Integrative Medicine for Depression

integrative medicine

Integrative medicine for depression is a holistic approach to treating this complicated and common illness. If someone has treatment resistant depression (therapy and medication don’t work) it’s likely there is an underlying physical cause of the depression.

Integrative Psychiatrist Dr. James Greenblatt has helped thousands of people with treatment resistant depression see a reduction or complete remission of their symptoms. Dr. Greenblatt has authored many books including Integrative Medicine for Depression: A Breakthrough Treatment that Eliminates Depression Naturally. He has kindly given me permission to share an excerpt from his book. 

The content below is excerpted from Dr. James Greenblatt’s groundbreaking book, Integrative Medicine for Depression, and while edited for length is otherwise unaltered.  It is presented here with Dr. Greenblatt’s express permission, which has been exclusively granted to David Minor of Solidarity Coaching and Counselling.


Traditionally, nutrition and overall physical fitness have not been a part of psychiatric evaluation. But in integrative psychiatry, they are critical parts of understanding potential treatable causes of depression. Results from such evaluations are used as a basis for developing personalized nutritional and health programs that optimizes function and helps ensure patients’ recovery and long-term well-being. 

Rather than treating symptoms, it makes more sense to treat underlying nutritional and metabolic imbalances that are getting in the way of positive mood and healthy functioning. By restoring balance, symptoms should lessen or even vanish. First, however, we must discover where those imbalances lie. 

One of the best ways to accomplish this is through lab testing. In the nutritional assessment of a person with depression, a number of tests are critical. Some are commonly performed in a doctor’s office, while other tests are not as well known. It’s also possible that they won’t be covered by health insurance. 

However, all of them are important. Testing for and correcting any identified nutrient deficiencies through proper supplementation can do much to help you feel better, and can make it easier for you to become an active participant in your own recovery

Getting Started 

For a comprehensive assessment of depression, I recommend the following tests, which can be ordered by any physician:

  • Amino acids
  • Complete blood count (CBC) with differential
  • Comprehensive chemistry panel
  • Celiac disease screening (antitissue transglutaminase antibody and anti gliadin antibody tests)
  • C-reactive protein
  • DHEA-S and pregnenolone
  • Essential fatty acids
  • Fasting amino acids
  • Folate and vitamin B12
  • Food allergies
  • Homocysteine
  • Hormones (estrogen, progesterone, and testosterone)
  • Iron and ferritin
  • Kryptopyrrole
  • Lipid panel
  • Lithium levels
  • Magnesium
  • MTHFR genetic test
  • Red blood cell trace minerals
  • Thyroid panel and thyroid antibodies
  • Urinary organic acids
  • Urinary peptides (including casomorphin and gliadorphin)
  • Vitamin D
  • Zinc and copper

Here’s a brief summary of each of the laboratory tests listed above. 

Amino Acids

As the building blocks of the proteins found in every tissue and organ of the body, amino acids help regulate neurotransmitters, form antibodies, and produce energy inside the cells. Amino acid depletion, then, especially of any of the nine essential amino acids, can cause serious health problems, some of which are related to mood and cognitive function. 

For example, a deficiency of tryptophan can lead to depression, while a lack of tyrosine or phenylalanine can contribute to fatigue and difficulty concentrating. Both blood and urine tests can be used to detect amino acid levels. Blood tests may mean a blood draw or just a finger stick. If amino acid levels prove to be abnormally low or high, they can usually be adjusted through supplementation or diet. 

Complete Blood Count with Differential 

The CBC measures white blood cell count and types (called differential), red blood cell count and characteristics, hemoglobin, hematocrit, and platelets. Anemia, which can lead to depression, is revealed by low red blood cell count, low hemoglobin, and low hematocrit. Certain characteristics of the red blood cell, designated MCH, MCV or MCHC, can pinpoint the nutrient deficiency causing the anemia, whether it’s copper, folate, iron, or vitamin B12. 

White blood cell levels can be abnormally high due to an infection, an allergic reaction, or leukemia, or abnormally low due to medication reactions or low levels of zinc, which is needed for white blood cell production. Platelets play a role in blood clotting, and both high and low levels are abnormal. Low levels can cause excessive bleeding and bruising.

