Is NADH The Best Form of Vitamin B3?

Written by Andy Mobbs
featured image for article on vitamin b3 nadh

In this article, get to know the benefits of taking Vitamin B3 as NADH (Nicotinamide Adenine Dinucleotide + Hydrogen). What is it and what does the science say about it? Scroll down to find out more about this nutrient!

What is NADH?

NADH is one of the active forms of Vitamin B3. Many people have heard of NAD+ (Nicotinamide Adenine Dinucleotide) which is the oxidized form of NADH because it’s been associated with an increased lifespan. But most people don’t realize that it’s the reduced formNADH – that is most likely to be deficient in people.

oxidation vs reduction

Oxidation

Oxidation is when a molecule loses an electron (or electrons). It’s called oxidation because this is what happens when a molecule reacts with oxygen and is where the term ‘oxidative stress’ comes from. However, oxidation doesn’t have to involve oxygen, it could happen as a consequence of a molecule coming into contact with any free radical.

Reduction

Reduction is the opposite of oxidation when a molecule gains an electron. In the case of NADH, it gains hydrogen, which has one electron. Although we tend to think of oxidizing something as bad, it’s also very necessary. In the human body, there are redox reactions happening all the time as molecules change from oxidized forms to reduced forms and back again. This is certainly the case with NADH and NAD+.

Can NADH help with energy production?

NADH – as the reduced form of B3 – is hugely important for human health. Its main role in the body is the production of energy. NADH is needed in our mitochondria, which are the powerhouses of our cells, and produce the vast majority of the energy we use. They do this by splitting the hydrogen ion off NADH and pumping the H+ across a membrane into the intermembrane space of the mitochondria. When the H+ ion is broken off, the NADH turns into NAD+.

the mitochondria

Getting the H+ ions in the intermembrane space allows us to produce energy (aka ATP). The H+ ions build up in the space creating a big chemical gradient, which means the H+ ions want to leave because there are so many of them in one place.

The mitochondria then open a gate, which allows the hydrogen ions to escape. This gate is called ATP synthase, which is an enzyme that acts like a hydroelectric dam. The Hydrogen ions flow through ATP synthase, and it turns like a ‘mill’ and allows us to produce energy as ATP.

ATP synthase

Because NADH is central to energy production, it means it’s needed for every process that happens in the body and is connected to every aspect of health. Without enough NADH, we don’t produce enough energy. And if we aren’t producing enough energy, our health suffers… both physically and mentally.

nadh to nad+

NAD+ and NADPH: The other active forms of B3

There are 2 other active forms of vitamin B3 which are NAD+ and NADPH. Both are formed from NADH, so increasing our NADH pool can lead to more of both of them.

NAD+

As we’ve seen, once NADH has been used for energy production it becomes NAD+. NAD+ is used by both the Sirtuin and PPAR genes that are associated with reducing inflammation, increasing energy usage, DNA repair, and an increased lifespan.

NADPH

NADPH is an NADH molecule with a phosphate molecule added (which is the ‘P’ in NADPH), via the enzyme Pyridine nucleotide transhydrogenase (1). NADPH is a hugely important molecule around the body and is involved in many different processes, including the production of nitric oxide. In nitric oxide production, the amino acid arginine is combined with oxygen and NADPH to produce citrulline, NADP, and nitric oxide (1).

Nitric Oxide

Nitric Oxide is probably best known by gym-goers as the substance that causes a ‘good pump’ by increasing blood flow to the muscles. This is because nitric oxide or NO is primarily produced by the cells lining the blood vessels causing them to relax and improve blood flow. Nitric oxide is also produced in the neurons of the brain and central nervous system. It improves neuronal function, memory formation, synaptic plasticity, and the differentiation of male and female personality traits (2).

Whilst nitric oxide in the blood vessels or neurons is a good thing, there is a third type of Nitric Oxide called inducible nitric oxide that often isn’t so good. When this type of nitric oxide is produced, it can combine with superoxide to form peroxynitrite, which is a highly reactive molecule that can cause lots of damage.

