138 replies to this topic

[Kingsley]

 

I think the real information that arises from the statistics of genetics is a question that reads something like "how aught I to live happily to best serve myself and humanity given my genetic predisposition and what role do my genetics play in having a fulfilling and productive life?" I'm not military, but studying genetics has made the US Army's "Be all you can be" slogan feel like genius in simplicity. Speaking of novelty, now that we know the Army has it right, they need a symbol that looks as cool and novel as the one the Air Force has (saying stuff like that or thinking down on something because it lacks apparent novelty) would be an example of improper or unproductive use of the novelty gene). Just live it right, it's how we've survived and prospered. Live it wrong and you're into an unknown.

 

 

I do think that sifting through one's gene profile and reflecting on genetic predisposition grants a unique perspective and encourages self-honesty and self-improvement.  I question the degree to which particular SNP's produce a significant effect on personality or behavior, though surely there are at least a handful that do.

 

I recall reading a study on the effects of the val/met COMT SNP on the subjective experience of pleasure.  Those homozygous for the less active version (met/met) reported a dramatically greater feeling of pleasure than those with the more active version (val/val) in response to experiences normally deemed mildly pleasurable.  Val/met people were somewhere in between.  I am met/met and from early childhood have always had a pronounced pleasure response to the oddest little things.  For example just listening to a voice that I find appealing can practically hypnotize me with pleasure.  As can a gentle breeze, certain smells, etc.  I wonder if this subjective experience is tied to my COMT SNP and consider it a gift if so.   

 

 

[world33]

The last time I took a blood test there was no indication of kidney problems. My only abnormal value was the Urea one which was higher than the normal range.
The source where I learnt that hydroxocobalamin is unstable is this page http://www.nutri-spe...es/hfm-b12.html ; not sure whether it is reputable or based on scientific studies but I know that hydroxocobalamin injections have the highest positive impact on me. Let me know how you go if/when you try them.

[YOLF]

 

 

I think the real information that arises from the statistics of genetics is a question that reads something like "how aught I to live happily to best serve myself and humanity given my genetic predisposition and what role do my genetics play in having a fulfilling and productive life?" I'm not military, but studying genetics has made the US Army's "Be all you can be" slogan feel like genius in simplicity. Speaking of novelty, now that we know the Army has it right, they need a symbol that looks as cool and novel as the one the Air Force has (saying stuff like that or thinking down on something because it lacks apparent novelty) would be an example of improper or unproductive use of the novelty gene). Just live it right, it's how we've survived and prospered. Live it wrong and you're into an unknown.

 

 

I do think that sifting through one's gene profile and reflecting on genetic predisposition grants a unique perspective and encourages self-honesty and self-improvement.  I question the degree to which particular SNP's produce a significant effect on personality or behavior, though surely there are at least a handful that do.

 

I recall reading a study on the effects of the val/met COMT SNP on the subjective experience of pleasure.  Those homozygous for the less active version (met/met) reported a dramatically greater feeling of pleasure than those with the more active version (val/val) in response to experiences normally deemed mildly pleasurable.  Val/met people were somewhere in between.  I am met/met and from early childhood have always had a pronounced pleasure response to the oddest little things.  For example just listening to a voice that I find appealing can practically hypnotize me with pleasure.  As can a gentle breeze, certain smells, etc.  I wonder if this subjective experience is tied to my COMT SNP and consider it a gift if so.   

 

 

Hmmm, I'd say I do that too. I love the sound of rain and/or a thunderstorm. It's wonderful! The met/met has higher baseline dopamine, and I'll assume, though I don't remember that you have the some combination of MTHFR and have more sensitivity this stuff? Experiences certainly have novelty value and if you like it for a particular reason you can bump up the association with added catecholamine release if you want to add something to it or use it to form a behavior or fondness. I just make sure I never delude myself into overvaluation. I will stay chemically happy for the most part like this as a positive mindset is always better for learning, but I think we always recognize the underly value of experiences etc. through logical analysis. That part is important. I don't think even oxytocin changes that and I do get ticks occasionally when I'm over experiencing something and the logical "snap to" hits me. Mostly it's pleasure, on some occasion it's pain with a permanent mnemonic association to the novelty... That's why I hated it for a while. But for that we can just build new expectations of novelty from the basic elements and find new and improved inspiration for creating newer and better novel experiences After that, you really never have anything to fret for but rejuvination. I'm also of the opinion that it associates strongly with the desire to live and stay young as does the hightened sensitivity to aging from MTHFR and the novelty of experiencing youth grows stronger the older we get. I'd really like to genotype everyone here and look for what makes us us. It would be a great asset for marketing our movement. There's another novelty

 

I'm afraid my reply might be missing some narrative, it's getting late for me...

