Serine + Vitamin B6: No Effect On Homocysteine (Test #2)
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- Опубликовано: 30 сен 2024
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Paper referenced in the video:
Comparison of the effects of nicotinic acid and nicotinamide degradation on plasma betaine and choline levels
pubmed.ncbi.nl...
That's a one fantastic video. Tje best and most reliable approach. Talking from experience. Congrats!
I personally wouldn't worry much about the conversion from homocysteine to methionine. I see homocysteine as the clearly less desirable compound of the two. Did you check your methionine blood levels? Depending on what levels you have, if you were able to convert 5 µmol of your homocysteine to methionine, that would be 50% less homocysteine, but only e.g. 20% more methionine, I think. (Typical levels are around 25 µmol/L.)
Anyway good luck with your next result. Thanks a lot for your insights and updates.
Thanks @bottlenecks. I do have methionine blood levels, but how much is optimal in people is debatable, as few large epi studies have quantified it.
@@conqueragingordietrying123 and @bottlenecks -- ah biology, if only it were that simple. There are usually feedbacks in place that are hard to understand and in this case there is evidence that methionine supplementation actually increases homocysteine acutely: Effect of L-methionine supplementation on plasma homocysteine and other free amino acids: a placebo-controlled double-blind cross-over study, Ditscheid et al 2005.
Not withstanding Mike's point about few all cause mortality studies, it would seem keeping methionine low(er) may be beneficial for homocysteine. I am left wondering if this entire pathway is full of rate limiting steps and feedbacks, meaning the best way forward might be to reduce homocysteine formation in the first place and then supplement to keep the outputs of the cycle high (e.g. for high glutathione), along with taking reasonable steps to increase the flow through the pathway with serine+B6 or B12.
Hey there, I came across your channel through your videos addressing homocysteine. I see that you've been trying to move the needle through the CBS pathway as it presents itself as an outflow. Intuitively, I'd agree that this seems like the best approach, however following your videos of trying to take advantage of the CBS pathway, and your history with B12, I think one thing you've overlooked is the idea surrounding folate/b12 or BHMT recycling back into the methylation cycle implying that there would be a zero-sum difference in homocysteine levels. I don't think this is the case, in fact, the more opportunity that homocysteine has to turn over back into methionine then the more likely it is for a synthesis to take place where the end products aren't SAH or homocysteine. Essentially meaning that the recycle pathways are also drainage pathways, albeit not as self-evident as the CBS pathway.
Cheers, thanks for the great content.
One other perspective is that you could look at a list of all endogenous compounds that homocysteine is a byproduct of. Theoretically, increasing intake of these compounds should reduce homocysteine production in some (not all) instances.
Thx for the data.
Maybe my N=1 experiment is interesting for you.
I started with Homocysteine of 11.42 nmol/l. I supplemented daily with 800 micrograms of folic acid, 400 micrograms of B12, 15mg of B6, 10mg of B2 and 500mg of betaine. After 3 month the test came back with 6,1 nmol/l.
I try now the same dose every other day and will test in a month.
That's definitely good news-did you track other biomarkers on the same day? The goal is to reduce homocysteine without messing up anything else.
@@conqueragingordietrying123 I had a normal panel + apo B and HC. Nothing unusual to see. At what should I look especially next time ?
You should try NAC to lower homocystein "Effects of Oral N-Acetylcysteine on Plasma Homocysteine and Whole Blood Glutathione Levels in Healthy, Non-pregnant Women"
A lot of minerals are associated with lower homocysteine:
> Traditional regression model showed that higher intake of calcium, phosphorus, potassium, magnesium, iron, zinc, copper, and manganese was associated with lower blood Hcy levels. Both Qg-comp and BKMR results consistently indicate that higher intake of mixed minerals is associated with lower blood Hcy levels. Calcium exhibits the highest weight in the joint effect in the WQS model. In Qg-comp, iron has the highest positive weight, while manganese has the highest negative weight. The BKMR results of the subsample after 10,000 iterations showed that except for sodium, all nine minerals had the high weights in the joint effect on the effect of blood Hcy levels
"Relationships between minerals’ intake and blood homocysteine levels based on three machine learning methods: a large cross-sectional study"
This is fantastic. Naked Mole Rats are reported to have exquisite metabolomic processing shunning homocysteine and favoring glutathione even on standard mouse Chow. Is there a follow-up video #3 on the higher serine/B6 dosage?
