Folate, Genetics & Mental Health | A Healthy State of Mind

Posted by Mary R. Fry, N.D. on Friday, January 31, 2014

Folic acid has been widely researched for the treatment of depression. In this post we will continue our Micronutrients in Mental Health Series, covering the 3rd nutrient implicated in depression and anemia with our discussion of folate. The name ‘folate’ is derived from the Latin ‘folium’ which means foliage, as it is abundant in leafy green vegetables and was first isolated from spinach.  A deficiency of folate (also known as folic acid and vitamin B9) has been associated with depression, with regular supplementation of the nutrient returning one to euthymia (or a normal mood). Prescription forms of active folic acid (Deplin, Metanx and others) are readily prescribed to augment the effects of antidepressant medications (improve the efficacy of antidepressant medications) and to treat ‘treatment resistant’ depression.

Symptoms of a deficiency

A holistic evaluation of a patient with depression often includes a nutritional history and may include genetic testing to determine if there are genetic polymorphisms that limit absorption and metabolism of this nutrient. A set of genetic polymorphisms that can affect folic acid absorption include those coding for an enzyme required for folate metabolism, Methylenetetrahydrofolate reductase (MTHFR). If an individual has such a polymorphism,  reduced enzyme activity results and they are increasingly likely to suffer from depression (and are also at higher risk of heart disease, gastrointestinal tract issues, megaloblastic anemia, birth defects, infertility, cervical dysplasia, cognitive difficulties and a number of other symptoms/conditions associated with folate deficiency). Other signs and symptoms of folate deficiency include weakness, fatigue, shortness of breath, irritability, forgetfulness, dizziness, headaches, palpitations, a sore tongue, gum disease, diarrhea, loss of appetite, weight loss and abnormal liver enzyme results on labs.

The following questionnaire, produced by Mark Hyman, MD is a helpful tool to determine if your methylation pathways (which require vitamins B12, B (folate)& B to function optimally) are impaired due to a deficiency of one or more of these nutrients. Assign a ‘1’ beside each of those questions which you answer ‘yes’ to.

Scoring the test:

0-8; generally indicates a low-level problem with methylation

≥9; may indicate a severe problem with methylation. A visit to a skilled medical provider who works with nutrient supplementation and diet is advised.

Diagnosing deficiencies

Naturopathic physicians often evaluate patients for genetic polymorphisms and can also investigate other causes of poor folate status (including food allergies, a variety of medical conditions and medications). Those suffering from Ulcerative Colitis, Celiac disease and any condition with gastrointestinal inflammation are at increased risk of deficiency due to malabsorption.  Smokers and those with high alcohol consumption also have lower folate status. Those with liver disease and on dialysis also have lower folate status and are thus potentially more prone to deficiency and depression. Medications that adversely affect folate status include oral contraceptives (or birth control pills), anticonvulsants (which are prescribed in some cases of bipolar disorder), methotrexate, diuretics and proton pump inhibitors.

Laboratory evaluations are highly recommended prior to supplementing folic acid as folic acid supplementation can mask a vitamin B12 deficiency, causing potentially severe neurological effects. Serum folate is often measured, but this test is not a good indicator of folate status over time (it is sensitive to short-term changes in folate intake).  To get a more reliable sense of folate stores, erythrocyte (or red blood cell) folate is preferred. Other laboratory tests that may be performed to assess folate status include Homocysteine, Methyl Malonic Acid and serum B12. Ruling out iron-deficiency anemia is often a part of the work-up as well.

Treating folate deficiency & MTHFR polymorphisms

Supplements with the active form of folate (L-methylfolate, 5-MTHF or Metafolin) are preferred over most prescription forms as they do not contain potentially harmful colorings, flow agents and fillers commonly found in the prescription preparations.

Foods rich in folate include liver, asparagus, legumes, dark green leafy vegetables and whole grains. Folate is lost as vegetables are stored at room temperature and with excessive cooking. While many grains and cereals are fortified with folate, most gluten-free grains/grain products are not. Fortification is potentially harmful for those with the MTHFR polymorphism and may need to be avoided as part of their treatment regimen.

