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Folic Acid

Vitamins & Minerals for Depression: Folic Acid is Important; Others Might Help

Since vitamin-mineral supplements are very inexpensive and most have no significant side-effects, if they can help depression, they should be taken. A wide variety of vitamins one mineral have been found to be helpful in treating depression, but the total number of studies on each and the numbers of patients involved are quite small. The most promising and best researched are thiamine and folic acid or folate. Thiamine, vitamin B-1, is reported to have been shown to be of benefit in four older double-blind trials and folate of value in five more recent, higher quality double-blind studies of depression and schizophrenia.  Multivitamins also helped in four more recent double-blind studies, but all four had folate in the multivitamin tablet, so maybe it was just the folate.  Also, I personally do not like multivitamins since vitamin A has been shown to significantly increase the risk of death.

Folic Acid (or folate), officially vitamin B-9, besides helping depression, also helps with heart disease and several nervous system diseases. Folic acid is the only vitamin whose blood levels have been found to correlate with cognitive functioning in the elderly. According to prospective Canadian research, individuals suffering strokes or dementia have also been found to have low blood levels. Three difference double-blind studies from England and the U.S. have found that patients given folate or a folic acid derivative in addition to their SSRI or lithium anti-depressant medication do significantly better. Two recent Harvard studies adds further support to the findings. An Italian study found that a folic acid derivative did as well as a low dose of a standard anti-depressant. Red blood cell levels of folate, but not serum levels, have been found decreased in mania.

Two double-blind studies with zinc and just single double-blind studies have documented decreases in depression or stress from selenium (Biol Psychiatry ’91;29:1092; Biol Psychiatry 39:121-8 ’96), vitamin D (USA Weekend 1/3/99), and chromium. Several studies report lower levels of vitamin E, thiamine, riboflavin, and B-6 in depressed patients, but this doesn’t prove the low levels were at all involved in causing the depression.

In summation, the research with vitamin-mineral therapy for depression is still very limited. It seems unwise to rely on vitamin therapy alone to treat depression.  However, in view of the general health benefits and the existing research, it seems reasonable to recommend folate 800-1600 micrograms per day, plus one tablet of a multivitamin with minerals per day as part of any treatment for depression along with selenium 200 micrograms per day and thiamine 10 mg per day.

I recommend buying inexpensive generic brands from major chain stores or pharmacies rather than the more expensive brand names.  Men over 40 should avoid calcium supplements or multivitamins with high levels of calcium due to large increases in prostate cancer and Parkinson’s disease in men caused by calcium supplements or high calcium intake. Adults over 50 may try to find multivitamins with lower levels of iron, although the harm of excess iron on cardiac health is still debated. Excessive vitamin A has been found to cause fractures and appears to have little health benefit for Americans as a supplement.

B-12 has been found decreased in depression.  An extra 500 mcg tablet of B12 on alternating days is a good idea, especially for older individuals for reasons other that depression.  Taking one or two a day might be a good idea for depression.  The total cost of these vitamins should be around $5 per month and will have health benefits for other parts of the body besides the brain. Vitamins E and C are okay, but have not been proven to have any beneficial effect for depression.

Some herbal medicine websites promote magnesium for depression, but I have found no evidence to support this even though taking one or two tablets of magnesium 250 mg/day in addition to the 100 mg found in most multivitamins is a good health habit in general. Actually, most studies find slightly elevated serum and red blood cell magnesium levels in depressed individuals.  Despite comments that low iron could contribute to depression, a large study found no relationship between blood tests measure the bodies hemoglobin and iron stores and measures for depression. Unfortunately, herbal medicine websites are full of useless and harmful information on herbal remedies for depression. (I cover St. John’s wort elsewhere).

The Other Vitamin & Mineral Studies:

Multivitamin-Mineral Decreases Stress in DB: In a DB PC study, 300 high stress patients in South Africa treated for 30 days on the supplement had significantly less stress measured by four psychometric tests. A double-blind, placebo-controlled, double-centre study of the effects of an oral multivitamin-mineral combination on stress. Schlebusch L, Bosch BA, Polglase G, Kleinschmidt I, Pillay BJ, Cassimjee MH. S Afr Med J 2000 Dec;90(12):1216-23

Multivitamin Helps Mood & Cognition in DB: Large DB PC. J Aff Disorder ’01;64:107-19

