Roadblocks to Successful Methylation Treatment

[Katy131]

Thank you so much for your helpful thoughts! So much is very reassuring

In your situation it is perfectly normal to have this huge need for potassium. It can be outright dangerous to cut your intake down. Your symptoms are telling you that you need potassium. GP/nurse are dangerously unaware about this need for potassium when the body starts to rebuild.

I agree, but my concern is how to convince the mainstream GP/nurse that I need to take so much Potassium if my blood levels happen to be above the range at my annual blood test. My private functional medicine doctors know and agree that I should take Potassium according to my symptoms, but they are not mainstream and often dismissed by regular doctors and consultants. What happens when people like us are hospitalised for some other reason and removed from our supplements or have to convince hospital staff that we need what to them would be dangerous amounts of Potassium? I guess I'm just anxious about the future in general.

Important thing is: you need to get enough potassium. You can probably slow it down by taking less b12, but don't stop alltogether, since it is basically a healthy process. You might develop other deficiencies along the way since the process takes other nutrients than potassium too (cofactors).

I may consider cutting down the B12 somewhat. In your experience, what might be a more maintenance dose? I do need the salt element for my POTs so would need to compensate. What other nutrient deficiencies might I be on the look out for?

Thanks again so much for your time

 

[Bluebluesky]

I agree, but my concern is how to convince the mainstream GP/nurse that I need to take so much Potassium if my blood levels happen to be above the range at my annual blood test. My private functional medicine doctors know and agree that I should take Potassium according to my symptoms, but they are not mainstream and often dismissed by regular doctors and consultants. What happens when people like us are hospitalised for some other reason and removed from our supplements or have to convince hospital staff that we need what to them would be dangerous amounts of Potassium? I guess I'm just anxious about the future in general.

If you have deficiency symptoms regularly I would't worry too much about high blood levels. But maybe getting as much potassium as possible from food would feel safer?

That being said I can totally relate to the fear of being hospitalized and getting completely misunderstood by the staff there! And I can also relate to that sort of wrong feeling of taking 'too much' of something. I also need A LOT of sodium and it just feels wrong because you are warned against too much sodium all the time. It can be such a challenge to listen to your symptoms and not to what you are told by people who know nothing about your special situation.

I may consider cutting down the B12 somewhat. In your experience, what might be a more maintenance dose? I do need the salt element for my POTs so would need to compensate. What other nutrient deficiencies might I be on the look out for?

1000 mcg seems to be the standard dose, but you might need less. You can cut or break a sublingual into several pieces. You just have to adjust your dose so you can keep up with potassium.

I have been deficient in pretty much every vitamin and mineral along the way since I started my b12 journey, vitamin A and C excluded. I go by symptoms, and I have been trying out all vitamins and minerals, reading about symptoms and cofactors as I have moved along. This sunshine salt or probably a double or triple dose of any multivitamin should keep you covered, theoretically. But if you have persistent symptoms it could be wise to check out if they could also be caused by some sort of deficiency and then try that supplement/nutrient out separately. I have seen several times that taking a supplement separately suddenly solves a problem, despite the fact that I was already getting that nutrient in a complex/multi type of supplement. And taking them separately allows you to establish which symptoms relate to what nutrient (if you have deficiencies, of course).

By the way I have noticed that biotin helps for me for racing heart and problems with standing up for longer periods. I'm not diagnosed with pots. It is just a personal observation and I haven't seen the connection made elsewhere. I just thought that I would share the information. Biotin is one of those nutrients that suddenly worked when I took it separately compared to taking a b complex.

 

[caledonia]

I will get back to you soon. I need to refresh my knowledge on the subject and look back in my symptom journal.

In the meantime, I remember was taking 3000mg of potassium per day for several years. You get that much in food (assuming you can digest it from your food which you may not be able to at this time). So I don't think it would necessarily show up high on a lab test.

 

[Bluebluesky]

@caledonia your documentation is awesome! I just read the last question and answered it when I got into the thread. It's understandable if you somehow felt surpassed. I'm looking very much forward to seeing your answers here.

 

[Blazer95]

Sorry for being a brickhead but I have a hard time understanding the loads of information.

I do have +/+ allele on CBS and i want to a CBS protocol to see if i start to get things working in my favour.

