Depression is an increasingly common issue in the United States. The Centers for Disease Control in 2010 estimated that 11.1 percent of the American population suffers from significant depression — a whopping 35 million individuals — and this figure seems to be steadily rising. Prescribed mood modifiers are everywhere, starting as early as elementary school and continuing on into old age. How successful are these pharmacologic approaches? Not very. Optimistic estimates maintain that such interventions are reasonably successful in only one half of those treated. Less optimistic observers note that in those currently taking an SSRI (selective serotonin reuptake inhibitor) antidepressant drugs such as Prozac, despite a host of side effects, most do not attain relief. Nearly two-thirds of elderly patients treated for depression fail to achieve symptomatic remission and functional recovery with first-line pharmacotherapy; they obtain better results with, for instance, tai chi.¹ For major depressive disorder, a condition for which one would think that pharmacological treatments would win out over nonpharmacological therapy, it turns out that nonpharmacological therapy not only is just as effective, but also involves far fewer adverse events.^2,3

The causes of depression and mood disorders remain an area of controversy. Human beings are prepared to react to vastly varied environmental factors. Not surprisingly, many biological and psychological factors cut in more than one direction. Metabolic factors (inflammation, insulin resistance, and oxidative stress) are not necessarily one-direction in terms of causation, for example, with regard to emotional and physical stress and the resulting stress hormones (glucocorticoids). Sex hormones (testosterone, estrogen), likewise, both influence and are influenced by emotional and physical factors.

Is Inflammation the Central Issue?
The concept of inflammation in the last few years has been stretched to cover more and more forms of illness and dysfunction. One reason is that inflammation is actually a set of responses that occur naturally all the time, yet each of which can itself escape proper regulation. You get a sense of this from the article on inflammation available online from Wikipedia: “Inflammation is a protective response that involves immune cells, blood vessels, and molecular mediators. The purpose of inflammation is to eliminate the initial cause of cell injury, clear out necrotic cells and tissues damaged from the original insult and the inflammatory process, and to initiate tissue repair.” Inflammation thus involves both destruction and repair.

A number of researchers are looking into the issue of neuroinflammation outside of the traditional medical areas of concern, such as stroke. For instance, psychological stress has been demonstrated to increase neuroinflammation in animal models.⁴ Similarly, there is evidence to support the position that links chronic depression to chronic brain inflammation and acute depression to stress-triggered neuronal microdamage.⁵ Another line of argument is that the “metabolic syndrome and its individual components induce a proinflammatory state that damages blood vessels. This condition of chronic inflammation may damage the vasculature of the brain or be directly neurotoxic.”⁶

Countering Depression without Drugs
Inflammation and the metabolic syndrome are closely linked in physiology and biochemistry. Therefore, it should not come as a surprise that studies on obesity, diet and exercise habits often turn up implications for preventing and treating depression. For example, a large study of 15,093 people published in 2015 indicated that depression could be linked with nutrient deficits. The best results were found with two essentially Mediterranean-style diets. These diets overlapped in terms of foods such as omega-3 fatty acids, vegetables, fruits, legumes, nuts and moderate alcohol intake. Another finding was that there apparently is a threshold effect, meaning that a certain level of protective foods needed to be in the diet, but that benefits in terms of reduced risk of depression plateaued after this threshold was passed.⁷

It is difficult to find many nutrients that can be given as dietary supplements that cross the blood-brain barrier. Many of the nutrients that are of use are from berries. Pterostilbene, but not resveratrol, is a potent neuromodulator in aging and Alzheimer’s disease.⁸ “Blueberry, strawberry, blackberry, grape and plum juices or extracts have been successfully tested in cognitively impaired rodents. Published trials of the benefits of grape and blueberry juice in the treatment of small numbers of cognitively impaired persons have recently appeared.”⁹ Another potentially useful item in this regard is the Chinese herb known as blue dogbane, Apocynum venetum. This interesting item, virtually unknown outside of Asia, exerts proven anti-depressant effects, in part, via brain monoamine levels and the dopaminergic system. The latter, again, is influenced by pterostilbene, but not resveratrol.¹⁰ Of importance regarding the impact of Apocynum venetum on inflammation is its high content of the potent antioxidant / anti-inflammatory, isoquercitrin.¹¹

