That’s very relevant information to consider. Thanks Mew for posting.
It was part of a Metametrix Organix test. Have since been on Folinic Acid Drops, B12 drops, and tried out B12 injections. Neither of these have brought any improvements of any sort.
Also my homocysteine shows nothing out of the ordinary.
@moonman1, I think taking Folinic Acid is precisely counter productive. Your genotype says that you are not efficient at converting Folic/Folinic Acid into the active form: methlyfolate.
I say counter productive because people on the boards who take the non-active form of folate (Folic/Folinic Acid) get a ‘paradoxical folate deficiency.’ This is all described somewhat in Dr. Van Konynenburg’s talk (3rd part at around 5 minutes in).
iaomt.media.fnf.nu/2/skovde_2011 … Bweburl%7D
As far as B12, what versions are you taking? cyanocobalamin? The CFS/ME groups take on this is is that cyanocobalamin is again an inactive form and requires conversions.
From what I’ve read, when you’ve been deficient for a long time and then start taking active vitamins, it can cause some 'start up symptoms. One example is hypokalemia (low potassium) - as described here:
forums.phoenixrising.me/index.ph … eta.15690/). The people on this board supplement with coconut water and bananas.
I also want to note that I’m not sure these tests prove you don’t have methylation cycle issues. Dr. Van Konynenburg tests different things when talking about methylation cycle.
Honestly, I would just say watch the full 3 part lecture that is linked above.
What does any of this means?
It is all very groundbreaking stuff. Most doctors probably would not even know where to start and how to read these tests.
These are all methylation genes. The red are full mutations. The yellow are SNPs with risk allele. The green are normal/good.
My results really don’t mean anything unless we can compare them to other PFSers results and try to find common mutations…
============================================
[Size=4] ACE Gene[/size]
rs4343 - ACE Del16 (Use this substitute SNP as a very reliable proxy.) (Risk Allele: G)
This enzymes leads to high levels of angiotensin II which causes an increase in aldosterone. High aldosterone leads to increase potassium loss in the urine and increased sodium retention. Animal studies show a correlation between high angiotensin II with increased anxiety and decreased learning and memory. Decreased potassium can lead to fatigue and decreased energy production as cellular membrane activation, particularly for the brain and peripheral nervous system is dependent upon sodium:potassium balance. Blood pressure regulation as well. Low frustration threshold. Increased anxiety. Worsened by stress. An MAO-A mutation makes this worse. The ACE Del16 mutation may have been removed from Yasko’s current genetic tests.
[edit]
[Size=4]COMT Gene[/size]
rs4680 - COMT V158M (Risk Allele: A)
rs4633 - COMT H62H (Risk Allele: T)
rs769224 - COMT P199P (Risk Allele: A)
This gene helps break down dopamine and norepinephrine. A defect will cause higher dopamine due to slower breakdown. Implicated in ADD/ADHD. More susceptible to dopamine fluctuations, therefore mood wings. People without COMT mutations are generally more even tempered.
[edit]
[Size=4]VDR Gene[/size]
rs1544410 - VDR Bsm (Risk Allele: T)
rs731236 - VDR Taq (Risk Allele: G)
rs10735810 - VDR Fok (Risk Allele: T, 23andMe: A)
Vitamin D receptor. VDR Fok is involved with Blood sugar regulation. VDR mutations oppose COMT mutations in the regulation of dopamine levels. A VDR mutation means that a person is less sensitive to methyl group supplement levels. (Mood swings.) A VDR mutation can result in behaviors opposite to a COMT mutation. See Dr. Roberts comments at heartfixer.com/AMRI-Nutrigen … bnormality
[edit]
[Size=4]MAO-A Gene[/size]
rs6323 - MAOA R297R (Risk Allele: T)
Slower breakdown of Serotonin. Can lead to high/low cycling of neurotransmitter. Mood swings, aggressive behaviors. ACE deletions will also increase anxiety and lower frustration thresholds. Because this is on the X chromosome, males will have only one allele.