Do pick up this as correct information?
- Keep sulfur balanced via diet and maybe some sparga supplementation
- plasters actually do more then seal wounds (lol)
- Take molybdenium, b12 and boron
- Do active charcoal every 2nd or 3rd day
- avoid methylfolate before you get the cbs cleared
- eh uh ah? uga uga? blazer stupid?

 

[Katy131]

@caledonia your documentation is awesome! I just read the last question and answered it when I got into the thread. It's understandable if you somehow felt surpassed. I'm looking very much forward to seeing your answers here.

No worries! I posted my question to anybody who was able to help, not just for @caledonia. I found your thoughts very helpful

 

[caledonia]

Help! Why do I still need so much potassium after stopping my methylation supplements?

I stopped taking all my methylation supps in the Autumn (one by one I cut down, not all at once) because I think I was over methylating and getting symptoms like migraines from it. I even stopped the multi I was taking because it contained the active and methylated versions of B vits. I didn't want to halt all the good work I'd done getting my body to methylate better over the previous six months or so - just to get to a balance point. However I'm still on huge amounts of potassium - about 1335mg from Potassium Gluconate alone - and that barely covers me - I often wake in the night with nightmares and palpitations. Taking a Potassium settles it very quickly. I have been drinking high potassium juices as well but recently cut them back because of the sugar intake (thinking of my annual blood tests in a few months' time). I'm on a rotation diet so I can't just drink Coconut water every day.

There is 5000 mcg B12 (methyl cobalamin) in my Sunshine salt mineral mix but that's the only B supplement I am taking.

https://www.salesatdrmyhill.co.uk/sunshine-salt-300-g-392-p.asp

So questions:

Could this B12 dose be continuing my symptoms and high potassium need all by itself? Do I need to worry about my potassium intake - my regular GP/nurse would be shocked. Is it in fact a good sign that my body is methylating well by itself now? How long will it be before it normalises and I can reduce the potassium?

Thanks for any thoughts and ideas in advance

When you take B12 and folate (folic acid), that will crank up the methylation cycle. It's like a runaway train - it will take a long time to stop even if you discontinue all the B12 and folate.

It doesn't really sound like you're having overmethylation symptoms except for needing a lot of potassium.

You could try discontinuing the B12 and also taking niacin (as described in my document) to soak up methyl groups and slow down methylation.

The symptoms of potassium and magnesium deficiency are pretty much the same. It's possible you might also need magnesium (you didn't mention if you're taking that or not).

My good doc had me do things in the following order - first work out how much potassium you need, then how much magnesium you need, then how much sodium you need. Start low and gradually increase until you find your "sweet spot". There is a lag time of a few to several days for the electrolytes.

Keep a symptom journal of how much you're taking and how your feeling. Pay attention to deficiency symptoms like heart palpitations, muscle twitches, constipation, sleep quality, etc. Pay attention to overdose symptoms like nausea, a metallic taste in the mouth, diarrhea.

Whenever I've tried this, invariably I get into overdose territory, then have to cut back a bit. Then that is my "sweet spot".

You may have to dose electrolytes 3-4 times a day to get enough in. I dose 3 times during the day, and once overnight. Lately, I've needed more magnesium than I get in orally, so I've added an Epsom salt foot bath in the evening.

Getting my electrolytes worked out has been huge for me. Way better than any methylation protocol.
In general, my opinion on methylation protocols has changed over time. I don't think people should be doing them because they're too difficult to predict or control. I can't tell you how many people I have had to talk down from a crisis over-methylation situation.

If you have methylation issues, consider that you may have an underlying issue with toxic metals like mercury. A methylation protocol is just a bandaid. Removing mercury should help restore your methylation cycle.

I've tried a number of types of chelation, and the Andy Cutler protocol has worked the best for me. I have more info on that in my signature link.

 

[Judee]

eh uh ah? uga uga? blazer stupid?

No you're not.

You have smarts. You joined PR, didn't you? That's pretty smart.

Our brains are just buried under this awful brain fog in the same way a car parked on the street can sometimes become completely obscured in a heavy fog. Our fog just doesn't roll away that often but that doesn't mean the car isn't still parked there.

 

[caledonia]

Sorry for being a brickhead but I have a hard time understanding the loads of information.

I do have +/+ allele on CBS and i want to a CBS protocol to see if i start to get things working in my favour.

