Even though methylation is a hot topic in the world of medicine right now, most of the conversation revolves around undermethylation. Becoming overmethylated in the process, which is actually pretty common in people who are working to correct an undermethylation problem.
Brief Recap – What is Methylation?
Methylation is a biochemical process that’s actually used throughout your body. Simply put, methylation is when one carbon atom and three hydrogen atoms are added to a molecule. One carbon plus three hydrogen atoms is called a methyl group, which is why this process is called methylation. Methyl groups can be thought of as little light switches for very important processes, including:
- Stress response
- Flight or flight reactions
- Synthesis of neurotransmitters
- Synthesis of glutathione (your body’s master antioxidant)
- Folate metabolis
- Hormone regulation
- Energy production
- DNA repair
- Gene expression
- Scavenging free radicals
- Supporting appropriate immune system response
Methyl groups turn on many of these processes and if you don’t have enough of them, it can cause a lot of health problems. For example, maybe you have plenty of a neurotransmitter, but you don’t have enough methyl groups to activate it – then it might not be doing you any good.
You’re probably thinking, methylation sounds great and in most cases it is. Which is why there was a flare of concern when scientists discovered MTHFR gene mutations that can cause people to not produce enough methyl groups.
Having a shortage of methyl groups is a big deal because it can cause a vital process to become compromised, making you sick. Abnormal methylation has been linked to conditions like autoimmune disease, so it’s something I regularly check for in my practice. But what’s been largely overlooked is that some people cause overmethylation in their body when they are treating their undermethylation. Though more often than not, an overmethylator has been experiencing overmethylation beginning at birth. Due to the lack of information, they are completely unaware this is a problem for them.This leads us to the obvious next question. What does overmethylation look like?
If you’ve struggled most of your life with depression and nervousness, or even tend to feel a little down in the dumps, you might want to check to see if you are undermethylating. Methylation status something I regularly check patients for because it’s a process the body needs to run diverse and vital functions, but oftentimes their methylation processing isn’t quite balanced – causing them to undermethylate or overmethylate.
So let’s briefly revisit methylation. Methylation is a biochemical process used throughout your body like a little light switches for turning on repairing DNA, producing energy, regulating hormones, detoxification, synthesizing neurotransmitters, and more. Undermethylation occurs when someone doesn’t have enough methyl groups to switch on certain processes. Most people methylate properly but if you fall on either end of the spectrum, you’re going to feel it
12 Symptoms of Undermethylation
Though undermethylation and overmethylation both share anxiety as a symptom, people who are experiencing a lack of methylation are typically experiencing anxiety that’s more geared towards perfectionism tendencies. Where as people with overmethylation tend to have extreme anxiety accompanied with panic attacks in some cases.
Here are 12 symptoms of undermethylation:
- Nervousness and perfectionism
- Low serotonin activity
- Obsessive compulsive behaviors
- High libido
- Ritualistic behavior
- Digestive issues
Undermethylation is associated with MTHFR mutations C677T, A1298C, MS, BHMT, MAT and SAHH. Please keep in mind that when you get a genetic test, you getting a list of possibilities and it is not definitive to whether or not you are undermethylating or overmethylating. That being said, it’s a good way to know which way your body might tend to behave.
What Causes Undermethylation?
There’s a common misconception that the genetic mutations associated are what cause under or overmethylation. However, it’s not that simple. While genetic mutations might make it more likely that you’re not methylating enough and there are also likely environmental causes. Toxin and mold exposure, high-stress environments, nutrient deficiencies, and even emotional trauma seem to potentially affect methylation in the body.
While there’s no one definitive cause of undermethylation, if you come to the conclusion that that’s what’s happening in your body and causing your symptoms, you’ll want to address the underlying causes by restoring the related factors. When it comes to naturally healing your body so it begins to methylate at a normal rate, it’s a good idea to make sure you’re getting enough precursors, co-factors, and supporting your body’s detoxification processes.
An Undermethylation Diet
Here are some of those precursors and cofactors you should add to your diet to help with your undermethylation:
- Choline – An important methyl donor.
- Glutathione – Low glutathione levels can impair methylation.
- Copper – Many methylation enzymes require copper for reactions.
- Magnesium – Plays an important role and gene methylation.
- Folate – An important methyl donor.
- Zinc – Insufficient zinc levels can reduce the body’s ability to use methyl groups.
- Vitamin B2 – Helps recycle folate so it’s a usable methyl donor form.
- Vitamin B3 – Maintains proper methylation of genes, which helps resist tumor formation.
- Vitamin B6 – A cofactor for an important enzyme that helps transfer methyl groups.
