter, which gives NMN the advantage as it’s also a more direct NAD+ precursor.

However, most of the NAD+ precursor research is done with NR. 

Pitting NR and NMN against each other is, for now, somewhat of a moot point because the two molecules have never been studied side by side in humans. The biggest, and most obvious, difference between NMN and NR is size. NMN is simply larger than NR, meaning it often needs to be broken down to fit into the cell. NR (Nicotinamide Riboside), when compared to other NAD+ precursors (like nicotinic acid or nicotinamide) reigns supreme in efficiency.

But give NMN a new door, one it can fit through, and it’s a whole new game. This is where cellular transporters come into play. Transporters are proteins that are doors on the cell; they allow molecules to enter the cell without needing to chemically transform.

As research grows, it is likely to become clearer that NMN and NR may have differing benefits depending on the part of the body and their use. Where NMN transporters are found, they could make one more preferable over the other. NMN has also been found to improve insulin activity and production which could help to accelerate metabolisms and make the body more glucose tolerant.

That said, according to David Sinclair in this podcast:

NAD is a big molecule relative to vitamin B3. It's got those phosphates on there. It's got a sugar. It's got the vitamin B attached. So you've got all these components that come together to make this very complicated molecule called NAD. And when you give NMN, it contains all three components that the body needs to make NAD. If you give NR or just vitamin B3, which is an even smaller molecule, the body has to find these other components from somewhere else. So where do you get phosphate? Well, body needs it for DNA, needs it for bones. So high doses of something that requires additional phosphate makes me a little concerned, and we have compared NMN and NR head-to-head in mouse studies. We've shown that NMN makes mice run further, old mice can run 50% further because they better blood flow, better energy. NR the same dose did not do that. In fact, it had no effect.



Supplement manufacturer ChromaDex alleges that testing has revealed that more than half of NMN anti aging supplements being sold on Amazon contained almost none of the bioactive molecule. Source: ChromaDex NMN Report (Oct 2021)

ChromaDex markets TruNiagen, which is based on its branded Niagen ingredient, which is a form of nicotinamide riboside (NR), the form of nicotinamide that actively crosses into the cell to participate in the NAD+ pathway. Boosting this pathway, and thus maintaining cellular function at a lively, youthful level, has become a prominent theme in recent anti aging research.

Recently researchers have argued that a transporter exists for NMN too, which is something that ChromaDex disputes. It claims that NMN must first be converted into NR in the blood before it can be used by the cells.

In the several years since the NMN transporter discovery was asserted, the NAD+ anti aging field has become crowded with NMN based supplements all seeking a piece of the pie created by ChromaDex and its competitor and one time customer Elysium. (The two companies have been locked in various patent infringement and breach of contract suits for several years.)

Last fall, ChromaDex obtained 22 samples of NMN products being sold on Amazon. Of these, 14 claimed to contain 500 mg of NMN. A further two products calimed 300 mg on the label; five claimed 250 mg and one product claimed 125 mg.

Only one of the 500 mg products came close to meeting label claim. It had 456 mg of NMN. All of the other 13 products in the 500 mg group either came in at below reporting limit (BRL, defined as less than 1% of the stated amount) or, in the case of 3 products, no NMN was detected at all.

Almost all of the rest of the products performed better, having at least 88% of the label claim. A lone 250 mg product was identified as BRL.

In summary, ChromaDex said that 64% of the products tested contained less than 1% of the stated amount of the active ingredient, which should give consumers pause, the company said.

"While this is a limited snapshot of the vast NMN finished product landscape, it does provide a glimpse into the high variability of product quality that is available... According to this study, the majority of the products one might purchase online contain such a small amount of NMN that there would be no clinical benefits achieved from the dose. Another concern with these adulterated products is that the actual contents are not known and could pose a risk to the user," the company said in a statement.

Can you take NR and NMN together?

There have been no studies on taking NMN & NR together, and it would be best to test both separately and find which one you respond better to. You may be wasting your time (and money) taking both NMN & NR together as studies show that the majority of the time, NR is turned into NMN which is then turned into NAD+.