The last time I took a blood test there was no indication of kidney problems. My only abnormal value was the Urea one which was higher than the normal range.
The source where I learnt that hydroxocobalamin is unstable is this page http://www.nutri-spe...es/hfm-b12.html ; not sure whether it is reputable or based on scientific studies but I know that hydroxocobalamin injections have the highest positive impact on me. Let me know how you go if/when you try them.

 

Will do, just got the 5mg/day patches. Will be seeing a doctor early next week.

[Kingsley]

 

I will stay chemically happy for the most part like this as a positive mindset is always better for learning, but I think we always recognize the underly value of experiences etc. through logical analysis. That part is important. I don't think even oxytocin changes that and I do get ticks occasionally when I'm over experiencing something and the logical "snap to" hits me.

 

 

Good point, though I'm sure you'd also agree that some experiences have value precisely because of the feeling that they produce.  I think that living a meaningful life depends in large part on the ability to feel that certain experiences are meaningful, not just to recognize their value logically, thus the crippling nature of anhedonia and depression.  Though perhaps the most meaningful experiences are those that appeal to both the emotions and the intellect.
 

[Kingsley]

For that reason I tried Molybdenum and the first pill I tried, only 100MCG (Solgar Brand), I felt like I took Valium withouth side effects, like a wave of relaxation, all my brain fog disappeared. I realised how bad I have been been feeling for such a long time. That means I have been having sulfites sensitivity issues for a long time and it explained why I used to get cramps after drinking most white wines or eating hot dogs which are full of sulfites.

Big update on molybdenum. 

 

As stated in a previous post, I have tried molybdenum in the past with no noticeable effect.  However, I have had it on my mind lately based on this thread.  Lately, I have been feeling absolutely ill after eating and drinking certain things, and I began to speculate that the common denominator may be sulfur (coffee, banana, curcumin, NAC, etc.).

 

Anyway, on a long shot I tossed back a molybdenum, and WOW: almost instantly the sick feeling went away and I felt more energy and mental clarity.  Plus, my hands, which are usually cold, became dramatically warmer, red, and rosy (almost splotchy), indicating improved circulation.  Haven't had a problem with sulfur-containing foods/supplements since then.

 

I suspect that I was overloading on sulfur from the sulfur-containing supplements that I have been taking (NAC, curcumin, quercetin) and may have depleted my molybdenum stores thus impairing my sulfur metabolism.  Anyway, it's an interesting turn of events for me and I'm glad this thread made me think of molybdenum.    

[world33]

For that reason I tried Molybdenum and the first pill I tried, only 100MCG (Solgar Brand), I felt like I took Valium withouth side effects, like a wave of relaxation, all my brain fog disappeared. I realised how bad I have been been feeling for such a long time. That means I have been having sulfites sensitivity issues for a long time and it explained why I used to get cramps after drinking most white wines or eating hot dogs which are full of sulfites.

Big update on molybdenum. 
 
As stated in a previous post, I have tried molybdenum in the past with no noticeable effect.  However, I have had it on my mind lately based on this thread.  Lately, I have been feeling absolutely ill after eating and drinking certain things, and I began to speculate that the common denominator may be sulfur (coffee, banana, curcumin, NAC, etc.).
 
Anyway, on a long shot I tossed back a molybdenum, and WOW: almost instantly the sick feeling went away and I felt more energy and mental clarity.  Plus, my hands, which are usually cold, became dramatically warmer, red, and rosy (almost splotchy), indicating improved circulation.  Haven't had a problem with sulfur-containing foods/supplements since then.
 
I suspect that I was overloading on sulfur from the sulfur-containing supplements that I have been taking (NAC, curcumin, quercetin) and may have depleted my molybdenum stores thus impairing my sulfur metabolism.  Anyway, it's an interesting turn of events for me and I'm glad this thread made me think of molybdenum.

