Mood, Mind and Methylation


Depression has become an epidemic in the United States. According to the National Institutes of Mental Health (NIMH), in 2013, 9.2 percent of adults in the U.S. reported either chronic, low-grade depression, or having had a major depressive episode, defined as a two week or longer period of low mood, coupled with other symptoms such as poor self-image, sleep difficulty, loss of appetite, poor concentration and low energy. Among U.S. adolescents, a disturbingly high 11.2 percent reported having experienced either major depression or low-grade depression lasting two years or more during their their lives, with 1.9 million (7.7 percent) severely impaired in their ability to function due to depression. (By comparison, about 5% of the world’s population is depressed, according to the World Health Organization.)

These statistics do not distinguish between depression that arises for no obvious reason, and what may be referred to as “situational” depression, which occurs in the face of a significant loss or life event, such as death of a loved one, chronic illness, or divorce. Depression, to a point, is a normal and necessary adaptive response to the inevitable changes and phases of life, so as diagnoses of depression have steadily increased over the past decades, some question whether this increase in diagnosis (and the ever-expanding range of conditions considered treatable by antidepressants) has been strategically fostered by “Big Pharma” to justify escalating antidepressant prescriptions as a response to increasing need. (Spend an evening watching network or cable television, and this theory doesn’t seem so far-fetched.)

On the other hand, many of the nutritional, lifestyle, social and environmental factors that strongly influence our ability to maintain a healthy “brain ecology” and adapt to the stress of loss and life changes have become increasingly disturbed in recent decades, contributing to a pervasive decline in mood.

For those depressed and/or anxious people who seek treatment (and a significant number do not), common treatment strategies increasingly include pharmaceuticals, often more than one prescribed in combination. Pharmaceutical antidepressants work by indirect methods to improve the balance of stress hormones such as norepinephrine (a form of adrenaline) and neurotransmitters (brain messengers such as serotonin and dopamine that influence mood, energy, focus and motivation).

Psychotherapy is another common treatment avenue for mood disorders. The benefits of appropriate psychotherapy can be profoundly and positively transformative and are without question a part of any committed approach to treatment of significant depression and/or anxiety.

Depression is not a chemical imbalance

The idea that “depression is a chemical imbalance in the brain” has come to be generally accepted as fact, a medical explanation for depression’s varied symptoms. If this statement is true, then it seems reasonable to apply to the problem of chemical imbalance, a chemical (pharmaceutical) solution. However, this statement is inaccurate in that it sidesteps the more precise and clinically important distinction that we humans are biochemical, not chemical beings. Moreover, the misperception that chemistry provides the best answer to biochemical imbalance denies the powerful therapeutic potential of non-drug , biochemical approaches that actually have the ability to promote true healing of the mind’s biochemical imbalances. (If this were merely a semantic distinction, the extensive field of biochemistry, distinct from that of chemistry, would not have come to exist as it does today.)

There is certainly a place for pharmacologic treatment for mood disorders, including depression. However, it is important to note that while pharmaceutical antidepressants have the ability to modulate levels of neurotransmitters and stress hormones, they do not support the brain’s innate ability to attain and maintain balance in this system. Even when pharmaceutical treatment is indicated, and in view of its associated risks and side effects, doesn’t it make sense to also address existing biochemical dysfunction?

Biochemical Treatment of Depression

Given the proper support, the body/mind has incredible recuperative ability. Humans do not have deficiencies of the chemical antidepressants Zoloft, Wellbutrin, or Elavil, helpful though they may be in some situations. However, we may have imbalances of biochemical such as serotonin, norepinephrine, dopamine, and cortisol, and the underlying mechanisms that naturally support healthy levels and interaction among them.

Elements of a biochemical, “functional” approach to depression and other imbalances of mood may include:

  • Nutritional evaluation and optimization, particularly focused on vitamin D, the Omega-3 fatty acids, the family of B-vitamins, amino acids as the raw materials for neurotransmitters, and other vitamin and mineral co-factors for healthy brain balance.
  • Functional laboratory evaluation of sex hormones, stress hormones and neurotransmitters, to identify and address imbalances.
  • Attention to lifestyle: improving eating habits to stabilize blood sugar; identifying and minimizing exposure to food intolerances; exercising; integrating mind and body through practices such as mindfulness, yoga, Tai Ch’I, or spending time in contact with Nature and the earth.
  • Detoxification: improving digestive tract function and microbe ecology; cleaning up one’s personal environment; obtaining guidance and support for identification and detoxification of internal and external toxicants.
  • Support for impaired methylation cycles.

