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My methylation-experience so far (Side effects - need guidance)

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by kraken, Feb 27, 2014.

  1. kraken

    kraken

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    I've been on a methylation protocol for 3 weeks after recieving my 23andme results. But now I'm in a situation where I dont really know what to do and hoping for some input and guidance on how to progress. I'm mainly troubleshooting anxiety/light depression and cognitive decline but also a whole couple of other symtoms like burning feet, muscle weakness and stiffness, low energy. My initial experience however has been overly positive, I really think this approach could resolve a lot of symptoms I have. Thought I shared my start-up experience on a weekly basis, this could potentially help/direct others which are troubleshooting same symptoms as well :)

    Potassium level before beginning supplements: 3.8
    Homocysteine: 14
    Gene status 23andme:
    methylation.jpg
    [​IMG]

    Week 1: 2-3 mg Jarrow Methyl B12 - 800 (start) -1200mg Metafolin. Occasional 500 mg TMG and 100 mg DMAE.
    Experience: Some ups and downs in mood (mostly up!), cognition improved a bit (like verbal expression, focus etc), more energy, lowered anxiety. Experienced some increase in my burning sensations, also another thing that was very prominent was TINGLING in some of my fingers throughout the day.
    Interesting note: Around 17:30+ Day 6 was accompanied by an extreme tiredness, like really ready to go to bed-tiredness. Almost couldn't keep my eye up for a couple of hours. Day 7 was followed by an extreme increase in well-being (other half of the day I was like EUPHORIC, hadn't felt so good in years).

    Week 2: Except for the first two days, Methyl B12 and Metafolin same dosage as week 1 (excluded the other ones from this week)
    Experience: First 2 days I got this tightness/anxiety that I've never felt before (I'm very prone to anxiety but this was more physical). My heartrate was around 45bpm at one point also feeling like the beat was inconsistent, felt like I had trouble breathing and sort of panicky. Immediately thought low potasssium so stopped the methylation until I had some Potassium gluconate at hand. Got it (been taking around 500mg/day) and resumed the methylation protocol at day 3. On this day I caught a really nasty cold which didn't really resolve until 10 days later. However, felt that my cognitive functions and my depression still was lifted, although I experienced an increase in anxiety from time to time and shortness of breath. Tingling in my fingers was still present.

    Week 3: Same dosage for Methyl B12, ocassional 3-4 mg / day. Metafolin increased to 1200 - 1600 mg.
    Experience: Beginning of week I really felt anti-depressant effects (most prominent end of week 1 to start of week 3). I must definitely been depressed prior to this, but my anxiety increased on a general basis. Could suddenly get the tightness and pain-like feeling more often at home which worried me. Also got more stomach problems (doctor said I probably have IBS before this as well). Tingling in fingers still present as well as some increase in burning sensations (not only foots now).

    To summarize my situation now: Feel that my mood is slowly decreasing to my "baseline" before supplementing. For example, this day I was very low until i ate my lunch, then my mood was "more back to normal". In spite of this I do feel somewhat BETTER than before in terms of depression. Significant increases in anxiety from time to time (like social and general). Cognition nearly not as good as beginning of week although lifted. Trouble breathing (shortness of breath) has been felt more or less everyday the last 2 weeks. Tingling and occasional sensations in my legs/fingers. However, I feel that my energy/motivation is still elevated to some degree which is really good.

    My speculation:
    • Still low potassium? I'm taking at least 500mg/day and feel that I get some relief from it. Maybe too low dosage?
    • Paradoxical folate deficiency? When I had the cold, I increased the dosage of folate and felt that the symptoms actually lessened a bit.
    • Inability to tolerate methyl donors? Concerning my COMT status (+/-) but my VDR TAQ is (+/+) which I've interpreted as a need for methyl donors, and able to tolerate them.
    • Overmethylation?

    Would really appreciate some input. I know there are a lot of experienced and smart people on this forum :)
  2. whodathunkit

    whodathunkit Senior Member

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    kraken, your experience sounds an awful lot like mine.