Thanks greggdavison5769. Unfortunately not yet-so many videos to make, so little time-the highest serine+B6 dose didn't lower homocysteine.
Where can I read more about the the methylation of the naked mole rat?
Isn't the main benefit of methionine restriction that is lowers homocysteine anyway, or are there any other specific downsides of methionine? Of course converting homocysteine to glutathione would be double whammy, but I wonder which is the most important biomarker.
Reduce methionine, although vegetarian usually have higher homocystiene
It would be interesting to measure glutathione/GSH at the end of the 6g serine + B6 experiment. Maybe this pathway can only reduce Hcy 10-20%, but increasing glutathione could be worthwhile regardless.
Definitely-I've been told a major company in the US will offer that relatively soon, so we'll be able to measure GSH and GSSG...
Fascinating and compelling.
May be you have a gomozygous mutation in SHMT1 ?😄
Homocysteine was about half of what it is now 15y ago, which argues against a genetic component.
Serine makes me tired.
Have you tried me measuring b12 levels in the blood? Despite supplementation, this vitamin can be difficult to absorb for many reasons.
I would also try creatine supplementation, which in some groups lowered the level of homocysteine, but I do not know in what mechanism.
If that fails, I'd try betaine anyway. A diet rich in methionine may increase the level of other sulfur amino acids such as homocysteine and thus shorten life, in this case pushing homocysteine towards methionine and further metabolic pathways make sense. Great content, regards
I see you tried betaine, ok. Anyway i will keep up withe your videos. Good luck
Betaine (up to 3g/d) has no effect on my homocysteine. B12 is significantly correlated with lower Hcy (in my data)-I may go back to that sooner than later.
@@conqueragingordietrying123
As ability to absorb vitamin B12 decreases with age, that could be a truly anti-aging effect. Consider i.m. if oral doesn't work
There is a sublingual form.
I'm 62.
I get asked out on dates all the time from 18 year olds and 20 year olds of various makings and derivatives.
I equate this to my very youthful appearance and hot looking tan.
Good for you, @rdallas81!
@@conqueragingordietrying123 I'm joking.
I'm actually 42. I live a healthy lifestyle.
I take vitamin c daily, Omegas, liver aid, Milk Thistle, apple cider vinegar with Mother, and a few other vitamins. I have a full head of hair, and never took the Jab. When I feel a cold or illness come on, I triple my vitamin c and add Zinc and Magnum to the mix.
I eat a lot. I eat a lot of leafy green vegetables, and steak and chicken.
I on occasion eat oatmeal.
@@conqueragingordietrying123 thanks for this video.
Glycine is said to counter the effect of high methionine in the diet. And low methionine is said to mimic calorie restriction.
Which should indicate that Glycine might mimic calorie restriction, perhaps.
How glycine has that effect on methionine, I don't know!
But this might make homocysteine into methionine less of a problem. Just increase glycine!
The Homocysteine level in Korean centenarians was very high at about 25 umol/L. How could this be? The study was from 2010 title: Discovery of Novel Sources of Vitamin B12 in Traditional Korean Foods from Nutritional Surveys of Centenarians. Their fiber consumption was low about 7 grams per day for men.
Yep, that's very high. It shows that one can live long with high homocysteine, but I doubt that functional health was great. I covered that in this video:
ruclips.net/video/MwtsA391OZ0/видео.html
now it is getting tricky... my guess is that through the high NAD the de-methylation reactions are favored, leading to an abundance of methyl groups, and a feedback effectively slowing down the conversion of HCys to methionine.
Your other results showing higher protein associated with lower HCys where from times when you were low in NAD. Now, with much higher NAD levels a methionine restriction could make sense.
There is also a linear relationship of plasma HCys and (e)GFR, even when GFR is very good (>90), maybe, fluctuations in GFR are masking the expected drop of HCys. Even the specific clearance of HCys varies, and could be dependent on the HPA axis, as well as a (still unknown) further regulation of the methionine synthase. Which brings me to Zn as an important co factor of that.
