Maximizing Methylation: The Key to Healthy Aging

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TAKING JUST A FEW vitamins CAN optimize the function of ALL your body’s systems. It’s true. But you have to know what to take and you have to know why these supplements work …

That’s why, in this week’s blog, I am going to discuss one of the most important biochemical processes for long-term health and how you can keep it running at its very best with supplements and other measures.

Unfortunately, many people suffer from one or more of the 8 factors that negatively impact this biochemical process, so problems in this area are widespread though many don’t realize they are suffering.

The good news is that there are MANY things that you can do right now to optimize this critical biochemical process that may have a dramatic impact on your health. In today’s blog I will review the 8 factors that can lead to problems in this area, and outline 12 tips that will help you optimize this essential part of your biology.

But first, I’d like to tell you about two of my patients with seemingly unrelated health problems that were actually caused by a breakdown in this biochemical process. And I want to share a study done on Chinese babies who had a birth defect known as spina bifida.

You’ll be amazed at how all three — my two patients and these Chinese babies — were affected by the exact same thing …

Interestingly, these Chinese babies, Mr. Roberts, and Mr. McNally all have something very important in common. They all have inadequate levels of specific vitamins, either acquired or genetic, …

What an Elderly Golfer, a College Professor, and Chinese Babies have in Common

One of my patients, Mr. Roberts, was an 88-year-old businessman who didn’t let his age slow him down. He still golfed three times a week, worked two days a week, flew around the world in his private jet, and was “romantic” once a week with a wife 30 years his junior. He also loved his 6 ounces of Grey Goose vodka every night.

Of course, he did have some health problems. Mr. Roberts had been treated well for mild heart disease. His doctor even recommended 800 mcg of folic acid and 250 mcg of vitamin B12 — megadoses by any standard.

Mr. Roberts also had a check-up at the Mayo Clinic and was told that he was healthy, despite having mild anemia and large red blood cells. Yet he still complained of mild fatigue and trouble with his short-term memory. Plus, I noticed a slightly wide gait common in someone with poor balance.

Then there was Mr. McNally, a Boston college professor who was 50 years old, fit, and lean but wore a worried look as he walked into my office.

He recounted the sad tale of his 7 brothers. Four had died of a heart attack and three others had had bypass operations at a young age. Concerned about his own fate, he ate a low-fat diet, exercised regularly, didn’t smoke, had normal blood pressure and cholesterol levels, and took antioxidants and a multivitamin. Perhaps his only vice was the multiple Starbuck’s grande lattes he downed each day. Living under a constant state of impending doom, Mr. McNally came to me asking for a stress test to see how his heart was doing.

Strange as it may seem, these two men reminded me of my time in China. When I lived in Beijing, a study was done on a group of women in Harbin, the northern most industrial city in the Gobi desert, just north of Beijing. It seemed that there was an unusually high rate of birth defects in the area, specifically spina bifida.

The Chinese have a tradition of holding weddings during the Chinese New Year in February. In Harbin, many of the babies born 9 months later had birth defects. This study sought to determine what the link was and found that the major factor was the lack of fresh greens or vegetables in the Gobi desert in the middle of winter.

Interestingly, these Chinese babies, Mr. Roberts, and Mr. McNally all have something very important in common. They all have inadequate levels of specific vitamins, either acquired or genetic, and their methylation systems are not working properly as a result. I’ll explain more about what “methylation” is in a second. First let’s analyze the similarities in these cases.

Take Mr. Roberts. Our romantically active 88-year-old took high doses of B vitamins. But he still had very high levels of homocysteine and methylmalonic acid — indicators of folic acid and B12 deficiency.

Mr. McNally had similar problems. Our college professor had a genetically sluggish metabolism of homocysteine which caused extremely high levels of this toxic amino acid to build up in his blood. This was the likely cause of all the heart disease in his family.

Again we see a similar set of problems in those Chinese babies. Their mothers were conceiving in the middle of winter — when their folate intake was low from the absence of fruits and vegetables. This is what triggered such a high rate of birth defects.

The common link in all three of these cases is a problem with methylation. Let me tell you more about that that actually means.

