Within the last hundred years, researchers have explored vitamins, minerals, hormones, proteins, and a whole host of other cellular components with hopes of unlocking the secret to a long, healthy life. Now, scientists believe they have found that key in a cellular compound known as NADH, or nicotinamide adenine dinucleotide.
What is NADH?
Nicotinamide adenine dinucleotide (NADH) is a coenzyme found in every cell in your body. It is essential to the chemical process you use for energy production and exists on more than a metaphysical plane.
To fully understand how NADH works, we need to return to high school biology and recall the term “oxidative phosphorylation” also known as “cellular respiration”. If you’re drawing a blank you may remember something about mitochondria, ATP, and the electron transport chain.
Mitochondria are the powerhouses of the cell. It’s where the cell makes energy by turning adenosine diphosphate (ADP) into adenosine triphosphate (ATP). That process occurs in the electron transport chain which requires electrons to make everything happen. Want to guess where mitochondria get the electrons? That’s right: nicotinamide adenine dinucleotide!
NAD medical abbreviation
Depending on which resource you are reading, you may see nicotinamide adenine dinucleotide shortened to NAD, NAD+, or NADH. Regardless of which abbreviation is used, the compound that is being referred to is the same. The only difference is where the molecule is in the electron transport process.
Health Benefits of nicotinamide adenine dinucleotide
Because NADH plays such a vital role in energy production, the potential health benefits are numerous. NADH can improve cognitive function, physical performance, and immune response. People supplement NADH to treat blood pressure, reduce cholesterol, and reverse aging. Physicians utilize NADH to help with multiple diagnoses such as Parkinson’s, Alzheimer’s, and depression.
Nicotinamide adenine dinucleotide levels are a direct link to your overall quality of life. Understanding the causes and effects of low NADH and how to increase NADH will give you the opportunity to optimize your health both mentally and physically.
Effects of low NAD+
We’ve already discussed how NADH works in the mitochondria to supply energy to your cells. NADH is used by several pathways to activate a whole host of different processes within our bodies. It can get real complicated real quick with all the different abbreviations, chemical reactions, precursors, and substrates. In order to focus on the issue rather than getting lost in the jungle of details, let’s simplify the concept into an every-day analogy.
Think about it like this: NADH is a battery. Batteries power a variety of tools and gadgets necessary for everyday life. If the batteries are low, the tools don’t work, and the job doesn’t get done. To explain the effects of low NADH, we have to consider the whole pathway from the batteries to the tools and all the way to the completed task.
Low nicotinamide adenine dinucleotide quickens aging
Two of the tools that require NADH “batteries” are poly ADP ribose polymerase (PARP) and sirtuins (SIRT).
SIRT enzymes activate at least a dozen different processes that control aging by regulating blood sugar, fat storage, and inflammation just to name a few. PARP repairs damaged DNA. Without PARP, damaged DNA triggers cell death.
As we age, DNA damage increases which reduce the available amount of NADH. Reduction in NADH leads to fewer batteries to power both SIRT and PARP. This increases those processes listed above resulting in more DNA damage. The cycle continues to reduce NADH and thereby speeding up the aging process.
Remember this idea, especially the relationship between NADH and SIRT. It will be a common theme in many of the problems associated with low NADH.
Increases sunburn and skin cancer
Anytime we are out in the sun, we are exposed to its harmful UVA and UVB rays. Without protection, this exposure leads to irritating sunburns and harmful skin cancer.
Both sunburns and skin cancer start out as cell damage and we’ve already discussed how NADH plays a role in repairing damaged cells through SIRT and PARP activation. A University of Arizona study showed NADH is vital to human skin cells in relation to sun exposure. The study also confirmed NADH deficiency increases both sun sensitivity and the ability for damaged DNA to survive and lead to cancer.
Low NAD+ decreases cellular antioxidants
Antioxidants are important enzymes that reduce oxidative stress in our bodies. Oxidative stress is a fancy term for the imbalance between the level of free radicals and our body’s ability to clear them from our system. Free radicals are unstable atoms that cause illnesses and promote the aging process. Basically, we want less free radicals and more antioxidants so we can live longer, healthier lives.
Superoxide dismutase 2 (SOD2) is one of those antioxidants and its ability to reduce oxidative stress is increased by the expression of SIRT3. Without NADH, there is a reduction in both SIRT3 and SOD2, and an increase in overall oxidative stress which, as we already know, leads to disease, aging, and eventually death.
Decreases metabolism along with thyroid hormones
NADH controls metabolism which is directly related to every other process in your body including thyroid hormone production. Low NADH reduces metabolism and thyroid levels. These, in turn, produce secondary problems such as weight gain, fatigue, and feeling cold.
Harms immune balance and Function and increase inflammation
Think about the last time you were sick or injured. Your body when into overdrive to correct the problem whether it was a broken bone or the flu. Your immune system needs NADH to fuel the recovery process. Without it, sicknesses progress and inflammation increases. Low NADH can allow an acute issue to turn into a chronic problem.
