Serotonin's effects on multiple body systems

One Dangerous Deficiency Links IBS, Migraines, and More Health News By VRP Staff When you think of serotonin deficiency, the first consequence that might spring to mind is depression. And if so, you’d be right. But there’s more to this neurotransmitter than meets the eye—a lot more. Migraines, irritable bowel syndrome, fibromyalgia, obesity, even asthma… believe it or not, all of these serious conditions can be traced back to depleted serotonin levels. And the effects on your body can be as damaging as they are diverse. Serotonin is one of your brain’s most crucial messengers. It’s released by your neurons to send signals to other neurons, after which it’s returned to its original parent neuron to be reused. But if your levels are low, serotonin’s time on your synapse is cut short. It’s recaptured before it can finish its job—at a very high cost to your health, mentally and physically. In addition to depression, low levels of serotonin–and its precursor tryptophan–have been linked to binge eating, carbohydrate cravings, and weight gain.1 Studies show that obese and overweight diabetic patients have levels that are well below normal–and in clinical trials, increased brain serotonin led to both reduced caloric intake and resulting weight loss.2–4 But it’s not just your waistline that benefits from this critical neurotransmitter. Studies have shown that increasing serotonin levels can fight insomnia by improving sleep continuity.5 Research also shows that increased serotonin relieves migraines as effectively as standard drug therapy and aids in relief of chronic tension headaches.6–7 This same ability has made it a unique target in the treatment of fibromyalgia, with serotonin deficiency implicated for lower pain thresholds and higher clinical measures of perceived pain in patients.8–10 In an even more surprising connection, serotonin has also been identified as a major player in gut motility.11–12 Special serotonin–releasing cells can be found throughout your digestive system, responsible for stimulating peristaltic motion and pushing waste through your digestive tract.13 Even the development and severity of asthma has been linked to depression, anxiety, and low–serotonin related disorders—revealing yet another function under this neurotransmitter’s powerful influence.14 Proper levels of serotonin are essential for your health—and one way to ensure higher levels of this neurotransmitter is by boosting your intake of tryptophan, an essential amino acid found in high–protein foods that is responsible for serotonin synthesis in your brain. Research has shown that supplementing with tryptophan (and its metabolite 5–hydroxytryptophan, or 5–HTP) can replenish serotonin naturally and effectively—easing depression, anxiety, migraines, insomnia, and fibromyalgia symptoms in several clinical studies.15–17 References: 1. Gendall KA, Joyce PR. Meal–induced changes in tryptophan:LNAA ratio: effects on craving and binge eating. Eat Behav. 2000 Sep;1(1):53–62. 2. Breum L, Rasmussen MH, Hilsted J, Fernstrom JD. Twenty–four–hour plasma tryptophan concentrations and ratios are below normal in obese subjects and are not normalized by substantial weight reduction. Am J Clin Nutr. 2003 May;77(5):1112–1118. 3. Ceci F, Cangiano C, Cairella M, et al. The effects of oral 5–hydroxytryptophan administration on feeding behavior in obese adult female subjects. J Neural Transm 1989;76(2):109–117. 4. Cangiano C, Ceci F, Cascino A, et al. Eating behavior and adherence to dietary prescriptions in obese adult subjects treated with 5–hydroxytryptophan. Am J Clin Nutr 1992 Nov;56(5):863–867. 5. Riemann D, Vorderholzer U. Treatment of depression and sleep disorders. Significance of serotonin and L–tryptophan in pathophysiology and therapy. Fortschr Med. 1998 Nov;116(32):40–42. 6. Titus F, Dávalos A, Alom J, Codina A. 5–Hydroxytryptophan versus methysergide in the prophylaxis of migraine. Randomized clinical trial. Eur Neurol. 1986;25(5):327–329. 7. Ribeiro CA. L–5–Hydroxytryptophan in the prophylaxis of chronic tension–type headache: a double–blind, randomized, placebo–controlled study. For the Portuguese Head Society. Headache. 2000 Jun;40(6):451–456. 8. Birdsall TC. 5–Hydroxytryptophan: a clinically–effective serotonin precursor. Altern Med Rev. 1998 Aug;3(4):271–280. 9. Hrycaj P, Stratz T, Muller W. Platelet 3Himipramine uptake receptor density and serum serotonin levels in patients with fibromyalgia/fibrositis syndrome. J Rheumatol. 1993;20:1986–1988. [letter] 10. Russell IJ, Michalek JE, Vipraio GA, et al. Platelet 3H–imipramine uptake receptor density and serum serotonin levels in patients with fibromyalgia/fibrositis syndrome. J Rheumatol 1992;19:104–109. 11. Fayyaz M, Lackner JM. Serotonin receptor modulators in the treatment of irritable bowel syndrome. Ther Clin Risk Manag. 2008 Feb;4(1):41–48. 12. Gershon MD. The enteric nervous system: a second brain. Hosp Pract (Minneap). 1999 Jul 15;34(7):31–32,35–38,41–42. 13. Grider JR. Desensitization of the peristaltic reflex induced by mucosal stimulation with the selective 5–HT4 agonist tegaserod. Am J Physiol Gastrointest Liver Physiol. 2006 Feb;290(2):G319–G327. 14. Goodwin RD, Sourander A, Duarte CS, et al. Do mental health problems in childhood predict chronic physical conditions among males in early adulthood? Evidence from a community–based prospective study. Psychol Med. 2008 May 28:1–11. 15. Poldinger W, Calanchini B, Schwarz W. A functional approach to depression: serotonin deficiency as a target syndrome in a comparison of 5–hydroxytryptophan and fluvoxamine. Psychopathology. 1991;24:53–81. 16. Kahn RS, Westenberg HG. L–5–hydroxytryptophan in the treatment of anxiety disorders. J Affect Disord. 1985 Mar–Apr;8(2):197–200. 17. Puttini PS, Caruso I. Primary fibromyalgia and 5–hydroxy–L–tryptophan: a 90 day open study. J Int Med Res. 1992;20:182–189.