 
Very glad to hear Kingsley. You experienced the same effect The CBS gene mutation rs1801181:AA is probably having an effect on you as well; It affects only about 7% of the population. I guess we need to supplement on a regular basis with it to keep our sulphites low and converted to the less harmful sulphates. I am trying to avoid foods high in sulfur (thiols) as listed in this useful webpage: http://www.livingnet...phur-food-list/ Honestly it is too hard to avoid all food containing sulphur.
I also want to try manganese as suggested by nutrahacker.
I wonder whether this gene is related somehow to raynaud's syndrome. You mentioned cold hands and poor circulation. My grandmother suffered from raynaud's syndrome.

[ceridwen]

Could that be why I feel worse when taking J147 and quercetin? J147 seemed to improve my memory at first but I feel so ill now after I got more serious taking it. It is based on curcumin and I have been experimenting with different forms of curcumin for about a month now

[world33]

Could that be why I feel worse when taking J147 and quercetin? J147 seemed to improve my memory at first but I feel so ill now after I got more serious taking it. It is based on curcumin and I have been experimenting with different forms of curcumin for about a month now

Unless you take a genetic test with 23andme.com and plug your raw data into nutrahacker.com it is really hard to find out what your issue is with your health or those two supplements. I am not sure how much sulphites curcumin or quercetin have by the way.

Edited by world33, 20 August 2015 - 03:04 AM.

[YOLF]

 

 

I will stay chemically happy for the most part like this as a positive mindset is always better for learning, but I think we always recognize the underly value of experiences etc. through logical analysis. That part is important. I don't think even oxytocin changes that and I do get ticks occasionally when I'm over experiencing something and the logical "snap to" hits me.

 

 

Good point, though I'm sure you'd also agree that some experiences have value precisely because of the feeling that they produce.  I think that living a meaningful life depends in large part on the ability to feel that certain experiences are meaningful, not just to recognize their value logically, thus the crippling nature of anhedonia and depression.  Though perhaps the most meaningful experiences are those that appeal to both the emotions and the intellect.

 

Yes, ability to feel comes from positive experiences. The most meaningfully rich experiences are even more The more levels of appeal, the more meaningful an experience is and the more you begin to understand . Though that's not to say small things aren't meaningful, just that small things can be meaningful . 

[Kingsley]

Could that be why I feel worse when taking J147 and quercetin? J147 seemed to improve my memory at first but I feel so ill now after I got more serious taking it. It is based on curcumin and I have been experimenting with different forms of curcumin for about a month now

 

It's very hard to say.  Unfortunately we are shooting in the dark here, and all we can really do is speculate and experiment.

 

I will say that your experience sounds similar to mine: I initially benefitted from curcumin and quercetin but after a while began feeling sick after taking either.  I have read that both are high in sulfur.  After adding a daily dose of molybdenum (250-500 mcg per day), the issue COMPLETELY resolved, and I'm back to taking curcumin and quercetin to great effect.  I have to conclude that my issue was sulfur-related, but who really knows. 

 

It couldn't hurt to try molybdenum and see if it helps.  For me the benefits were almost instantaneous.     
 

[ceridwen]

Thanks will do

[YOLF]

The molybdenum sounds like a good idea. I'm taking a ton of sulfur containing supps to maintain my joints and have been wondering if it's robbing me of some energy levels.

 

In particular, I'm taking quercetin, MSM, and who knows what else that contains sulfur... I haven't concerned myself so much with that yet. Anyone got a link to safe dosing for it handy?

[Kingsley]

The molybdenum sounds like a good idea. I'm taking a ton of sulfur containing supps to maintain my joints and have been wondering if it's robbing me of some energy levels.

 

In particular, I'm taking quercetin, MSM, and who knows what else that contains sulfur... I haven't concerned myself so much with that yet. Anyone got a link to safe dosing for it handy?

 

The Institute of Medicine has established the RDA for molybdenum as 45 mcg and the safe upper limit as 2mg (for adults).  They also note that those deficient in copper intake or with a dysfunction of copper metabolism could be at increased risk of molybdenum toxicity.

 

I still cannot seem to post a link!  Anyone have any tips, or is it because I'm a relatively new member?  In any event, you can go to the Institute of Medicine website and look up "Dietary Reference Intakes: Elements."

