NAD+
Pathways
Studies (63)
Relationship between dietary niacin intake and erectile dysfunction: a population-based study
A large U.S. study found men with higher dietary niacin (vitamin B3) intake had a lower risk of erectile dysfunction (ED). Men in the highest third of niacin intake were 56% less likely to have ED compared to those in the lowest third. This link held true even after accounting for other factors like age, weight, and health conditions.
Effects of dietary nicotinic acid supplementation on meat quality, carcass characteristics, lipid metabolism, and tibia parameters of Wulong geese
Feeding geese nicotnic acid improves muscle & fat tone, bone density, lipid metabolism. 80mg/kg per day was found to be optimal dose for improving quality of geese tibia ( longest bone in leg ).
Dietary Niacin Intake Predicts the Decrease of Liver Fat Content During a Lifestyle Intervention
In 58 patients with fatty liver disease, the ones with the most niacin in their diet had the most favorable outcome, with a 37% reduction in liver fat after 9 months of lifestyle interventions, vs only 10% reduction in the patients eating the least niacin.
Iron deficiency reduces the efficacy of tryptophan as a niacin precursor
Iron deficiency impairs body converting tryptophan to niacin. Chicks fed the iron-deficient diets had markedly lower hemoglobin concentrations than those fed the iron-adequate diets. Regardless of iron level, chicks had linear growth responses to either nicotinic acid or tryptophan supplementation. Low bio-available iron contributes to niacin deficiency in populations.
Dietary nicotinic acid supplementation improves hepatic zinc uptake and offers hepatoprotection against oxidative damage
In rats, supplementing with high levels of nicotinic acid in diet before experiencing cell damage (induced by tert-butyl hydroperoxide injections) helped protect the liver, preserving its normal structure and improving its ability to absorb zinc, a beneficial element. This effect was less pronounced if the NA was increased after the cell damage had occurred. Rats with a deficiency of nicotinic acid in their diet exhibited the highest level of liver damage.
A prospective and comparative investigation of blood sFlt-1, P1GF, and niacin concentrations in women with premature ovarian insufficiency
Niacin supplementation may prevent premature menopause. Women with premature menopause have significantly lower levels of niacin. Niacin levels lowest in women most severe symptoms.
Effectiveness of niacin supplementation for patients with type 2 diabetes: A meta-analysis of randomized controlled trials
Review of many clinical trials concludes niacin supplementation can improve lipid profiles without affecting the glycemic levels for patients with Type 2 diabetes.
Effects of Niacin and Vitamin C on Blood Sugar
Rats in group 1 received no treatment. Rats in group 2 received daily 100 mg/kg body weight niacin injections. Rats in group 3 received daily 50 mg/kg body weight vitamin C injections. Rats in group 4 received both niacin and vitamin C injections. Blood sugar levels were measured before and after treatment. The results showed that niacin and vitamin C both lowered blood sugar levels in normal rats. Niacin was more effective than vitamin C in lowering blood sugar levels in diabetic rats. The combination of niacin and vitamin C was the most effective in lowering blood sugar levels in diabetic rats.
Low NAD+ Levels Are Associated With a Decline of Spermatogenesis in Transgenic ANDY and Aging Mice
A study in mice found that niacin supplementation increased NAD+ levels in the testes, which led to an improvement in sperm count and sperm motility. NAD+ deficient mice have ~30% smaller testes (balls) than the control mice (~1.5g vs ~2.17g). NAD+ is essential for spermatogenesis and that NAD+ deficiency leads to male infertility.
Studies on Tryptophan-Niacin Metabolism in Streptozotocin Diabetic Rats
Rats where split into 2 groups, one group was injected with a single does of streptozotocin at a dose of 60 mg/kg body weight, which is a chemical that is used to induce diabetes. After 12 weeks it was found that the diabetes group was only able to convert half as much tryptophan to niacins as the control group. The rats in the diabetic group had twice the excretion of xanthurenic acid in their urine. Xanthurenic acid is a waste product that is produced when tryptophan is not converted into niacin.