    Check out my thread from last week:

    http://forums.phoenixrising.me/inde...starting-methylation-supps.28312/#post-431808

    It sounds like you may indeed have what Freddd calls "donut hole" methylfolate insufficiency. Essentially that's when your body speeds up processes but you're not taking enough folate to keep up with the healing. So you get insufficiency symptoms until your folate intake catches up to what you're body is using/needs (which includes folate as well as necessary co-factors).

    What I did to get over being sick was up my potassium intake drastically (1500mg/day supplemental, also eat high potassium foods), upped my vitamin C intake drastically (6000mg/day for a week), upped my zinc intake drastically (60mg/day for a week), and upped my folate intake significantly, although incrementally (like 3-5mg/day or until I felt better). By the end of the week I was taking 30mg/day. I also added some sublingual MeCbl with every dose of folate, as obviously I have to take 30mg of tablets in divided doses. Still taking all the folate, potassium, and MeCble (although cut back on zinc and Vit C) and still doing fine.

    For health reasons I won't discuss here, I plan to stay on this big dose of mfolate for a couple of months to see if it affects this one chronic problem of long-standing duration that I have. Otherwise I'd probably begin stepping down the mfolate now that my donut-hole symptoms have resolved and everything seems stabilized. I'm looking forward to when I can step down the dose because this much mfolate is quite 'spensive. ;)

    Anyway...suffice it to say I was a pretty sick puppy...just felt really, really bad for a few days. Got a little worse before things began to get better. Then I slept a lot for the next few days. At the end of a week of being out sick, I woke up feeling fine. Never had a cold/flu like that that didn't linger around. But this one did not. I'm ready to start working out again tomorrow, less than two weeks later. A little miracle, IMO.

    I realize this drastic approach of increasing folate and co-factors might not be advisable or tolerable for some. I've done a lot of other work on my health in the past couple/few years that probably prepped me for tolerating this methylation protocol as well as I have. I've already chelated, done detox diet, corrected some mineral deficiencies, etc., before I ever discovered this wonderful forum.

    And I can't really speak to your genetic info, because I'm not knowledgeable about that. But worth noting is that even if I had my own genetic information, I would try things and go on symptoms rather than whatever is on paper. IMO one of the biggest problems with our medical system is that our healthcare practitioners do not pay enough attention to what we tell them; they look at lab values or whatever as the only possible evaluation criteria, and if the piece of paper says everything is fine or that some process should work this way, then that's it. But that's wrong. We need to listen to our bodies as well as consult the piece of paper.

    I'm just throwing my experience out there because it does sound like you're describing a "donut hole" mfolate deficiency, as Freddd terms it, and radically increasing folate and some other co-factors until I got over it what worked for me.

    Final edit: I am also having some shortness of breath that I've been chalking up to starting a particular breathing method around the same time I started methylation. After re-reading your post I'm wondering now if it's not something related to donut hole. Or maybe we just had the same virus...? :p

    Anyway, I know my lungs are an area of weakness (former smoker and exposed to second hand smoke for entire first 35 years of life) and in desperate need of healing. For me, the shortness of breath is not serious, and it's not impacting my activity level, it's just annoying. I'm chalking it up to healing right now and think I'll ride it for a while to see what happens.

    Is your shortness of breath what you would consider serious?

    Interesting that we're having almost the same experience.
    Last edited: Feb 27, 2014
  3. girlfromeurope

    girlfromeurope

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    I get those symptoms when I have low potassium, and sometimes low magnesium.
    So magnesium may help, and maybe higher dose potassium.
  4. kraken

    kraken

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    @whodathunkit , very interesting that we're sharing sort of the same story! :) I've thought pretty much about Freddds donut hole theory in regards to my symptoms and after your post i'm very inclined to up my folate dosage. Will probably do right it now right away to see if things get better. Along with that, potassium intake sounds reasonable to increase as well. Actually think my diet is pretty poor in potassium, started eating a lot more bananas though.

