Methylation Support

This compound, also known as S-adenosylmethionine, is support for the methylation pathway

Now, if you look at clinical trials of nutritional supplements for depression, one of the most important of those is SAMe.

"If you don't have the energy reserves, you're not going to be able to do it. And one of the things that we see in people with low methylation in their brain is that they get mentally exhausted because they're investing what seems like all the energy they have in their brain in fighting off these negative thoughts. And if they can't do it, if they give up too easily, those negative thoughts overcome them and that can then interact and synergize to produce a chronic problem of depression."

Why methylated B vitamins alone don't fix methylation

Dr. Cabral explains the big misunderstanding about methylation supplements -- people believe methylfolate and methylcobalamin will fix methylation pathways, but these are incomplete without the cofactors that actually move methyl groups.

"People are believing that methyl folate B9 and methylcobalamin B12 are going to fix the methylation-based pathways, but it's simply not true. They are there to provide methylation or methyl."

B2 (riboflavin) is the engine that drives methylation

Riboflavin (vitamin B2) converts to FAD, which acts as the conveyor belt that shuttles methyl groups from B9 and B12 to where they need to go. Without B2, the methylated cargo has no engine.

"So if B9 and B12 are the cargo, B2 is the engine. Why is that? Because riboflavin is converted to FAD, something called flavin adenine dinucleotide. What does that mean? It's simply an electron carrier, but it moves things. It's the conveyor belt."

Foundation first, then targeted methylation support

Rather than cherry-picking individual B vitamins, Cabral recommends starting with a complete daily multivitamin that covers all B vitamins plus minerals, then layering on additional methylated B9 or B12 only if needed.

"So, what we're typically doing is we're using something called daily nutritional support, which has all your vitamins and minerals and electrolytes. And it also has essentially a lot of other cofactors as well, or the daily activated multivitamin, two at breakfast, two at dinner. Very simple."

Symptoms of methylation supplement overload

Taking methylated B vitamins without proper cofactors can cause anxiety, overstimulation, insomnia, heart palpitations, headaches, and brain fog -- signs that methyl donors are flooding the bloodstream without being properly utilized.

"So, if you are dealing with anxiety or overstimulation, insomnia, heart palpitations, headaches, irritability, tired and wired, brain fog, and you have those things, you started taking a B vitamin or let's say an MTHFR formula, you felt better maybe temporarily and then got worse, it is most likely because you flooded your bloodstream."

Avoid folic acid and cyanocobalamin supplements

Most supplements, energy drinks, and fortified foods contain synthetic folic acid and cyanocobalamin instead of the methylated forms your body needs.

"Your folate is likely folic acid. Your energy drink, your cereal, your supplements, your multivitamin, these all have these things."

MTHFR gene affects methylation in every cell

Brecka explains MTHFR mutations using a sandbag analogy -- defects at one point create downstream deficiencies throughout the body.

"You're not as sick as you think you are, you're just deficient. If you hunt for the deficiency, you could fix a lot of what we face."

Methylation Support Discussion

The problem is that this program gets completely rewritten with aging.

"The problem is that this program gets completely rewritten with aging. And we don't know exactly why, whether it's errors or whether it's just the program kind of having glitches along the way."

Methylation Support Discussion

I don't know what it's called, but... Yeah, surviving to the next.

"And it was interesting because the suppression of inflammation was the only thing that could predict going to the next age group or engineering. I don't know what it's called, but... Yeah, surviving to the next. Right."

Methylation Support Discussion

This measurement may be more fundamental, more interesting than many other markers, because, as we'll discuss in a moment, it's predictive value. In this episode, we're going to talk about two generations of epigenetic clocks.

"This measurement may be more fundamental, more interesting than many other markers, because, as we'll discuss in a moment, it's predictive value. In this episode, we're going to talk about two generations of epigenetic clocks."

Methylation Support: How To

The reason why this is not yet a viable strategy is because people who get a transplant often get so-called graft versus host disease. It's a dangerous procedure, but in theory, it could work.