[Kingsley]

 
Very glad to hear Kingsley. You experienced the same effect The CBS gene mutation rs1801181:AA is probably having an effect on you as well; It affects only about 7% of the population. I guess we need to supplement on a regular basis with it to keep our sulphites low and converted to the less harmful sulphates. I am trying to avoid foods high in sulfur (thiols) as listed in this useful webpage: http://www.livingnet...phur-food-list/ Honestly it is too hard to avoid all food containing sulphur.
I also want to try manganese as suggested by nutrahacker.
I wonder whether this gene is related somehow to raynaud's syndrome. You mentioned cold hands and poor circulation. My grandmother suffered from raynaud's syndrome.

 

 

Interestingly, my mother has always complained of sulfite sensitivity, and she has the same issues with cold hands as me, though neither of us is at the level of Raynaud's syndrome.  It does make you wonder.

 

As for the CBS SNP rs1801181 (the "A360A" variation) that we share, I found an interesting discussion here by some one who has looked at the studies on CBS upregulation: http://web.mit.edu/london/www/cbs.html. 

 

According to the referenced studies, the A360A variation represents a less significant CBS upregulation than another variation (the "Y233Y" variation, which I don't have), which a study showed to result in only 2.7% less homocysteine (thus a relatively minor upregulation?).  The A360A variation was found to be less significant, and to only show a significant effect on homocysteine in the absence of two other polymorphisms.  Another study showed no effect of the SNP's on homocysteine levels in people over 40.  The discussion concludes that there is no evidence that CBS upregulation produces any negative effects.  However, it appears that the referenced studies only measured homocysteine levels and did not measure the levels of CBS product cystathionine. 

 

Another study cited by the author found that children with Down's syndrome (which is known to involve significant CBS upregulation), had 25% lower homocysteine and 3.8 times more cystathionine.  That's a lot more cystathionine (and thus presumably sulfite, one of its metabolites).  This suggests to me that even a much less significant upregulation like Y233Y could still result in the production of significantly more cystathione from homocysteine, thus potentially straining sulfur metabolism.  Our SNP (A360A) is apparently even less significant, but perhaps enough to burden sulfur metabolism in some people?

 

In any case, we now have two demonstrated cases of sulfur/sulfite sensitivity occurring in two people homozygous for A360A (you and me), which is suggestive.  I would also suspect that anyone could strain their sulfur metabolism and deplete molybdenum by taking in too much sulfur/cysteine/sulfites, so I wouldn't necessarily base the decision to try molybdenum on the presence of any particular SNP.  

[YOLF]

 

The molybdenum sounds like a good idea. I'm taking a ton of sulfur containing supps to maintain my joints and have been wondering if it's robbing me of some energy levels.

 

In particular, I'm taking quercetin, MSM, and who knows what else that contains sulfur... I haven't concerned myself so much with that yet. Anyone got a link to safe dosing for it handy?

 

The Institute of Medicine has established the RDA for molybdenum as 45 mcg and the safe upper limit as 2mg (for adults).  They also note that those deficient in copper intake or with a dysfunction of copper metabolism could be at increased risk of molybdenum toxicity.

 

I still cannot seem to post a link!  Anyone have any tips, or is it because I'm a relatively new member?  In any event, you can go to the Institute of Medicine website and look up "Dietary Reference Intakes: Elements."

 

 

Hmmm... not sure what the required post count is for posting links is these days, but getting a membership gives it to you within 24 hours. 

 

I take a copper supplement, so I'm guessing I should be fine with 500mcg doses. That seems to be the most commonly available dose.

[world33]

Very glad to hear Kingsley. You experienced the same effect The CBS gene mutation rs1801181:AA is probably having an effect on you as well; It affects only about 7% of the population. I guess we need to supplement on a regular basis with it to keep our sulphites low and converted to the less harmful sulphates. I am trying to avoid foods high in sulfur (thiols) as listed in this useful webpage: http://www.livingnet...phur-food-list/ Honestly it is too hard to avoid all food containing sulphur.
I also want to try manganese as suggested by nutrahacker.
I wonder whether this gene is related somehow to raynaud's syndrome. You mentioned cold hands and poor circulation. My grandmother suffered from raynaud's syndrome.

 
Interestingly, my mother has always complained of sulfite sensitivity, and she has the same issues with cold hands as me, though neither of us is at the level of Raynaud's syndrome.  It does make you wonder.
 