- Vitamin B12 – A key enzyme used in the synthesis of your body’s most important methyl donor, S-adenosylmethionine (SAMe).
- SAMe, methionine, or TMG can also be taken
Foods to avoid:
- Vegetable oils
- Processed foods
Foods to enjoy:
- Organic fresh vegetables
- Grass-fed beef
- Wild caught salmon
- Full fat yogurt
- Eggs (if tolerant)
Basically, the key here is to eliminate things that often cause people problems such as common food sensitivities and inflammatory foods. It’s going to be really important for you to go on a whole food plant-based diet. Then you’ll want to focus on the nutrients listed above because they are essential for methylation.
Juicing probably won’t feel great for you because there’s high concentrations of folic acid, which can cause people who are undermethylating problems. Folic acid depletes methyl groups in the nucleus of the cell where DNA is made. Outside the nucleus, folic acid can actually contribute to the methyl groups in your body. This can be confusing because it seems to contradict itself, but the most important thing to remember is that folic acid usually inhibits detoxification processes and therefore it doesn’t feel great for somebody who’s undermethylating.
You’ll also likely benefit from reducing histamine in your diet. This is because high histamine levels and undermethylation are associated.
Undermethylation & Histamine
Another thing that can contribute to undermethylation besides the MTHFR gene mutations and environmental causes, are high levels of histamine in the body. Histamine is an important mediator released by your mast cells to cause acute inflammation. Histamine gets a bad name but in reality we need histamine to help get important immune system elements to injuries and to attack Invaders. That being said, it’s fairly common to experience high histamine in such a way that it becomes problematic. What can contributes to histamine levels?
- Overactive mast cells
- Fermented foods
- Cured meats
- Smoked meats
- Canned foods
- Pickled foods
Noticing a theme in the foods listed above? This is because as foods sits, it breaks down and creates histamine.
12 Symptoms of Overmethylation
Genetics, nutrition, and environment can all lead to both undermethylation and overmethylation. Though overmethylation is less common, it’s still a problem I see in my office fairly regularly. So I suspect that overmethylation is actually a bigger problem than we’ve yet to discover. The end product of methylation is called SAMe, when your body becomes overmethylated there’s too much SAMe floating around.
Symptoms of overmethylation include:
- Panic attacks
- Attention deficit hyperactivity disorder (ADHD)
- Behavior disorders
- Sleep disorders
- Histamine intolerance
- Sensitive to environmental toxins
- Highly creative
- High energy
People who are experiencing overmethylation are generally very anxious. This is because overmethylation can create high levels of dopamine, norepinephrine, and epinephrine in the brain. In general, your neurotransmitter activity is strongly associated with your ability to appropriately use methyl groups. Which is why if you’re struggling with any mental health disorders, it’s a good idea to look into your methylation potential.
MTHFR genetic mutations that can contribute to overmethylation include: AGAT, GAMT, CBS and MT. Keep in mind that just because you have an MTHFR mutation doesn’t mean that you’re going to experience under or overmethylation. In fact, if there is one thing you take away from today’s blog I hope it’s that.
Easy access to genetic testing like 23andMe has led to people discovering that they have the potential for over or undermethylation and becoming unnecessarily worried. This is why I strongly recommend if you suspect you are experiencing overmethylation, you seek the support of a functional medicine doctor.
Methylation & Histamine
We can tell if you’re overmethylated because we can measure the concentration of methyl groups in the body. Plus, there is an inverse relationship between methyl groups and histamine. So if you tend to have high methyl groups, you’ll also likely be low in histamine. This is why people who are overmethylated also often struggle with histamine intolerance.
Another interesting interaction between methylation and histamine is when there’s too much histamine in the body, and there is already inflammation due to some other cause (maybe it’s environmental toxins or something else) – high histamine can become depleted (histamine intolerance), which then contributes to overmethylation. This can become a reinforcing cycle.
When we compare methyl groups to histamine levels, we can get a better idea of what exactly is going on in your methylation process.
What To Do if You’re an Overmethylator
If you’re an overmethylator, you’re going to respond really well to plant-based diets because of the high levels of folate. In fact, if you’ve ever done a juice cleanse and it felt fantastic, there’s a good chance that you are overmethylating.
Foods high in methionine (an essential amino acid) are likely to contribute to higher levels of methyl groups because it’s needed in the methylation process. Foods high in methionine include things like red meat, eggs, and milk. If you think you are overmethylating, you might want to cut back in some of these.
