Maintaining high levels of NAD in a body is key to longevity! Learn here what NAD+ is; what it does; why we need it; what happens with its levels at aging, etc. Not interested in “scientific stuff”? Just scroll down to learn information on what to eat, what supplements to take, and what special treatments to apply in order to support or increase NAD+ levels in your body.
The hunt for the fountain of youth is not new. More and more purported anti-aging products continue to pop up in the supplement market. NAD+ boosters are one relatively new class of anti-aging supplements that are creating significant hype and some controversy.
All living things on our planet are made of cells. While cells come in various shapes, sizes and functions, they have quite a few fundamental characteristics in common. They use a similar genetic code to store information in DNA. They all require energy to survive, whether from food, the sun, or thermal vents deep in the ocean. This cellular energy provides fuel for your life. And gives power to your brain, heart, and muscles, protects against DNA damage, and increases your longevity.
And all cells contain an important molecule called nicotinamide adenine dinucleotide, or NAD for short. The human body is made up of trillions of cells, at least 37.2 trillion of them, which all rely on NAD to carry out their day-to-day functions. It’s a coenzyme that’s found in the mitochondria — the powerhouse of the cell. It plays a critical role in helping the body form ATP (adenosine triphosphate), the substance that powers our cells and many other vital processes. It’s so crucial to our functioning that if our levels were to drop to zero, we would die. Our other post will help you to understand how your body gets NAD+, how it uses it, and why its level decrease with age based on the latest studies and discoveries.
English biochemists Arthur Harden and William John Young discovered NAD at the very beginning of the last century. Then, throughout the XX century, it was studied extensively. Many scientists received Nobel Prizes for discovering its unique properties. Nowadays, the whole world follows the discoveries in the field of NAD since the latest data show that this element is directly related to the aging of living organisms.
What exactly is NAD?
Converting food into energy
Repairing damaged DNA
Fortifying cells’ defense systems
Setting your body’s internal clock or circadian rhythm
It’s basically a power generator for your body and a natural fountain of youth.
NAD+ is written with the “+” because of the positive charge on one of its nitrogen atoms. It is the oxidized form of NAD. It is considered an “oxidizing agent” because it accepts electrons from other molecules. NAD+ is what you might call the “raw” form of NAD. It simply acts as a vehicle.
NADH stands for nicotinamide-adenine dinucleotide (NAD)+ hydrogen (H). NADH is what you might call the “loaded” form of NAD. In this form, NADH carries a charged hydrogen molecule with two electrons. NADH’s primary purpose is to bring these charged electrons to the mitochondrial enzymes needed for the energy-making process. It is also used interchangeably with NAD+.
Why do we need it?
Nicotinamide-adenine dinucleotide is described as a “helping molecule” because it binds to other enzymes and triggers body reactions that positively affect your health.
Other factors that make this coenzyme so important for healthy aging include its effects on “anti-aging” proteins, mitochondrial activity, and involvement in the regulation of oxidative stress (the cause of many chronic diseases) and circadian rhythms (our “internal clock”).
To be precise, NAD+ is involved in redox reactions and transfers electrons from one molecule to another. It takes electrons from some molecules and transfers them to others – so the energy that a person receives from food is converted into one that nourishes our body and brain. In particular, the energy stored in the electrons of NADH can then be converted to ATP in the mitochondria via a process called “oxidative phosphorylation” or “cellular respiration”.
On a microscopic level, our mitochondria are the battery packs of our cells. They use energy to do the things they need to do to maintain homeostasis and repair themselves in case of damage or stress. Mitochondrial dysfunction can have significant trickle-down effects, particularly in terms of age-related brain disorders. In fact, based on mice studies, researchers believe impaired mitochondrial function and oxidative stress are linked to Parkinson’s and Alzheimer’s.
A group of proteins associated with a rejuvenating effect, called sirtuins, rely on NAD+ for proper functioning. Sirtuins have been found to play a role in regulating cellular and mitochondrial health.
NAD+ in aging, metabolism, and neurodegeneration
NAD+ metabolism and its roles in cellular processes during ageing
NAD+ and sirtuins in aging and disease
Quantitation of NAD+: Why do we need to measure it?