Supplementation of nicotinic acid and its derivatives up-regulates cellular NAD+ level rather than nicotinamide derivatives in cultured normal human epidermal keratinocytes
In cultured skin cells, nicotinic acid supplementation 1.3-fold up-regulated intracellular NAD+ level significantly and its metabolites nicotinic acid mono nucleotide also increased NAD+ level by 1.5-fold with 100 μM application. Surprisingly, NAM and its derivatives could not up-regulate cellular NAD+ levels in keratinocytes.
Acne Vulgaris Is a Special Clinical Type of Pellagra
People with acne often have abnormal lipid profiles and elevated oily secretion on their skin. Foam cells are an important pathological change in acne lesions. Acne is not a skin disease induced by infection, because no bacteria, fungi or parasites can be seen in early phase of acne lesion. The foam cells in acne lesions are white blood cells that have ingested large amounts of lipids. Niacin is the only vitamin that promotes the ability of HDL to scoop up cholesterol particles from plaques in the heart's blood vessels and move those particles to the liver for disposal, which prevents foam cell formation. Foam cells in acne lesions suggest that patients with acne are deficient in niacin and that acne can be considered a type of pellagra (niacin deficiency).
Vitamin b3 and Seborrheic dermatitis - a phase IV clinical study of FDA data
Study of 4,269 people that take niacin or have Seborrheic dermatitis finds no cases of Seborrheic dermatitis in people who take niacin.
Deficiency of metabolite sensing receptor HCA2 impairs the salutary effect of niacin in hemorrhagic shock
Niacin improves organ function and survival following hemorrhagic shock. Rats and mice where bled 60% of their blood volume, and replaced with Ringers lactate solution to induce hemorrhagic shock ( deprive tissue of oxygen and blood ). After 10 minutes of shock the animals where split into 3 groups and injected with nicotinic acid, NMN or DMSO, at 3 levels of dosing. Niacin at 10mg/kg, which was the highest dose given, had by far the best level of survivability. Rats, given NMN even at a 5x higher dose than niacin at 50mg/kg did not achieve a survival rate to the level observed in the 10mg/kg or the even 5mg/kg treated mice. Use of GPR109A knockout mice confirmed that the niacin GPR109A receptor plays a major role in the survivability enhancing effect of niacin.
Pharmacological bypass of NAD+ salvage pathway protects neurons from chemotherapy-induced degeneration
Axon degeneration from NMN accumulation can be prevented by bypassing the NAD+ salvage pathway (which is associated with the production of NMN) by providing nicotinic acid riboside (a precursor to nicotinic acid mononucleotide) as substrate for the body to make NAD+ via the primary Preiss Handler pathway instead.
Wallerian Degeneration Is Executed by an NMN-SARM1-Dependent Late Ca2+ Influx but Only Modestly Influenced by Mitochondria
Nicotinamide mononucleotide (NMN) accumulation in the extra cellular environment contributes to the breakdown of axons (nerve fibers).
Bacteria Boost Mammalian Host NAD Metabolism by Engaging the Deamidated Biosynthesis Pathway
This research used stable isotope tracing and microbiota-depleted mice to reveal that salvage NAD+ precursor supplements like nicotinamide (NAM) and nicotinamide ribose (NMR) don't actually boost NAD+, but depend on bacteria to first convert them into nicotinic acid. And that the resulting nicotinic acid is the converts to NAD+ via the Preiss Handler pathway.
Bacterial PncA improves diet-induced NAFLD in mice by enabling the transition from nicotinamide to nicotinic acid
Gut bacteria play an important role in NAD production. NAD boosting effect of oral NAM (nicotinamide) NR (nicotinamide riboside) is largely dependent on gut bacteria breaking them down to nicotinic acid, and that nicotinic acid being processed via Preiss Handler pathway. Nicotinic acid highly efficient at boosting NAD in mammals.