Methylation is a key biochemical process that is essential for the proper function of almost all of your body’s systems. It occurs billions of times every second; it helps repair your DNA on a daily basis; it controls homocysteine (an unhealthy compound that can damage blood vessels); it helps recycle molecules needed for detoxification; and it helps maintain mood and keep inflammation in check.

To keep methylation running smoothly you need optimal levels of B vitamins. Without enough B vitamins methylation breaks down, and the results can be catastrophic. In these cases we see more birth defects like spina bifida (as with the Chinese babies), more cases of Down’s syndrome, and more miscarriage.

A breakdown in methylation also puts you at higher risk for conditions like osteoporosis, diabetes, cervical dysplasia and cancer, colon cancer, lung cancer, depression, pediatric cognitive dysfunction ( mood and other behavioral disorders), dementia, and stroke. And like Mr. Roberts and Mr. McNally, you may be at higher risk for cardiovascular disease.

To avoid all of these problems, the key is to maximize methylation. That means avoiding the things that cause your methylation to break down, testing to find out how well your methylation is working, and including the things that support proper methylation. Let’s look at how to do that.

8 Factors that Affect Your Methylation Process

  1. Genetics – Like an estimated 20 percent of us, you could be genetically predisposed to high homocysteine
  2. Poor diet – The word “folate” comes from “foliage.” You need to eat plenty of leafy greens, beans, fruit, and whole grains to get adequate levels of vitamins B6 and B12, betaine, and folate. Egg yolks, meat, liver, and oily fish are the main dietary sources of vitamin B12 — so long-term vegan diets can be a problem. Plus, certain compounds can raise levels of homocysteine and deplete the B vitamins. These include excess animal protein, sugar, saturated fat, coffee, and alcohol. Irradiation of food depletes nutrients, so foods treated this way may be lower in B vitamins, too
  3. Smoking – The carbon monoxide from cigarette smoke inactivates vitamin B6
  4. Malabsorption - Conditions like digestive diseases, food allergies, and even aging can reduce absorption of nutrients
  5. Decreased stomach acid – Aging and other conditions can reduce stomach acid — and therefore absorption of vitamin B12
  6. Medications – Drugs like acid blockers, methotrexate (for cancer and arthritis and other autoimmune diseases), oral contraceptives, HCTZ (for high blood pressure), and Dilantin (for seizures) can all affect levels of B vitamins
  7. Other conditions – These include hypothyroidism, kidney failure or having only one kidney, cancer, and pregnancy
  8. Toxic exposures – Some toxins can interfere with vitamin production

Watch out for these factors and you will go a long way toward protecting your methylation.

Measuring Your Own Methylation Process

To find out if your methylation process is optimal, ask your doctor for the following tests:

  • Complete blood count – Like our friend Mr. Roberts, large red blood cells or anemia can be a sign of poor methylation. Red blood cells with a mean corpuscular volume (MCV) greater than 95 can signal a methylation problem
  • Homocysteine – This is one of the most important tests you can ask for. The normal level is less than 13, but the ideal level is likely between 6 and 8
  • Serum or urinary methylmalonic acid – This is a more specific test for vitamin B12 insufficiency. Your levels may be elevated even if you have a normal serum vitamin B12 or homocysteine level
  • Specific urinary amino acids – These can be used to look for unusual metabolism disorders involving vitamins B6 or B12 or folate, which may not show up just by checking methylmalonic acid or homocysteine

12 Tips to Optimize Your Methylation Process

Just as there are many causes of poor methylation, there are lots of things that support its proper functioning. Here’s how to maximize methylation — and prevent conditions like heart disease, cancer, dementia, depression, and more.