Quantitative Analysis of NAD Synthesis-Breakdown Fluxes
Loss of NAD Homeostasis Leads to Progressive and Reversible Degeneration of Skeletal Muscle
NAD+ Precursors: A Questionable Redundancy
Recent research into nicotinamide mononucleotide and ageing
Extracellular Nicotinamide Phosphoribosyltransferase Is a Component of the Senescence-Associated Secretory Phenotype
Age-Dependent Decline of NAD+—Universal Truth or Confounded Consensus?
Healthy aging and muscle function are positively associated with NAD+ abundance in humans
Restoring NAD(+) Levels with NAD(+) Intermediates, the Second Law of Thermodynamics, and Aging Delay
NAD+ levels decline with age—a change that scientists now consider a hallmark of aging. Lower NAD+ levels have been linked to health problems. They are also responsible for many age-related conditions like cardiovascular disease, neurodegenerative diseases, and cancer.
Multiple factors can play a role in the decline, including dietary deficiencies for NAD+ precursors, changes in the expression levels of enzymes that transform dietary precursors to NAD+, or changes in the activity of enzymes that break down NAD+.
Can we support the NAD+ level?
Our body independently produces NAD+. An important reason for the decrease in NAD+ levels as we age is chronic inflammation. Inflammation causes an increase in the cellular enzyme CD38 levels, which breaks down NAD+.
Data analyses show that NAD+ is reduced in everyone, regardless of the quality of life and health of a person. By the age of 40, NAD+ is reduced by 50%, and by the age of 60 – by 80%. Recent studies show that this directly affects the aging of the body since a link has been established between a decrease in coenzymes and the occurrence of age-related diseases. A decrease in the level of NAD+ means that less ATP is produced – therefore, organs and tissues receive less and less energy, and cells are increasingly depleted and die as a result.
Although your NAD+ levels naturally decline as you get older, it doesn’t necessarily mean you can’t do anything to counteract it.
The body’s function in making and maintaining NAD+ is a natural process. Our cells take certain raw materials, i.e., a specific set of molecules that are NAD+ precursors. They go through a series of chemical transformations that turn them into NAD+. Just as there are multiple ways to manufacture a vehicle that can hit the road, there are many ways NAD+ can be manufactured, too. Some pathways are more efficient than others, some provide more NAD+, and some provide less, but all of them lead to the same thing: NAD+.
Delivering NAD+ precursors to your body has exciting therapeutic potential for aging, metabolic and neurodegenerative diseases. In particular, two key NAD+ intermediates, nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), have been extensively studied over the past several years (see more below).
How to deliver? Well…
The NAD+ precursors are contained in natural foods, such as cow milk, vegetables, meats, etc. Therefore, altered NAD+ metabolism can be a practical target for nutritional intervention. Mitochondrial NAD+ biosynthesis is modulated in response to nutritional stimuli, and the right food can contribute to your NAD+ level by providing its components and precursors. Some scientists believe that a person in the Paleolithic era, i.e., hunter-gatherer, did not have the same health problems as we do now due to the fact that by eating mainly raw food (not processed), he was receiving a sufficient amount of niacin and did not have such a deficiency of NAD+ as modern man.
What can we get with food & supplements?
NA – Niacin
NMN – Nicotinamide Mononucleotide
NR – Nicotinamide Riboside
T – Tryptophan
R – Resveratrol
A – Apigenin
L – Leucine
MA – Malic Acid
SA – Succinic Acid
F – Fructose
You can find here a presentation on dietary forms of Vitamin B3.
Niacin (vitamin B3)
Niacin is an essential vitamin required for processing fat in the body, lowering cholesterol levels, and regulating blood sugar levels. NAD+ is the main active form of Niacin in the body.
Niacin is a nutrient — meaning that you must obtain it from food since your body cannot produce it on its own. Moreover, since Niacin is water-soluble, any surplus is excreted through your urine rather than stored in your body. Therefore, it’s important to consume niacin-rich foods regularly.
Food sources of niacin (contain from 18.8 to 0.5 mg per 100g of food and listed as the niacin content decreases): yellowfin tuna, beef liver, turkey breast, sockeye salmon, chicken breast, portobello mushrooms, pork chops, brown rice, canned white tuna, steak, peanuts, fortified breakfast cereals, baked potato, white rice (enriched), lentils, sunflower seeds, bulgur, avocado, whole-wheat bread, pumpkin seeds, banana, coffee (see Table here). By the way, 100 g of rose hips contain niacin at 7% of the daily value.
