TL;DR: Two simple markers — SAMe/SAH (plus homocysteine) — help you understand your methylation status and choose a safe action plan.

Educational content. Not medical advice.

***

If this helped you, collect this post on Paragraph to support my work. Thank you!

***

We marvel at every new technological breakthrough humans create, yet we rarely stop to admire the most advanced, efficient, and complex technology in the known universe: the human organism. No human invention comes close, in complexity and adaptability, to this marvel of evolution—a self-organizing system that sustains, repairs, and continually adapts itself.

But let’s start at the beginning, because the most extraordinary part is how it all began: from nothing.

About 4 billion years ago, Earth was just a mass of physical and chemical matter. Simple molecules drifted aimlessly, with no “memory” of anything. Over time, they began to combine until one of them acquired a revolutionary property: it could copy itself.

That instant changed everything. For the first time, matter began to store information about its own structure. It didn’t just exist; it could replicate and pass itself on. As if nature had written the first lines of a program able to run, maintain itself, and improve over time.

From there, life set out on its path: those first molecules gave rise to simple cells, then to more complex ones. Multicellular organisms emerged, animals appeared, and much later, the first hominids. All of us—from a bacterium to a human being—share that origin point: the moment chemistry became biology and information began to organize itself and evolve.

Now we’ll delve into one of the most sophisticated mechanisms of that self-organization: epigenetics, the system that regulates how genetic information is used so organisms can adapt to a constantly changing environment.

Without information there is no organization, and without organization there is no life. As we saw, life began when matter learned to store information. In biology, that information is arranged on two levels: genetics and epigenetics.

It’s our factory manual. It tells how the organism should be built and how it should function, setting its limits and possibilities. It’s stored in DNA and doesn’t change: we’re born with it and we die with it. Although tools like CRISPR can modify it, in everyday life it is, for all practical purposes, unalterable.

Epigenetics regulates which parts of the DNA are switched on or silenced, and when. It doesn’t change the content of the manual, but it does change how it’s interpreted: it arranges, orders, and gives meaning to genetic information. Like accents and commas in a text, its role is decisive. Its advantage? We can modify it and improve it.

Imagine a piano and a pianist. The piano represents our genetics: the instrument. The pianist is epigenetics: the one who decides which keys to press and when. A great performer with a mediocre piano can still produce a beautiful melody. But a perfect piano in clumsy hands won’t prevent disaster. That is the power of epigenetics.

Epigenetics allows us to interpret the information contained in DNA through two essential mechanisms. I explain both in more detail in my book Nutritional Epigenetics, but here we’ll focus on one of them: DNA methylation.

Our bodies use a molecule called S-adenosylmethionine (SAMe, for short) that carries something valuable: a methyl group. SAMe transfers this chemical tag to specific regions of DNA to mark them as not to be read or activated.

Returning to the piano analogy, SAMe places signals on certain keys (segments of DNA), telling the pianist (epigenetics) not to play them so the melody—the organism’s functioning—keeps its harmony.

This process performs two vital functions for the organism’s health, longevity, and stability:

1. Stabilization of the genome: it prevents the activation of DNA regions that are prone to generating mutations.

2. Cellular differentiation: it tells each cell which genes to ignore according to the tissue it belongs to. For example, a cell in the eye doesn’t need to switch on the same instructions as a liver cell.

As you can imagine, having enough SAMe is essential for this process to work properly.

Although it’s the second most widely used molecule in our bodies—surpassed only by ATP—SAMe is still largely unknown. It’s time to recognize its role.

Carlos López-Otín, in his influential article “The Hallmarks of Aging,” identified two key factors in the aging process: epigenetic alterations and genomic instability. Sitting right between the two is DNA methylation, a process essential for keeping the genome stable. And who supplies the raw material for that methylation? Exactly: SAMe.

The problem is that, with age, SAMe levels decline—and they do so exponentially.

Without SAMe, there are no chemical tags, and without tags, the process fails. In biology, this deterioration is known as global hypomethylation: a state that destabilizes the genome, accelerates aging, and opens the door to multiple diseases.

That’s why one of the goals of the practical section of my book is precisely this: to show how to raise SAMe levels, improve methylation, and, in doing so, reduce disease risk and slow aging.

As if its epigenetic role weren’t enough, SAMe also takes part in numerous processes vital to the body.

