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Have you heard about epinutrients? Surprisingly, they’re barely mentioned in research papers and yet they are potent epigenetic regulators (i.e. they control how our genes are expressed). And I think it’s time to shine some light on these longevity superstars.

But first, have you ever wondered why food has such powerful effects on our health and lifespan? There’s more than the energy it provides to keep us alive. The real secret lies in what I like to call “epinutrients”. These incredible compounds have the remarkable ability to regulate gene expression (that is, they have an epigenetic effect, hence epinutrient). It is this ability, I believe, that drives all the extraordinary downstream beneficial effects of whole natural foods, including their anti-inflammatory, anti-cancer, and antimicrobial properties.

Isn’t it exciting to think that it is precisely this epigenetic regulation at the root of all of these benefits? Of course, we’ve known for a long time that whole foods, that is foods in their original form, have incredible healing abilities. Even so, we’re only beginning to understand the role of their gene-modulating nutrients and the synergistic interplay between them.

In the words of Dr. Valter Longo, director of the Longevity Institute at the University of Southern California: “Other than genes, it’s hard to think of something that can be more powerful than food in determining whether someone is going to make it to 100 or die before 50.” And it may have taken us almost twenty-five hundred years since Hippocrates famously said “Let food be thy medicine”, but we’re finally starting to prove just how effective the nutrients contained within whole foods can be.

What Are Epinutrients?

By this point, you may be wondering exactly what these so-called epinutrients are. Putting it simply, epinutrients are those nutrients found in whole foods that have an epigenetic effect, such as folate and quercetin. As my dear friend and colleague, Dr. Lucia Aronica, said in one of my podcasts, epinutrients are our royal jelly. Just like eating royal jelly can make the epigenetic difference between a queen bee and a worker bee, epinutrients work through an epigenetic mechanism to turn on processes that benefit our health and lifespans.

This epigenetic mechanism switches genes on and off via several processes, one of which is called DNA methylation. By adding or removing methyl groups, epinutrients turn on the genes that make us stronger and younger and turn off bad genes that accelerate aging. Balance is key here – we don’t want too much or too little methylation going on, but just the right amount.

We can think of epinutrients as molecules that regulate gene expression by providing the building blocks for and directing methylation processes. Essentially, they are doing the heavy lifting at the level of the epigenome, modulating our DNA methylation patterns and creating all these positive downstream effects such as antioxidant, anti-inflammatory, detoxification-supporting benefits.

As I write in my Younger You book: “When viewed through the lens of how they impact DNA methylation, you can see the awesome power of the things you eat, drink, and do to nourish your genetic expression and make you biologically younger (and if you plan to have children, to improve their epigenetic inheritance, too).”

It’s clear that food is so much more than calories – it’s medicine, it’s information, it’s a code that can downgrade or upgrade our DNA software literally with every bite. And that’s precisely what we discovered in our groundbreaking study – we don’t need expensive drugs or extreme interventions such as 22-hour fasts. Instead, just by eating more whole foods, exercising a little, sleeping better, and taking much-needed rest, we can reverse biological age.

It’s simple and yet truly remarkable – when you give your body what it needs, without beating it over the head with pharmaceuticals and synthetic hormones, you empower your body’s own innate wisdom to lead the way.

Whole foods are the centerpiece of our approach because they contain these beautiful compounds that have time immemorial use histories, like the catechins in green tea, curcumin, luteolin, resveratrol or quercetin, and that appear to direct methylation traffic.

And so we designed this very polyphenol-dense, methylation-supporting diet, picking certain foods that have very particular compounds in them, including methyl donors like choline & betaine, but also these phytochemicals or methylation adaptogens that also regulate our genes, enzymes, and biology. This is why the Younger You food plan was more successful – it specifically prioritizes foods that modulate DNA methylation patterns to change the expression of your genes. Simply put, the diet aims to turn off bad genes (like genes associated with cancer or even inflammation) and turn on good ones.

All of these compounds that we know and love and eat and prescribe are the epinutrients, the methylation adaptogens and methyl donors, which are our golden ticket to reversing aging and achieving optimal health.

How Do Epinutrients Work?

As I’ve hinted above, there are two main categories of epinutrients – methyl donors and methylation adaptogens. The former provide the primary ingredients necessary for methylation reactions, including DNA methylation, while the latter direct those ingredients in the right places.

Methyl donors are the foods that the body uses to create methyl groups – the molecules used in the biochemical process of methylation which is needed for many bodily functions, as outlined in a previous blog, and also for optimal gene expression (i.e. DNA methylation). The most important methyl donors are folate (not synthetic folic acid) and vitamin B12 because they are the primary components the body uses to produce S-adenosylmethionine (SAMe), a key player in the methylation cycle. Other supporting methyl donors include betaine and choline, as well as several minerals, vitamins, amino and fatty acids. Having the right amount of methyl donors is crucial for balanced DNA methylation – we have about 20 million DNA methylation sites in every cell that need constant replenishment! And eating whole foods is the best way to ensure you hit the sweet spot of methyl donor intake and not get too much by over-relying on high dose supplements or inadvertently taking in too much through fortified foods.

