There is a tendency today to use the word “depression” to describe the inevitable periods of sadness that each of us experience from time to time. Indeed, for many, during these periods, it is not always easy to discern where normal sorrow ends and clinical depression begins. Yet, anyone who has ever experienced a major depression knows – at least after the depression has lifted – that what they feel is more than just persistent sadness.
Clinical depression is an illness characterized by a cluster of feelings, thoughts, and behaviors that are strikingly different from a person’s normal range of feelings and functioning. Caused by a complex interaction of biological, social and psychological factors, a major depressive disorder can make a person exquisitely sensitive to life circumstances, the least of which can throw him into total black despair.
During a major depression, a person becomes enveloped by feelings of sadness, emptiness and worthlessness. Like an impenetrable curtain descending, these feelings distort every thought and experience, rendering life meaningless and hopeless. Feelings of being deeply, continually deprived, insignificant, inadequate and guilt-ridden build on feelings of sadness. At the same time, a depressed person may feel chronically irritated, occasionally erupting in frustration and anger.
While a major depression may be triggered by some life circumstance or event, the mood reaction seems greatly exaggerated. In all likelihood, depression has less to do with events that occur than with a individual’s inherent vulnerability to the condition.
In rare cases a person may experience a major depression as a single episode. However, in most instances, clinical depression tends to recur periodically, reactively or cyclically.
Milder depressive states lasting two years or more are called dysthymic disorders. It is likely that these low-grade, intermittent or chronic depressive states form in some people the temperamental basis from which major depressions arise. For those with dysthymic disorder, certain life circumstances – the end of a relationship, the loss of a job, going away to college, for example – might provoke a deeper depression.
For some people, there is a seasonal aspect to their depression. Seasonal affective disorder (SAD) is a form of depression that is more prevalent in northern parts of the country where the climatic extremes are greater. Typically affecting people in the fall or winter, seasonal affective disorder is characterized by fatigue, carbohydrate craving, overeating and oversleeping. While the exact cause of the disorder is not certain, it may be related to the way in which the light-responsive pineal gland in the brain functions.
* An acute and persistent sense of despair, sadness and hopelessness that seems to have little correlation to life circumstances.
* A lack of interest or pleasure in most activities
* Feelings of sluggishness, fatigue, or agitation
* Certainty that everything is worthless and hopeless
* Preoccupation with thoughts of suicide or death
* A change in appetite and/or weight
* Difficulties in sleeping or a tendency to oversleep
* Diminished ability to concentrate and make decisions
* Dramatic changes in working and social patterns
* Social Withdrawal
NOTE: If you are in the throes of depression, you may well believe that you are beyond help. Yet depression can be effectively treated and managed. If your state of gloom persists more two weeks, you find that you can’t get out of bed; you are increasingly isolated from family and friends and you have lost any sense of enjoyment or interest in your usual activities, call your physician. Also, if you find yourself ruminating about death and the meaningless of life, and you are considering suicide, seek help immediately.
Approximately seventeen million Americans suffer from true clinical depression each year, and over twenty-eight million Americans take antidepressant drugs or anxiety medications.
One of the most powerful techniques for producing the necessary biochemical changes in the brains of depressed individuals is to teach them to be more optimistic.
Low levels of serotonin contribute to depression.
It is important to rule out the simple organic factors that are known to contribute to depression, i.e., nutrient deficiency or excess, drugs (prescription, illicit, alcohol, caffeine, nicotine, etc.), hypoglycemia, consumption, hormonal derangement, allergy, environmental factors, and microbial factors.
Cognitive therapy has been shown to be as effective as antidepressant drugs in treating moderate depression.
Depression is often a first or early manifestation of thyroid disease.
Increased cortisol levels are common in depression. Use a 24-hour salivary cortisol test.
Elimination of sugar and caffeine has been shown to produce significant benefits in clinical trials.
Increased participation in exercise, sports, and physical activities is strongly associated with decreased symptoms of anxiety, depression, and malaise. Thirty minutes of exercise daily may be the most powerful natural antidepressant available.
A deficiency of any single nutrient can alter brain function and lead to depression, anxiety, and other mental disorders.
Hypoglycemia can cause depression. Therefore, hypoglycemia must be avoided to provide a generous supply of blood to the brain.
An insufficiency of omega-3 oils in the diet has been linked to depression.
Stomach hydrochloric deficiency is common in endogenous depression
Numerous double-blind studies have shown 5-hydroxytryptophan (5-HTP) to be as effective as antidepressant drugs, but it is better tolerated and is associated with fewer and much milder side effects.
Extracts of St. John’s wort standardized for hypericin (usually 0.3 percent) are the most thoroughly researched natural antidepressants.
