NADH and NAD+ are forms of a coenzyme that help the body generate energy and perform many other biological processes. But what exactly is the difference between the two and how do they work to maintain the balance of your cells? 

Read on to learn more about the important functions of these molecules and the ways low NAD+ levels can negatively impact your health and well-being.

Is NAD+ and NADH the Same Thing?

NAD+ and NADH, collectively referred to as NAD, are the two forms of nicotinamide adenine dinucleotide, a coenzyme found in every cell of your body. 

A coenzyme is a small “helper molecule.” Its main role is to activate enzymes—molecules that help speed up chemical reactions—that convert food into energy within the cell. 

The two forms of NAD constitute a redox couple. This term is used to describe reduced and oxidized forms of the same molecule. The NAD+ Is the oxidized form, that is, a state in which it loses an electron. NADH is a reduced form of the molecule, which means that it gains the electron lost by NAD+. Redox reactions involving electron transfers play a central role in energy creation. 

So what exactly are NAD+ and NADH, and what is the difference between the two? 

What is NAD+?

NAD+, sometimes also referred to as NAD, supports the optimal function of the cells. NAD+ is the main carrier of electrons in the energy-producing processes that take place in a cell’s mitochondria. 

Mitochondria are known as the “powerhouses of the cell.” These membrane-bound organelles are found in almost every living cell in the body, including the heart, brain, muscles, and lungs. They generate most of the energy needed to power the cell's biochemical reactions. The energy produced by the mitochondria is stored in the adenosine triphosphate molecule (ATP). 

NAD+ and energy creation

NAD+ participates in energy creation by acting as a delivery mechanism. This molecule donates and accepts electrons to and from enzymes in the mitochondrial membrane. It is these electrons that fuel chemical reactions in the mitochondria. ​Without a sufficient supply of NAD+, the mitochondria can’t adequately convert the nutrients from the foods we eat into usable energy.

To get a better understanding, you can think of NAD+ coenzymes as tiny shuttle buses that take electrons to work inside the cell. The more buses there are, the more electrons can be transported and the more energy will be created. When there aren’t many NAD+ buses to transport electrons, fewer nutrients will get processed in the mitochondria, and fewer reactions can happen within the cell. As a result, cells will begin to age and eventually die. 

NAD+ and sirtuins

Besides its role in energy creation, NAD+ is also indispensable for the function of sirtuins. Sirtuins are a family of seven proteins, three of which are found in the mitochondria, that play an essential role in cellular health. They regulate cellular homeostasis, that is, keep the cells in balance. Sirtuins require the presence of NAD+ to function properly. 

NAD+ decline with age

Although NAD+ is naturally produced in the human body, its levels inevitably decrease as we age. This decline is accelerated by factors such as stress, poor sleep, lack of healthy nutrition, and the use of drugs and alcohol. By the age of 60, your NAD+ levels are less than half of what they were in your 40s. Low NAD+ levels are associated with signs of aging and age-related chronic conditions including diabetes, vision loss, heart diseases, as well as Alzheimer’s and Parkinson’s diseases.

What is NADH?

NADH, also known as coenzyme 1, is the activated carrier molecule that transfers electrons to the cell. The letter “H” stands for hydrogen and indicates that the molecule is in the most active form possible. 

NAD+ to NADH transformation

NAD+ and NADH depict the same molecule that undergoes a transformation. 

To perform its role as an electron carrier, NAD must revert back and forth between the two forms. When NAD+ takes an electron from glucose, it becomes NADH, the reduced form of the molecule. NADH transports this electron to mitochondria where the cell can take the energy that is stored in the electron. NADH then donates the electron to oxygen, converting it back to NAD+.

You can imagine NAD+ as an empty shuttle bus waiting to be put in use. It’s ready to transport the electrons into the mitochondria. The ability to switch between the two forms allows NAD to transport electrons from one reaction to another in the process of energy production. Shifting between the (oxidized) NAD+ and (reduced) NADH forms is central to cellular respiration, a metabolic process that transforms glucose into energy. 

NAD+ to NADH ratio

The NAD+ to NADH ratio in the cells is extremely important. The balance of the two forms of the molecule determines how effectively cells are capable of producing energy. Their ratio declines with age, with NAD+ levels decreasing and NADH levels increasing as you get older. Studies suggest that a high ratio of NAD+ to NAD might be even more important for promoting healthy aging than the amount of NAD+ alone.