Although the body can use peroxynitrite in the immune system where it’s used to chemically burns pathogens, if it’s produced at other times when we are not mounting an immune reaction, it can be dangerous. This is unless we have a molecule called Biopterin available that can stop the production of peroxynitrite and prevent damage.

NADPH is needed to make biopterin, so any deficiency in NADPH can lead to reduced levels of biopterin. As well as its ability to stop nitric oxide from becoming peroxynitrite, biopterin is also necessary for producing the neurotransmitters dopamine, norepinephrine, epinephrine, and serotonin. All of these neurotransmitters are vital for peak cognitive function and mood.

NADPH in the Immune System

As well as using nitric oxide, the immune system also uses NADPH itself in something called the respiratory burst. This is when immune cells are activated and start producing lots of the chemicals hypochlorous acid and hydrogen peroxide to kill invaders. If we were using hypochlorous acid and hydrogen peroxide in our houses we would call them bleach, however, our immune systems also use these same chemicals to kill pathogens!

Fatty Acids and Cholesterol

NADPH is also vital for the production of fatty acids and cholesterol. Whilst this might have a negative connotation for some people, fatty acids and cholesterol are absolutely necessary for health. If we don’t have enough, we can forget about reaching our potential.

Fatty acids, for example, form one-half of phospholipids that make up the cell membranes of all of our 20 trillion cells. They also make up the membranes of the countless other organelles that act like organs in our cells such as the mitochondria and endoplasmic reticulum. Cholesterol also provides stability to these membranes, and we simply cannot live without it.

Steroid Hormones and CoQ10

Cholesterol also forms the basis of all the steroid hormones in our body as well as CoQ10. CoQ10 along with NADPH is a vital part of the energy production pathway. It’s also an important antioxidant in our cell membranes and plays an important role in autophagy, which is a form of cellular ‘clean up’, that allows us to break down old and misfunctioning cell parts and regenerate new cells.

Steroid hormones include Testosterone, Estrogen, Cortisol, DHEA, and Pregnenolone. They are fundamental to every part of our health. They provide energy, alertness, and are vital for cognitive function, and allow us to feel good. Arguably, apart from our ability to produce and use energy, there is no greater impact on our behavior than from our hormones and NADPH is integral to their production.

Show Me the Science!

Chronic Fatigue Syndrome

CFS is an incredibly debilitating condition, not least because mainstream medicine has no answers for it, with many sufferers still being told it’s all in their heads. The likelihood is that there are multiple contributing factors in any individual with CFS, and to fully help people with CFS we need to identify and remove all of them.

However, NADH along with Magnesium, are the only single-supplement approaches that have shown any promise in helping CFS patients (3). In one study, 31% of patients responded to 10mg of NADH per day for 4 weeks, whereas only 8% of controls did. This led to the authors suggesting that NADH may be a ‘valuable adjunctive therapy for CFS symptoms’ (4).

A further study gave patients 5 mg of NADH per day for 24 months and found ‘a dramatic and statistically significant reduction of chronic fatigue symptoms’, in the first 3 months of the study. However, improvement in symptoms somewhat plateaued and only continued to improve slightly for the remaining 18 months, indicating that a lack of NADH isn’t the only factor in CFS (5).

Alzheimer’s

In a randomized controlled trial (although with only 26 subjects), subjects with symptoms consistent with Alzheimer’s were given either 10mg a day of NADH or a placebo for 6 months. At the end of the 6 month period, all of the subjects given NADH showed no sign of progression of their cognitive deterioration. And scored significantly higher on dementia tests (the MDRS scale), than those given a placebo.

The researchers pointed out that by giving the subjects preformed vitamin B3, they are reducing the body’s need to produce it. The pathway that forms B3 in the body is called the kynurenine pathway, and one of the chemicals formed in the pathway prior to B3 is quinolinic acid which is a known neurotoxin. So by taking preformed B3, we are reducing the body’s exposure to quinolinic acid (6).

Also, the amino acid tryptophan is the initial starting molecule in this pathway, which is also what the body uses to make serotonin and melatonin. By taking B3 as a supplement, we are also sparing tryptophan for serotonin and melatonin production.