What is Methylation?

Methylation is an essential biochemical process that occurs in every cell of the body, billions of times per second. The common currency of methylation is the “methyl group”, a biochemical “widget” that contains one carbon and three hydrogen atoms. These methyl group widgets are used to drive many different biochemical processes, through revolving “cycles” of methylation, like a biochemical game of poker, during which methyl groups are exchanged and passed around to perform necessary functions.

In the brain, the importance of methylation to healthy mood cannot be overstated. Methylation is involved in making hormones and neurotransmitters (such as melatonin, serotonin, cortisol, epinephrine and dopamine) that interact to promote a mind-state of serene, alert wellbeing and tolerance for stress. Methylation is also essential to the necessary metabolism, or breaking down for elimination, of hormones and neurotransmitters, among them dopamine, cortisol, histamine, norepinephrine, epinephrine, and glutamate. If methylation is impaired, the exquisite balance between production and elimination of stress hormones and neurotransmitters is skewed, and mental function and mood are negatively affected.

Supporting MTHFR, MTRR and COMT enzymes

MTHFR (methylene tetra-hydrofolate reductase), MTRR (methionine synthase reductase) and COMT (catechol-O-methyltransferase) are enzyme systems that act synergistically as brain methylation pathways to promote balanced brain biochemistry. Reduced activity of these enzymes can occur because of inadequate nutritional cofactors required for their function due to poor diet, nutrient depletion from stress, inflammation or toxicity, or because of genetic influences. Impairment of these enzymes increases vulnerability to depression (and other disorders such as anxiety, attention problems, and bipolar illness).

With the relatively recent identification of gene SNPs (single nucleotide polymorphisms, or mutations) involving these and other enzyme systems, genetic influences on depression have become more clear. Fortunately, it’s possible to reduce the impact of genetic vulnerability, by providing specific nutrient support targeting the genetic vulnerability associated with the SNP. In this way, the symptomatic expression of depression (and other mood disorders) may be “epigenetically” modified in a positive direction through nutrition and lifestyle. For example, if through testing a person learns that they received a SNP from both parents for the MTHFR mutation, which interferes with folate metabolism, she/he is significantly more vulnerable (36% according to one study) to depression. The good news is that this genetic vulnerability may be significantly neutralized by adequate nutritional intake of appropriate nutrients, including folate. It’s like taking a detour around a roadblock.

Nutritional “Antidepressant” Support for Methylation

The amino acid nutrients SAMe (S-adenosyl methionine) and MSM (methyl sulfonyl methane) provide raw material for and broad general support for methylation. Essential cofactors used in these pathways include the B-vitamin folate in the form of 5-MTHF (5-methyl tetrahydrofolate), vitamin B12 (as methylcobalamin), and activated, or phosphorylated forms of pyridoxine (vitamin B-6) and riboflavin (vitamin B-2). Additional nutritional methylation cofactors are trimethylglycine (also called betaine) and the minerals selenium and magnesium. For optimal bioavailability, particularly for those with genetic vulnerability to poor methylation, these nutrients must be provided in ready-to-go, partially metabolized forms, as noted above.

Because of the complex interrelationships between these enzyme processes and the nutrient cofactors that support them, it is recommended that nutritional intervention be undertaken under the supervision of a healthcare practitioner with a background in functional medicine and biochemistry as it relates to methylation and mood.

How Well Are You Methylating?