In fact, around 90% of available SAMe is used for two key functions: the synthesis of creatine—essential for energy production in muscles and the brain—and phosphatidylcholine—crucial for the integrity and fluidity of cell membranes, especially in the brain, where it helps protect against neurodegenerative disease.

In addition, SAMe is needed to:

• Break down molecules that, in excess, are harmful: histamine, vitamin B3, estrogens, dopamine, adrenaline…

• Synthesize neurotransmitters like serotonin and polyamines such as spermidine, which have anti-inflammatory and antioxidant effects and play a key role in cellular longevity.

• Regulate circadian rhythms, eye health (lens and retina), and the immune system by promoting the proliferation and specialization of T cells.

No small thing.

Without enough SAMe, the body can’t carry out key processes or slow aging. Its deficiency creates a state of global hypomethylation, which is linked to many of today’s most prevalent—and rising—conditions: cardiovascular disease, cancer, neurodegenerative disorders (such as Alzheimer’s, Parkinson’s, ALS, or multiple sclerosis), diabetes, depression, autism, addictions, autoimmune diseases, allergies, migraines, fibromyalgia, ADHD, and, finally, the “mother” of all diseases: aging.

In all these conditions, studies have observed hypomethylation when compared with healthy individuals.

Like everything in the body, SAMe requires balance: its deficiency (hypomethylation) is harmful, and so is its excess (hypermethylation).

Although less common, hypermethylation is also associated with specific conditions such as schizophrenia, bipolar disorder, epilepsy, and acute myeloid leukemia.

That’s why, before taking steps to raise SAMe levels, it’s essential to know each person’s methylation status.

Homocysteine is an unavoidable byproduct of any methylation process. Every time SAMe donates a methyl group—whether to regulate genes, synthesize neurotransmitters, or produce energy—homocysteine is generated.

This amino acid isn’t used to build proteins and, if it isn’t recycled properly, it can accumulate and become toxic. Excess homocysteine harms the cardiovascular system, reduces the availability of SAMe (negatively impacting epigenetics and aging), and has neurotoxic effects.

For all these reasons, elevated homocysteine is implicated in numerous modern diseases: cardiovascular disease, Alzheimer’s, Parkinson’s, cancer, diabetes, autoimmune disorders, among others.

Is it possible to improve your methylation status? Can we at least partially offset an imbalance that favors disease or speeds up aging?

Yes, it’s possible. But before taking action, the first step is to know your methylation profile—that is, your methylation index. We need to determine whether your methylating capacity is normal and, if it isn’t, whether you’re in a state of hypomethylation (deficit) that should be boosted, or hypermethylation (excess) that should be reduced.

You might think it’s enough to look at whether you have any of the diseases linked to these imbalances and deduce your methylation status from there. But that would be only a theoretical approximation. It may be suggestive, but it isn’t sufficient.

Before applying any strategy, it’s essential to confirm whether a real imbalance exists and, if so, how pronounced it is. For that, you need a blood test.

To assess methylation status, it’s enough to measure two biomarkers in a blood test: SAMe and SAH (a byproduct of any methylation process).

These are the ideal values:

• SAMe: 95-120 nmol/L

• SAH: <12 nmol/L

• SAMe/SAH ratio: 8–12

This is the best method because it directly measures the amount of SAMe available in the body for methylation, giving us a clear picture of the current state.

• If SAH is elevated relative to SAMe (ratio < 8), SAMe availability is reduced, favoring hypomethylation.

• If, on the other hand, SAMe is too high relative to SAH (ratio > 12), there is likely an excess of SAMe, which could lead to hypermethylation.

The best part of all this is that it can be improved.

Despite the problems and diseases linked to methylation imbalance, there are effective strategies to correct it. The ones below are explained in detail in my book Nutritional Epigenetics.

If hypomethylation is detected—a fairly common condition—or if, even within normal ranges, we want to optimize our methylation capacity to offset its natural decline with age (and thus reduce disease risk), several strategies can help:

• Supplement with creatine

• Increase phosphatidylcholine (by consuming soy lecithin)

• Supplement with SAMe

• Increase choline intake (through choline-rich foods)

• Avoid alcohol

• Don’t smoke

• Exercise (aerobic, anaerobic, and strength training)

• Get enough sleep and ensure good sleep quality

• Reduce exposure to endocrine disruptors such as phthalates and bisphenol A

Although SAMe levels tend to decline with age, in some cases—due to genetic predisposition or nutritional imbalances—a state of hypermethylation can appear. As we saw, excess SAMe is also harmful and has been linked to serious diseases.

