We’ve had many people ask about homocysteine.
Homocysteine gets a little bit technical. It gets into things called poor methylators. ZdoggMD is a physician with a large social media following. He did a video on poor methylation. He said, “it’s real, but it doesn’t matter.”. But he’s an intensivist; his patients are already in the ICU. He sees people usually for three days, at most for a few weeks. In his world, he’s right; methylation doesn’t matter. When you’re already in the ICU, it’s too late to worry about methylation. But methylation is real for those of us in the real world trying to avoid the ICU.
By the way, I’m a poor methylator. There’s an enzyme called MTHFR (Methyl Tetra Hydro Folate Reductase). It’s what our body uses for the opposite of oxidation (which is reduction). There is significant variation in our ability as humans to do reverse oxidation (which we do through methylation). Over half of us have a sub-maximal ability to methylate. We will review three articles about methylation.
IT STARTS WITH OXIDATION
Let me give you a bit of a core understanding of the issue. There is something called oxidation. Sometimes the things that are our greatest strengths are also our most significant weaknesses. One of our greatest strengths is our ability to oxidize food products like fats, proteins, and carbohydrates.
In fact, for six carbon molecules, we get 36 energy units. They are ADP energy units in the Krebs cycle. A fungus, mold, or yeast gets only six energy units, but we get six times that amount. Why? Because we use oxygen to completely oxidize each of the six carbons & the multiple organic chemistry bonds.
We use the oxygen molecule to completely disintegrate the six carbon carbohydrates. We get a lot more energy out of it.
IT’S ALSO CALLED FIRE – OR EVEN RUST
If we’re using oxygen, that’s what fire is: oxidation. Engineers and mechanics also call it rust. We have these little furnaces in our cells called mitochondria. That’s where this process happens.
A KEY MECHANISM OF AGING
Mitochondria are analogous to furnaces. When you look at the key mechanism for aging for the past 50 years, it has been the mitochondrial theory of aging.
The theory says each of these little mitochondria, which can be several hundred of them in a heart cell, is so active that each of those little furnaces begins to burn out just like any other 60-year-old furnace. You get holes the in the iron casing. You get burning embers lying around smoking.
ANTIOXIDANTS – A $7 BILLION INDUSTRY
The mitochondrial theory of aging has caused the antioxidant market (mostly preparations containing vitamins A, C & E) to grow to a $7 billion industry.
But the body actually has a different way of dealing with this problem. It’s called methylation. Instead of adding a hydrogen atom (like chemists do in the lab), our body adds a methyl group.
LET’S BACK UP A SECOND: WHAT’S REDUCTION?
Fire is oxidation. In the lab, oxidation literally consists of adding an oxygen atom. (That’s why human bodies get so much more energy by using oxygen).
PUTTING OUT THE FIRE WITH WATER
Putting out that fire is called reduction. As we just stated, in the lab, oxidation is accomplished by adding oxygen. Reduction is accomplished by adding a hydrogen atom. (You might have remembered that adding a couple of hydrogen atoms to an oxygen atom makes a very stable molecule – water – or H2O).
So, adding oxygen is oxidation; adding hydrogen is reduction. But our bodies don’t do it the same way. Our bodies use a methyl group instead of a lone hydrogen atom.
OVER HALF OF US DO NOT METHYLATE COMPLETELY
Now, we understand the importance of methylation as our body’s natural antioxidant mechanism. Let’s discuss the challenges in our body’s antioxidation mechanism and the body’s ability to put out the fire with methyl groups.
OVER HALF OF US HAVE SUB-OPTIMAL MTHFR GENES
As I mentioned before, human beings have different levels of methylation. There’s a gene called MTHFR. There are three significant variations of the gene. I have not one of those suboptimal variations; that makes me a poor methylator.
I’M A POOR METHYLATOR
Remember my numbers: I technically fit the diagnosis of full diabetes with multiple recorded glucose values over 200. And I have the least effective genetic variation of the MTHFR gene. So I have the worst human mechanisms in the human gene pool for decreasing the oxidation in diabetes. And diabetes is a very oxidative process.
LIFESTYLE IS SAVING MY TISSUE
But using mostly lifestyle, I’m able to keep my numbers good. For example, my last HDL reading was in the 80s. & my tissue damage is minimal. I have one druse. (Most doctors don’t know what a druse is. It’s a single cholesterol deposit in the retina of the eye. They know what drusen are, but they never hear of the singular (druse), because this damage is usually seen in the plural form). I’ll explain a little later.
BUT YOU DON’T NEED GENETICS – CHECK YOUR HOMOCYSTEINE
I worked at a human genetics lab for a few years; I could get MTHFR genetics without cost. It’s usually expensive. But you don’t need to go through costly genetic testing. Look at this crucial bioindicator: homocysteine. Elevated homocysteine was discovered long ago to be a CV risk factor. Like many bioindicators, we’ve found out why it’s important. It’s an indicator of poor methylations. Let’s go over three articles covering different aspects of homocysteine & methylation.
HOMOCYSTEINE & FOLATE DEFICIENCY
This article is from Clinical Lab and Hematology, 2011. The study was from the UK, “Homocysteine and Folate Deficiency”. They looked at pregnant women with deficiencies of folates. The lack of folate is important because it can cause spina bifida in the child. But they’re not looking at spina bifida in the child.