Celiac Screening 

Celiac disease is a sensitivity to the gluten found in wheat and other grains, in which the body mistakenly identifies gluten as a foreign invader and launches an immune attack. A good amount of evidence suggests that people with celiac disease have higher rates of anxiety and depression than others. 

It appears that an activation of the inflammatory response system occurs with major depression, and that certain proinflammatory substances like cytokines can trigger symptoms of depression. Screening for celiac disease involves examining a blood sample to deter- mine the presence of two antibodies that the body makes in response to gluten: antitissue transglutaminase and antigliadin. 

To confirm a positive result, a biopsy of the small intestine can be performed. An endoscope is inserted down the throat, through the stomach and into the small intestine. Tissue samples taken from its lining are examined under a microscope to identify characteristic changes of celiac disease, including shrunken, flattened villi, which are the hair-like projections lining the intestine. 

Comprehensive Chemistry Panel 

This group of blood tests is used to evaluate organ function and is a preliminary check for diabetes, liver disease, and kidney problems. The test results give important information about electrolyte status, acid-base balance, kidney function, liver function, and blood sugar and protein levels. This panel can also test a person’s zinc status by measuring alkaline phosphatase, an enzyme produced in the presence of zinc. 

A low alkaline phosphatase level often indicates a zinc deficiency. C-Reactive Protein C-reactive protein (CRP) is a protein produced by the liver and commonly used as a marker to ascertain inflammation in the body. Elevated CRP 272 Integrative Medicine for Depression levels may be due to a lack of sleep, stress, excessive exercise, infections, overeating, and obesity. 

Chronic inflammation can lead to a higher risk of cardiovascular disease, diabetes and depression. One large-scale study completed in Copenhagen examined 73,131 men and women aged twenty to one hundred years old and found that higher levels of CRP were associated with an increased risk for distress and depression. 

Several studies suggest that lifestyle changes such as regular exercise can help normalize levels, often resulting in improvement in treatment outcomes and symptoms. Levels of CRP can be detected through a simple blood test. 

DHEA and Pregnenolone 

Dehydroepiandrosterone (DHEA), the most common steroid hormone in the body, is the “raw material” used to produce the sex hormones testosterone and estrogen and as many as one hundred and fifty other steroid hormones. Production of DHEA is at its peak in your mid twenties,after which it drops precipitously, falling about ninety percent between ages twenty and ninety.

Age-related weight gain and abdominal obesity are believed to be at least partially due to this drop in DHEA. Low levels of DHEA have been linked to depression. Levels are checked by measuring a form of the hormone called DHEA-sulfate in the blood. Pregnenolone is synthesized from cholesterol and is the precursor to several steroid and hormones. Similar to DHEA, pregnenolone levels decline as we age. 

A lack of pregnenolone is associated with impaired brain function, memory, and depression. In fact, researchers have found significantly lower levels of pregnenolone in the cerebrospinal fluids of depressed patients compared with healthy counterparts. 

Essential Fatty Acids 

Two kinds of fatty acids are considered essential because the body cannot make them itself: the omega-3s and the omega-6s. The omega-3s, EPA and DHA, help fuel the brain and control the inflammation in degenerative brain diseases such as Alzheimer’s disease. EPA helps maintain nerve cell membranes, while DHA improves communication between brain cells. 

Studies support the use of omega-3 fatty acids in depressed pregnant women; omega-3s have no effect on the fetus. Omega-6s are also crucial to brain function. People who have essential fatty acid deficiencies are at risk for many symptoms,including depression. In addition, depression can result from omega-6 levels that are too high relative to omega-3s. 

Tests of blood serum and red blood cells can confirm omega-3 and omega-6 levels, as well as the ratio of the two. Abnormally high or low levels of the various fatty acids can be treated with supplementation or dietary changes. 

Folate and Vitamin B12 

Folate and vitamin B12 are essential for normal psychological function. Deficiencies are commonly found in depressed individuals. Folate is needed to make brain neurotransmitters, while B12 is needed to make red blood cells. Folate deficiencies have been linked to depression and anemia, while vitamin B12 deficiencies can contribute to many psychiatric and neurological symptoms, including depression, anxiety, hallucinations, memory loss, and confusion.