    Yes, the shortness of breath has actually been pretty serious from time to time, I was indeed very scared when it first occured. It hit me with a brick, even have had some trouble swallowing foods sometimes getting a reaction of not having enough air in my lungs. Although I'm not sure if it is some sort of anxiety tied to this, but I never experienced this earlier on in my life. Hopefully it could be the mfolate!

    @girlfromeurope , been taking magnesium from time to time but might try to include it more frequently. Thanks for the tip!
  5. whodathunkit

    whodathunkit Senior Member

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    @kraken--been thinking some more and realized it could also be inflammation (which is another donut hole symptom). My breathing symptoms seems to come from the upper part of my chest, not deep in the bronchii (or whatever, hope you get what I mean). It feels irritated in there. Sorry to hear your symptoms have been serious. Like you, I've never really had any respiratory problems in my life (no allergies, asthma, not even coughing when I was a smoker) so this is kind of new for me, too. I'll up my vitamin C intake again to see if that helps it, in case it is inflammation.

    Also, @girlfromeurope is right...magnesium is one of the crucial minerals. That's true even if you're not undertaking methylation therapy, as magnesium deficiency is another wide-spread problem like B-12 deficiency. Correcting my long-standing magnesium deficiency (which I did a couple of years ago) did me loads of good. Unless you have a known health problem that prevents from trying this, you might consider, upping your mag intake to at least 500mg daily for a while. Unless it gives you poop symptoms, that is...it can be rather a powerful laxative. :eek: Mag citrate is a good, bio-available form. I take between 300 - 600mg/day just because I'm still above ground. ;)
    Last edited: Feb 27, 2014
  6. Martial

    Martial Senior Member

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    @kraken, @whodathunkit

    You both describe the flu like symptoms/cold like symptoms of paradox folate deficiency perfectly! I had the same EXACT thing happen! had to up the folate to over 10,000mcg a day but want to still push it a bit higher, also supplemented with methyl b12 at 15mg a day, adob12 10mg a day, and carnatine at 500mg a day... I needed a bit more folate to keep up with everything else for sure.

    I even got a blood test drawn that said I was slightly anemic and had low alkp ranges during methyl trap! :O

    Definitely keep up magnesium supplementation, as if you are deficient you will not hold onto any potassium... I started taking at least 2,000mg of potassium in supplement form on top of high potassium low salt diet recently..


    I also have a lot of issues from lyme disease though that can hamper things, I don't have CFS but Lyme can wreck havoc with methylation even while on supplements... At least till the infection is down.
  7. kraken

    kraken

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    @Martial

    Wow this paradoxical folate deficiency is as it seems actually very real! Good to hear from people having the same issues and how they resolved it. Pretty scary stuff about your tests there! Hope they're back to more normal now?

    Anyways, I found the paper about my lab reports. Magnesium in my blood was 0,76 mmol/L. Apparantly acceptable range was 0,7 - 0,9. So at least I'm not deficient according to that. Could probably be a good idea to supplement anyway to be sure.

    Yesterday I took additional 1,6mg of folate and some Potassium, felt better. Today my total folate intake was 3,8mg (from 1,6mg). Right in the middle of lunch, I felt this massive "drop" again. Harder to breathe, became a bit disoriented, panicky and dizzy. Also been very tired the whole day and sort of spacey. Took 500 mg Potassium and when I came home another 1000 mg. Feels a little bit better but shortness of breath isn't eliminated though. Guess I should try massive doses of Potassium instead.

    On to that: I do feel that it's very hard on my stomach (Potassium gluconate). Getting the runs after taking larger doses. Is there any good replacement/alternative?

    Some other questions I have now: I have Dibencozide (Adb12?) at home but havn't started it yet, good idea to introduce now? Also, i have ALCAR (acetyl l-carnitine) - I guess this will work as good as regular carnitine if I were to introduce it?

    Thanks guys, really. All help is VERY MUCH appreciated :)
  8. ahmo

    ahmo Senior Member

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    @kraken, When my need for K+ went up, I started using it in footbaths. I've been doing this for many months now, works great. I don't need any more than I did orally. I'm taking all my aminos, mg, ca this way now. I've just switched from K+gluconate to K+ chloride, which is used for substitute salt. This comes out cheaper (both NOW from iherb), but the chloride tastes pretty awful, so I'll be keeping gluconate on hand for those times when I need extra, like during the night, and need it orally. cheers, ahmo
  9. whodathunkit

    whodathunkit Senior Member

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    @kraken, ahmo's idea is good. My thing with footbaths is they can take some time and I don't always have that.