[edit]
[Size=4]ACAT1 Gene[/size]
rs3741049 - ACAT1-02 (Risk Allele: A)
Plays a major role in ketone body metabolism. Defects cause a 3-ketothiolase deficiency. Yasko believes it will cause an increase in gut bugs (particularly clostridia) as well as elevated fatty acid metabolites.
[edit]
[Size=4] MTHFR Gene[/size]
rs1801133 - MTHFR C677T (Risk Allele: A)
rs1801131 - MTHFR A1298C (Risk Allele: G)
rs2066470 - MTHFR P39P (Risk Allele: A)
MTHFR mutations are the centerpiece of the work by Yasko, Rawlins and others, and is the most important to understand. An MTHFR mutation can starve the entire methylation cycle, which has some very large health impacts.
The C677T mutation is associated with a general set of problems: elevated homocysteine, increase in heart disease, increased stroke, increased deep vein thrombosis, peripheral neuropathy, placental vascular problems (stillbirth), preeclampsia, neural tube defects, cleft lip.
The A1298C mutation is assoicated with a second set of problems: depression, anxiety, irritable bowel syndrome, fibromyalgia, chronic fatigue, migraines, dementia, nerve pain, chizophrenia, parkinson’s, tetrahydrobiopterin (BH4) problems. Although not addressed by Yasko, if your Promethease report includes Gs223 or Gs224, you may have additional BH4 impairment.
A person who is compound heterozygous (a single C677T mutation and a single A1298C mutation, each on a different strand) will see symptoms from both defects, but the symptoms tend to be more severe. Rawlins also believes that blood clots are more prevalent. As bad as that is, a person with a single mutation on one gene and a double mutation on the other can be worse. A person who is compound homozygous (double mutation on both genes) is also worse.
[edit]
[Size=4]MTR Gene[/size]
rs1805087 - MTR A2576G (Risk Allele: G)
Helps produce methionine from homocysteine. Likely needs a methylated B12. A mutation here causes increase function and increased methyl group depletion. This can be made worse by MTRR mutations.
[edit]
[Size=4]MTRR Gene[/size]
rs1801394 - MTRR A66G (Risk Allele: G)
rs10380 - MTRR H595Y (Risk Allele: T)
rs162036 - MTRR L350A (Risk Allele: G)
rs2287780 - MTRR R415T (Risk Allele: T)
rs2303080 - MTRR S257T (Risk Allele: T)
rs1802059 - MTRR A664A (Risk Allele: A)
Necessary to regenerate Methyl-B12 for use by MTR. Mutation can cause shortage, suggesting a need for more B12.
[edit]
[Size=4]BHMT Gene[/size]
rs585800 - BHMT-01 (Risk Allele: T)
rs567754 - BHMT-02 (Risk Allele: T)
rs617219 - BHMT-04 (Risk Allele: C)
rs651852 - BHMT-08 (Risk Allele: A, 23andMe: T)
The product the BHMT gene is central to the ‘short cut’ through the methylation cycle, again helping to convert homocysteine to methionine. The activity of this gene product can be affected by stress, by cortisol levels and may play a role in ADD/ADHD by affecting norepinephrine levels.
Yasko believes that believes BHMT-02 and BHMT-04 play a role in the gut environment. Yasko also believes that BHMT-08 is related to the impact that psychological stress has on a patient’s attention levels.
[edit]
[Size=4]AHCY Gene[/size]
rs819147 - AHCY-01 (Risk Allele: C)
rs819134 - AHCY-02 (Risk Allele: G)
rs819171 - AHCY-19 (Risk Allele: C)
Catalyzes the hydrolysis of AdoHcy to adenosine and homocysteine. AdoHcy hydrolysis serves not only to sustain the flux of methionine sulfur toward cysteine, but is believed also to play a critical role in the regulation of biologic methylations.
[edit]
[Size=4]CBS Gene[/size]
rs234706 - CBS C699T (Risk Allele: A)
rs1801181 - CBS A360A (Risk Allele: T, 23andMe: A)
rs2298758 - CBS I278T (Risk Allele: G)
Limits homocystine into downstream path. People with CBS mutations will need to be careful with sulfur containing supplements. Increased risk for ammonia detoxification issues. Puts a burden on SUOX.
