Low Toxin Supplements Unlike niacin(nicotinic acid), nicotinamide does not activate NIACR1/HCA2

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"HCA2 binds and thereby is activated by D-β-hydroxybutyric acid, butyric acid, and niacin (also known as nicotinic acid).β-Hydroxybutyric and butyric acids are regarded as the endogenous agents that activate HCA2. Under normal conditions, niacin's blood levels are too low to do so: it is given as a drug in high doses in order to reach levels that activate HCA2"

Niacin is an NAD+ precursor which when converted to NAD+ can alter over 500 enzymatic reactions that play key roles in regulating inflammation, mitochondrion functions, autophagy, and apoptosis

Studies, done mostly in animals and the cells taken from animals or humans, show or suggest that HCA2 functions to 1) inhibit lipolysis and 2) inhibit inflammation and thereby suppress the development of certain diseases in which inflammation contributes to their development and/or severity. These diseases include: atherosclerosis, stroke, Alzheimer's disease, Parkinson's disease, multiple sclerosis, pathological pain (i.e. pain due to the abnormal activation of neurons), mastitis, hepatitis due to heavy alcohol consumption, inflammatory bowel diseases, cancer of the colon, and, possibly, psoriasis and brain damage due to heavy alcohol consumption.

HCA2 is expressed by: 1) certain cells in the immune system, e.g., neutrophils, monocytes, macrophages, dermal dendritic cells,[18] and lymphocytes;[13] 2) cells in the small intestine and colon epithelum that face the intestinal lumen;[26] 3) the skin's epithelial cells, keratinocytes, and Langerhans cells;[27] 4) brown and white adipose tissue fat cells;[28] 5) cells in the mammary gland's epithelium;[20] 6) hepatocytes; 7) multinucleated osteoclasts in bone tissues; 8) kidney podocytes;[13] and 9) cells in the nervous system, e.g., microglia cells in the brain's cerebral cortex and hippocampus,[24] cells in the eye's retinal pigment epithelium,[29][30] the astrocytes and neurons in the brain's rostral ventrolateral medulla, and the peripheral nervous system's Schwann and satellite glial cells.


So other than supplementing nicotinic acid, this receptor is also activated by fasting states and healthy gut bacteria breaking down fermentable fiber. The health benefits seem endless...I remember Abram Hoffer when asked of the health benefits of nicotinic acid he replied it would be quicker to list the things it doesn't do!!

Anyway this is just from wiki that I found interesting, it seems all the health benefits people report on fasting is due to activating this receptor and curing all matter of ailments. Haven't seen much mention of this receptor on here so thought i'd start a thread.

 

[charlie]

Niacin is life. Thank you for sharing.

 

[cfeehan]

Studies, done mostly in animals and the cells taken from animals or humans, show or suggest that HCA2 functions to 1) inhibit lipolysis

As someone who packed on the pounds on the general principles of Ray Peat style eating (yes, I know...it was never a 'diet' but dairy, table sugar and tropical fruit I now know are not my friends), I used to cringe when I saw the phrase "inhibits lipolysis" being discussed as a good thing.

But I do remember Haidut stressing that it was "excessive lipolysis" that was the problem - the runaway scary type that often hits older folks and turns them into what Garrett Smith would call an 'Under'.' There a big difference between the every-day lipolysis that will just help you slim down a bit vs. that 'excessive lipolysis' wasting state.

I'm just sharing that for others who may also be struggling with weight issues as a reminder to not skip something that could be very helpful just because of that phrase (it's a mistake I used to make in the past).

 

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Microglia are key cells in overall brain maintenance—they are constantly scavenging the CNS for plaques, damaged or unnecessary neurons and synapses, and infectious agents.[7] Since these processes must be efficient to prevent potentially fatal damage, microglia are extremely sensitive to even small pathological changes in the CNS.[8] This sensitivity is achieved in part by the presence of unique potassium channels that respond to even small changes in extracellular potassium.

Accounting for approximately 10–15% of all cells in the brain, microglia have long been known to act as macrophages, the first line of immune defense, within the central nervous system by actively surveying their surrounding microenvironment (Nimmerjahn et al., 2005; Bachiller et al., 2018; Chen et al., 2018; Muzio et al., 2021). Microglial cells are activated upon the stimulation of a host of pro-inflammatory receptors, including chemokine receptors (CX3CR1), purinergic receptors (P2X4R, P2X7R, P2Y12, P2Y13), Toll-like receptor 4 (Kobayashi et al., 2008; Taves et al., 2013; Tsuda et al., 2013; Grace et al., 2014), and colony-stimulating factor 1 receptor (Guan et al., 2016; Yan et al., 2017). Activation of such receptors results in the production of pro-inflammatory mediators and microglial proliferation (Kobayashi et al., 2008; Taves et al., 2013; Tsuda et al., 2013; Grace et al., 2014; Guan et al., 2016; Yan et al., 2017). Much less is known about the anti-inflammatory receptors expressed on microglial cells. Emerging studies indicate that G-protein-coupled receptor 109A (GPR109A), an anti-inflammatory G-inhibitory (Gi) protein-coupled receptor, regulates neuroinflammation in neurological diseases and chronic pain by regulating microglial activation