If you prefer supplements, you can buy Niacin at your pharmacy or online. If your doctor prescribes niacin, you might want to take it with food. This can prevent an upset stomach or reduce flushing, a harmless but uncomfortable side effect of niacin, causing redness and warmth in the face and neck. By the way, Life Extension has No Flush Niacin supplements.
|Table: Recommended Dietary Allowances (RDAs) for Niacin|
|Birth to 6 months*||2 mg||2 mg|
|7–12 months*||4 mg NE||4 mg NE|
|1–3 years||6 mg NE||6 mg NE|
|4–8 years||8 mg NE||8 mg NE|
|9–13 years||12 mg NE||12 mg NE|
|14–18 years||16 mg NE||14 mg NE||18 mg NE||17 mg NE|
|19+ years||16 mg NE||14 mg NE||18 mg NE||17 mg NE|
* Adequate Intake
Nicotinamide mononucleotide (NMN) is one of the intermediates in NAD+ biosynthesis. It is a bioactive nucleotide formed by the reaction between a phosphate group and a nucleoside containing ribose and nicotinamide (NAM).
NMN’s safety as a dietary supplement has been proven in a number of FDA-approved clinical trials. David Sinclair, a Harvard professor who studies aging, recommends taking NMN to remain healthy and prevent aging on The Joe Rogan Experience podcast. Sinclair takes 1 gram of NMN every day, along with other supplements. He recommends NMN-C from Elevant, which is a pharma-grade NMN. It is claimed to be ultra-pure, highly stable, and has shown to be more tolerable than other molecules that boost NAD+. Dr. Frank Lipman explained the role NMN-C in healthspan and why he recommends it in his interview.
Nicotinamide Riboside (NR) is a member of the vitamin B3 family, which also includes niacin and niacinamide. Once it is within your body, Nicotinamide Riboside is converted into NAD+, increasing its levels and improving mitochondrial function.
The promising results from a recent study demonstrated that high-dose NR was safe and well-tolerated, almost doubling whole blood NAD+ levels, increasing white blood cell mitochondrial respiratory function, and decreasing the expression of inflammatory markers.
Cow’s milk is an excellent source of Nicotinamide Riboside. It is also present in yeast and beer.
In terms of supplements, the brand leader in sales of Nicotinamide Riboside is Chromadex’s Niagen. Niagen’s recommended serving size is 300mg (1 capsule). According to David Sinclair, it may be less efficient at raising NAD+ levels than 1g of NMN.
Tryptophan is an amino acid that, in addition to being a precursor to serotonin, is necessary for the synthesis of NAD+. It’s also used to produce niacin, which is essential in creating the neurotransmitter serotonin. More than 99% of Tryptophan, which does not go to protein synthesis, goes to the formation of NAD+!
Turns out many foods contain the drowsiness-inducing amino acid Tryptophan. Some of them are shown in the image. The extended list is here.
If you want to go with supplementation, be sure that you are buying only products from companies with strong reputations for providing quality customer service and prompt shipping. We would like to add to the list Life Extention as well.
Resveratrol is a beneficial antioxidant and anti-inflammatory compound known to help prevent the development of neurodegenerative diseases. Moreover, Resveratrol has been shown in several studies to enhance NAD+ synthesis and increase intracellular NAD+ levels.
Resveratrol is one of the most promising compounds in anti-inflammatory drug formulation with many benefits. It is produced by many companies, although its application is still being a major challenge for the pharmaceutical industry due to its poor solubility and bioavailability.
If you pop resveratrol into an Amazon search, you’ll find a host of different options, many of (potentially) dubious quality. Be sure that you are buying trans-resveratrol and not cis-resveratrol with at least 98% purity.
Malic Acid, also known as malate, is an intermediate of the Krebs cycle. It’s a key step in the pathway of energy production by the mitochondria. Malic Acid has been shown to greatly increase NAD+ and strongly increase the NAD/NADH ratio.