  1. Eat more dark, leafy greens – You want to eat l cup a day of vegetables like bok choy, escarole, Swiss chard, kale, watercress, spinach, or dandelion, mustard, collard, or beet greens. These are among the most abundant sources of the nutrients needed for optimal methylation
  2. Get more Bs in your diet – Good food sources include sunflower seeds and wheat germ (vitamin B6); fish and eggs (vitamin B6 and B12); cheese (B12); beans and walnuts (vitamin B6 and folate); leafy dark green vegetables; asparagus, almonds, and whole grains (folate); and liver (all three)
  3. Minimize animal protein, sugar, and saturated fat – Animal protein directly increases homocysteine. Sugar and saturated fat deplete your body’s vitamin stores
  4. Avoid processed foods and canned foods – These are depleted in vitamins
  5. Avoid caffeine – Excess amounts can deplete your B vitamin levels
  6. Limit alcohol to 3 drinks a week – More than this can deplete your B vitamin levels
  7. Don’t smoke – As noted above, smoking inactivates vitamin B6
  8. Avoid medications that interfere with methylation – See notes on this above
  9. Keep the bacteria in your gut healthy – Take probiotic supplements and use other measures to make sure the bacteria in your gut are healthy so you can properly absorb the vitamins you do get
  10. Improve stomach acid – Use herbal digestives (bitters) or taking supplemental HCl
  11. Take supplements that prevent damage from homocysteine – Antioxidants protect you from homocysteine damage. Also make sure you support methylation with supplements like magnesium and zinc
  12. Supplement to help support proper homocysteine metabolism – Talk to your doctor to determine the best doses and forms for you.  Here are a few suggestions:
    Folate (folic acid):
    Amounts can vary based on individual needs from 200 mcg to 1 mg. Some people may also need to take preformed folate (folinic acid or 5 formylTHF) to bypass some of the steps in activating folic acid
    Vitamin B6: Take 2 to 5 mg a day. Some people may need up to 250 mg or even special “active” B6 (pyridoxyl-5-phosphate) to achieve the greatest effect. Doses higher than 500 mg may cause nerve injury
    Vitamin B12: Doses of 500 mcg may be needed to protect against heart disease. Oral vitamin B12 isn’t well absorbed; you may need up to 1 or 2 mg daily. Ask your doctor about B12 shots
    Betaine: This amino acid derivative is needed in doses from 500 to 3,000 mg a day, depending on the person

By working to optimize your methylation you can protect yourself from virtually all the so called “diseases of aging.” When you do, you will be well on the road to lifelong vibrant health.

Now I’d like to hear from you …

Do you have symptoms of poor methylation?

What are you doing to optimize this process?

Do you take B-vitamin supplements? Have you noticed any results?

Please share your thoughts by adding a comment below.

To your good health,

Mark Hyman, M.D.

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22 Responses to Maximizing Methylation: The Key to Healthy Aging

  1. Bonita Poulin February 10, 2013 at 12:41 pm #

    I have been found to be allergic/sensitive to B1 and B2 through provocation and neutralization testing. I get nauseous when I try to take B Complex or a mulitvitamin, however regular foods naturally high in these vitamins do not seem to cause reactions. Could a deficiency in these nutrients be the cause of my left-sided parial paralysis that is slowly getting worse over the years? I’ve tried to eliminate this allergy/sensitivity with several energy medicine techniques and have eliminated many other allergies successfully that way, but this one won’t go away. Any ideas?

    • Avatar of HymanStaff
      HymanStaff February 27, 2013 at 6:39 pm #

      Thank you for your message and your interest in Dr. Hyman’s work. Your question and constellation of symptoms represents a complex medical condition. Questions regarding conditions like these cannot be answered in a responsible manner via the Internet.

      Wishing You the Best of Health!

      Dr. Hyman Staff

    • Holly Longuski April 20, 2013 at 1:55 pm #

      Thank you so very much for this article. I suffer from MDS q-5 which is a bone marrow problem in which red cells are large and do not mature. I have some anemia and elevated MCV etc., but have controlled this condition for years without having to take Revlimed, however, I can’t get rid of the problem which will probably grow worse with age. I am now a young 73. I take no medication at all.

      A phone consultation with Dr. LeBeau who works with Dr. Mark Stengler alerted me to the fact that I might be a non-methylator. So I very recently started taking methylated B vitamins.

      Do you have any suggestions? I have been to Dr. Nicholas Gonzalez in NYC and he put me on a meat diet and 100 pancreatic enzymes a day plus huge doses of vitamins and coffee enemas which helped for a while then stopped. Do you have any suggestions. No one seems to know anything about any of the 4 types of MDS. I would be very interested if you have any information on this.

      A couple of years ago, I took a test given by a vitamin company which revealed I was a non methylator of folate. All this ties in with my problem but at the time, I didn’t link this to MDS. Now it all makes sense.

