Unfolded Protein Response and A Possible Treatment for CFS

[Tunguska]

More correctly : We must know the proportion of people that have tried the full regimen and they've seen results as opposed to the number of people that have tried the regimen and saw no effect.

I'd already tried virtually everything you've listed in different patterns, except for TUDCA, so have not much reason to adhere to it.

I tried TUDCA for a month recently and it does help provide energy, surprisingly. It's no cure but I would say, I don't know, a good 20%-30% depending on which specific symptom we're talking about. No drastic mental or physical effect but simply increased energy and mental endurance (for someone otherwise broken, that is). I would call it similar to ubiquinol back when that worked. In addition, appears to assist eye health.

I'm not taking it alone but most of the others I rotate and none are new.

I guess that T4->T3 conversion would be the reason it's noticeable for me.

My only concern is the highly sketchy quality of the supplements. Price is not great.

 

[mariovitali]

I'd already tried virtually everything you've listed in different patterns, except for TUDCA, so have not much reason to adhere to it.

I tried TUDCA for a month recently and it does help provide energy, surprisingly. It's no cure but I would say, I don't know, a good 20%-30% depending on which specific symptom we're talking about. No drastic mental or physical effect but simply increased energy and mental endurance (for someone otherwise broken, that is). I would call it similar to ubiquinol back when that worked. In addition, appears to assist eye health.

I'm not taking it alone but most of the others I rotate and none are new.

I guess that T4->T3 conversion would be the reason it's noticeable for me.

My only concern is the highly sketchy quality of the supplements. Price is not great.

OK, Thanks for the update @Tunguska

Some questions :

-Have you taken supplements according to your SNPs or just tried randomly supplementing with -say- Choline and Inositol then TUDCA then using Methylation supplements etc etc.

I am asking this because of what you said here :

I'd already tried virtually everything you've listed in different patterns, except for TUDCA, so have not much reason to adhere to it.

-Have you checked your Liver thoroughly?

-Can you send me a CSV with your SNPs that are listed in the latest PDF Document i sent?

-Finally what are your symptoms and what kind of supplements are you are using?


@all

I started doing personal consultations with a couple of people (under their Doctor's supervision). I do not charge anything of course.

I keep finding interesting things such as "intermediate metabolites" and how -for example ubiquinol- can help. I also started NAC. This previously would be problematic but now i feel nothing. Nevertheless i believe that NAC is a good addition because of its Glutathione-boosting qualities.

I will keep you all updated on how these two people are doing and i will also ask them to write here.

I recently done a nutrahacker test and whatever they list in their suggestions is very close to what i am doing (apart from TUDCA).

My current regimen is as follows :

08:00 : Metafolin, FMN, Dibencozide
09:00 : Magnesium, Taurine, Niacin, Pantothenic Acid, Biotin, Thiamine, Manganese, Molybdenum, Zinc
10:00 Phosphatidylserine, Alpha GPC, Ubiquinol (for intermediate metabolites)
12:00 TUDCA, P5P, Selenium
14:00 D-Limonene (for boosting Phase I, Phase II detox)
15:00 NAC
16:00 Vitamin C, Vitamin K
20:00 Phosphatidylserine, Alpha GPC,Selenium
24:00 TUDCA

I want to drop TUDCA (second attempt) and will try doing so soon (mainly because of cost)

 

[ahmo]

@mariovitali I've just replaced Ubiquinol w/ MitoQ, as part of the MitoQ study. I'm not actually on the study arm, which means that I don't have a placebo, and I got the expensive MitoQ half price for 6 weeks. Just finishing a week, it appears to significantly reduce my oxidative stress, and my nearly insatiable need for antioxidants. If I continue to have such good results, I'll be willing to continue on with it at full price after the trial.

 

[mariovitali]

@mariovitali I've just replaced Ubiquinol w/ MitoQ, as part of the MitoQ study. I'm not actually on the study arm, which means that I don't have a placebo, and I got the expensive MitoQ half price for 6 weeks. Just finishing a week, it appears to significantly reduce my oxidative stress, and my nearly insatiable need for antioxidants. If I continue to have such good results, I'll be willing to continue on with it at full price after the trial.

That's great @ahmo.


To be honest i tried Mito-Q without any positive results. However at the time i tried it i had several other problems (mainly because i hadn't addressed other important aspects of CFS).

