GPR109A
Pathways
Studies (38)
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.
Niacin ameliorates ulcerative colitis via prostaglandin D2‐mediated D prostanoid receptor 1 activation
Out of 26 patients with moderate ulcerative colitis (inflammation of the colon) who were unresponsive to conventional treatments, 92.3% responded positively and 88.5% went into remission after receiving a daily niacin enema treatment for 6 weeks. The had no serious side effects, showed notable improvements in intestinal healing, reduced symptoms like rectal bleeding and stool frequency. Niacin is a promising, well-tolerated alternative for inducing clinical remission of ulcerative colitis.
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.
Intravenous Niacin Acutely Improves the Efficiency of Dietary Fat Storage in Lean and Obese Humans
24 healthy men and women with a mean age of 35 years, where injected Intravenously w/ 1g of niacin or placebo for 2 weeks. The niacin group ended up with acutely lower levels of FFAs (free fatty acids, fats floating around in the bloodstream) and significantly higher levels of triglyceride stored in visceral adipose tissue. This may help to reduce the amount of fat that is stored in the liver and other organs, which can help to improve insulin sensitivity and reduce the risk of metabolic complications. IE niacin may help people with diabetes and obesity to lose weight and improve their health.
Nicotinic Acid Treatment Shifts the Fibrinolytic Balance Favourably and Decreases Plasma Fibrinogen in Hypertriglyceridaemic Men
23 hypertriglyceridaemic men took 4g/day of niacin for 6 weeks and saw very significant improvements in lipoprotein concentrations (reducing very low density cholesterol and triglycerides by ~50%) as well as reduced blood clotting and thrombosis factors.
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.
Emerging roles of GPR109A in regulation of neuroinflammation in neurological diseases and pain
Summary of GPR109A (niacin receptor) role in inflammation of the nervous system, especially the brain, and how activation of GPR109A plays a role in healing may conditions such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, stroke, and pathological pain.
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.
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.
The β-hydroxybutyrate receptor HCA2 activates a neuroprotective subset of macrophages
Nicotinic acid mimics the effect of a ketogenic diet in activating HCA2, which induces a neuroprotective phenotype in bone marrow-derived macrophages that infiltrate the brain and that this results in an improved outcome in a mouse model of stroke.
Plasma acetylcholine and nicotinic acid are correlated with focused preference for photographed females in depressed males: an economic game study
This study showed depressed males have a narrower preference for female photographs (only preferring good looking ones) which is a marker for lower cognitive flexibility. The less nicotinic acid in their body, the narrower their preference. This indicates nicotinic acid may regulate human social decision-making (especially preference-related behaviors) by acting on the HCAR2 in microglia (the resident immune cells of the brain and spinal cord which constantly patrol the cerebral microenvironment to respond to pathogens and damage).
Niacin reduces abdominal fat: pilot study
Participants in an open label study at Kaiser Permanente in San Francisco supplemented ~3g niacin a day. After about 1 year, 81% of patients had an by an average reduction of 27% in intra-abdominal fat. The degree of fat loss was associated with the degree of increase in HDL cholesterol and a reduced Total Cholesterol/HDL cholesterol ratio.
Treatment of Asthma by Nicotinic Acid
Relief of the asthma attacks was obtained in 21 out of 30 cases with niacin either via intravenous injection (16 out of 21 patients relieved) or orally (5 out of 9 patients relieved). A series of 50 or 100 mg doses used. Relapse was common once niacin was discontinued.
Action of nicotinic acid on the reversion of hypoxic-inflammatory link on 3T3-L1 adipocytes
Niacin reduces inflammation caused by low levels of oxygen in tissue that is associated with obesity.
Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis
Niacin, a pharmacological Gpr109a agonist, suppressed colitis and colon cancer in a Gpr109a-dependent manner in mice. Thus, Gpr10a has an essential role in mediating the beneficial effects of gut microbiota and dietary fiber in colon.
Inflammation stimulates niacin receptor (GPR109A/HCA2) expression in adipose tissue and macrophages
Many of the beneficial and adverse effects of niacin are mediated via GPR109, which is highly expressed in adipose tissue and macrophages. Multiple infectious and inflammatory stimuli stimulate GPR109A expression in adipose tissue and in macrophages.
Effects of an oral mixture containing glycine, glutamine and niacin on memory, GH and IGF-I secretion in middle-aged and elderly subjects
42 people drank a 10g mixture of glycine, glutamine and niacin daily for 3 weeks saw an increase in serum growth hormone (GH) levels by 70%, but this GH increase was not associated with improvement in mood or memory. Circulating Insulin-like growth factor 1 (IGF-I) levels did not change.
Activation of Gpr109a, Receptor for Niacin and the Commensal Metabolite Butyrate, Suppresses Colonic Inflammation and Carcinogenesis
GPR109A expressed in immune cells as well as in colonic tissue is necessary for protection against colitis and colon carcinogenesis. Niacin suppresses colitis and colon cancer in a GPR109A-dependent manner. GPR109A is key in mediating the beneficial effects of gut microbiota and dietary fiber in colon. Niacin suppresses atherosclerosis by activating GPR109A in immune cells. GPR109A mediates butyrate effects in colon and is a critical molecular link between colonic bacteria and dietary fiber and the host.
