NAD+ vs NADH: What's the Difference?

NAD+ vs NADH? Due to the small alphabetical difference, these nutrients are often mixed up and confused by most consumers. 

NAD+, or nicotinamide adenine dinucleotide, is a coenzyme found in every single living cell. But sometimes it’s referred to, colloquially, as just NAD (no plus). That plus sign matters, though, because the term NAD is used to collectively refer to the different forms of NAD: the molecules NAD+ and NADH.

We will cover the essentials and explain about each of these nutrients below.

NAD

NAD or nicotinamide adenine dinucleotide is derived from Nicotinamide Riboside (NR). NR is one of the 3 main forms of Niacin (vitamin B3).

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/

NAD+ and NADH

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.

These two forms of NAD are known as a "redox couple," a term that is used to describe a reduced (the "red" in redox) and oxidized (the "ox" in redox) form of the same atom or molecule. The term "oxidized" can be misleading, though, as it does not necessarily require oxygen. Redox reactions involve the gaining or loss of electrons. If something becomes oxidized, it’s losing electrons. Meanwhile, if something is reduced, it is gaining electrons.

To put it simply: NAD+ is simply an oxidised version of NADH.

The charge of a molecule informs how it interacts with other molecules. For example, NADH can’t do what NAD+ does, and vice versa.

The bond between NAD+ and -H is what creates NADH. Once the electrons are in the inner membrane of the mitochondria, they are donated to a structure called the electron transport chain - NADH acts as an electron donor. NADH converts back to NAD+ in a reverse reaction. There will be NAD+ left over which can be used as an electron acceptor when more food enters the system.

The conversion of NAD+ to NADH and then NADH back to NAD+, help to convert the nutrients in your food into a form of energy your cells can use.

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.

Naturally Boosting NAD Levels

But there is good news. 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 Riboside Nicotinamide (RN). A litre of fresh cow’s milk contains about 3.9µmol of NAD+. So while you’re enjoying a refreshing glass of milk, you’re actually getting younger and healthier!
• 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 Riboside Nicotinamide (RN), 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 RN, 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.

Read more: https://www.springfieldwellnesscenter.com/mental-health-blog/how-to-increase-nad-levels-naturally/

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.

NR or Nicotinamide Riboside 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, or niagen, is an alternative form of vitamin B3.

Like other forms of vitamin B3, nicotinamide riboside is converted by your body into nicotinamide adenine dinucleotide (NAD+), a coenzyme or helper molecule.

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

Most of the NAD+ precursor research is done with NR. However, as you can see from the image above, NMN converts to NAD+ whereas NR must first be converted into NMN before it can be converted into NAD+, so it makes more sense to use NMN for NAD+ augmentation.

The image above also shows how niacin (NA) also finds its way to become NAD+. Niacin is also a useful supplement to use in increasing NAD+ levels. You just need to limit the dose to about 25 mg, which most is a dose low enough not to cause any flushing. Higher doses are not likely as effective as NMN and exercise in producing NAD+.