Finally, lest I get too reductionistic in discussing folate metabolism, it is helpful to take a step back and appreciate that human physiology and biochemistry is anything but simple. In its complexity we see that there is much interdependence between nutrients and synergy in absorption and metabolism in some cases. To properly process and utilize folate in our diet, we need to have a balance between dietary protein, vitamin B12 and folic acid levels. Those with deficiencies of any of these nutrients will also have imbalances in the other nutrients,.

Addressing Mental Health Concerns with Folate

If you or someone you know suffers from depression (and/or some of the deficiency symptoms listed herein), a comprehensive evaluation by a physician skilled in nutrition is advised to determine the cause(s) or factor(s) contributing to this mood disorder. Supplementation in the absence of such evaluation and testing may lack efficacy or even pose harm.

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  1. Hyman, M. (2009). The UltraMind Solution Companion Guide. Retrieved from – page 10
  2.  Herbert, V. & Kshitish, C.D. (1994). In Shils, M.E. , Olson, J.A. & Shike, M. S. (Eds.), Modern Nutrition in Health and Disease. (8th ed.). (pp. 402-423). Philadelphia, PA: Lea & Febiger.
  3. Marz, R.B. (1999). Medical Nutrition from Marz. (2nd ed.). Portland, OR: Omni-Press.
  4. Masterjohn, C. (2012). Beyond Good and Evil: Synergy and Context with Dietary Nutrients. Wise Traditions, 13 (3), 15-26.

Categories: Depression, Diet & Nutrition, Supplements Tags: 5-MTHF, Anemia, anticonvulsants, Deplin, genetic polymorphism, medication, Metafolin, Mood, MTHFR, oral contraceptives, proton pump inhibitors, vegetables, vitamins

Non-toxic Foods and Promoting Detoxification

Posted by Mary R. Fry, N.D. on Friday, September 28, 2012



Why do we need Detoxification? As the Environmental Medicine blog series draws to a close, we are working our way from toxins found outside our bodies to those that are found inside. The main route of entry to ingested toxins is through the food and water we consume. As our environment and food supply have become increasingly complex and modernized, so too have our food choices.

To eat well we must become educated about not only what is in our food (micronutrients, macronutrients, phytochemicals…), but also what isn’t supposed to be in it (pesticides, phthalates, bisphenol A, heavy metals, hormones, antibiotics, Genetically Modified Organisms (GMOs) and more).

These chemicals and agents can exert a variety of deleterious effects on mental and physical health; ranging from neurodevelopmental disorders, neurological and psychological complaints to hormonal imbalances, infertility, inflammation, cancer, obesity, and insulin resistance.

Below are some key things to watch out for in the food you eat, the water you drink and how you store and prepare your food. Lastly, I will give you a resource to assess your body burden of toxins and tips on foods you can eat to boost your body’s detoxification capacity.

Produce (Fruit & Vegetables) 

Whenever possible, opt for organic and locally grown fruits and vegetables to have the most vital and fresh foods. If organic is not available or is too costly, you can still relatively safely consume the following non-organic foods (known as the ‘Clean 15’): asparagus, avocado, cabbage, cantaloupe, corn, eggplant, grapefruit, kiwi, mangoes, mushrooms, onions, pineapples, sweet peas, sweet potatoes, and watermelon.

If you can’t find the Dirty Dozen fruits and vegetables (apples, bell peppers, blueberries, celery, cucumbers, grapes, lettuce, nectarines, peaches, potatoes, spinach, strawberries, kale/greens, and green beans) in organic, it is best to eat something else! To download a handy guide of the Clean 15 and Dirty Dozen Plus for your smartphone or to print, click here. Remember to wash all produce thoroughly (even if it is organic and even if it has a peel or rind that you will remove).

Meat, Eggs
Choose organic, free-range or pasture-raised meat/eggs whenever possible to minimize your intake of antibiotics, hormones, pesticides and poor-quality fats (wild game and pasture-raised meat have a healthier fat profile than conventionally raised animals).

