The Powerful NAD+& Its Role in Anti-Aging.

The quest for a healthy, and longer life has always been an important factor since early human history. Juan Ponce de Leon set out in the 16th century on a quest to obtain the mythical fountain of youth. It was thought that anyone who drank from this stream of water would live eternally. We’re not sure if he ever found the fountain of youth or not. Nicotinamide Adenine Dinucleotide (NAD+), a chemical molecule found in practically every cell of the body, has lately been identified as a new and modern fountain of youth by scientists.

What is NAD+?

NAD is an acronym that stands for “nicotinamide adenine dinucleotide.” This chemical occurs naturally in the body and is involved in the chemical process that produces energy.

NAD+ serves as a direct link between your metabolism and cellular messages. As a co-enzyme for vitamin B3, NAD+ is involved in a greater number of processes in the body than any other vitamin-derived molecule. Additionally, it plays a critical part in aging, namely the below points. To read more on its connection to aging, and the hallmarks of human aging, check out this article.

• Repairing DNA damages associated with aging.
• Food to energy conversion
• Providing assistance to cell defense systems
• Syncing the circadian cycles required for sleep.
• Helps to regulate circadian rhythm.

The amount of NAD in our bodies dictates the rate of aging. NAD levels are higher in younger cells and tissues. As a result, younger people have higher levels of physical activity, cognitive performance, and the ability to repair and regenerate cells. As we age, our body’s NAD levels begin to fall. This is manifested by a slower cognitive response, memory loss, and decreased agility.

Methods Of Increasing NAD+ Levels in Body

1. Fasting

Reduced calorie intake, whether through fasting or calorie restriction, is a good means of indirectly increasing the body’s NAD levels. Fasting has been demonstrated to boost the amounts of NAD+ and sirtuins in the body, which are proteins that have been linked to a reduction in the rate of the aging process. While fasting has been shown to be useful in raising NAD+ levels, extreme reductions in calorie consumption or fasting have been shown to have a negative impact on health.

How much to reap benefits? Popular fasting regimens (Intermittent fasting) frequently involve 16-24 hours fasting periods twice a week, followed by nutritious meals. This eating pattern induces a state of shock in the body, which might increase your natural supply of NAD+. Other human studies on time-restricted eating have revealed that eating within 8 hours or fewer results in increased expression of autophagy genes and sirtuins, as well as improved insulin sensitivity, as compared to eating over a 12-hour period. Another research indicates, that fasting 16 to 24 hours twice a week followed by a nutritious meal promotes the body’s shock reaction, which increases NAD+.

2. Exercise

Exercise is another effective way to naturally increase NAD+ levels. Our bodies require energy while we exercise, which comes from NAD+. Human investigations have shown that aerobic exercise training or any sort of exercise/sports activity raises NAD+ levels by stimulating skeletal muscle NAMPT expression. Essentially, exercise promotes the synthesis of mitochondria in our body muscles, which serve as the cells’ powerhouses. Increased mitochondrial production leads to a natural rise in the body’s NAD+ levels. After exercising, researchers have found that intracellular NAD+ levels rise.

In another recent study of Feb 2022, NAD levels were linked to age and exercise. The study included over 50 people from various age groups 20-64 with different activity levels. They discovered that NAD, an important molecule in mitochondrial energy generation, was considerably decreased in elderly individuals.  But elderly people who exercised frequently had nearly the same amount of NAD as the young. The researchers found that regular exercise can reverse most metabolic changes caused by muscle aging.

How much to reap benefits?

• A study shows aerobic exercise training raised NAMPT and NAD+ levels by 13% and 28% in young and older adults, respectively, whereas strength exercise training increased NAMPT & NAD+ levels by 25% and 30% in young and older adults, respectively.
• Another research shows that 10 weeks of resistance training doubles NAD+ levels in muscle tissue in 60-Year-Olds.
• New research published in Feb 2022 shows that even walking 10,000 steps helped to increase NAD+ levels.

3. Limit the Sun Exposure

If you spend a lot of time in the sun, you risk diminishing your own NAD+ supply prematurely. In research, it has been found that too much direct sunlight exposure can make the body’s NAD+ levels drop. When skin is exposed to the sun for an extended period of time, it not only develops medical diseases such as melanoma but also changes its physical look, commonly referred to as photo-aging. This is because our bodies use NAD+ to fix cells that have been damaged by direct sunlight.

How to reduce exposure?  In a study, 5% Nicotinamide  NAM cream was applied twice daily for 12 weeks throughout the experiment, this resulted in reduced fine lines and wrinkles, hyperpigmented spots, red blotchiness, skin sallowness, and enhanced skin suppleness. So, when you’re outside, minimize your time in the sun, use sunscreen and protect exposed skin with loose-fitting, lightweight clothes. Short-term exposure to sunshine is beneficial for your general health—particularly those early morning doses when the UV rays are at their lowest.