Niacin Reverses Migratory Macrophage Foam Cell Arrest Mediated by oxLDL In Vitro
Oxidized Low Density Cholesterol, oxLDL induced inhibition of macrophage migration may be reversed by Niacin, which explains part of Niacin's atheroprotective effects on cardiovascular disease independent of its effects on plasma lipids. Macrophage foam cells are a type of macrophage that localize to fatty deposits on blood vessel walls. Niacin also inhibited the formation of peroxynitrite (which is a powerful oxidant exhibiting a wide array of tissue damaging effects)
Anti-inflammatory effects of nicotinic acid
Niacin has multi-faceted anti inflammatory properties that act in both localized and systemic ways. A major area of its activity is in tissue related to fat storage via the GPR109A receptor. Dosing cells with TNF-alpha ( an inflammatory substance ) showed that niacin treated cells increased the atheroprotective hormone adiponectin and reduced macrophage chemotaxis
Niacin attenuates the production of pro-inflammatory cytokines in LPS-induced mouse alveolar macrophages by HCA2 dependent mechanisms
Explores protective effect of niacin on lung tissue by dosing mouse lung white blood cells with niacin and exposing them to inflammatory toxins (Lipopolysaccharides). This demonstrated strong anti-inflammatory effects of niacin ( reduced levels of TNF-α, IL-6 and IL-1β) and that the protective effect depends on expression of GPR109A.
Niacin attenuates lung inflammation and improves survival during sepsis by downregulating the nuclear factor-κB pathway
Rats injected with e coli bacteria to induce lung inflammation survived better with high dose (~1% of diet) niacin supplementation. The reduced lung inflammation and damage was associated with downregulation of the NF-κB (Nuclear Factor Kappa B) pathway.
The Niacin/Butyrate Receptor GPR109A Suppresses Mammary Tumorigenesis by Inhibiting Cell Survival
The expression of niacin receptor GPR109A is decreased by over 70% in breast cancer samples. It's reduced in early stages, and almost undetectable in advanced stages. Increasing expression of GPR109A seems to act as a tumor suppressor in breast tissue, but interestingly can also acts as tumor protective in other tissues like skin, mechanism of differentiation unknown.
Physiological and Anti-obesity Effects of Melatonin and Niacin Supplements in Rat Models
Rats where given unlimited access to food and a controlled amount of exercise. Those taking niacin + melatonin lost statistically significantly more weight, compared to control, niacin only and melatonin only groups. Suggests a synergy between niacin & melatonin supplementation for anti-obesity. It's noted that mice lacking the niacin receptor GPR109A had progressive weight gain and liver fat accumulation.
Niacin Attenuates Pulmonary Hypertension Through H-PGDS in Macrophages
When mice are induced with pulmonary hypertension via drugs and low oxygen, those on niacin have less severe outcomes, due to enhanced macrophage activity and release of PGD2.
Decreased expression of G-protein-coupled receptors GPR43 and GPR109a in psoriatic skin can be restored by topical application of sodium butyrate
Psoriatic skin has reduced GPR109A expression, topical sodium butyrate increases GPR109A expression in skin and is potentially useful in psoriasis therapy.
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.
Control of brain tumor growth by reactivating myeloid cells with niacin
Niacin treatment of mice bearing intracranial brain tumor initiative cells increased macrophage representation within the tumor, reduced tumor size, and prolonged survival.
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 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.
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.
Melatonin alleviates titanium nanoparticles induced osteolysis via activation of butyrate/GPR109A signaling pathway
Supplementing mice with melatonin increases butyrate production in their gut via bacteria, conversely antibiotics severely impair this butyrate production. When mice are poisoned with titanium nanoparticles to induce bone deterioration, butyrate has a protective effect against bone loss. This protective effect is specifically dependent on the GPR109A receptor that seems to be activated by the butyrate enriched gut microbiota.
Activated niacin receptor HCA2 inhibits chemoattractant-mediated macrophage migration via Gβγ/PKC/ERK1/2 pathway and heterologous receptor desensitization
GPR109A (aka HCA2) is highly expressed in immune cells and together with niacin seems to inhibit proinflammatory aspects of immune cell activity.
Activation of the receptor (Gpr109a) for niacin and the commensal metabolite butyrate suppresses colonic inflammation and carcinogenesis
GPR109A plays an essential role in gut health. GPR109A deficiency worsens colitis and colonic inflammation in mice. GPR109A expression is necessary for immune health. Antibiotics mess up butyrate producing gut bacteria, thus reducing GPR109A.
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.
Niacin fine-tunes energy homeostasis through canonical GPR109A signaling
When fed a high fat diet + niacin, mice deficient in niacin receptor GPR109A got fat and had fatty livers. While mice with normal GPR109A receptors didn't get fat and didn't end up with fatty livers.
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.
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.