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An Orthomolecular Approach to the Prevention and Treatment of Psychiatric Disorders
Mark Zell, PhD, and Oliver Grundmann, PhD aBstract Orthomolecular medicine is based on the use of endogenous and naturally occurring substances to supplement deficiencies in vitamins, minerals, and other essential substances in the human body. Although the medical community has long regarded it as a nonscientific approach to healing, scientific and clinical evidence is emerging for the supplemental use of orthomolecular medicine in the treatment of schizophrenia, depression, bipolar disorder, generalized anxiety disorder, and attention deficit hyperactivity disorder. Psychiatrists currently treat these common psychiatric disorders using a wide range of pharmacological approaches that often have significant side effects, resulting in patients’ noncompliance. With newly gained knowledge about the neurophysiology and neuropathophysiology of psychiatric disorders, researchers now can link potential mechanisms for both pharmacological and orthomolecular treatments to physiological processes. In many cases, the use of orthomolecular supplements may provide a feasible addition to conventional drug therapy. (Adv Mind Body Med. 2012;26(2):14-28.)
Mark Zell, PhD, is a graduate assistant in the College of Pharmacy at the University of Florida. Oliver Grundmann, PhD, is a clinical assistant professor in the College of Pharmacy at the University of Florida. Corresponding author: Mark Zell, PhD E-mail address: email@example.com
n 1969, Linus Pauling first used the term orthomolecular medicine to describe the use of natural materials in the prevention and treatment of diseases.1 Modern orthomolecular medicine, classified as an alternative or complementary medical therapy, attempts to prevent and/or treat diseases by achieving balance in substances that are natural to the body through administration of vitamins, minerals, amino acids, and other naturally occurring chemical compounds.2 Orthomolecular medicine, sometimes also called megavitamin therapy, focuses on the use of dietary supplements, as well as diet modification, to ensure, in the words of Linus Pauling, that the individual is consuming “the right nutrients in the right amounts.”3 The basis of orthomolecular medicine is the concept that disease processes commonly occur when the physiological balance of essential nutrients is thrown off,
and orthomolecular physicians can prevent or treat many diseases by balancing the nutrient intake of a patient with the proper supplements.3 Orthomolecular physicians focus on diseases that they can trace to a specific biochemical imbalance.4 They have realized that sometimes orthomolecular techniques will be effective, sometimes standard medical treatments will be effective, and sometimes a combination of both techniques will provide the best approach to prevention and treatment of a disease state. For a long time, the medical community has pushed orthomolecular medicine to the fringes of modern medical practice due to a lack of scientific rigor and proof of efficacy. Since its wider recognition in the 1960s, orthomolecular medicine has developed significantly, with many physicians around the globe adopting the orthomolecular approach. In some cases, valid preclinical and clinical data have indicated that orthomolecular medicine has benefited many patients. This review provides an overview of the history of orthomolecular medicine and the current state of scientific data on its use for several psychiatric disorders. History of ortHomolecular medicine Linus Pauling’s ideas about increasing the intake of naturally occurring substances through the use of dietary supplements and about changing the diet were not new. In fact, historians can trace the relationship between diet and
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Japanese. NO.com. One of the classic examples of the impact of diet on health comes from the British Navy. Zell—Psychiatric Disorders X ADVANCES. vitamins.16 In particular. and diseases specifically related to malnutrition (eg. there is usually a combination of nutrients that can achieve the same thing without side effects. Pfeiffer said. FALL 2012. Linus Pauling had a profound impact on the field of orthomolecular psychiatry in the 1970s. One of the earliest modern orthomolecular physicians was Max Gerson.19 For example. and several amino acids. Dr Carl Pfeiffer was another 20th-century orthomolecular physician. but he firmly believed until his death in 1994 that the use of high-dose.6% in the adult population—and the poor results and high side-effect burden of current pharmacological treatments. Orthomolecular physicians thought this regime was a useful treatment against many diseases. ariboflavinosis. when he defined the field as “the treatment of mental disease by the provision of the optimum molecular environment for the mind. gastrointestinal diseases. in addition to a thorough evaluation of the symptoms via physician-guided questionnaires. and it has come to be known as the Gerson Therapy.13 Pauling’s greatest contribution to the field of orthomolecular medicine involved his investigation of the use of vitamin C for many applications. and many other diseases. and the diseases are often multifactorial. intravenous vitamin C held great promise for the treatment of disease. 6.19-22 The major nutritional deficiencies observed in mentally ill patients include omega-3 fatty acids. indicating that practitioners should use caution in using it to treat cancer. and fiber can prevent the development of several chronic disorders such as cancer. 26. They often conduct the initial evaluation of biochemical imbalances using urine. referring to research that demonstrates a link between nutritional deficiencies and an increase in mental illnesses. goiter. or Finnish natives who consume diets that are high in fish oils (omega-3 fatty acids).11 He is noted for his treatments.This article is protected by copyright. which involved the hourly administration of fresh vegetable juice.18 Treating mental illnesses using both standard pharmacological and orthomolecular treatments is difficult because scientists do not understand the underlying pathophysiologies of these illnesses very well. please visit copyright. multifactorial regimen of vitamins and minerals and any applicable lifestyle changes. and he became interested in what he termed molecular medicine in 1941 after being prescribed a low-protein. ortHomolecular PsycHiatry One of the major areas of study for practitioners of orthomolecular medicine is the field of psychiatry. 2 15 . vegetables. have lower incidences of mental illness. cardiovascular diseases.6 Today. and enzymatic activities. Based on this profile. and pellagra).7%. rickets. the orthomolecular practitioner prescribes a patient-specific. The goal of orthomolecular psychiatrists is restoration of the balance of these natural. generalized anxiety disorder.” Perhaps the most famous of the orthomolecularists. Hoffer was a strong proponent of the use of niacin for treating the symptoms of schizophrenia.7-10 Orthomolecular medicine blossomed in the 20th century. mainly schizophrenia and bipolar disorder.14 The medical community ostracized Pauling for this work. fresh citrus fruits on long voyages. with several notable physicians making contributions to the field. perhaps because of the prevalence of psychiatric illnesses in the United States—depression. Many unanswered questions exist regarding the validity of the Gerson Therapy as a stand-alone treatment because no scientific trial data supported his findings. Dr Gerson suggested that medical practitioners could cure certain cancers using a combination of nutrition and systemic detoxification. which he founded in 1967. was Linus Pauling. supplementation with vitamins and nutrients or consumption of a diet high in fresh fruits. such as Inuit-Yupik. served as the editor of the Journal of Orthomolecular Medicine. and until his death. Hoffer came to view the conventional treatments available for psychiatric patients under his care as poor and looked for a better way to treat them. Orthomolecular psychiatrists and other researchers have proposed that the increase in mental illnesses in Western countries is related to the change in the composition of the Western diet. Subsequent evaluations determine both biochemical and psychological improvements and are the basis for adjustment of the supplementation to suit an individual’s requirements. VOL. Use ISSN#1470-3556. the B vitamins. schizophrenia. 2. To subscribe. which successfully eliminated scurvy from its ships by supplying sailors with. “If there is a drug that exists that can alter the brain’s biochemistry.7%. the medical community knows that scurvy occurs because of a deficiency in vitamin C. blood. visit advancesjournal.3 Until his death in 2009. salt-free diet as part of his own treatment for Bright’s disease. essential substances. Dr Abram Hoffer continued Pauling’s work.17 He published numerous articles on his use of orthomolecular treatments. and bipolar disorder. Furthermore. Pauling is one of a very limited number of individuals who have won more than one Nobel Prize.15 Hoffer’s work in the field of orthomolecular medicine has focused primarily on the use of vitamin therapy in the treatment of schizophrenia. and he investigated the use of vitamins and minerals for the treatment of psychiatric illnesses. and requiring them to consume.5 The understanding of the relationship between diet and health has improved since ancient times.com good health back to the ancient Egyptians who used certain foods to treat medical illnesses. the common cold.12 In perhaps his best known statement.23 The following sections discuss these supplemental treatments in addition to pharmacological interventions for the major psychiatric illnesses. ~1%. minerals. To share or copy this article. and hair analysis of minerals. especially the optimum concentrations of substances normally present in the human body.”2 Orthomolecular psychiatry is a significant area of study today. studies have shown that populations. including the treatment of cancer. and the person who coined the term orthomolecular in 1969. beri-beri. 2.