Do pick up this as correct information?
- Keep sulfur balanced via diet and maybe some sparga supplementation
- plasters actually do more then seal wounds (lol)
- Take molybdenium, b12 and boron
- Do active charcoal every 2nd or 3rd day
- avoid methylfolate before you get the cbs cleared
- eh uh ah? uga uga? blazer stupid?

I did the CBS protocol and was able to get my sulfur reduced. But it didn't help me feel any better, other than I could tolerate sulfur foods and supplements better. You would need urine sulfate strips to monitor things.

If you do have a CBS/sulfur issue, consider that you could have an underlying toxic metal issue, such as with mercury.

Things like getting my electrolytes balanced, and the Andy Cutler mercury chelation protocol have been much more helpful for me.

The Cutler protocol also has a method for dealing with sulfur issues. The real issue is thiols, not all sulfur. For example, magnesium sulfate (aka Epsom salts) is fine.

First you can do a thiol challenge test to see if it really is an issue for you. Then, if so, simply avoid thiol foods and chelate until you can tolerate them. So it's simpler and easier to grasp the concept of what to do. Plus the diet is easier than what Yasko recommends.

 

[almost]

You joined PR, didn't you? That's pretty smart.

@Judee for the win!

 

[Katy131]

When you take B12 and folate (folic acid), that will crank up the methylation cycle. It's like a runaway train - it will take a long time to stop even if you discontinue all the B12 and folate.

It doesn't really sound like you're having overmethylation symptoms except for needing a lot of potassium.

You could try discontinuing the B12 and also taking niacin (as described in my document) to soak up methyl groups and slow down methylation.

The symptoms of potassium and magnesium deficiency are pretty much the same. It's possible you might also need magnesium (you didn't mention if you're taking that or not).

My good doc had me do things in the following order - first work out how much potassium you need, then how much magnesium you need, then how much sodium you need. Start low and gradually increase until you find your "sweet spot". There is a lag time of a few to several days for the electrolytes.

Keep a symptom journal of how much you're taking and how your feeling. Pay attention to deficiency symptoms like heart palpitations, muscle twitches, constipation, sleep quality, etc. Pay attention to overdose symptoms like nausea, a metallic taste in the mouth, diarrhea.

Whenever I've tried this, invariably I get into overdose territory, then have to cut back a bit. Then that is my "sweet spot".

You may have to dose electrolytes 3-4 times a day to get enough in. I dose 3 times during the day, and once overnight. Lately, I've needed more magnesium than I get in orally, so I've added an Epsom salt foot bath in the evening.

Getting my electrolytes worked out has been huge for me. Way better than any methylation protocol.
In general, my opinion on methylation protocols has changed over time. I don't think people should be doing them because they're too difficult to predict or control. I can't tell you how many people I have had to talk down from a crisis over-methylation situation.

If you have methylation issues, consider that you may have an underlying issue with toxic metals like mercury. A methylation protocol is just a bandaid. Removing mercury should help restore your methylation cycle.

I've tried a number of types of chelation, and the Andy Cutler protocol has worked the best for me. I have more info on that in my signature link.

Thank you so much for the helpful information

I was only working on my methylation for about 6 months last year and it's been almost 6 months I guess since I stopped taking those. I'm not taking any extra folate now and only the B12 in the Sunshine salt. I am considering cutting that down but will have to leave it a few weeks because I'm about to have an allergen immunotherapy treatment next week and can't be changing anything while that does its work. What might be a level of B12 intake I should aim for? It's currently 5,000 mcg in the Sunshine salt daily dose. I need the sodium but thinking I could replace the sodium element with Himalayan salt as I cut down.

I discontinued all my B vitamins (including niaicinamide and multivitamins) last Autumn because they were also giving me symptoms and I felt better without them. It's possible they were always contributing to methylation which was a bit too much for my body to deal with. I had been taking them since 2008 and have an excellent varied diet so my doctor and I considered it was OK to stop the supplements. I wouldn't want to restart niacin unless I have to. If I did, would it undo all the work I did on my methylation last year? There have been some positive results - I feel generally stronger underneath, for example.

If I'm not having overmethylation issues, what might be causing this extreme need for Potassium? I didn't get palpitations etc much until I cranked up the methylation last year, and as I said, Potassium supplements fix it quickly.