As for the CBS SNP rs1801181 (the "A360A" variation) that we share, I found an interesting discussion here by some one who has looked at the studies on CBS upregulation: http://web.mit.edu/london/www/cbs.html. 
 
According to the referenced studies, the A360A variation represents a less significant CBS upregulation than another variation (the "Y233Y" variation, which I don't have), which a study showed to result in only 2.7% less homocysteine (thus a relatively minor upregulation?).  The A360A variation was found to be less significant, and to only show a significant effect on homocysteine in the absence of two other polymorphisms.  Another study showed no effect of the SNP's on homocysteine levels in people over 40.  The discussion concludes that there is no evidence that CBS upregulation produces any negative effects.  However, it appears that the referenced studies only measured homocysteine levels and did not measure the levels of CBS product cystathionine. 
 
Another study cited by the author found that children with Down's syndrome (which is known to involve significant CBS upregulation), had 25% lower homocysteine and 3.8 times more cystathionine.  That's a lot more cystathionine (and thus presumably sulfite, one of its metabolites).  This suggests to me that even a much less significant upregulation like Y233Y could still result in the production of significantly more cystathione from homocysteine, thus potentially straining sulfur metabolism.  Our SNP (A360A) is apparently even less significant, but perhaps enough to burden sulfur metabolism in some people?
 
In any case, we now have two demonstrated cases of sulfur/sulfite sensitivity occurring in two people homozygous for A360A (you and me), which is suggestive.  I would also suspect that anyone could strain their sulfur metabolism and deplete molybdenum by taking in too much sulfur/cysteine/sulfites, so I wouldn't necessarily base the decision to try molybdenum on the presence of any particular SNP.

 
I read that article in the past :-). Funny enough I am Homozygous for CBS A360A rs1801181 and Heterozygous for CBS C699T rs234706 so I am possibly in a worse position than you. I guess if the CBS Upregulation is just a myth we would not feel any better by taking molybdenum. The title of the article can be misleading. I guess sometime it is better a trial and error strategy with supplements rather than relying on scientific studies or articles alone. Without nutrahacker.com I would have never tried molybdenum and, to be honest, I did not even know it existed as a supplement.
I have never suffered from cold hands so there must be other genes coming into play for your condition.
I wonder whether 23andme.com test for the suox genes which are also involved in the Sulfite Oxidase process for which molybdenum is a cofactor. We might have some polymorphisms that cause Sulfite oxidase deficiency. Just a guess.

[YOLF]

Cold hands come from blood flow and slowed metabolism AFAIK. I always had cold hands that couldn't stay warm enough in the winter and would crack constantly. Became a coffee drinker and that problem went away. I was now driving to work without ever turning the heat in my car on.

[ceridwen]

Could people with Downs syndrome ever have upregulation?

[Kingsley]

 

 I guess sometime it is better a trial and error strategy with supplements rather than relying on scientific studies or articles alone. Without nutrahacker.com I would have never tried molybdenum and, to be honest, I did not even know it existed as a supplement.

 

 

Agreed.  If I limited myself to only substances that have been shown effective for adhd in studies, I'd be so far behind where I'm at currently that it's ridiculous.  I bring up the studies out of curiosity and to try to figure out what the heck is going on and to build my knowledge base.  But when it comes to supplements I say: when in doubt, try it out! 

[Kingsley]

Could people with Downs syndrome ever have upregulation?

 

I'm not sure I understand the question.  As I noted, Down's Syndrome has been associated with dramatic upregulation of the CBS enzyme (cystathionine beta synthase) resulting in a much higher metabolism of homocysteine down the transsulfuration pathway.

[ceridwen]

Does that mean people with Downs Syndrome have low homocysteine?

[Kingsley]

Does that mean people with Downs Syndrome have low homocysteine?

 

Yes, according to my reading, people with Down's Syndrome tend to have low homocysteine. 
 

[ceridwen]

Thanks for replying. Let me explain why I'd like to know I'd like to know if someone with Downs syndrome would have a low homocysteine over all or just lower than a normal person's given the morbidity that an individual might be suffering from. I seem to be suffering from early onset dementia and I was wondering without being genetically tested wethever I am Mosaic Downs as I look as if I might be but my homocysteine is elevated. Would that indicate that with this illness the homocysteine levels would be much  more elevated in a normal person or is it perhaps indicating that I do not have Downs Syndrome? I would be interested in what you think. I don't want to go to 23 and me. It's something I've been wondering about for some time ever since I found that people can be a little bit Downs.