Since the cost of Mito-Q is quite high i will not be trying it out. OTOH i do recall that the Research behind it appeared to be convincing.

May i ask how you feel from a scale of 1 to 10 at the moment? (10 being best)

 

[ahmo]

May i ask how you feel from a scale of 1 to 10 at the moment? (10 being best)

oh dear...how do i feel...how about 5-6. why do I find this a difficult question? MitoQ has let me decrease antioxidants, which for me means less carrots and seed/nut mix. I don't know why my body has settled on this duo for the ongoing oxidative stress symptoms, but, along w/ acai these are my go-to response to the headachey, irritable symptoms. So I'm delighted to decrease my caloric intake. And my recovery seems to be improved. Has this *cured* me or made me feel normal? no. just more comfortable.

 

[Gondwanaland]

Finding my way thru the darkness:

Be Wary of These Supplements
Histamine producing bacteria:

• L casei (R)
• L reuteri (R)
• L bulgaricus (R)

DAO Inhibitors:

• Alcohol (R)
• Curcumin (R)
• Cimetidine (R) – an antihistamine

Other:

• Inositol
• NAG
• Sialic acid
• Supplements that decrease Th1/Increase Th2

 

[mariovitali]

Finding my way thru the darkness:

Hmm, so it seems that Inositol mobilizes Calcium. That is not good -at least for ER Stress that is- so it is great that you pointed this out.

I do not take any of these Supplements at the moment. I stopped Curcumin a long time ago, plus i also discovered that Curcumin inhibits Phase I detox (but induces Phase II).

Thanks @Gondwanaland !

 

[op2pig]

OK, Thanks for the update @Tunguska[/USE

I recently done a nutrahacker test and whatever they list in their suggestions is very close to what i am doing (apart from TUDCA).

My current regimen is as follows :

08:00 : Metafolin, FMN, Dibencozide
09:00 : Magnesium, Taurine, Niacin, Pantothenic Acid, Biotin, Thiamine, Manganese, Molybdenum, Zinc
10:00 Phosphatidylserine, Alpha GPC, Ubiquinol (for intermediate metabolites)
12:00 TUDCA, P5P, Selenium
14:00 D-Limonene (for boosting Phase I, Phase II detox)
15:00 NAC
16:00 Vitamin C, Vitamin K
20:00 Phosphatidylserine, Alpha GPC,Selenium
24:00 TUDCA

I want to drop TUDCA (second attempt) and will try doing so soon (mainly because of cost)

@mariovitali, shallow question, but if you remove TUDCA from the regime does that mean it's okay to consume alcohol on the protocol moderately.... or is alcohol pretty much hands off across the board with any variant of this protocol?

I'd like to start this protocol after the new year and add, in doing so, increase the participant N values. I am waiting to get my 23andMe results back; I'm also waiting to get the results back from a comprehensive Methylation test to benchmark my levels pre-protocol. (It would be great to compare this after the protocol).

Glad to hear that others have tried this protocol and are seeing results.

CHEERS!

 

[Gondwanaland]

lus i also discovered that Curcumin inhibits Phase I detox (but induces Phase II).

It was me who told you that

Mario, my issues are obviously autoimmune, which trigger inflammation histaminosis etc.

I suspect if I crack this Th1 Th2 Th17 code I might stop chasing my tail... Plus I believe it might help anyone here, since if one takes the same supplements on and on and on it is possible to switch the Th domination (for the better AND for the worse)

• Supplements that decrease Th1/Increase Th2

 

[mariovitali]

It was me who told you that

Haaahaha, Well it seems my memory didn't quite improve as much i thought! Exactly right!

Mario, my issues are obviously autoimmune, which trigger inflammation histaminosis etc.

I suspect if I crack this Th1 Th2 Th17 code I might stop chasing my tail... Plus I believe it might help anyone here, since if one takes the same supplements on and on and on it is possible to switch the Th domination (for the better AND for the worse)

I *strongly* believe that the solution lies to boosting your Glutathione levels : Have you tried taking NAC?

Intracellular glutathione redox status in human dendritic cells regulates Th1/Th2 balance through IL-12 and IL-27 production
Kunio Dobashi, Yosuke Kamide, Mitsuyoshi Utsugi, Akihito Ono, Tamotsu Ishizuka, Takeshi Hisada, Yasuhiko Koga, Masatomo Mori
DOI: Published 1 September 2012

• Article
• Info & Metrics
• PDF

Abstract
Glutathione redox status, changes in intracellular reduced (GSH) or oxidized (GSSG) glutathione, plays a significant role in cellular function. We examined whether intracellular glutathione redox status in human dendritic cells (DCs) regulates the production of polarizing signals, such as IL-27, IL-12, and Th1/Th2 responses.