Calcium Imbalance

Proper Name: Calcium Common Name: Calcium Evidence of Efficacy: statement to the effect of Calcium deficiency or imbalance plays a role in the symptoms of mood disorders. Observational and experimental studies have shown an association between calcium and aggression1,2, anxiety3,4,5,6,7 and ADHD8,9, bipolar disorder10,11,12,13,14,15,16,17, depression18,19,20,21,22,23 and premenstrual syndrome24,25,26,27,28. References: 1. Walsh, William J., analytical chemist, Argonne National Laboratory; Sci News 124:122-2, 1983. 2. Schmidt K, Wier WR, Asch M. Clinical ecology treatment approach for juvenile offenders. J Behav Ecology: Bioscocial 2(1), 1981. 3. Carlson RJ. Longitudinal observations of two cases of organic anxiety syndrome. Psychsomatics 27(7):529-31, 1986. 4. Lawlor BA. Hypocalcemia, hypoparathyroidism, and organic anxiety syndrome. J Clin Psychiatry. 1988 Aug;49(8):317-8. 5. Crammer JL. Calcium metabolism and mental disorder. Psychol Med 7(4):557-60, 1977. 6. Houssain M. Neurological and psychiatric manifestations in idiopathic hypoparathyroidism: Response to treatment. J Neurol Neurosurg Psychiatry 33:153-6, 1970. 7. Joborn C etal. Psychiatric symptomatology in patients with primary hyperparathyroidism. Ups J Med Sci 91(1):77-87, 1986. 8. Kozielec T, Starobrat-Hermelin B, Kotkowiak L. Deficiency of certain trace elements in children with hyperactivity. Psychiatr Pol. 1994 May-Jun;28(3):345-53. 9. Walker S III. Drugging the American child: We’re too cavalier about hyperactivity. J Learn Disabil 8:354, 1975. 10. Bowden CL, Huang LG, Javors MA, Johnson JM, Seleshi E, McIntyre K, Contreras S, Maas JW. 11. Calcium function in affective disorders and healthy controls. Biol Psychiatry. 1988 Feb 15;23(4):367-76. 12. Groat RD, Mackenzie TB. The appearance of mania following intravenous calcium replacement. J Nerv Ment Dis 168:562-3, 1980. 13. Dubovsky SL, Christiano J, Daniell LC, Franks RD, Murphy J, Adler L, Baker N, Harris RA. Increased platelet intracellular calcium concentration in patients with bipolar affective disorders. Arch Gen Psychiatry. 1989 Jul;46(7):632-8. 14. Dubovsky SL, Murphy J, Thomas M, Rademacher J. Abnormal intracellular calcium ion concentration in platelets and lymphocytes of bipolar patients. Am J Psychiatry. 1992 Jan;149(1):118-20. 15. Dubovsky SL, Murphy J, Christiano J, Lee C. The calcium second messenger system in bipolar disorders: data supporting new research directions. J Neuropsychiatry Clin Neurosci. 1992 Winter;4(1):3-14. 16. Carman JS, Wyatt RJ. Calcium: pacesetting the periodic psychoses. Am J Psychiatry. 1979 Aug;136(8):1035-9. 17. Carman JS, Wyatt RJ. Calcium: bivalent cation in the bivalent psychoses. Biol Psychiatry. 1979 Apr;14(2):295-336. 18. Depression and hypercalcemia. Am J Med. 1996 Jul;101(1):111-7. 19. Joborn C etal. Psychiatric symptomatology in patients with primary hyperparathyroidism. Ups J Med Sci 91(1):77-87, 1986. 20. Alarcon RD, Franceschini JA. Hyperparathyroidism and paranoid psychosis. Br J Psychiatry. 1984 Nov;145:477-86. 21. Webb WL Jr, Gehi M. Electrolyte and fluid imbalance: neuropsychiatric manifestations. Psychosomatics. 1981 Mar;22(3):199-203. 22. Linder J, Brismar K, Beck-Friis J, Saaf J, Wetterberg L.Calcium and magnesium concentrations in affective disorder: difference between plasma and serum in relation to symptoms. Acta Psychiatr Scand. 1989 Dec;80(6):527-37. 23. Levine J, Stein D, Rapoport A, Kurtzman L. High serum and cerebrospinal fluid Ca/Mg ratio in recently hospitalized acutely depressed patients. Neuropsychobiology. 1999;39(2):63-70. 24. Thys-Jacobs S. Micronutrients and the premenstrual syndrome: the case for calcium. J Am Coll Nutr. 2000 Apr;19(2):220-7. 25. Goei GS, Abraham GE. Effect of a nutritional supplement, optivite, on symptoms of premenstrual tension. J Reprod Med. 1983 Aug;28(8):527-31. 26. Abraham GE. Nutritional factors in the etiology of the premenstrual tension syndromes. J Reprod Med. 1983 Jul;28(7):446-64. 27. Alvir JM, Thys-Jacobs S. Premenstrual and menstrual symptom clusters and response to calcium treatment. Psychopharmacol Bull. 1991;27(2):145-8. 28. Thys-Jacobs S, Ceccarelli S, Bierman A, Weisman H, Cohen MA, Alvir J. Calcium supplementation in premenstrual syndrome: a randomized crossover trial. J Gen Intern Med. 1989 May-Jun;4(3):183-9.

Potassium Imbalance

Proper Name: Potassium Common Name: Potassium Evidence of Efficacy: statement to the effect of Potassium deficiency or imbalance plays a role in the symptoms of mood disorders1. Observational and experimental studies have shown an association between potassium and aggression2,3,4, anxiety5 , bipolar disorder6,7,8,9, and depression10,11. References: 1. Webb WL, Gehi M. Electrolyte and fluid imbalance: Neuropsychiatric manifestations. Psychosomatics 22(3):199-203, 1981 2. William J. Walsh, analytical chemist, Argonne National Laboratory – reported in Sci News 124:122-5, 1983 3. Schmidt K, Wier WR, Asch M. Clinical ecology treatment approach for juvenile offenders. J Behav Ecology: Biosocial 2(1), 1981 4. Von Hilsheimer G, Philpott W, Buckley W, Klotz SC. Correcting the incorrigible. A report on 229 “incorrigible” adolescents. Am Lab 107:22-49, 1977 5. McCleane GJ, Watters CH. Pre-operative anxiety and serum potassium. Anaesthesia 45(7):583-5, 1990 6. Klemfuss H. Dietary potassium effects on lithium concentration and toxicity in humans. Biol Psychiatry 37:42-7, 1995 7. Jefferson JW. Potassium supplementation in lithium patients: a timely intervention or premature speculation? J Clin Psychiatry 53:10, 1992 8. Bkaskara Rao Tripuraneni, fellow in child psychiatry, Harbo-UCLA Medical Center, Torrance, California – reported in Clin Psychiatry News 18(10):3, October, 1990 and presented to the 143rd Annual Mtg of the Am Psychiatric Assoc, May 12-17, 1990, Abstracts NR 100 and NR 210 9. Cater RE. The use of sodium and potassium to reduce toxicity and toxic side effects from lithium. Med Hypotheses 20(4):359-83, 1986 10. Webb WL, Gehi M. Electrolyte and fluid imbalance: Neuropsychiatric manifestations. Psychosomatics 22(3):199-203, 1981 11. Cox JR et al. Changes in sodium, potassium and fluid spaces in depression and dementia. Gerontology Clin 13:232-45, 1971 Aggressive Behavior