[Kingsley]

Thanks for replying. Let me explain why I'd like to know I'd like to know if someone with Downs syndrome would have a low homocysteine over all or just lower than a normal person's given the morbidity that an individual might be suffering from. I seem to be suffering from early onset dementia and I was wondering without being genetically tested wethever I am Mosaic Downs as I look as if I might be but my homocysteine is elevated. Would that indicate that with this illness the homocysteine levels would be much  more elevated in a normal person or is it perhaps indicating that I do not have Downs Syndrome? I would be interested in what you think. I don't want to go to 23 and me. It's something I've been wondering about for some time ever since I found that people can be a little bit Downs.

 

Interesting.  Based on my limited knowledge and review of a few studies, at least one study failed to show a significant difference in homocysteine levels between adults with Down Syndrome vs. adults without Down Syndrome.  The authors speculated that reduced homocysteine may be more characteristic of Down Syndrome children than Down Syndrome adults.  Further, I'm unaware whether any studies have measured homocysteine levels in people with mosaic Down Syndrome and whether this would make a difference. 

 

Either way, I would think that homocysteine levels would be a very inexact and unreliable way to determine whether one has this disorder.  If you really suspect that it is a possibility, I think it would be a very good idea to see a doctor and get it tested, as it is really not the type of thing you want to be guessing about.  Good luck!

[world33]

Kingsley I tried manganese and it has a similar effect as molybdenum. I am starting wondering whether the sulfites sensitivity due to the CBS mutation plays a bigger role than the C667T mutation in my system. It is hard to accept that I have to go on a low thiol diet to find out. There so many foods to avoid ... http://www.livingnet...phur-food-list/

[world33]

I forgot to mention that the first time I tried manganese it made me very sleepy and tired so I suggest you to try it at night.

[Kingsley]

Kingsley I tried manganese and it has a similar effect as molybdenum. I am starting wondering whether the sulfites sensitivity due to the CBS mutation plays a bigger role than the C667T mutation in my system. It is hard to accept that I have to go on a low thiol diet to find out. There so many foods to avoid ... http://www.livingnet...phur-food-list/

 

Interesting that you are benefiting from manganese.  I wasn't aware it was involved in sulfur/sulfite metabolism.  Any idea how it is supposed to help, from a theoretical standpoint, i.e. which enzymes it is a co-factor for?

 

I have tried manganese and noticed a mildly stimulating effect, though not always consistent.  I understand that it is very important for antioxidant protection via the superoxide dismutase enzyme, but that elevated levels of manganese are associated with cognitive impairment.  Interesting though, and will research more.

 

I myself began to doubt recently the role my homozogous C677T mutation was playing in my cognitive issues since I was no longer noticing a subjective effect from each dose of methylfolate, and decided to experiment by going a few days without it.  Suffice to say it was not pretty, and I no longer have any doubt as to my need for methylfolate. 

 

By the way, have you ever noticed an increased need for potassium from taking methylfolate?  From time to time if I take too much methylfolate, methylb12, or SAM-E, I begin to feel downright ill, but it resolves once I take a bunch of potassium.  I have dramatically upped my potassium intake and am having a lot less instances of side effects, though I have to make sure to stay on top of the potassium.  Increased potassium need is consistent with a lot of anecdotal accounts out there--won't go into the purported reasons.

Edited by Kingsley, 28 September 2015 - 04:22 PM.

[ceridwen]

@Kingsley I have not approached my Dr with this anxiety because when I look at him I wonder if he doesn't have the problem as well. I don't want to worry him. So I have not asked to be tested. He is the best Dr with the most caring manner at the clinic. I have not mentioned it to any of the others in case they start to look at him and wonder too. There might not be much that can be done so not worth worrying people

[world33]

Kingsley I tried manganese and it has a similar effect as molybdenum. I am starting wondering whether the sulfites sensitivity due to the CBS mutation plays a bigger role than the C667T mutation in my system. It is hard to accept that I have to go on a low thiol diet to find out. There so many foods to avoid ... http://www.livingnet...phur-food-list/

 
Interesting that you are benefiting from manganese.  I wasn't aware it was involved in sulfur/sulfite metabolism.  Any idea how it is supposed to help, from a theoretical standpoint, i.e. which enzymes it is a co-factor for?
 
