English corner. Potential roles of Vit B6 in inflammation and immunity

Potential roles of Vit B6 in inflammation and immunity.
Preventive role of B6 against chronic diseases & downregulation of the inflammatory mediators
Main ideas
·      Preventive role of B6 against chronic diseases. Several diseases are mediated, at least in part, by lower inflammation, possibly through modulation of several kinases. (1)
·      Vit B6 deficiency is associated with lower immune function and higher susceptibility to viral infection. (2) Megadoses do not produce additional benefits after repletion. (3-4) But elderly should benefit from cyclic supplement (with pauses and moderate amounts, aka 50 mg pyridoxamine).
·      Plasma PLP levels were inversely correlated with systemic inflammation markers such as CRP. (5) Vitamin B6 supplementation suppressed IL-6 and increased total lymphocytes in patients with chronic conditions. (6)
·      Vitamin B6 supplementation improved immune function in both human and animal studies. ( 7-8 ) It improves the immune response, causing increased antibody production, and enhances communicative interactions between cytokines and chemokines. (9-11)
·      The authors of this study (0) assume that vitamin B6 is possible to suppress hyperinflammation, at least in part, through NLRP3 inflammasome inhibition, limiting virus spread and cytokine storm. Together with the notion that NLRP3 inflammasome plays a central role in chronic diseases, including CVD, diabetes, and acute viral pneumonia (12–14), the anti-inflammasome effect of vitamin B6 suggest its therapeutic role in reducing the severity of COVID-19 and its complications.
·      Studies indicate that B6-vitamers can reduce superoxide radical and lipid peroxide levels induced by H₂O₂ in vascular endothelial cells (15). Too much sulfites (H₂O₂) exhaust B6 PLP.
·      Pyridoxamine has anti-glycation activity and inhibits the formation of AGEs. (16)
·      It was identified that high-dose vitamin B6 has a global anti-inflammatory effect on lipopolysaccharide-induced inflammation in monocyte/macrophage cells by downregulating the key broad-spectrum inflammatory mediators. (17-18)
Sources and References
0. This post is widely based on this study:
Potential Role of Vitamin B6 in Ameliorating the Severity of COVID-19 and Its Complications
Thanutchaporn Kumrungsee et al. Front. Nutr., 29 October 2020. [Vous devez être inscrit et connecté pour voir ce lien]
1. Novel preventive mechanisms of vitamin B6 against inflammation, inflammasome, and chronic diseases. Peipei Zhang et al. 2020
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Since the late 1990s a number of studies have associated the vitamin with lower risks of chronic diseases such as cardiovascular disease and cancers. Such preventive effects of B6 are considered to be, at least in part, mediated by lower inflammation, possibly through modulation of the [Vous devez être inscrit et connecté pour voir ce lien], sphingosine-1-phosphate, and nuclear factor-kappa B. Recent studies have revealed novel antiinflammatory mechanisms of B6 by inhibition of the NLRP3 [Vous devez être inscrit et connecté pour voir ce lien] and by elevation in the levels of [Vous devez être inscrit et connecté pour voir ce lien] and anserine (antiinflammation, antioxidant, and antiglycation imidazole dipeptides). These findings are of great importance to understand the preventive roles of B6 against chronic diseases. 
2. Vitamin B6 and Immune Competence
Laura C. Rail et al. 2013 [Vous devez être inscrit et connecté pour voir ce lien]
Abstract
Animal and human studies suggest that vitamin B₆ deficiency affects both humoral and cell-mediated immune responses. Lymphocyte differentiation and maturation are altered by deficiency, delayed-type hypersensitivity responses are reduced, and antibody production may be indirectly impaired. Although repletion of the vitamin restores these functions, megadoses do not produce benefits beyond those observed with moderate supplementation. Additional human studies indicate that vitamin B₆ status may influence tumor growth and disease processes. Deficiency of the vitamin has been associated with immunological changes observed in the elderly, persons infected with human immunodeficiency virus (HIV), and those with uremia or rheumatoid arthritis. Future research efforts should focus on establishing the mechanism underlying the effects of vitamin B₆ on immunity and should attempt to establish safe intake levels that optimize immune response.