Selenium Imbalance

Proper Name: Selenium Common Name: Selenium Evidence of Efficacy: statement to the effect of Selenium deficiency or imbalance plays a role in the symptoms of mood disorders1. Observational and experimental studies have shown an association between selenium and anxiety1, depression2,3, and schizophrenia4,5,6,7,8,9,10. References: 1. Benton D, Cook R. The impact of selenium supplementation on mood. Biol Psychiatry 29(11):1092-8, 1991. 2. Hawkes WC, Hornbostel L. Effects of dietary selenium on mood in healthy men living in a metabolic research unit. Biol Psychiatry 39:121-8, 1996. 3. Benton D, Cook R. The impact of selenium supplementation on mood. Biol Psychiatry 29(11):1092-8, 1991. 4. Brown JS Jr. Role of selenium and other trace elements in the geography of schizophrenia. Schizophr Bull 20(2):387-98, 1994. 5. Foster HD. Schizophrenia and esophageal cancer: comments on similarities in their spatial distributions. J Orthomol Med 5(3):129-34, 1990. 6. Foster HD. The geography of schizophrenia: possible links with selenium and calcium deficiencies, inadequate exposure to sunlight and industrialization. J Orthomol Med 3(3):135-40, 1988. 7. Alertsen AR, Aukrust A, Skaug OE. Selenium concentrations in blood and serum from patients with mental diseases. Acta Psychiatr Scand 74(2):217-19, 1986. 8. Buckman TD, Kling AS, Eiduscon S, et al. Glutathione peroxidase and CT scan abnormalities in schizophrenia. Biol Psychiatry 22(11):1349-56, 1987. 9. Abdalla DS, Monteiro HP, Oliveira JA, Bechara EJ. Activities of superoxide dismutase and glutathione peroxidase in schizophrenic and manic-depressive patients. Clin Chem 32(5):805-7, 1986. 10. Berry T. A selenium transport protein model of a sub-type of schizophrenia. Med Hypotheses 43(6):409-14, 1994.