and China) that do not treat their corn properly with an alkali agent to make niacin nutritionally available.36.25. Mexico. this disease had struck as many as 100 000 Southerners. B Vitamins.32 Pellagra reached epidemic proportions in the southern United States in the early 1900s. and other substances that individuals commonly consume as part of a balanced diet.31. and cognitive changes). Indonesia. Negative symptoms of schizophrenia are those in which decrease of normal sensation occurs. including the loss of the ability to experience pleasure. minerals. autonomic instability.37 The generation of PGD2 in response to niacin ingestion leads to vasodilation of blood vessels. The side-effect burden of both the first generation and atypical antipsychotics is the primary reason for treatment noncompliance in schizophrenic patients. thinking.com Schizophrenia One of the earliest areas of interest to the orthomolecular psychiatrist was the treatment of schizophrenia. such as chlorpromazine and haloperidol. becoming progressively worse as a function of time. please visit copyright. lack of or reduced emotionality. even to the degree that the symptoms are nearly indistinguishable. amino acids. and loss of motivation. with the symptoms typically divided into positive and negative. Interestingly. Many of these regions are a major target of pharmacotherapy and may also account for some of the orthomolecular effects. FALL 2012. and disorganized speech and behavior. To subscribe.25 Psychiatrists and physicians more frequently use the newer atypical antipsychotics because of their effectiveness and a reduced sideeffect burden. with doses of up to 30 g per day for schizophrenic episodes. whereas for schizophrenia a dose ranging from 1 to 6 g per day may be necessary. bipolar. Medical practitioners often consider pellagra.24 Positive symptoms are psychotic symptoms. 26. hallucinations. as is often the case with corn-cultivating societies (rural Africa. NO. VOL. dermatitis. visit advancesjournal. which interestingly match some of the early symptoms of schizophrenia. such as irreversible tardive dyskinesia (a movement disorder) and neuroleptic malignant syndrome (characterized by muscle rigidity. aggression. For pellagra. To share or copy this article. to be a well-suited model of schizophrenia.34 Such large doses of vitamin B3 are associated with side effects.35 They believe that the flush response. The medical community established special pellagra hospitals to help treat the disease. researchers have observed increased dopamine activity in certain brain regions of schizophrenic patients. and diabetes—and a reduced but nonnegligible risk of tardive dyskinesia and neuroleptic malignant syndrome.31 Pellagra typically develops over a period of 3 to 5 years. although psychiatrists and physicians still use older antipsychotics for specific indications and for cases in which atypical antipsychotics prove to be less effective in relieving symptoms. Use ISSN#1470-3556. Many symptoms in the two diseases28 are similar. 2 Zell—Psychiatric Disorders . which has triggered the search for new treatment approaches. Postmortem analysis of brain-tissue samples from control. are effective mainly at treating the positive symptoms of schizophrenia but do so at the risk of causing serious side effects. such as clozapine.27 In addition. including supplementation with various essential nutrients—vitamins. with changes in perception. although their pharmacology and side-effect profiles vary.26 Estimates of the lifetime prevalence of schizophrenia range anywhere from 0. and risperidone.This article is protected by copyright. observed upon the ingestion of niacin. Atypical antipsychotics have a distinctly different mechanism of action from the older antipsychotics. a vitamin deficiency most commonly caused by a chronic lack of niacin (vitamin B3) consumption.8% of the adult population worldwide. research has shown that niacin binds and activates a class of hydroxycarboxylic acid receptors referred to as HM74. personality problems. In many cases.25 The first generation of antipsychotic agents (termed typical antipsychotics). such as reversible liver damage.33 Medical practitioners often describe fullblown pellagra by the four progressive stages of diarrhea. results from the conversion of arachidonic acid to the prostaglandin D2 (PGD2) inside dermal macrophages.32 In 1937. weakness and/or paralysis of the extremities. Medical practitioners have used vitamin B3 for years to treat pellagra effectively. Schizophrenia is a mental disorder that affects the perception of reality. fatigue. and death. The development of pellagra is associated with the consumption of a diet that is lacking in niacin (vitamin B3). few physicians are familiar with this disease today.28 These supplemental treatments typically focus on megadoses of vitamin B3. and some orthomolecular physicians have proposed that practitioners also can use it as a supplemental treatment for many cases of schizophrenia due to the many similarities between the two diseases. such as delusions. By 1916. and eventually dementia. mostly acting on dopaminergic nerve transmission. The newer atypical antipsychotics. pose a much lower risk of tardive dyskinesia than the first generation antipsychotics but still have a relatively high side-effect burden—such as weight gain. which presents as the characteristic red skin flush observed with immediate-release drug formulations of niacin. Researchers now point to the involvement of niacin receptors in the development of schizophrenia. many antipsychotic drugs that are currently used are not able to resolve both the positive and negative symptoms of schizophrenia. the second of which is life-threatening and requires close monitoring of the patient.com. atypical antipsychotics lead to better compliance by patients. Other symptoms of pellagra that develop over time include mental confusion. and many other symptoms. The early symptoms of pellagra include depression. fever. and schizophrenic patients shows similar levels of the G-protein 16 ADVANCES. Conrad Elvehjem determined that the vitamin niacin treated pellagra in dogs. sertindole. hyperglycemia.30 Because the Western world mostly has eradicated pellagra. a discovery that led to the rapid elimination of this terrible but preventable disease.1% to 1. and mood occurring in both. insomnia. effective doses of vitamin B3 may be only 50 mg/day. dementia.38 Furthermore.29 The most pronounced difference between the two diseases is that pellagra typically produces changes in skin pigmentation.