Food Allergies 

Food allergies may contribute to many psychiatric illnesses, including depression,ADHD, and anxiety.It is clear that people with food allergies tend to have depression more often than their healthy counterparts. These food allergies, as you recall from Chapter 9, lead to the production of excess IgG antibodies. 

There are now several ways to test for IgG antibodies. For many years, the standard test for allergies to various kinds 274 Integrative Medicine for Depression of foods was a skin-prick test. This consisted of scratching the patient’s skin and then dropping an extract of a particular food into the wound. 

If a reddened bump that looked like a mosquito bite appeared, the person was deemed to be allergic to that food. Now, a blood test, taken from either a blood draw or a finger prick, is often used. 

For this test, blood is drawn and sent to a lab, where extracts of individual foods are mixed with the blood to see if specific elements of the immune system within the blood, the IgG antibodies, react to them. The test measures whether IgG antibodies are produced. If they are, the person is considered allergic to thatfood. 


Homocysteine, an amino acid produced by the body, is normally converted quickly to another amino acid called cysteine. But if this conversion is somehow impaired, homocysteine levels rise. High homocysteine levels harm the body, as they are linked to an increase in free radical activity,the formation of blood clots, and heart disease. 

A link also exists between high homocysteine levels and major depression. Although not all depressed people have high homocysteine levels, and not all of those with elevated homocysteine are depressed, data from the Health in Men Study, which involved 3,752 men age seventy and older, found that higher levels of homocysteine increased the risk of depression. 

On the other hand, lowering homocysteine by 0.19 mg/L reduced the odds of depression by about twenty percent. Because folate, vitamins B12 and B6, and zinc convert homocysteine to the non-harmful cysteine, individuals lacking these nutrients can develop a buildup of homocysteine. 

In fact, high homocysteine levels can indicate early-stage folate deficiency, or deficiencies of vitamins B6 or B12, even before blood levels of these nutrients reflect any problems. Oral doses of folic acid, B6 and B12 may help improve treatment outcomes in depression. 

Hormones (estrogen, progesterone, and testosterone) 

As discussed in Chapter 8, the sex hormones testosterone, progesterone and estrogen are essential to healthy bodily functioning, and research has revealed that many are also linked to mood and behavior. The interplay between these hormones is complicated, and what levels are ‘normal’ will differ greatly not only between men and women but also between different individuals of the same gender. 

These variations aside, a substantial body of scientific evidence links sex hormone levels with depression and depressive susceptibility; for this reason, I recommend the following: 



All depressed men should have their testosterone levels checked. There is a strong link between depression and low testosterone and, in some men, depression cannot be relieved until their levels are raised. 

Testosterone is checked with a simple blood test. The “normal” values vary from laboratory to laboratory, with about 270 to 1,000 ng/dL considered normal for men aged twenty to forty.The top of the range declines as men age, falling to the 700s for most men aged sixty and older. But remember—what may be “normal” for one man can be low for another, so test results must be interpreted in light of all other findings. 


Female patients presenting with depressive symptoms should be tested for levels of three different hormones: testosterone,estrogen, and progesterone. 


Women’s bodies do make testosterone! Secreted primarily by the ovaries, testosterone in women helps to sensitize serotonin receptors, maintain bone mineral density, and support a healthy libido.

Just as in men, a testosterone deficiency in women can be associated with negative 276 Integrative Medicine for Depression symptoms such as fatigue, high blood pressure, muscle weakness, and a loss of lean body mass. 


The primary sex hormone in females, estrogen is actually an umbrella term for a class of steroid hormones. Secreted primarily by the ovaries (and, during pregnancy, by the placenta), estrogens are responsible for the development of secondary sexual characteristics and the regulation of the reproductive system in the female body. 

The most important of the estrogens are estrone (which accounts for about thirty-three percent of all circulating estrogens in women who maintain a menstrual cycle), estriol (which accounts for approximately ten percent of all circulating estrogens), and estradiol (accounting for up to forty-four percent of all circulating estrogens). 

