OVERVIEW: Depression is one of the most frequent complaints seen in any medical office with up to 25% of al American adults exhibiting some symptoms.1 As with insomnia, those with major depression suffer a four fold increase in mortality in the next five years and major depression may account for up to 60% of all suicides2.
Although depression and schizophrenia, for example, may be seen in some families, the environmental factors that include 1) sun light, 2) diet, 3) family stressors now appear to be more important that genetic or family disposition.3
Therefore, if we are to focus on the limbic and hypothalamic systems as they impact depression, we then chose to evaluate the biologic amines involved in neurotransmission — norepinephrine, serotonin and, to a lesser extent, dopamine, acetylcholine and epinephrine. The role of sleep disturbances and Vitamin D (calciferol) is treated in a separate article.
Although there has been an evolution from the use of mono-amine oxidase inhibitors (MAO), to tricylic antidepressants like Elavil® — both affecting norepinephrine levels, present day antidepressants are predominantly selective serotonin reuptake inhibitors. Serotonin deficiency is now considered an integral part of the physiology of depression.4
Amino Acid Supplements
Good nutrition is the basis of treatment for every disease. Specific supplementation with these three amino acids may be somewhat effective in treating some forms of depression. They are L-tyrosine, D,L-phenylalanine and especially L-tryptophan and its derivative, 5-hdroxy-tryptophan (5-HTP).
L-Tyrosine: Precursor to the biogenic amine norepinephrine and may be a natural substitue for those who respond favorably to amphetamines. Dosage 50-100mg/kg before breakfast or 2-3 times daily if better tolerated.
D,L-Phenylalanine: Precursor to L-tyrosine. When the D,L form is used, some will convert to phyenylethlamine (PEA) which has amphetamine like and mood elevating like properties. Whether D,L-phenylalanine can be effective as an anti-depressant is determined by trial-and-error with the patient. Side effects are usually limited to those with severe blood pressure problems.
5-HTP My choice of treatment for depression, after treating for Vitamin D deficiency, is 5-HTP. Not only will to assists in normalizing the sleep pattern, but it will be useful during the day to treat both depression and carbohydrate craving. 200mg at night; 100mg twice daily during the day.
Vitamin and Mineral Therapy
Vitamin B6, is necessary to convert L-tryptophan to serotonin and L-tyrosine to norepinephrine. Vitamin B6 deficiency care noted in with certain diets, the oral contraceptives, and selective medication.
Folic acid deficiency has been identified in patients with severe depression.. Psychiatric symptoms of folate deficiency include depression, insomnia, anorexia, forgetfulness, hyperirritability, apathy, fatigue and anxiety.13
Vitamin B12 deficiency can also manifest as depression.15 In depressed patients with documented vitamin B12 deficiency, parenteral (intravenous) administration of the vitamin has resulted in dramatic improvement.16 Vitamin B12, 1 mg/day for two days (route of administration not specified), also produced rapid resolution of postpartum psychosis in eight women.17
Vitamin C, as the cofactor for tryptophan-5-hydroxylase, catalyzes the hydroxylation of tryptophan to serotonin.18 Vitamin C may therefore be valuable for patients with depression associated with low levels of serotonin. In one study, 40 chronic psychiatric inpatients received 1 g/day of ascorbic acid or placebo for three weeks, in double-blind fashion.19 In the vitamin C group, significant improvements were seen in depressive, manic and paranoid symptom complexes, as well as in overall functioning.
Magnesium deficiency can cause numerous psychological changes, including depression. The symptoms of magnesium deficiency are nonspecific and include poor attention, memory loss, fear, restlessness, insomnia, tics, cramps and dizziness.20 Plasma magnesium levels have been found to be significantly lower in depressed patients than in controls.21 These levels increased significantly after recovery. In a study of more than 200 patients with depression and/or chronic pain, 75 percent had white blood cell magnesium levels below normal.22 In many of these patients, intravenous magnesium administration led to rapid resolution of symptoms. Muscle pain responded most frequently, but depression also improved. A nutritional supplement that contains 200400 mg/day of magnesium may therefore improve mood in some patients with depression.
St. John’s wort: Having been unimpressed with the anti-depressant effect of St. John’s wort, it is listed here for completeness.
Ginkgo (Ginkgo biloba) extract, while clearly not a primary treatment of choice for most patients with major depression, should be considered an alternative for elderly patients with depression resistant to standard drug therapy. This is because depression is often an early sign of cognitive decline and cerebrovascular insufficiency in elderly patients. Frequently described as resistant depression, this form of depression is often unresponsive to standard antidepressant drugs or phytomedicines like St. John’s wort. One study showed a global reduction in regional cerebral blood flow in depressed patients older than 50 when compared with age-matched, healthy controls.31
In that study, 40 patients, ages 51 to 78, with a diagnosis of resistant depression (insufficient response to treatment with tricyclic antidepressants for at least three months), were randomized to receive either Ginkgo biloba extract or placebo for eight weeks.32 Patients in the ginkgo group received 80 mg of the extract three times daily. During the study, patients remained on their antidepressant drugs. In patients treated with ginkgo, there was a decline in the median Hamilton Depression Scale scores from 14 to 7 after four weeks. This score was further reduced by 4.5 at eight weeks. There was a one-point reduction in the placebo group after eight weeks. In addition to the significant improvement in symptoms of depression for the ginkgo group, there was also a noted improvement in overall cognitive function. No side effects were reported.