---since you are ramping up your metabolism, what is your Zn status? I supplement such to get 30..50 mg per day into the diet.
Definitely possible about NAD. Average Zn intake is 14mg/d. Correlations with blood biomarkers don't suggest to go higher.
@@conqueragingordietrying123That's not that much, given its importance. The metabolic availability could be suboptimal. zinc is tricky, since it is a co-factor for so many contexts, I am not sure whether simple one-dimensional correlations across all conditions are meaningful. I think, a stratification of the data, or multi-dim profile analysis could be helpful. Also maybe, from what you have shown elsewhere, around beginning of 2022 your state improved a lot, so the influence of zinc could be different now.
To lower homocysteine, why not decrease methionine intake, and increase betaine to support methylation whilst continuing your Nicotinic acid…..this may be the way to go.
In my data, a higher protein (and correspondingly, methionine) intake is significantly correlated with lower homocysteine, which argues against lowering my methionine intake. I've tried up to 3g/d for betaine, no effect on homocysteine.
If the latest Serine + B6 test doesn't work, it will be back to B12, which has the strongest correlation with lower homocysteine (for me).
@@conqueragingordietrying123 try lowering methionine without lowering protein. Remember goal is to lower all cause mortality and increase health span…(at least this is my goal)
Also, higher intake of Nicotinic acid I believe increases the need for more betaine.
@@conqueragingordietrying123 Could the protein correlation be because the protein sources in your diet also contain substantial amounts of B12?
Its hard to lower methionine much further in a whole foods approach without making a designer protein...that's been done elsewhere, but even then that approach doesn't have zero methionine. The crux is you need leucine to turn mtor on to maintain body composition and the leucine has to decouple from methionine which is difficult in a whole foods approach.
Have you tried folate or methyl folate supplementation in the past for Hcy? That might lower MCV so should be easy to monitor.
I have, but it's not significantly correlated with homocysteine in my data. Only B12 is, I may go back to that sooner than later.
As far as I gathered, serine is one of those things where enantiomers could matter, especially in the brain. Was this accounted for or do you think this might skew your results?
It's L-serine-I'd have to use D-serine to try to lower homocysteine to compare...
@@conqueragingordietrying123 Thanks for validating my concerns.
Methionine is the precursor of homocysteine, a sulfur amino acid intermediate in the methylation and transsulfuration pathways. Elevated plasma homocysteine (hyperhomocysteinemia) is associated with occlusive vascular disease.
To decrease homocysteine just eat less meat dairy eggs?
Interestingly, in my data, a higher protein intake is significantly correlated with lower homocysteine, so there may be more to the story than that...
@@conqueragingordietrying123
Animal protein=high methionine vs
Veggies=lower methionine
@@drrutledgemdDifferent for different people.
I take 5 grams of creatine monohydrate per day. Creatine monohydrate is made of L-arginine, glycine, and L-methionine. Although creatine monohydrate is made partly of L-methionine, it has been shown to reduce homocysteine levels when combined with resistance training.
What are your homocysteine levels with, without creatine?
@@conqueragingordietrying123 I did not test before and after. This is the study that I am referring to- "Creatine supplementation alters homocysteine level in resistance trained men".
That's a good suggestion. It seems to address one of the formation pathways, with a variety of small studies showing homocysteine reduces by about 3 umol/L for every 5g/day creatine. But there may be a dark side in that it may also reduce glutathione and maybe taurine:
Effects of creatine supplementation on homocysteine levels and lipid peroxidation in rats, Deminice 2008.
Whole Body Creatine and Protein Kinetics in Healthy Men and Women: Effects of creatine and amino acid supplementation, Kalhan 2016
Perhaps creatine monohydrate fixes one of the formation pathways but then creates more problems downstream, but those appear fixable.
@@jamesgilmore8192 Thanks! I get most of my protein from legumes. They are very low in L-methionine, so I figured that the amount of L-methionine from creatine might be okay. It is considered to be an essential amino acid. I hope that Dr. Lustgarten experiments with creatine supplementation in the future.
@@jamesgilmore8192I take creatine.
I'm 109 years young.