In menstruating women, estrogen levels rise and fall according to the menstrual cycle phase; in women approaching menopause or those who have entered menopause, overall levels of the estrogens within the body begin to drop. What levels are “normal” or “ideal” thus depend on a huge number of factors that may fluctuate over periods of time. 

Estradiol maintains a unique significance when it comes to the assessment of hormones, mood, and cognition in women, as estrogen receptors in the female brain are specific to estradiol. It is unsurprising, then, that low levels of estradiol have been linked to depression and depressive symptoms. 

Studies have shown that women with major depressive disorder have estradiol levels twenty-five percent lower than those of non- depressed women at the midpoint of the monthly menstrual cycle; other reports have documented estradiol levels being up to thirty percent lower in depressed women during the follicular phase of the menstrual cycle than healthy women. 


The most important member of a class of steroid hormones known as progestogens, progesterone has a number of vital functions within the female body. It is produced by the ovaries and the brain and is the primary sex hormone involved in the menstrual cycle and pregnancy. 

It is also a critical metabolic intermediate necessary for the manufacture of other sex hormones and corticosteroids, which are involved in processes ranging from stress and immune responses to the regulation of inflammation. 

Progesterone is not just a simple sex hormone, however; it is also a neurosteroid, meaning that it is capable of directly affecting the function and activity of neurons. Neurosteroids such as progesterone are neuro- protective and involved in mechanisms by which neurons transmit signals (neurotransmission). 

Deficiencies of progesterone are thus associated with both physical and neurologic symptoms, which may include weight gain, joint aches, headaches, agitation, anxiety, insomnia, and depression. A note on hormone level testing in females It is difficult to understate how important testosterone, estrogen, and progesterone are to health and well-being in women; the biochemical and metabolic relationships that link these hormones, however, are incredibly complex, and absolutely specific to the individual. 

Even in healthy, non-depressed women, hormone levels will rise and fall naturally according to age, the presence or absence of a menstrual cycle, the presence of other metabolic or endocrine disorders, diet…and the list goes on.

The presence of depression or other mood disorders may further muddy an already-complicated picture, as stress and inflammation may affect not only the individual levels of testosterone, estrogen, and progesterone, but the delicate ratios between them that can profoundly influence physical and mental health. 

It is for this reason that I do not offer any parameters for what levels of, for example, testosterone may be “ideal” for one individual versus another, or what estrogen and progesterone ratios are “healthy.” In line with the concept of biochemical individuality (detailed in Chapter 5), what levels and ratios are ideal in one patient may be low or high in another. 

My message regarding the female sex hormones is, then, a simple one: get them tested! Results should be reviewed with the ordering physician as well as (if necessary) an endocrinologist. These medical professionals can help you interpret what are often confusing sets of numbers. If any abnormalities are detected, a treatment plan to balance hormone levels may be implemented under the close supervision of your endocrinologist. 

Iron and Ferritin 

Because iron is needed to make hemoglobin, which helps red blood cells carry oxygen to the cells of the body, a chronic iron deficiency can cause fatigue, weakness, and depression. Lack of iron can also impair memory and motor skills and may worsen emotional and psychological problems. Iron influences levels of the enzymes tyrosine hydroxylase and tryptophan hydroxylase, which regulate the production of dopamine and serotonin, respectively. 

Two common tests screen for levels of serum iron and ferritin, a protein that stores iron. These tests are often ordered together. Sometimes, blood levels of iron appear normal, but the stored supplies are low. If ferritin levels are below normal, or even in the low-normal range (less than 100 ng/mL), I recommend additional iron supplements. Taking iron with vitamin C can help with absorption. 


When it comes to integrative treatments for depression, it can be as important to test for factors that influence key nutrients as it is to test for key nutrients themselves! Kryptopyrroles are a perfect example of this. Pyrroles are organic compounds that make up part of the heme molecule (heme is the component of hemoglobin responsible for hemoglobin’s ability to bind and transport oxygen). 