      Thank you for your wonderful blog.

      If you give phone consultations I would be interested in talking to you.

      Sincerely,
      Holly Longuski

    • Ina O'Connor May 15, 2013 at 9:31 am #

      When you have the MTHFR genetic defect, folic acid in supplements can cause many problems as well as the shortage of folate in you cells because you do not convert folic acid (synthetic vitamin) to its usable form methylfolate. Same goes for b12. I suggest you get tested for this defect and find a knowledgeable practitioner.

      • William May 23, 2013 at 10:36 am #

        I agree Ina, and recently discovered of having homozygous MTHFR, MTRR, & CBS mutations which have affected my ability to Methylize all my life. Now at 39yrs my life is highly lacking in excitement feeling due to high homocysteine, low hormones, extremely low neurotransmitter levels, ect…

        Taking Methylfolate & Methylcobalamine only irritates the situation more at this point due to a burned out nervous system prone to anxiety & pain.

        I am working with a specialist now but my hope for the future is still very low with fatigue, nausea & headaches all the time.

  2. Debra Kirkham February 17, 2013 at 6:55 pm #

    Hello Dr. Hyman!

    I first started listening to you from the Daniel Plan! Thank you so very much for all you do in helping everyone with vibrant health!
    I am taking a Homocysteine Contol tabs that disolve twice a day called Utra Homocysteine Control and I am wondering if I can find a better product from you. I just wrote down all food suggestions from this article thank you!

    Debra J. Kirkham

  3. Crystal February 27, 2013 at 4:25 pm #

    Thanks for this info, it is very much appreciated.

    How do I select a methylated multivitamin? Do you have any recommendations?

  4. Gwendolyn M. Knowlton March 23, 2013 at 2:01 pm #

    Dear Dr. Hyman,

    I was diagnosed with homocysteinura at a very young age. I suffered for many years because traditional practioners did not believe me (I was adopted at an older age and couldn’t locate my med records) and they were not interested in learning about methylation. Learning about this has taken over my life once both daughters got diagnosed with a copy of MTHFR and started having symptoms. Here’s what I’ve been able to put together.

    Most people who have bad responses to certain B vitamins typically need them in methylated form. When I take b6 I get sicker than a dog, yet I feel like a new woman when I take P5P. P5P however seems to help regulate magnesium and potassium stores, so when I first started taking it, I hurt! Then a few people blogged and said they took potassium and magnesium (separately) and they symptoms subsided. It worked.

    The methylfolate seems to serve as an adhd cure. I worked up to 7/800mg solgar methylfolate pills per day. Its my wonder drug. literally. It allows me to organize my thoughts, complete a to-do list and kills my social anxiety. It increases the speed of my life without acting like speed. I am extreme case though. When too much or these are taken together it causes overmethylation and niacin (1/4 tab) at a time will stop the extreme anxiety or shakiness if someone has taken too much.

    B-12 worked like confidence in a pill for me. For whatever reason I felt very relaxed and at ease when I took it. It was sublingual. I took 5000mg a day, which was a little too much. When I took 3000 mg it made me irritable. So I got mad one day and took too more thinking “Dammit, I’ll take it till it works”. I popped 2 more 1000 mg sublinguals. It was magic. Calm. BUT after about a year. I started having nerve sensitivity issues in my shoulders which subsided when I stopped taking it.

    All of this, I have had to learn on my own. I am now a licensed health coach and eclectic herbalist intern. We encourage people to take this to their docs all the time. Your site is the simplest easiest to understand out there. Thank you and please keep up the good work.

  5. Shiroko Sokitch MD April 12, 2013 at 10:50 am #

    Thank you for your article, I’m an MD who practices a blend of Chinese and Western medicine, I work at making explanations easy for people to understand, and I love this article.
    I will post it on my page, and send it to a few of my patients.
    Thank you again.
    All the best!

  6. Judy April 23, 2013 at 1:58 am #

    Hi! What does it mean when blood work comes back positive for A1298C mutation?