We’ve seen the difference between NAD+ and NADH, but how exactly is NAD+ produced in our bodies? 

How Is NADH Produced?

The food we consume has to go through three phases of cellular respiration before it turns into energy: 

• Glycolysis
• The Krebs cycle 
• Electron transport chain. 

After glucose is broken down into smaller molecules during glycolysis, the energy from these molecules is transferred to electron carriers  in the Krebs cycle. They will be used in the electron transport chain to produce ATP. 

Glycolysis occurs in the liquid inside the cells called cytosol, whereas the Krebs cycle and electron transport chain occur inside the mitochondria. NADH molecules are formed from NAD+ during the first two phases: glycolysis and the Krebs cycle. 

Glycolysis

Glycolysis is the first step in the breakdown of glucose in cellular metabolism. It consists of an energy-requiring phase and an energy-releasing phase. In the process of glycolysis, NAD+ is reduced to form the NADH molecule.

Krebs cycle

The Krebs cycle is found in all cells that use oxygen. The main function of the Krebs cycle is to produce energy, which is stored and transported as ATP. It consists of a series of chemical reactions required for cellular respiration, including redox, dehydration, hydration, and decarboxylation. 

These reactions produce ATP, a coenzyme energy carrier for cells, and create carbon dioxide and water as byproducts. For one Krebs cycle, three molecules of NADH and two molecules of carbon are produced along with one molecule of ATP. The Krebs cycle produces more than 95 percent of the energy used by the cells.

Electron transport chain

As we have seen above, NADH transfers these extra electrons to the inner membrane of the mitochondria. After that, the electrons are donated to the electron transport chain. This chain is a series of electron transporters located within the inner mitochondrial membrane that shuttles electrons from one molecule to another, to eventually create ATP. 

Now, let’s see what is the purpose of NAD+ and NADH molecules in the cell.

What Is the Purpose of NAD+?

The cells in your body rely on NAD+ to carry out hundreds of metabolic functions ranging from energy creation to maintaining healthy DNA. 

NAD+ is a key player in metabolism where it helps enzymes turn nutrients into energy. Its reaction with oxygen in the mitochondria creates energy that enables essential body functions such as breathing, thinking, moving, and digestion. 

As a helper molecule, NAD+ also binds with other proteins to allow DNA repair and reduce DNA mutations that can contribute to conditions such as immunodeficiency, atherosclerosis, and cancer. 

And that’s not all. Besides converting food into energy and repairing damaged DNA, NAD+ serves as fuel for many indispensable biological processes like strengthening the immune system and setting the body’s internal clock. Scientists also believe that NAD+ is the most powerful antioxidant in our body. 

What Is the Purpose of NADH?

NAD+ is the “raw” form of NAD that simply acts as an electron carrier. It’s like an empty shuttle bus without anything to transport. However, with the help of NADH, it’s able to use its cargo space to carry crucial components to the enzymes of the cell.

NADH is the “loaded” or activated form of NAD, a shuttle bus with cargo to transport. Its primary purpose is to bring charged electrons to the mitochondrial enzymes needed for the energy-making process. Once NADH arrives at the mitochondria, it drops off its positively charged electrons and expels the hydrogen atom, once more becoming NAD+. NAD+ is now an empty shuttle bus again, ready to transport more positively charged electrons.

NAD+ holds multiple health benefits from helping battle chronic conditions and age-related illnesses to reducing the effects that aging has on your body. But is it safe to take in elevated doses? 

Is Too Much NAD+ Bad for You?

Because NAD+ is a vitamin supplement and naturally produced by the human body, the FDA has not assessed NAD+ supplementation and therapies. Besides, there has been limited research investigating the long-term safety of NAD+ and its interaction with other supplements and medications. 

NAD+ is for the most part completely safe when taken in moderation and without exceeding the recommended intake of 10 milligrams per day for up to 12 weeks. Even though they are presumed to be safe, NAD+ supplements and therapies should not be used in children, when pregnant, or nursing. You should consult your doctor if you’re taking any other supplements or medicines to avoid any unexpected side effects or complications.

Are there any side effects?