A complementary option to the foregoing nutrients is to reduce the impact of stress. Phosphatidylserine (PS) supports the brain’s physiological processing of stress and promotes neuronal communication by its effect on cell membrane fluidity. It is a natural phospholipid that is an essential component of cell membranes. PS promotes brain function by increasing neuronal membrane fluidity (cell-to-cell communication), resulting in improved cognition. Also, PS protects against stress by mitigating the actions of cortisol (catabolic stress hormone.) Human research routinely demonstrates these benefits and suggests the usefulness of a combination with DHA, e.g., “The results demonstrate that consumption of 100 mg/day of PS-DHA might be associated with improving or maintaining cognitive status in elderly subjects with memory complaints.”¹²

Finally, there is the issue of the relation between Alzheimer’s and sugar consumption. In old age, there tends to be an increasingly significant association between forms of cognitive impairment and depression. Some believe there’s a connection between sugar intake and Alzheimer’s disease. There are a number of theories as to why this might be. One argument is that increased consumption of simple carbohydrates leads to blood brain barrier degradation and subsequently to damage to the hippocampus.¹³ A related argument is that increased consumption of simple carbohydrates leads to elevations of specific advanced glycation end products (AGEs), especially the neurotoxic methyl-glyoxal derivatives (MG). High levels of AGEs also are correlated with reduced insulin sensitivity in older human adults. These factors promote chronic oxidant stress and inflammation in the brain.¹⁴

Endnotes:

1. Lavretsky H, Alstein LL, Olmstead RE, Ercoli LM, Riparetti-Brown M, Cyr NS, Irwin MR. Complementary use of tai chi chih augments escitalopram treatment of geriatric depression: a randomized controlled trial. Am J Geriatr Psychiatry. 2011 Oct;19(10):839–50.
2. Gartlehner G, Gaynes BN, Amick HR, Asher G, Morgan LC, Coker- Schwimmer E, Forneris C, Boland E, Lux LJ, Gaylord S, Bann C, Pierl CB, Lohr KN. Nonpharmacological Versus Pharmacological Treatments for Adult Patients With Major Depressive Disorder [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2015 Dec.
3. Gartlehner G, Gaynes BN, Amick HR, Asher GN, Morgan LC, Coker- Schwimmer E, Forneris C, Boland E, Lux LJ, Gaylord S, Bann C, Pierl CB, Lohr KN. Comparative Benefits and Harms of Antidepressants, Psychological, Complementary, and Exercise Treatments for Major Depression: An Evidence Report for a Clinical Practice Guideline From the American College of Physicians. Ann Intern Med. 2016 Feb 9. [Epub ahead of print]
4. Barnum CJ, Pace TW, Hu F, Neigh GN, Tansey MG. Psychological stress in adolescent and adult mice increases neuroinflammation and attenuates the response to LPS challenge. J Neuroinflammation. 2012 Jan 16;9:9.
5. Wager-Smith K, Markou A. Depression: a repair response to stress-induced neuronal microdamage that can grade into a chronic neuroinflammatory condition? Neurosci Biobehav Rev. 2011 Jan;35(3):742–64.
6. Cherniack EP. A berry thought-provoking idea: the potential role of plant polyphenols in the treatment of age-related cognitive disorders. Br J Nutr. 2012 Sep;108(5):794–800.
7. Sánchez-Villegas A, Henríquez-Sánchez P, Ruiz-Canela M, Lahortiga F, Molero P, Toledo E, Martínez-González MA. A longitudinal analysis of diet quality scores and the risk of incident depression in the SUN Project. BMC Med. 2015 Sep 17;13:197.
8. Chang J, Rimando A, Pallas M, Camins A, Porquet D, Reeves J, Shukitt- Hale B, Smith MA, Joseph JA, Casadesus G. Low-dose pterostilbene, but not resveratrol, is a potent neuromodulator in aging and Alzheimer’s disease. Neurobiol Aging. 2012 Sep;33(9):2062–71.
9. Cherniack EP. A berry thought-provoking idea: the potential role of plant polyphenols in the treatment of age-related cognitive disorders. Br J Nutr. 2012 Sep;108(5):794–800.
10. Zheng M, Fan Y, Shi D, Liu C. Antidepressant-like effect of flavonoids extracted from Apocynum venetum leaves on brain monoamine levels and dopaminergic system. J Ethnopharmacol. 2013 May 2;147(1):108–13.
11. Butterweck V, Nishibe S, Sasaki T, Uchida M. Antidepressant effects of apocynum venetum leaves in a forced swimming test. Biol Pharm Bull. 2001 Jul;24(7):848–51.
12. Vakhapova V, Cohen T, Richter Y, Herzog Y, Kam Y, Korczyn AD. Phosphatidylserine containing omega-3 Fatty acids may improve memory abilities in nondemented elderly individuals with memory complaints: results from an open-label extension study. Dement Geriatr Cogn Disord. 2014;38(1–2):39–45.
13. Hsu TM, Kanoski SE. Blood-brain barrier disruption: mechanistic links between Western diet consumption and dementia. Front Aging Neurosci. 2014 May 9;6:88.
14. Cai W, Uribarri J, Zhu L, Chen X, Swamy S, Zhao Z, Grosjean F, Simonaro C, Kuchel GA, Schnaider-Beeri M, Woodward M, Striker GE, Vlassara H. Oral glycotoxins are a modifiable cause of dementia and the metabolic syndrome in mice and humans. Proc Natl Acad Sci U S A. 2014 Apr 1;111(13):4940–5.