4. Embrace the Heat & Cold

Heat. While prolonged exposure to direct sunlight is detrimental to your general health and NAD+ levels, spending time in natural or artificial heat might help enhance them as it has been proven in research as well. The enzyme nicotinamide mononucleotide adenylyltransferase (NMNAT), catalyzes nicotinamide adenine dinucleotide (NAD+) production, is raised under heat shock conditions, and is transcriptionally controlled by heat shock factor (HSF) and hypoxia-inducible factor 1 (HIF1). Heat sources such as hot tubs, saunas, and heated pools cause your heart to beat quicker, causing your body to use additional energy to stay cool. This results in an increase in the generation of NAD+, which is required to provide energy.

Cold. Along with heat stress, cold stress-induced physiological reactions including activation of brown adipose tissue (BAT) have been shown to be beneficial to health. This adipose has been studied to have a good effect on NAD+ synthesis and other health advantages, such as the lack of low-grade inflammation, an improvement in insulin sensitivity, and a reduction in liver fat.

5. Foods

Certain foods have been shown to increase the body’s NAD levels. Among them are the following:

• Dairy. The results of the research have shown that cow’s milk is a good source.  In one liter of fresh cow’s milk, around 3.9 mol of NAD+ can be found. So, daily consumption of two to three glasses of cow’s milk may also support NAD+ synthesis. Milk also has nicotinamide riboside (NR), which is a NAD+ precursor vitamin.
• Green Veggies. Green vegetables have recently been discovered to be an excellent source of NAD for the body. Peas and asparagus are two of these vegetables which are abundant in this substance. Both vegetables contain 3.2mg and 2mg of NAD+ respectively.
• Mushroom. It is one of the few foods that contain NAD. Each cup of Crimini Mushroom has 3.3mg NAD+.
• Grains. Whole grains, such as whole wheat and brown rice, contain a significant amount of niacin which is a NAD precursor. However, when vegetables, food items, or grains are cooked or processed, nutrition and vitamin supply are lost. As a result, it is recommended that you consume raw vegetables and healthy grains in addition to processed foods.
• Fish. Tuna, anchovies, and salmon have a sufficient amount of NAD levels giving you another reason to enjoy this seafood. Tuna contains 20.5mg (milligrams) of NAD+ per cup, while salmon contains 10.1mg.  Additionally, fish is an excellent source of vitamin B12 and omega-3 fatty acids — two nutrients critical for human health and good aging.
• Turkey. Turkey is an excellent source of niacin and tryptophan, two precursors of NAD.
• Beef. It is the most abundant source of NAD+ naturally. A 6-oz portion of lean beef has nearly double the daily recommended amount of niacin.
• Chicken. Chicken meat has a significant amount of NAD. This compound is present in this product with a concentration of 9.1mg (milligrams).
• Yeast. It includes Nicotinamide Riboside, which is unusual (NR). This compound is a precursor of NAD+. As a result, ingesting yeast-containing pastries can help you grow younger. Indeed, yeast has more NAD+ per gram than milk.

Above all, a variety of foods have been discovered that are all made up of the youth-restoring molecule NAD+. Incorporating them into your diet is one of the healthiest choices you can make right now. However, there are many other fast ways to replenish your needs for NAD.

6. Supplementations

Along with these methods for enhancing your NAD levels, some supplements have been associated with increased NAD levels in human studies.  Two different forms of vitamin B3 — nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) — are gaining interest for their alleged ability to increase NAD levels.

Increased NAD+ levels in the body have been shown to protect the brain against degenerative illness and to help manage cholesterol levels. As a result, the benefits of boosting NAD+ through supplements seem more notable for older people. These boosters operate in conjunction with fish oil, eye vitamins, and vitamin B12 to promote the overall health and well-being of older people. Learn more about how supplements work and how we should incorporate them into daily life in our article here.

The following NAD boosting supplements have been identified to work for the human body by recent research:

• NR Supplementation (precursor of NAD+)
• NMN Supplementation (precursor of NAD+)
• NAD+ Supplementation
• Others

Most of the studies were carried out on mice but now researchers are trying to generate comparable outcomes in humans. A randomized trial (considered the gold standard of scientific research) from the journal Nature discovered that individuals who took a daily supplement containing NAD+ sources had a considerable, steady rise in their NAD+ levels over a two-month period. You should always check with your physician before adding or removing any supplements.

Oral Vs Intravenous supplementation

Oral NAD+ supplementation has not been shown to increase NAD+ levels in the body. Precursors like NMN or NR may give these benefits. Unlike medicines, supplements have a relatively low relative bioavailability (the amount that your body can really utilize). Because oral NAD supplements are poorly absorbed, they are less effective than IV infusions.

