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SOME NOTES ON HOW NIACIN, C, AND TRYPTOPHAN COUNTER GASTROINTESTINAL COMPLICATIONS:
Without addressing C and T deficits alongside niacin’s as with CNT, the conversion of niacin to NAD+ is likely growing incapable over these unaddressed deficiencies over the life course, given the tissue containing the actual proteins + peptides and thus enzymes upon which these conversions happen (for instance, NAPRT for nicotinic acid to nicotinic acid mononucleotide) becomes itself deficient/wasted away. And this is the case given the fact that tryptophan (with the reducing power support of vitamin C) is the actual precursor substrate chemical constituting the construction (and maintenance, i.e., not wasting away over the life course eventually) of all the body’s tissues. When tryptophan (in conjunction with C) is instead over the life course perpetually trying to make up for the NAD+ requirement in lieu of the needed nicotinic acid supplemented, they are limited away from their other roles including making + maintaining tissue/proteins.
When all three are given together finally, the body should experience a much gentler, more stabilizing effect—what used to feel overwhelming with niacin alone often becomes a warm, calming “reset.” I think with the worst of what niacin (unequipped) was capable of having happened already, she should immediately (or by at least the third dose) realize how much different and pleasant it feels now. Just in case, I would make sure the first few doses at least are after good meal(s) and maybe start a little lower dose (like 40% of a teaspoon-worth of CNT powder, which is around 420 mg niacin level) and build up to comfort (but meanwhile not too slowly). Also, make sure it is completely fully dissolved in ample distilled water, which should make the gastric processing down ideally crisp/to the T.
For IBS and acid reflux specifically, many members have reported:
* Less irritation and bloating as the gut lining heals.
* Better regulation of stomach acid production (not too much, not too little).
* Calmer digestion overall: a big missing piece here was not enough tryptophan available to make enough serotonin to help fully regulate motility.
GPR109A Is a G-protein–Coupled Receptor for the Bacterial Fermentation Product Butyrate and Functions as a Tumor Suppressor in Colon
Activation of Gpr109a, Receptor for Niacin and the Commensal Metabolite Butyrate, Suppresses Colonic Inflammation and Carcinogenesis
Role of HCA2 in Regulating Intestinal and Suppressing Colon Carcinogenesis
https://www.frontiersin.org/journals/immunology/articles/10. 3389/fimmu.2021.606384/full
GPR109a: The Missing Link between Microbiome and Good Health?
Protected/microencapsulated Butyrate has shown efficacy in a few RCTs: https://onlinelibrary.wiley.com/doi/10.1111/j.1463-1318.2012.03152.x, https://www.tandfonline.com/doi/full/10.1080/19490976.2025.2545414, https://pmc.ncbi.nlm.nih.gov/articles/PMC8942000, and https://www.mdpi.com/2077-0383/14/1/6?. But we know butyrate is properly tackled and restored endogenously via ultimately activation of GPR109A by nicotinic acid exogenously (for instance: https://www.mdpi.com/2076-2615/11/8/2186, https://www.mdpi.com/1422-0067/23/15/8332). That is the permanent, causal solution, rather than trying to force butyrate through exogenously for what will be relatively meager effects versus niacin alone (https://cfsremission.com/2017/04/15/real-niacin-improves-ibdibs-and-likely-cfsfm/) and especially CNT. Without the CT parts though in combo with N, just like the enzymes from the tissue that wastes away over the life course leading to downregulation and literal loss, limiting niacin more, the same will be for the GPR109A receptor protein. In turn, the actual recognition and signaling of the inflammation/insult/destruction/damage through the body diminishes as the receptor diminishes in activity/expression/content as the tissues accumulatively get damaged and waste away over the life course. In this way, standalone niacin will also grow unequipped to address IBS (and rectification of gastric motility too, tied into acid reflux I will address below)…
From:
https://www.sciencedirect.com/science/article/pii/S0261561422003843
“A mix of SCFAs (including butyrate) administered into the lumen of the proximal colon of rats stimulated intestinal contractions and shortened intestinal transit; these effects were mediated by an increase in serotonin release into the lumen [55]. Similarly, butyrate treatment rescued the delayed transit time seen in germ-free mice but did not rescue transit time in germ-free mice lacking tryptophan hydroxylase-1, an enzyme involved in serotonin synthesis [56]. This suggests that butyrate is important for maintaining normal colon function by increasing serotonin synthesis and release. Serotonin has also been implicated in visceral perception [57].”
