From the perspective of supplementing NAD+, it can supplement the four types of precursors of NAD+, niacin, tryptophan, nicotinamide and NMN/NR in the three metabolic cycles. Niacin, nicotinamide and tryptophan have a certain limit in intake, the combination of nicotinic acid (NA) and GPR109A will cause severe flushing in patients, and excessive intake of tryptophan and nicotinamide will also There are side effects. (1) Nicotinamide (NAM) can inhibit Sirtuins and cause liver toxicity. (2)
Niacin becomes NMN through the Preiss-Handler pathway, while tryptophan becomes NMN through the de novo synthesis pathway. Nicotinamide and NMN/NR become NMN through the salvage synthesis pathway, and the NAD+ generated by the salvage synthesis pathway accounts for the NAD+ source in the body. 85% of NMN/NR is obviously the key substance for supplementing the synthetic pathway, which is an ideal choice for supplementing NAD+ in the body. Since NAMPT is the rate-limiting enzyme of the supplementary synthetic pathway, supplementation with nicotinamide (NAM) cannot bypass the bottleneck of NAMPT, and NNM/NR is a more competitive choice.
| Supplement | Way | Introduction | Rich in Food | Side Effect |
| Niacin | Preiss-Handler Approach | Niacinamide synthesizes vitamin PP, which is one of the 13 kinds of vitamins necessary for the human body. It is a water-soluble vitamin and belongs to the vitamin B family. | Widely present, especially in liver, milk, eggs, vegetables, yeast, mushrooms, broccoli, whole grains, and some fruits. |
1. There is almost no toxic reaction when the renal function is normal. General adverse reactions include: feeling warm, skin redness, especially on the face and neck, headache and other vasodilation reactions. 2. Large-dose medication can cause diarrhea, dizziness, fatigue, dry skin, itching, dry eyes, nausea, vomiting, stomach pain, high blood sugar, high uric acid, cardiac arrhythmia, and hepatotoxic reactions. 3. Generally, after taking niacin for 2 weeks, vasodilation and gastrointestinal discomfort can be gradually adapted, and the above reactions can be avoided by gradually increasing the dosage. In case of severe skin flushing, itching, or gastrointestinal discomfort, the dose should be reduced. |
| Tryptophan | De Novo Synthesis Pathway | People who lack vitamins B1, B2, and B6 cannot produce niacin from tryptophan; the conversion ratio of tryptophan to niacin in mammals is 60:1. | Pinto beans, milk, meat, fish, bananas, peanuts and all protein-rich foods. | Adult daily intake 100~500mg. |
| Nicotinamide | Complementary Synthetic Pathway | Usually together with niacin, it is called vitamin PP. | Animal liver and kidneys, lean meat, fish, eggs, white poultry meat. | Intramuscular injection of this product can cause severe pain, so intramuscular injection is not suitable. Individual patients may experience dizziness, nausea, upper abdominal discomfort, loss of appetite, skin flushing, heat and itching, which may disappear on their own. Overdose during pregnancy may cause teratogenicity and is therefore contraindicated. |
| NMN/NR | Complementary Synthetic Pathway | NAD+* immediate precursor. | Broccoli, Edamame, Avocado, Avocado, Cucumber. | No adverse reactions have been found. |
Compared with other substances, NMN and NR are more direct ways to supplement NAD+. After NR enters the human body, it needs to be phosphorylated by NPK1~2 to become NMN, and there are no enzymes of NPK1 and NPK2 in the mitochondria to convert NR into NMN. (3) More importantly, after oral administration, most of NR is not converted into NMN, but is digested into NAM:
“Oral administration of NR increases NAM, while NMN remains unchanged.” (4)
“The evidence suggests that NR is converted to NAM before absorption occurs and that this reaction is the limiting step.” (5)
“NR is converted into NAM before reaching tissues or being absorbed.” (6)
Changes of NR/NAM/NMN in blood after oral administration of NR
Source: Effects of a wide range of dietary nicotinamide riboside (NR) concentrations on metabolicflexibility and white adipose tissue (WAT) of mice fed a mildly obesogenic diet
Oral NR is digested into NAM in the body, which still fails to change the restriction of the rate-limiting enzyme NAMPT in the salvage synthesis pathway, and the ability to supplement NAD+ is limited. To sum up, supplementing NMN is the most direct and effective way to supplement NAD+.
Compared with other supplementary methods of NAD+, NMN bypasses the bottleneck of the NAMPT rate-limiting enzyme and can quickly replenish NAD+ in the body. In a 2017 study, after supplementing NMN for four days, the activity of NAD+ and SIRT1 in the body increased significantly. Taking NMN Aged mice had higher levels of NAD+ and SIRT1 activity than young mice that did not take NMN. (7)
NMN itself is a naturally occurring substance in the human body, and it also exists in many foods. It is purely natural and harmless. Studies have confirmed that supplementing NMN will not affect the activities of various enzymes in the supplementary synthesis pathway. After oral administration of NMN, it has no effect on the activities of various enzymes in the supplementary synthesis pathway, such as NAMPT, PARP, and NMNAT. It directly changes the level of NAD+ in the body. (8)
Changes in supplementary synthesis-related enzymes after adding NR, NMN and control group
Source: The NAD+ PrecursorNicotinamide Riboside Enhances Oxidative Metabolism and Protects againstHigh-Fat Diet-Induced Obesity
NMN is absorbed very quickly in the body and can quickly increase NAD+ levels in the body: (9)
A, absorbed intact through the digestive system;
B, enters the blood in 2 to 3 minutes;
C, Increase the NMN content in tissue within 15 minutes;
D. Rapidly increase NAD+ levels in blood, liver and other organs;
NMN and NAD+ concentration curves after oral administration of NMN
Data source: Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice. Cell Metabolism, v.24, no.6, 2016 Dec 13, p.795(12)
Cited documents：
1，Nicotinic acid, nicotinamide, and nicotinamideriboside: amolecular evaluation of NAD+ precursor vitamins in human nutrition.Bogan KL,Brenner C Annu Rev Nutr. 2008; 28():115-30.
2，Resistance Exercise Training Alters Mitochondrial Function in HumanSkeletal Muscle
3，Pathways and subcellular compartmentation of NADbiosynthesis in human cells: from entry of extracellular precursors tomitochondrial NAD generation.
4，Loss of NAD Homeostasis Leads to Progressive andReversible Degeneration of Skeletal Muscle (Fredrick 2016)
5，Digestion andabsorption of NAD by the small intestine of the rat (Henderson, 1983)
6, Effects of a widerange of dietary nicotinamide riboside (NR) concentrations on metabolicflexibility and white adipose tissue (WAT) of mice fed a mildly obesogenic diet
7,，Nicotinamide Mononucleotide, an NAD+ Precursor, Rescues Age-AssociatedSusceptibility to AKI in a Sirtuin 1-Dependent Manne
8，The NAD+ Precursor Nicotinamide Riboside Enhances OxidativeMetabolism and Protects against High-Fat Diet-Induced Obesity
9，Long-Term Administration of Nicotinamide Mononucleotide MitigatesAge-Associated Physiological Decline in Mice.Cell Metabolism, v.24, no.6, 2016Dec 13, p.795(12)