Vitamin B6 Imbalance

Proper Name: Pyridoxine Hydrochloride Common Name: Vitamin B6 Evidence of Efficacy: statement to the effect of Vitamin B6 deficiency or imbalance plays a role in the symptoms of mood disorders. Observational and experimental studies have shown an association between vitamin B6 and aggression1, anxiety2,3,4, ADHD5,6,7,8,9,10,11,12, bipolar disorder13,14, depression15, 16 ,17 ,18 ,19 ,20 ,21 ,22 ,23 ,24 ,25 ,26, obsessive compulsive disorder27,28, premenstrual syndrome29, 30, 31, 32, 33,3 4,3 5,36 ,37, 38, ,39 ,40, 41, 42,43 ,44, 45, 46, 47, 48, 49, 50 ,5 1,52, 53,and schizophrenia54, 55, 56, 57, 58, 59,6 0,6 1,62 ,63 ,64 .65 References: 1. Noted in McLaren DS. Clinical manifestations of nutritional disorders, in ME Shils, VR Young, Eds. Modern Nutrition in Health and Disease, Seventh Edition. Philadelphia, Lea & Febiger, 1988. 2. Heseker H, Kubler W, Pudel V, Westenhoffer J. Psychological disorders as early symptoms of a mild-moderate vitamin deficiency. Ann N Y Acad Sci 669:352-7, 1992. 3. Hoes MJ et al. Hyperventilation syndrome, treatment with L-tryptophan and pyridoxine; Predictive value of xanthurenic acid excretion. J Orthomol Psychiatry 10(1):7-15, 1981. 4. Buist RA. Anxiety neurosis: The lactate connection. Int Clin Nutr Rev 5:1-4, 1985. 5. Coleman M et al. Serotonin in Down’s syndrome. Amsterdam, North Holland, 1973. 6. Kleijnen J, Knipschild P. Niacin and vitamin B6 in mental functioning: a review of controlled trials in humans. Biol Psychiatry 29(9):931-41, 1991. 7. Haslam RH, Dalby JT. Blood serotonin levels in the attention-deficit disorder. Letter. N Engl J Med 309(31):1328-9, 1983. 8. Brenner A. The effects of megadoses of selected B complex vitamins on children with hyperkinesis: Controlled studies with long-term follow-up. J Learn Disabil 15(5):258-64, 1982. 9. Klieger JA, Altshuler CH, Krakow L, Hollister L. Abnormal pyridoxine metabolism in toxemia of pregnancy. Ann N Y Acad Sci 166:288-96, 1969. 10. Coleman M et al. A preliminary study of the effect of pyridoxine administration in a subgroup of hyperkinetic children: A double-blind crossover comparison with methylphenidate. Biol Psychiatry 14(5):741-51, 1979. 11. Brenner A, Wapnir R. A pyridoxine-dependent behavioral disorder unmasked by Isoniazid. Am J Dis Child 132:773-6, 1978. 12. Bhagavan HN et al. The effect of pyridoxine hydrochloride on blood serotonin and pyridoxal phosphate contents in hyperactive children. Pediatrics 55:437-41, 1975. 13. Moller SE et al. Tryptophan availability in endogenous depression – relation to efficacy of L-tryptophan treatment. Adv Biol Psychiatry 10:30-46, 1983. 14. The pharmacokinetics of oral L-tryptophan: Effects of dose and concomitant pyridoxine, allopurinol or nicotinamide administration. Adv Biol Psychiatry 10:67-81, 1983. 15. Noted in McLaren DS. Clinical manifestations of nutritional disorders, in ME Shils, VR Young, Eds. Modern Nutrition in Health and Disease, Seventh Edition. Philadelphia, Lea & Febiger, 1988. 16. Bell I et al. Complex vitamin patterns in geriatric and young adult inpatients with major depression. J Am Geriatr Soc 39:252-7, 1991. 17. Stewart TW, Harrison W, Quitkin F, et al. Low B6 levels in depressed outpatients. Biol Psychiatry 19(4):613-16, 1984. 18. Russ CS et al. Vitamin B6 status of depressed and obsessive-compulsive patients. Nutr Rep Int 27(4):867-73, 1983. 19. Carney MW, Ravindran A, Rinsler MG, et al. Thiamine, riboflavin and pyridoxine deficiency in psychiatric inpatients. Br J Psychiatry 141:271-2, 1982. 20. Carney MW, Williams DG, Sheffield BF. Thiamin and pyridoxine lack in newly-admitted psychiatric patients. Br J Psychiatry 135:249-54, 1979. 21. Nobbs B. Pyridoxal phosphate status in clinical depression. Letter. Lancet i:405, 1974. 22. Bermond P. Therapy of side effects of oral contraceptive agents with vitamin B6. Acta Vitaminol Enzymol 4(1-2):45-54, 1982. 23. Adams PW, Wynn V, Rose DP, et al. Effect of pyridoxine hydrocholoride (vitamin B6) upon depression associated with oral contraception. Lancet ii:899-904, 1973. 24. Adams PW, Wynn V, Seed M, Folkard J. Vitamin B6, depression, and oral contraception. Letter. Lancet ii:516-17, 1974. 25. Benton D, Haller J, Fordy J. Vitamin supplementation for 1 year improves mood. Neuropsychobiology 32(2):98-105, 1995. 26. Hallert C, Astrom J, Walan A. Reversal of psychopathology in adult coeliac disease with the aid of pyridoxine (vitamin B6). Scand J Gastroenterol 18(2):299-304, 1983. 27. Yaryura-Tobias JA. Presentation to the Third World Congress of Biological Psychiatry, Stockholm – reported in Clinical Psychiatrty News. September, 1981. 28. Yaryura-Tobias JA, Bhagavan HN. L-tryptophan in obsessive-compulsive disorders. Am J Psychiatry 134(11):1298-9, 1977. 29. Mira M, Stewart PM, Abraham SF. Vitamin and trace element status in premenstrual syndrome. Am J Clin Nutr 47(4):636-41, 1988. 30. Gallant MP, Bowering J, Short SH, et al. Pyridoxine and magnesium status in women with premenstrual syndrome. Nutr Res 7:243-52, 1987. 31. Stewart A. Clinical and biochemical effects of nutritional supplementation on the premenstrual syndrome. J Reprod Med 32(6):435-41, 1987. 32. Richie CD, Singkamani R. Plasma pyridoxal-5’-phosphate in women with the premenstrual syndrome. Hum Nutr Clin Nutr 40C:75-80, 1986. 33. Parry GJ, Bredesen DE. Sensory neuropathy with low-dose pyridoxine. Neurology 35:1466-8, 1985; Waterston JA, Gilligan BS. Pyridoxine neuropathy. Med J Aust 146:640-2, 1987. 34. Guy Abraham – personal communication reported in Piesse JW. Nutrition factors in the premenstrual syndrome: A review. Int Clin Nutr Rev 4(2):54-81, 1984. 35. Abraham GE. Nutrition and the premenstrual tension syndromes. J Appl Nutr 36(2):103-17, 1985; Hargrove JT, Abraham GT. Effect of vitamin B6 on infertility in women with the premenstrual syndrome. Infertility 2:315: 1979. 36. Leklem JE. Vitamin B6: The pill, pregnancy and premenstrual syndrome. Abstract. J Am Coll Nutr. 11(5):624, 1992. 37. Kleijnen J, Ter Riet G, Knipschild P. Vitamin B6 in the treatment of premenstrual syndrome – a review. Br J Obstet Gynaecol 97(9):847-52, 1990. Berman MK et al. Vitamin B-6 in premenstrual syndrome. J Am Diet Assoc 90(6):859-61, 1990. 38. Doll H, Brown S, Thurston A, Vessey M. Pyridoxine (vitamin B6) and the premenstrual syndrome: A randomized crossover trial. J R Coll Gen Pract 39:364-8, 1989. 39. Brush MG, Bennett T, Hansen K. Pyridoxine in the treatment of premenstrual syndrome: A retrospective survey in 630 patients. Br J Clin Pract 42(11):448-52, 1988. 40. Kendall KE, Schnurr PP. The effects of vitamin B6 supplementation on premenstrual symptoms. Obstet Gynecol 70(2):145-9, 1987. 41. David R. Rubinow, biological psychiatry branch, National Institute of Mental Health (USA) – quoted by Clin Psychiatry News, December, 1987. 42. Hagen I et al. No effect of vitamin B-6 against premenstrual tension: A controlled clinical study. Acta Obstet Gynecol Scand 64:667, 1985. 43. Williams MJ, Harris RI, Dean BC. Controlled trial of pyridoxine in the premenstrual syndrome. J Int Med Res 13:174-9, 1985. 44. Barr W. Pyridoxine supplements in the premenstrual syndrome. Practitioner 228:425-7, 1984. 45. Mattes JA, Martin D. Pyridoxine in premenstrual depression. Hum Nutr Appl Nutr 36(2):131-3, 1982. 46. Abraham GE, Hargrove JT. Effect of vitamin B-6 on premenstrual symptomatology in women with premenstrual tension syndrome: A double-blind crossover study. Infertility 3:155-65, 1980. 47. Day JB. Clinical trials in the premenstrual syndrome. Curr Med Res Opin (Suppl 6) 5:40-5, 1979. 48. Kerr GD. The management of the premenstrual syndrome. Curr Med Res Opin (Suppl 4) 4:29-34, 1977. 49. Stokes J, Mendels J. Pyridoxine and premenstrual tension. Letter. Lancet i:1177-8, 1972. 50. Piesse JW. Nutrition factors in the premenstrual syndrome. Int Clin Nutr Rev 4(2):54-81, 1984. 51. Lee CM, Leklem JE. Blood magnesium constancy with vitamin B-6 supplementation in pre- and post-menopausal women. Ann Clin Lab Sci 14(2):151-4, 1984. 52. Abraham GE et al. Effect of vitamin B6 on plasma and red blood cell magnesium levels in premenopausal women. Ann Clin Lab Sci 11(4):333-6, 1981. 53. Holley J et al. Effect of vitamin B6 nutritional status on the uptake of [3H]-oestradiol into the uterus, liver and hypothalamus of the rat. J Steroid Biochem 18:161-6, 1983. 54. Pfeiffer CC, Audette L. Pyroluria – Zinc and B6 deficiencies. Int Clin Nutr Rev 8(3):107-10; 1988. 55. Pfeiffer CC. The schizophrenias ’76. Biol Psychiatry 2:773-5, 1976. 56. Pfeiffer CC, Bacchi D. Copper, zinc, manganese, niacin and pyridoxine in the schizophrenias. J Appl Nutr 27:9-39, 1975. 57. Pfeiffer CC. Observations on trace and toxic elements in hair and serum. J Orthomol Psychiatry 3(4):259-64, 1974. 58. Cruz R, Vogel WH. Pyroluria: A poor marker in chronic schizophrenia. Am J Psychiatry 135(10):1239-40, 1978. 59. Parry GJ. Sensory neuropathy with low-dose pyridoxine. Neurology 35:1466:8, 1985. 60. Kleijnen J, Knipschild P. Niacin and vitamin B6 in mental functioning: a review of controlled trials in humans. Biol Psychiatry 29(9):931-41, 1991. 61. Brooks SC et al. An unusual schizophrenic illness responsive to pyridoxine HCl (B6) subsequent to phenothiazine and butyrophenone toxicities. Biol Psychiatry 18(11):1321-8, 1983. 62. Yamauchi M. Effects of L-dopa and vitamin B6 on electroencephalograms of schizophrenic patients: A preliminary report. Folia Psychiatrica et Neurologica Japonica 30(2):121-51, 1976. 63. Sandyk R, Pardeshi R. Pyridoxine improves drug-induced parkinsonism and psychosis in a schizophrenic patients. J Neurosci 53(3-4):225-32, 1990. 64. Petrie WM, Ban TA, Anath JV. The use of nicotinic acid and pyridoxine in the treatment of schizophrenia. Int Pharmacopsychiatry 16(4):245-50, 1981. 65. Ananth JV, Ban TA, Lehmann HE. Potentiation of therapeutic effects of nicotinic acid by pyridoxine in chronic schizophrenics. Can Psychiatr Assoc J 18:377-83, 1973.