If you don’t exceed the recommended daily NAD+ amounts, you will most probably not experience any harmful side effects. Some people may have very mild reactions to NAD+ like nausea, fatigue, headaches, diarrhea, stomach discomfort, or indigestion.

If they are used in excess, however, NAD+ supplements can cause jitteriness, anxiety, headaches, nausea, dizziness, and insomnia. If you have NAD+ infused intravenously for less than 2 hours during your IV therapy session, you may feel increases in physiological activity including chest pressure, increased energy, intestinal cramps, lightheadedness, and nausea. What’s more, when delivered by injection, NAD+ may cause injection site pain, swelling, and redness. In very rare cases, complications such as vein inflammations and infections may occur. 

NAD+ provides a host of benefits and its deficiency may be detrimental to your health and well-being. 

Potentially Harmful Effects of Low NAD+ 

Low NAD+ levels can have a range of detrimental effects ranging from chronic fatigue to anxiety and depression, weak immune system, headaches, sleep problems, focus and concentration defects, as well as the development of chronic diseases. 

Aging

NAD+ activates sirtuin enzymes that repair damaged DNA and boost your stress resistance, thus promoting healthy aging. However, during the aging process, increased DNA damage reduces NAD+ levels. This leads to the restricted activity of sirtuins, which is associated with aging.

NAD+ deficiency is associated with several age-related diseases, such as metabolic disorders and neurodegenerative diseases. In fact, levels of NAD+ are thought to be one of the main causes of age-related problems. NAD+ supplementation has been shown to extend the lifespan of laboratory animals, and could potentially have the same effect in humans.

Sunburn and Skin Damage

The cells in your body use NAD+ to help activate sirtuins that create the energy necessary for responding to long-term sun exposure. NAD can protect from skin damage in the sun and skin cancer: while NAD+ strongly absorbs mainly the UVB rays, NADH absorbs the UVA rays. This is also why people with low NAD+ levels tend to burn more easily in the sun.

Fatigue

Fatigue may be one of the signs of lower NAD+. Studies have found that around two-thirds of people suffering from chronic fatigue syndrome reported positive improvements when taking 10 milligrams of NADH daily. That’s why NAD+ supplementation can be effectively used to increase your physical and mental energy. 

Weight gain and metabolic syndrome

One of the essential functions of NAD+ is energy metabolism. We’ve seen that our cells use NAD+ to turn the food we consume into energy. NAD+ activation of sirtuins turns on genes that improve metabolism. Scientists have discovered that increasing the amount of NAD+ in the body directly influences metabolism, helps burn fat, and keeps weight off. 

Multiple sclerosis (MS)

NAD+ deficient neurons are more vulnerable to degeneration that occurs in conditions such as multiple sclerosis. NAD+ can boost the immune system in people suffering from this chronic illness. Increasing NAD+ levels by supplementation with NAD+ precursors is shown to help with multiple sclerosis in laboratory animals.

Cardiovascular diseases

NAD+ depletion and subsequent mitochondrial dysfunction can accelerate heart failure. Increasing NAD+ levels has been proposed as a supplemental treatment for heart diseases. 

Oxidative stress

Although free radicals are a normal byproduct of cellular oxidation, they become harmful when they accumulate faster than your body can process them. Having more free radicals than antioxidants can cause an imbalance known as oxidative stress. 

Low levels of NAD+ have been shown to lead to oxidative stress. NAD+ increases the activities of the antioxidant enzyme which plays an important role in reducing oxidative stress. Lack of NAD+ can, therefore, increase the risk of chronic and degenerative diseases, such as cardiovascular disease and certain types of cancer. 

Brain function

NAD+ deficiency can decrease brain energy and dopamine levels. Mitochondrial dysfunction caused by low NAD+ levels and a decline in NAD+/NADH ratio can contribute to the development of mental health issues as well as a range of neurodegenerative diseases. Treatment using NAD+ has been suggested to improve the cognitive function of Alzheimer’s and Parkinson’s disease patients.

Immune function and inflammation

Chronic illnesses like diabetes, heart disease, and cancer, are accompanied by high levels of inflammation. Injuries and allergies can also provoke an inflammatory response. But due to environmental toxins, poor diet, and stress, inflammations don’t always subside and, as a result, you may suffer from chronic inflammations. NAD+ and by extension sirtuins, create an optimal and balanced environment for your immune system to dampen inflammation and fight infections.