English corner: B6 leads to decrease of cytokines in neuropathy

Pyridoxine PLP as pain inhibitor in peripheral neuropathy
Efficacy of Vitamin B1, B6, and B12 in Peripheral Neuropathy
People taking a UL dose of 25 mg B6 on a usual way for peripheral neuropathy could have problem or not, depending on the fact that B6 has a half-life of up to 30 days. So repetitive small doses taken over a period of months can accumulate, resulting in high blood concentrations. Too much of a good thing is bad (inverse U-shaped curve benefits with pyridoxine). 
Evidence from the literature [[Vous devez être inscrit et connecté pour voir ce lien]] has shown that chronic intake of high levels of vitamin B6, higher than the recommended dosage, leads to severe and progressive sensory neuropathy accompanied by ataxia or loss of control of bodily movements. 
Note: "Evidence from literature" => Not so evident at the end of this post. 
When people taking medications for treating health problems that increased catabolism of pyridoxine (like epilepsy or chronic lung diseases), they should adapt their treatment in agreement with their therapist. Taking UL B6 is going to change the posology needed.
Apart from effectively reducing homocysteine levels, when targeting the right dose of B6 (in association with [Vous devez être inscrit et connecté pour voir ce lien], [Vous devez être inscrit et connecté pour voir ce lien], not necessarily every day), we should take into account a right window for the degradation of the pyridoxal metabolites to 4-pyridoxic acid. Otherwise, there will be a return of the crank with UL of B6. Expressed in a different way, we need to take breaks to optimize profits. More details will be given on the way to adapt the levels when taking high doses of B6 and the kind of B6 you could manage with.
Vocabulary. UL = Upper Limit.
Can vitamin B6 help with neuropathy?
            There are two sides in the approach (case-studies).
First side: No proof – More studies are needed to elucidate how …
Many studies suggest [Vous devez être inscrit et connecté pour voir ce lien]of neuropathy symptoms in patients suffering from periphery neuropathy (PN) of various etiologies after receiving B6 supplementation.
Indeed, current scientific evidence supports a neurotoxic role of B6 at high level. However, no data about B6 administration as a monotherapy exist, only as part of a combination treatment, usually with other vitamins. In the brain, PLP is required for the synthesis of the neurotransmitters serotonin, norepinephrine, epinephrine, and GABA, and as such is involved in both neuronal excitation and inhibition.
B6 modulates the activity of GABA
PLP is used as a cofactor to synthesize and degrade GABA and modulate its activity. In this way pyridoxine administration facilitates GABA turnover.
PLP is the cofactor for the enzyme glutamate decarboxylase, which converts glutamate (the main excitatory neurotransmitter) into GABA (the main inhibitory neurotransmitter).
B6 as antioxidant and antipain
B6 helps relieve [Vous devez être inscrit et connecté pour voir ce lien](in combination with folic acid): B6 leads to a decrease in IL-6 and TNF-A cytokines, which play an important role in the inflammatory reaction and in joint deterioration due to synovial cell proliferation: Indeed, but a weak level of B6 (cofactor of the synthesis of prostaglandins) can no longer reduce inflammation (B6 is also used for other purposes).
B vitamins are useful in treating neuropathy
B vitamins are useful in treating neuropathy since they support healthy nervous system function. Peripheral neuropathy is sometimes caused by a vitamin B deficiency. Supplementation should include vitamin B1 (thiamine and benfotiamine), B6, and B12. You may choose to take these separately instead of as a B complex. Not necessarily every day (half-live).
How does vitamin B6 reduce inflammation?
Vitamin B6 is anti-inflammatory by reducing the accumulation of sphingosine-1-phosphate in a sphingosine-1-phosphate lysate-dependent manner [2], which is not seen by standard anti-inflammatory drugs.
Monocytes and macrophages are key players in the inflammatory process and are the first line of defense against infection caused by bacteria, viruses, and other microorganisms. Monocytes are particularly sensitive to lipopolysaccharides (LPS), which is the major component of Gram-negative bacteria cell walls. LPS is useful for studying the effects of inflammation in monocytes and macrophages due to the profusion of inflammatory mediators triggered via LPS stimulation. 
Vitamin B6 has been shown to have anti-inflammatory properties, which makes it an interesting nutraceutical agent. Vitamin B6 deficiency is well established as a contributor to inflammatory-related conditions, whilst B6 supplementation can reverse these inflammatory effects.
Here are some downregulated inflammatory key mediators (3) when taking B6 supplementation:
CCL2, CCL5, CXCL2, CXCL8, CXCL10, CCR4, CCR5, CXCR3, IL-1β, IL-5, IL-6, IL-10, IL-18, IL-23-a, TNF-α, CSF2, DDX58, NLRP3, NOD1, NOD2, TLR-1 -2 -4 -5 -7 -8 -9, MYD88, C3, FOXP3, STAT1, STAT3, STAT6, LYZ, CASP-1, CD4, HLA-E, MAPK1, MAPK8 MPO, MX-1, NF-κβ, NF-κβ1A, CD14, CD40, CD40LG, CD86, Ly96, ICAM1, IRF3, ITGAM, and IFCAM2.
Complex regional pain syndrome: A vitamin K dependent entity?
            If you’ve suffered from PN (pain neuropathy) after a fall or a car-accident, peripheral pain (CRPS) may be the result of a deficiency in vitamin K when the metabolism is trying to repair. Osteocalcin is vitamin-K dependent and plays a role in bone formation.
            In case of vitamin K deficiency at the distal site of traumatism, classic inflammation starts. Classic inflammation and neurogenic inflammation, sympathetic dysregulation, which are the pathogenic mechanisms of CRPS, and patchy osteoporosis which occur due to high level of under-carboxylated osteocalcin could not be prevented. (4)
Vitamin C could prevent complex regional pain syndrome type I
            When suffering from excess toxins and low grade inflamed tissues, we need more vitamin C. Analysis of the literature suggests that a daily 500-1000 mg VC supplementation may reduce the onset of CRPS-I in trauma of upper/lower extremities and in orthopedic surgery. (5)
End Point
- When taking high supplement of Vit B6, the type and the way must be taken into account. Otherwise, do not take into account the warning.
No Pyridoxine high dose (PN / PNP). High dose PN is toxic. So, no Pyridoxine HCl.
- PLP is the active form (pyridoxal 5’-phosphate) but too much of a good thing is bad: metabolites in excess from PLP are not well evacuated and are toxic because of aldehydes. The brain will block the passage. Problems will then happen because of a lack of GABA.
- Half-life of PLP and PMP (pyridoxamine) must be taken into account. Let’s say 30 days.
- The dose needed can highly vary. With neuro-sensitive persons, 25 mg every day could be too high after one week reload. Adapt yourself with posology, according to the symptoms (level of inflammation and antioxidant required). Make breaks. E.g. take 20 mg 5 days, the weekend off, during 3 weeks. Then stop for one month (half-life).
- PMP (pyridoxamine) could be a better choice for avoiding side-effects of high dose (> 25 mg) but I haven’t seen such supplements at a lower dose (12 - 20 mg).
Zn status may be important in the regulation of vitamin B6 metabolism
Zinc will be needed in the process. If deficient, it won't function...


