Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: The Impact of Supplementation With Multi-vitamins/Minerals, With and Without Fatty Acids, on Impulsivity and Aggression

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.

Eligibility: Inclusion Criteria:
  -  Only male participants are being studied of self-reported good health who do not regularly consume seafood. They will be of a minimum age of 18 years of age and a maximum of 35 years of age. They will not be currently taking any medication and have no acute or chronic medical condition
  Exclusion Criteria:
  -  If they had consumed n-3 fatty acid ro vitamin/mineral supplements during the previous six months.
  -  If they have any history of food intolerance

Relevance to patient case: not relevant