Opt for an organic cow or goat milk, yogurt, cheese, and other dairy products to minimize exposure to milk produced from cattle treated with recombinant bovine growth hormone (rBGH) and to minimize exposure to antibiotics, hormones, and pesticides.

Fish and seafood are touted as healthy foods and properly selected, the omega-3 fat, lean protein, and other nutrients they contain do make for very healthy food. Fish that are lower in mercury include Wild Alaskan salmon, Clams, Catfish, Scallops, Sole, Shrimp, and Catfish. Smaller fish such as anchovies and sardines do not concentrate mercury as readily as larger fish and are thus some of the healthiest options. Shark, Swordfish, Sea Bass, Halibut, Tuna (except for albacore), and snapper are best avoided.

Genetically Modified Organisms (GMOs)
We are at a pivotal point in the regulation of GMO foods in this country. Thus far, the FDA and USDA do not require mandatory labeling of GMO foods. California is in the midst of a potentially groundbreaking change in GMO labeling with Proposition 37, a bill that, if passed, would require labeling of all genetically engineered food.

The safety of GMO foods is hotly debated and is beyond the scope of this blog post, but to revisit a principle mentioned in an earlier blog post, until we know more conclusively, perhaps the Precautionary Principle (as followed by Europe, Japan, Canada, and several other countries) is best adhered to. Until labeling of GMO foods is mandated in this country, you can learn more about what foods have GMO ingredients in them by downloading the Non-GMO Shopping Guide.

To learn more about how to determine the safety of your water and how to filter or treat it appropriately, see my earlier blog post (Home Improvement for Health Improvement).

Cooking your food with non-toxic cookware is imperative. Non-stick/Teflon pans are best avoided as they can leach toxins when heated (particularly if the coating is scratched). Microwaving food with plastic or plastic wraps is unwise as phthalates, BPA and other chemicals in the plastic can readily leach into your foods once heated. Safe forms of cookware include stainless steel, ceramics, porcelain-enameled cast iron, Pyrex glass, and cast iron (provided your iron levels are not excessive and you don’t suffer from an iron storage disorder).

Food Storage Containers
It is hard to purchase foods without plastic anymore, but whenever you can find a food packaged in glass, paper, or BPA-free cans, this is best. As chemicals found in plastic can readily leach into fat, fatty foods are the most important to buy/store in less toxic containers. Thus, BPA-free cans are most important for higher fat foods. Here is some information on food manufacturers using BPA-free cans. To find plastics that are BPA-free, look at the numbers on the bottom of the container (avoid numbers 3 & 7) and see the following Guide for more.

Minimizing your toxic burden can have a huge impact on your well-being now and for years to come. Unfortunately in current times, most of us have some chemical burden from the environment we live in, our food and water supply, our home medical interventions that we have had. Testing can be performed to most accurately assess your toxic burden, but to get a rough idea of your current body burden, you can take this Online Body Burden Assessment Test.

Foods You Can Eat to Promote Detoxification
There are several foods and culinary herbs and spices that support and optimize liver health, the key organ in detoxifying ingested chemicals. To boost your liver function, include berries, wolfberries, beets, green tea, broccoli and other Brassica vegetables (cauliflower, cabbage, kale, collards, Brussel sprouts, mustard greens, arugula, bok choy, watercress & more ), and dark green leafy vegetables, artichokes, brown rice, turmeric, chiles and rosemary into your diet.

If more intensive detoxification is needed, herbal supplements and a variety of other methods can be employed by a physician trained in Environmental Medicine.

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References & Resources:

-Crinnon, W. (2010). Clean, Green & Lean. Get Rid of the Toxins That Make You Fat. Hoboken, NJ: John Wiley & Sons, Inc.

-University of Arizona Integrative Medicine Continuing Education:

-Environmental Working Group:

Categories: Diet & Nutrition, Environmental Medicine Tags: body burden, BPA, detoxification, environmental medicine, GMO, Heavy Metals, Hormonal imbalances, liver health, organic.