55^: https://journals.physiology.org/doi/full/10.1152/ajpregu.00442.2002
56^: https://journals.physiology.org/doi/full/10.1152/ajpgi.00237.2017
57^: https://gut.bmj.com/content/53/12/1794
And some other relevant ones I will outline below too: https://bpspubs.onlinelibrary.wiley.com/doi/10.1038/sj.bjp.0705762, https://faseb.onlinelibrary.wiley.com/doi/abs/10.1096/fj.14-259598
As with all other enzymatic conversions stemming from tryptophan, vitamin C is also CRITICAL in tryptophan hydroxylase 1 (TPH1) activity (which is rate-limiting for serotonin production) by acting as a reducing agent, to maintain the flow and cycling of the iron, copper, and tetrahydrobiopterin involved in TPH1’s function in synthesizing serotonin from tryptophan –> See here:
https://nyaspubs.onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.1961.tb46120.x, https://pmc.ncbi.nlm.nih.gov/articles/PMC6793230/#:~:text=Protection%20of%20TPH%20from%20DA,DA%20(data%20not%20shown), https://www.sciencedirect.com/science/article/abs/pii/S0006899313013140?via%3Dihub and https://pubs.acs.org/doi/10.1021/acs.jmedchem.4c02342, and https://www.sciencedirect.com/science/article/abs/pii/S0304394019307591. Need niacin (NADP here) meanwhile too: https://www.jstage.jst.go.jp/article/jnsv1954/16/4/16_4_276/_pdf! Of course, we need tryptophan itself too (https://www.pnas.org/doi/full/10.1073/pnas.2000047117… to make the melatonin too: https://jnanobiotechnology.biomedcentral.com/articles/10.1186/s12951-021-00915-3).
Bottom line: niacin via GPR109A restores butyrate properly when production is low as with IBS—while vitamin C and tryptophan stabilize the lining and motility, which in turn enables niacin to do this completely via GPR109A.
As for acid reflux:
Do note the downhill spiral of proton pomp inhibitors to try to “treat” reflux issues first of all: https://pubmed.ncbi.nlm.nih.gov/16167970/, https://pmc.ncbi.nlm.nih.gov/articles/PMC4110863/, and https://flipper.diff.org/app/items/5513.
Here are some relevant human clinical trials showing l-tryptophan supplementation’s beneficial influence on reducing reflux: https://onlinelibrary.wiley.com/doi/10.1111/j.1600-079X.2006.00359.x,
And some studies demonstrating vitamin C’s role: https://onlinelibrary.wiley.com/doi/10.1155/2013/691026, https://www.nature.com/articles/s41416-018-0113-y, and https://jn.nutrition.org/article/S0022-3166%2822%2907107-3/fulltext?.
Lastly, specific clinical report relevant for nicotinic acid: https://isom.ca/wp-content/uploads/2020/01/JOM_2002_17_3_06_Niacin_Nicotinic_Acid_a_Putative_Treatment_for-.pdf.
Further, let’s not forget the anti-inflammatory actions put into work by niacin binding to its GPR109A receptor in counter of destructive inflammation left unchecked to the GI, and remember the mechanism involved:
https://jn.nutrition.org/article/S0022-3166%2822%2907107-3/fulltext?
If you noticed a few things from the above reflux-related literature on CNT, let me point the key theme out:
“protective functions of l-tryptophan possibly involve mobilization of factors such as COX-2 derived PGE2”
“niacin-induced flushing results from COX-1–dependent formation of PGD2 and PGE2 followed by COX-2–dependent production of PGE2.”
In addition, developing human-cell screens and reviews propose HCAR3/GPR109B (the human-specific niacin receptor paralog) as a putative Kynurenic acid (a Trp metabolite) target: https://linkinghub.elsevier.com/retrieve/pii/S0021925819477223 https://www.pnas.org/doi/full/10.1073/pnas.2000430117, and https://www.mdpi.com/1422-0067/25/13/6933.
The core aim of the completely formulated CNT is to prevent tryptophan from being burned to make NAD⁺ by providing nicotinic acid and stabilizing redox/enzymes with vitamin C, while replenishing tryptophan so its structural and neuromodulatory roles recover.