Over twenty-five double-blind studies have shown St. John’s wort to produce as good or better results compared to standard antidepressant drugs, but with significantly fewer side effects.
a. Food allergy/sensitivity.
b. Psychological stress.
c. Thiamine deficiency.
d. Endocrine hypo-function. (Pituitary, Thyroid, Adrenal)
e. Carbohydrate sensitivity resulting in dysinsulinism.
f. Rule out these organic and physiological causes of Depression:
Heavy metals – Use Hair Analysis and 24-hour Urine to
Preexisting physical condition:
Tranquilizers and sedatives
Stress/low adrenal function
a. Sip 2 to 3 oz. (1 mouthful) of distilled or filtered water every 30 minutes, while awake, daily (no well water or water containing fluoride or chlorine); drink more if you are perspiring.
b. Eliminate all gluten containing grains and dairy products.
c. Eliminate all refined carbohydrates, alcohol and caffeine containing foods such as coffee, tea, cola and chocolate.
d. Eliminate hydrogenated fats and oils. Eat only fish oils, coconut oil and extra virgin olive oil as your only source of dietary oils.
e. Increase raw vegetables and protein like sea vegetables.
1. BIO-MULTI PLUS IRON FREE – 2 tablets, 2 times daily after meals.
2. BIO-C PLUS 1000 ? 1 tablet, 3 times daily after meals.
3. M S M POWDER – 1/2 teaspoonful 2 to 4 times daily depending on the severity of symptoms. NOTE: Try to take MSM with your Vitamin C.
4. IODIZYME-HP – 1 to 4 tablets daily for Iodine
5. BIO-D MULSION FORTE DROPS – 8 drops once daily for Vitamin D
6. SUNFLAX CAPS — 2 capsules, twice daily after meals for Essential Fatty Acids
Specific Nutrients: When symptoms or condition begins to subside, gradually, as needed, wean yourself from the Specific Nutrients & stay on the Primary Nutrients. If any symptoms re-occur resume taking Specific Nutrients.
B12 2000 LOZENGES – 1 tablet, once daily after a meal.
RB-ZYME – 3 tablets, 3 times daily after meals.
LI-ZYME FORTE – 3 tablets, 3 times daily after meals.
ST. JOHN?S PLUS – 1 capsule, 3 times daily after meals.
**INOSITOL – 5 tablets once daily after breakfast. Increase dosage by 5 tablets every 4 to 5 days until you either reach about 15 Grams daily or you begin to experience the beneficial effects.
HYDROZYME – 2 tablets, during meals if you are having a problem with digestion.
DHEA ? 1 tablet, twice daily if over 40 years of age or salivary testing reveals a need for supplemental DHEA.
GINKO BILOBA ? 2 tablets, 3 times daily after meals. If depression is severe, you may use in combination with ST. JOHN?S PLUS.
MELATONIN 3 mg — 1 tablet at bedtime for sleep.
5-HYDROXYTRYPTOPHAN (5-HT) – 100 mg to 200 mg 3 times daily after meals.
PHOSHPATIDYLSERINE — 3 capsules daily for one month, then 1 to 2 capsules daily thereafter for maintenance.
Natural Remedies for Depression
**INOSITOL: In most studies individuals begin to see positive results within 4 to 6 weeks. Many people actually begin to see results in a matter of days. It is worth continuing the effective dose you find yourself for at least a couple of months if you do not get a response that quickly.
L-Tryptophan: Nature’s Answer to Prozac?
by James South, M.A.
The ‘serotonin deficiency syndrome? is one of the most common and widespread disorders of human psychobiology in the modern world. Prozac? allegedly increases the amount of serotonin in the synaptic gap that slightly separates nerve cells from each other. (For more on the ?allegedly? see the excellent book, Talking Back to Prozac, by psychiatrist Peter Breggin).
Greater amounts of serotonin in the synaptic gap increases communication between serotonin-using neurons, allowing the brain’s multiple and critically important serotonin neural circuits to function more reliably, powerfully and effectively.
Tryptophan and Serotonin Action
Studies with humans and animals conducted over the past 30 years show that serotonin nerve circuits promote feelings of well being, calm, personal security, relaxation, confidence and concentration.
Serotonin neural circuits also help counterbalance the tendency of brain dopamine and noradrenaline circuits to encourage over-arousal, fear, anger, tension, aggression, violence, obsessive-compulsive actions, over-eating (especially carbohydrates), anxiety and sleep disturbances.