Sources and references: See next post.

Sources and References
1. Evidence from the literature leads to PN.
[Vous devez être inscrit et connecté pour voir ce lien]
2. Du, X.; Yang, Y.; Zhan, X.; Huang, Y.; Fu, Y.; Zhang, Z.; Liu, H.; Zhang, L.; Li, Y.; Wen, Q.; et al. Vitamin B6 prevents excessive inflammation by reducing accumulation of sphingosine-1-phosphate in a sphingosine-1-phosphate lyase–dependent manner. J. Cell. Mol. Med. 2020, 24, 13129–13138. [[Vous devez être inscrit et connecté pour voir ce lien]] [[Vous devez être inscrit et connecté pour voir ce lien]]
3.  High-Dose Vitamin B6 (Pyridoxine) Displays Strong Anti-Inflammatory Properties in Lipopolysaccharide-Stimulated Monocytes
[Vous devez être inscrit et connecté pour voir ce lien]  2023
Vitamin B6 deficiency is well established as a contributor to inflammatory-related conditions, whilst B6 supplementation can reverse these inflammatory effects. There is less information available regarding the effects of high-dose vitamin B6 supplementation as a therapeutic agent. This study set out to examine the effects of high-dose vitamin B6 on an LPS-stimulated monocyte/macrophage cell population.
4. Complex regional pain syndrome: A vitamin K dependent entity?
DOI:[Vous devez être inscrit et connecté pour voir ce lien]  2010
5. Vit C supplementation
DOI:[Vous devez être inscrit et connecté pour voir ce lien]  2021
Only one study found no benefit in VC supplementation compared with placebo to prevent CRPS-I. Analysis of the literature suggests that a daily 500-1000 mg VC supplementation may reduce the onset of CRPS-I in trauma of upper/lower extremities and in orthopedic surgery.
6. Efficacy of Vitamin B1, B6, and B12 Forte Therapy in Peripheral Neuropathy Patients
Mar. 2021. [Vous devez être inscrit et connecté pour voir ce lien] M. Silviana, D. et al.
Results: There were 30 patients aged 18 - 65 years, consisted of 70% female and 30% male. The etiology of peripheral neuropathy were idiopathic (40%), CTS (26.7%), DM (23.3%), and HNP (10%). There were significant differences of the VAS scale and TSS at every evaluations.
Conclusion: Administration of VitB1, B6, and B12 forte relieved symptoms of moderate peripheral neuropathy with improvement of VAS and TSS scores
VAS score: [Vous devez être inscrit et connecté pour voir ce lien]
TSS score: Total Symptom Score.