Can impair brain function
The human brain can perform 38 thousand-trillion operations per second. That much computational power requires a massive amount of energy. As we already know, energy comes from mitochondria. The brain must contain a large number of mitochondria in order to function correctly. Low NADH and the resulting mitochondrial dysfunction are associated with varying levels of cognitive decline from simple “brain fog” to diseases such as Alzheimer’s disease and Parkinson’s.
Possible effects of low NAD+
Can suffocate the cells (hypoxia)
In the last steps of the electron transport chain, oxygen is required to finish the process and accept the electrons. This final step creates water that is used or removed from the body. If oxygen is not available, the body slows down mitochondria function and the conversion of NADH. Low NADH has also been shown to induce a “pseudohypoxia” where NADH and SIRT activity is decreased despite normal oxygen levels.
Low NAD+ is associated with chronic fatigue syndrome
While several NADH dependent conditions (thyroid levels, metabolism, immune response, inflammation, and hypoxia) have already been associated with low NADH, chronic fatigue is directly related to NADH by the body’s inability to produce energy. Without energy, the cells simply cannot function properly. Chronic fatigue, in turn, compounds the problems of those conditions already mentioned.
May worsen weight gain and metabolic syndrome
Metabolic syndrome is a combination of various disease states – high blood pressure, obesity, diabetes, and high cholesterol – in a single person. Metabolic syndrome also increases the risk for other reactions that turn into problems, such as heart disease, stroke, heart attacks, and premature death. Low NADH results in defective mitochondria and impaired SIRT signaling, both of which have been linked to cardiovascular disease, diabetes, and high cholesterol.
Likewise, low NADH worsens weight gain by not being the energy source the body needs. Without energy, processes like metabolism start to slow down. Low NADH compounds the problem by also promoting weight gain through secondary sources like diabetes and heart failure.
May worsen cardiovascular diseases
Like the brain, the heart is one of the hardest working organs in our bodies. Reduced NADH levels in the heart make it work harder to perform that crucial life function known as a heartbeat. Added stress to the heart correlates into increased DNA damage (which cannot be repaired due to low NADH) and increased risk for complications such as heart attack, stroke, and heart failure.
May contribute to multiple sclerosis (MS)
Multiple sclerosis is an abnormal immune response to the body’s own central nervous system. In MS, patients experience an increase in NADH in their immune system and a decrease in their nervous system. This imbalance leads to NADH deficiency for the nervous system and an inability to make repairs to neurons. Neurons deficient in NADH are more likely to degenerate which can lead to a progression in MS symptoms.
MS patients are also more likely to be deficient in the NADH precursor tryptophan. While NADH supplementation and calorie restriction have been shown to improve NADH levels, supplementing with tryptophan can increase lymphocytes and worsen MS overall.
What decreases NADH?
Alcohol
Anyone who has ever been hungover knows the negative effects alcohol has on the body. Alcohol stresses the body in a variety of ways. In order for the body to recover from the effects of alcohol and to metabolize the alcohol out of the body, NADH is consumed at an increased rate. NADH levels have been shown to drop 20 percent in response to alcohol consumption and the associated metabolism.
Overeating
Overeating is never a good idea. In addition to feeling miserable in the short term, overeating can lead to diabetes, high cholesterol, heart disease and immobility in the long term. The problems, both individually and combined as metabolic syndrome, wreak havoc on the availability of both NADH and SIRT.
Overeating, especially a carbohydrate and sugar-dense Western diet, increases demand for metabolism and insulin secretion. These processes, along with others, must work overtime to accommodate the overload of food and result in depleted NADH stores. One study showed calorie restriction reduced oxidative stress (look back at the antioxidant discussion from earlier) by increasing SIRT3 levels.
Chronic inflammation
One byproduct of the oxidative stress is the development of chronic inflammation. While inflammation in the acute stage is rapid and helps the body heal and recover, chronic inflammation can be very harmful. It is the result of the body’s inability to fix the acute problem. The body cannot repair itself, remove toxins, or defeat the virus. Chronic inflammation has been shown to reduce NADH synthesis and compromise the genes that control circadian rhythm.
Reduced sirtuin activity
This one may seem backward from everything we’ve already talked about. If NADH controls SIRT activity, how can reduced SIRT activity cause low NADH?
Two ways: First, SIRT controls our sleep and wake cycle, also known as circadian rhythm. Circadian rhythm affects the body’s ability to produce NADH. Second, SIRT influences overall mitochondrial function through the various other enzymes it activates along the way. Reduced SIRT activity inhibits the mitochondria to replenish NADH stores and the cycle begins again.
Disrupted circadian rhythm
Circadian rhythm affects the body’s ability to produce NADH because it controls the production of a precursor enzyme nicotinamide phosphoribosyltransferase (NAMPT). NAMPT is one piece of a rather large puzzle that converts nicotinamide into NADH. No NAMPT means no NADH. Circadian rhythm declines as we age leading to further loss of NAMPT production. This, again, accelerates the aging process and reduces the amount of NADH through various causes.