Multivitamin with Minerals Helps Normals in DB: In a DB PC study, 80 healthy males were treated Berocca brand for 4 weeks. Better concentration and less anxiety and less fatigue was reported with the supplement. The effects of an oral multivitamin combination with calcium, magnesium, and zinc on psychological well-being in healthy young male volunteers: a double-blind placebo-controlled trial. Carroll D, Ring C, Suter M, Willemsen G. Psychopharmacology (Berl) 2000 Jun;150(2):220-5

Multivitamin Megadose Said Helpful in DB: 129 normal young adults DB 9 vitamins and 10 times recommended dose. After 1 year, vitamin group felt more "agreeable." Says low initial thiamine associated with poor mood. Not an impressive study design. Vitamin supplementation for 1 year improves mood. Benton D, Haller J, Fordy J. Neuropsychobiology 1995;32(2):98-105

Thiamine B-1: Moderate thiamine deficiency was found in 40% of hospitalized elderly with higher with depression, Alzheimer's disease, cardiac failure and falls. Belgium, Pepersack, Gerontology 3/99;45:96

Thiamine Supplement Helped Elderly Irish: 80 healthy elderly Irish women were treated in a DB PC study with 10 mg/day of thiamine for 6 week. Increased appetite, weight, well-being, and decreased fatigue occurred in the thiamine group. Smidt, UC Davis, J Gerontol ’91;46:M16;

Thiamine Claimed to Help Post-ECT Confusion: Three cases of elderly patients getting ECT for depression. Using thiamine to reduce post-ECT confusion. Linton CR, Reynolds MT, Warner NJ. Int J Geriatr Psychiatry 2002 Feb;17(2):189-92

Vitamin B1, B2, B6 DB with Nortriptyline Helpful Trend: In a very small DB PC study of 14 elderly treated with nortriptyline for depression, seven received 10 mg/day of each vitamin and showed trends toward better cognitive functioning and decreased depression as well as higher nortriptyline levels and B-12 levels. Harvard. Brief communication. Vitamin B1, B2, and B6 augmentation of tricyclic antidepressant treatment in geriatric depression with cognitive dysfunction. Bell IR, Edman JS, Morrow FD, Marby DW, Perrone G, Kayne HL, Greenwald M, Cole JO. J Am Coll Nutr 1992 Apr;11(2):159-63. Harvard.

Says Four DB Thiamine Studies Show Benefit, Iron Decreased in Women: In four double-blind studies an improvement in thiamine status was associated with improved mood. Iron deficiency anemia is common, particularly in women, and is associated with apathy, depression and rapid fatigue when exercising. The effects of nutrients on mood. Benton D, Donohoe RT. Public Health Nutr 1999 Sep;2(3A):403-9

Riboflavin B-2 Deficiency Common in Depressed Women: 17% of 52 acute psych admits had B-2 deficiency as measured by insufficient flavin adenine dinucleotide activity, a B-2 dependant enzyme in the folate-dependant methylation pathway. Only women were found deficient and none were deficient in other vitamins except one for folate. Thyroxine levels were lower with low B-2. Bell, McLean Hosp, Acta Scand Psych, ’92;85:360; IR Bell also did DB PC with B-1, B-2, and B-6 at 10 mg each to augment tricyclics with trend favoring supplementation in 14 geriatrics with depression. J am Coll Nutr ’92;11:159

B-2, B-6, B-12 deficiency Found, Not Folate or B-1: 20 geriatric and 16 non-alcoholic young psych patients assays and 28 deficient in at least one of the three but none to folate or B-1. Deficient tended to be more depressed. Psychotic depression lower for B-12. IR Bell, J Am Geriatric Soc ’91;39:252

B-6 Helps PMS in DB: DB PC crossover 63 pts rx B-6 50mg/d found supplement helped depression, irritability and fatigue 3 months each. Doll, Oxford, JR Coll Gen Prac ’89;39:364

B-6 Helped Elderly Memory: DB PC 76 men 70-79yo 3 month 10mg/d. No impact on mood. Mental performance improved. Vitamin B-6 supplementation in elderly men: effects on mood, memory, performance and mental effort. Deijen JB, van der Beek EJ, Orlebeke JF, van den Berg H.