How can you find out if you have a problem with these naturally mood-stabilizing pathways? One of the most obvious indications of methylation impairment is a serum test for the blood protein homocysteine, available from any clinical laboratory. A serum homocysteine level above 8.0 tells you that methylation is not proceeding smoothly. Another indicator is an elevated MCV (Mean Cell Volume) on a CBC (Complete Blood Count). That said, a normal MCV can coexist in someone with an elevated homocysteine level, and not all methylation impairment can be identified through homocysteine. However, with the advent of relatively inexpensive genetic testing, it’s easy to find out if you have SNPs in methylation-relevant enzyme systems (including MTHFR, COMT, and MTRR). Armed with that information, it’s possible to create a truly personalized plan for improved methylation and better mood.

Simple Natural Tips to Balance Blood Sugar

Whether you’re aware that your energy slumps, cravings for sweets or breads, bouts of irritability, or poor concentration relate to patterns of poor eating; or you need to pull out of a stall in the weight loss program you started earlier in the year; or you just want to improve your eating habits for greater health and vitality, better blood sugar balance is essential.  We now know that there are serious consequences for long-term uncontrolled blood sugar and its evil sister, hyperinsulinemia (high blood levels of the hormone insulin): increased risk for stroke and cardiovascular disease; high serum cholesterol/ triglycerides; Type 2 diabetes mellitus; inflammation; dementia, and many more members of the dysfunctional family of chronic degenerative diseases.  So achieving and maintaining blood sugar stability may be one of the most important and simplest strategies for health promotion in the short term and disease prevention for the long run.

While blood sugar balance involves complex interactions between the food we eat, many hormones, and multiple organs and body systems, when it comes down to it there are two essential elements around which the whole process revolves: the pancreas, which secretes the blood sugar-regulating hormone insulin, and the membrane of each cell, where glucose leaves the blood to be put to use inside the cells.

Blood Glucose and Insulin

Glucose is an end-product of the digestion of carbohydrate-containing foods from our diets: healthy, complex carbs are found in fruits; grains; vegetables, particularly the starchy ones such as potatoes; nuts; seeds; and beans.  Whether you have the garden-variety form of blood sugar imbalance called hypoglycemia (low levels of blood glucose); or the opposite problem of high blood glucose (hyperglycemia, which when advanced and chronic becomes diabetes mellitus), the net effect is the same:  not enough glucose inside the cell, where it can be put to use making energy and helping cells work properly.  Glucose enters the cell by crossing the cell membrane, and it does this through “doorways” in the membrane called glucose channels.  These doorways have “locks” on them called insulin receptors, which will only open if the “key” to the insulin receptor – the hormone insulin – turns smoothly in the lock.  When that happens – abracadabra! – the glucose channels open, glucose streams into the cell, and the cell makes energy with it.  The whole cell is happier, healthier, and more productive when this lock and key system works well; when it doesn’t, your cells can’t function well and neither can you.

Re-sensitize your insulin receptors

At the cellular level, balanced blood sugar depends on healthy, sensitive insulin receptors – so if your blood sugar is out of whack, it’s smart to ask, What will make my insulin receptors work better?

Just as an insensitive person may have poor listening skills, insensitive insulin receptors don’t “hear” insulin knocking at the door, so they don’t respond as they are supposed to, letting glucose into the cell.  While there are many nutrients that can help your insulin receptors to hear better, to keep it simple I’ll mention just a few of the most important:  the trace mineral chromium (the “trivalent” nutritional form, not the toxic, shiny metallic form); the antioxidant alpha-lipoic acid; the omega-three class of essential fatty acids; a high-potency B-complex vitamin.

Chromium picolinate or polynicotinate (yeast-free):  these two versions of chromium have shown better absorption than others; named “Glucose Tolerance Factor” when first discovered, trivalent chromium has been shown to improve glucose balance in numerous studies.  It is estimated to be present in low amounts in 90% of diets. Though I may use higher dosages clinically, daily intake of between 200 and 600 mcg. is reasonable and has been demonstrated to be safe and beneficial in human studies.

Alpha-Lipoic Acid:  this super antioxidant has been shown in studies to positively affect glucose balance and insulin sensitivity by means of several mechanisms.  While opinions differ as to which version is most effective (the R-form or a mixture of the two biochemical forms, the R and S forms), I have come down on the side of the R-form, and routinely prescribe a stabilized R-Alpha- Lipoic Acid, in doses ranging from 100-200 mg. twice to three times daily.