A broad array of emotional and behavioral problems, including depression, PMS, anxiety, alcoholism, insomnia, violence, aggression, suicide and compulsive gambling, has been designated the serotonin deficiency syndrome. The serotonin deficiency syndrome is caused by a chronic deficit of serotonin in the nerves that use it as their neurotransmitter. This deficit in turn derives from various problems relating to the nutritional biochemistry of tryptophan.
Tryptophan: The Essential Amino Acid
Tryptophan is one of the eight essential amino acids found in the human diet. Essential amino acids must be obtained preformed from food or supplements. Non-essential aminos (there are 14) can be made from the essential aminos, or other non-essential amino acids.
In any normal diet, tryptophan is the least plentiful of all 22 amino acids. A typical diet provides only 1 to 1.5 grams of tryptophan per day. To compound the problem, there is much competition in the body for this scarce amino acid. Tryptophan is used to make various proteins, and in people with low to moderate intakes of vitamin B3 (niacin/niacinamide), tryptophan may be used by the liver to make B3 at the expensive ratio of 60 mg tryptophan to 1 to 2 mg B3.
In people who are even marginally vitamin B6 deficient, tryptophan may be rapidly degraded into mildly toxic metabolites such as hydroxykynurenine, xanthurenic acid and hydroxyanthranilic acid.
The brain typically receives less than one percent of ingested tryptophan. However, getting even this meager share of tryptophan (the only normal dietary raw material for serotonin manufacture) is a difficult task for the brain, due to the blood brain barrier (BBB).
The BBB serves as a protection to prevent toxins (and even excessive levels of nutrients which might temporarily overwhelm and dysregulate brain function) from entering the brain. Thus, the BBB makes it hard even for brain essential nutrients to enter the brain. Serotonin by itself cannot penetrate the BBB, but its precursor, tryptophan, can. Nutrients must be ferried through the BBB by transport molecules, like passengers on a bus. Unfortunately for the serotonin-using nerves, tryptophan must share its ‘transport bus? with five other amino acids: tyrosine, phenylalanine, valine, leucine and isoleucine. Thus, tryptophan is typically out-numbered about 8 to 1 in the competition to secure its transport through the BBB into the brain.
Tryptophan’s Effects on Carbohydrates and Obesity
Eating a high protein diet to provide more tryptophan only worsens the problem by increasing the intake of the five competing aminos even more. Ironically, the only dietary strategy that increases brain tryptophan supply is to eat a high carbohydrate diet.
When large amounts of carbohydrates are eaten, the body secretes large amounts of the hormone insulin to lower the ensuing high blood sugar. The insulin also clears from the blood most of the five amino acids that compete with tryptophan for a ride to the brain. Tryptophan then has the ?bus? all to itself, allowing more tryptophan to reach the brain.
This strategy is instinctively known and practiced by many people who consume large amounts of carbohydrates such as bread, cakes, pies, ice cream, chips, pizza and candy?especially when they are feeling depressed, stressed or anxious.
The increased brain serotonin produced by this practice lowers arousal and anxiety, promoting a (temporary) sense of well-being and security. However, this strategy comes at a price. The same insulin that enhances brain serotonin also enhances the conversion of the fats, carbohydrates and amino acids cleared from the blood into stored body fat!
Hence the carbohydrate addiction/ obesity/serotonin connection.
Taking tryptophan as a supplement is the most natural way to defeat the brain’s serotonin production problems. Unlike ingesting a high protein diet, isolated supplemental tryptophan intake will not increase blood levels of its five amino competitors. Since the normal dietary intake is only 1 to 1.5 grams per day, even a modest amount of tryptophan supplementation (500 mg to 3,000 mg) will have a significant effect in boosting blood and brain tryptophan levels.
Under normal conditions, the brain enzyme tryptophan hydroxylase (TH) is only 50 percent saturated. This means the serotonin production machinery is 50 percent idle. Thus, an increase in raw material (tryptophan) will tend to automatically increase brain serotonin production.
TH converts tryptophan to 5-hydroxytryptophan (5-HTP). A vitamin B6-dependant carboxylase enzyme then converts 5-HTP to serotonin, and more serotonin more effectively activates the calming, mood-elevating, impulse and appetite-controlling serotonin neural circuits.
Tryptophan?When Less is More!
In the case of tryptophan supplements, more is not always better. In the many human clinical studies using tryptophan to treat depression, published since the 1970s, studies using moderate tryptophan doses (1 to 3 gm daily) have frequently shown better results than high doses (6 to 9 grams daily). This is due to a liver enzyme called tryptophan pyrrolase (TP). TP is a key enzyme in the normal pathways for liver-tryptophan breakdown.