B-6: No Help for Cognition or Mood: In a research review of all studies to date, no trials of vitamin B6 involving people with cognitive impairment or dementia were found. The two trials (Bryan 2002; Deijen 1992) used a double-blind, randomized, placebo-controlled design and involved 109 healthy older people. One trial restricted enrolment to women and the other to men. Vitamin B6 supplementation and healthy older women: Bryan 2002 enrolled 211 healthy women from various age groups into a 5-week study. The trial was of multifactorial design with folic acid, vitamin B12, vitamin B6 and placebo in its four arms. Twelve healthy women aged 65 to 92 years received 75 mg vitamin B6 orally per day and were compared with 21 healthy women who were allocated to placebo. No statistically significant benefits from vitamin B6 on mood or cognition were observed. Vitamin B6 supplementation and healthy older men: Deijen 1992 recruited 76 healthy men aged 70 to 79 years. They were divided into 38 matched pairs, one member of each pair randomly allocated to 20 mg of vitamin B6 (pyridoxine hydrochloride) per day for 12 weeks the other to placebo. No statistically significant differences between treatment and placebo were found in their effects on cognition or mood. The effect of vitamin B6 on cognition. Malouf R, Grimley Evans J. Oxford, UK. Cochrane Database Syst Rev. 2003;(4):CD004393

B-6 and Schizophrenia with Depression: A very poor quality small open study of 9 schizophrenic patients with depression given 150 mg. B6 for 4 weeks. Two had a 25% decrease in HAM-D. Shiloh, Israel, Harefuah 2001 May;140(5):369-73, 456.

B-6 Pyridoxine Helped Women on BCP in DB: DB PC crossover for depressed women who had no previous history of depression. Adams, Lancet pg 897, ‘73

B-12 Didn't Help Seasonal Affective Disorder: DB PC 27 pts 2wk washout and 2 wk rx 1.5mg TID B-12 vs. placebo = no diff in depression. Oren, NIMHY, J Aff Disorder 94;32:197

B-12 Linked to Elderly Depression, Not Folate: 3,884 Dutch elderly screened for depression. The 278 depressed and 416 controls blood tested. B-12 deficiency may play causal role in depression, but folate did not appear to do so. Vitamin B12, folate, and homocysteine in depression: the Rotterdam Study. Tiemeier H, van Tuijl HR, Hofman A, Meijer J, Kiliaan AJ, Breteler MM. Am J Psychiatry 2002 Dec;159(12):2099-10

B-12 Levels Linked to Depression Improvement on Meds, Not Folate Levels: In 115 young and middle aged outpatients with DSM-III-R major depressive disorder, measurements at baseline and serum of vitamin B12 level again on six-month follow-up found that higher levels at baseline and higher levels at follow-up were each related to decreases in depression. Most patients were on anti-depressant medication and most were in counseling. There was no relationship between B-12 levels initially and the level of depression. No supplements were used. Folate levels were only weakly related to response. Kuopio Univ. Finland. High vitamin B12 level and good treatment outcome may be associated in major depressive disorder. Jukka Hintikka. BMC Psychiatry 12/2003, 3:17 

B-12: Studies Mentioned As Poor Evidence of Help: Lindenbaum J, Healton EB, Savage DG, et al. Neuropsychiatric disorders caused by cobalamin deficiency in the absence of anemia or macrocytosis. N Engl J Med 1988;318:1720–8. Mentioned on herbal medicine site as proving that taking B-12 alone is effective in combating depression. Still older study mentioned = Ellis FR, Nasser S. A pilot study of vitamin B12 in the treatment of tiredness. Br J Nutr 1973;30:277–83. on 1/10/03 (Don't trust herbal sites!)

B-12 Lower in Elderly Depressed: Study 700 women over 65 in community. 14% mild 17% severe depression. Of depressed, 17% mild and 27% severe B-12 deficient. Found double rate severe depression in those with low B-12. Folate deficiency unrelated to depression in study. Penninx, Natl Inst Aging. Am J Psychiatry 2000;157:715

B-12: Anemia, Macrocytosis No Help in Predicting Deficiencies: Anemia and macrocytosis should not be used to predict folate or B12 deficiencies, or refractoriness to antidepressants. Measurement of folate and B12 should be considered when evaluating treatment refractoriness. 12% of 213 depressed with B12 deficiency and 19% with folate deficiency. Therefore, get vitamin blood levels in refractory. Mischoulou, MGH, J Psychosom Res 2000 Sep;49(3):183-7 