Omega-3 Fatty Acids (EPA and DHA): these healthy fats (EFAs, or essential fatty acids) are found in certain fatty fish, calamari, and krill, and have been found to improve glucose and insulin balance in Type 2 diabetics.  They keep cell membranes supple, enabling the receptors and channels seated in the membrane to work better, and their anti-inflammatory effects improve insulin receptor sensitivity for better glucose balance.  I may prescribe between 2000 and 6000 mg. daily of total omega-3’s when addressing glucose/ insulin intolerance.  Fish oil quality varies widely, and I am careful to choose those from manufacturers which adhere to pharmaceutical-level production practices and are sustainably sourced, are third-party assayed for contaminants (mercury, arsenic, cadmium, dioxins, PCBs), and are stabilized with natural antioxidants (such as tocopherol [vitamin E], ascorbyl palmitate [a form of vitamin C], or rosemary) to reduce the rate of deterioration in the bottle.

B-Complex vitamins: because of their role in turning glucose into energy, increasing chromium bioavailablilty, and promoting healthy essential fatty acid metabolism, no program for better blood sugar balance is complete without attention to B-vitamin status.  In my practice, I often prescribe 50-100 mg. daily of many of the B-vitamin family members; I also provide counsel regarding potential for and symptoms of toxicity for Pyridoxine (vitamin B-6).

Preserve your pancreas!

The pancreas, remember, is another major player in blood sugar regulation.  One of its primary functions is to secrete insulin from special cells called beta-cells.  In someone with insulin-dependent diabetes mellitus, the beta cells don’t make enough insulin, so the person must take it daily to keep blood sugar in balance.  When insulin receptors have become “hard of hearing” as described above, the pancreas tries to fix the situation by flooding the bloodstream with insulin, hoping to overcome the insulin insensitivity and push glucose into the cell.  This condition of hyperinsulinemia is bad enough, because it is associated with a host of serious, undesirable health issues, some of which have been described.  But even worse is the unfortunate reality that over time, the pancreas just can’t continue to secrete so much insulin; it becomes fatigued, so to speak, and can’t put out enough to manage blood sugar.  Of course, the best way to protect your pancreas from overwork and exhaustion is to minimize refined carbohydrates (foods which contain processed sugars and flours – so-called “white foods”), eat a whole foods, low-glycemic burden, Mediterranean diet, balancing complex carbohydrate and protein in five or six smaller meals and snacks spread through the day; to exercise; and to balance your stress response.

Gymnema sylvestre and Beta-cell regeneration

But what if your pancreas is close to burn-out, what can you do?  A number of botanicals have been found to positively affect glucose/ insulin balance, among them Momordica charantia (bitter melon), Vaccinnium myrtillus (bilberry) and Cinnamonium cassia (cinnamon).  A standout among botanicals for blood sugar control, however, is the herb Gymnema sylvestre (known in Hindi as gurmar, or sugar destroyer, because it reduces the taste of sweetness for a couple of hours after chewing on its leaves).  This mellifluously named herb has been used in India for 2,000 years to treat diabetes, and over the past decades extracts of Gymnema have become a focus of scientific research for their ability to increase pancreatic beta-cell insulin production and normalize blood glucose.  In naturopathic medicine, Gymnema is an important tool for improving insulin secretion in people with “pancreatic fatigue” and declining or low insulin output; in my practice I prescribe a formula which contains 100 mg. of Gymnema extract, standardized to contain 25% of the gymnemic acids which are thought to be the active components of the herb.  I usually prescribe Gymnema in two divided daily doses of 100-200 mg. each.

Take it slow and steady

Because they are very effective, if you have severe blood sugar imbalance and in particular if you take pharmaceutical medication for blood sugar/insulin regulation, you must start with lower amounts of these natural agents and you must monitor blood glucose carefully as you increase them.  If you take too much, too soon, it can cause an excessive drop in blood sugar: the goal is balance, so it’s best to take a gradual approach. If you’re on medication, adding these natural assists for healthier blood sugar may well enable you to reduce it over time, with the help of the physician who prescribed it (who knows, s/he might want to know how you did it!).