If you related to many of the symptoms listed above and you found that you do really well on a heavily plant-based diet, there’s a good chance that you are experiencing overmethylation. Folate will also help if you are overmethylating, which might seem counterintuitive if you already know that it is also what’s recommended to people who undermethylate. But in an overmethylator, methyl-folate helps reduce the activity of the neurotransmitters that are contributing to the high-energy and anxiety.
For most people who experience overmethylation, it can be easily managed if you know that’s what you’re working with. But because there isn’t a lot of information on overmethylation, most people don’t realize that it’s a huge factor contributing to their overall health. This is why experimenting with your food and supplementation safely is so important. Methylation is in a perfect example of how our bodies are unique and require individualized practices.
9 Signs and Symptoms of Vitamin B6 Deficiency
Vitamin B6, also known as pyridoxine, is one of eight vitamins in the B complex group. Even though it was discovered in 1932, scientists are still learning new things about it.
Most people get enough B6 in their diet, but if you are deficient in other B complex vitamins, such as folate and B12, you’re more likely to be deficient in vitamin B6 as well (1).
In your body, B6 is involved in more than 150 enzyme reactions. These help your body process the protein, carbs and fat you eat. B6 is also closely linked with the functions of your nervous and immune systems (3, 5, 6).
More recently, it’s been found that B6 has antioxidant and anti-inflammatory properties. This means that it may play a role in helping prevent chronic conditions like heart disease and cancer (5, 7, 8).
Here are 9 signs and symptoms of vitamin B6 deficiency.
1. Skin Rashes
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Vitamin B6 deficiency is one cause of a red, itchy rash called seborrheic dermatitis.
The rash can appear on your scalp, face, neck and upper chest. It’s known for its oily, flaky appearance and may cause swelling or white patches (9).
One reason B6 deficiency may result in skin rashes is that the vitamin helps synthesize collagen, which is needed for healthy skin. In these cases, consuming B6 may clear up the rash quickly (10, 11).
Some people affected with seborrheic dermatitis may have higher requirements for B6. A B6 face cream has helped some people improve symptoms from seborrheic dermatitis (12).
An itchy, oily and flaky rash is a common sign of B6 deficiency. Consuming enough B6 generally helps clear up the rash quickly in cases of deficiency.
2. Cracked and Sore Lips
Cheilosis, which is characterized by sore, red and swollen lips with cracked mouth corners, can result from B6 deficiency. Cracked areas may bleed and become infected.
In addition to being very painful, having cracked and sore lips can make activities like eating and talking difficult.
Correcting B6 deficiency with foods rich in the vitamin or a supplement may clear up these symptoms.
Sore lips with cracks in the corners of your mouth can be a sign of B6 deficiency. If that’s the case, getting enough B6 through food or a supplement could heal your lips.
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3. Sore, Glossy Tongue
If you have a B6 deficiency, your tongue may become swollen, sore, smooth, inflamed or reddened. This is called glossitis.
The glossy, smooth surface of the tongue is due to the loss of papillae. Those are the bumps on your tongue. Glossitis can cause problems chewing, swallowing and talking.
Replenishing B6 treats glossitis, provided that a deficiency is the only cause.
A swollen, inflamed, glossy-looking tongue is a sign of B6 deficiency. Shortfalls of other nutrients, particularly folate and B12, may also contribute to the condition.
4. Mood Changes
Shortfalls of B6 may affect your mood, sometimes contributing to depression, anxiety, irritability and increased feelings of pain (16).
That’s because B6 is involved in the making of several neurotransmitters, such as serotonin and gamma-aminobutyric acid (GABA). Both serotonin and GABA help control anxiety, depression and feelings of pain.
The role of B6 in combating such mood issues is being tested in a variety of conditions.
For example, in about half of individuals with autism, supplementing with B6 helps decrease behavioral problems, possibly because it helps produce neurotransmitters (17).
One possible reason B6 may help with PMS is because it helps make serotonin, which lifts your mood. Scientists are doing more research to figure out if women who experience PMS may actually have vitamin and mineral deficiencies (19, 20, 21).
Mood changes like irritability, anxiety and depression can happen when you’re low in B6. That’s because B6 is needed to make nerve messengers that help control your mood.
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5. Weakened Immune Function
A well-working immune system is key to preventing infections, inflammation and various cancers. Nutrient deficiencies, including B6, can disrupt the immune system.
More specifically, a deficiency in B6 can result in the decreased production of antibodies needed to fight infections (22).
A B6 deficiency may also reduce your body’s production of white blood cells, including T cells. These cells regulate immune function, helping it respond appropriately.
Additionally, B6 helps your body make a protein called interleukin-2, which helps direct the actions of white blood cells (23).
People with autoimmune disorders (in which the immune system turns against itself), can have increased destruction of B6, which increases the need for the vitamin (2).