    I, too, found potassium caps very hard on my stomach last time I tried to take them (when I did Atkins over 10 years ago). I won't do that again.

    Now I drink potassium chloride powder in some orange juice, about 1/4 tsp. at a time. That little bit in 8oz of OJ doesn't taste bad at all, IMO, although when I run out I will try K+gluconate powder just to compare. If you can sip it over about 10 minutes instead of gulp it down it's easier on your system. Putting it in juice does not make my stomach hurt.

    Worth noting is that poop issues can also be a symptom of the donut hole.

    ALCAR does not act in the same way as l-carnitine fumarate (LCF). They both act in some of the same ways, but LCF seems to more strictly help mitochondria produce energy, while ALCAR acts more on the nervous system. I don't understand all about it yet (still need to read some more), but Freddd has made the distinction between the two here and there. And this is a good succinct explanation of ALCAR from a poster called @Leopardtail :

    Freddd and many others (myself included) seem to have little to no reaction to ALCAR, from what I can tell by reading the forum. In fact, I took ALCAR for a while back when Nick Perricone published his first skin care book and ALCAR + ALA supplementation was all the rage. I was less than impressed. My reaction was basically "What's all the fuss about? This stuff doesn't work!" :meh:

    LCF is a different matter. I noticed an immediate increase in energy and stamina when I started that + AdCbl. I find LCF very stimulating and in fact took myself down to half a cap (250mg instead of the whole 500mg) of the Doctor's Best because it made me feel a little wired. I plan to try to bump it back up but will wait a while on that. I want to let everything settle for a couple weeks, see where I land.

    My take is if you're comfy go ahead and add the AdCbl. I like to jump in with both feet, but that's just me. Or it may be best to wait since you're already having donut hole symptoms. Maybe someone with more experience can chime in. But from my own personal experience, I'd say your decision should be based on whether or not you're willing to work with some more sides for a while, in case they happen due to introduction of more of the "Deadlock Quartet". More sides may not happen (you could actually get better instead of worse), but they could. What's your tolerance right now for things getting muckier before they get better?
    Last edited: Feb 28, 2014
  10. Leopardtail

    Leopardtail Senior Member

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    My understanding is that ALCAR does actually act on Mitochondrial energy production. The differences I saw in Insulin response would strongly indicate that to be correct. Actually all forms of Carnitine end up converted in ALCAR inside cells - it's the only form that can get into Mitochondria.

    Since ALCAR is not pure carnitine but a compound a higher weight of ALCAR is needed to get the same amount of Carnitine. It can however be bought as powder very cheaply, hence once the dose is high enough, you get the same effect but for less cost. From my experience the mistake often made with ALCAR is taking tablets
    in doses that are too small.

    I am unsure whether the same applies with LCF, but with ALCAR taking less more often works better.

    That said people do react uniquely to supplements, for me CQ10 did nothing at all but many PWME swear by it.
  11. kraken

    kraken

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    Thats exactly where & how I feel also! I've also thought about inflammation being the cause as it feels very physical. Strange thing when I been taking higher doses of folate is that sensations first seems to lessen a bit, but then come on again stronger for a while. Maybe the healing are stirring up some unresolved things in there. This might explain the accompanied anxiety as well. At least according to Hip on this forum, who believes that a lot of anxiety is caused by inflammation. Got NAG which is anti-inflammatory, gonna try that for a while again (it did work good when I was on it earlier).