[edit]
[Size=4]SUOX Gene[/size]
rs??????? - SUOX S370S (Risk Allele: C)
This gene product helps to detoxify sulfites in the body. Sulfites are a natural byproduct of the methylation cycle and are also ingested from foods. Made worse with CBS and NOS mutations.
[edit]
[Size=4]NOS Gene[/size]
rs1799983 - NOS-3 D298E (Risk Allele: T)
Helps in the formation of nitric oxide which has a role in ammonia detoxification, oxidative stress, and chemical production. Mutations here are made worse by MTHFR A1298C mutations and CBS mutations. A mutation here is also made worse by a lack of mutations in SUOX.
[edit]
[Size=4]SHMT1 Gene[/size]
rs1979277 - SHMT-1 C1420T (Risk Allele: A)
Helps to shift the emphasis of the methylation cycle toward the building blocks needed for new DNA synthesis and away from the processing of homocysteine to methionine.
moonman – is there a way to tell from a full on mutation that you have in what way it’s doing something for better or for worse. what i am saying is, and sorry i don’t 100% understand interpreting the results yet, but say you have a problem with the NOS gene, would the result say if it’s creating too much precursor, or too little precursor?
or what i am saying is, is there more than one possibilty in waht is wrong with a mutated gene, where it could be difficult to pinpoint how to fix the problem, or is it pretty straight forward? i mean straight forward as in, if you have a mutated gene, all you need is X amt of whatever supplements and hopefully that will help you?
also moonman, do you beleive that PFS or propecia could mutate the gene themselves, or is this all ready a problem beforehand? (as in, nothing can turn them on or off?) i read something in the past that environment stressors could activate or de activate certain gene processes, so I’m wondering if that is a possibilty or not?
thanks.
From what I understand, it depends on what exactly that specific gene is encoded to do. For example, as Droit pointed out, the MTHFR gene encodes to create an enzyme. This enzyme breaks down folate into a more active form. So if you have this mutation then there will be an issue with that enzyme and you will not get enough of the active form of folate. You would need to supplement with 5-MHTF. So to answer your question it just depends on the specific function of the mutated gene.
It is possible that Propecia/Saw Palmetto/any other 5ar inhibitor could cause an epigenetical change, but I dont think I personally believe that happened. Will have to wait for Awors research to know for sure.
I think it is more probable that we all have some sort of genetic commonality, maybe a mutation of some specific gene that made us more likely to “break” once 5ar/androgens/neurosteroids were inhibited. I had a phone conference the other week with William Downs who is a dopamine researcher and this was exactly what he said. He believes that we all had similar genetic predispositions and 5ar inhibitors break our system by over-regulating our systems.
Adding to what I wrote above…and hopefully not hijacking the thread, here is a comment from some a very smart guy who knows his shit…
The thing you need to understand is that it is VERY unlikely that Propecia has caused a mutation of the androgen receptor gene through epigenetics. Past-users would notice a SEVERE wasting in muscle mass, down to levels of the average female. Since this does not appear to be a side effect, it is highly unlikely that Propecia has somehow mutated a gene, through methylation or otherwise. It is much more likely that Propecia has somehow “fried” the neurons in the brains response to androgens, which explains the loss of sex drive and “brain fog”. It’s much more likely a neuronal issue than an AR related one.
Very interesting. This would coincide with post SSRI syndrome. It would also verify the many studies of Finasteride’s neuronal brain effects. Any suggestion what to do about it?
ok he did not take fin. Can you tell me how saw palmetto is different from Fin?
Especially when the official Mew/Awor research proposal states it as a 5ar inhibitor syndrome from all 5ar inhibitors and specifically says saw palmetto, accutane, and finasteride and not only finasteride.
That was interesting to me because saw palmetto is a weaker anti-androgen than fin. My assumption is that saw palmetto is less likely to break the camel’s back that gets one into this state that we’re all investigating. For example, you might need more mutations in the methylation pathway enzymes (methylation pathway is just one hypothetical) to react to saw palmetto.
That might be controversial, but don’t let it upset anyone… we’ve certainly seen saw palmetto cause the same issues as fin.
Droit, if MTHFR was an issue then my homocysteine would be elevated and mine is not.
