BDNF (Brain-Derived Neurotrophic Factor) rs6265

Gene function:
Brain-derived neurotrophic factor (BDNF) is a neuroprotective protein that supports mood, memory and long-term brain health. It plays vital roles in the survival, maintenance and growth of many types of neurons and is expressed in the hippocampus, hypothalamus, and cerebral cortex. These areas of the brain mediate the formation and retrieval of memories. Aging, poor diet, stress, lack of physical activity and genetic polymorphisms are associated with decreased BDNF levels.

Effect of the SNP:
Carriers of the Met (+) allele are more likely to have lower BDNF production than individuals with the Val (-) allele.

Specialized nutritional support:
Exercise is one of the most effective lifestyle strategies to increase and maintain the body’s ability to make BDNF. Magnesium and trace minerals such as zinc and lithium also play a role in BDNF production. Polyphenols from fruits, tea and turmeric are also beneficial. In a recent preclinical study, a polyphenol blend from grape and blueberry (Neurophenol™) maintained BDNF levels in aging rats. CurcumaSorb Mind provides a broad range of polyphenols, including Neurophenol™, curcumin, green tea catechins and proanthocyanidins from pine bark extract to support cognitive function and emotional wellness.

Nutritional assessment considerations:
Serum zinc or alkaline phosphatase are effective methods to assess and monitor zinc status. Lithium and magnesium status may be assessed through hair analysis and RBC magnesium, respectively.

The multivitamin is optional foundational support

COMT (Catechol O-Methyltransferase) rs4680

Gene function:
Encodes the COMT enzyme, which methylates and degrades catecholamine neurotransmitters (dopamine, norepinephrine, and epinephrine). COMT also assists in the detoxification of estrogens.

Effect of the SNP:
The Val (-) allele encodes a stable, efficient form of COMT that catalyzes rapid degradation of catecholamines, resulting in a reduction in dopamine and norepinephrine levels. Clearance of estrogens is also relatively efficient. Clinical manifestations of the Val allele primarily affect people who are homozygous (-/- or Val/Val), who often exhibit high stress tolerance, but slightly diminished executive cognitive performance has been suggested in studies. More research is needed to confirm this association.

The Met/Met (+/+) genotype is associated with instability of COMT and reduced enzyme activity. As a result, dopamine, norepinephrine, epinephrine and estrogens may reach higher levels in the body. While elevated catecholamines may confer improved alertness and performance in certain mental tasks, these individuals may exhibit reduced stress tolerance, tendency to worry, and sensitivity to stimulants. Because catecholamine neurotransmission depends on numerous genetic and environmental factors, not all individuals with COMT variants will show clinical manifestations or require specific support.

Specialized nutritional support:
For Met/Met genotypes: SAMe, the methyl donor for COMT, may support enzyme stability. SAMe supports cognitive function and mood through mechanisms involving dopamine and other neurotransmitter systems. Magnesium supports healthy stress responses through COMT-independent mechanisms. Lithium supports mood, emotional wellness, behavioral health and memory. When using vitamin B12, hydroxycobalamin is preferable to methylcobalamin in these patients because it tends to be less stimulating. Use caution with stimulants, including caffeine. Green tea may produce a stimulant effect by further inhibiting COMT in these individuals, although clinical evidence to support this effect is inconclusive. To support estrogen detoxification, consider cruciferous vegetable bioactives such as DIM (diindolylmethane).

For Val/Val and Val/Met genotypes: Dopamine precursors (L-tyrosine and L-DOPA) and cofactors (zinc, vitamin B6 and folate) promote the production of dopamine to support daily cognitive function and performance on mental tasks. Rhodiola maintains healthy adrenal catecholamine activity*

The multivitamin is optional foundational support

DRD2 (Dopamine D2 Receptor) rs6277

Gene function:
The DRD2 gene encodes the D2 subtype of the dopamine receptor, which plays critical roles in neurotransmission. DRD2 recognizes dopamine produced by other neurons and orchestrates many of its positive effects on cognition.

Effect of the SNP:
This SNP alters dopamine signaling in areas of the brain that orchestrate cognitive functions. Studies have associated the C allele with reduced performance on tests of executive function and working memory.

Specialized nutritional support:
L-tyrosine is a precursor of L-DOPA, which is converted to dopamine. Zinc, folate and vitamin B6 serve as cofactors in this pathway.*

Nutritional assessment considerations:
This SNP does not affect micronutrient levels, but dopamine neurotransmission is dependent on adequate zinc, folate and vitamin B6 status. Consider assessing these nutrients.

The multivitamin is optional foundational support

MTHFR (Methylene Tetrahydrofolate Reductase) A1298C

Gene function:
Encodes the MTHFR enzyme, which converts folic acid and 5,10-methylene THF to 5-MTHF, the active form of folate.

Effect of the SNP:
With this SNP, MTHFR functions at approximately 30-45% of its normal rate. In contrast to the C677T SNP, A1298C does not typically affect homocysteine levels, but is linked to reduced production of tetrahydrobiopterin (BH4), an integral cofactor in nitric oxide and neurotransmitter biosynthesis.

Specialized nutritional support:
Metafolin® bypasses MTHFR SNPs by providing 5-MTHF, the active, universally metabolized form of folate.*

The multivitamin is optional foundational support

MTHFR (Methylene Tetrahydrofolate Reductase) C677T

Gene function:
Encodes the MTHFR enzyme, which converts folic acid and 5,10-methylene THF to 5-MTHF, the active form of folate.

Effect of the SNP:
With this SNP, MTHFR functions at only 30-35% of its normal rate in individuals who are homozygous (both gene copies have the SNP) and 70% of its normal rate in individuals who are heterozygous (only one copy has the SNP). As a result, folate conversion to 5-MTHF is reduced and homocysteine is not methylated as readily. This SNP also limits the production of SAMe, a methyl donor needed for neurotransmitter synthesis.

Specialized nutritional support:
Metafolin® bypasses MTHFR SNPs by providing 5-MTHF, the active, universally metabolized form of folate.*

The multivitamin is optional foundational support

TPH2(Tryptophan Hydroxylase 2) rs4570625

Gene function:
TPH2 is an enzyme in the brain that converts the amino acid, tryptophan, to 5-HTP, the precursor of serotonin. Serotonin helps to maintain a positive emotional state and promotes relaxation and healthy eating behavior.

Effect of the SNP:
The T allele is associated with reduced enzyme activity. In a 2012 meta-analysis, individuals with the T allele were more likely to require medical support for mood than those with the G allele.

Specialized nutritional support:
5-HTP is the activated serotonin precursor. Consider 5-HTP supplementation if mood and emotional well-being are important clinical objectives.

Nutritional assessment considerations:
Serotonin biosynthesis requires vitamin B6, folate, magnesium, zinc and vitamin D. Consider assessing levels of these nutrients. Optimizing levels of these nutrients may additionally support mood.*

The multivitamin is optional foundational support
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Sample Report

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