If you don’t get enough B6, your body can’t make the antibodies, white blood cells and other immune factors it needs to fight germs and ward off diseases.
Indication and Important Safety Information
Glucagon is a treatment for very low blood sugar (severe hypoglycemia) which may occur in patients with diabetes. Symptoms include disorientation, unconsciousness, and seizures or convulsions.
Important Safety Information for Glucagon
What is the most important information I should know about Glucagon?
- You should NOT use Glucagon if you have a pheochromocytoma or if you are allergic to Glucagon. (A pheochromocytoma is a tumor, typically of the adrenal gland, that may lead to increased heart rate, blood pressure, sweating, and anxiety.)
- Make sure you tell your healthcare provider if you have been diagnosed with or have been suspected of having an insulinoma, as Glucagon should be used cautiously in this situation. (An insulinoma is a pancreatic tumor that secretes insulin.)
- You and anyone who may need to help you if your blood sugar becomes very low (severely hypoglycemic), should become familiar with how to use Glucagon before an emergency arises. Read the Information for the User provided in the kit.
- Make sure that your relatives or close friends know that if you become unconscious, medical assistance must always be sought. If you are unconscious, Glucagon can be given while awaiting medical assistance.
- Do not use the kit after the date stamped on the vial of Glucagon.
- If you have questions concerning the use of this product, consult a doctor, nurse, or pharmacist.
WARNING: YOU MAY BE IN A COMA FROM SEVERE HYPERGLYCEMIA (VERY HIGH BLOOD SUGAR) RATHER THAN HYPOGLYCEMIA (VERY LOW BLOOD SUGAR). IN SUCH A CASE, YOU WILL NOT RESPOND TO GLUCAGON AND REQUIRE IMMEDIATE MEDICAL ATTENTION.
What are the possible side effects of Glucagon?
- Side effects may include nausea and vomiting, a temporary increase in heart rate, and allergic reactions to Glucagon or to one of the inactive ingredients in Glucagon.
You are encouraged to report negative side effects of Prescription drugs to the Food and Drug Administration (FDA). Visit www.fda.gov/medwatch or call 1-800-FDA-1088.
How should I take Glucagon?
- Act quickly. Prolonged unconsciousness may be harmful.
- Make sure your family and friends know to turn you on your side to prevent choking if you are unconscious.
- The contents of the syringe are inactive and must be mixed with the Glucagon in the accompanying vial immediately before giving the injection. Do not prepare Glucagon for Injection until you are ready to use it.
- Glucagon should not be used unless the solution is clear and of a water-like consistency.
- The usual adult dose is 1 mg. For children weighing less than 44 lbs (20 kg), give ½ adult dose (0.5 mg). For children, withdraw ½ of the solution from the vial (0.5 mg mark on syringe). Discard unused portion.
- You should eat as soon as you awaken and are able to swallow. Inform a doctor or emergency services immediately.
How should I store Glucagon?
- Store the kit at controlled room temperature between 20° to 25°C (68° to 77°F) before mixing Glucagon with the diluent.
- Glucagon that has been mixed with diluent should be used immediately. Discard any unused portion. Glucagon should be clear and of a water-like consistency at time of use.
Glucagon is available by prescription only.
For more safety information, please see Information for the User and Information for the Physician.
HI GLUC CON ISI 18APR2018
Glucagon design is a trademark of Eli Lilly and Company.
©Lilly USA, LLC 2018.
All rights reserved.
6. Tiredness and Low Energy
A vitamin B6 deficiency can leave you feeling unusually tired and sluggish.
A big reason is vitamin B6’s role in helping make hemoglobin. That’s the protein in your red blood cells that helps carry oxygen throughout your body.
If your cells don’t get enough oxygen as a result of too little hemoglobin, it’s called anemia. That can make you feel tired and weak.
There have been select cases of B6-related anemia in which taking the inactive pyridoxine hydrochloride (HCl) form of the vitamin didn’t help. However, supplementing with the body’s most active form of B6, called pyridoxal 5’-phosphate (PLP), resolved the anemia (16).
You can buy either form of B6 as a supplement, but pyridoxine HCl is more common and generally costs less than PLP.
Vitamin B6 is needed to help make the red blood cells that transport oxygen throughout your body and help you feel energized.
7. Tingling and Pain in Hands and Feet
Deficiency of B6 can cause nerve damage called peripheral neuropathy.
Symptoms may include burning, shooting and tingling pain in your arms, legs, hands and feet. Some describe it as a “pins and needles” feeling.
The nerve damage may also result in clumsiness, balance problems and difficulty walking (26).