Malic Acid is a naturally produced compound by the human body when sugar or carbohydrates break down into energy. It is also naturally available in several fruits and vegetables.
Food sources of Malic Acid: apple, watermelon, banana, lemon, guava, blackberry, apricot, plum, cherry, kiwi, grapes, mango, lychee, orange, peach, pear, strawberry, gooseberry, raspberry, broccoli, potato, pea, beans, carrot, tomato, corn.
Malic acid is generally recognized as safe (GRAS) by the United States Food and Drug Administration (FDA). When a compound is given a GRAS designation, it means that experts have decided that it poses little to no health risk at normal levels of consumption.
A simple Google search will give you a variety to choose from.
Apigenin can be found in many fruits, vegetables, and herbs, including parsley, celery, celeriac, red and white sorghum, tarragon, yarrow, basil, rutabagas, oranges, kumquats, onions, wheat sprouts, thyme, spearmint, and cilantro (see Table here).
As we mentioned before, not all supplements are created equal. If you want to try Apigenin supplementation, then make sure you are selecting a product from a trusted brand. Every product on this list is GMP (good manufacturing practices certified) and third-party tested. Some companies even go above and beyond this.
Food sources of Apigenin.
Leucine benefits the body in many different ways. It is one of the nine essential amino acids and one of the three branched-chain amino acids. Research shows that Leucine supplementation increases intracellular NAD+ levels and prevents mitochondrial dysfunction.
It cannot be produced in the body and must be obtained through dietary sources.
You can get Leucine from protein-rich foods, such as fish, chicken, and turkey, as well as from lentils, chicken, peanuts, cottage cheese, beef, navy beans, salmon, yogurt, oats, pumpkin seeds, hemp seeds, soybeans, eggs, spirulina, sesame seeds (see Table here).
Leucine is given a GRAS designation by the United States Food and Drug Administration (FDA). It means that experts have decided that it poses little to no health risk at normal levels of consumption.
Here you can find the top 10 L-Leucine supplements to choose from.
Succinic Acid, also known as succinate, is an intermediate molecule of the Krebs cycle that plays a significant role in the electron transport chain. It has also been shown to increase NAD+ levels and increase the NAD+/NADH ratio.
Succinic Acid is one of the natural acids found in foods such as broccoli, rhubarb, sugar beets, fresh meat extracts, various kinds of cheese, and sauerkraut. All of these products have very distinct flavors, more likely due to the presence of Succinic Acid.
In terms of supplements, at this time, there is not enough scientific information to determine an appropriate range of doses for succinate. Keep in mind that natural products are not always necessarily safe, and dosages can be important. Be sure to follow relevant directions on product labels and consult your pharmacist or physician, or other healthcare professional before using.
You can buy it here.
Fructose is a type of sugar known as a monosaccharide. It was shown that Fructose could increase SIRT1 function and activate the enzyme that converts NADH to NAD+ in the mitochondria.
Fructose is also known as “fruit sugar” because it primarily occurs naturally in many fruits. It also occurs naturally in other plant foods such as honey, sugar beets, sugar cane, and vegetables (see Figure here).
However, it has side effects that can increase inflammation and promote weight gain. Thus, it is necessary to be very careful with dosage and be sure to consume a lot of fiber.
No supplementation is needed.
As you already understood, to supplement NAD+ you will need to take its precursors from the list above. The most effective ones are Nicotinamide Riboside (Niagen) and Nicotinamide Mononucleotide (NMN).
What else can you do to boost NAD+ levels?
Right food and supplementation with NAD precursors are not the only ways to increase NAD+ levels.
NAD+ supplements can help support healthy aging, as well as other critical biological processes. However, it is very difficult to deliver active forms of molecular. In order for the level of NAD+ to somehow increase, horse doses are needed if you take NAD+-containing pills orally.
There is no evidence that the work on supplement development is slowing down. There is news on new products at least every month. And, it is getting harder and harder to make a choice from a growing range of products that claim to make you feel healthier, and more alert, and keep you younger for longer.
At least, NOVOS, a company that develops science-based products to slow down aging, has announced the results of two studies demonstrating that the combination of ingredients in its products, NOVOS Core and NOVOS Boost, protect against DNA damage and cellular aging (senescence).