As a psychiatrist, I am clearly familiar with the psychodynamic issues underlying eating disorders, and I see psychotherapy as a vital part of treatment. At the same time, I would like to share my experience with observing and treating some of the biochemical underpinnings, hastening recovery and helping to maintain it as well.

Many years ago, a psychologist who specializes in eating disorders began to send me her clients because she had heard that antidepressant medications worked for these patients. I had by then shifted to a more holistic approach, so I told her that before I prescribed antidepressants, I wanted to try some more natural methods. I had discovered that in many cases of eating disorders, there is an underlying biochemical issue—a combination of food sensitivity, blood sugar imbalance and nutrient deficiency. She agreed, her patients cooperated, and we had some excellent, medication-free results. This encouraged me to continue on this natural path as I have to this day. Here are some of my discoveries, as well as subsequent research by others in this growing field.

Food Sensitivity
We crave the foods that we are sensitive or “allergic” too. Not a typical allergy with hives or stomach aches, these sensitivities are intolerances, often inherited, and show up in any number of ways—for example, depression, inability to lose weight, eating disorders, tinnitus, unexplained aches and pains—many, many others. The very foods we crave will create the most symptoms and are the most damaging. In fact, food cravings are similar to an addiction to alcohol. As you withdraw from the foods you're addicted to, you begin to have withdrawal symptoms and the cravings begin. And if you happen to be addicted to wheat or baked goods, you can never get enough of them, so you binge on them, despite your best intentions to the contrary. People addicted to grains may drink excessive amounts of grain-based liquor or beer and can become alcoholics. They're sensitive to and addicted to the alcohol, but it's the grain-base that is causing the problem. They can even feel “drunk” after eating cereal or baked goods. Not so different from your regular carb-binger, except the target is alcohol instead of refined carbs.