I've got my magnesium into a good place finally after years of experimentation. I'm currently taking a Potassium/Magnesium complex (recommended by one of my doctors) which seems to be my sweet spot of magnesium. I was having to nebulise magnesium sulfate for much of the last two years in order to get my red cell magnesium into the normal range but I think the Pot/Mag complex now keeps it there, going by my symptoms. I take extra Potassium Gluconate for the palpitations etc. I've been keeping a symptom diary since 2014 so I'm already taking careful note and yes - nausea is one of my overdose symptoms (for example too much magnesium).

I agree about the electrolytes. Since I found Potassium eases many of my symptoms, I've realised that it's not just magnesium and salt I have to look at, but a balance. The Pot/Mag complex was a bit of a game changer for that.

Thanks also for the comment on Mercury. I was diagnosed MCS in 2010 and had all my mercury amalgams replaced in 2011. Generally I've been working on avoidance of the heavy metals I am sensitive to (eg I have to avoid titanium dioxide, which is in EVERYTHING) I take Toxaprevent daily which helps mop up the toxins generally and I've noticed my sweat doesn't smell metallic any more, so I think I'm doing OK there.

My doctor and I think my methylation issues stem from an ancient Lyme Disease infection that went undiagnosed and untreated when I was a child. My body has been struggling ever since and it has got worse and started to affect my life in a major way as I got older.

 

[Bluebluesky]

No worries! I posted my question to anybody who was able to help, not just for @caledonia. I found your thoughts very helpful

Well, maybe I overreacted a bit there. I get so overwhelmed when I realize just how much insight people have in here . But of course it should be legitimate to answer a question. Thank you for your kind answer!

I noticed that you mentioneed in previous posts that you had deficiency in vitamin b6 and vitamin b2. Have you looked into the work of dr. Greg Russell Jones, b12oils.com? He claims that there is a pathway where vitamin b12, b2 and b6 won't work if you are deficient in either selenium, iodine og molybdenum. I have had the same deficiencies, and supplementing with those minerals has helped for me. He is very specific that it has to be potassium iodide, sodium selenite and sodium molybdate, and that is what I saw too. The other types just don't work for me.

 

[Katy131]

Thanks for that - I will look into it I definitely don't have a deficiency of selenium as my serum levels have been above the range for a few years after I supplemented too much with it some years back. I supplement iodine and molybdenum in my sunshine salt mineral mix and took B2 and B6 as part of my methylation protocol last year, so hopefully that is corrected now. I will ask my doctor about it when I see him in a few months' time.

 

[caledonia]

What might be a level of B12 intake I should aim for? It's currently 5,000 mcg in the Sunshine salt daily dose. I need the sodium but thinking I could replace the sodium element with Himalayan salt as I cut down.

I wouldn't want to restart niacin unless I have to. If I did, would it undo all the work I did on my methylation last year? There have been some positive results - I feel generally stronger underneath, for example.

If I'm not having overmethylation issues, what might be causing this extreme need for Potassium? I didn't get palpitations etc much until I cranked up the methylation last year, and as I said, Potassium supplements fix it quickly.

I agree about the electrolytes. Since I found Potassium eases many of my symptoms, I've realised that it's not just magnesium and salt I have to look at, but a balance. The Pot/Mag complex was a bit of a game changer for that.

Thanks also for the comment on Mercury. I was diagnosed MCS in 2010 and had all my mercury amalgams replaced in 2011. Generally I've been working on avoidance of the heavy metals I am sensitive to (eg I have to avoid titanium dioxide, which is in EVERYTHING) I take Toxaprevent daily which helps mop up the toxins generally and I've noticed my sweat doesn't smell metallic any more, so I think I'm doing OK there.

My doctor and I think my methylation issues stem from an ancient Lyme Disease infection that went undiagnosed and untreated when I was a child. My body has been struggling ever since and it has got worse and started to affect my life in a major way as I got older.

 

[caledonia]

The Recommended Daily Allowance for B12 is 2.4 mcg. So at least that much. I think I was only taking about 20mcg because more than that was making me jittery. I don't think anybody really knows what is the correct or right amount of B12. If you're a vegan or have digestive issues, you might need more. Also if you take a high amount of B12, but don't have enough of the co-factors, then it won't be utilized.

Unfortunately, the testing isn't very good. It can be high, and that can mean your low. It can look normal, but you can still be low. However, if it's low, then you're low.