Human PBMCs were obtained from healthy adult volunteers, and monocyte-derived DCs (MD-DCs) were generated from PBMCs. MD-DCs treated with glutathione reduced form ethyl ester (GSH-OEt) or L-buthionine-(S,R)-sulfoximine (BSO) were stimulated by LPS, and the levels of Th1 and Th2 cytokines were measured. Then, DCs matured by LPS or TSLP were cocultured with allogeneic CD4(+) naive T cells and Th1/Th2 balance was evaluated.

Monocyte-derived DCs exposed to GSH-OEt and BSO had increased and decreased intracellular GSH contents, respectively. LPS-induced IL-27 and IL-12 production was enhanced by GSH-OEt and suppressed by BSO. Mature GSH-OEt-treated MD-DCs enhanced interferon (IFN)-γ production from CD4(+) T cells compared with nontreated MD-DCs, and siRNA against IL-27 and anti-IL-12 mAb suppressed the effect of GSH-OEt on IFN-γ production. Although human myeloid DCs activated by TSLP (TSLP-DCs) prime naïve CD4(+) T cells to differentiate into Th2 cells, treatment of TSLP-DCs with GSH-OEt reduced IL-13 production and enhanced IFN-γ production by CD4(+) T cells. Interleukin-27 p28 siRNAs and anti-IL-12 mAb attenuated the inhibitory effect of GSH-OEt on Th2 polarization.

These results indicate that Th1 and Th2 balance are controlled by intracellular glutathione redox status in DCs through the production of IL-27 and IL-12.

EDIT : After putting Th1/Th2 to my software i got this. Notice that RAR and RXR are towards the top of the list