If we detect hypermethylation due to excess SAMe, there are effective strategies to correct the imbalance and restore homeostasis:

• Increase glycine (through foods and supplementation)

• Supplement with vitamin B3 (nicotinamide)

• Adopt a ketogenic diet

• Consume chlorogenic acid (via green coffee extract)

Regardless of whether we’re in a state of hypomethylation or hypermethylation, elevated homocysteine is always harmful. It provides no biological benefit and should be corrected.

These are the main strategies to recycle it, depending on the root cause of the problem:

• Supplement with vitamins B9 and/or B12 in their active (methylated) forms

• Supplement with TMG (trimethylglycine or betaine)

• Supplement with active vitamin B6 (P-5-P)

• Supplement with vitamin B2

Regardless of whether we’re in a state of hypomethylation or hypermethylation, elevated homocysteine is always harmful. It provides no biological benefit and should be corrected.

In recent years, various molecules found in foods have been identified with the ability to modulate epigenetic processes. Some of them can reactivate beneficial genes, such as tumor suppressors or those associated with longevity.

Among the most notable are:
alpha-ketoglutarate (α-KG), curcumin, EGCG (epigallocatechin-3-gallate), allicin, kaempferol, proanthocyanidins, genistein, resveratrol, butyrate, chlorogenic and caffeic acids, selenium, quercetin, sulforaphane, vitamin D, and omega-3.

Now that you know your methylation status, you need a clear plan to optimize it and maintain it over time. The goal is simple: improve your quality of life, reduce disease risk, and extend your healthy years.

In the practical section of Nutritional Epigenetics you’ll find:

• Step-by-step protocols to correct hypo- or hypermethylation

• Detailed information on supplements and recommended doses

• Lifestyle habits that enhance results

***

Enjoyed this? Collect this post on Paragraph to support more research like this.

***

👉 Get your copy here:

Buy Nutritional Epigenetics on Amazon—available for Kindle, Audiobook, hardcover and in paperback.

TL;DR: Two simple markers — SAMe/SAH (plus homocysteine) — help you understand your methylation status and choose a safe action plan.

Educational content. Not medical advice.

***

If this helped you, collect this post on Paragraph to support my work. Thank you!

***

We marvel at every new technological breakthrough humans create, yet we rarely stop to admire the most advanced, efficient, and complex technology in the known universe: the human organism. No human invention comes close, in complexity and adaptability, to this marvel of evolution—a self-organizing system that sustains, repairs, and continually adapts itself.

But let’s start at the beginning, because the most extraordinary part is how it all began: from nothing.

About 4 billion years ago, Earth was just a mass of physical and chemical matter. Simple molecules drifted aimlessly, with no “memory” of anything. Over time, they began to combine until one of them acquired a revolutionary property: it could copy itself.

That instant changed everything. For the first time, matter began to store information about its own structure. It didn’t just exist; it could replicate and pass itself on. As if nature had written the first lines of a program able to run, maintain itself, and improve over time.

From there, life set out on its path: those first molecules gave rise to simple cells, then to more complex ones. Multicellular organisms emerged, animals appeared, and much later, the first hominids. All of us—from a bacterium to a human being—share that origin point: the moment chemistry became biology and information began to organize itself and evolve.

Now we’ll delve into one of the most sophisticated mechanisms of that self-organization: epigenetics, the system that regulates how genetic information is used so organisms can adapt to a constantly changing environment.

Without information there is no organization, and without organization there is no life. As we saw, life began when matter learned to store information. In biology, that information is arranged on two levels: genetics and epigenetics.

It’s our factory manual. It tells how the organism should be built and how it should function, setting its limits and possibilities. It’s stored in DNA and doesn’t change: we’re born with it and we die with it. Although tools like CRISPR can modify it, in everyday life it is, for all practical purposes, unalterable.

Epigenetics regulates which parts of the DNA are switched on or silenced, and when. It doesn’t change the content of the manual, but it does change how it’s interpreted: it arranges, orders, and gives meaning to genetic information. Like accents and commas in a text, its role is decisive. Its advantage? We can modify it and improve it.