Magnesium Imbalance

Proper Name: Magnesium Common Name: Magnesium Evidence of Efficacy: Magnesium deficiency or imbalance plays a role in the symptoms of mood disorders. Observational and experimental studies have shown an association between magnesium and aggression 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, anxiety 11, 12, 13, 14, 15, ADHD 16, 17, 18, bipolar disorder 19, 20 ,21, depression 22,23,24,25,26,27,28,29,30,31,32,33,34,35, premenstrual syndrome 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, and schizophrenia 58, 59, 60, 61, 62, 63, 64, 65 ,66 ,67 ,68 ,69, 70. References: 1. Izenwasser SE et al. Stimulant-like effects of magnesium on aggression in mice. Pharmacol Biochem Behav 25(6):1195-9, 1986. 2. Henrotte JG. Type A behavior and magnesium metabolism. Magnesium 5:201-10, 1986. 3. Bennett CPW, McEwen LM, McEwen HC, Rose EL. The Shipley Project: treating food allergy to prevent criminal behaviour in community settings. J Nutr Environ Med 8:77-83, 1998. 4. Kirow GK, Birch NJ, Steadman P, Ramsey RG. Plasma magnesium levels in a population of psychiatric patients: correlation with symptoms. Neuropsychobiology 30(2-3):73-8, 1994. 5. Kantak KM. Magnesium deficiency alters aggressive behavior and catecholamine function. Behav Neurosci 102(2):304-11, 1988. 6. Izenwasser SE, Garcia-Valdez K, Kantak KM. Stimulant-like effects of magnesium on aggression in mice. Pharmacol Biochem Behav 25(6):1195-9, 1986. 7. Struempler RE et al. Hair mineral analysis and disruptive behavior in clinically normal young men. J Learn Disabil 18(10):609-12, 1985. 8. Banki CM, Vojnik M, Papp Z, et al. Cerebrospinal fluid magnesium and calcium related to amine metabolites, diagnosis, and suicide attempts. Biol Psychiatry 20(2):163-71, 1985. 9. Schmidt K, Wier WR, Asch M. Clinical ecology treatment approach for juvenile offenders. J Behav Ecology: Biosocial 2(1), 1981. 10. Von Hilsheimer G, Philpott W, Buckley W, Klotz SC. Correcting the incorrigible. A report on 229 "incorrigible" adolescents. Am Lab 107:22-49, 1977. 11. Buist RA. Anxiety neurosis: The lactate connection. Int Clin Nutr Rev 5:1-4, 1985. 12. Seelig MS, Berger AR, Spieholz N. Latent tetany and anxiety, marginal Mg deficit, and normocalcemia. Dis Nerv Syst 36:461-5, 1975. 13. Durlach J, Durlach V, Bac P, et al. Magnesium and therapeutics. Magnes Res 7(3/4):313-28, 1994. 14. Kirov GK, Tsachev KN. Magnesium, schizophrenia and manic-depressive disease. Neuropsychobiology 23(2):79-81, 1990. 15. Weston PG et al. Magnesium sulphate as a sedative. Am J Med Sci 165:431-3, 1923. 16. Durlach J. Clinical aspects of chronic magnesium deficiency, in MS Seelig, Ed. Magnesium in Health and Disease. New York, Spectrum Publications, 1980. 17. Kozielec T, Starobrat-Hermelin B. Assessment of magnesium levels in children with attention deficit hyperactivity disorder (ADHD). Magnes Res 10(2):143-8, 1997. 18. Starobrat-Hermelin B, Kozielec T. The effects of magnesium physiological supplementation on hyperactivity in children with attention deficit hyperactivity disorder (ADHD). Positive response to magnesium oral loading test. Magnes Res 10(2):149-56, 1997. 19. George MS, Rosenstein D, Rubinow DR, et al. CSF magnesium in affective disorder: lack of correlation with clinical course of treatment. Psychiatry Res 51(2):139-46, 1994. 20. Kirov GK, Birch NJ, Steadman P, Ramsey RG. Plasma magnesium levels in a population of psychiatric patients: correlations with symptoms. Neuropsychobiology 1994;30(2-3):73-8, 1994. 21. Chouinard G, Beauclair L, Geiser R, Etienne P. A pilot study of magnesium aspartate hydrochloride (Magnesiocard) as a mood stabilizer for rapid cycling bipolar affective disorder patients. Prog Neuropsychopharmacol Biol Psychiatry 14(2):171-180, 1990. 22. Kirow GK, Birch NJ, Steadman P, Ramsey RG. Plasma magnesium levels in a population of psychiatric patients: correlation with symptoms. Neuropsychobiology 30(2-3):73-8, 1994. 23. Linder J et al. Calcium and magnesium concentrations in affective disorder: Difference between plasma and serum in relation to symptoms. Acta Psychiatr Scand 80:527-37, 1989. 24. Frazer A et al. Plasma and erythrocyte electrolytes in affective disorders. J Affect Disord 5(2):103-13, 1983. 25. Bjorum N. Electrolytes in blood in endogenous depression. Acta Psychiatr Scand 48:59-68, 1972. 26. Cade JFJA. A significant elevation of plasma magnesium levels in schizophrenia and depressive states. Med J Aust 1:195-6, 1964. 27. Kirov GK, Tsachev KN. Magnesium, schizophrenia and manic-depressive disease. Neuropsychobiology 23(2):79-81, 1990. 28. Hall RCW, Joffe JR. Hypomagnesemia: Physical and psychiatric symptoms. JAMA 224:1749-51, 1973. 29. Frizel D, Coppen A, Marks V. Plasma magnesium and calcium in depression. Br J Psychiatry 115:1375-7, 1969. 30. Frizel D et al. Plasma calcium and magnesium in depression. Br J Psychiatry 115:1375-7, 1969. 31. Hasey GM, D'Alessandro E, Cooke RG, Warsh JJ. The interface between thyroid activity, magnesium, and depression: A pilot study. Biol Psychiatry 33:133-5, 1993. 32. Linder J et al. Calcium and magnesium concentrations in affective disorder: Difference between plasma and serum in relation to symptoms. Acta Psychiatr Scand 80:527-37, 1989. 