Excess pyrroles have no function in the body and are normally excreted in urine; if pyrrole levels accumulate, however, as is the case in the condition pyroluria, they can contribute to nutrient imbalances and exacerbate depressive symptoms. The issue lies with the fact that pyrroles bind with vitamin B6 and then with zinc, and thus deplete levels of both nutrients. As discussed in Chapters 13 and 10, respectively, deficiencies of vitamin B6 and zinc lead to disruptions in the metabolism of neurotransmitters such as serotonin, dopamine, and GABA. 

Symptoms of pyroluria include nervousness and anxiety, mood swings, severe inner tension, poor short-term memory, and depression, all of which are related to the depletion of B6 and zinc by excess pyrroles. Pyroluria can be diagnosed by evaluating a patient’s level of hydroxy- hemopyrrolin-2-one (HPL; also known as kryptopyrrole) through a kryptopyrrole quantitative urine test. 

Borderline levels (10-15mcg/dL) high levels indicative of pyroluria (>15mcg/dL) can be treated with supplementation of vitamin B6 and zinc. For individuals whose HPL levels exceed 15mcg/dL, I recommend 100- 400mg per day of vitamin B6 (in the form of pyridoxal-5- phosphate) per day, along with 25-100mg per day of zinc (in the form of zinc picolinate). 

Lipid Panel 

A lipid panel measures levels of total cholesterol, triglycerides, HDL, and LDL through a blood test. As we discussed earlier in the book, recent studies suggest that low total cholesterol levels are linked to depression and suicidal thoughts. One study published in the Journal of Psychiatric Research in 2009 found that death from suicide, accidents, and other unnatural causes was seven times more likely to occur in men with low total cholesterol (below 165 mg/dL) than in men with healthy levels. 

Some experts believe that having low cholesterol results in lowered pro- duction of serotonin and fewer serotonin receptors. And, of course, low serotonin levels are linked to depression as well as decreased levels of the hormones progesterone and testosterone (both of which are also associated with depression.) 


Lithium is present in our environment, food, and water, and is an essential nutrient for the human body. The most common source of lithium in the modern diet is tap water. In the mid-nineteenth century, mineral water containing high lithium levels sourced from springs in Europe and the 280 Integrative Medicine for Depression United States was bottled and sold to grocers, pharmacists, and other merchants. 

The popular soft drink 7-Up originally contained added lithium as an ingredient and was first marketed as a both a hangover cure and a mood-uplifting tonic. (Lithium was removed from 7-Up in 1948 and is not found in 7-Up today.) Research has revealed that low levels of environmental lithium are associated with increased rates of depression, volatile mood, aggressive behavior, and suicide. 

One study found that violent criminals had little to no stores of lithium in their hair analyses. Lithium levels can be measured through a urine test or a hair tissue mineral analysis (HTMA). Hair tissue mineral analysis is a noninvasive and relatively inexpensive procedure that analyzes levels of minerals and metals in a sample of hair. 

Hair samples can provide accurate information about mineral stores that have accumulated over the last three months. Lithium has long been the standard and most effective treatment for bipolar disorder and for quelling the urge to commit suicide. Supplementation with low dose nutritional lithium between 2.5 mg to 20 mg is particularly helpful in patients at risk of depression, suicide, and dementia. 


The mineral magnesium is needed for several hundred bodily functions, including the conversion of carbohydrates, fats, and proteins into energy, and the maintenance of normal heartbeat, blood coagulation, insulin production, and muscle and nerve function. A magnesium deficiency can result in depression, anxiety, weakness, cardiac complications, insomnia, and difficulty concentrating, among other problems. 

Testing for magnesium deficiency is not as simple as taking a blood sample. Most of the body’s magnesium is locked away within its cells, with only about 1 percent of the body’s total magnesium free-circulating within the bloodstream. 

It is entirely possible for a person to achieve a normal result from a blood test and still be magnesium-deficient, as blood levels reflect neither the magnesium content of the body’s tissues, nor the magnesium level within the fluid surrounding the brain. 

MTHFR Genetic Testing 

Genetic research is a useful tool, and almost any physician can order a genetic test for a patient. By analyzing an individual’s genetic and biological markers, these simple tests, often performed by a saliva collection, can inform physicians as to the most appropriate and effective treatment for the patient based on his or her own unique genetic profile. 