Methylation adaptogens are those foods that provide the molecules that direct DNA methylation and ensure the methyl donors are used in the right amounts and in the right places. They make sure that the genes we don’t want turned on get methylated (and, thus, are inhibited) and the genes we do want turned on don’t get methylated (and thus, are expressed). They can do this by either supporting the active removal of methyl groups from genes or by passively inhibiting methyl groups from being added to genes. The end result is balanced DNA methylation that happens in just the right amount and in just the right places and methylation patterns that support youthful gene expression and inhibit pro-aging genes.

Methylation-Cycle

You may be familiar with many of the DNA methylation adaptogens I’m about to list. They are foods that have been used in many traditional cultures around the globe for their health-giving properties, including turmeric, green tea, cruciferous vegetables, and soy. They fall largely into two groups – flavonoids (part of the polyphenol family) and nutrients. Members of the flavonoid team include curcumin (found in turmeric), EGCG (green tea), rosmarinic acid (rosemary), and many more; whereas in the nutrients group we have vitamins A, C, and D3, and alpha-ketoglutarate. The flavonoid adaptogens work by primarily inhibiting the hypermethylation of DNA, while the nutrients help actively remove unfavorable methylation marks.

The most fascinating part is that these DNA methylation adaptogens appear to be selective in their influence. They harness the body’s wisdom to remove methyl groups where they are causing harm and leave them where they are doing good. Whether that’s due to the low-dose combination of many different flavonoids found in whole foods or some other mechanism, such as their senolytic properties, is yet to be discovered. And in case you were wondering, many of the flavonoid epinutrients are also senolytics. This means that they inhibit the accumulation of senescent cells (a sort of dying cell that doesn’t get cleared away, a zombie of the cellular world) and thus slow down the inflammatory damage caused by these cells and the aging process itself. Natural senolytics include curcumin, EGCG, quercetin, resveratrol and many more.

What Are The Top Epinutrients?

Now that you’ve got a good idea of what epinutrients are and how they work, let’s take a closer look at a few specific ones. In the Younger You book we have compiled the most comprehensive, first-of-its-kind DNA Methylation Nutrient Reference List where you can find all of the methylation–supportive epinutrients and the foods that contain them. And while there are many methyl donors and methylation adaptogens, and even more foods that contain them, here are the superstars:

  1. Folate

Category: Methyl donor

Function: As the single most important involved in genetic expression, folate is essential for DNA synthesis and repair. It works together with vitamin B12 to donate methyl groups in the methylation cycle.

Food sources: green leafy vegetables, asparagus, mushrooms, eggs, poultry, sunflower seeds, rosemary, sage, cilantro, and many more.

  1. Vitamin B12

Category: Methyl donor

Function: A key player in folate metabolism and the methylation cycle, vitamin B12 is essential for mitochondrial energy production and neuronal cell membranes (known as myelin sheaths), among many other roles.

Food sources: seaweed, shiitake mushrooms, liver, fish, beef, eggs, poultry, nutritional yeast, and more.

  1. Betaine

Category: Methyl donor

Function: Used in the methylation cycle to convert homocysteine back to methionine by donating a methyl group, betaine can also be converted into folate.

Food sources: spinach, beet, egg yolk, liver, sunflower seeds, and more.

  1. Choline

Category: Methyl donor

Function: A precursor to betaine, choline is involved in the synthesis of neurotransmitters and healthy lipid membranes and is essential for cognitive development and brain function.

Food sources: cauliflower, seaweed, shiitake & maitake mushrooms, egg yolk, liver, flaxseeds, fish, and more.

  1. Epigallocatechin gallate (EGCG) 

Category: DNA methylation adaptogen

Function: An important flavonoid, EGCG is a powerful methylation adaptogen that may prevent hypermethylation and may support the re-expression of good genes through passive demethylation.

Food sources: berries, apples, plum, avocado, pear, nuts & teas (green, white, oolong, and black).

  1. Curcumin 

Category: DNA methylation adaptogen

Function: Another member of the flavonoid family, which may be able to both add and reverse excess or erroneous methylation marks on our DNA.

Food sources: turmeric, curry.

  1. Rosmarinic acid 

Category: DNA methylation adaptogen

Function: Other than having potent antioxidant and anti-inflammatory properties, rosmarinic acid can also help optimize and rebalance DNA methylation.

Food sources: rosemary, mint, thyme, sage, oregano, basil, lemon balm, marjoram, and more.

  1. Quercetin

Category: DNA methylation adaptogen

Function: A DNA methylation adaptogen and a potent senolytic, quercetin helps to optimize genetic expression and slow down aging.