Vitamin D: Seasonal Affective Disorder Helped: In a very small 15-patient randomized study, the eight patients given 100,000 I.U. of vitamin D supplementation showed a significant decrease in depression by 1 month follow-up but those giving light therapy did not. Vitamin D status improved in both groups (74% vitamin D group, p < 0.005 and 36% phototherapy group, p < 0.01). Improvement in 25-OH D was significantly associated with improvement in depression scale scores (p=0.05). Baltimore. Vitamin D vs. broad spectrum phototherapy in the treatment of seasonal affective disorder. Gloth FM 3rd, Alam W, Hollis B. J Nutr Health Aging. 1999;3(1):5-7

Vitamin D: Might Help Winter Depression : In a poorly done Australian DB PC study of 44 healthy adult lasting only 5 days (way too short), those receiving vitamin D 400 IU or 800 IU vs. placebo had an increase in positive mood and some decrease in negative affect. Vitamin D3 enhances mood in healthy subjects during winter. Lansdowne AT, Provost SC. Psychopharmacology (Berl). 1998 Feb;135(4):319-23

Vitamin D: Depressed Mood Not Helped in Normal Women: A 1 year DB PC study found POMS scores for anxiety and depression highest in fall and lowest in spring and summer. Vitamin D at 400 IU/day for one year was of no benefit in reducing anxiety and depression in 250 normal females ages 43-72. Tufts University, Boston, Seasonal mood changes in 250 normal women. Harris S, Dawson-Hughes B, Psychiatr Res ’93;49:77. Ed: Since 400 IUs is often inadequate at treating osteoporosis, 800 IUs per day would have been a better test. Of course, vitamin D might help individuals with high levels of anxiety and depression more than those with average levels.

Vitamin D: Depressed Women Have Lower Bone Density: In a study of 24 depressed women and 24 controls, the bone density in the women with past or current depression was was an average of 11% lower at the four different areas of bone measured. In addition, women with past or current depression had higher urinary cortisol excretion (71 vs. 51 micrograms per day, P=0.006), lower serum osteocalcin concentration (P=0.04), and lower urinary excretion of deoxypyridinoline (P=0.02). Bone mineral density in women with depression. Michelson D, Stratakis C, Hill L, Reynolds J, Galliven E, Chrousos G, Gold P. N Engl J Med. 1996 Oct 17;335(16):1176-81

Vitamin D Tanning Spa Effect?: Steven R Feldman of Wake Forest published in J Amer Acad Derm about a 6 week, 14 person study using tanning beds twice a week. One of the beds had a UV filter. Those using the bed giving out UV light tested more content and relaxed and 11 of 12 subjects preferred the UV bed without knowing of the difference. 7/13/04. Ed: UV light is the type of light that makes vitamin D.

Vitamin E Decreased in Depression: Major depression is accompanied by significantly lower serum vitamin E concentrations, suggesting lower antioxidant defenses against lipid peroxidation. The results could, in part, explain previous findings, which suggest increased lipid peroxidation in major depression. J Affect Disord 2000 Jun;58(3):241-6 @

Vitamin E Levels Not Related to Elderly Depression:3884 elderly screened for depression then 262 tested and over 400 controls. Vitamin E and depressive symptoms are not related. The Rotterdam Study. Tiemeier H, Hofman A, Kiliaan AJ, Meijer J, Breteler MM. J Affect Disord 2002 Oct;72(1):79-83

Tryptophan No Help Demented Depression: 27 elderly Rx 3g/d DB PC without benefit in crossover 1 month each study. DF Smith, Acta Psychiat Scand ’84;70:470

DL-phenylalanine Might Help: 40 depr pts Rx DB imip 150-200mg/d vs DL-phenylalanine 150-200mg/d. No diff. Author urges cautious interpretation. Beckmann, Germany, Arch Psychiatr Nervenkr '79;227:49-58

No Association Dietary Amino Acids and Depression: Finnish study of 27111 smokers 50-69yo 5-8 yr f/u. no consistent association between dietary intake of amino acids and low mood. Association of dietary amino acids with low mood. Hakkarainen R, Partonen T, Haukka J, Virtamo J, Albanes D, Lonnqvist J. Depress Anxiety. 2003;18(2):89-94


Iron Unrelated to Depression: 365 healthy women given MMPI. The frequency of elevated MMPI Depression scores was unrelated to the frequency of low hemoglobin, transferrin saturation, or ferritin. The results do not support the hypothesis that low iron status contributes to symptoms of depression in women. Grand Forks, Iron status and depression in premenopausal women: an MMPI study. Minnesota Multiphasic Personality Inventory. Hunt JR, Penland JG. Behav Med 1999 Summer;25(2):62-8.