TP is known to be activated by at least two factors. The first is the stress hormone cortisol. Cortisol, produced by the adrenal glands, is the ‘state of siege? stress hormone. It is released in response to unremitting chronic stress, which we can neither fight against nor flee from. Cortisol is known to be frequently elevated in the very conditions, such as depression, insomnia and obesity, for which tryptophan/serotonin might be helpful.
Thus, taking tryptophan while under elevated cortisol-stress conditions might supply little extra to the brain, because of cortisol’s activation of TP.
The other factor known to elevate liver TP activity is, ironically, increased intake of tryptophan. Since the TP-using kynurenine pathway is the major tryptophan degradation pathway, significantly elevated tryptophan intake automatically induces higher TP activity. Again, if liver TP activity seriously increases, more supplemental tryptophan will not necessarily translate into increased brain serotonin.
Thus, the lowest tryptophan dose that successfully alleviates serotonin-deficiency symptoms is the most efficacious (i.e., more is not always better).
Fortunately, clinical and anecdotal evidence shows that even 500 mg to 1,500 mg of supplemental tryptophan, taken at bedtime on a regular basis, is frequently sufficient to ease serotonin-deficiency problems.
This low dose will usually not seriously elevate tryptophan-destroying TP activity. Niacinamide (vitamin B3) is known to inhibit liver TP; it is also the vitamin that activates the enzyme that converts tryptophan to 5-HTP. Thus, taking 100 mg B3 several times daily with meals will also serve to enhance the effectiveness of low-moderate tryptophan doses.
Taking 25 mg to 50 mg of vitamin B6 once or twice daily with meals will also augment tryptophan-serotonin conversion, since B6 activates the decarboxylase enzyme that converts 5-HTP to serotonin.
Tryptophan: The Natural Antidepressant
The published research of S.N. Young and H.M. van Praag (two of the world’s chief experts on tryptophan-serotonin metabolism and psychobiology), suggest that tryptophan will likely be of most benefit to people suffering from depression of the type that Young refers to as ?anxious-agitated.? Young notes that increased brain production of serotonin through tryptophan supplementation does not automatically increase serotonin nerve activity.
Young’s research indicates that at low levels of psychobiologic arousal, there will be adequate neuronal serotonin to support the correlative low-level serotonin nerve activity, even when nerve serotonin levels are low. At higher levels of arousal, however, the more rapid turnover of serotonin in the synaptic gap will require higher levels of serotonin production to adequately maintain the greater activity of serotonin circuits. Young refers to those suffering depression of a more vegetative, passive, quiescent variety to as the ?apathetic inhibited? type.
Given that serotonin neural circuits frequently serve to counterbalance the arousing activating dopamine/noradrenaline circuits (the neural circuits activated by cocaine and amphetamine, and to a lesser extent, coffee), Young’s observations make perfect sense.
Anxious, agitated depression occurs when a person’s dopamine/noradrenaline activating arousal circuits (Yang) are functioning strongly, without the calming, relaxing, mellowing serotonin circuits (Yin) functioning strongly as a complementary counterbalance.
Tryptophan provides the anxious agitated depressive with that needed ?Yin? counterbalance, thereby restoring a sense of well being and behavioral self-control.
Van Praag’s research has shown that for many people suffering depression, combining the amino-acid tyrosine with tryptophan works much better than taking tryptophan alone. These would be Young’s ?apathetic inhibited? types, where both the serotonin tranquility/well- being circuits and the ?get up and go? (vigorous action) dopamine/noradrenaline circuits are underactive.
Tyrosine is the precursor for both dopamine and noradrenaline. The enzyme that converts tyrosine to its next step on the dopamine/noradrenaline pathway is tyrosine hydroxylase. Tyrosine hydroxylase is normally at least 25 percent unsaturated (i.e., 25 percent ?idle?), so that providing supplemental tyrosine (100 to 500 mg with meals) increases brain dopamine/noradrenaline production and nerve activity.
The increased dopamine/noradrenaline neural activity then requires greater complementary serotonin neural activity, which is provided by the tryptophan supplementation.
Tryptophan’s General Uses
Research has shown that tryptophan/ serotonin is effective for more than depression. Various forms of defective impulse control and obsessive compulsive disorders are also strongly affected by serotonin nerve activity. Suicidal behavior, compulsive gambling, irrationally dangerous thrill seeking behavior and pyromania (compulsive fire-starting), have been shown to be correlated with low serotonin neural activity, combined with excessive dopaminergic/noradrenergic activity.