33. Frazer A et al. Plasma and erythrocyte electrolytes in affective disorders. J Affect Disord 5(2):103-13, 1983]. 34. Banki CM et al. Aminergic studies and cerebrospinal fluid cations in suicide. Ann N Y Acad Sci 487:221-30, 1986. 35. Banki CM et al. Cerebrospinal fluid magnesium and calcium related to amine metabolites, diagnosis, and suicide attempts. Biol Psychiatry 20:163-71, 1985. 36. Posaci C, Erten O, Uren A, Acar B. Plasma copper, zinc and magnesium levels in patients with premenstrual tension syndrome. Acta Obstet Gynecol Scand 73(6):452-5, 1994. 37. Rosenstein DL et al. Magnesium measures across the menstrual cycle in premenstrual syndrome. Biol Psychiatry 35:557-61, 1994. 38. Chuong CJ, Dawson EB., Magnesium levels in premenstrual syndrome. Nutr Res 14(11):1623-34, 1994. 39. Mira M, Stewart PM, Abraham SF. Vitamin and trace element status in premenstrual syndrome. Am J Clin Nutr 47:636-41, 1988. 40. Sherwood RA, Rocks BF, Stewart A, Saxton RS. Magnesium and the premenstrual syndrome. Ann Clin Biochem 23(6):667;70, 1986. 41. Stebbing JB et al., Reactive hypoglycaemia and magnesium. Magnesium Bull 4(2):131-4, 1982. 42. Rosenstein DL et al. Magnesium measures across the menstrual cycle in premenstrual syndrome. Biol Psychiatry 35:557-61, 1994. 43. Stewart A., Clinical and biochemical effects of nutritional supplementation on the premenstrual syndrome. J Reprod Med 32:435-41, 1987. 44. Sherwood RA, Rocks BF, Stewart A, Saxton RS. Magnesium and the premenstrual syndrome. Ann Clin Biochem 23(6):667-70, 1986. 45. Stebbing JB et al., Reactive hypoglycaemia and magnesium. Magnesium Bull 4(2):131-4, 1982. 46. Abraham GE. Magnesium deficiency in premenstrual tension. Magnesium Bull 1:68-73, 1982. 47. Abraham GE, Lubran MM. Serum and red cell magnesium levels in patients with premenstrual tension. Am J Clin Nutr 34(11):2364-6, 1981. 48. Rosenstein DL et al. Magnesium measures across the menstrual cycle in premenstrual syndrome. Biol Psychiatry 35:557-61, 1994. 49. Stewart A., Clinical and biochemical effects of nutritional supplementation on the premenstrual syndrome. J Reprod Med 32:435-41, 1987. 50. Stebbing JB et al. Reactive hypoglycaemia and magnesium. Magnesium Bull 4(2):131-4, 1982. 51. Brown RC, Bidlack WR. Regulation of glucuronyl transferase by intracellular magnesium, in Proceedings of the International Symposium on Magnesium and its Relationship to Cardiovascular, Renal and Metabolic Disorders. Los Angeles, 1985:24. 52. Curry DL et al. Magnesium modulation of glucose-induced insulin secretion by the perfused rat pancreas. Endocrinology 101:203, 1977. 53. Abraham GE. Management of the premenstrual tension syndromes: Rationale for a nutritional approach, in J Bland, Ed. 1986: A Year in Nutritional Medicine. New Canaan, CT, Keats Publishing, 1986:125-66. 54. Brown RC, Bidlack WR. Regulation of glucuronyl transferase by intracellular magnesium, in Proceed Int Sympos Magnesium and its Relationship to Cardiovascular, Renal and Metabolic Disorders. Los Angeles, 1985:24. 55.Cunnane SC, Horrobin DF. Parnteral linoleic and gamma-linolenic acids ameliorate the gross effects of zinc deficiency. Proc Soc Exp Biol Med 164:583, 1980. 56. Facchinetti F, Bolrella P, Sances G, et al. Oral magnesium successfully relieves premenstrual mood changes. Obstet Gynecol 78(2):177-81, 1991. 57. Facchinetti F et al. Magnesium prophylaxis of menstrual migraine: effects of intracellular magnesium. Headache 31:298-304, 1991. 58. Levine J, Rapoport A, Mashiah M, Dolev E. Serum and cerebrospinal levels of calcium and magnesium in acute versus remitted schizophrenic patients. Neuropsychobiology 33(4):169-72, 1996. 59. Kirow GK, Birch NJ, Steadman P, Ramsey RG. Plasma magnesium levels in a population of psychiatric patients: correlation with symptoms. Neuropsychobiology 30(2-3):73-8, 1994. 60. Kanofsky JD et al. Is iatrogenic hypomagnesemia common in schizophrenia? Abstract. J Am Coll Nutr 10(5):537, 1991. 61. Kirov GK, Tsachev KN. Magnesium, schizophrenia and manic-depressive disease. Neuropsychobiology 23(2):79-81, 1990. 62. Chhatre SM et al. Serum magnesium levels in schizophrenia. Ind J Med Sci 39(11):259-61, 1985. 63. Paul EA et al. Serum calcium and magnesium in schizophrenia. Relationship to clinical phenomena and neuroleptic treatment. Br J Psych 133:143-9, 1978. 64. Daly RM, Gold G. Serum magnesium levels in nonacute schizophrenics. N Y State J Med 76:188-9, 1976. 65. Hakim AH et al. A comparative study of serum calcium and magnesium in cases of endogenous depression, reactive depression, schizophrenia and conversion reaction. J Assn Phys Ind 23:513-17, 1975. 66. Pandey SK et al. An estimation of magnesium and calcium in serum and CSF in schizophrenia. J Assn Phys Ind 21:203-5, 1973. 67. Chugh TD et al. Magnesium in schizophrenia. Ind J Med Res 61:998-1001, 1973. 68. Cade JFJ. A significant elevation of plasma magnesium level in schizophrenia and depressive states. Med J Aust 1:195-6, 1964. 69. Kornhuber J, Lange KW, Kruzik P, et al. Iron, copper, zinc, magnesium, and calcium in postmortem brain tissue from schizophrenic patients. Biol Psychiatry 36(1):31-4, 1994. 70. Levine J, Rapoport A, Mashiah M, Dolev E. Serum and cerebrospinal levels of calcium and magnesium in acute versus remitted schizophrenic patients. Neuropsychobiology 33(4):169-72, 1996.