*********Topic : th1/th2 ***************
th1th2.csv : 97.51 %
il_10.csv : 2.14 %
pbmc.csv : 1.14 %
immune_response.csv : 0.75 %
stat1.csv : 0.41 %
mcp-1.csv : 0.37 %
probiotics.csv : 0.31 %
inflammatory_response.csv : 0.23 %
hpa_axis.csv : 0.18 %
inducible_nos.csv : 0.13 %
rar.csv : 0.13 %
rxr.csv : 0.12 %
hypobaric_hypoxia.csv : 0.11 %
mast_cell_activation.csv : 0.11 %
crohns_disease.csv : 0.10 %
microbiome_humans.csv : 0.10 %
dhea.csv : 0.09 %
p450scc.csv : 0.09 %
zinc_supplementation.csv : 0.09 %
gut.csv : 0.08 %
sulforaphane.csv : 0.08 %
cox-2.csv : 0.08 %
glycoproteins.csv : 0.07 %
histamine.csv : 0.07 %
glucocorticoid_receptor.csv : 0.07 %
omega3.csv : 0.07 %
cannabidiol.csv : 0.07 %
cortisol_levels.csv : 0.07 %
adrenergic_receptor.csv : 0.06 %
cortisol.csv : 0.06 %
thioredoxin.csv : 0.06 %
nac.csv : 0.06 %
heat_shock_protein.csv : 0.06 %
sinusitis.csv : 0.06 %
microglia.csv : 0.06 %
hmgb1.csv : 0.06 %
ginkgo.csv : 0.06 %
hmgcoa.csv : 0.06 %
bdnf.csv : 0.05 %
resveratrol.csv : 0.05 %
ebv.csv : 0.05 %
nrf2.csv : 0.05 %
reactive_metabolites.csv : 0.05 %
selenium_deficiency.csv : 0.05 %
gluten.csv : 0.05 %
gsh.csv : 0.05 %
redox_regulation.csv : 0.04 %
vcam-1.csv : 0.04 %
irritable_bowel.csv : 0.04 %
ckd.csv : 0.04 %
liver_disease.csv : 0.04 %
reduced_glutathione.csv : 0.04 %
misfolded_proteins.csv : 0.04 %
liver_injury.csv : 0.04 %
testosterone_production.csv : 0.04 %
human_proteinuria.csv : 0.04 %
biliary_cirrhosis.csv : 0.04 %
hsp70.csv : 0.04 %
ggt.csv : 0.04 %
rituximab.csv : 0.04 %
oxidative_stress_markers.csv : 0.03 %
endothelial_nos.csv : 0.03 %
advanced_glycation_end.csv : 0.03 %
hgh.csv : 0.03 %
vitamin_d3.csv : 0.03 %
cyp3a4.csv : 0.03 %
ros.csv : 0.03 %
glutamine.csv : 0.03 %
oxidative_stress_protection.csv : 0.03 %
selenium.csv : 0.03 %
curcumin.csv : 0.03 %
peroxiredoxin.csv : 0.03 %
histone_deacetylase.csv : 0.03 %
sirt1.csv : 0.03 %
ngf.csv : 0.03 %
astrocytes.csv : 0.03 %
nafld.csv : 0.03 %
neuronal_nos.csv : 0.03 %
n-acetylglucosamine.csv : 0.02 %
acetylation.csv : 0.02 %
cimetidine.csv : 0.02 %
pdhc.csv : 0.02 %
glycosylation.csv : 0.02 %
l_tryptophan.csv : 0.02 %
sod1.csv : 0.02 %
hepatotoxicity.csv : 0.02 %
acetylcholine.csv : 0.02 %
nachr.csv : 0.02 %
phosphorylation.csv : 0.02 %
ubiquitination.csv : 0.02 %
l-arginine.csv : 0.02 %
upr.csv : 0.02 %
n-acetyltransferase.csv : 0.02 %
conjugation.csv : 0.02 %
cholestasis.csv : 0.02 %
steatohepatitis.csv : 0.02 %
cyp2d6.csv : 0.02 %
detoxification.csv : 0.02 %
norepinephrine.csv : 0.02 %
glutathione_stransferase.csv : 0.02 %
caloric_restriction.csv : 0.02 %
mastocytosis.csv : 0.02 %
freet3.csv : 0.02 %
hydrogen_sulfide.csv : 0.02 %
cfs.csv : 0.02 %
caspase_human.csv : 0.01 %
phospholipid_human.csv : 0.01 %
glutamate.csv : 0.01 %
calcium_homeostasis.csv : 0.01 %
peroxynitrite.csv : 0.01 %
adrenal_insufficiency.csv : 0.01 %
cofactor.csv : 0.01 %
hepatocytes.csv : 0.01 %
catalase.csv : 0.01 %
choline.csv : 0.01 %
l-cysteine.csv : 0.01 %
insulin_resistance.csv : 0.01 %
triiodothyronine_levels.csv : 0.01 %
nadph.csv : 0.01 %
inositol.csv : 0.01 %
bilirubin.csv : 0.01 %
serotonin_levels.csv : 0.01 %
chaperones.csv : 0.01 %
amyloid.csv : 0.01 %
xanthine_oxidase.csv : 0.01 %
flavoprotein.csv : 0.01 %
chop.csv : 0.01 %
liver_regeneration.csv : 0.01 %
phosphatidylserine.csv : 0.01 %
biotin.csv : 0.01 %
p450.csv : 0.01 %
dysautonomia.csv : 0.01 %
autism.csv : 0.01 %
protease_inhibitor.csv : 0.01 %
insomnia.csv : 0.01 %
iron_deficiency.csv : 0.01 %
sshl.csv : 0.01 %
tau.csv : 0.01 %
p53.csv : 0.01 %
methionine.csv : 0.01 %

I then looked for "Th1/Th2 and RAR and RXR" and got this :

Retinoic acids exert direct effects on T cells to suppress Th1 development and enhance Th2 development via retinoic acid receptors.
Iwata M1, Eshima Y, Kagechika H.
Author information