    @ahmo, @whodathunkit, Potassium footbaths does indeed sound a bit impractical but it sure does would be a good idea avoiding stomach problems etc. Think I'll go for the Chloride next time ordering, its dirt cheap on iHerb compared to gluconate. Usually I dont have a problem with tastes as long as I know it will benefit me :)

    As for the ALCAR, I will try that first if I decide to include it. Have to read up on it a bit more on its role in methylation though, I understand that its involved in the KREBS cycle and supportive for the mitochondria. I actually bought it for cognitive purposes and remember that I got some anxiety from it. Probably why I quit.
  12. whodathunkit

    whodathunkit Senior Member

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    @Leopardtail, @kraken: actually I didn't meant imply that ALCAR doesn't work on the mitochondria...sorry if that's how it came out. I just meant that while they have some of the same actions, ALCAR works on nervous system/cognitive functions moreso than LCF. My understanding right now, anyway. And for whatever reason some don't get the benefit of ALCAR, whereas they do from LCF. I seem to be one of those, although I may try to find some Sigma Tau ALCAR to see if the brand/manufacturer makes any difference like it's supposed to with LCF. I've never used any LCF except the Doctor's Best that uses Sigma Tau manufactured powder, but I've tried several different kinds of ALCAR (none of which worked).
  13. kraken

    kraken

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    Update on my experience in case anyone interested: 4.8 mg folate, 4 mg B12, crumb of Adb12 and around 2g Potassium today.
    Much better! Actually beginning to feel pretty great. Also worth mentioning that I ate a big portion of salmon for lunch (Omega 3). I never found the capsules to do much at all, but then I could be dosing too low..
    Still feel that my cold is lingering somewhat though so might up the folate even more the coming days.
  14. Leopardtail

    Leopardtail Senior Member

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    Kraken,

    I had the symptom with ALCAR too, more energy but short term anxiety. I just persisted with it and waited it out - it took around 12 weeks to wear off. ALCAR affects so many things that without lots of testing its impossible to work out what's going on. Resurrection of the immune system can cause these problems, a side effect of better ATP production without full healing. It can also (like all other methods working on ATP production cause improvement in Insulin action with temporary side effects (post on that elsewhere on Phoenix). On the other hand what ALCAR does as a Neurotransmitter is reactivate the para-sympathetic (calming) nervous system with a massive range of positive effects outside of that system. This can make it a double edged sword however helpful long term.

    @kraken - have you thought of combining it with LCF taking a little of each in order to curb the size of this effect? Or do you no longer need Carnitine? If it's working correctly, you should not need to take in indefinitely.
  15. Leopardtail

    Leopardtail Senior Member

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    @whodathunkit - No worries, just trying to clarify the position. The dose is the bigger issue ALCAR needs twice the dose of LCF to produce the same effect but is so much cheaper it still costs less.
  16. whodathunkit

    whodathunkit Senior Member

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    @Leopardtail: thanks, appreciate that clarification. I myself may try combining a little ALACR with LCF to see what happens.

    Would you mind amplifying a little on this statement

    Like, can you easily find any links to threads/posts about this? If not I can search, I don't want you to do my work for me ;) , just askin'.
  17. kraken

    kraken

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    @Leopardtail - alright, guess I'm not the only one to experience anxiety from ALCAR then. Its nice to hear that it eventually wore off, 12 weeks on the other hand - that's a pretty long time. However, may be worth it of course. Guess I could use some improvement of my calming nervous system. Back before, my flight-and-fight response was sort of out of control but I'm doing much better now.

    I havn't thought about buying LCF or to include ALCAR yet. At the moment, I'm actually doing pretty good on just the Folate and B12 with some cofactors. Is it really essential to add in? Did it make a big difference for you?
  18. Leopardtail

    Leopardtail Senior Member

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    For me the combination of Ribose and ALCAR (once done for long enough) produced a huge difference that lasted after I stopped taking them, so a permanent improvement. Before taking them my winter state involved inability to cope with stairs, severe trouble standing, inability to walk more than to the next room and a concentration span on about 20seconds. After taking them for six months and stopping them six months I can now concentrate for 60mins at a time in several bursts throughout the day, walk the shops without strain and get up and down stairs.

    Some indications that you might need it are: issues with fine motor control (e.g. shaving perfectly, tying shoe laces), lack of hunger symptoms, poor sweating when you overheat...