Blood levels of nicotinic acid negatively correlate with hearing ability in healthy older men
Higher levels of nicotinic acid in blood are strongly correlated with better hearing ability in 42 Japanese senior men.
Reversing Chronic Kidney Disease with Niacin and Sodium Bicarbonate
25 individuals with CKD (chronic kidney disease) stages 2-4 treated with a combination of supplements, including 500mg niacin 3x/day for three months, improved the disease by at least one stage.
NAD+ repletion rescues female fertility during reproductive aging
Loss of fertility is associated with lower NAD+ levels. Restoring NAD+ in aged mice by putting nicotinamide mononucleotide (NMN) in their drinking water at 2g/L restored their fertility as well as the adverse effect of old age on the development of the embryo.
Antidepressants may lead to a decrease in niacin and NAD in patients with poor dietary intake
Authors hypothesis that antidepressants tilt tryptophan metabolism towards making serotonin instead of niacin, which in turn can lead to niacin/NAD+ deficiency that exacerbates common psychiatric problems.
Effect of pharmacological doses of niacin on testicular structure and function in normal and diabetic rats
Feeding normal and diabetic rats 800mg of niacin per kg of diet increased testicular weight in all rats and decreased testicular MDA (a biomarker for cancer). Normal rats, but not diabetic ones, also had an increase in sperm count and serum testosterone.
The Importance of "Folic Acid" in Rations low in Nicotinic Acid
Dogs with severe niacin deficiency required folic acid to be administered in tandem with niacin in order to recover and avoid death.
Niacin regresses collagen content in human hepatic stellate cells from liver transplant donors with fibrotic non-alcoholic steatohepatitis (NASH)
Taking niacin ~1-3g daily clears up liver collagen and fat deposits which are associated with liver disease. It also prevents them from forming.
Politics and Pellagra: The Epidemic of Pellagra in the U.S. in the Early Twentieth Century
The 1906 to 1940 epidemic of pellagra was around 3 million cases, with 1 in 30 resulting in death. A Dr Goldberger was appointed to study the cause. Even though correctly identified the root cause as a nutritional deficiency (later to be confirmed as niacin specifically) his prognosis was rejected by politicians in affected regions since they basically didn't want to admit that a diet consisting of largely degerminated cornmeal (which was a key economic export) was not appropriate for human wellbeing. The invention of degerminating corn, which removes nutrients but prolongs shelf-life, coincided with the appearance of the disease. Goldberger would cure orphans suffering from pellagra by feeding them a more varied diet including fresh milk and meat.
Protective effects of niacin against methylmercury-induced genotoxicity and alterations in antioxidant status in rats
Rats being poisoned with methylmercury have less adverse effects when their diet is supplemented with niacin (50md/day).
Impact of Nuclear De Novo NAD+ Synthesis via Histone Dynamics on DNA Repair during Cellular Senescence To Prevent Tumorigenesis
The de novo production of NAD+ in the cell nucleus is central to the DNA repair capacity of aging cells and thus against preventing tumors.
A Detoxification Intervention for Gulf War Illness: A Pilot Randomized Controlled Trial
~30% of Gulf War veterans got Gulf War Illness, which is likely caused by toxic exposure to pesticides and chemical warfare agents. There is no known medical treatment. A regimen of niacin, sauna and exercise cured 11 of 22 participants.
NAD+ homeostasis in human health and disease
In depth review of NAD+, how its made in the human body, how it becomes deficient, and how its deficiency is a causal factor of a wide range of diseases. And how boosting NAD+ via enhancing agents like niacin ( especially niacin since it is the primary, so called Preiss-Handler pathway of manufacture ) can help cure a wide range of diseases.