Iron Stores When Low Linked to Increased Depression in Small Study: In a study of 192 female medical students (67 depressed, 35%), measurement of hemoglobin level, serum ferritin, erythrocyte sedimentation rate, C-reactive protein, folic acid, and vitamin B12 found that the mean ferritin level in students with depression was significantly lower than the healthy ones (P<0.001). By changing the status from normal ferritin level to low ferritin level, odds of depression was increased by 1.92 (P<0.05). The relationship between depression and serum ferritin level. Vahdat Shariatpanaahi M, et al. Free Islamic University, Tehran, Iran. European Journal of Clinical Nutrition, 25 October 2006.

Lead Not Related to Depression in Retired Smelters: 340 smelters tested and compared to serial blood lead testing. POMS psychological adjustment was not related to lead exposure. The factor structure of the Profile of Mood States (POMS) and its relationship to occupational lead exposure. Lindgren KN, Masten VL, Tiburzi MJ, Ford DP, Bleecker ML. J Occup Environ Med 1999 Jan;41(1):3-1

Magnesium Helps PMS in DB: In a DB PC 2 month study, researchers found 200 g/d of Mg (as MgO) decreased bloating, and weight gain but apparently had no benefit for moods symptoms. Walker, UK, J Women Health 11/98;7:1157;

Magnesium Higher in Depression: Most research shows serum Mg and RBC Mg is actually higher in moderate and severe depression and tends to return to normal with improvement. Evolution of blood magnesium, sodium and potassium in depressed patients followed for three months. Widmer J, Bovier P, Karege F, Raffin Y, Hilleret H, Gaillard JM, Tissot R. Neuropsychobiology 1992;26(4):173-9. One study did find CNS Ca/Mg ratio higher in more severe depression.

Magnesium & Depression: Magnesium is promoted for depression on some herbal websites. Unipolar depressed patients exhibit significantly lower serum magnesium levels than the appropriate controls (depression 19.1+/-2.2 mg/l; control 21.0 mg/l). There is no correlation between serum magnesium levels and the severity of depression. A significant positive correlation between serum magnesium/copper ratio and the severity of depression indicates a clear relationship between alterations of the homeostasis of these two ions in human depression. Krakow study on 19 unipolars and 16 normals. Serum trace elements in animal models and human depression: Part III. Magnesium. Relationship with copper. Zieba A, Kata R, Dudek D, Schlegel-Zawadzka M, Nowak G. Hum Psychopharmacol 2000 Dec;15(8):631-635. Evidence that Magnesium affects the nervous system is presented along with a recommendation for controlled research. Magnesium and affective disorders. Murck H. Nutr Neurosci 2002 Dec;5(6):375-89

Magnesium and B6 in Strange Russian Study: 20 endogenous depressed and 31 schiz. Apparently an open trial. moderate or marked reduction of extrapyramidal disorders (according to ESRS) was observed in 74% of patients treated by cerebrolysin and in 72% treated by magnesium and B6; somato-vegetative adverse effects reduced (by SARS) in 86% and in 84% respectively. Both drugs showed equally high efficacy against hyperkinetic and cardiovascular side effects (symptoms relief was in 59-62% and 65-69%, respectively). Cerebrolysin is more preferable in cases of side vegetative events, dysomnia and dysuria; magne B6 was more effective in correction of akineto-hypertonic and hyperkinetic-hypertonic syndromes as well as in cholinolytic side effects. Cerebrolysin and magnesium-B6 in the treatment of side effects of psychotropic drugs Panteleeva GP, Bondar' VV, Krasnikova NI, Raiushkin VA. Zh Nevrol Psikhiatr Im S S Korsakova 1999;99(1):37-41

Magnesium & B6 Might Help PMS Moods: Small study of 44 women with mild PMS took Mg 200mg/d, B6 50mg/d, both or placebo one month each. There was no difference on global but on anxiety-related premenstrual symptoms (nervous tension, mood swings, irritability, or anxiety), the combo better p=.04. Authors measured urinary Mg and said one month of supplementation was not enough to make up for the deficits found. A synergistic effect of a daily supplement for 1 month of 200 mg magnesium plus 50 mg vitamin B6 for the relief of anxiety-related premenstrual symptoms: a randomized, double-blind, crossover study. U Reading, UK. De Souza MC, Walker AF, Robinson PA, Bolland K. J Womens Health Gend Based Med 2000 Mar;9(2):131-9

Magnesium: Depression Model in Rats Helped by Adding Magnesium to Imipramine:  Poleszak E, et al. Medical University School, Lublin, Poland. Pharmacol Biochem Behav. 2005 Jul;81(3):524-9. 