Nutrients

It's not just a matter of willpower. In order to break the addiction cycle, in addition to avoiding the undesirable foods, you have to supply the body with a good, supportive nutritional program of healthful food, vitamins, minerals, and amino acids. Then, the cravings will often simply go away! It's quite remarkable; with a nutrient rich diet, and good vitamin and mineral formula, you can stop the cycle. In fact, once the diet and nutrients are in place, the cravings and addictions will often just fall away. Remember that nutritional supplements are not a substitute for healthy food, but a supplement to restore missing ingredients and balance biochemistry.

Magnesium is often deficient, and taking it can be very helpful. It's great, too, for muscle tension, insomnia, and even, heart palpitations. The amino acid glutamine is also useful for reducing cravings. I've had former alcoholics (yes, former) say that the glutamine cut their cravings for good; they no longer were battling the desire to drink. They were done for good. Glutamine works similarly with bulimics and binge eaters.

Zinc: Some years ago, researcher Alex Schauss did a study on patients who were suffering from anorexia nervosa. By using a simple test called a zinc taste test, he found that they were zinc-deficient. He then gave them liquid zinc therapeutically, with very successful results. The test consists of the person taking some liquid zinc sulfate solution in their mouth, and if they describe it as having a bad or strong taste, they usually have sufficient levels of zinc. On the other hand, if they can't taste the solution or if it tastes just like water, then they may have a cellular zinc deficiency, even if their blood levels look adequate. It's a vicious cycle since zinc deficiency affects taste; so zinc-deficient anorexics don't taste their food, so are less motivated to eat it. Zinc supplementation has continued to be used in nutritionally oriented settings, including my own practice.

Serotonin: Bulimia and binge-eating is often treated with the SSRI antidepressants such as Prozac, Zoloft and Lexapro They raise brain levels of serotonin, a neurotransmitter or chemical messenger in the brain that causes a feeling of well-being and relaxation, and reduces hunger. Rather than using medication, my preference is to prescribe the materials that make serotonin, the amino acids L-tryptophan or it's relative, 5-HTP (5-hydroxytryptophane), and there is research to back it.

In her book, The Diet Cure, Julia Ross refers to a study where bulimics were deprived of tryptophan. In reaction, their serotonin levels dropped and they binged more violently, ingesting and purging an average of 900 calories more each day. In another study, adding extra tryptophan to the diet reduced bulimic binges and mood problems by raising serotonin levels. More recently, an Oxford researcher, Katherine Smith, reported that even years into recovery, bulimics can have a return of their cravings and mood problems after only a few hours of tryptophan depletion, concluding that, “Our findings support suggestions that chronic depletion of plasma tryptophan may be one of the mechanisms whereby persistent dieting can lead to the development of eating disorders in vulnerable individuals.”

The herb St. John's Wort provides another way to raise serotonin levels. I have discussed this along with dosages of tryptophan and other nutrients in my book, Natural Highs.

Thiamine: As we have seen, nutrient deficiencies can aggravate anorexia, and it should be treated with nutrient rich diets. For example, restricting your diet will make you deficient in such vitamins as vitamin B1 (thiamin). It's found in foods that people with eating disorders rarely eat—including beans, whole grains, seeds, meats and vegetables. Common signs of thiamine deficiency are loss of appetite, weight loss, constipation, anxiety, chest pain and even sleep disturbance along with depression and irritation. Sound familiar?

Blood Sugar Swings
One mechanism underlying the craving and eating (or drinking) cycle is blood sugar imbalance: low blood sugar sets off the craving. The brain experiences this dip as life-threatening starvation, followed by a frantic search for whatever will raise blood sugar. Just picture our ancestors in the jungle, short on food, and having to hunt for their next meal—or die. We, on the other hand, just go to the refrigerator. The quickest fixes here are sugary foods or other refined carbs such as bread or pastries. And we don't even burn any calories on our hunt.

Bottom Line: Treat Nutrient Deficiency with Nutrients
I will often order a blood test to see which amino acids are low. By replacing them the body (and brain) comes into balance. As a result the food cravings will often be greatly relieved or even come to a halt, as noted in the case of glutamine for acute cravings.