That statistic sounds familiar, but I don’t remember where from. Just from looking at the link of the folate cycle and the methylation cycle in the below slides (See slide titled ‘Methylation cycle and associated biochemical pathways’), I could see how the methylation cycle could get backed up with a weak folate cycle leading to high homocysteine.
iaomt.media.fnf.nu/networks/iaom … art_1R.pdf
If there is some literature that says homocysteine would be high with your SNP, then maybe at one point in your life it may have been. But these systems are complex and we are deep into an unusual state. What I do know is: from the sequence of your DNA, you have a weak MTHFR - but don’t take offensive, its not too uncommon.
I think a more thorough analysis would have be done of your SNPs to see if your levels fit with the rest of your SNPs.
droit,
Both my C677T’s have mutations, but my A1298C is normal. I’ve had moderately elevated homocysteine, which is why I ran the genetic test.
For the record, I never took saw palmetto, but did take fin for over a year.
Be curious as to your thoughts in folic acid vs. methylfolate vs methylcobalimine supplementation in my case.
kaz, can you tell me your results on this:
CBS C699T snp: rs234706
CBS A360A snp: rs1801181
CBS N212N snp: rs2298758
moonman, per your mutation on CBS A360A:
heartfixer.com/AMRI-Nutrigenomics.htm
you can read more on this particular mutation on the page.
moon, have you tried showing your results to any methylation doctors? or pursued any treatments in this area? it’s obvious some stuff is going on here that is a problem…
kazman,
Thank you for posting this data - I hope we can get more for the others on this forum. My understanding is that if you have C677T (even worst 2 C677Ts), you have to supplement active folate (methylfolate) to have good health - and specifically stay away from folic acid since un metabolized folic acid will compete with methylfolate for receptors.
If you didn’t have PFS, and no other mutation in the methylation pathway than C677T, I don’t know if you have to supplement the active B12s.
However, I’m betting that this late in the game, you and me, have a block in the methylation pathway and thus we need to supplement active B12 to reboot it (the ‘methylation block’ is a working theory).
I started taking methylfolate, Adenosyl-B12 and Methyl-B12 (both B12 as a sublingual in the upper lip for 45 minutes) after I came across the material I linked in viewtopic.php?f=27&t=7178
There is a popular guy on the phoenixrising forum named ‘freddd’ who seems to have the worst collection of methylation pathway genes ever. He said before he figured this out, he neurosystem was a wreck… he couldn’t walk.
Then he started supplementing all the things his body couldn’t activate (B12’s and folate) and he said was like his body woke up.
This thread is very much where I’ve been living the last five months.
Until this week, I suspected my symptoms were caused not by fin, but by CFS/ME. So I spent a lot of time at Phoenix Rising last summer, studying Rich Van Konynenburg and many others studying the methylation cycle. Problems here have been correlated with numerous diseases.
In August, I did the Methylation Panel (and other tests). Most of my folate/SAM cycle intermediates were just below or just above the “low” threshold. Reduced glutathione was under the threshold, while oxidizedwas high-normal. Note that I’m homozygous on MTHFR C677T. (I realize this won’t mean much to most of you, but I’d be happy to talk through it if anyone is interested.)
The bottom line is, when your reduced glutathione level is below threshold, you have a problem. Your body either has too much oxidative stress, or you aren’t producing enough glutathione to counter it. Either now or ten years from now, this will lead to disease. And if you’re homozygous on MTHFR C677T (10% of the population is), you again have a problem worth addressing, which might extend your health.
So I began supplementing, using Rich’s Simplified Methylation Protocol (B12/5-MTHF are the critical components). It had the appearance of helping me pull out of the extreme fatigue I had in June-August. I now mostly have my physical energy back. I’ll probably still re-test in 1-2 months, to see if my levels have improved.
I don’t know if methylation cycle issues are related to PFS or not. On one hand, this cycle has tremendous reach across critical cell functions. On the other, it’s so generalized that my feeling is that it wouldn’t by itself be the genetic differentiator that characterizes us. I think it should be included in any disease’s root cause investigation, but shouldn’t be the only place you look.