The results reveal how a patient may metabolize or respond to different medications. One biological marker that is analyzed in genetic testing is the methlentetrahydrofolate reductase (MTHFR) gene. People with genetic mutations called methlentetrahydrofolate reductase (MTHFR) polymorphisms have impaired folate metabolism. 

As mentioned earlier in the book, several studies show that people with variants of the MTHFR gene have a higher incidence of depression and require higher levels of folate supplementation. Genetic testing to determine whether you have MTHFR polymorphisms can be invaluable in treating depression. Red Blood Cell Trace Minerals When assessing any disorder linked to a zinc deficiency, including depression, a red blood cell analysis is recommended. 

This test evaluates levels of a variety of nutrients, including calcium, phosphorous, zinc, selenium, boron, chromium, and vanadium, as well as potentially toxic elements, all of which have important effects on blood cells or blood cell membranes. Selenium, which is found in groundwater and is also available as a supplement, is thought to strongly protect against depression. 

One study showed that low levels of selenium increased the likelihood of major depressive disorder. Selenium levels should be in the range of 82-85 µg/L 282 Integrative Medicine for Depression in adults; elevated levels of selenium have been shown to worsen depression. 

In one study, high doses of selenium were shown to increase depressive symptoms, a doubling of selenium level being found to correlate with a fifty-six percent higher likelihood of depression. There are a number of elements that are toxic to the human body, can interfere with its functioning, and undermine health. They include mercury, lead, cadmium, aluminum, and arsenic. The blood or cellular levels of these toxic elements should always be zero. 

Thyroid Panel and Thyroid Antibodies 

Thyroid hormones play a role in circadian rhythms and are responsible for regulating the rate at which the body uses energy. The thyroid gland takes up iodine and converts it into the thyroid hormones thyroxine (T4) and triiodothyronine (T3). When concentrations of these hormones drop too low, the pituitary gland releases thyroid-stimulating hormone (TSH), which prompts the thyroid gland to produce more hormones. 

When levels normalize, the thyroid stops producing these hormones. A thyroid panel is a group of tests that measures the amount of TSH, T4, and T3 in the bloodstream. Too little T4 and T3 causes hypothyroidism, a condition that lowers the metabolic rate and increases the tendency toward weight gain, loss of appetite, fatigue, constipation, cold intolerance, and menstrual irregularities. 

On the other hand, too much T4 and T3 causes hyperthyroidism, which steps up the metabolic rate and causes weight loss, an increased heart rate, anxiety, insomnia, weakness, and loss of appetite. Low thyroid hormones contribute to depression, anxiety, and other psychological problems. Screening for thyroid problems is an important step in diagnosing and treating depression. Levels of thyroid hormones can be assessed through a simple blood test. 

Urinary Organic Acids 

Abnormally high levels of organic acids result from the blockage of one or more of the body’s metabolic pathways, which prompts excretion of these acids through urine. Organic acids in the urine indicate problems with biological processes, including neurotransmitter function, detoxification, digestive imbalances, energy production, and nutrient deficiencies. For example, high levels of a urinary organic acid called methylmalonic acid can indicate a vitamin B12 deficiency in its early stages, even before it’s detectable through other methods. 

B12 is necessary for various chemical reactions that keep methylmalonic acid levels in check, so when B12 levels drop, methylmalonic acid levels rise. Combined with the results of a homocysteine test, high methylmalonic acid levels can confirm a mild or early vitamin B12 deficiency —even if blood levels of B12 appear normal. 

Similarly, high levels of an organic acid called kynurenate may indicate a deficiency of vitamin B6, a vitamin required to make all major neurotransmitters. When there are reduced amounts of B6, kynurenate levels increase in the urine. Testing for urinary organic acids requires a first-morning urine sample. Dietary changes, nutrient supplementation or antifungal/antibiotic medications may be used to correct the underlying conditions leading to abnormally high levels. 

Urinary Peptides 

The opiate peptides casomorphin and gliadorphin appear in the urine when the naturally occurring proteins casein (found in milk) and gluten (found in wheat, rye, barley, and certain other grains) are broken down incompletely. 