24 Glutamate is the main excitatory neurotransmitter. bipolar. to disrupted DNA methylation. To share or copy this article.61 Another small. open trial evaluated the benefit of glycine supplementation of up to 60 g/day and showed a 20% to 30% reduction in negative symptoms compared to conventional treatment alone. NO. which produced few.com associated with the HM74 receptor in all the populations. and schizophrenics do not appear to benefit from its supplementation.55 Amino Acid Glycine.51. many of the clinical trials have suffered from poor trial design. visit advancesjournal.62 Research has shown that this enzyme is consistently present in lower amounts in schizophrenic patients.com. altered glutamatergic nerve transmission. Researchers have evaluated both niacin and the structurally closely related niacinamide in a number of clinical trials and meta-analyses that have had equivocal outcomes. 26.61 Interestingly. side effects. particular those affecting the emotions.57 Researchers have shown that high doses of glycine (~ 30 g) can help reduce some of the negative symptoms of schizophrenia. VOL. An additional orthomolecular supplement for schizophrenia has focused on the use of the amino acid glycine.53 the Western diet is commonly not deficient in this vitamin.56. which regulates both absorption of folate from the gut and glutamate activity at NMDA receptors. One drawback of glycine supplementation Zell—Psychiatric Disorders ADVANCES. please visit copyright.60 An open-label clinical trial conducted in 1996 evaluated the tolerability of glycine administration to schizophrenic patients at 0.52 Although Cruz and Vogel have suggested that pyridoxal phosphate (vitamin B6) deficiency may cause psychosis. specifically PGE2 and PGD2 from immune cells in the skin39 upon exposure to niacin. in addition to conventional therapy. such as small sample size.35. such as N-methyl-D-aspartate (NMDA) receptors.47-49 Some case-control studies indicate that schizophrenic patients show lower serum-folate levels due to chronic malnutrition and potential influences of antipsychotic medications on absorption.50 Researchers have shown that supplementation with methylfolate. which resulted in an insignificant number of studies on niacin supplementation being included in Kleijnen and Knipschild’s 1991 metaanalysis review. The receptors currently are an area of significant interest to the mainstream pharmaceutical industry because of the increase in brain glutamate concentration following atypical antipsychotic therapy.41 Understanding this altered response and using it to develop effective tools for diagnosing and treating schizophrenia are two of the goals of the studies that researchers currently are carrying out in this area.19. 17 of 18 bipolar patients. however.59. in schizophrenic patients. Interestingly. To subscribe. which medical practitioners commonly observe in schizophrenics. reduces positive and negative symptoms further in schizophrenic patients as compared to the reduction from conventional treatments alone. if any. E. This analysis. FALL 2012. with 17% of schizophrenic patients showing a skin reddening and elevated PGD2 blood levels compared to 77% of controls. and all of the healthy controls presenting with vasodilation. lack of randomization. activation of the latter occurs more easily. and high homocysteine level. 2 17 .45 Another vitamin that may improve both negative and positive symptoms in schizophrenic patients is folic acid. such as social and emotional withdrawal as well as apathy.36 Morrow et al have observed this difference in a skin-flushing test after participants’ exposure to dermal methyl nicotinate. Use ISSN#1470-3556.54 Therefore.19 Research also suggests that genetic differences in schizophrenic patients involve the altered expression of glutamate receptors.19 This study demonstrated both a significant increase in glycine blood levels and a significant reduction in negative symptoms using the SANS (Scale for the Assessment of Negative Symptoms).This article is protected by copyright. and researchers have linked both altered glutamate neurotransmission and hypoexcitability of glutamatergic receptors to the development of positive and negative symptoms in schizophrenic patients. all of which are potential contributors to the exacerbation of positive and negative symptoms in schizophrenia. a relationship exists between low brain folate and low glutamate levels through the enzyme glutamate carboxypeptidase II (GCPII). although the data are inconsistent.35 Because niacin is less specific to and binds less easily with HM74 than HM74A. researchers frequently do not observe the skin-flush response that the administration of niacin typically induces. and altered activation frequently relates to the development of the negative symptoms in schizophrenia.45 Vitamins C. Some small clinical trials and a number of case reports showed an improvement in psychotic symptoms for participants receiving supplementary doses of 3 to 8 g/day of nicotinamide in addition to conventional antipsychotic medication as opposed to participants using only conventional drugs. E. explaining the absence of the skin reddening. and β-carotene. and the omission of a control group receiving a placebo. Another study examined niacin-induced and PGD2mediated vasodilation in schizophrenic. such as vitamins C. and normal control patients with 16 of 28 schizophrenic patients. orthomolecular psychiatrists and physicians may ameliorate symptom worsening with antioxidant supplementation.36 This difference indicates that the lower expression of HM74A niacin receptors in schizophrenic patients links to reduced PGD2 levels. also reveals a significantly reduced level of a protein associated with the closely-related HM74A receptor in schizophrenic patients. which might influence the development of schizophrenic symptoms. and β-carotene. A strong correlation exists between the worsening of schizophrenic symptoms and oxidative stress due to abnormalities in specific antioxidant systems that are related to mitochondrial function as well as to excitatory and inhibitory neurotransmission.8 g/kg and showed that they could safely tolerate high levels of glycine.46 Researchers have linked folic-acid deficiency. HM74A mediates synthesis of prostaglandins.42-44 While a subset of schizophrenic patients have shown benefits from supplementation with niacin.58 Glycine activates excitatory glutamate receptors.40 The role of HM74A in schizophrenia is currently not well understood and is the subject of much research.