Nicotinic acid inhibits glioma invasion by facilitating Snail1 degradation
This study grafted malignant gliomas cells (which are one of the most common types of primary brain tumors) into rat brains to see if nicotinic acid administration would help regulate the implanted tumor. ~70% of the allografted rats that were continuously administered with nicotinic acid were still alive on day 58. 100% of control group died by day 24. Biopsy showed much less tumor spread in nicotinic acid rats. Their results suggest that niacin the helps prevent the invasion of other kinds of malignant cells such as melanoma ( skin cancer ) cells and that this points to a general role of nicotinic acid in regulating tumor invasion.
Nicotinic Acid Long-Term Effectiveness in a Patient with Bipolar Type II Disorder: A Case of Vitamin Dependency
Case report of a patient with bipolar disorder who had been on lithium and other bipolar meds who was able to get off all meds after starting taking 1g niacin 3 times a day. He has been stable for 11 years on this niacin supplementation regimen. Stopping niacin leads a return of his symptoms within 2-3 days and clears up in one day after resuming the niacin regimen.
Treatment of Arthritis by Nicotinic Acid and Nicotinamide
Reports of patients successfully managing or curing various forms of arthritis via nicotinic and/or nicotinamide supplementation. A daily dosage of about one gram per 50 lb. body weight is necessary.
Antiatherothrombotic effects of nicotinic acid
Niacin reduces blood viscosity through a variety of mechanisms, thus improving blood flow and perfusion through choke points of the vasculature. Finally, niacin has cardioprotective effects that may limit ischemia–reperfusion injury. By preserving glycolysis during periods of inadequate blood supply and improving blood flow to the heart after a stroke, niacin can improve the functional recovery of the muscular tissue of the heart.
Coronavirus infection and PARP expression dysregulate the NAD metabolome: An actionable component of innate immunity
The antiviral activities of noncanonical PARP isozyme activities are limited by the availability of NAD and that nutritional and pharmacological interventions to enhance NAD levels may boost innate immunity to coronaviruses.
The Lifespan Extension Ability of Nicotinic Acid Depends on Whether the Intracellular NAD+ Level Is Lower than the Sirtuin-Saturating Concentrations
Cultural cell study indicates the lifespan extension ability of niacin depends on whether the intracellular NAD+ level was lower than the sirtuin-saturating concentration.
Leucine-nicotinic acid synergy stimulates AMPK/Sirt1 signaling and regulates lipid metabolism and lifespan in Caenorhabditis elegans, and hyperlipidemia and atherosclerosis in mice
Low dose niacin (50 mg/kg diet and 250 mg/kg diet) when supplemented in combination with leucine (24 g/kg diet) has a similar effect on lowering cholesterol in mice than standard therapeutic dose (1000 mg/kg diet) of niacin without leucine supplementation. Leucine amplifies niacin effect on lipid metabolism, hyperlipidemia and atherosclerosis in mice, at least in part by activation of the AMPK/Sirt1 axis.
Niacin protects against UVB radiation-induced apoptosis in cultured human skin keratinocytes
Niacin pretreatment of skin cells protects against UV-induced cell death and apoptosis by enhancing the pro-survival pathways including AKT, mTOR and S6 in skin keratinocytes. Oral and external niacin is safe and appears to be a promising chemo-preventive supplement for reducing the mutagenic, immunosuppressive and cell damage effects of sunlight. This is also the first study providing a molecular mechanism to support that niacin can be utilized as a skin photo-damage protective agent.
Gut dysbiosis dysregulates central and systemic homeostasis via decreased melatonin and suboptimal mitochondria functioning: pathoetiological and pathophysiological implications.
In depth review of how deficiency of butyrate and melatonin compromise gut and overall mitochondrial function and lead to lower levels of other key molecules in cellular metabolism like sirtuins, PGC-1α and NAD+.
Effect of Huntington's and Alzheimer's diseases on the transport of nicotinic acid or nicotinamide across the human blood-brain barrier
Looked into how niacin and nicotinamide cross blood brain barrier in control, Huntington & Alzheimer patients. Nicotinamide had higher uptake in brain tissue than niacin. No statistical difference in concentrations across the groups. It was observed that niacin and nicotinamide concentrated in red blood cells vs plasma over time.