Hydroxycarboxylic acid receptor 3 (HCA3), also known as niacin receptor 2 (NIACR2) and GPR109B

 

[purple pill]

As someone who packed on the pounds on the general principles of Ray Peat style eating (yes, I know...it was never a 'diet' but dairy, table sugar and tropical fruit I now know are not my friends), I used to cringe when I saw the phrase "inhibits lipolysis" being discussed as a good thing.

But I do remember Haidut stressing that it was "excessive lipolysis" that was the problem - the runaway scary type that often hits older folks and turns them into what Garrett Smith would call an 'Under'.' There a big difference between the every-day lipolysis that will just help you slim down a bit vs. that 'excessive lipolysis' wasting state.

I'm just sharing that for others who may also be struggling with weight issues as a reminder to not skip something that could be very helpful just because of that phrase (it's a mistake I used to make in the past).

Yeah that used to annoy me too while reading about all the benefits of niacin and aspirin. I seem to be dropping weight pretty easy on a low toxin diet though while still taking niacin at night. I'm guessing just taking the load of the liver allows the body to dig in to the fat stores a lot easier not having too worry too much about liberating toxins from them.

 

[purple pill]

On Cancer:

Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a family of transcription factor protein complexes that controls transcription of DNA, cytokine production and cell survival. NF-κB is found in almost all animal cell types and is involved in cellular responses to stimuli such as stress, cytokines, free radicals, heavy metals, ultraviolet irradiation, oxidized LDL, and bacterial or viral antigens. NF-κB plays a key role in regulating the immune response to infection. Incorrect regulation of NF-κB has been linked to cancer, inflammatory and autoimmune diseases, septic shock, viral infection, and improper immune development. NF-κB has also been implicated in processes of synaptic plasticity and memory.
NF-κB is widely used by eukaryotic cells as a regulator of genes that control cell proliferation and cell survival. As such, many different types of human tumors have misregulated NF-κB: that is, NF-κB is constitutively active. Active NF-κB turns on the expression of genes that keep the cell proliferating and protect the cell from conditions that would otherwise cause it to die via apoptosis. In cancer, proteins that control NF-κB signaling are mutated or aberrantly expressed, leading to defective coordination between the malignant cell and the rest of the organism. This is evident both in metastasis, as well as in the inefficient eradication of the tumor by the immune system

Niacin:

GPR109A/butyrate suppresses nuclear factor-κB activation in normal and cancer colon cell lines as well as in normal mouse colon. These studies show that GPR109A mediates the tumor-suppressive effects of the bacterial fermentation product butyrate in colon. [Cancer Res 2009;69(7):2826–32]

. GPR109A is expressed in normal colon but is silenced in colon cancer. This phenomenon is also seen in colon cell lines; normal cell lines express the receptor whereas cancer cell lines do not. Activation of the receptor in normal colon cells does not induce cell death. However, when the receptor is expressed ectopically in colon cancer cells, activation of the receptor with butyrate or other ligands leads to apoptosis

Because our studies show that inhibition of DNA methylation in colon cancer cells induces GPR109A expression and that activation of the receptor causes tumor cell–specific apoptosis, the efficacy of DNA methylation inhibitors in the treatment of colon cancer might be enhanced by cotreatment with GPR109A ligands such as nicotinate.

The present studies show that GPR109A functions not only as a tumor suppressor but also as a blocker of LPS-induced NF-κB activation. The NF-κB signaling pathway plays a critical role in colonic inflammation as well as in inflammation-induced cancer (39). Our present findings suggest that butyrate mediates the protective effects of gut bacteria against inflammatory bowel disease by serving as a ligand for GPR109A

GPR109A Is a G-protein–Coupled Receptor for the Bacterial Fermentation Product Butyrate and Functions as a Tumor Suppressor in Colon

Abstract. Short-chain fatty acids, generated in colon by bacterial fermentation of dietary fiber, protect against colorectal cancer and inflammatory bowel disease. Among these bacterial metabolites, butyrate is biologically most relevant. GPR109A is a G-protein–coupled receptor for nicotinate...

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