and psychiatrists have prescribed it in the United States since the 1970s. is the prototypical mood stabilizer. with reductions in akathasia (restlessness) and the side effects of antipsychotic treatments.68 Another study conducted in Denmark revealed that the prognosis for schizophrenic patients is better in countries that have a high consumption of omega-3 fatty acids in their diets. Taking more than one medication can especially lead to unbearable side effects. participants who were taking clozapine benefited the most from EPA supplementation in terms of reduction in symptoms and side-effect burden. in conjunction with prescribed pharmacological treatments. in which the person will experience an increase in their energy level. suggest that omega-3 fatty acids may have a role in the supplementation of current pharmacological treatments for schizophrenia. FALL 2012. visit advancesjournal. loss of interest in pleasurable activities.79 One of the difficulties in the treatment of bipolar disorder is that bipolar patients will experience significant depressive episodes. Another study was not able to support the supplementation with ethyl-EPA for the treatment of residual schizophrenic symptoms in patients already on medication. Use ISSN#1470-3556. As with schizophrenia.73. Other studies. please visit copyright.72. The symptoms of these depressive episodes are similar to those of major depression. and gabapentin. were superior in reducing the symptoms of schizophrenia compared to pharmacological treatments alone.79 Treatment of these depressive episodes with either tricyclic or selective serotonin reuptake inhibitor (SSRI) antidepressants can induce either mania or hypomania. such as rats64and is also one hypothesis for the development of schizophrenia.com is the high daily dose of 30 to 60 g/day.66 Researchers have observed a better outcome for schizophrenic patients with a higher daily consumption of fish and seafood. is responsible for lowering levels of brain-derived neurotrophic factor (BDNF) in the hippocampus of animals.79 The prevalence of bipolar disorder in the United States is around 3. Psychiatrists typically use most mood-stabilizing medications in the treatment of bipolar disorder to control mania or hypomania. including ongoing feelings of sadness. prototypical of the diets in most industrialized nations. To share or copy this article. treatment noncompliance is typically a result of the high side-effect burden of pharmacological treatments.63 Molteni et al have demonstrated that a diet high in both saturated fat and refined sugar. mood disorders. carbamazepine.com.79 The more disabling features of bipolar disorder are the depressive episodes that may occur. growth. To subscribe.80 Bipolar disorder is one of the most complex psychiatric illnesses to treat because of the multicomponent nature of the disease. Omega-3 Fatty Acids.78 The current scientific literature indicates that supplementation with omega-3 fatty acids may benefit patients in the early stages of the disorder—specifically. despite its multiple side effects.79 A manic or hypomanic episode is a period either of extremely elevated or irritable mood. 2 Zell—Psychiatric Disorders . and differentiation of neurons and synapses in development and throughout life.65.67 In two clinical trials.63 This research demonstrated that a diet high in sugar and saturated fat is correlated with worse outcome measures for schizophrenic symptoms.5%. a combination of EPA and DHA supplementation with vitamins C and E showed significant improvements over the course of 4 months in schizophrenic symptoms in drug-naïve and medicated patients. numerous treatments for depressive episodes in bipolar patients are currently available. and a number of additional studies have confirmed that finding. treatment-refractory schizophrenic patients—who in addition to antipsychotic medication also received 1 to 4 g/day of ethyl-EPA.77 Interestingly. those on clozapine treatment— and that orthomolecular psychiatrists and physicians should recommend supplementation based on the general health benefits that omega-3 fatty acids provide. racing thoughts. that plays a central role in the maintenance. all of which pharmaceutical companies and academic research groups primarily developed for the treatment of epileptic seizures but which research has shown also have mood-stabilizing properties. as lithium carbonate or another comparable lithium salt.76.67 BDNF is a protein in the neurotrophin family. and possible suicidal thoughts. The impact of diet on many disease symptoms is often not well understood.This article is protected by copyright.79 while they often use lithium. Bipolar disorder or manic depression is a mood disorder in which people experience both periods of elevated mood (mania in bipolar I disorder and hypomania in bipolar II disorder) and periods of depression. and schizophrenia. 18 ADVANCES. 26. causing the patient to stop taking his or her medications and leading to a relapse of symptoms. and the atypical antipsychotics specifically to control the depressive symptoms of bipolar disorder. VOL. and a reduction in the need for sleep. which is impractical in terms of patients’ compliance. Lithium. NO.70-72 Other studies have suggested that doses of up to 2 g of EPA.74 In another larger clinical study. Researchers have observed suicide rates as high as 10% in bipolar populations. Other mood stabilizers include valproic acid. or a placebo—showed significant improvement with ethyl-EPA supplementation compared to placebo. is helpful in the treatment of depression. a precursor of EPA. Bipolar Disorder A second disease state of interest to the orthomolecular psychiatrist is bipolar disorder.75 The researchers observed the largest improvement with a daily dose of 2 g of ethyl-EPA. however. lamotrigene. a component of omega-3 supplements.69 Some studies have shown that eicosapentanoic acid (EPA). Peet has investigated the relationship between diet and outcome measures related to schizophrenia. but research has not demonstrated them as adequate for use as stand-alone treatments. located in the central and peripheral nervous system. however. Suicidal thoughts are of specific concern in patients suffering from bipolar disorder because the manic period might actually stimulate the execution of these thoughts.
NO. and a relationship between hyperthyroidism and the development of bipolar disorder appears to be likely. while omega-3 fatty acids aid in membrane fluidity and receptor function. enhance BDNF.89 Orthomolecular physicians recommend supplements containing the B vitamins (vitamin B complex) for the supplemental treatment of bipolar disorder. B Vitamins.84 Vanadium is thought to cause both mania and depression through the generation of reactive oxygen species (ROS) in specific brain regions.90 Omega-3 Fatty Acids. as well as a number of sexual impairments. in addition to pharmacological treatments. lack of motivation to perform simple tasks or movements. To subscribe. Tryptophan is a precursor in the synthesis of serotonin. do not involve it as an endogenous (internally derived) substance. FALL 2012. a loss of interest in daily activities.19 Psychiatrists and physicians know that B vitamins can both prevent and aid in the treatment of depressive disorders based on their function as cofactors in the synthesis pathway for neurotransmitters and other signaling molecules. The theory behind the use of the omega-3 fatty acids is that brain cells require these oils to aid in the transmission of signals that regulate thought processes. please visit copyright.com Orthomolecular supplements for bipolar disorder include vitamin C. and amitriptyline.81 They often recommend 100 to 200 mg/day of vitamin B6. doxepin. akathisia (general restlessness and discomfort).92 Specifically. These supplements include the use of several amino acids (tryptophan.98 SSRIs—such as fluoxetine.95. the amino acid taurine. Additionally. the minimization of stimulants such as caffeine and elimination of foods that may be causing food allergies may also aid in reducing symptoms. omega-3 fatty acids. Vitamin C. According to the National Institutes of Mental Health. insomnia. hyperactivity. and emotion. to be orthomolecular treatments.94 Physicians have now widely accepted this practice. and 300 to 600 μg/day of vitamin B12. 