Read More: NMN vs NR - Best Way to Increase Your NAD+ Levels

Naturally Boosting NAD Levels

If you want to remain youthful and enjoy a long and healthy life, then there are ways in which you can naturally enhance the levels of NAD in your body. Continue reading to find out how:

1. Fasting - Fasting is practiced in many religions throughout the world. In addition to its spiritual benefits, it turns out that fasting is also beneficial for our health. Fasting, or reducing your calorie intake is an excellent method for indirectly boosting the body’s NAD levels. Fasting has been shown to increase the levels of NAD+ and surtuins; the proteins which have been found to slow the aging process. While fasting is effective in increasing NAD+ levels, drastic reduction in calorie intake or fasting can have a counterproductive effect. There is also some speculation that intermittent fasting or adopting a low carb-ketogenic diet may also provide similar positive results.

2. Nicotinamide Riboside Dietary Supplements - Nicotinamide Riboside has recently been discovered in Vitamin B3. No one really paid attention to this molecule until research showed that our bodies can use NR to metabolise NAD+! After this discovery, several NR supplements became available in the markets. Various studies have shown that NR supplements are beneficial in boosting the levels of NAD+ in the body.

3. Exercise - Exercise is one of the easiest and most cost-effective methods for boosting NAD+ levels. When we exercise, our bodies need energy, which comes from NAD+. Basically, exercise forces our body muscles to produce more mitochondria, which are the powerhouses of cells. The increased production of mitochondria results in a natural boost in NAD+ levels in the body.

4. Too Much Sunlight May not be Good! - Research has shown that too much direct sunlight exposure can deplete the body of NAD+ levels. This is because our body uses NAD+ to repair cells which get damaged as a result of direct UV ray exposure from the sunlight. In case you feel that excessive sunlight exposure is inevitable for you, then you should wear sunblock, sunscreen or sunglasses.

5. Foods which Boost NAD Levels - There are certain foods which can boost NAD levels in the body. Some of them include:
  • Dairy Milk – research has indicated that cow’s milk is a good source of Nicotinamide Riboside (NR). A litre of fresh cow’s milk contains about 3.9┬Ámol of NAD+. 
  • Fish – here’s another reason for you to enjoy fish! some varieties of fish like tuna, salmons and sardines are rich sources of NAD+ for the body.
  • Mushrooms – many people like mushrooms and them as a regular food item in their regular diet. But did you know that mushrooms, especially the crimini mushrooms, also help in naturally boosting NAD levels? Yes, that’s true. So, enjoy eating the mushrooms and continue to look and younger and more youthful!
  • Yeast – yeast is an ingredient which is used for making bread and other bakery products. Yeast contains Nicotinamide Riboside (NR), which is a precursor of NAD. Here’s another reason for you to enjoy your favorite pastries or buns whenever you visit the bakery! Enjoy your favorite food while boosting NAD levels at the same time. How cool is that!
  • Green Vegetables – green vegetables contain all sorts of nutrients in them which are beneficial in a variety of ways. Recently, it has come to light that green vegetables are also a good source of NAD for the body. Some of these vegetables include peas and asparagus.
  • Whole Grains – as discussed earlier, Vitamin B3 also contains Nicotinamide Riboside (NR), the precursor for NAD. However, when vegetables, food items or grains are cooked or processed, they lose their nutrition as well as the vitamin source. Therefore, it is recommended that you should also eat raw vegetables and take whole grains instead of processed foods.
  • Cut Down on Alcoholic Beverages – NAD is responsible for maintaining the overall metabolic processes of the body. Alcohol tends to interfere with these processes and reduce the efficacy of NAD. Therefore, you should avoid excessive intake of alcoholic drinks since they are also not good for your health.

Want to Live Longer Life?

If your objective is to live a longer, healthier life, a study conducted by Harvard’s T.H. Chan School of Public Health lays out five practices, none of which needs to involve a fad.

The five low-risk factors are the following:

1. Avoid smoking. Low risk is defined as low exposure to smoking.

2. Maintain a healthy weight. Low risk is defined as a Body Mass Index in the range of 18.5 to 24.9. BMI is a ratio of weight to height that, though imperfect, offers a quick and easy assessment of weight status.

3. Exercise regularly. Low risk is defined as moderate- or ­vigorous-intensity exercise for 30 or more minutes a day.

4. Consume moderate amounts of alcohol. Low risk is defined as one-half to one drink per day for women and one-half to two drinks per day for men.
Editor's view: We are not big fans of consuming alcohol. 

5. Maintain an overall healthy diet. Low risk is defined as a diet with high intakes of vegetables, fruit, nuts, whole grains and long-chain omega-3 fatty acids, and low intakes of red and processed meats, sugar-sweetened beverages, trans fat and sodium.

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