Many nutrition-oriented practitioners have found that the answer to depression is as simple as one’s diet. A diet low in sugar and refined carbohydrates (with small, frequent meals) can produce symptomatic relief in some depressed patients. Individuals most likely to respond to this dietary approach are those who develop symptoms in the late morning or late afternoon or after missing a meal. In these patients, ingestion of sugar provides transient relief, followed by an exacerbation of symptoms several hours later.
Primary Source of material: Donald Brown, N.D., teaches herbal medicine and therapeutic nutrition at Bastyr University, Bothell, Wash. Alan R. Gaby, M.D., is past president of the American Holistic Medical Association. Ronald Reichert, N.D., is an expert in European phytotherapy and has an active medical practice in Vancouver, B.C.
Excerpted with permission from Depression (Natural Product Research Consultants, 1997).
References: From The February 1999 Issue of Nutrition Science News
1. Risby ED, et al. Mood disorders. In: Stoudemire A, editor. Clinical psychiatry for medical students. 2nd ed. New York: J.B. Lippincott Co.; 1994. p 198.
2. El-Mallakh RS, et al. Clues to depression in primary practice. Postgrad Med 1996;100:85.
3. Freeman PS, et al. Psychopathology. In: Sierles FS, editor. Behavioral science for medical students. Baltimore: Williams and Wilkins; 1993. p 253.
4. Rush AJ, et al. Neurobiological basis for psychiatric disorders. In: Rosenberg RN, editor. Comprehensive neurology. New York: Raven Press; 1991. p 563.
5. Goldberg IK. L-tyrosine in depression. Lancet 1980;2:364.
6. Gelenberg AJ, et al. Tyrosine treatment of depression. Am J Psychiatry 1980;137:622-3.
7. Sabelli HC, et al. Clinical studies on the phenylethylamine hypothesis of affective disorder: urine and blood phenylacetic acid and phenylalanine dietary supplements. J Clin Psychiatry 1986;47:66-70.
8. Hawkins WW, Barsky J. An experiment on human vitamin B6 deprivation. Science 1948;108:284-6.
9. Azuma J, et al. Apparent deficiency of vitamin B6 in typical individuals who commonly serve as normal controls. Res Commun Chem Pathol Pharmacol 1976;14:343-8.
10. Stewart JW, et al. Low B6 levels in depressed outpatients. Biol Psychiatry 1984;19:613-6.
11. Russ CS, et al. Vitamin B6 status of depressed and obsessive-compulsive patients. Nutr Rep Int 1983;27:867-73.
12. Adams PW, et al. Effect of pyridoxine hydrochloride (vitamin B6) upon depression associated with oral contraceptives. Lancet 1973;1:897-904.
13. Howard JS III. Folate deficiency in psychiatric practice. Psychosomatics 1975;16:112-5.
14. Ghadirian AM, et al. Folic acid deficiency and depression. Psychosomatics 1980;21:926-9.
15. Hector M, Burton JR. What are the psychiatric manifestations of vitamin B12 deficiency? J Am Geriatr Soc 1988;36:1105-12.
16. Geagea K, Ananth J. Response of a psychiatric patient to vitamin B12 therapy. Dis Nerv Syst 1975;35:343-4.
17. Daynes G. Cyanocobalamin in postpartum psychosis. S Afr Med J 1975;49:1373.
18. Cooper JR. The role of ascorbic acid in the oxidation of tryptophan to 5-hydroxytryptophan. Ann NY Acad Sci 1961;92:208-11.
19. Milner G. Ascorbic acid in chronic psychiatric patients: a controlled trial. Br J Psychiatry 1963;109:294-9.
20. Freyre AV, Flichman JC. Spasmophilia caused by magnesium deficit. Psychosomatics 1970;11:500-2.
21. Frizel D, et al. Plasma magnesium and calcium in depression. Br J Psychiatry 1969;115:1375-7.
22. Shealy CN, et al. Magnesium deficiency in depression and chronic pain. Magnesium Trace Elem 1990;9:333.
23. Facchinetti F, et al. Oral magnesium successfully relieves premenstrual mood changes. Obstet Gynecol 1991;78:177-81.
24. Morgan KJ, et al. Magnesium and calcium dietary intakes of the U.S. population. J Am Coll Nutr 1985;4:195-206.
25. Singh A, et al. Magnesium, zinc, and copper status of US Navy SEAL trainees. Am J Clin Nutr 1989;49:695-700.
26. Holzl J, et al. Investigations about antidepressive and mood changing effects of Hypericum perforatum. Planta Med 1989;55:643.
27. Muller WE, Rossol R. Effects of Hypericum extract on the expression of serotonin receptors. J Geriatr Psychiatry Neurol 1994;7(Suppl 1):S63-4.
28. Holzl J. Constituents and mechanism of action of St. John’s wort. Zeitschrift Phytother 1993;14:255-64.
29. Ernst E. St. John’s wort, an antidepressant? A systemic, criteria-based review. Phytomedicine 1995;2:67-71.
30. Monograph, Hyperici herba (St. John’s wort), Bundesanzeiger 1984 Dec 5.
31. Lesser IM, et al. Reduction in cerebral blood flow in older depressed patients. Arch Gen Psychiatry 1994;51:677-86.
32. Schubert H, Halama P. Depressive episode primarily unresponsive to therapy in elderly patients: efficacy of Ginkgo biloba extract (EGb 761) in combination with antidepressants. Geriatr Forsch 1993;3:45-53.