200 μg/day of vitamin B9. orthomolecular physicians commonly evaluate a patient for thyroid function prior to reaching a diagnosis of bipolar disorder.72. omega-3 fatty acids are commonly reduced in the Western diet. 26. drowsiness. Side effects of the SSRIs are milder but include headache.93 Thyroid Hormones. mood. such as irritability.93 As mentioned previously. These symptoms may last for short periods of time and subside or may last for periods of many years. phenylalanine. VOL. Researchers have estimated that up to 80% of bipolar patients have a deficiency in one or more of the B vitamins. orthomolecular psychiatrists typically do not consider lithium to be an orthomolecular treatment since the natural processes in the central nervous system (CNS). and reduce inflammatory processes through modulation of the arachidonic acid cascade. most notably St. tyrosine. and thoughts of death or suicide. since the 1950s for the treatment of depression as well as for other conditions such as insomnia and generalized anxiety disorder.19 Supplementation with amino acids serves the purpose of increasing neurotransmitters that are directly involved in mood disorders (dopamine. omega-3 fatty acids aid in membrane fluidity and receptor function.87 Taurine. and it has a calming effect.97 The symptoms of major depression include very low mood with feelings of sadness or hopelessness. Orthomolecular psychiatrists also commonly recommend the omega-3 fatty acids for supplementation in bipolar disorder. The liver produces it. hyperthyroidism is a condition that orthomolecular physicians think causes symptoms similar to those of bipolar disorder.91. A wide range of orthomolecular supplements are available for depression. sufficient tryptophan intake in the diet Zell—Psychiatric Disorders ADVANCES. and omega-3 fatty acids. such as nerve transmission and receptor function. John’s wort. visit advancesjournal. is withdrawal effects that require a slow tapering off of the drug. although clinical data is lacking to date. Because serotonin deregulation seems to contribute to the development of depressive symptoms and SSRIs are effective.86 A double-blind. norepinephrine.com. such as imipramine.85 Vitamin C is a potent antioxidant and is useful for protecting the body from the damage that elevated levels of vanadium cause through ROS scavenging activities. which is more prominent with SSRIs. changes in appetite that cause either significant weight loss or gain.81-83 Despite lithium carbonate being a naturally occurring compound. Researchers have reported that bipolar patients have high levels of vanadium. and methionine). placebo-controlled study showed that 3 g of vitamin C were effective at controlling vanadium levels and decreasing manic symptoms.88 Researchers have hypothesized that deficiencies in taurine intake may be responsible for the manic episodes that bipolar patients experience. the yearly incidence of patients suffering from a major depressive disorder is approximately 5% or 17 million people in the United States. and magnesium. 2 19 . Amino Acids.99 One additional difficulty of antidepressant use.98 Psychiatrists and physicians have used tricyclic antidepressants. Depression Major depressive disorders are a significant medical problem in the United States. and an increasing number of clinical trials in bipolar patients indicates that supplementation with these essential compounds alleviates both manic and depressive symptoms. Use ISSN#1470-3556. to correct for this deficiency. the B vitamins. and serotonin).100 Orthomolecular physicians do not consider the herbal treatments that complementary and alternative practitioners have used with some success to treat depression. Finally. and depression.This article is protected by copyright. Taurine is a derivative of the amino acid cysteine. To share or copy this article. Because several of the symptoms of hyperthyroidism overlap those of bipolar disorder.96 Balancing the thyroid hormones may reduce the mood problems that led to the diagnosis of bipolar disorder and may lead to a reduction in mood-stabilizing medications. and paroxetine—generally have replaced tricyclic antidepressants. sertraline. insomnia or hypersomnia.84. the B vitamins.
112 If membrane fluidity is compromised.114 Clinical trials have evaluated the potential benefit of omega-3 fatty acid supplementation on depression. avoidance. which research has shown prevents depressive symptoms.115. are also essential factors for normal serotonergic functioning.121-124 Magnesium.4 mg/day of vitamin B12 may be beneficial in the treatment of depression. therefore. to be an essential amino acid. and the development of depression. methylenetetrahydrofolate reductase and methionine synthase.8 mg/day of folic acid or 0. visit advancesjournal.90 Studies on nutritional intake of B vitamins suggest that either 0. FALL 2012. The precursor tryptophan.100.100 A cross-sectional Finnish study in men also concluded that high folate levels prevent or reduce the incidence of depression. have antidepressant properties. in conjunction with standard antidepressant pharmacotherapy.119 Researchers have postulated and some research has found a link between elevated homocysteine levels. as well as the signaling cascade. and despair— which all are characteristic of depressive and anxiety disorders and which application of antidepressants and anxiolyt- 20 ADVANCES. In addition. DHA provides the fluidity of cell membranes and is especially important for neuronal development. To share or copy this article. Cofactors can be organic or inorganic compounds that often require supplementation in the diet. Research has shown a link between low levels of folate (vitamin B9) and the development of depression. and enzymatic activities. it is a contributor since supplementation with DHA alone does not result in normal brain development and function.19 Researchers also believe that tyrosine increases dopamine levels. prostaglandins. Cofactors are nonprotein compounds that are necessary for a protein (often an enzyme) to perform its function. Both folic acid and methyl-vitamin B12 are cofactors. which are components found in most supplements of omega-3 fatty acids. in combination with standard antidepressant treatment. upon the loss of a terminal methyl group that is essential for various C1 transfer cycles. and psychosis in vitamin B deficiencies to the vitamins’ critical roles as enzymatic cofactors in the biosynthesis pathway of neurotransmitters. hormones. dementia. confusion. which has an impact on mood. and differentiation. Researchers have shown that doses of 1. leukotrienes. namely epinephrine.117. the receptor response to binding of serotonin or epinephrine is also reduced. VOL. these molecules are necessary for development. Omega-3 Fatty Acids. orthomolecular psychiatrists think that omega-3 fatty acids and their metabolites (including thromboxanes.This article is protected by copyright. to the development of depressive disorders through dysregulation of neurotransmitter synthesis. and metabolic functions. such as epinephrine and DNA synthesis. Use ISSN#1470-3556. because folate plays a central role in cell and tissue growth. growth. via the enzyme methionine synthetase.com contributes to adequate production of serotonin. however. increases in their synthesis via supplementation are important approaches in orthomolecular treatment. receptor function. supplements containing tyrosine increase arousal and alertness and help to alleviate stress by increasing the production of epinephrine.125 Several animal models of depression and anxiety have demonstrated that hypomagnesemia can lead to defensive behavior—aggression.106-108 Orthomolecular physicians believe that both EPA and docosahexanoic acid (DHA). The vitamin B complex is very important for the maintenance of the normal function of the brain and nervous system. in the metabolism and degradation of homocysteine back to methionine.106 Due to the essential contribution of DHA and EPA in building and maintaining cell membranes by integration as phospholipids.116 B Vitamins. NO. To subscribe.111 For supplementation in depression.104.0 g of omega-3 fatty acids can decrease depressive symptoms and improve mood.110 and play a vital role in brain development before and after birth. was successful in resolving depressive symptoms within 7 days for many patients when compared to pharmacotherapy alone.101-103 Enzymes active in serotonin biosynthesis. dopamine. since the body can synthesize it from phenylalanine. during regeneration of vitamin B12 (Figure 1).126 Szewczyk et al found that treatment with 125 to 300 mg of magnesium glycinate or taurinate with meals and at bedtime.com. please visit copyright. social withdrawal. 2 X Zell—Psychiatric Disorders . another important compound in the biosynthesis of serotonin. such as in states of malnutrition related to omega-3 fatty acids. and differentiation of cells109.105 Since mood and reward involve all monoamine neurotransmitters. While the role of EPA is not as clear.5 to 2. Most of the currently available pharmacological treatment strategies also target neurotransmitter concentrations in the CNS. via the enzyme S-adenosylmethionine (SAM) synthetase. and a review concluded that patients benefit from combined supplementation with DHA and EPA in doses of 1 to 2 g/day. converts predominantly into serotonin. Researchers also have linked magnesium deficiencies to depression. which play a vital role in homocysteine and C1 metabolism. Decreases in the amount of omega-3 fatty acids in the Western diet appear to correlate strongly with an increase in the incidence of depression.120 Impaired C1 metabolism might contribute. when taken on an empty stomach. and serotonin. development.113 Indications also exist that omega-3 fatty acids directly interfere with serotonin neurotransmission and metabolism by increasing the serotonin metabolite 5-hydroxyindoleacetic acid. Researchers have linked observations of mood disorders.118 A cohort study conducted over the past 10 years evaluated the association between folate and vitamin B12 intake in a sample of over 9000 participants and established a lower prevalence of depression in men with high folate and in women with high vitamin B12 intake. via their respective receptors in the CNS. Methionine generates homocysteine. and phospholipids) contribute to the delicate homeostasis of membrane fluidity and maintenance of optimal neurotransmitter and inflammatory receptor function. Researchers do not consider tyrosine. 26.125. Several studies found a relationship between low folate and vitamin B12 levels with polymorphisms in genes encoding for two enzymes. the metabolite of the essential amino acid methionine. however. researchers have linked low folate serum levels to several neurodegenerative and cardiovascular disorders as well as to a higher incidence of breast and ovarian cancer in women.