They’re looking at the mom and her metabolism. Deficiency of folate during pregnancy is associated with megaloblastic anemia; elevated homocysteine and methylmalonic acid correlate with folate deficiency.
https://pubmed.ncbi.nlm.nih.gov/11553056/
METHYL MALONIC ACID IS THE BEST TEST FOR FOLATE DEFICIENCY
We look for folate deficiency when screening for MMA (methylmalonic acid). If you are one of my patients, we may have tested you for it and have that discussion.
This study took 263 pregnant women and measured red cell folate, serum folate, vitamin B12, homocysteine, and methylmalonic acid. Higher homocysteine levels were found in subjects with lower red cell folate levels. To get that result, we went through many details: low folate, high homocysteine. Again, high homocysteine may mean low folate.
THE NEXT ARTICLE: HOMOCYSTEINE & FOLATE SUPPLEMENTATION
Here is a piece of effective multivitamins on homocysteine in women over 60. It was published in the European Journal of Nutrition in 2005. This deficiency of folic acid, vitamin B6, and vitamin B12 can result in elevated total homocysteine.
The authors evaluated the effect of a six-month supplementation with B6, B12, and folate on the total plasma level, homocysteine, and methylmalonic acid. After supplementation, homocysteine and methylmalonic acid concentration decreased significantly, especially in those with lower vitamin concentration.
Remember we covered above the whole antioxidant craze of vitamins A, C, and E? Remember it forgets what the body’s natural method of antioxidant activity? The body reduces with an entire methyl group, not just a hydrogen ion.
https://pubmed.ncbi.nlm.nih.gov/15309436/
WHY FOLATE & THE OTHER B VITAMINS?
Why are we talking about the B complex vitamins? The body uses the B vitamins, folate, B6 and B12 as a storage pool for the methyl groups. That’s why the vitamin B complex is more important in oxidation-reduction in managing that process than vitamins A, C, and E.
If you can help the body’s own natural mechanisms, it’s more effective than using artificial mechanisms. Natural is better.
NATURAL IS BETTER; SO USE METHYLATED B COMPLEX
After supplementation with B6, B12, and folate, the total plasma homocysteine methylmalonic acid concentrations decreased, especially in those with lower vitamin concentrations at baseline.
THE LINK BETWEEN ELEVATED HOMOCYSTEINE & POOR METHYLATION
The Journal of Inborn Errors of Metabolism and Screening, 2017, published a study by a Portuguese research team. The link was between hyperhomocysteinemia (too much homocysteine in the blood) and too little methylation. It demonstrated that poor methylation is a risk factor for CV disease.
This is a review article & a meta-analysis of multiple other studies. They showed that mild hyperhomocysteine anemia is an independent risk factor for cardiovascular disease.
We had Craig Brown on the YouTube show a while back. He’s an ophthalmologist who works with this issue. He’s been giving methylated B vitamins as a medical food. He showed some of the pictures of retinae in people with diabetes. These people had severe collections of drusen. He is giving the methylated B complex & the AREDS2 supplement combination (lutein, vitamin C, vitamin E, zinc, copper) to prevent blindness.
DIABETIC EYE DAMAGE (DRUSEN) ARE FROM OXIDATION OF TISSUE
As mentioned earlier, I have one druse. Drusen are the cholesterol packets found in the retinae of someone with diabetes and retinopathy. For a 65-year-old man with full diabetes, it’s very unusual to just see just one druse. As I mentioned, that’s due to my care (mostly lifestyle) of my condition.
It’s not so hard to manage this problem after you know what you have. You don’t have to go full keto every day with a bit of discipline.
OXIDATION DRIVES DAMAGE TO THE LIVING OF THE ARTERIES
Oxidation is the key driver of endothelial dysfunction. The endothelium of arteries is called the intima. We need to watch out more for intimal damage and less for stress test abnormalities. Stress tests simply tell us about blood flow. Inimal damage tells us about oxidation, damage to artery walls, & the risk for forming clots. It’s the clots that cause tissue damage, not the level of flow.
OXIDATION DRIVES SOFT PLAQUE
Remember that we discussed Tim Russert passing his stress test? His flow was good; he was an avid runner. But soon after the normal results on his stress test, he died of a heart attack. That’s because he had a lot of CV inflammation. The coroner said his arteries looked like they had acne, full of inflammatory pimples. CV inflammation results from inadequate cooling (reduction or methylation) of oxidative processes, like diabetes. Undiagnosed prediabetes is the most common driver of excessive oxidation.
SUMMARY
So, what we have seen today is that high homocysteine levels can indicate poor methylation. Methylation is our body’s natural method for antioxidants. Antioxidants are critical to health & longevity. The need for the antioxidant activity goes back to our core metabolism, the ability to obtain more energy from food using complete oxidation. And that’s why we carry oxygen in our blood.
If you found this article helpful and want to start taking steps toward reversing your chronic disease, Dr. Brewer and the PrevMed staff are ready to serve you no matter where you’re located.
To find out more, schedule a consult here: prevmedhealth.com
REFERENCES:
1. https://prevmedhealth.com/vitamin-d-should-you-supplement/
2. https://prevmedhealth.com/how-to-identify-and-handle-chronic-inflammation/
3. https://prevmedhealth.com/diabetic-retinopathy-methylation-methylfolate-ared/
4. https://prevmedhealth.com/olive-oil-and-cv-inflammation/
5. https://prevmedhealth.com/inflammation-not-cholesterol-is-the-bigger-heart-disease-risk/
6. https://prevmedhealth.com/estimating-heart-attack-risk-with-framingham-risk-score/
7. https://prevmedhealth.com/cardiovascular-inflammation-and-plaque-formation/
8. https://prevmedhealth.com/stress-tests-cardiac-cath-stents-the-unnecessary-triad/