IV drips are the only technique to achieve 100% bioavailability of NAD+. Your body will absorb the greatest possible coenzymes and transform them into molecular energy. IV treatment is an excellent technique to rapidly and efficiently increase NAD levels and the associated advantages. IV therapies are injected straight into the person’s circulation. Due to the fact that intravenous NAD therapies skip the digestive system entirely, this kind of supplementation assures 100% absorption. NAD is immediately accessible to your cells for usage. Most cases require daily 500mg-1000mg infusions lasting 2-4 hours for 4-10 days.

Side effects. No serious side effects have been reported by researchers. However, some trials have reported modest side effects such as headaches, nausea, diarrhea, and flushing of the skin.

What to take: NAD+, NR or NMN Supplement?

NAD+ Supplement

While a healthy balanced diet is a basis for an appropriate supply of NAD+ in our bodies, there are times when additional measures may be necessary. Individuals over the age of 50 require more NAD+ than a regular balanced diet can provide. Supplements containing NAD are really beneficial in this case.

Following research has been associated with benefits to humans with NAD+ therapy.

• DNA Repairing Property. NAD+ is a substrate for DNA-repairing proteins including PARP1, PARP2, and PARP3, as well as enzymes like SIRT1 and SIRT2. Optimal amounts of NAD+ in the body might directly impact DNA repair pathway activities.
• Boosts Immunity. Beyond participating in several cellular enzymatic activities, NAD+ has been shown to influence both natural and adaptive immunity. Pathogens hijack enzymes that regulate NAD+ homeostasis, lowering NAD+ levels and eventually causing metabolic failure. Nicotinamide adenine dinucleotide (NAD) treatment supports overall health and wellness by naturally reducing systemic inflammation.
• Exercise Performance. A group of Australian scientists conducted research to determine the effects of taking antioxidant supplements prior to exercise in 72 participants. The subjects of this study were given an oral dosage of 300mg supplement that promotes the synthesis of NAD+, and the results were quite compelling.
• Helps in Withdrawal. There is mounting evidence that this powerful chemical helps to alleviate addictions, especially those associated with drug and alcohol withdrawal. NAD+ detoxifies the brain using natural and therapeutic co-enzymes. These flush out drugs accumulated in organs and help rebalance the brain. Among the benefits include better mental clarity, attention, concentration, mood, and vitality.
• Brain Functions. NAD supplementation has been proven to improve age-related mental decline by increasing mental clarity, problem-solving skills, and memory, and helping to fight depression and anxiety. Additionally, NAD’s neuroprotective capabilities may aid in preventing this damage from occurring in the first place in the case of Alzheimer’s and Parkinson’s disease.

What is NAD Dosage? While NAD+ is a natural substance, it must be used in moderation. The Food and Drug Administration (FDA) recommends a maximum daily dose of NAD+ of 2 grams. The recommended duration of treatment is 7-16 days, depending on the user’s medical history.

Nicotinamide Riboside NR Supplement

Nicotinamide riboside is a naturally occurring molecule that serves as a precursor to NAD+. It is an alternative form of vitamin B3 also known as niacin. It has been proven to work for the human body and is also available in supplementary form. Nicotinamide riboside is transformed into NAD, once it reaches your system and promotes mitochondrial activity. According to researchers, a single dosage of nicotinamide riboside can boost NAD+ levels in the blood by up to 2.7-fold. Numerous studies have demonstrated that NR supplements are useful for increasing the body’s NAD levels.

NR has been proven in clinical studies to significantly boost NAD levels in as little as two weeks, and these levels are maintained with continuing daily NR administration.

• Increases Lifespan. Increased NAD+ levels lengthen the longevity of mice. One research found that supplementing mice with the NAD+ precursor NR increased their longevity by around 5%.
• Promotes Healthy Aging. As we have read NR helps to increase NAD levels in the body, as a result, NAD+ stimulates many enzymes that may contribute to healthy aging. One group of enzymes is sirtuins. They have been shown to repair damaged DNA, increase stress tolerance, decrease inflammation, and promote healthy aging.
• Increases Blood Levels. The research presents a 2021 study demonstrating that supplementation with NR products increased blood levels of NAD in humans as proof of its efficacy.
• Protects Brain Health. In test-tube research, Nicotinamide riboside increased NAD+ levels and greatly enhanced mitochondrial performance in stem cells isolated from a Parkinson’s disease patient proving its efficacy for better brain health.
• Improves Mitochondrial Function. By maintaining normal NAD+ levels in the body, you may be able to preserve mitochondrial functioning and so promote healthy aging. That’s because NAD+ appears to assist sirtuins to execute their function. NAD boosts SIRT1 activity, which promotes mitochondrial growth and longevity.
• Lowers Heart Disease Risk. In humans, nicotinamide riboside increased NAD+ levels, assisted in the reduction of aortic stiffness, and decreased systolic blood pressure in individuals at risk of high blood pressure.
• Counter High Fat Diet. Even with a high-fat diet, NR supplementation appears to enhance metabolism and weight maintenance in animals. In one research, mice fed a high-fat diet with NR gained 60% less weight than mice fed the same diet without NR.
• Promotes Muscular Health. Following a 6-week NR supplementation regimen, healthy overweight or obese men and women saw increases in NAD+ and muscular metabolism, as well as small changes in body composition and sleeping metabolic rate. In 2019, another study team looked at NR availability in elderly skeletal muscle. In this randomized control crossover experiment, twelve 70-80-year-old males received 1000mg NR daily for 21 days. NR raised NAD+ in muscle and acted as an anti-inflammatory.