Abstract
The vitamin A metabolite, retinoic acid (RA), affects Th1 and Th2 development. The effect is partly exerted through the modulation of antigen-presenting cell functions, but it remains unclear whether RA directly exerts its effect on T cells to influence Th1/Th2 development. To clarify this problem, we used two experimental systems with isolated T cells in vitro. In one system, isolated CD4+CD8+ thymocytes differentiated into Th1 and Th2 by two transient stimulations with defined combinations of ionomycin and phorbol myristate acetate followed by treatment with IL-2 and IL-4 and/or IL-12. In the second system, functional differentiation was induced in purified naive CD4 T cells from DO-11.10 TCR-transgenic and RAG-2-deficient mice with cytokines and antibodies to CD3 and CD28. In both systems, all-trans-RA at > or = 1 nM concentrations suppressed Th1 development, but enhanced Th2 development. 9-cis-RA elicited similar effects. The optimal enhancement of Th2 development in the second system, however, was achieved with a delayed addition of RA. The presence of RA during the initial stimulation period often suppressed Th2 development. The RA receptor (RAR) antagonists, LE540 and LE135, but not the retinoic X receptor (RXR) antagonist, PA452, inhibited the effect of RA on Th1/Th2development. Accordingly, the RAR agonists, Am80 and Tp80, but not the RXR agonists, HX600 and TZ335, mimicked the effect of RA. The RXRagonists enhanced the effect of the RAR agonists only slightly, if at all. These results indicate that, via RAR, RA directly suppresses Th1 development and directly enhances Th2 development with its timely addition.

However i would be very cautious with supplementing with Vitamin A. Recall also that if one has a problematic liver, vitamins A,D,E and K are not processed efficiently.

So to recap : I would try minimal amounts of Vitamin A and also a small dose of NAC (say 200 mg) per day to see how it goes.

 

[Gondwanaland]

Thanks a lot for the research, Mario

My point is that anything I take that works, after a while stops working and I decline again

I belive that there is a shift from one Th into another happening, if that is possible

I do have NAC at home and am willing to try it, I just haven't figured out if it is the direction I want

http://selfhacked.com/2014/07/18/supplements-people-th2-dominant/#Top_13_Recommendations

1. NAC/Glutathione sufficiency decreases Th2 (R) and increases Th1 (R). 1 cap 2X a day with breakfast and lunch.

This week I was trialling with P5P and right now I am so much worse

• Vitamin B-6 (R) (Caution: also increase histidine decarboxylase)

 

[mariovitali]

@Gondwanaland

I too had problems with Histamine. If you see through my posts you will find that i had a really nasty case of Urticaria when my CFS/PFS (i believe CFS and PFS is one and the same) has occurred.

I also had Pruritus at several occasions all over my body and also rash across my sides from the armpits down to my waist.

All this is gone and a possible reason could be that i fixed my Liver.


Please see the following Link, it talks about Histamine Intolerance and the Role of Liver in breaking down Histamine :

I have dramatically improved my histamine tolerance, and put my mast-cell activation type symptoms into remission, and dropped by 2/3rds my inflammation markers, by supporting my liver.


And it makes sense that the liver plays a role in histamine intolerance.

Histamine is not just disassembled in the gut by diamine oxidase (DAO). It is also disassembled in the liver by histamine N-methyltransferase (HNMT or HMT) where it is in high concentrations.

Why would HNMT be in the liver? The liver disassembles ALL inflammatory material including histamine released from mast-cells, along with a long list of chemicals manufactured by the body and those ingested.

http://alisonvickery.com.au/what-if-this-was-about-the-liver/

 

[mariovitali]

@mariovitali, shallow question, but if you remove TUDCA from the regime does that mean it's okay to consume alcohol on the protocol moderately.... or is alcohol pretty much hands off across the board with any variant of this protocol?

I would say that dropping Alcohol in any case should be beneficial. Just my opinion of course.

 

[mariovitali]

I think that according to the Theory of this Thread i will add Cipro Toxicity Syndrome to the common theme of developing Chronic Fatigue, Post Finasteride syndrome, Post-Lyme disease syndrome, Post-Accutane Syndrome because of Liver Toxicity.

Please search "Cipro" on the Forum.


Cipro causes Liver Toxicity :

Recurrent drug-induced liver injury (DILI) with ciprofloxacin and amoxicillin/clavulanic.
Moreno L1, Sánchez Delgado J2, Vergara M3, Casas M4, Miquel M5, Dalmau B6.
Author information

Abstract
Ciprofloxacin and amoxicillin/clavulanic are two widely used antibiotics due to their high efficacy and few side effects. While the percentage of hepatotoxicity of these antibiotics is low, their frequent use has led to a progressive increase in the number of cases. Both antibiotics have been associated with a wide variety of hepatotoxic reactions, from a slight rise of transaminases to fulminant hepatitis. Once hepatotoxicity secondary to a drug appears, the first step is to discontinue the drug. Physicians may opt to administer an alternative treatment with a different chemical structure. It should be borne in mind, however, that different chemical structures may also cause recurrent drug-induced liver injuries (DILI). We present the case of a patient who consecutively developed DILI due to ciprofloxacin and amoxicillin/clavulanic.

http://www.ncbi.nlm.nih.gov/pubmed/26541512

and also :

http://livertox.nih.gov/Ciprofloxacin.htm

and here is a case where Cipro permanent side effects where reveresed (to 95%) using Glutathione (=known liver protectant).