Additionally, continually taking too much of the inactive form of B6 (pyridoxine HCl) from supplements can also cause neuropathy. This may happen because large amounts of inactive B6 can compete with and block the active PLP form of B6 in your body (27).
Nerve problems from B6 deficiency are reversible with adequate B6 intake. On the other hand, nerve problems from B6 toxicity may be more difficult to treat.
Burning, shooting pains in your limbs, hands and feet can be caused by nerve damage from B6 deficiency or overdose.
Seizures happen for different reasons, including B6 deficiency.
Without enough B6, you don’t make adequate amounts of the calming neurotransmitter GABA, so your brain may become overstimulated.
Seizures can cause symptoms such as muscle spasms, rolling eyes and jerky arms or legs. Sometimes people have rapid, uncontrollable shaking (convulsions) or lose consciousness.
A deficiency of B6 is well-known to cause seizures in newborns. The first cases were noted in the 1950s when babies were fed infant formula with insufficient B6 (26).
Correcting B6 deficiency has proven very successful in treating related seizures.
Seizures are an uncommon but possible result of B6 deficiency. This is more frequently seen in infants but has happened in adults as well.
9. High Homocysteine
Homocysteine is a byproduct created during protein digestion.
A B6 deficiency, as well as folate and B12, can result in an abnormally high blood level of homocysteine, as these B vitamins are needed to help process homocysteine (29).
Increased homocysteine levels have been linked with several health issues, most notably heart disease and stroke, as well as Alzheimer’s disease. When homocysteine is elevated, it can damage blood vessels and nerves (30, 31, 32, 33).
Fortunately, your homocysteine level can be checked with a simple blood test. Generally, elevated homocysteine can be lowered by taking B6, B12 and folate supplements.
Just keep in mind that other factors, such as your eating habits and physical activity, are also typically involved in diseases linked with high homocysteine and must be addressed.
A deficiency of B6, as well as folate and B12, may cause a high homocysteine level, which can damage blood vessels and nerves and increase the risk of disease.
Foods High in Vitamin B6
Your body isn’t able to store very much B6. To avoid deficiency, you need to consume it on a regular basis.
This is generally not hard to do, as B6 is widely found in many animal and plant foods. In addition, it’s often added to fortified foods like breakfast cereals and nutrition bars.
The reference daily intake (RDI) for vitamin B6 for non-pregnant adults is 1.7 mg (34).
Here are some of the top foods that naturally supply B6, as well as common serving sizes (35):
|Food||Serving Size||% RDI|
|Skinless turkey breast, roasted||3 oz (85 g)||40%|
|Pork loin, roasted||3 oz (85 g)||33%|
|Halibut, cooked||3 oz (85 g)||32%|
|Sirloin steak, broiled||3 oz (85 g)||29%|
|Skinless chicken breast, cooked||3 oz (85 g)||26%|
|Wild-caught coho salmon, cooked||3 oz (85 g)||24%|
|Banana||Medium-sized (118 g)||22%|
|Baked potato with skin||Small (138 g)||21%|
|Roasted pistachios||1 oz (28 g)||19%|
|Sweet red pepper slices, raw||1 cup (92 g)||16%|
|Prunes||1/4 cup (33 g)||14%|
|Frozen Brussels sprouts, boiled||1/2 cup (78 g)||13%|
|Sunflower seeds, roasted||1 oz (28 g)||11%|
|Avocado||1/2 fruit (68 g)||11%|
|Lentils, boiled||1/2 cup (99 g)||10%|
Notably, the forms of B6 in animal sources and fortified foods and supplements are generally better absorbed than the form found in plant foods.
If you eat only plant foods, you may need more B6 to make up for this difference (36).
If you regularly eat a variety of meat, poultry, fish, vegetables, fruits, nuts, seeds and legumes, you can easily meet your vitamin B6 needs.
The Bottom Line
Vitamin B6 doesn’t receive a lot of fanfare, but it’s a very hard-working nutrient.
Possible signs and symptoms of B6 deficiency include skin rashes, cracked lip corners, a glossy tongue, mood changes, impaired immune function, tiredness, nerve pain, seizures and elevated homocysteine levels.
If you’re concerned you may not be getting enough B6 or may have a deficiency, talk to your doctor to determine the best course of action.
Fortunately, B6 deficiency is generally easy to avoid as long as you have healthy eating habits that include a variety of fruits, vegetables, nuts, meats and fish.
In some cases, a vitamin B6 supplement may be advised as well.
Written by Marsha McCulloch, MS, RD on June 22, 2018
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How Collagen Can Boost Your Body’s Skin, Muscle, and Gut
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