The Impact of Supplementation With Multi-vitamins/Minerals, With and Without Fatty Acids, on Impulsivity and Aggression
Condition: Aggression
MeSH terms: Aggression; Impulsive Behavior
Study type: Interventional

Summary: 
      There is a series of well designed studies that have reported, in those with a history of
      anti-social behavior, that supplementation with vitamins / minerals, omega-3 fatty acids (n-3
      FA), or both, reduces the incidence of aggressive behavior. Although there is evidence that
      all these nutrients have a role, to date the relative contribution of fatty acids and
      vitamins / minerals has not been considered: for example the possibility of a synergistic
      interaction has not yet been examined. In addition the topic has to date been studied under
      real-life condition, such as a prison, making the topic difficult to study. The major aim of
      the present study was to develop a paradigm that would allow the study of the topic in a
      sample from the general population without a history of anti-social behavior. Subjects
      received either a vitamin/mineral supplement, a fatty acid supplement, both or neither for
      three months, Measures of impulsivity and aggression were assessed before and after
      supplementation. Although in the past measures of actual behaviour have proved to be
      sensitive to supplementation, questionnaire measures have not. The second major objective was
      therefore to consider whether such phenomena can be studied in a sample without a history of
      anti-social behavior, using standardized, sensitive laboratory based measures and to compare
      these with questionnaire measures.

      POLYMORPHISMS AND THE RESPONSE TO MICRO-NUTRIENT SUPPLLMENTATION The data set were
      subsequently used to test an a priori hypothesis not related to the initial hypothesis. A
      meta-analysis found a consistent pattern that micro-nutrient supplementation improved mood
      (Long SJ, Benton D. Effects of vitamin and mineral supplementation on stress, mild
      psychiatric symptoms, and mood in nonclinical samples: a meta-analysis. Psychosom Med 2013;
      75: 144-153). To produce evidence of possible mechanisms the extent was determined, to which
      the impact of micro-nutrient supplementation was influenced by a range of polymorphisms
      associated with neurotransmitter systems known to modulate mood.

      The primary outcome measure was the General Health Questionnaire, a 30-item self-report
      questionnaire that was developed to detect, in a community sample, those who would benefit
      from seeing a psychiatrist.

      Given the literature that relates polymorphisms to mood disorders, and the known pharmacology
      of anti-depressant drugs, a range of polymorphisms were chosen associated with serotonin and
      catecholamines.

      Dopamine The SNPs associated with the metabolism and functioning of dopamine were: Dopamine
      beta hydroxylase (DBH, rs16111115); Dopamine transporter (DAT1, rs2550946);
      Catechol-O-methyltransferase (COMT, rs4680, rs6269). Dopamine receptor D1 (DRD1, rs4532);
      Dopamine receptor D2 (DRD2, rs1079598, rs1800497); Dopamine receptor D3 (DRD3, rs6280);
      Dopamine receptor D4 (DRD4, rs1800955).

      Serotonin Ten SNPs associated with different aspects of serotonin metabolism were also
      considered. Rs1843809 is a SNP of the TPH2 gene that encodes Tryptophan hydroxylase.
      Rs1050565 is a SNP in the BLMH gene that influences the activity of 5HTT (SLC6A4), the
      serotonin transporter. SNPs associated with various serotonin receptors were also examined:
      genetic variations of the HTR1A gene (5-HT1A receptor, rs6295); HTR1B gene (5-HT1B receptor,
      rs6296); HTR2A gene (5-HT2A receptor, rs6311); HTR2B gene (5-HT2B receptor, rs1549339); HTR2C
      gene (5-hydroxytryptamine receptor 2C, rs518147); HTR3A gene (5-hydroxytryptamine receptor
      3A, rs1150226); HTR3B (5-HT3B receptor, rs1672717); HTR4 gene (5-HT4 receptor, rs2278392).

      Adrenergic mechanisms Finally six SNPs associated with adrenergic receptors were considered:
      ADRA2A (adrenoceptor alpha 2A, rs553668); ADRB1 (adrenoceptor alpha B1, rs1801253); ADRB2
      (adrenoceptor alpha B2, rs1042713; ADRB3 (adrenoceptor alpha B3, rs4994); SLC6AC
      (noradrenaline transporter, rs5569 and rs2242447).

      Analysis The data will be analyzed using analysis of variance with a change in GHQ from
      before to after supplementation as the dependent variable: Micronutrient/placebo X
      Polymorphism.
    

Detailed description: 
      Objective: To consider whether aggression and impulsivity respond to multi-vitamins /
      minerals or fatty acid supplementation and whether there is a synergistic interaction?

      In a between subjects design four groups will be contrasted. Those who for three months:

        1. Receive two placebos

        2. Receive multi-vitamin / mineral plus a placebo

        3. Receive fatty acids plus placebo

        4. Receive multi-vitamin / mineral plus fatty acids.
    

Intervention name(s): Placebo; Multi-vitamin/mineral; Docosahexaenoic acid; DHA plus vitamins/minerals
Intervention type(s): Dietary Supplement; Dietary Supplement; Dietary Supplement; Dietary Supplement
Intervention description(s): Placebo for DHA of identical appearance - based on olive oil
Placebo for vitamins/minerals of identical appearance; Each active tablet contained vitamins A (800µg); B1 (1.4mg); B2 (1.75mg); B6 (2mg); B12 (2.5mg); biotin 62.5 µg; folic acid 200 µg; niacin 20 mg; C (100mg); D (5µg); E (15mg); K (30µg); pantothenic acid (7.5 mg). In addition several minerals were administered: calcium (162mg); phosphorus (125mg); magnesium (100mg); potassium (40mg); chloride (36.3mg); iron (5mg); iodine (100µg); copper (500µg); manganese (2mg); chromium (40µg); molybdenum (50µg); selenium (30µg); zinc (5mg) as well as lutein (500 µg) . The placebo capsule was identical in color, size and appearance.; 22:6 (n-3) docosahexaenoic each capsule contained 224.2mg and three were taken per day; The DHA and vitamin/mineral supplements are as above
Other intervention name(s): Does not apply; Centrum Advance 50+ (Pfizer Inc, New York); Efalex (Efamol Ltd, Leatherhead, England); Efalex (Efamol Ltd); Centrum Advance 50+ (Pfizer Inc, New York)
Intervention MeSH terms: Vitamins; Evening primrose oil
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: Aggression DHA; Docosahexaenoic acid; Impulsivity; Minerals; Vitamins