A 36 year-old man who was in good health received Cipro for a urinary infection. While on the drug, he developed chronic fatigue, carpal tunnel syndrome, chronic multiple severe neuropathies (peripheral nerve injuries), fibromyalgia, a cardiac arrhythmia requiring a pacemaker, multiple joint pains. After 5 years, he remained disabled.

Despite the severity of these reactions and their close association with having received a fluoroquinolone antibiotic, many of these patients' doctors dismissed the possibility of a fluoroquinolone reaction.

http://www.medicationsense.com/articles/jan_dec_08/toxicity070508.php

 

[Tunguska]

OK, Thanks for the update @Tunguska
Some questions :

-Have you taken supplements according to your SNPs or just tried randomly supplementing with -say- Choline and Inositol then TUDCA then using Methylation supplements etc etc.

I am asking this because of what you said here :
-Have you checked your Liver thoroughly?

-Can you send me a CSV with your SNPs that are listed in the latest PDF Document i sent?

Sorry I can't keep up. My SNPs have provided little useful information except confirm a pattern for medication sensitivity and possibly folate receptor problems. I've stopped looking into them. Genetics and gene expression are guaranteed part of my complications, but they don't show up clearly in SNPs. I use supplements experimentally. My liver has never produced lab results worth writing about. Is there a script to extract the SNPs from a 23andme file?

-Finally what are your symptoms

All of them. I could fill a book.

supplements

Everything from alpha-gpc to individual vitamins to TUDCA to most of what you've listed, I alternate. Add to that beta-alanine, uridine/citicoline, full multivitamin on some days, gelatin + high does taurine, serine, TMG, chromium, copper. I no longer take NAC regularly.

 

[mariovitali]

@Tunguska

Can you tell me how you got Chronic Fatigue?

I am sure you understand that by cycling supplements you are going nowhere. You must use the correct supplements for a given amount of time (say a month) and *then* re-evaluate how you feel.

I also asked you whether you looked thoroughly at your Liver function. Did you have an Ultrasound?

If you want you can send me your DNA Data and i will do the rest for you.

 

[Tunguska]

Can you tell me how you got Chronic Fatigue?

Combination of genetics (surely), gut (likely), accutane (likely), antibiotics (surely), possibly sickness after infection (too far back to pinpoint), and likely other missing diagnoses. Started minimum one decade ago, from all of the above except antibiotics which came to the party later.

I am sure that you understand that by cycling supplements you are going nowhere. You must use the correct supplements for a given amount of time (say a month) and *then* re-evaluate how you feel.

I've done that. I cycle the supplements that had the best effect prior, and others for general nutrition. I notice the benefits of some that expired become noticeable again when cycled. Some are substitutes for each other. These are not the strongest results I've gotten but they are much more sustainable this way. I started alternating taurine and TUDCA after a month of it. $ limits involved.

I also asked you whether you looked thoroughly at your Liver function. Did you have an Ultrasound?

Liver ultrasound multiple occasions, nothing. Enzymes once or twice, nothing.

Will do the genetic data later, can't access my files.

 

[mariovitali]

Please find attached a new version of the document that summarises this Thread

 

[Valentijn]

Please find attached a new version of the document that summarises this Thread

I've taken a quick look at the first SNP which you list as being capable of altering gene function, rs2295639. However, I don't see any research suggesting that that SNP alters gene function. It was looked at in one study regarding cognitive performance, but they found that the SNPs tested had no impact. Is there research elsewhere suggesting that the SNP is at all relevant to MTHFD1?

Additionally, 23andMe and other testing services report SNPs in the forward orientation. Thus the possible results are either C or T, and no one will have G as a result. Hence G should not be listed at the risk allele - and if there is no research showing any risk, the SNP shouldn't be listed at all.

 

[mariovitali]

@Valentijn

We discussed previously about the "lack of Research" so i will not get into this sort of Conversation with you again.

As also discussed : Verba volant, Scripta Manent

Regarding the orientation, Thank you i will fix it.