Methylation Cycle

Maximizing Methylation: The Key to Healthy Aging

by Mark Hyman, MD

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

Genetics – Like an estimated 20 percent of us, you could be genetically predisposed to high homocysteine
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
Smoking – The carbon monoxide from cigarette smoke inactivates vitamin B6
Malabsorption – Conditions like digestive diseases, food allergies, and even aging can reduce absorption of nutrients
Decreased stomach acid – Aging and other conditions can reduce stomach acid — and therefore absorption of vitamin B12
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
Other conditions – These include hypothyroidism, kidney failure or having only one kidney, cancer, and pregnancy
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.

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
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)
Minimize animal protein, sugar, and saturated fat – Animal protein directly increases homocysteine. Sugar and saturated fat deplete your body’s vitamin stores
Avoid processed foods and canned foods – These are depleted in vitamins
Avoid caffeine – Excess amounts can deplete your B vitamin levels
Limit alcohol to 3 drinks a week – More than this can deplete your B vitamin levels
Don’t smoke – As noted above, smoking inactivates vitamin B6
Avoid medications that interfere with methylation – See notes on this above
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
Improve stomach acid – Use herbal digestives (bitters) or taking supplemental HCl
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
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.