Prevention of Cancer by Vitamin B3 (Nicotinamide and Nicotinic Acid)
Nicotinamide, Nicotinic acid (niacin) and the related aromatic amides have been shown to have striking indications of possessing anticarcinogenic properties.
Oral niacin prevents photocarcinogenesis and photoimmunosuppression in mice
Mice subjected to high dose ultraviolet light for about 6 months while fed a diet supplemented with 0%, 0.1%, 0.5%, or 1.0% (by dry weight of feed) of niacin showed 68%, 60%, 48%, and 28% rates of skin cancer respectively, indicating a protective effect. Elevated levels of NAD found in niacin supplemented mice. NAD modulates the function of DNA strand scission surveillance proteins p53 and poly(ADP-ribose) polymerase, two proteins critical in cellular responses to UV-induced DNA damage.
High dietary niacin intake is associated with decreased chromosome translocation frequency in airline pilots
Statistical analysis of 82 airline pilots showed a 42 % decrease in the frequency of chromosome translocations (ie DNA damage from higher rates of ionizing radiation while flying) for those with high compared with low dietary niacin.
Small Molecule Antagonists of NAADP-Induced Ca2+ Release in T-Lymphocytes Suggest Potential Therapeutic Agents for Autoimmune Disease
Ca2+ is one of the major ways that cells communicate and is involved in the regulation of many important cellular processes from proliferation to apoptosis. Ca2+ regulation is involved in many autoimmune conditions and nicotinic acid (niacin) and is key to this signaling.
Network Pharmacology and bioinformatics analyses identify intersection genes of niacin and COVID-19 as potential therapeutic targets
Computer modeling shows niacin a key to therapy for covid via enhancing the immune system, inhibiting inflammation and regulating cellular microenvironment.
Niacin-mediated rejuvenation of macrophage/microglia enhances remyelination of the aging central nervous system
Niacin via its ability to enhance macrophage and microglia is great for repairing (myelin) sheaths that protect nerve fibers, which deteriorate in diseases like multiple sclerosis.
The treatment of migraines and tension-type headaches with intravenous and oral niacin (nicotinic acid): systematic review of the literature
An overview of the evidence for using niacin to treat headaches. Mechanisms explored are vasodilation, improvement of mitochondrial energy metabolism, improved oxygenation, lowering of lactic acid.
The COVID-19 Burden or Tryptophan Syndrome: Autoimmunity, Immunoparalysis and Tolerance in a Tumorigenic Environment
Long covid is due to changes in the metabolism of tryptophan and the lack of niacin (NAD/NADH+). Tryptophan has its metabolism altered by the lack of intestinal absorption due to internalization of ACE-2 and hypoxemia and inflammation, diverting its products to the formation of toxic Kynurenine metabolites. The longer time under hypoxemia, the less niacin and the more tryptophan will deviate to Kynurenine in an inflamed environment
Melatonin in Mitochondria: Mitigating Clear and Present Dangers
It's inferred that the majority of melatonin is created inside the mitochondria, independent of the pineal daylight associated melatonin. Melatonin has a 3 billion year history of use inside cells as a highly efficient anti-oxidant. It functions as an anti-oxidant for both plants and animals. It stimulates synthesis of other antioxidants like glutathione. It's the "swiss army knife" of anti-oxidants and uniquely positioned as the "fox in the hen house" inside the mitochondria where many free radicals originate. Melatonin reverses the Warburg effect and aids in arresting cancer cell growth.
Niacin Cures Systemic NAD + Deficiency and Improves Muscle Performance in Adult-Onset Mitochondrial Myopathy
Patients with mitochondrial myopathy (which is associated with NAD+ deficiency) received ~1g niacin daily for 4 months. This resulting in increasing blood NAD+ levels in all patients, up to 8x, improved muscle strength, improved respiratory chain activity and reduced fatty liver.