  7. Avatar of Lynn
    Lynn April 23, 2013 at 1:41 pm #

    Dr Hyamn
    Thank you so much for all of the great information that you share with the public. Last year, I was diagnosed with mercury toxicity. This was caused through dental work. In addition I was subjected to a massive infection in a tooth and was on a round of antibiotics. I was also under immense stress at home and work. And lastly, I was a long term smoker.
    This “perfect storm” created a complete breakdown in my sytem – in that I ended up with digestive disorder, leaky gut, gut bacteria imbalance, yeast overgrowth in the digestive tract, vitamin B12, B6, Folic acid, Vitamin D and Vitamin A deficiencies (mal absorption); and ultimately elevated hycestine levels/poor methylation.

    I knew I did not feel well, but did not know what it was or how bad! I just happened to see you on Boston public television and subsequently bought your book. At your advice I sough out a functional medicine doctor (after a bad experience with a gastroenterologist). The two of you have literally saved my life and have changed my world.

    I am happy to report that I am now, 1 year later, in a much better place today. I feel great most of hte time now.
    My question: Anything else I can do to make sure my meythlation is at peak? I am afraid of the cardiovascular impact of poor methylation.

    THanks
    Lynn

    • Avatar of Dr. Hyman Nutrition Staff
      Dr. Hyman Nutrition Staff August 1, 2013 at 12:54 pm #

      Dear Lynn,
      Thank you for your interest in Dr Hyman’s work. Unfortunately Dr Hyman cannot provide personal medical advice in this forum. If you would like to make an appointment at Dr. Hyman’s UltraWellness Center in Lenox, MA please go to:http://www.ultrawellnesscenter.com/becoming-a-patient/ When you are finished reading through the material you may call the office at After you have reviewed this, please contact our office to make an appointment. By phone, (413) 637-9991; by email, office@ultrawellnesscenter.com

      It sounds like you are doing really well. What does your diet look like? For more personalized nutrition advice, Dr Hyman’s nutrition coaching team would be happy to work with you on an individual level to help you reach your goals. To work with the nutrition coaching team please go to:http://www.bloodsugarsolution.com/nutrition-coaching/ OR call (800) 892-1443 to get started.

      In good health,
      The Nutrition Team

  8. Pamela April 25, 2013 at 8:28 am #

    Thanks so much for this article! I am trying to increase my B12 levels and read that taking vitamin C at the same time as methylcobalamin will render the B12 less effective. Do you know if this is true?

    The same for niacin, apparently it gathers methyl groups…. High dose niacin helped me feel better for a year before I learned I was an under-methylator (homozygous a1298c mthfr). I’ve begun taking methyl folate and methyl cobalamin but wonder if I should stop taking the niacin. Dr. Hoffer certainly makes a great case that it can help prevent Alzheimer’s, gum disease, and depression, so I’m reluctant to give it up! What do you know about it’s effect on methylation?

  9. Ina O'Connor May 15, 2013 at 9:40 am #

    I recently decided to be tested for the MTHFR genetic defect. I am very healthy for my age, but it seems like I have to work very hard to stay that way. I was surprised to come back homozygous for the C677T defect. I was already on a gluten free diet so folic acid from foods in my diet was minimal. I stopped all supplements with folic acid and felt a 40 year depression go very quickly. It is taking a lot of tweaking with methylcobalomine and methyfolate, garlic, msm, etc, but I feel so much better. Incidentally I have never had an elevated homocysteine level, but have always had insulin resistance. Recently my white count has been on the low side. I eat raw vegetables by the pound which I attribute for doing better than one would expect with condition. Thank you for this article. We need more practitioners who are knowledgeable and do not tell positive people to triple their folic acid level.

  10. Ellen Hatch August 12, 2013 at 5:39 pm #

    Good article. I’m homozygous for C677T MTHFR gene mutation.

  11. Arnold December 13, 2013 at 6:55 am #

    I also wanted to add the importance of active b-vitamins to get the methyl process going. For B12 both methylcobolamin and adenosylcobalamin are good and should be used. For folic acid you would want methylfolate.

    A mehyl donor like SAM-e might also be very useful. There’s other methyldonors but that one comes to my mind as important as it is involved in the synthesize of several important compounds and neurotransmitters.

    Take care of yourself and to all of you with gene mutations. I hope you are on your way of getting better and feeling better with the help of methylation nutrients.

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