High blood sugar and insulin levels
As mentioned in the Overeating section, SIRT plays a role in regulating insulin secretion. Overexpression of SIRT improves insulin release and glucose tolerance by the pancreas. Additionally, SIRT can act as a mediator for other signaling pathways that respond to high blood sugar. Left uncorrected, either through diet modification or medication, high blood sugar decreases insulin sensitivity. The body then requires more insulin to control the same level of blood sugar. This increase in demand ramps up the need for SIRT and the NADH battery that powers it.
DNA damage (PARP Activation)
PARP activation is dependent on NADH. The more DNA damage, whether through aging or some other process, the more PARP activation is required to make repairs. The more PARP activation, the more NADH is needed for fuel. The increased need for NADH by PARP decreases the total amount available for other processes.
Increasing NADH intake
Low NADH is tied to a whole host of physical and mental conditions. Now that we have an idea of all the ways NADH can affect our daily lives, let’s look at ways we can increase our levels and improve our health through food, exercise, and supplementation.
Food
One way NADH is produced in the body is by converting the tryptophan found in our diet. Most people think of turkey when considering tryptophan, but it is found in a wide variety of protein-based foods. Tryptophan can be found in eggs, fish, poultry, almonds, peanuts, chocolate, and dairy products such as milk and yogurt.
The World Health Organization recommends a daily intake of 3.5 milligrams of tryptophan per kilogram of body weight. That works out to be about 215 milligrams for a 135-pound woman and around 320 milligrams for a 200-pound man.
Exercise and sauna
Exercise has been shown to increase NAMPT (the precursor enzyme controlled by circadian rhythm) expression. One study showed endurance-trained athletes had a twofold increase in NAMPT compared to both obese and non-obese sedentary subjects. In just three weeks of exercise, sedentary individuals increased their own production by twofold as well.
Saunas can also help improve NADH levels by removing the toxins and free radicals associated with oxidative stress. Allowing your body to remove these through sweat reduces the need to combat them with other NADH dependent pathways.
Supplements
There are two different types of NADH supplements: NADH precursors and supplements that increase NADH indirectly. The indirect NADH supplements increase levels by reducing oxidative stress or increasing other antioxidants in the body. Discussing them in depth is beyond the scope of this article but some examples include oxaloacetate, leucine, malic acid, apigenin, and resveratrol. NADH precursors are compounds that are part of the metabolism pathway that starts with tryptophan and ends with NADH. These include:
- Tryptophan ( sometimes labeled L-tryptophan)
- Niacinamide (also known as niacin or vitamin B3)
- Nicotinamide riboside (NR)
- Nicotinamide mononucleotide (NMN)
- Nicotinamide adenine dinucleotide (NADH)
NADH dosage
Depending on where you start in the metabolism pathway determines where the dosages start. Common doses for the NADH supplement precursors are:
- Tryptophan: 500mg to 1000mg
- Niacinamide: 250mg to 1000mg
- Nicotinamide riboside (NR): 100mg to 300mg
- Nicotinamide mononucleotide (NMN): 50mg to 250mg
- Nicotinamide adenine dinucleotide (NADH): 5mg to 30mg
The recommended starting dose for NADH is 5mg to 10mg taken first thing in the morning on an empty stomach. With the other precursors, it’s a good idea to start at the lowest dose and titrate up as needed. Precursor supplements can be metabolized to other things depending on what the body needs. This is especially true the higher up the pathway you start with supplementation. For example, tryptophan can be metabolized to serotonin and melatonin rather than niacin and eventually NADH.
NADH side effects and dangers
While no significant side effects have been reported with NADH supplementation, nothing is without the potential for side effects. Certain types of niacin, for example, can cause flushing. Extended-release or non-flushing formulations help to reduce this issue. Knowing where your supplement comes from and how it is made will also affect the quality of both the supplement and the results you gain from it.
Do your research and buy supplements from only reputable sources that follow good manufacturing practices and perform independent testing on their products. Another good practice is to consult your primary care provider or pharmacist. These healthcare professionals can help determine which supplement is best and how it fits into your overall health plan.
The fountain of youth
As research and human clinical trials continue, we will learn more about the anti-aging properties of NADH. What we do know shows that NADH is critical for metabolism, DNA repair, and overall healthy cellular function. Promoting good health at the cellular level translates into a healthy, long-lasting life. Investigators continue to prove the need for NADH supplementation to combat various conditions such as diabetes, heart disease, cognitive dysfunction, and even cancer.
Replenishing NADH stores through diet, exercise, and supplementation provides the building blocks of health needed by your body. We may never find a mystical water source, a magical tree, or a one-stop shop for all our health and fitness goals; but, with continued research and understanding, we may find the Fountain of Youth has been inside us all along.