For years, scientists have known that high homocysteine levels could cause stroke. The media blamed fat, particularly saturated fat, as the main culprit of hardened hearts and bursting brain vessels. The public at large was led to believe that some how, in some way, cholesterol-rich eggs and malevolent meats were raising homocysteine levels. But could a high fat diet explain all the people with high homocysteine levels? Nope, not at all.

If we dig a little deeper and peruse the pathways of metabolism, we stumble upon a potent homocysteine-raiser: poor methylation status. (1) Let’s look more closely at how methylation changed the life, and health of our friend Sara.

Sara’s Story

Sara ate a mostly cooked vegetarian diet with occasional eggs or seafood. Despite this healthful diet plan, she experienced frequent headaches- more often migraines- with no resolution, just a throbbing pressure that frightened her, but no intervention she tried helped except occasional relief from magnesium. In fact, NSAIDS made her dizzy, anxious, nauseous, and “hung-over” the next day, when she would crave sulfur foods like eggs, beans, and cabbage. Sara ate well, exercised, practiced yoga every day, and yet she barely maintained functionality.

Then, out of nowhere, her relatively healthy uncle dropped dead from a stroke at the ripe old age of 43.

After learning about methylation in her Functional Nutrition Training course, Sara thought about her uncle, had a hunch, and decided to test her genetics. She discovered that she had a small genetic change called a “single nucleotide polymorphism” or SNP called MTHFR C677T that could be addressed with careful supplementation and a shift in diet. She assessed this SNP, and others, from her nutritional perspective. Then she tried something new.

The first day she supplemented with methylated vitamins, she was forever changed. The persistent migraines and the “static in her head” just stopped. After some experimentation, she found the right support for her- the right B vitamins in the right forms at the right times- and the migraines haven’t come back for over 4 years. When Sara shares this story, she is excitable. She says she feels certain that learning about her genetics- and a bit about methylation- saved her life.

You might be thinking…  Methylation? The right B vitamins? What do these things mean? Does this apply to me if I have different genetics than your friend? How do nutrition and lifestyle support methylation? Find the answers to these and other questions below!

Methylation : Your Metabolic Magic Maker

Methylation is the process of adding a single carbon subunit, or methyl group (-CH3), to a molecule. As you might imagine, moving a single carbon is a fundamental chemical action. Your body converts methionine, an essential amino acid, into S-adenosyl-L-methionine (SAMe), your primary methyl donor. SAMe participates in billions of reactions each second all over your body. While there are other methyl donors, short-circuiting SAMe production is a primary place that methylation breaks down. You need several B vitamins for smooth methylation- folate and B12 are critical, but others like B6 and B2 and compounds such as choline, betaine,and glycine play major roles.

You move around billions of methyl groups every second because methylation is needed for so many critical tasks, including:

  • Cell division, Tissue repair, and Protein production: Reading and replicating your DNA.
  • Fetal Development: Growing a brain and spinal cord successfully. Before birth, impaired methylation can lead to serious birth defects, such as Spina Bifida, and less obvious effects, such as impaired cognitive development or a higher risk of insulin resistance.
  • Bowel Building. Making new digestive tract cells, which are replaced constantly.
  • Molecular Manufacturing: Helping you build phosphatidylcholine, carnitine, CoQ10, and other important compounds. (Luckily, we include choline, carnitine, and CoQ10 in our Nutreince multivitamin so you can breathe easier if you suspect you are a poor methylator.)
  • Powering Cells: Supporting cellular engines (mitochondria) as they make energy molecules.
  • Mood and Mind: Making and breaking down neurotransmitters, such as dopamine, norepinephrine, epinephrine, and serotonin, that affect your brain and gut. Methylation support for antidepressant effects and as addiction therapy is becoming more popular. (2)
  • Sound Sleep: Making melatonin, which supports REM sleep and is a powerful antioxidant. (3)
  • Driving Detoxification: Helps you make the antioxidant glutathione, your resident hormone/chemical/heavy-metal detoxifier, and methyl donors to support phase II of detoxification.
  • Putting the Fires Out: Supporting a healthy inflammatory response and safe homocysteine levels, which contributes to good cardiovascular health.
  • Letting the Outside In: Helping to break down histamine and supporting your immune response to infections.
  • Aging Gracefully: Avoiding chronic illness. Folate deficiency, and therefore impaired methylation, has been correlated with a higher risk of cardiovascular disease, cognitive dysfunction, and osteoporosis in the aged. (4)

As you can see, methylation reactions would be important to nourish in many situations, including repairing a damaged GI tract, healing wounds, processing drugs, feeling anxious or depressed, becoming pregnant, working to reduce heart disease risk… or aging. That’s pretty much everybody.