Regulation of GSK-3 is also coupled with BDNF gene expression through a negative feedback loop. Furthermore. Abbreviations: NADPH. which might indirectly reduce glutamatergic NMDA receptor activity through downregulation of the enzyme glycogen synthase kinase-3 (GSK-3). C1 Metabolism The figure shows utilization of vitamin B12 and folic acid in the methyl-transfer for the biosynthesis of deoxy thymidine monophosphate (dTMP) from deoxy uridine monophosphate (dUMP). To subscribe.138 Research has shown that lithium and magnesium inhibit the activity of GSK-3 through competitive action. 2 21 . is dysregulated in depressive disorders. with enhanced BDNF gene expression leading to reduced GSK-3 activity (Figure 2). FALL 2012. NO. Nicotinamide adenine dinucleotide phosphate. please visit copyright. Alzheimer’s disease. such as through the NMDA and AMPA receptors. To share or copy this article.130-135 Researchers have linked the mechanisms underlying the antidepressant activities of magnesium to an increase in BDNF gene expression. S-adenosyl methionine. and schizophrenia.com Figure 1.com.136 and which might have a direct inhibitory effect by magnesium itself on NMDA receptors (Figure 2). leading to hyperexcit- X Zell—Psychiatric Disorders ADVANCES.137 GSK-3 is a serine/ threonine kinase enzyme that is involved in a number of phosphorylation reactions leading to inactivation of various signaling molecules that researchers have implicated in the development of depression. visit advancesjournal. which may contribute to their antidepressant effects. glutamatergic activity. but research indicates that patients suffering from depressive disorders benefit from magnesium supplementation in addition to the standard antidepressant treatment.This article is protected by copyright. SAM.127-129 Human data show inconsistencies with regard to the relation between low serum magnesium levels and acute forms of depression and anxiety disorders. Use ISSN#1470-3556. bipolar disorder. The related methionine and homocysteine cycle contributes to the recycling of vitamin B12. ics can reverse. VOL. leading to better compliance by patients and reduced doses of pharmacotherapy. 26.
and interferon-γ levels. findings of deficient levels of zinc in depressed patients is quite common. ability of specific neurons that regulate normal synaptic transmission. Researchers have shown an enhanced gene expression of BDNF with suppression of NMDA receptor activity as well as a direct inhibitory effect of zinc on the NMDA receptors in animal and in vitro studies. Influence of Magnesium (Mg2+) and Zinc (Zn2+) on Various Receptor Systems in the Central Nervous System (CNS) Abbreviations: NMDA. 5-HT.139 Research has shown that magnesium.141. please visit copyright. FALL 2012. Magnesium enhances the effect of serotonin on 5-HT1A receptors140 and serves as a cofactor for the critical enzyme tyrosine hydroxylase in the biosynthetic pathway leading to serotonin synthesis. zinc is an agonist at the glutamatergic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid 22 ADVANCES.143-145 Both the effects of antidepressants on zinc levels in the CNS. tricyclic antidepressants. with both an acute phase and a long-lasting alteration in circulating cytokine. Brain-derived neurotrophic factor. although researchers have shown this activity only in vitro. VOL. Notes: Dotted line is proposed interaction. NO. showing a higher rate of responders in animals. To subscribe. can increase the antidepressant effect. Similar to magnesium.147-149 In addition. for the supplemental treatment of depression. Glycogen synthase kinase 3.81. and the fluctuations in serum zinc levels between depressed and nondepressed groups in animal experiments. prostaglandin. in conjunction with antidepressants that act on serotonergic neurotransmission. bold line is significant interaction.142 Orthomolecular physicians commonly recommend 50 mg/ day of zinc. and researchers have speculated that a chronic inflammatory response might also play a role in several forms of depression. suggest a significant influence of zinc in the mechanism of depressive disorders. visit advancesjournal. BDNF. To share or copy this article.125 They often use zinc for the treatment of immune-related illnesses.This article is protected by copyright. TCAs.142. GSK-3. Use ISSN#1470-3556. 146 The mechanisms involved in the antidepressant effects of zinc are similar to but distinct from those of magnesium (Figure 2).com Figure 2. AMPA. and regular line is interaction. α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate. 26. in the form of zinc gluconate lozenges.127 Zinc. selective serotonin reuptake inhibitors. 2 Zell—Psychiatric Disorders . 5-hydroxytryptophan.81. N-methyl-D-aspartate. SSRIs.com.
