1. Micro-nutrient supplementation affects mood depending on dopamine
and serotonin single nucleotide polymorphisms associated with psychiatric symptoms
David Benton & Hayley A. Young
Swansea University, United Kingdom
p<0.03
p<0.05
p<0.05
p<0.06
1. Abstract
One hundred and seventy three young male adults were recruited and under a double-blind procedure took either a micro-nutrient supplement, or placebo, for three months (13 vitamins / 11 minerals). The General Health Questionnaire, developed to detect those who would benefit from seeing a psychiatrist, was completed before and after supplementation.
From buccal swabs DNA was extracted. 5/7 dopaminergic and 5/12 serotonergic single nucleotide polymorphisms were found to influence the response to supplementation.
A meta-analysis found that micro-nutrient supplementation improved mood (1)
To explore the underlying mechanisms, gene-nutrition interactions were examined using polymorphisms associated with dopamine and serotonin as they are known to be associated with mood
For three months, in a double-blind trial, 173 young male adults took vitamin/mineral supplements, or a placebo, and rated their mood
Polymorphisms associated with the dopamine D1, D2 and D4 receptors, the dopamine transporter molecule and catechol-O-methyl transferase influenced the response to micro-nutrient supplementation
Similarly polymorphisms associated with the 5HT1B, 5HT2A, tryptophan hydroxlase and the serotonin transporter genes influenced the response
The finding of gene-nutrition interactions suggest the examination of genetic factors when establishing nutritional needs. As many drugs act via dopaminergic and serotonergic mechanisms, the possibility that dietary status may enhance or inhibit their action should also be considered
A meta-analysis of seven studies found that multi-vitamin/mineral supplementation reduced mild psychiatric symptoms (SMD = 0.30; 95% CI 0.43 to 0.18, p<0.001) (1).
To study the underlying mechanisms, gene-nutrition interactions were examined using polymorphisms associated with dopamine and serotonin neurotransmitters
Better
Mood
Better
Mood
AA = AG =82
CC = CT+TT = 132
Fig 2 The effect of rs (5HTT) on GHQ
Mean change before to after supplementation
A meta-analysis has reported an association
between suicidal behavior and the serotonin
transporter (5-HTT) gene (3).
3. Serotonergic mechanisms
Fig 4 The effect of rs (DRD4) on GHQ
Mean change before to after supplementation
p<0.01
p<0.04
A review found an association between the DRD4 gene, hyperactivity, substance dependence and the reaction to stress (5).
5. Discussion
4. Dopaminergic mechanisms
It has been argued that changes in mood are the most sensitive indicators of nutritional deficiencies (6). It appears, in this context, that genetic factors influence the need for micro-nutrients.
There are some who, for genetic reasons, have an inadequate intake of micro-nutrients
Both dopamine and serotonin are targets for drug therapy; for example the serotonin transporter is a main target for antidepressant drugs. A synergistic drug / nutrition interaction should be explored
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Mood
GG= CC+GC=96
2. Background / methods
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Fig 1 The effect of rs6296 (HTR1B) on GHQ scores
Mean change before to after supplementation
AA+GA= GG=49
6. References
Fig 3 The effect of rs4680 (COMT) on GHQ
Mean changes before to after supplementation
The 5-HT1B receptors are found on gamma-aminobutyric acid (GABA) terminals projecting from the nucleus accumbens to the ventral tegmental area, a pathway important for drug reward (2).
1) Long & Benton(2013) Psychosom Med75,144-53
2) Koob GF. (1992) Pharmacol Sci. 3, 177–184 
3) Li & He, (2007). Mol Psychiatr. 12, :
4) Stern et al..(2006) CNS Spectr. 11, :745-8.
5) Ptacek et al. (2011) Med Sci Monit.17, RA215–20
6) Benton (2013) Mol Nutr Food Res
Rs4680 has been described as the Worrier / Warrier gene (4).  Those with the A allele have a lower pain threshold and are more prone to stress and anxiety.