In fact, during stress, the body will up-regulate the production of B3 from tryptophan because it allows us to produce energy. It allows us to prioritize energy over serotonin and melatonin because, in an emergency, energy will keep us alive and so is more important than feeling good. Unfortunately, in today’s world, we often find ourselves in situations of chronic stress. From an evolutionary point of view, our body sees it as an emergency, so will chronically upregulate the production of B3 prioritizing it over serotonin and melatonin (7).

Serotonin is our feel-good neurotransmitter, and a deficiency is associated with depression and also reduced cognitive function. Melatonin is produced from serotonin and helps us fall asleep.

Kynurenine pathway

Parkinsons

A further study looked at 34 patients with Parkinson’s disease, who were given NADH intravenously. They found that 21 patients (61.7%) had an improvement in their symptoms after taking NADH (8).

Jet Lag

The effects of jet lag can easily affect cognitive function. In this study, researchers worked with 35 healthy people who flew from the West Coast to the East Coast of the USA. They found that on the morning after the flight, the 18 subjects that had taken 20mg of NADH orally before the flight performed better on tests that looked at memory, cognitive processing speed, and attention than subjects that had been given a placebo (17 subjects) (9).

NADH Types and Dose

NADH needs to be highly stabilized and there are currently 2 patented types of this NADH on the market, ENADA and Panmol. So far, studies that have found a benefit from taking NADH have used doses ranging from 5mg up to 20mg per day.

NADH in our Natural Nootropic

Our Seneca Nootropic complex includes 5mg of Vitamin B3 as Panmol®NADH, as well as Vitamins B1, B2, B6, B9, and B12, and herbal nootropics! If you want to know more about how nootropics can help boost your mental prowess, check our article on “What are nootropics and cognitive enhancing supplements?

References

(1) Ranji Singh, Joseph Lemire, Ryan J. Mailloux, and Vasu D. Appanna, A Novel Strategy Involved Anti-Oxidative Defense: The Conversion of NADH into NADPH by a Metabolic Network, PLoS One. 2008; 3(7): e2682.

(2) Melih Dagdeviren, Role of Nitric Oxide Synthase in Normal Brain Function and Pathophysiology of Neural Diseases, Nitric Oxide Synthase – Simple Enzyme-Complex Roles

(3) Penny Whiting, MSc; Anne-Marie Bagnall, PhD; Amanda J. Sowden, PhD; et al, Interventions for the Treatment and Management of Chronic Fatigue Syndrome
A Systematic Review, JAMA Network, September 19, 2001

(4) Forsyth, Linda M, Preuss, Harry G, MacDowell, Ana L, Chiazze, Leonard, Birkmayer, George D, Bellanti, Joseph A, Therapeutic effects of oral NADH on the symptoms of patients with chronic fatigue syndrome, Annals of Allergy, Asthma & Immunology 1999

(5) Santaella M.L., Font I., Disdier O.M, Comparison of oral nicotinamide adenine dinucleotide (NADH) versus conventional therapy for chronic fatigue syndrome, Puerto Rico Health Sciences Journal. 2004 Jun;23(2):89-93.

(6) V Demarin , Sarkanji S Podobnik, D Storga-Tomic, G Kay, Treatment of Alzheimer’s disease with stabilized oral nicotinamide adenine dinucleotide: a randomized, double-blind study, Drugs Exp Clin Res. 2004;30(1):27-33.

(7) Marx, W., McGuinness, A.J., Rocks, T. et al. The kynurenine pathway in major depressive disorder, bipolar disorder, and schizophrenia: a meta-analysis of 101 studies. Mol Psychiatry (2020).

(8) W Birkmayer, G J Birkmayer, K Vrecko, W Mlekusch, B Paletta, E Ott, The coenzyme nicotinamide adenine dinucleotide (NADH) improves the disability of parkinsonian patients, J Neural Transm Park Dis Dement Sect. 1989;1(4):297-302.

(9) G D Birkmayer, G G Kay, E Vürre, Stabilized NADH (ENADA) improves jet lag-induced cognitive performance deficit, Clinical Trial Wien Med Wochenschr. 2002;152(17-18):450-4.