Niacin in the Central Nervous System: An Update of Biological Aspects and Clinical Applications
In depth review of how niacin and its metabolites play a key role in brain and nerve health. Alzheimers and Niacin intake are inversely correlated. Niacin helps cells stay alive when blood supply is cutoff.
Niacin requirements for genomic stability
Niacin involved with over 400 NAD+ dependent reactions. Essentially all cancer patients are deficient in niacin. Exposing mice to high levels of UVB radiation to induce skin cancer showed that mice on the highest doses of niacin had the lowest rate of skin cancer at 28% compared to 68% in the control group.
Fifteen year mortality in Coronary Drug Project patients: long-term benefit with niacin
9 years after the conclusion of a long term study on various drugs to reduce risk of death of people who had a heart attack, only the niacin group showed a statistically significant, 11% reduction in mortality than in the placebo group. This was after they stopped taking the niacin 9 years earlier, indicating a long term benefit.
NAD Deficiency, Congenital Malformations, and Niacin Supplementation
Disruption of NAD synthesis caused a deficiency of NAD and birth defects in humans and mice. Niacin supplementation during pregnancy prevented the birth defects in mice.
The oxidative stress-induced niacin sink (OSINS) model for HIV pathogenesis
Talks about how intracellular niacin depletion along leads to tryptophan depletion as the body attempts to compensate by synthesizing niacin from tryptophan. And how this imbalance impairs the immune system in HIV.
The NAD + precursor nicotinic acid improves genomic integrity in human peripheral blood mononuclear cells after X-irradiation
Peripheral blood mononuclear cells (diverse mix of highly specialized immune cells) supplemented with nicotinic acid (niacin) and then blasted by x-ray radiation showed increased NAD+ levels, improved DNA repair efficiency and enhanced genomic stability compared to control.
Open AccessReview Minireview Exploring the Biological Cycle of Vitamin B3 and Its Influence on Oxidative Stress: Further Molecular and Clinical Aspects
Overview of how niacin and its metabolites like NAD, NADP, NADPH play a key role in cellular signaling, apoptosis, balancing intestinal flora and gene expression. Without external supply of supply of niacin, the genome becomes unstable via the antioxidant system no longer functioning efficiently, which ultimately leads to cell death.
A novel treatment target for Parkinson's disease
The GPR109A receptor and its agonists (niacin and butyrate) have anti-inflammatory actions in the skin, gut and retina. For Parkinson's disease, niacin supplementation may have 3 benefits: lower inflammation via GPR109A-related mechanisms, increase dopamine production in brain by supplying NADPH and boosting mitochondrial functions by increasing the NAD/NADH ratio.
The isolation and identification of the anti-black tongue factor
A study from 1937 showing supplementing niacin cures black tongue in dogs just as well as feeding them liver. Other studies from the time are also mentioned such as one that shows rats supplementing nicotinic acid (niacin) lived longer.
Pharmacological Intakes of Niacin Increase Bone Marrow Poly(ADP-Ribose) and the Latency of Ethylnitrosourea-Induced Carcinogenesis in Rats
Rats fed high niacin diet and then poisoned with ethylnitrosourea (a potent mutagen) survived for longer and had increase amounts of NAD+ (1-1.5x) and ADP-ribose in their bone marrow.
Niacin for treatment of nonalcoholic fatty liver disease (NAFLD): novel use for an old drug?
39 patients taking 2g/day extended release niacin for ~6 months had a ~40% reduction in liver fat. Other markers of inflammation such as CRP (C-reactive protein) where also reduced.
Effect of nicotinic acid on zinc and iron metabolism
Mice fed 3x the Niacin of a standard mouse diet increased zinc absorption by 70.9%, they also seemed to have more protein mass and denser skeletons.
Niacin and its metabolites as master regulators of macrophage activation
The focus is on how niacin and its metabolites enable white blood cells to react to a changing microenvironment (macrophage plasticity). It also discusses the anti-oxidant and anti-inflammatory aspects of niacin.