I have tried manganese and noticed a mildly stimulating effect, though not always consistent.  I understand that it is very important for antioxidant protection via the superoxide dismutase enzyme, but that elevated levels of manganese are associated with cognitive impairment.  Interesting though, and will research more.
 
I myself began to doubt recently the role my homozogous C677T mutation was playing in my cognitive issues since I was no longer noticing a subjective effect from each dose of methylfolate, and decided to experiment by going a few days without it.  Suffice to say it was not pretty, and I no longer have any doubt as to my need for methylfolate. 
 
By the way, have you ever noticed an increased need for potassium from taking methylfolate?  From time to time if I take too much methylfolate, methylb12, or SAM-E, I begin to feel downright ill, but it resolves once I take a bunch of potassium.  I have dramatically upped my potassium intake and am having a lot less instances of side effects, though I have to make sure to stay on top of the potassium.  Increased potassium need is consistent with a lot of anecdotal accounts out there--won't go into the purported reasons.

 

I tried it because it was suggested in the nutrahacker results. If you google manganese+cbs there are some info and reviews. Of course they are not peer reviewed publications/studies but try does not harm.
I take 10mg a day, which is under the upper limit of 11mg, to be safe.
I have not tried potassium yet, beside eating bananas on a regular basis, but when I feel I have taken too much methyfolate I take a very low dosage of vitamin B3 (niacin) as suggested by Dr Ben Lynch. It does work for me.
For our CBS rs1801181 mutation nutrahacker suggests SAMe inhibits; you might investigate whether SAMe could have a negative effect in terms of sulfites.
I also read that Boron might help for CBS mutations http://www.heartfixe...enomics.htm#CBS (Cystathionine Beta Synthase); I might try that in the future once I better learn its role and action.
Have you considered switching to hydroxocobalamin? Perque 2000mcg Sublingual Lozenges have good reviews https://www.pureform...-by-perque.html if you do not like the idea of IM injections.

Edited by world33, 30 September 2015 - 02:17 PM.

[Kingsley]

 

 

I tried it because it was suggested in the nutrahacker results. If you google manganese+cbs there are some info and reviews. Of course they are not peer reviewed publications/studies but try does not harm.
I take 10mg a day, which is under the upper limit of 11mg, to be safe.
I have not tried potassium yet, beside eating bananas on a regular basis, but when I feel I have taken too much methyfolate I take a very low dosage of vitamin B3 (niacin) as suggested by Dr Ben Lynch. It does work for me.
For our CBS rs1801181 mutation nutrahacker suggests SAMe inhibits; you might investigate whether SAMe could have a negative effect in terms of sulfites.
I also read that Boron might help for CBS mutations http://www.heartfixe...enomics.htm#CBS (Cystathionine Beta Synthase); I might try that in the future once I better learn its role and action.
Have you considered switching to hydroxocobalamin? Perque 2000mcg Sublingual Lozenges have good reviews https://www.pureform...-by-perque.html if you do not like the idea of IM injections.

 

Thanks for info.  When you say SAMe inhibits, I am assuming you mean that it could have a negative effect for those sensitive to sulfite.  That would be consistent, as SAMe upregulates the CBS enzyme thus directing more homocysteine toward the production of cystathione and its downstream metabolite, sulfite. 

 

I actually thought about this before when I found that I needed molybdenum to feel better, and I considered whether all my use of methyl donors could have burdened my sulfite metabolism and depleted molybdenum via their effect on the CBS pathway.  Also I take a lot of NAC which breaks down to cysteine, which would also not help.  However since adding molybdenum, the issues I was having with sulfite appear to have resolved.  I can still make myself feel badly by taking too many methyl donors, which I relate mostly to potassium, but the possibility that a sulfite bottleneck could also play into it is an interesting idea.

 

Haven't looked too much at boron but will look into it.  I would like to try hydroxocobalamin and see if I get any added benefit, though I do fine with cyanocobalamin and methylcobalamin.  With methylcobalamin though I have to make sure not to take too much since as I said too much methylation can make me feel ill.  I really am discovering how important balance is in methylation, at least for some of us.