Imagine a piano and a pianist. The piano represents our genetics: the instrument. The pianist is epigenetics: the one who decides which keys to press and when. A great performer with a mediocre piano can still produce a beautiful melody. But a perfect piano in clumsy hands won’t prevent disaster. That is the power of epigenetics.

Epigenetics allows us to interpret the information contained in DNA through two essential mechanisms. I explain both in more detail in my book Nutritional Epigenetics, but here we’ll focus on one of them: DNA methylation.

Our bodies use a molecule called S-adenosylmethionine (SAMe, for short) that carries something valuable: a methyl group. SAMe transfers this chemical tag to specific regions of DNA to mark them as not to be read or activated.

Returning to the piano analogy, SAMe places signals on certain keys (segments of DNA), telling the pianist (epigenetics) not to play them so the melody—the organism’s functioning—keeps its harmony.

This process performs two vital functions for the organism’s health, longevity, and stability:

1. Stabilization of the genome: it prevents the activation of DNA regions that are prone to generating mutations.

2. Cellular differentiation: it tells each cell which genes to ignore according to the tissue it belongs to. For example, a cell in the eye doesn’t need to switch on the same instructions as a liver cell.

As you can imagine, having enough SAMe is essential for this process to work properly.

Although it’s the second most widely used molecule in our bodies—surpassed only by ATP—SAMe is still largely unknown. It’s time to recognize its role.

Carlos López-Otín, in his influential article “The Hallmarks of Aging,” identified two key factors in the aging process: epigenetic alterations and genomic instability. Sitting right between the two is DNA methylation, a process essential for keeping the genome stable. And who supplies the raw material for that methylation? Exactly: SAMe.

The problem is that, with age, SAMe levels decline—and they do so exponentially.

Without SAMe, there are no chemical tags, and without tags, the process fails. In biology, this deterioration is known as global hypomethylation: a state that destabilizes the genome, accelerates aging, and opens the door to multiple diseases.

That’s why one of the goals of the practical section of my book is precisely this: to show how to raise SAMe levels, improve methylation, and, in doing so, reduce disease risk and slow aging.

As if its epigenetic role weren’t enough, SAMe also takes part in numerous processes vital to the body.

In fact, around 90% of available SAMe is used for two key functions: the synthesis of creatine—essential for energy production in muscles and the brain—and phosphatidylcholine—crucial for the integrity and fluidity of cell membranes, especially in the brain, where it helps protect against neurodegenerative disease.

In addition, SAMe is needed to:

• Break down molecules that, in excess, are harmful: histamine, vitamin B3, estrogens, dopamine, adrenaline…

• Synthesize neurotransmitters like serotonin and polyamines such as spermidine, which have anti-inflammatory and antioxidant effects and play a key role in cellular longevity.

• Regulate circadian rhythms, eye health (lens and retina), and the immune system by promoting the proliferation and specialization of T cells.

No small thing.

Without enough SAMe, the body can’t carry out key processes or slow aging. Its deficiency creates a state of global hypomethylation, which is linked to many of today’s most prevalent—and rising—conditions: cardiovascular disease, cancer, neurodegenerative disorders (such as Alzheimer’s, Parkinson’s, ALS, or multiple sclerosis), diabetes, depression, autism, addictions, autoimmune diseases, allergies, migraines, fibromyalgia, ADHD, and, finally, the “mother” of all diseases: aging.

In all these conditions, studies have observed hypomethylation when compared with healthy individuals.

Like everything in the body, SAMe requires balance: its deficiency (hypomethylation) is harmful, and so is its excess (hypermethylation).

Although less common, hypermethylation is also associated with specific conditions such as schizophrenia, bipolar disorder, epilepsy, and acute myeloid leukemia.

That’s why, before taking steps to raise SAMe levels, it’s essential to know each person’s methylation status.

Homocysteine is an unavoidable byproduct of any methylation process. Every time SAMe donates a methyl group—whether to regulate genes, synthesize neurotransmitters, or produce energy—homocysteine is generated.

This amino acid isn’t used to build proteins and, if it isn’t recycled properly, it can accumulate and become toxic. Excess homocysteine harms the cardiovascular system, reduces the availability of SAMe (negatively impacting epigenetics and aging), and has neurotoxic effects.

For all these reasons, elevated homocysteine is implicated in numerous modern diseases: cardiovascular disease, Alzheimer’s, Parkinson’s, cancer, diabetes, autoimmune disorders, among others.