researchers have also seen diet as a factor that might influence the symptoms of the disorder. C. orthomolecular psychiatrists have advocated the use of SSRIs and other antidepressants. supplementation with zinc may normalize dopamine transporter function and restore dopamine nerve signaling. serves as a competitive inhibitor of GSK-3. clinical rating scales such as the Hamilton Anxiety & Depression (HAD) scale aid the physician or psychiatrist in reaching a conclusive diagnosis. 26.170 Zinc serves as a potent noncompetitive blocker for dopamine at its transporter.18 The diagnosis of GAD may be quite complicated because of the wide range of relatively nonspecific symptoms.156 The current approaches to treatment of ADHD center on the successful use of psychostimulants.160-162 Omega-3 Fatty Acids. please visit copyright. vitamin C. researchers observed improved attention and learning and decreased behavioral afflictions. Research has shown that a critical enzyme in fatty acid metabolism.165 Researchers have conducted a number of clinical trials that either have supplemented DHA and EPA in addition to the standard drug regimen or have given the omega-3 fatty acids only. To share or copy this article. is operating less efficiently in many children and adults with ADHD symptoms. vomiting. VOL. and therefore.173 Orthomolecular physicians have used numerous supplements for the treatment of GAD. compared to a placebo.com (AMPA) receptor. studies suggest that zinc deficiencies are common among children and adults diagnosed with ADHD. visit advancesjournal. Although only observed in a few clinical trials. irrational worrying about something that is viewed to be out of proportion to the cause of the worry and causes significant impairment in daily functioning. 168 and supplementation with zinc might alleviate some ADHD symptoms.154 The pathophysiology of ADHD is not well understood.116 Zinc. and magnesium.158. Lepping and Huber have proposed that zinc deficiency decreases dopamine nerve signaling via overactivity of the dopamine transporter. but researchers have postulated genetic. To subscribe. inositol.18 GAD is characterized by excessive. to ADHD. but researchers do not completely understand the mechanisms by which these drugs cause behavioral changes and influence neurotransmitters (primarily dopamine and norepinephrine). Other symptoms of GAD may include nausea. EPA. with either one or both predominant in the observed symptoms.157 In addition.152 Attention Deficit Hyperactivity Disorder Mostly occurring in children but increasingly identified in adults as well. These include calcium and magnesium. which is difficult or impossible for the patient to control and which occurs on most days over a time period of at least 6 months. environmental.154 The causes of ADHD are not clear. like magnesium. especially in the centers for motivation and executive function.125. which in turn enhances BDNF gene expression. B6.164. One of the most promising areas of an orthomolecular approach to reducing ADHD symptoms is the use of omega-3 fatty acids. and impulsivity persist for at least 6 months and are above the normal level for the same age group.172 The approaches to clinical treatment for GAD include the use of the tricyclic (imipramine) and SSRI (fluoxetine and paroxetine) antidepressants and of benzodiazepines (diazepam and midazolam) as well as of other drugs. inattention. but researchers have hypothesized that the contributing factors are improvement in membrane fluidity and CNS plasticity and a decrease in circulating inflammatory markers.150 Zinc. The outcome of behavioral studies and ratings is mixed in these studies.163 Several studies have reported reduced levels of omega-3 fatty acids in the blood of children with behavioral and learning disorders.171 Thus. and dietary factors as possible contributors.81. In adults treated with a combination of omega-3 fatty acids (EPA and DHA) as well as with the omega-6 fatty acid gamma-linolenic acid (GLA) over the course of 3 months. fatty acid desaturase. such as dextroamphetamine and methylphenidate. Zinc serves as a cofactor in fatty acid metabolism and in the generation of endogenous DHA.111.169.116 Generalized Anxiety Disorder Generalized anxiety disorder (GAD) is one of the most common anxiety disorders and affects 3. is essential in the termination of dopaminergic nerve signaling. According to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) the criterion that must be met for a diagnosis of GAD is excessive worrying. 2 23 .174-176 Calcium. the B vitamins.116 Some of the studies showed a benefit if the researchers gave omega-3 fatty acids only.159 Researchers have evaluated numerous orthomolecular supplements for use in ADHD. NO. similar to their treatment of depressive disorders.166 The underlying mechanisms for DHA and EPA supplementation in ADHD are not well understood. Use ISSN#1470-3556. and stress may lead to low levels Zell—Psychiatric Disorders ADVANCES. such as buspirone and pregabalin. attention deficit hyperactivity disorder (ADHD) is one of the most prevalent neurological impairments during childhood with 6% to 9% of children and adolescents as well as 3% to 5% of adults being affected.167. Since the discovery of ADHD in children and adolescents. but the effectiveness diminished if the researchers gave omega-3 fatty acids as an add-on to the regular stimu- lant treatment.This article is protected by copyright.155 A physician can diagnose a child with ADHD only if the symptoms of hyperactivity.1 % of the population in the United States. but researchers have linked changes in the prefrontal cortex. and stomach pain as well as trembling or being startled easily. Orthomolecular physicians consider calcium to be a natural tranquilizer. namely EPA and DHA.com. FALL 2012. Other studies also have supplemented omega-6 fatty acids in adults. which all work through different mechanisms.172 As with depression and bipolar disorder.153 Inattentiveness and a lack of focus on everyday tasks characterizes it as does hyperactive and impulsive behavior. and zinc.151. with a trend toward beneficial effects in children who received supplemental omega-3 fatty acids over a period of at least 2 months. and GLA as do vitamins B3.
but the individual circumstances of the patient require close monitoring. although the field requires additional research to establish reliable dosage ranges and effectiveness for these recommended treatments. which results from long-term malnutrition or environmental stress factors that deplete vitamin B3.com of calcium in the body. has antianxiety and calming properties similar to those of benzodiazepines in doses of up to 2. Vitamin C. and reversal of these changes occurs with calcium supplementation.183. many well-designed clinical studies have provided evidence for the involvement of nutritional deficiencies and supplementation in the development and treatment of psychiatric disorders. Epidemiological studies have shown the interrelationship between depressive and anxiety disorders. a structurally.180 Magnesium. the treating health-care professional has to inform the patient that symptom improvement 24 ADVANCES.185.179 It is yet unclear how supplementation with calcium would affect this activity. initial results show the benefits of supplementation with certain vitamins.81 A few animal studies have provided scientific evidence for such an effect. Furthermore. it has a tranquilizing effect and helps to reduce stress. and in large doses. and muscle spasms.178 Calcium influx via voltage-gated calcium channels serves as a trigger for the release of several excitatory and inhibitory neurotransmitters from presynaptic storage vesicles. insomnia.131. researchers have not studied the role of zinc in anxiety disorders very well.186 Niacinamide does not have the same pharmacological effects as niacin.177 Calcium is an important intracellular second messenger that is involved in a number of signaling pathways as well as in mitochondrial processes that energy maintenance of the cell requires. This action prevents the release of the excitatory neurotransmitter glutamate.125 Animals supplemented with magnesium showed anxiolytic-like behaviors in models of anxiety.5 g/day.176. such as controlled clinical trials. visit advancesjournal.81. with a high correlation between the development of depression as a secondary illness to anxiety disorders.81 They often prescribe doses of 5 to 10 g due to the perceived calming effect of vitamin C. but only after chronic exposure to