These problems in breakdown occur because the protease enzyme DPP IV occurs in insufficient quantities in the small intestine or is simply inactive. Abnormally high levels of the opiate peptides cause psychological symptoms including depression. 284 Integrative Medicine for Depression The test requires a first-morning urine sample. 

Normally, test results should be negative, meaning that casomorphin and gliadorphin are not present in the urine. If they are, casein and/or gluten should be removed from the diet. Supplementation with the enzyme DPP IV facilitates complete digestion of these neuroactive peptides. 

Vitamin D 

A deficiency of vitamin D may be linked to depression, an increased stress response, high blood pressure, high blood sugar levels, and a host of diseases including heart disease, cancer, and multiple sclerosis. Vitamin D is changed in the liver to 25-hydroxyvitamin D, the form found circulating in the bloodstream and typically used to evaluate an individual’s vitamin D status. 

Low levels of 25-hydroxyvitamin D indicate that a person is not getting adequate dietary vitamin D or sun exposure, or that he or she has a problem absorbing the vitamin. Low levels should be treated with vitamin D3 supplementation, and the 25- hydroxyvitamin D status should be monitored every three months until levels are within the target range. 

Zinc and Copper 


Low levels of zinc have been linked to depressive disorders, and the lower they are, the worse the depression. Research has shown that people with major depression have zinc levels that are twelve to sixteen percent lower than those who are not depressed. A meta-analysis of seventeen studies including 1,643 depressed and 804 healthy controls concluded that those with depression had lower serum zinc concentrations. 

Zinc deficiencies also set off a cascade of other biological actions that together impair cognitive function and disrupt mood regulation. Symptoms of zinc deficiency include hair loss, skin lesions, acne, diarrhea, and depression.White marks on the fingernails are also an early sign of zinc deficiency. 

Taking zinc supplements has been shown to improve depression and make antidepressants work better. Because the body cannot store zinc, daily intake is necessary. Measuring blood level is not always a reliable way to detect a zinc deficiency. A better way to assess zinc status is to take the zinc taste test. This test can identify even a minor deficiency. 


Low copper levels can lead to symptoms of depression, which is not surprising considering that copper is required to make the neurotransmitters norepinephrine and dopamine. Deficiency of a form of copper called ceruloplasmin can cause anemia, which itself can bring on symptoms of depression. 

On the other hand, abnormally high levels of copper can be linked to psychological symptoms such as aggression, paranoia, and anxiety. Copper levels are determined by blood tests or, in some cases, a urinary test. Levels that are abnormal may be treated with supplementation or dietary changes. 

Zinc and Copper

Zinc and copper are both strongly associated with depression, and as such are important components of an integrative testing and treatment approach. The story does not end there, however, for not only are the individual levels of these micronutrients important, but the ratio between them is hugely significant. 

This significance arises from the fact that these minerals compete with each other for access to cell receptors, and an excess of one ‘crowds’ the other out, preventing absorption and leading to – or worsening – a deficiency. Excess copper can deplete zinc, and zinc depletion can lead to increased copper. 

See-sawing levels negatively impact health and may ultimately enhance susceptibility to depression. The takeaway here is that zinc and copper levels should be assessed both individually and together as opposing factors that must be balanced in order to sustain good health. 

It’s Worth the Effort 

Very few psychiatrists routinely request these laboratory tests. That’s an oversight, for they don’t take much time, and cost relatively little compared with the expense of paying for the wrong medication and the emotional toll of remaining in the grips of a depressive disorder. 

Having found that running a few blood tests can guide doctors toward the right treatment, I believe we need to investigate the causes of depression with the same energy and passion that we devote to medical testing for other illnesses. If we identify all the factors that contribute to or cause depression, we are closer to finding the correct therapies that will produce complete recovery and permanent remission. 

As I’ve described in this chapter, testing not only helps us to detect nutrient deficiencies or metabolic imbalances, but it can also help us better predict which medications may be more beneficial for you.This can minimize some of the frustrating and often costly guesswork involved when prescribing medication and can prevent unwanted side effects. 

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