To B or not to B … Methylated

While getting into the weeds of methylation will likely make your head spin, allow us to mention a few methylation-cycle enzymes known to have one or more common SNPs. For instance, about 60% of the US population has a SNP in the gene coding for MTHFR, (or methylenetetrahydrofolate reductase). Other important enzymes include CBS, COMT, VDR, MTR, and MTRR. Different SNPs lead to different changes in each enzyme- most work less well, but some may work faster. Some people are actually over-methylators, though being an under-methylator is more common.

Methylation and Pregnancy:

Beyond being unlucky in the gene pool, there are several reasons one could have altered methylation status. Of particular concern is pregnancy. (5) For years, prenatal and regular vitamins have been boasting the essentiality of folic acid to reduce your risk of having a child with neural tube defects. (6) But folic acid is not folate. If you cannot convert folic acid to the forms of folate you need, you may do more harm than good by taking folic acid. Choline, another critical methylation micronutrient, is essential for fetal brain development, and may require supplementation.(7) More recently, studies correlating low folate levels during pregnancy with a higher risk of giving birth to an autistic child have gotten a lot of press. (8)

Nature matters.

For those with a family trend of depression or anxiety, methylation status could be compromised. Folate has become more popular as an adjunct or substitute for SSRI-based therapy (medication often prescribed for depression). (9) Because methylation is required to both make and break down neurotransmitters that helps us both get-up-and-go (like epinephrine aka adrenaline) and calm down (like serotonin), some may become calmer and others more excitable with the same B vitamins. High homocysteine levels can further reduce feel-good-chemical production, making it harder to bounce back. (10)

Nurture matters, too.

If you are constantly exposed to drugs, toxins, or hormones (like estrogen) that methylation is required to detoxify, you could be underserved running other key reactions. Because it can help both speed the clearing of drugs from a person’s system and boost mood with increased dopamine and serotonin production, methylation support is being used more and more to support addiction recovery.

Because folate passes methyl groups to vitamin B12 to pass along to other compounds, folate cannot do its job with inadequate B12. As you age, you may have more difficulty absorbing B12, increasing likelihood of deficiency; hence, research showing vitamins B6, B12, and folate can help prevent cognitive impairment in those with deficiency. B12 deficiency is a risk factor for pernicious anemia and dementia-like symptoms. (11) Unfortunately, these may be misinterpreted in the elderly as simply the result of advancing age.  Low B12 with high folate is a risk factor for several chronic diseases! (12)

Motivate your Methylation Pathways

Here at Calton Nutrition we always like to break things down to our 3 simple step plan!

STEP ONE – FOOD: Choose foods that contain vitamins, minerals, and amino acids (protein pieces) needed to be a well-oiled methylation machine. Choose organic produce, meats, poultry, and dairy to limit your pesticide exposure.

  • Folate (Vitamin B9). Find folate in foliage (leaves), foods chemically prepared to grow (legumes, nuts, and seeds), asparagus, brussel sprouts, and broccoli. Avoid cooking with high heat to preserve folate.  Some of your probiotics- your good gut bacteria- can make folate, too!
  • Vitamin B12. Animal products like fish, meat, eggs, and dairy deliver premade B12. Fermented foods, like tempeh, can provide B12 directly. Seed your gut with B12-producing bacteria.
  • Vitamin B6. Vitamin B6 is very common with high concentrations in fish, organ meats, starchy produce like potatoes, bananas, and squash, and some fruits.
  • Riboflavin (Vitamin B2). Eggs, lean grass-fed meats, and dairy products provide riboflavin, but don’t forget to eat fermented foods to power up with probiotics that produce riboflavin as well.
  • Choline:  Found mainly in animal foods and sometimes as lecithin in plant foods, obtain choline from meat, eggs, poultry, fish, dairy products, and soybeans.
  • Magnesium. A muscle mineral and chlorophyll component, magnesium is easy to find in whole plant and animal foods such as dark leafy greens, legumes, nuts, seeds, whole grains, and fish. (learn more about magnesium here!)
  • Zinc.  Oysters, meat, poultry, crustaceans like crab and lobster, beans, nuts, seeds, and dairy products contain levels of zinc worth mentioning. Zinc is challenging to absorb. Chew your food well to boost stomach acid and encourage zinc absorption.
  • Betaine. Found in plant foods, turn to beets, spinach, quinoa, amaranth, and sweet potato for higher doses. If you tolerate wheat products, kamut, bulgur, and wheat bran are also rich in betaine.
  • Glycine. A brain-calming chemical in its own right, you manufacture some glycine in your body already. Boost your existing levels with fish, meat, dairy, and to a lesser extent with legumes, dark leafy greens, cucumber, pumpkin, and bananas. Bone broths are rich in glycine- sip in the evening to relax before bed!
  • Methionine. Unlike glycine, you must consume methionine, but the good news is that it is in all proteins. In general, choose nuts, meats, dairy, poultry, fish, legumes, and eggs. Hone in on top sources like beef, lamb, turkey, chicken, pork, tuna as well as okay sources like eggs, Parmesan cheese, and brazil nuts.
  • Fermented Foods. The right bacteria can boost your B vitamin intake! Different strains have been shown to make vitamins B1, B2, B7, B9, and B12! We suspect that poor probiotic status is a critical part of the incredible micronutrient deficiency we see all around us today! Vary your ferments– try miso soup, beet kvass, or yogurt to enjoy fermented foods rich in other nutrients listed above!