3. Megadoses do not produce additional benefits after repletion. But elderly should benefit from cyclic supplement. Make pauses and take moderate amounts, aka 50 mg pyridoxamine. If B6 PLP, I would take it 5 days, not the weekend, during 3 weeks. Afterwards reduce the dose to 25 mg or take it every other month if you don’t find the appropriate supplement / dose.
4. Make pause
One banana provides 34 percent of the daily requirement of vitamin B6 (1.3 – 1.7 mg), also called pyridoxine. Dr. Andrew Weil, M.D. But banana contains amines. So if you suffer from excess histamine, moderate the intake. Not every day.
How Do You Get Enough Vitamin B6 From Foods?
Good food sources of vitamin B6 include brewer’s yeast, bananas, cereal grains, legumes, vegetables (especially carrots, spinach and peas), potatoes, milk, cheese, eggs, fish and sunflower seeds. 
Are bananas high in amines?
High levels of biogenic amines may also occur in tomatoes and bananas (tyramine, tryptamine), plums (tyramine), spinach (histamine), and legumes. Ripe banana contains less amine. Histamine is one type of biogenic amine that occurs in many foods. Histamine and other biogenic amines, such as tyramine, putrescine and cadaverine are also compounds formed during the course of fermentation of food or as a consequence of food spoilage.
Higher levels of biogenic amines are toxic and cause symptoms. Certain foods naturally contain high levels of histamine, tyramine and/or other biogenic amines. These include: cheeses (especially ripe cheeses) wine, kefir, dry sausage, fermented meats, sauerkraut, mushrooms, miso and soy sauce, chocolate and yeast …
5. 17. Friso S, Jacques PF, Wilson PW, Rosenberg IH, Selhub J. Low circulating vitamin B6 is associated with elevation of the inflammation marker C-reactive protein independently of plasma homocysteine levels. Circulation. (2001) 103:2788–91. doi: 10.1161/01.CIR.103.23.2788
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6. Huang SC, Wei JC, Wu DJ, Huang YC. Vitamin B 6 supplementation improves pro-inflammatory responses in patients with rheumatoid arthritis. Eur J Clin Nutr. (2010) 64:1007–13.
doi: 10.1038/ejcn.2010.107 [Vous devez être inscrit et connecté pour voir ce lien] | [Vous devez être inscrit et connecté pour voir ce lien] | [Vous devez être inscrit et connecté pour voir ce lien]
7. Ueland PM, McCann A, Midttun Ø, Ulvik A. Inflammation, vitamin B6 and related pathways. Mol Aspects Med. (2017) 53:10–27. doi: 10.1016/j.mam.2016.08.001
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8. Zhang P, Suda T, Suidasari S, Kumrungsee T, Yanaka N, Kato N. Novel preventive mechanisms of vitamin B6 against inflammation, inflammasome, and chronic diseases. In: Vinood BP, editor. Molecular Nutrition. Cambridge, MA: Academic Press (2020). p. 283–99.
doi: 10.1016/B978-0-12-811907-5.00032-4 
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9. Rail LC, Meydani SN. Vitamin B6 and immune competence. Nutr Rev. (1993) 51:217–25. doi: 10.1111/j.1753-4887.1993.tb03109.x
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10. Kunisawa J, Kiyono H. Vitamin-mediated regulation of intestinal immunity. Front Immunol. (2013) 4:189. doi: 10.3389/fimmu.2013.00189
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11. A previous study has implicated the lipid mediator sphingosine 1-phosphate (S1P) in vitamin B6-mediated immune regulation ([Vous devez être inscrit et connecté pour voir ce lien], [Vous devez être inscrit et connecté pour voir ce lien]). S1P regulates cell trafficking, especially cell egress from organized lymphoid tissues in thymus, bone marrow, lymph nodes, and intestinal mucosa ([Vous devez être inscrit et connecté pour voir ce lien]).