Chronic alcoholism may also have a serotonin component. Research with animals and humans has shown that alcohol initially increases serotonin nerve activity; yet chronic alcohol use impairs tryptophan entry into the brain. Thus, chronic alcoholism may involve a vicious spiral of a brief alcohol-induced increase of serotonin neural activity, with consequent sense of well-being, combined with an ever-worsening baseline state of serotonin nerve activity due to alcohol’s impairment of brain tryptophan transport.
Tryptophan and Sleep
In recent years, melatonin has gained the reputation as the natural answer to insomnia. Yet the fact that melatonin is made in the pineal gland from serotonin is frequently overlooked.
Thus, supplemental tryptophan may induce one’s pineal gland to naturally increase its melatonin production. Also, important sleep-regulating nerve circuits in the brainstem (the raphe nuclei) use serotonin as their neurotransmitter, so it is unreasonable to expect melatonin alone to provide optimal insomnia relief.
Low dose melatonin (0.5 mg to 1 mg) plus tryptophan (500 mg to 1, 500 mg) may prove more effective for many people with serious insomnia.
Tryptophan’s Role in Dementia
Recent research has shown that the depression that frequently accompanies and even predates the movement disorders of Parkinson’s disease is primarily due to the hypofunction of serotonin nerves. Consequently, tryptophan may be a useful adjunct to L-Dopa/deprenyl treatment of Parkinson’s.
In the latter stages of Alzheimer’s disease, heightened irritability and unprovoked aggression frequently accompany the mental decline. Recent research has shown partial destruction of key serotonergic neural circuits to be involved. Supplemental tryptophan may optimize the activity of remaining serotonergic.
Tryptophan and 5-HTP
Supplemental 5-Hydroxytryptophan (5-HTP), the intermediary between tryptophan and serotonin, is also available as a natural remedy for the serotonin deficiency syndrome, yet tryptophan offers a major advantage over 5-HTP for many people.
There are nerves that line the intestinal tract that use serotonin as their neurotransmitter. These nerves contain the carboxylase enzyme that converts
5-HTP to serotonin, but not the hydroxylase enzyme that converts tryptophan to 5-HTP. Thus, when 5-HTP is swallowed, large amounts of 5-HTP may be picked up by these intestinal serotonergic neurons and quickly converted to serotonin, leading to hyperactivity of these nerves.
This in turn may lead to nausea, vomiting, cramping, constipation and/or diarrhea. Indeed, the research published on 5-HTP since the 1970s has consistently shown various forms of intestinal discomfort to be the main side effect of 5-HTP use. Because these intestinal neurons cannot convert tryptophan to 5-HTP, tryptophan does not cause intestinal distress.
Tryptophan: Its Synergistic Combinations
A practical program to relieve the many forms of serotonin deficiency syndrome will ideally combine moderate amounts of tryptophan (500 mg to 1,500 mg), 5-HTP at 33 mg to 100 mg (if well tolerated) and melatonin (0.5 mg to 1 mg) taken at bedtime.
Melatonin actually promotes in-creased brain serotonin through its ability to reduce cortisol levels. Reduced cortisol levels will lessen the activity of liver pyrrolase, the enzyme that degrades tryptophan.
GH3/KH3, Dilantin (phenytoin) and magnesium may also lower cortisol activity. Standardized extracts of St. John’s Wort (0.3 percent hypercin) may also synergize with tryptophan to optimize serotonin levels. Research summarized in Hypericum and Depression by H. Bloomfield and colleagues suggests three complementary mechanisms of action whereby St. John’s Wort may increase serotonin.
St. John’s Wort seems to be a weak serotonin reuptake inhibitor (and thus a more natural and safer equivalent of Prozac), a weak MAO inhibitor (MAO enzymes break down neuronal serotonin), and a cortisol inhibitor. The standard St. John’s Wort dosage is 300 mg three times daily?however, less may be needed when combined with tryptophan.
Poeldinger W et al ?Functional dimensional approach to depression? Psychopathology 1991; 24:53-81.
Sandyk R ?L-Tryptophan in neuro psychiatric disorders, a review? Int J Neuroscience 1992 67:124-144.
Young SN, Teff KL ?Tryptophan availability, 5HTP synthesis and 5HT function? Prog Neuro Psychopharmacol and Biol Psychiat 1989; 13:373-79.
Maurizi CP, ?The therapeutic potential for tryptophan and melatonin? Med Hypoth 1990; 31:233-42.
Van Praag HM et al ?Therapeutic indications for serotonin potentiating compounds, a hypothesis? Biol Psychiat 1987; 22:205-12.
Van Praag HM ?In search of the action of anti-depressants: 5HTP, tyrosine mixtures in depression? Neuropharmacol 1983; 22:433-40.
Robertson J, Monte T. Natural Prozac, San Francisco, Harper 1997.