NAD+ IV Therapy
IV therapies, or intravenous therapies, administer nutrients through a vein using a standard saline solution. These treatments usually happen in clinics, wellness spas, or via at-home services where customers opt for monthly or even weekly IV sessions.
Unlike NAD+ boosting supplements that use precursor ingredients like nicotinamide riboside or niacin, IV therapy sessions typically use NAD+ as the direct delivery. Providers of NAD+ IV therapy claim that an intravenous solution is more effective because it bypasses the digestive system, allowing your body to feel the effects quicker. Studies also showed positive effects of the NAD+ infusion.
The problem? Price. At least for some of us.
NAD+ IV sessions cost around $600 for up to 60 minutes of treatment. The course of the therapy ranges anywhere from six to eight weeks, and some providers even offer packages of sessions, much like physical training packages at gyms.
While it depends on the length of treatment and the location, a full course of treatment might cost up to $15,000 over the span of a year.
However, there are cheaper solutions as well.
NAD+ Patches, Nasal Spray, Facial Cream, and Injections
You can find products like NAD+ patches, nasal sprays, facial creams, and injections on the market. One of the companies that sell them online is AgelessRX.
NAD+ patches are based on iontophoresis, which is a procedure in which an electrical current is passed through skin soaked in a solution containing an anticholinergic medication, which allows ionized (charged) particles to cross the normal skin barrier. We tried them just a few times. Honestly, we did not feel any effect. Maybe, it is required a long-term commitment to get obvious results.
We did also try NAD+ injections and had very positive results.
One thing to consider is safety. We know a lot about NAD+ boosters from animal experiments, but we still know very little about their effects on humans. NAD+ supplements are generally well-tolerated and do not appear to pose much risk of side effects when used for about 12 to 24 weeks. However, some side effects are still possible and may include nausea, fatigue, headaches, diarrhea, stomach discomfort, and indigestion. Therefore, we recommend taking NAD+ supplements under the supervision of a doctor or nutritionist. So far, the safety is shown for short use, but how safe long-term use is, we do not yet know.
Ok, what else?
Meanwhile, you also can increase your NAD+ level naturally. There are many ways to do it. For example, fat-burning states such as ketosis can increase NAD+. Ketogenic diets can help you enter this state without having to fast.
It was documented that proper lifestyle, including physical activity and diet, can influence healthspan via increasing the level of sirtuins.
Other possible approaches include strength training, upregulation of critical enzymes involved in NAD salvage, and inhibiting NAD degradation (e.g., with bioavailable flavonoids to inhibit CD38), which are part of NAD pharmacology development.
Results obtained in recent years have shown that NAD+ precursors can play important protective roles in several diseases. However, in some cases, these precursors may vary in their ability to enhance NAD+ synthesis due to their location in the NAD+ formation pathway.
In the next few years, it is expected the refinement of personalized therapy for the use of NAD+ precursors. It requires improved detection methodologies allowing the administration of specific NAD+ precursors in the context of patients’ NAD+ levels. It will lead to a better understanding of the therapeutic role of NAD+ precursors in human aging and disease prevention.
There are many methods that can help you to increase and/or maintain NAD+ levels in your body. According to our current knowledge, they can be divided into three groups in relation to NAD+ biosynthesis pathways and its consumption.
Know your NAD+ levels!
Technology is making home diagnostics faster, more efficient, and easier. Home diagnostic kits come packed with cutting-edge technology, apps, and Internet of Things (IoT) integration, making them sophisticated diagnosis tools.
Nowadays, you can measure NAD+ levels in the comfort of your home. A few companies are providing this service by sending you a sample kit with instructions.
Jinfiniti offers two different NAD tests: circulating NAD and intracellular NAD. The circulating NAD is based on measuring NAD in serum, which means the sample has to be out of your arm and into Jinfiniti’s lab in the US in 24-48 hours.
Wanting to bring easy NAD testing to a wider audience, Jinfiniti has launched a second and new NAD test that measures NAD levels inside the cells; any cell can be measured, but currently, this test focuses on blood cell NAD.
BioTech Life Sciences also provides kits for testing NAD+ levels.
More information on measuring your NAD levels you can find in our other post.
What is next?
New information on longevity supplements and treatments will be added periodically. Be sure to check back!
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