Is it possible to improve your methylation status? Can we at least partially offset an imbalance that favors disease or speeds up aging?

Yes, it’s possible. But before taking action, the first step is to know your methylation profile—that is, your methylation index. We need to determine whether your methylating capacity is normal and, if it isn’t, whether you’re in a state of hypomethylation (deficit) that should be boosted, or hypermethylation (excess) that should be reduced.

You might think it’s enough to look at whether you have any of the diseases linked to these imbalances and deduce your methylation status from there. But that would be only a theoretical approximation. It may be suggestive, but it isn’t sufficient.

Before applying any strategy, it’s essential to confirm whether a real imbalance exists and, if so, how pronounced it is. For that, you need a blood test.

To assess methylation status, it’s enough to measure two biomarkers in a blood test: SAMe and SAH (a byproduct of any methylation process).

These are the ideal values:

• SAMe: 95-120 nmol/L

• SAH: <12 nmol/L

• SAMe/SAH ratio: 8–12

This is the best method because it directly measures the amount of SAMe available in the body for methylation, giving us a clear picture of the current state.

• If SAH is elevated relative to SAMe (ratio < 8), SAMe availability is reduced, favoring hypomethylation.

• If, on the other hand, SAMe is too high relative to SAH (ratio > 12), there is likely an excess of SAMe, which could lead to hypermethylation.

The best part of all this is that it can be improved.

Despite the problems and diseases linked to methylation imbalance, there are effective strategies to correct it. The ones below are explained in detail in my book Nutritional Epigenetics.

If hypomethylation is detected—a fairly common condition—or if, even within normal ranges, we want to optimize our methylation capacity to offset its natural decline with age (and thus reduce disease risk), several strategies can help:

• Supplement with creatine

• Increase phosphatidylcholine (by consuming soy lecithin)

• Supplement with SAMe

• Increase choline intake (through choline-rich foods)

• Avoid alcohol

• Don’t smoke

• Exercise (aerobic, anaerobic, and strength training)

• Get enough sleep and ensure good sleep quality

• Reduce exposure to endocrine disruptors such as phthalates and bisphenol A

Although SAMe levels tend to decline with age, in some cases—due to genetic predisposition or nutritional imbalances—a state of hypermethylation can appear. As we saw, excess SAMe is also harmful and has been linked to serious diseases.

If we detect hypermethylation due to excess SAMe, there are effective strategies to correct the imbalance and restore homeostasis:

• Increase glycine (through foods and supplementation)

• Supplement with vitamin B3 (nicotinamide)

• Adopt a ketogenic diet

• Consume chlorogenic acid (via green coffee extract)

Regardless of whether we’re in a state of hypomethylation or hypermethylation, elevated homocysteine is always harmful. It provides no biological benefit and should be corrected.

These are the main strategies to recycle it, depending on the root cause of the problem:

• Supplement with vitamins B9 and/or B12 in their active (methylated) forms

• Supplement with TMG (trimethylglycine or betaine)

• Supplement with active vitamin B6 (P-5-P)

• Supplement with vitamin B2

Regardless of whether we’re in a state of hypomethylation or hypermethylation, elevated homocysteine is always harmful. It provides no biological benefit and should be corrected.

In recent years, various molecules found in foods have been identified with the ability to modulate epigenetic processes. Some of them can reactivate beneficial genes, such as tumor suppressors or those associated with longevity.

Among the most notable are:
alpha-ketoglutarate (α-KG), curcumin, EGCG (epigallocatechin-3-gallate), allicin, kaempferol, proanthocyanidins, genistein, resveratrol, butyrate, chlorogenic and caffeic acids, selenium, quercetin, sulforaphane, vitamin D, and omega-3.

Now that you know your methylation status, you need a clear plan to optimize it and maintain it over time. The goal is simple: improve your quality of life, reduce disease risk, and extend your healthy years.

In the practical section of Nutritional Epigenetics you’ll find:

• Step-by-step protocols to correct hypo- or hypermethylation

• Detailed information on supplements and recommended doses

• Lifestyle habits that enhance results

***

Enjoyed this? Collect this post on Paragraph to support more research like this.

***

👉 Get your copy here:

Buy Nutritional Epigenetics on Amazon—available for Kindle, Audiobook, hardcover and in paperback.