Have you done testing for B12?

The need for potassium is due to starting up cell rebuilding (like a pregant woman needs a lot of potassium to "build" a fetus/baby). It might last for years. This happened to me. I was taking something like 3000mg of potassium gluconate along with a lesser amount of magnesium for several years. Then it reversed, and now I'm taking something like 3000mg of magnesium with 50mg of potassium.

Mercury - that's great you got out your mercury fillings. However, since you haven't chelated, there will still be mercury in your body and brain. The zeolite won't remove that.

Sometimes people get diagnosed with Lyme, but it can actually be mercury.

 

[Katy131]

Thanks again for your comprehensive reply and apologise for the late response - I have been away from my PC for a few days.

Have you done testing for B12?

Yes - about a year ago, before I started methylation supps, it was 880 pmol/l where the range was 400-2000 pmol/l. I was taking the fortified Sunshine Salt then too, with its 5,000 mcg B12 Methylcobalamin daily, plus another 50 mcg Methyl B12 in my multi. Still taking the salt but not the multi.

Mercury - that's great you got out your mercury fillings. However, since you haven't chelated, there will still be mercury in your body and brain. The zeolite won't remove that.

Interesting - my doctor prescribed daily zeolite drops and chlorella for about 18 months after I had my fillings replaced in order to chelate the mercury and I then had a couple of years of remission. This was a long time ago but as I mentioned I've been taking Toxaprevent cliniptolite daily, sometimes more than once a day for about the last 5 years to help mop up heavy metals, histamine and other nasties, and I do feel better for it. There are also a number of peer-reviewed research studies on PubMed showing that zeolite does remove mercury including:

https://pubmed.ncbi.nlm.nih.gov/36972873/

and

https://pubmed.ncbi.nlm.nih.gov/35712111/

So I'm curious why you would say zeolite won't remove mercury, when these studies, my doctors' advices and the positive results of their prescriptions on my health has shown that it does.

Sometimes people get diagnosed with Lyme, but it can actually be mercury.

I certainly have had a problem with heavy metals, including mercury, and I know this is something I will have to deal with always, but I think I'm doing the best I can and have the tools to keep the effects to a minimum - knowledge is half the battle too! However, the beginning of my illness started when I was bitten by a tick as a child which resulted in undiagnosed, untreated Lyme Disease. I had the signs of two bullseye rashes which I now know indicated Second Stage Lyme Disease, and I also remember having a little "beetle" stuck on my head under my hair, which my Mum said was only a scab. It's only recently, after years of reading and research and discussion with my doctors that it's become clear this was the underlying cause of my illness. My body's inability to adequately detoxify heavy metals through the normal pathways is a result of the trauma caused to my system by the untreated Lyme, and that's why I have a problem with mercury and other heavy metals.

I had a urine test for Toxic Elements a few years ago and Mercury was 0.1 umol/mol where the range should be less than 2.00 umol/mol. It's always going to be a struggle but I feel I am "on top" of it.

 

[caledonia]

Thanks again for your comprehensive reply and apologise for the late response - I have been away from my PC for a few days.



Yes - about a year ago, before I started methylation supps, it was 880 pmol/l where the range was 400-2000 pmol/l. I was taking the fortified Sunshine Salt then too, with its 5,000 mcg B12 Methylcobalamin daily, plus another 50 mcg Methyl B12 in my multi. Still taking the salt but not the multi.



Interesting - my doctor prescribed daily zeolite drops and chlorella for about 18 months after I had my fillings replaced in order to chelate the mercury and I then had a couple of years of remission. This was a long time ago but as I mentioned I've been taking Toxaprevent cliniptolite daily, sometimes more than once a day for about the last 5 years to help mop up heavy metals, histamine and other nasties, and I do feel better for it. There are also a number of peer-reviewed research studies on PubMed showing that zeolite does remove mercury including:

https://pubmed.ncbi.nlm.nih.gov/36972873/

and

https://pubmed.ncbi.nlm.nih.gov/35712111/

So I'm curious why you would say zeolite won't remove mercury, when these studies, my doctors' advices and the positive results of their prescriptions on my health has shown that it does.