the mineral.or hypermagnesemia. to evaluate orthomolecular supplements as adjuvant therapies in conjunction with modern pharmacological treatments. nervousness. such as lowering blood lipids and vasodilation. magnesium is a mineral that the orthomolecular psychiatrist uses to aid in the relief of anxiety. Orthomolecular psychiatrists also have used zinc as a treatment for GAD. 26.This article is protected by copyright. including their effectiveness in the supplemental treatment of psychiatric disorders. although the disorders were not related specifically to either hypo. Table 1 summarizes the suggested dose ranges for some of the investigated orthomolecular supplements and psychiatric conditions.com. minerals. To subscribe. and researchers have shown that vitamin C can serve as a memory enhancer as well as reduce anxiety in mice. NO. The orthomolecular psychiatrist typically recommends magnesium in combination with calcium at doses of 600 to 1000 mg/day. Typical doses of calcium for supplementation in GAD are up to 2000 mg/day.81 Case reports have suggested that niacinamide. Researchers consider vitamin C to be necessary to the proper functioning of both the adrenal gland and the maintenance of brain chemistry.188. Although further evidence in larger clinical studies is necessary.140 A vitamin B complex taken at the recommended daily dose is useful in maintaining the proper functioning of the CNS.187 Zinc. in addition to depressive disorders. Pregabalin is a relatively new treatment option for generalized anxiety disorder and acts as an inhibitor of calcium channels located on presynaptic nerve terminals by reducing the influx of calcium. conclusions Orthomolecular medicine is an alternative approach that an increasing number of physicians and allied healthcare professionals are using because of a concern with the therapeutic limitations and side-effect burden of current pharmacological treatments.182 B Vitamins. which counteracts the anxiolytic effects of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) at its receptors.189 In contrast to depressive disorders. unlike its immediate antidepressant effects. thus.181 Some indications point to an abnormal magnesium concentration in patients suffering from psychiatric disorders. and amino acids as well as fatty acids.184 Regarding the effectiveness of niacinamide in treating anxiety symptoms in certain patients. This article intended to summarize the most common orthomolecular approaches to treatment that have appeared in the published scientific literature. although some animal experiments show a behavioral change in response to calcium withdrawal (decreased social interaction and increased avoidance behavior).81 The scientific data are sparse for confirming the direct anxiolytic activities of calcium. A recent study in women evaluated serum calcium and magnesium levels and concluded that the odds of developing depressive or anxiety disorders are greater in women who have low levels of magnesium as well as a low ratio of calcium to magnesium compared to women with normal magnesium levels and calcium to magnesium ratios. closely-related compound of vitamin B3 (niacin). To share or copy this article. respectively. As this article has mentioned previously. please visit copyright. researchers propose as one theory that these patients may have a vitamin-B3 dependency. The use of orthomolecular treatments is promising for many psychiatric disorders and may lead to patients’ heightened compliance. it does not cause the skin to flush. FALL 2012. 184 Niacinamide also has shown anxiolytic-like activities in animal models of anxiety. with the hypothesis that it might exert some of its activity as a ligand at the benzodiazepine binding site on GABAA receptors. 2 Zell—Psychiatric Disorders . The medical community is slowly accepting the research on orthomolecular supplements as researchers use more rigorous methods of testing. Orthomolecular physicians have used vitamin C in the treatment of GAD. Use ISSN#1470-3556. In recent years.176 They use doses of 50 to 80 mg/ day due to a supposed calming effect that zinc may exert on the CNS. The B vitamins are a mainstay of the orthomolecular approach as a supplement for GAD. tension. VOL.
8 mg 0. orthomolecular approaches may also be associated with side effects. Furthermore. especially when prescribing very high doses. a need for lower doses of conventional pharmacological agents.5 g 5-10 g 50-80 mg References 34 19 71. An individual’s genetic uniqueness provides for a wide variety among individuals in metabolic activities. and better treatment outcomes for patients. antipsychotics. please visit copyright. and Reference Source for the Discussed Psychiatric Disorders Indication Schizophrenia Orthomolecular supplement Vitamin B3 (Niacin) Glycine Omega-3 fatty acids (EPA) Vanadium Bipolar disorder Vitamin B6 (pyridoxine) Vitamin B9 (Folic acid) Vitamin B12 (Cyanocobalamin) Tryptophan Omega-3 fatty acids (EPA.2 mg 03. such as antidepressants.com. VOL. Orthomolecular Supplements. visit advancesjournal. If the patient’s initial evaluation and diagnosis shows an imbalance in nutrients. Zell—Psychiatric Disorders ADVANCES. Use ISSN#1470-3556. receptor functions. take opposing sides) but should consider the overall benefit of the combined approach for the patient.-0. in addition to pharmacological therapy. since psychiatric disorders. 192. 193 84 81 90 90 102.6-1 g 2. 176 ments. 103 106 100.190. To share or copy this article. If nutrient supplementation. The scientific basis for the use of orthomolecular nutrients mainly relates to supplementation of traditional treatDaily dosage 1-6 g 30 g 2g 3g 100-200 mg 0. 2 25 . 118 100 125 81. whereas they may be beneficial in conjunction with pharmacological therapy if more severe symptoms are present.5-2 g 0. 117. The medical community should not approach the discussion of the use of orthomolecular nutrients in the treatment of psychiatric disorders as controversial (ie. 170 81 125 184 81 81. NO. FALL 2012. To subscribe. DHA) Depressive disorders Vitamin B9 (Folic acid) Vitamin B12 (Cyanocobalamin) Magnesium Zinc Attention deficit and hyperactivity disorder DHA (omega-3 fatty acid) EPA (omega-3 fatty acid) GLA (omega-6 fatty acid) Zinc Calcium Magnesium Anxiety disorders Vitamin B3 (Niacinamide) Vitamin C (Ascorbic acid) Zinc may take weeks after treatment initiation due to the slow adjustment of the affected systems in the body. Suggested or Studied Daily Dosage. require application of the best pharmacological therapy practice. Another important factor that affects the development of psychiatric disorders as well as their various treatment approaches is biochemical individuality. and changes in biological processes over time as aging occurs. the psychiatrist may consider orthomolecular approaches to treatment as a stand-alone treatment in mild cases. 125 116 116 116.191 Orthomolecular physicians have to consider initial measurements of nutrients in the blood—age has a profound effect on the concentration of various nutrients—and the individual’s treatment regimen and doses for orthomolecular therapy.6 mg Not known 1. This latency period is similar to that observed for many pharmacological treatments. especially severe cases. and anxiolytics. 26. the medical community should consider it on a patient-by-patient basis.com Table 1. 166 169. leads to reduced side effects.This article is protected by copyright.4 mg 125-300 mg 50 mg 480 mg 80 mg 60-96 mg 55-150 mg 2g 0.
2009. Vieira KF.98(5):812-815. 1992. 2001. 1968. Varying the concentrations of substances normally present in the human body may control mental disease. controlled trial. III. Nicotinamide in the treatment of schizophrenia. 42. Sutherland J. Nutrition classics. 2001. 36. Ferraguti F. 1996.24:677-736. 44.70(4):417-422. Studies of niacin requirement in man. Int Z Klin Pharmakol Ther Toxikol. Christensen O. Kleijnen J. 3. Goldsmith GA. Brain Res Bull. refined sugar diet reduces hippocampal brain-derived neurotrophic factor. Proc Natl Acad Sci U S A. MDCCLIII. 2006.16(9):797799.41(5):439-449. 27. 51. Casimir Funk: his discovery of the vitamins and their deficiency disorders. Reichardt LF. Br J Psychiatry.128(1-3):7-14. Zukin SR. Tanskanen A. Carney MW. 1967. Psychiatric agriculture: systemic nutritional modification and mental health in the developing world. Pandey SK. 1996. Megavitamin and dietary treatment in schizophrenia: a randomised. Nutritional therapies for mental disorders. 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