NBC Nightly News & Dr. Isaacson Tonight

[SusanJ]

Circ,

677 (rs1801133) - CC (GG) is wild type, TT (AA) is the variant
- TT is up to 70% less effective enzyme

1298 (rs1801131) - AA (TT) is wild type, CC (GG) is the variant
- not as much research on this one, but perhaps not as bad as 677

rs9651118 - TT (AA) is wild type, CC (GG) is the variant
- very few studies look at this one, so don't know

So you don't have MTHFR issues. Probably why the methylated stuff gave you side effects.

Stavia,

I would try bringing the B12 up before throwing in the methyl folate (see the methyl trapping ref above). I am homozygous 677 variant and I take 1000mcg methylcobalamin and 2000mcg (half calcium folinate and half 6(S)-5-methyltetrahydrofolic acid) along with riboflavin, B6 and Betaine. Your doses might be a bit high without the variants?

I will say that a few of us here have tried to drive down homocysteine with B vitamins without success. Even with high doses of B vitamins, my homocysteine has not budged one iota from 8. And going higher just makes my brain buzz, so it's not an option.

Poking around, I just found this one - haven't read it yet, but might have some info.
Gender and single nucleotide polymorphisms in MTHFR, BHMT, SPTLC1, CRBP2, CETP, and SCARB1 are significant predictors of plasma homocysteine normalized by RBC folate in healthy adults.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3417835/

[jacquie]

I saw the NBC piece too, with Nancy Snyderman and Max. Prevention is key and it is good to start now if you have the gene for it. But I did think that Max appeared to be in pretty good shape though.

I am wondering about something - do they know from bloodwork what exactly is the trigger that causes the amyloid plaques, and is that what they will concentrate on preventing? I read Dr. Bredesen's paper, and remember he mentions in there a certain substance that turns on the switch for the amyloid plaques to start building up, and with the right intervention, he felt the switch could be turned off again. I am just wondering if it is something that does show up in the bloodwork, and what we should be looking for... I hope that this will be discussed at some point more, with the people running the trial and that we can ask our doctors to look for it, if we are following along.

Also, what is considered a good level for homocysteine? I am A1298C homozygous. I don't think I have raised homocysteine levels, but I know that A1298C's are different from the 677 variants, in terms of their homocysteine levels and issues.

[LillyBritches]

Guys, I know I've said this before on another thread...but Dr. Trutt told me that TMG (betaine), 2,000-3,000 mg daily, was the way to go to reduce homocysteine. Mine was higher than it's ever been last lab - it was 10.5. I believe it was 9 in my prior lab. He wasn't worried, but he wanted it more around 7-8 (if memory serves) (mwah). 10.5 is certainly NOT acceptable to me.

And my husband's is higher than normal (not by much, but still) - so we're both on TMG 2,000 mg per day.

It just occurred to me that the one thing I had changed (besides the Medifast diet) between last labs and these most recent labs that might impact homocysteine levels was coffee. Yep. I had gone from one eight-ounce cup to 16 ounces per day. Coffee will raise homocysteine levels every time.

But if y'all haven't yet, you might want to look into TMG...the way Dr. Trutt put it...if you're optimized on all your Vitamin B levels, the addition of TMG (high mgs) should do the trick.

There's a lot of solid science out there re TMG reducing homocysteine.

[Welcomeaboard]

I am playing connect the dots here. In my coffee and hydrochloric acid and other chain of recent posts. BETAINE raises hydrochloric acid in the stomach, which is a great thing if you are low HCL on your dipstick. The dipstick can be checked with the betaine test that I mentioned was out there in the ether of the internet, or even the baking soda and water test in the ether as well,
As well as the numbers( percentage wise )of low on the dipstick HCL sufferers.

So now we have raise your HCL and lower your homocysteine issue that you may have created or exacerbated by diet choices or worse by just growing old. I guess some forgot about their youthful Peter Plan pledge and now are suffering the consequence. However, after the last three hour live rendition of Peter Pan, I can fully understand why someone would want to cancel their contract without reading the fine print clause. See subsection J, paragraph 3 b of the bodily functions that can and will be effected as craftily worded by Captain Hook, I surmise.

[Gilgamesh]

Speaking of Golden - Gilgamesh! Nice to see you 'round here. So does this mean your non-academic sabbatical is no more?

Hey friend,

Missed a flight, and therewith found myself with some free time. Otherwise, still struggling with my writing deadline. Will be back in woodshed mode shortly.

Meanwhile, I'd love to know whether Trutt thinkgs TMG would help people who have bad versions of the BHMT SNPs. I can't figure out whether having a suboptimal BHMT enzyme means I need more TMG, or whether (my suspicion) it means it would be worthless to throw TMG at it.

GB

[SusanJ]

G,

After reading WA's other post on betaine in human nutrition on another thread, I went to the paper.

It doesn't say specifically that betaine can push BHMT variants, but it did point to the inverse relationship between betaine levels and homocysteine.

Betaine can improve both risk factors, and in humans with cardiovascular disease, there is a significant inverse relation between plasma betaine and homocysteine concentrations in fasting (199) and postmethionine (200) states. A betaine-rich diet might lower cardiovascular disease risk in healthy humans (201)...

Prevention or treatment, such as activation of defective (mutant) enzyme activity with the relevant cofactor or its precursor (eg, folic acid or vitamins B-12 or B-6), is based on the cause and severity of the defect. If homocysteinemia does not respond to this treatment, pharmacologic doses of betaine or folic acid have been used to enhance the alternative pathway of homocysteine turnover (203, 204).

Their comment on supplementing:

Mild homocysteinemia can be reduced immediately and in the long term by ingesting a combination of vitamin B-6, folic acid, and betaine (244, 245) or betaine (1.5-6 g/d) alone (57, 189, 198, 201, 246). Betaine, but not folic acid, is effective at preventing an increase in postmethionine homocysteine concentrations (198, 201, 244, 247, 248). Betaine-dependent remethylation occurs mainly in the liver and kidney, whereas folate-dependent remethylation occurs in most cells. Serum homocysteine concentrations may be represented by the extrahepatic supply to the liver via folate remethylation and by the hepatic output via betaine remethylation (198). Therefore, combined ingestion of folic acid and betaine may be the most effective method of lowering homocysteine.

http://ajcn.nutrition.org/content/80/3/539.full

The pharmacologic doses seem to match Trutt's suggestions to Lilly.

Top sources of betaine are whole wheat, spinach and shrimp. Betaine is a choline derivative, so choline intake appears to be related, too.

I only take 500mg of betaine per day. Might not be enough for me to see any results.

[Stavia]

Thanks Susan. It all seems very complex. If I dont have MTHFR defects do I need folate supplements at all?

[Welcomeaboard]

Folate, Vitamin B12 and Human Health.

[SusanJ]

Stavia, yes, methylation is mind boggling at times. It's such an important process that there are numerous (backup) paths to the same end for us humans. So when you push one side of the process it has a major ripple effect downstream.

Personally, if I was in your shoes, I would stick with the B12, and talk to your doc about trying higher doses of betaine (show your doc the study I ref'd above on the effects of betaine). You don't have the MTHFR variants, so I don't see how methyl-folates will help there, unless you are short on methyl donors in general due to a different reason.

B12 and betaine might be all you need.

[Welcomeaboard]

Some of the problem can be the lack of synergy together and or lack as in eating betaine foods in the morning and folate in the evening. Or eating foods that counter each other or one that dilutes the other. There are foods brassicas and I forgot the other but it is on 23and me under coffee thread that I posted, one slows the metabolism out of the body and the other increases the time of metabolism in the body.