I certainly have had a problem with heavy metals, including mercury, and I know this is something I will have to deal with always, but I think I'm doing the best I can and have the tools to keep the effects to a minimum - knowledge is half the battle too! However, the beginning of my illness started when I was bitten by a tick as a child which resulted in undiagnosed, untreated Lyme Disease. I had the signs of two bullseye rashes which I now know indicated Second Stage Lyme Disease, and I also remember having a little "beetle" stuck on my head under my hair, which my Mum said was only a scab. It's only recently, after years of reading and research and discussion with my doctors that it's become clear this was the underlying cause of my illness. My body's inability to adequately detoxify heavy metals through the normal pathways is a result of the trauma caused to my system by the untreated Lyme, and that's why I have a problem with mercury and other heavy metals.

I had a urine test for Toxic Elements a few years ago and Mercury was 0.1 umol/mol where the range should be less than 2.00 umol/mol. It's always going to be a struggle but I feel I am "on top" of it.

This is from the perspective of the Andy Cutler mercury chelation protocol.

Andy Cutler became mercury toxic from his amalgam fillings. He had the scientific background to see that current mercury chelation protocols didn't make scientific sense. He developed his own protocol and cured himself. Then he wrote a book and shared it with others. Basically, all chelation protocols are variations on the original Klinghart protocol. Cutler's protocol is an improvement over that.

Chlorella is bad. It can move mercury out of your body and into your brain.
Zeolite may be doing something in the body, but it won't remove mercury from your brain.
https://cutlersuccessstories.weebly.com/what-not-to-do.html

Cutler uses hair tests to determine the presence of mercury. My urine test looks good too, but my hair test indicates mercury. The more mercury I get out, the better I feel.

Those are classic symptoms of Lyme. Have you tried a course of antibiotics? If so, what happened?

 

[Katy131]

Thanks for the info on Andy Cutler. I will check it out.

As for the Lyme infection, it was undiagnosed and therefore untreated at the time (we are talking over 50 years ago now). Part of the pieces of the puzzle I put together concerned when my GP prescribed a low dose of doxycycline for three months in 2020 for an eye condition. My health and wellbeing were surprisingly good during that time, when it was expected the opposite would happen. It was only some time after that I discovered that Doxy is the antibiotic used for Lyme disease infections and putting together with my memories of the signs of Lyme disease as a child, hypothesised that the Doxy was keeping my Lyme and coinfections at bay while I took it, as well as treating the eye condition. However, I had daily diarrhoea during that time and of course long term antibiotics play havoc with the gut, so my functional medicine doctors aren't happy to prescribe it without a clear diagnosis. Having the blood tests to check for Lyme and all the coinfections would cost over £1,000 and I can't do that. So that's where we are with that at the moment - discussing a way forward .... together with all my other issues including methylation!

 

[caledonia]

Thanks for the info on Andy Cutler. I will check it out.

As for the Lyme infection, it was undiagnosed and therefore untreated at the time (we are talking over 50 years ago now). Part of the pieces of the puzzle I put together concerned when my GP prescribed a low dose of doxycycline for three months in 2020 for an eye condition. My health and wellbeing were surprisingly good during that time, when it was expected the opposite would happen. It was only some time after that I discovered that Doxy is the antibiotic used for Lyme disease infections and putting together with my memories of the signs of Lyme disease as a child, hypothesised that the Doxy was keeping my Lyme and coinfections at bay while I took it, as well as treating the eye condition. However, I had daily diarrhoea during that time and of course long term antibiotics play havoc with the gut, so my functional medicine doctors aren't happy to prescribe it without a clear diagnosis. Having the blood tests to check for Lyme and all the coinfections would cost over £1,000 and I can't do that. So that's where we are with that at the moment - discussing a way forward .... together with all my other issues including methylation!

That's very interesting that the doxy helped. I hope you can find a way to come up with $1000+ if you think that could be a good treatment for you.

 

[Katy131]

You could try discontinuing the B12 and also taking niacin (as described in my document) to soak up methyl groups and slow down methylation.

I take Niacinamide as part of the mitochondria protocol I'm on. In your document, you describe taking Nicotinic acid, which is also a kind of Niacin, to slow down methylation. Would Niacinamide also work in the same way as Nicotinic Acid to slow down methylation?

Also, if you use Niacin to slow down/stop methylation, do you undo the work of months/years by this, or should the body continue to methylate generally better anyway?

TIA