Food sources: apples, berries, broccoli, cocoa, capers, chia seeds, leafy greens, onion, pomegranate, fenugreek, cinnamon, basil, dill, and more.

  1. Iron

Category: DNA methylation adaptogen/active demethylating nutrient

Function: This mineral contributes to DNA synthesis and is a cofactor for the TET enzymes that remove methyl groups from hypermethylated genes.

Food sources: spinach, tomato, liver, salmon, beef, legumes, cashews, dark chocolate and more.

  1. Vitamin A

Category: DNA methylation adaptogen/active demethylating nutrient

Function: This fat-soluble vitamin is essential for many functions in our body, including stem cell reprogramming and the growth and specialization of all cells. It can also increase the expression of the TET enzymes mentioned above.

Food sources: liver & eggs contain preformed vitamin A, whereas many colorful veggies contain its precursors, carotenoids, such as sweet potato, spinach, pumpkin, carrot, grapefruit, orange tomato, broccoli, dark leafy greens, and more.

  1. Vitamin D

Category: DNA methylation adaptogen/active demethylating nutrient

Function: An important regulator of the expression of hundreds of genes, this sunshine vitamin is essential for overall health and optimal aging.

Food sources: salmon, sardines, liver, egg yolk, turkey, chicken, and sun-exposed mushrooms.

  1. Vitamin C

Category: DNA methylation adaptogen/active demethylating nutrient

Function: Besides being a well-known antioxidant, vitamin C works together with iron to support TET enzyme function and vitamin A to increase stem cell reprogramming.

Food sources: kiwis, grapefruit, strawberries, red bell peppers, broccoli, Brussels sprouts, apple, spinach, and many more.

Can I Just Supplement?

Reading all of this you may be so impressed with the superpowers of these nutrients that you may think, “Well, can’t I just supplement and live longer, better?” Not so fast – there are several reasons why supplementing with individual nutrients may not be the best idea.

Firstly, when we isolate nutrients we lose the benefit of synergistic interactions between the myriad components in any whole food, and in so doing we’re creating the possibility of unforeseen risk. In fact, scientists studying epigenetics suggest that the “combinatorial” approach of a whole foods diet providing many lower-dose nutrients simultaneously is probably more effective than a single nutrient.

Another point to consider is the quantity of nutrients. Remember, not only do you want the right nutrients to support DNA methylation, but you want them in the right amounts. Of course, there may be cases where lab testing or clinical experience demonstrates a need for a certain supplement in high doses. Still, I would be much more cautious with higher-dose nutrients in supplement form because, as we’ve learned, these nutrients strongly influence epigenetic expression – for better or for worse.

Especially now that we can see that you can influence the epigenome positively with much more moderate amounts of nutrients, why run the risk of nudging the needle toward “for worse.” In fact, we’re seeing that the right combinations and the right amounts of nutrients delivered in a whole-food package, in what we’re calling orthomolecular nutrition, may be our most powerful—and safest—ally yet. I truly believe that supporting nature to lead the way with the right nutrients in the right doses is powerful, and it works.

What You Can Do Next

Wondering where to start? The Younger You book has a wealth of information and includes simple, easy-to-follow guides with meal plans and recipes. And if you’re ready to take it to the next level and make the Younger You program your new way of life, consider joining our Younger Program, where you’ll be guided by a dedicated nutritionist and have access to one of the most advanced DNA methylation and biological age tests. And as always, I appreciate your time reading this blog and hope it has left you inspired to become a younger you.

Dr. Kara Fitzgerald

Dr. Kara Fitzgerald

Kara Fitzgerald, ND, received her doctor of naturopathic medicine degree from the National University of Natural Medicine in Portland, Oregon. She completed the first Counsel on Naturopathic Medicine-accredited post-doctorate position in nutritional biochemistry and laboratory science at Metametrix Clinical Laboratory under the direction of Richard Lord, PhD. Her residency was completed at Progressive Medical Center, a large, integrative medical practice in Atlanta, Georgia. Dr. Fitzgerald is the lead author and editor of Case Studies in Integrative and Functional Medicine and is a contributing author to Laboratory Evaluations for Integrative and Functional Medicine and the Institute for Functional Medicine (IFM)’s Textbook for Functional Medicine. With the Helfgott Research Institute, Dr. Fitzgerald is actively engaged in clinical research on the DNA methylome using a diet and lifestyle intervention developed in her practice. The first publication from the study focuses on reversal of biological aging and was published 04-12-2021 in the journal Aging. She has published a consumer book titled Younger You as well as a companion cookbook, Better Broths and Healing Tonics and has an application-based Younger You Program, based on the study. Dr. Fitzgerald is on the faculty at IFM, is an IFM Certified Practitioner and lectures globally on functional medicine. She runs a Functional Nutrition Residency program, and maintains a podcast series, New Frontiers in Functional Medicine and an active blog on her website, www.drkarafitzgerald.com. Her clinical practice is in Sandy Hook, Connecticut. Additional publications
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