12. Liu D, Zeng X, Li X, Mehta JL, Wang X. Role of NLRP3 inflammasome in the pathogenesis of cardiovascular diseases. Basic Res Cardiol. (2018) 113:5. doi: 10.1007/s00395-017-0663-9
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13. Dixit VD. Nlrp3 inflammasome activation in type 2 diabetes: is it clinically relevant? Diabetes. (2013) 62:22–4. doi: 10.2337/db12-1115
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14. Ravi Kumar S, Paudel S, Ghimire L, Bergeron S, Cai S, Zemans RL, et al. Emerging roles of inflammasomes in acute pneumonia. Am J Respir Crit Care Med. (2018) 197:160–71. doi: 10.1164/rccm.201707-1391PP
15. Mahfouz MM, Zhou SQ, Kummerow FA. Vitamin B6 compounds are capable of reducing the superoxide radical and lipid peroxide levels induced by H₂O₂ in vascular endothelial cells in culture. Inter J Vit Nutr Res. (2009) 79:218–29. doi: 10.1024/0300-9831.79.4.218
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16. How Does Pyridoxamine Inhibit the Formation of Advanced Glycation End Products? The Role of Its Primary Antioxidant Activity
DOI: [Vous devez être inscrit et connecté pour voir ce lien] Rafael Ramis et al. 2019
17. Inverse association observed between inflammation markers and vitamin B6 status.
High-Dose Vitamin B6 (Pyridoxine) Displays Strong Anti-Inflammatory Properties in Lipopolysaccharide-Stimulated Monocytes
Kathleen Mikkelsen et al. Biomedicines 2023, 11(9),2578; 
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It was identified that high-dose vitamin B6 has a global anti-inflammatory effect on lipopolysaccharide-induced inflammation in monocyte/macrophage cells by downregulating the key broad-spectrum inflammatory mediators. These include interleukin (IL)-6, IL-1β, TNF-α, NF-κB, and Toll-like receptor (TLR)-4. The evidence from this study suggests that high-dose vitamin B6 may be useful as a broad-spectrum anti-inflammatory agent and a possible adjunct to current anti-inflammatory treatments. Namely in arthrosis.
18. Higher vitamin B-6 intakes might be of value in preventing inflammation and maintaining vitamin B-6 adequacy when inflammation is present.
Inflammation increases the need for vitamin B-6
Vitamin B-6 Intake Is Inversely Related to, and the Requirement Is Affected by, Inflammation Status.
Preventing inflammation is important because several chronic diseases of considerable public health importance are characterized by chronic inflammation ([Vous devez être inscrit et connecté pour voir ce lien]). 
MS Morris et al. 2010 Jan; 140(1): 103–110. doi: [Vous devez être inscrit et connecté pour voir ce lien]
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18. Inflammation, vitamin B6 and related pathways 
a) Magne Ueland et al. DOI: [Vous devez être inscrit et connecté pour voir ce lien]
Vitamin B6 may serve as a co-factor in pathways producing metabolites with immunomodulating effects
b) Other diseases, such as rheumatoid arthritis, are associated with reduced vitamin B6 levels. Simonetta Friso et al. June 2001
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It is likely that low levels of PLP may reflect a higher utilization of the coenzyme in an underlying inflammatory process, rather than a defective intake or excessive vitamin B₆ catabolism.
c) Sakakeeny L, et al. Plasma pyridoxal-5-phosphate is inversely associated with systemic markers of Inflammation in a population of U.S. adults. J Nutr 142:1280-5, 2012.
Conclusion — The relationship between inflammation and low B6 status may partially explain the findings of previous epidemiological studies.