            Hungry yet? Consider these delicious methylation-friendly menu ideas:

  • A cumin-rich stew made with lamb, sprouted chickpeas, and swiss chard
  • A Caesar salad topped with baked salmon and sunflower seeds
  • An arugula salad topped with chicken and roasted beets
  • A healthy dessert of whole milk organic yogurt topped with banana, cinnamon, and mango

STEP TWO – LIFESTYLE: Reduce your exposure to the toxin load and toxic stress that can overwhelm and exhaust methylation pathways.

  • Soothe unnecessary stress. Constant stress raises our stress hormones, which we need methylation both to build up and break down. Engage in one stress-soothing activity per day, whether it be exercise, a hot bath loaded with Epsom salts, trading foot massages with a willing partner, cooking an easy and delicious meal, or curling up with a great book (like Micronutrient Miracle).
  • Reduce your exposure to endocrine disruptors, aka xenoestrogens. Methylation pathways handle these steroid hormone-like compounds, found in phthalates and other parts of plastic, artificial fragrance, parabens, pesticides, synthetic hormones, and more. Choose grass-fed, organic animal foods. Be vigilant when purchasing beauty products, clean your home with simple solutions.
  • Tank the toxins.  If you live in a smoggy place, invest in an air purifier. Filter your water. Avoid cigarette smoke, marijuana, NSAIDs like tylenol, and limit or avoid caffeine and alcohol. Avoid mercury fillings and limit all heavy metal exposure. Love your liver and it will love you back.

STEP THREE – SUPPLEMENTATION: Reduce your exposure to the toxic load and toxic stress that can exhaust methylation pathways. In particular, those following a vegan diet may want to supplement to ensure adequacy.

  • Folate (Vitamin B9). If you choose to supplement folate, buyer beware! 5-MTHF, or 5-methyltetrahydrofolate, is your best option to get around genetic challenges, improve absorption in a compromised GI tract, and know that your body is getting a ready-to-use form of folate. That’s why 5-MTHF is in our Nutreince multivitamin!
  • Vitamin B12. This vitamin is notoriously hard to absorb, so if you have low levels causing dementia-like symptoms, fatigue, or anemia, you may need a B12 injection to boost your levels quickly. To support methylation pathways, methylcobalamin is preferred. Found in most multivitamins, cyanocobalamin is a sometimes hard-to-use (and potentially damaging to kidney patients) of B12 compared to methylcobalamin (found in Nutreince).
  • Vitamins B2 and B6. Vitamin B6 is so heavily utilized during protein making, breaking down, and conversion that anyone turning over tissues quickly (e.g. heavy exercise, illness, skin growth, gut repair) may need additional B6 support. We put the active form of B6 (pyridoxal-5-phosphate) and B2 (riboflavin-5-phosphate) in our Nutreince multivitamin so you benefit from robust B6 activity without a lot of metabolic work.
  • Magnesium and Zinc. While most multivitamins contain zinc, most do not contain magnesium. We go the extra mile with Nutreince, separating calcium from magnesium for maximum absorption!    
  • Choline and Betaine. Supplemental hydrochloric acid complexed to betaine (Betaine HCl) may support poor methylators with low stomach acid production. Beyond providing betaine, boosting stomach acid helps break down proteins and improves absorption of B vitamins, magnesium, and zinc. You will find 425 mg of choline in Nutreince, which you can convert into betaine if needed.
  • Glycine and Methionine. Not enough protein in your diet to get enough of these important amino acids? Try a boost from our whey or plant proteins! Short on time? Blend protein powder with Nutreince and a delicious healthy fat to create an easy smoothie with every nutrient mentioned in the above list (and more)!
  • Probiotics. If fermented foods aren’t enough to do the trick, take probiotics in a pill form to seed your gut with the good guys. Your bacterial buddies can make vitamins you need for a methylation B-oost!

Even if the word methylation sounds big and scary, don’t fret. Just know that it is too important for your brain, your heart, and graceful aging to ignore. The take-home: keep calm, eat seafood and salad, and fill your nutritional gaps with a high quality multivitamin. Let us support you so you can love your liver, nourish your neurotransmitters, and make the most of methylation.