Selenium No Impact on Mood: Three small, published studies have suggested an effect of selenium supplementation or deprivation on mood in healthy volunteers. In a much larger 6-month DB PC study of 501 UK adults ages 60-74 randomized to 100, 200 or 300 mug selenium/d as high-selenium yeast or placebo yeast, selenium increased blood levels, but had no affect on total mood or mood-subscale scores or on quality of life scores. Impact of Selenium on Mood and Quality of Life: A Randomized, Controlled Trial. Rayman M, et al. University of Surrey, United Kingdom. Biol Psychiatry. 2005 Sep 19.

Selenium Reportedly Found Low in Five Studies of Depressed Mood: Suggestions that oxidative injury plays a role in normal aging, schizophrenia, Parkinson's and Alzheimer's disease, the possible role of selenium is considered. Selenium intake, mood and other aspects of psychological functioning. Benton D. U Wales Swansea, Nutr Neurosci 2002 Dec;5(6):363-74; One a very small study of 11 patient with 120 day diets. Biol Psychiatry 1/96;39:121

Selenium: Better Mood with Supplementary Selenium in DB: 50 healthy adults in DB crossover study.  More depression, fatigue, and anxiety with lower selenium and improved on 5 weeks of supplemental selenium at 100 microg/d with less anxiety, depression, and more energy. Benton & Cook, Psychopharm 1990;102:549-50 also in Benton, Biol Psychiatry 29:1092. 1990;

Selenium Might Help: In a preliminary trial of healthy young men, consumption of a high-selenium diet (226.5 mcg selenium per day) was associated with improved mood (i.e., decreased confusion, depression, anxiety, and uncertainty), compared to consumption of a low-selenium diet (62.6 mcg selenium per day). Finley JW, Penland JG. Adequacy or deprivation of dietary selenium in healthy men: Clinical and psychological findings. J Trace Elem Exp Med 1998;11:11–27.

Zinc Reported to Help Depression in Very Small DB: In a 20-patient, 12-week Polish DB PC study of unipolar depression, half were given 25 mg/day of zinc in addition to their SSRI or tricyclic antidepressants. Data was analyzed on only 6 zinc and 8 placebo patients. At weeks 6 and 12, but not week 2, the zinc patients had significantly lower BDI and HAM-D depression scores. Krakow. Effect of zinc supplementation on antidepressant therapy in unipolar depression: a preliminary placebo-controlled study. Nowak G, Siwek M, Dudek D, Zieba A, Pilc A. Pol J Pharmacol. 2003 Nov-Dec;55(6):1143-7. Ed: This is far too small a study to jump to any conclusions. The authors note multiple studies showing depressed patients tend to be lower in zinc and animal models of depression being helped by zinc as an adjunct. Several Polish studies report zinc beneficial for rat swim tests, an research equivalent for human depression. Brain Res Bull. 2003 Jul 15;61(2):159-64.

Zinc Low in Anorexics and Depression and Anxiety Lessened in DB: In a DB PC study of teen anorexics, zinc intake was found one-half that of controls and zinc excretion one-third that of controls. Those randomized to 50 mg/day zinc had a decrease in the level of depression and anxiety as assessed by the Zung Depression Scale (p less than 0.05) and the State-Trait Anxiety Inventory (p less than 0.05). Stanford. Zinc deficiency in anorexia nervosa. Katz RL, Keen CL, Litt IF, Hurley LS, Kellams-Harrison KM, Glader LJ. J Adolesc Health Care. 1987 Sep;8(5):400-6

Zinc Levels Found Low: In a study measuring blood zinc levels in 48 depressed patients and 32 controls, zinc levels were found to be low in major depression but not in minor depression. There was no relationship between zinc and anorexia or weight loss. Case Western. Hypozincemia in depression. Maes M, D'Haese PC, Scharpe S, D'Hondt P, Cosyns P, De Broe ME. J Affect Disord. 1994 Jun;31(2):135-40; In a Belgium study of 48 depressed patients, the results suggest that lower serum Zn in depression is in part explained by lowered serum Alb and by another depression-related mechanism. It is suggested that lower serum Zn in depression may be secondary to sequestration of metallothionein in the liver, which may be related to increased production of interleukin-6. J Affect Disord. 1999 Dec;56(2-3):189-94