Copper imbalance

Proper Name: Copper Common Name: Copper Evidence of Efficacy: statement to the effect of Copper deficiency or imbalance plays a role in the symptoms of mood disorders. Observational and experimental studies have shown an association between copper and ADHD1,2,3, depression4,5,6, premenstrual syndrome7, and schizophrenia8,9,10,11,12,13,14,15,16,17,18,19,20. References: 1. Kozielec T, Starobrat-Hermelin B, Kotkowiak L. [Deficiency of certain trace elements in children with hyperactivity.] Psychiatr Pol 28(3):345-53, 1994. 2. Brenner A. Trace mineral levels in hyperactive children responding to the Feingold diet. J Pediatr 94 (60):944-5, 1979. 3. Pfeiffer CC, Mailloux R. Excess copper as a factor in human diseases. J Orthomol Med 2(3):171-82, 1987. 4. Hansen Cr Jr et al. Copper and zinc deficiencies in association with depression and neurological findings. Biol Psychiatry 18(3):395-401, 1983. 5. Narang RL, Gupta KR, Narang AP, Singh R. Levels of copper and zinc in depression. Indian J Physiol Pharmacol 35(4):272-4, 1991. 6. Ali SA et al. Blood levels of vanadium, caesium, and other elements in depressive patients. J Affect Disord 9:187-91, 1985. 7. Choung C, Dawson E. Zinc and copper levels in premenstrual syndrome. Fert Steril 62:313-20, 1994. 8. Kornhuber J, Lange KW, Kruzik P, et al. Iron, copper, zinc, magnesium, and calcium in postmortem brain tissue from schizophrenic patients. Biol Psychiatry 36(1):31-4, 1994. 9. Shore D et al. CSF copper concentrations in chronic schizophrenia. Am J Psychiatry 140(6):754-7, 1983. 10. Tyrer SP et al. CSF copper in schizophrenia. Am J Psychiatry 136(7):937-9, 1979. 11. Gillin JC et al. Zinc and copper in patients with schizophrenia. Encephale 8(3):435-44, 1982. 12. Olatunbosun DA at al. Serum copper in schizophrenia in Nigerians. Br J Psychiatry 127:119-21, 1975. 13. Pfeiffer CC, Illiev V. A study of zinc deficiency and copper excess in the schizophrenias. Int Rev Biol Suppl 1, 1972. 14. Heilmeyer L, Keiderling W, Struve C. Kupfer and eisen als. Korpereigene Wirkstoffe und Ihre Bedeutung Beim Krankheitgeschehen. Fischer, Jena, Germany, 1941. 15. Pfeiffer CC, LaMola S. Zinc and manganese in the schizophrenias. J Orthomol Psychiatry 12:215-34, 1983. 16. Bowman MB, Lewis MS. The copper hypothesis of schizophrenia: a review. Neurosci Biobehav Rev 6:321-8, 1982. 17. Gillin JC et al. Zinc and copper in patients with schizophrenia. Encephale 8(3):435-44, 1982. 18. Mattke JD, Adler M. Mode of action of D-penicillamine in chronic schizophrenia. Dis Nerv Sys 32:388, 1971. 19. Affleck JW et al., Penicillamine and schizophrenia – A clinical trial. Br J Psychiatry 115:173, 1969. 20. Nicholson GA et al. Effect of D-penicillamine on schizophrenic patients. Lancet i:344, 1966.

Zinc Imbalance

Proper Name: Zinc Common Name: Zinc Evidence of Efficacy: statement to the effect of Zinc deficiency or imbalance plays a role in the symptoms of mood disorders. Observational and experimental studies have shown an association between zinc and aggression2,3,4,5,6, ADHD7,8,9,10,11,12,13, depression14,15,16,17,18,19, and premenstrual syndrome20,21,22,23,24. References: 1. Walwork JC et al. Distribution of minerals and catecholamines in rat brain: effects of zinc deficiency, in CJ Frederickson et al, Eds. The Neurobiology of Zinc, Part B: Deficiency, Toxicity and Pathology (Neurology and Neurobiology V. 11B). New York, Alan R. Liss, 1984:49-64. 2. Prasad AS. Clinical manifestations of zinc deficiency. Nutr Rev 41(7):197, 1983. Schauss AG et al. A critical analysis of the diets of chronic juvenile offenders, Part II. J Orthomol Psychiatry 8(4):222-6, 1979. 3. William J. Walsh, analytical chemist, Argonne National Laboratory – reported in Sci News 124:122-5, 1983. 4. Von Hilsheimer G, Philpott W, Buckley W, Klotz SC. Correcting the incorrigible. A report on 229 “incorrigible” adolescents. Am Lab 107:22-49, 1977. 5. William J. Walsh. Zinc deficiency, metal metabolism, and behavior disorders. Unpublished monograph. Health Research Institute, 1804 Centre Point Dr., Suite 106, Naperville, IL 60503, March 1995. 6. Bennett CPW, McEwen LM, McEwen HC, Rose EL. The Shipley Project: treating food allergy to prevent criminal behavior in community settings. J Nutr Environ Med 8:77-83, 1998. 7. Ward NI. Assessment of chemical factors in relation to child hyperactivity. J Nutr Environ Med 7:333-42, 1997. 8. Bekaroglu M, Aslan Y, Gedik Y, et al. Relationships between serum free fatty acids and zinc, and attention deficity hyperactivity disorder: a research note. J Child Psychol Psychiatry 37(2):225-7, 1996. 9. Kozielec T, Starobrat-Hermelin B, Kotkowiak L. [Deficiency of certain trace elements in children with hyperactivity.] Psychiatr Pol 28(3):345-53, 1994. 10. Ward NI et al. The influence of the chemical additive tartrazine on the zinc status of hyperactive children – a double-blind placebo-controlled study. J Nutr Med 1:51-7, 1990. 11. Arnold LE, Votalato NA, Kleykamp D, et al. Does hair zinc predict amphetamine improvement of ADD/hyperactivity? Int J Neruosci 50(1-2):103-7, 1990. 12. Barlow PJ. A pilot study on the metal levels in the hair of hyperactive children. Med Hypotheses 11(3):309-18, 1983. 13. Golub MR, Takeuchi PT, Keen CL, et al. Activity and attention in zinc-deprived adolescent monkeys. Am J Clin Nutr 64:908-15, 1996. 14. Tasman-Jones C. Zinc deficiency states. Adv Intern Med 26:97-114, 1980. 15. Maes M, Vandoolaeghe E, Neels H, et al. Lower serum zinc in major depression is a sensitive marker of treatment resistance and of the immune/inflammatory response in that illness. Biol Psychiatry 42(5):349-58, 1997. 16. Maes M, D’Haese PC, Scharpe S, et al. Hypozincemia in depression. J Affect Disord 31(2):135-40, 1994. 17. Narang RL, Gupta KR, Narang AP, Singh R. Levels of copper and zinc in depression. Indian J Physiol Pharmacol 35(4):272-4, 1991. 18. McLoughlin IJ, Hodge JS. Zinc in depressive disorder. Acta Psychiatr Scand 82(6), 451-3, 1990. 19. Little KY, Castellanos X, Humphries LL, Austin J. Altered zinc metabolism in mood disorder patients. Biol Psychiatry 26:646-8, 1989. 20. Posaci C, Erten O, Uren A, Acar B. Plasma copper, zinc and magnesium levels in patients with premenstrual tension syndrome. Acta Obstet Gynecol Scand 73(6):452-5, 1994. 21. Choung C, Dawson E. Zinc and copper levels in premenstrual syndrome. Fert Steril 62:313-20, 1994. 22. Mira M, Stewart PM, Abraham SF. Vitamin and trace element status in premenstrual syndrome. Am J Cin Nutr 47(4):636-41, 1988. 23. Stewart A. Clinical and biochemical effects of nutritional supplementation on the premenstrual syndrome. J Reprod Med 32:435-41, 1987. 24. Chuong CJ et al, Baylor College of Medicine, Houston – presented at the 46th Annual Mtg. Of the Am. Fertility Society, Washington, DC, 1991.