    During that 'agitated period' I had raised levels of both Cortisol and T4 and was feeling quite hot, this was a marked changed for me. This was likely to have caused agitation.

    It felt as though I were not quite fevering for those weeks, but trying to. There is not much research into this, so we are talking my pet theory here, rather than 'proven fact' - its important to make that clear. Both these hormones are involved in a fever response lasting more than a few hours hence it seems likely that the bodies attempts to mount an immune response via fever. I also cleared up a lot of infective symptoms during this time. The body reverts to fever following attempts with Th1/Th2 immune systems.
  19. Leopardtail

    Leopardtail Senior Member

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    The issue of Insulin sensitivity in ME is under researched. It's been touched on by Titelbaum, Howard & others in clinical settings. The book 'Living with ME' touches in this briefly but the reference is hard to find an in passing. I also experienced this first hand (I have diabetes as well as ME) - in my case I had to drop my injected Insulin by 20% in Summer and by 50% in Winter..

    This will be hard work and you will need to understand some medicine to interpret the material.

    I would suggest you first search PubMed for material on ATP & ME - you will get a small number of results - Sarah MyHill did work on this. That first part will be easy.

    To establish the stuff on ATP and Insulin resistance you will need to look for Mitochondrial Disease, Type II diabetes, or Polycysistic Ovarian Syndrome and ATP or Insulin Resistance. Alternatively get a copy of "Oxford Textbook of diabetes and Endocrinology" requested from your local Library and look up those same diseases.

    The underlying cause needs you to read a lot of research and have a good understanding of endocrinology. It basically boils down to ATP - all disease featuring Insulin resistance also feature poor ATP production. That is also true of ME. For that reason it seems very likely that this causes the clinical symptom. I am trying to get a research project organised at the moment that proves this conclusively.

    What's also interesting is that when people suffer negative side effects of Ribose/CQ10/ALCAR they exactly match the aftermath of hypoglycaemia as recorded in diabetic textbooks. Be aware that the symptoms during a hypoglycaemia and those following one are not the same. My virtue of being diabetic I have been able to actual test my blood sugars and those of friends to check this is occurring.
  20. whodathunkit

    whodathunkit Senior Member

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    @Leopardtail: I'm beginning to have a pretty good understanding of the role ATP plays in insulin resistance and diabetes. I was just hoping for a quick summary. ;)

    FWIW, I have not been diagnosed as diabetic but have had trouble with insulin resistance and blood sugar control as evidenced by my own personal, out-of-pocket purchase of glucose monitor and test strips. Eating habits were sole driver of my blood sugar problems...no history in my family on either side. After my experience with Freddd's protocol I now believe my out-of-control appetite was my body's attempt to get the raw material to produce ATP. Now that I'm apparently making ATP the galloping munchies are *GONE*. Plus, I just don't want to overeat any more. Eating too much makes me feel physically uncomfortable now, instead of merely making me feel like a spineless piece of crap psychologically. I never thought I would ever really get control of my appetite. Kick-starting methylation/ATP production has truly been a minor miracle. For me at least. Now I'm just beginning to be afraid it's all going to go away for some reason and I'm going to wind up back in the pit again, as has always happened in the past.

    For years (decades) I've been hearing that "All disease is a problem of energy" or some variation thereof. I don't remember who is originally credited with that. Possibly lots of people. I never really got that statement. Now I 100% *do* get it.

    I never had negative sides with any of those supps and in fact ALCAR did nothing. But I'm going to try a good brand (maybe look for Sigma Tau produced ALCAR, since ST produces good LCF) and see what happens.

    FWIW, the combo of MeCbl, AdCbl, LCF, methylfolate, and ribose first thing in the a.m. is 100x better than coffee for me. I also am feeling more refreshed on less sleep. This extra hour in the morning will make a big difference for me. Hopefully these beneficial effects will continue with no more crashes.

    Now I just need to get some more test strips to see where my glucose is. I ran out and didn't buy again because frankly, before I started all this, it was a little depressing. :(

    Thanks for the research tips. :)
    Last edited: Mar 6, 2014

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