There are more than 40 clinical trials going on to prove NAD booster’s efficiency for humans. Current evidence indicates that NR is safe.

What is Nicotinamide Ribose (NR) Dosage? Clinical research has shown that NR supplements up to 1,000 mg per day are safe for most people (1)(2).

Side effects associated with NR supplementation were reported as nausea, drowsiness, headaches, diarrhea, stomach pain, and indigestion.

Nicotinamide Mononucleotide NMN Supplement

Nicotinamide Mononucleotide (NMN) is one of the most efficient ways to increase NAD synthesis. However, NMN supplements are demonstrating anti-aging properties independent of NAD synthesis.

The benefits of taking NMN have been reported in the following animal as well as human studies.

• Increases Stamina. The first effect of NMN is that it improves energy metabolism and physical activity. Frequently, individuals report feeling more energized after using NMN. To obtain an energy boost, it is recommended to take a suitably large dose. Some people have an impact after taking 250 mg of NMN, while others require at least 500 mg. A study found that dosing 18-month-old mice with NMN improved their endurance by 56-80% after two months. The benefits were evident in mice as young as 32 months old, or as elderly as 80 years old.
• Improves Eye Function. According to a study, long-term administration of NMN has been shown to dramatically improve visual function as well as tear production. According to another study, NMN can help preserve eye cells and reduce inflammation in dry eye illness through the activation of DNA maintenance and the production of a health-promoting protein.
• Suppresses the Onset of Age-Related Obesity. Muscle mass declines with age, but fat mass increases. This fat mass growth contributes to age-related weight gain. After 12 months, NMN administration significantly reduced age-associated body weight gain in mice without apparent harm in research. Additionally, the data indicated that the effect of NMN on body weight was not attributable to growth problems or appetite decrease.
• Improves Brain Function. NMN administration has been shown to improve cognitive performance in aged mice by dilatation of blood vessels of the brain and increased blood flow.
• Improves Fertility. According to a study, NMN promotes fertility by improving the amount and quality of maternal eggs and fertilizing them in mice. The findings reveal a viable way to increase women’s reproductivity in their late maternal years.
• Improves Stem Cell Health. During aging, stem cells decrease, and the surviving stem cells often become dysfunctional. This adds to aging because stem cells make new cells and sustain our tissues. Various studies demonstrate that NMN, or raising NAD levels, can promote stem cell health and self-renewal.
• Enhances Cardiovascular Health.  Research has demonstrated that short-term injection of NMN effectively protected the mutant mice against heart failure by maintaining mitochondrial ultrastructure and preventing cell death in the heart. The studies have also suggested that NMN administration might be a viable treatment for heart disorders.

NMN Dosage? Taking the human and animal studies of efficacy and safety into consideration and determining optimal NMN dosages, the suggested amount that individuals between 30- and 60-years old take is 500 mg per day. People over age 65 can safely take 750 mg per day to enhance NMN’s effects. Harvard professor David Sinclair who researches aging has talked about using NMN to stay healthy and avoid aging. Dr. Sinclair has stated that he takes 1,000 mg / 1 gram of NMN every day.

Side Effects. An international team of researchers performed the first human clinical trial for NMN in Japan to examine the safety of the substance. NMN’s safety as a dietary supplement has been verified in a number of FDA-approved research trials. Currently, no negative effects of nicotinamide mononucleotide have been observed in humans.

OTHER SUPPLEMENTS

In addition to these methods for boosting your levels of NAD+, there are also various supplements that have been related, during human studies, to increasing NAD+ levels. More studies in this regard are being carried out to prove the efficacy of these molecules. Some of these NAD+-increasing supplements are:

• Resveratrol.
• Quercetin.
• Succinic Acid.
• Tryptophan.
• Apigenin.

NAD is vital for numerous of your body’s important processes, which would stop without NAD. NAD supports healthy aging, helps our DNA repair itself, makes our cells resilient to stress while protecting our brains, and helps us eat and sleep at the proper times according to our body’s demands. The production of NAD+ gives an edge when it comes to the anti-aging game, allowing us to slow down the aging process.

Also check out these anti-aging molecules based on researches.