Common Treatments: Inositol

	Inositol, an 'unofficial' B-vitamin, is a cyclic 6-carbon compound quite similar to glucose. In animal cells, it occurs as a component of phospholipids and it stored predominantly in the brain, spinal cord nerves, cerebral spinal fluid, skeletal muscle, and heart muscle. The human body contains more inositol than any other vitamin except niacin. Source Inositol is available from both plant and animal sources. The plant form in which inositol is available is phytic acid, which can bind with minerals and so affect their absorption negatively. The action of the intestinal bacteria liberates inositol from phytic acid, which is found in citrus fruits, nuts, seeds and legumes, wheat germ, brewers yeast, bananas, liver, beef brains and heart, whole grains such as brown rice, oat flakes, unrefined molasses, raisins and vegetables such as cabbage. Function; Reasons For Use Inositol is simply a hexane molecule (ringed structure of 6 carbons) with 6 hydroxyl groups (OH) attached. Inositol is used by the body to complete the synthesis of certain phospholipids, important components of every cell membrane. Inositol is also used to make Inositol Triphosphate (IP3), an important secondary messenger in various cell signaling events. Inositol is also lipotropic, meaning it associates with lipids (fats). Its lipotropic characteristics have been used to help move fatty material from the liver, into the intestines where they can be effectively removed with fiber. Inositol works closely with choline as one of the primary components of the cell membrane. It is also needed for growth and survival of cells in bone marrow, eye membranes, and the intestines. Inositol appears to be a precursor of the phosphoinosities (compounds that may be important in hormonal action) especially in the brain. Proper action of several brain neurotransmitters, such as acetylcholine and serotonin, require inositol. Inositol encourages hair growth and can help prevent baldness. Like choline, inositol helps to move fat out of the liver, and helps prevent serious liver disorders, as well as disorders involving high cholesterol. Serotonin and acetylcholine, two neurotransmitters, both depend upon inositol, and supplementation can therefore assist in the reduction of depression and panic attacks. A reduction in brain inositol levels may induce depression as evidenced by low inositol levels in the cerebrospinal fluid of patients with depression. In a 1-month, double-blind, placebo-controlled study of 28 patients with depression, inositol demonstrated therapeutic results similar to tricyclic antidepressants without the side-effects. Additional studies have revealed that inositol supplementation is an effective treatment in panic and obsessive compulsive disorders. Loss of inositol from nerve cells is the primary reason for diabetic neuropathy, so inositol supplementation can assist in improving this condition. Phytic acid, the plant source of inositol, has been shown to have anticancer properties, which may be one reason why a high-fiber diet protects against many cancers. Inositol also has a prominent calming effect on the central nervous system, so it may be helpful to those with insomnia. Studies on brain waves have shown that it has an effect similar to that of librium or valium. It can gradually lower blood pressure, and can be helpful in cases of schizophrenia, hypoglycemia, and those with high serum copper and low serum zinc levels. Because it stimulates muscles of the alimentary canal, inositol is helpful in cases of constipation. It can also induce labor contractions in pregnant women. Intake of caffeine is known to deplete the bodies supply of inositol. Directions The RDA is 100mg per day, but be aware that this dosage is the minimum that you require to ward off deficiency of this particular nutrient. In the therapeutic use of this nutrient, the dosage is usually increased considerably, but the toxicity level must be kept in mind. It is best used with choline, which should be taken in the same amount as inositol. It is best to take the entire B-group vitamins with it. Vitamin E, vitamin C as well as folic acid and linoleic acid are thought to increase the functioning of inositol. Side-Effects Although no toxic effects are known, diarrhea has been noted with the intake of very high dosage.

Low Cholesterol May Be Related to Impulsivity

Original Article The cholesterol conundrum - low cholesterol levels may lead to impulsive behavior Why do people on low-cholesterol diets die somewhat less often what less often of heart disease, yet a lot more often of suicide, accidents, and homicide than the rest of the population? Although the finding has cropped up in numerous studies over the past decade, it has met with much disbelief in medical circles. Nevertheless, an expert in heart disease research decided to test whether there might be any behavioral basis for the results. His studies link cholesterol in the diet with the neurotransmitter serotonin and its manifestation in impulsive behavior. Jay Kaplan, Ph.D., looked at monkeys who were eating diets high in fat, but either low or high in cholesterol. After eight months, he found that the low-cholesterol monkeys, who had cholesterol readings of about 220, had no heart disease but were more hostile than the monkeys on a cheeseburger-like diet, whose levels hit 600. "These monkeys went at it hammer and tong," says Kaplan, a professor of comparative medicine. "They engaged in more contact aggression - highly charged impulsive fighting - than the other monkeys." Impulsivity, an increasingly scrutinized category of behavior, plays out in violence, suicide, and risk taking. And, impulsive people are likely to have a deficit of serotonin. "People in cholesterol-lowering trials might have been experiencing impulsivity, which led to the higher rates of suicide and accidents," suggests Kaplan. He then measured serotonin levels in the monkeys' cerebrospinal fluid. Sure enough, the low-cholesterol aggressive monkeys had less serotonin than the high-cholesterol monkeys. Cholesterol is a major component of brain-cell membranes. Alterations in dietary cholesterol affect the fluidity and viscosity of the membranes, which house receptors for serotonin. So altering the condition of neuronal membranes may well alter the function of these serotonin receptors, explains Kaplan. The findings, reported in Psychosomatic Medicine (Vol. 56), raise questions about the National Cholesterol Education Program recommendations that Americans over the age of two significantly lower their intake of fat and cholesterol. "Can this diet do harm?" asks Kaplan. "For people who already have low serotonergic activity, a low-cholesterol diet might shove them across some threshold that makes them more likely to do things they might not otherwise do." Or into depression. A recent study of men being treated for heart disease showed that those receiving cholesterol-lowering drugs experienced more symptoms of depression and anxiety than those who were not on the drugs. Kaplan is swimming against a strong current. "The NIH," he laments, "has billions of dollars tied up in the [cholesterol] hypothesis." COPYRIGHT 1995 Sussex Publishers, Inc. COPYRIGHT 2004 Gale Group