"A grim age is a pretty good predictor of time to coronary heart disease. Surprisingly, these clocks even predict time to cancer. These are no doubt exciting times for the aging field. I want to tell you about two really profound experiments that tell us very interesting things about some of the drivers of epigenetic age. One is an accidental human experiment happening inadvertently in the clinic every single day. The other, an animal experiment notable especially for its ingenuity. Scientists have long known that paracrine signaling, the molecular and cellular niche created from cell-to-cell interactions, is extremely crucial in maintaining tissue health and integrity, and even, as it turns out, youth maintenance. In other words, keeping our tissues young. But what happens if you can bring an older animal into a younger animal's network of cellular signals on a daily, minute-to-minute basis? That's the question. In animals, the experimental surgical union of their vascular systems, known as parabiosis, leads to the transference of blood-borne factors from the younger animal into the older animal. Some evidence has shown that this can lead to a youthful phenotype and rejuvenating effect in certain tissues. While these experiments have been the excitement of the aging field for a while, despite their somewhat clinical impracticality, the results of Dr. Horvath's lab, he says, have been somewhat mixed. However, humans have been doing a somewhat modified version of this experiment too, but inadvertently. Surprisingly, at least insofar as epigenetic clocks are concerned, the results here are even more exciting than animal research. Let's say you take a 50-year-old and you give this person a bone marrow transplant from a 20-year-old. And so after the transplant, the blood in the recipient reconstitutes itself. The person has now new blood. And the question is, what's the age of the blood? Is that blood, does the blood have the age of the 20-year-old donor or the age of the 50-year-old recipient? There are now several scientific papers that really give an unequivocal answer, which is the reconstituted blood in the recipient has the age of the donor. And that effect persists for decades. Bone marrow transplants are different from parabiosis. For example, in leukemia, it is sometimes necessary to irradiate, destroy, and ultimately replace the entire hematopoietic system via a bone marrow transplant. This ultimately results in the recipient having cells that no longer track with their own epigenetic clock. Rather, they track with the donors. That means if you're unlucky enough to have leukemia, but lucky enough to have a younger donor, you might ultimately be able to enjoy younger T-cells, macrophages, white blood cells, and natural killer cells. A tissue-specific epigenetic age reversal effect that lasts, as you heard a moment ago, for decades. Unfortunately, cancer treatment as a whole does accelerate epigenetic age. So that's on some level a very exciting finding because it kind of hints to an idea that you could possibly rejuvenate people through transplantation. The reason why this is not yet a viable strategy is because people who get a transplant often get so-called graft versus host disease. So disease. So there are all sorts of complications. It's a dangerous procedure, but in theory, it could work. There are a few experimental ideas for how to interfere with the epigenetic clock or otherwise rejuvenate the methylome. One is using drugs to play with inhibiting the enzymes that directly interact with DNA methylation, known as DNA methyltransferases. These drugs already exist, and in mice, with disorders of the epigenetic machinery, these drugs are able to reverse some effects of those conditions. The other avenue, which is a bit more promising in my opinion, is manipulating the expression of genes that encode for transcription factors already known to reverse epigenetic age. Right now, there's an idea in the aging field to rejuvenate people by leveraging this fundamental insight that you call, it's called reprogramming. You can take an old cell, you administer certain factors. Called Yamanaka factors, these factors can revert a differentiated somatic cell back in epigenetic age to an embryonic or near embryonic state. Even more interesting, scientists know that by genetically engineering a switch, one that is turned on by a chemical, they have been able to add these Yamanaka factors to animals to reverse even certain aspects of tissue aging by pulsing these factors. But don't switch them on for too long, says Dr. Horvath, because too much of the Yamanaka factors may revert cells too far back, ultimately inducing malignancy. One of the biggest challenges in repeating this experiment in humans, however, is that genetic engineering is not without risk."

Methylation Support Discussion

Then if you followed them for 60 years, you know, you would find this consistency that people who are slow agers at age 20, they also slow agers at age 60 or 80.

"Yes. So that's one line of evidence, but there's another. So people have these longitudinal epidemiological studies, and they may have collected a blood sample from a person when they were, let's say, 40 years old."