There are other natural treatments, as well, for cravings due to food sensitivities. Acupuncture and acupressure has been shown to help, especially some techniques such as NAET that can actually eliminate the food sensitivities themselves.

The point is, instead of simply taking an antidepressant, there are many other ways to approach what at first appears to be strictly a psychological problem. The combination of psychotherapy and a nutritional/biochemical approach is the most useful, and I have successfully treated many patients without resorting to medication at all. Not only does this approach work as well as medication but in my experience working with the body's chemistry, rather than introducing more chemicals in the form of medication, is often superior. It's faster, has none of the side effects, and has many side benefits. I developed Brain Recovery AM & PM formula to provide many of the nutrients mentioned here and more, to balance amino acids, serotonin, blood sugar, and mood.

For more information, see my books, Natural Highs, and 8 Weeks to Vibrant Health. Also sign up for my free e-newsletter, and get a free copy of my e-book, Reclaim Your Brain.

Dear Readers,

You've been programmed to believe that serotonin deficiency causes depression. If SSRI antidepressants actually cured people, we would not see escalating rates of suicide, agitation, anxiety, depression, bipolar disorder and PTSD.

The secret sadness that people carry is not always apparent to the rest of the world. For example, I went to lunch with a new friend who has a picture perfect life by most standards. She confided to me that she has tried to kill herself three times and suffers with chronic depression. More than 2 decades has passed and not one psychiatrist or physician has ever suggested magnesium to this lovely lady. Not one! Unbelievable considering the studies that suggest magnesium plays some role in depression, even with suicidal tendencies. The type of magnesium matters though.

Studies suggest that cardiac problems may occur in the fetus when mothers take SSRI drugs during the first trimester, yet one in four women trying to get pregnant are taking an antidepressant.

Antidepressants target several neurotransmitters, usually epinephrine, dopamine or serotonin. But there are about 100 different brain chemicals involved in making you feel "happy" so targeting just those three is silly. No wonder there were nearly 37,000 suicides in 2009, and about a million attempts according to the CDC. It's ideal to get information and/or track your progress if you have severe depression. Here's how:

Interleukin 10 or IL-10. A blood test will measure this cytokine. Reduced IL-10 is seen with depression, feelings of helplessness, insomnia and migraines. Lift your IL-10 with resveratrol, vitamin D and exercise.

C Reactive protein. You're more likely to be depressed when it's elevated. Vitamin E and C, probiotics and CoQ10 can lower this.

TNF alpha. This cytokine (measured in the blood) is high in depression, narcolepsy, bowel disease and psoriasis. Reduce TNF (tumor necrosis factor) with probiotics, magnesium, lipoid acid, curcumin, boswellia and essential fatty acids.

Thyroid hormone. Evaluate your Free T3. If it's low, it's a slam dunk for depression, fatigue and weight gain. I suggest you get this between 3.5 and 4.3 using thyroid medicine or supplements. Read my book, Thyroid Healthy.

Neopterin and biopterin. It's a urine test and these two compounds are by-products of chemical reactions involving tetrahydrobiopterin (BH4) which is required to make epinephrine, norepinephrine and dopamine. This ratio is important if you have depression, Parkinson's, Alzheimer's, depression or autism.

Healing depression takes time, and requires relaxation. Breathing deeply reduces cortisol, a stress hormone which makes you tired, overweight and sad! Balancing estrogen levels, raising progesterone, thyroid or testosterone can help. Deficiencies of magnesium, vitamin C, B12 or folate are often involved. Methylation difficulties, definitely involved! Your gut is key, yet so overlooked. Probiotics improve your microbiome and positively influence your ability to deal with stress and make neurotransmitters. The cause of depression differs for everyone. Please don't give up on life. You are loved and needed by someone. I love you! I study every day to help you. And finally, don't let anyone dismiss nutrients, that is honestly your best mood food.