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Understanding Methylation, Gene
Regulation and the Methyl Detox Profile
As Always…
Tonight’s discussion does not take into consideration
your patient’s medical history, drug/supplement
interactions and/or allergies/sensitivities. It is the
responsibility of the practitioner to determine
appropriate supplement and dosing choices for each
patient.
About the Commentators
Amy Pieczarka, RD,LDN,CCN,CDE
Director of Nutrition Services
PreviMedica
Andrew W. Campbell, M.D.
Medical Advisor
Cell Science Systems
About the Speaker
• Friedrich Schiller Universitaet – Heidelberg, Germany
• Institut National de La Recherche Agronomique - France
• Krankenhaus Harlaching -Germany
Dr. Dino Celeda holds a Ph.D in Biology specialized in
Human Genetics from the Ruprecht Karls Universitaet,
Heidelberg, Germany. He completed his training and held
positions at many renowned institutions including:
Dr. Celeda has authored numerous publications in the field of Human Genetics. Included in
his experience are Senior R&D, Scientific Advisor, Director of Genetic Testing and Director of
Science positions.
Dr. rer. nat. Dino Celeda (Ph.D)
Scientific Officer
Objectives
Identifythemostimportantgenesinvolvedinthemethionine/
homocysteinecycle:
• their mutations (SNPs), controlling methionine/homocysteine cycle.
• their impact on homocysteine levels.
Personalizedinterventionaccordingtothegenetictestresult:
• Targeted nutrition
• Targeted supplementation
• Monitoring of individual progress by measuring homocysteine
levels in the blood
Genetic Polymorphism (SNP)
Genetic Polymorphism (SNP):
Genetic Polymorphism (SNP)
A SNP can lead to a change in protein sequence and thus influence the 3-D conformation. In
the example here, the SNP disrupts hemoglobin formation and causes sickle cell anemia.
Functional Genetic Test Results
The individual’s functional genetic test results are shown on a level
of functionality and/or expression of the corresponding enzyme.
• homozygous positive, -;-, both alleles from both parents show
mutation. Reduced function/expression.
• heterozygous +;-, one allele from one parent shows mutation,
the other allele shows the normal, wild-type. 50% of the genes
are normal
• homozygous negative +;+, both alleles from both parents have
no mutation and show the normal, wild type. 100% of the genes
are normal.
Genomic Insights TM
– TEST
Individual’s current status: testing of relevant SNPs and
corresponding metabolic markers in blood
– TARGET
Targeted intervention: personalized, specific supplementation
according to individual results of relevant of SNPs, and
corresponding metabolic markers in blood
– MONITOR
Individual progress: monitoring and maintaining the progress
of personalized, specific supplementation with measurement
of metabolic markers in blood
Applying Functional Genetics for targeted intervention by
personalized, specific supplementation
Genomic Insights TM
Importance of personalized targeted nutrition
Overload of Supplements
can impact metabolic process and lead to side effects.
Individual Genetic SNPs
may require personalized supplementation of specific vitamins, minerals, trace elements and
/or amino acids for the maintenance and optimization of metabolic processes.
Side Effects
can influence a variety of functions in the organism like immune responses (reduced NK-
cytotoxicity).
Genes in the Methionine/Homocysteine Cycle
• MTHFR (Methylenetetrahydrofolate reductase)
C677T and A1298C mutations in the MTHFR gene are known to cause a diminished methylation
capacity, by a reduction in 5-MethylTHF synthesis.
• Methionine synthase (MS)
MS is encoded by the 5-methyltetrahydrofolate-homocysteine-methyltransferase gene (MTR). Its task
is to generate methionine from homocysteine by using methylcobalamin (methylated vitamin B12)
obtained when 5-MethylTHF donates its methyl group to vitamin B12. The mutation at position
C3518T in the gene is described with a reduced activity of the resulting enzyme.
• COMT (Catechol-O-Methyltransferase)
COMT is responsible for the transfer of the methyl group from SAMe to specific substances (e.g.
catecholamines) for removal. COMT is also involved in drug metabolism/clearance, neurotransmitter
regulation, gene expression as well as in the detoxification of a variety of environmental toxins.
The mutations at position G472A (Val108/158Met) and G304A (Ala52/102Thr) are described with a
reduced activity of the resulting enzyme.
Treatment Monitoring
• Homocysteine
Measurement of homocysteine levels in serum for monitoring and
maintaining treatment progress.
Methyl Detox
Profile
Methyl Detox
Profile
MTHFR, mutation positions:
1. C677T
2. A1298C
Presence of 1 and/or 2 SNPs
effects enzyme activity in
biosynthesis of 5-MethylTHF
Supplementation: 5-MethylTHF
Methyl Detox
Profile
5-MethylTHF: methyl donor for methylcobalamin
Methyl Detox
Profile
Methyl Detox
Profile
MTR, mutation position: c.3518C>T,
methylcobalamin-deficiency (cblG) (Mutation
Pro1173Leu). Presence affects enzyme activity
in biosynthesis of methionine.
Supplementation: Methylcobalamin
Methyl Detox
Profile
SAM-e (S-Adenosyl-methionine): Methyl donor for
degradation of specific substances by COMT.
Methyl Detox
Profile
COMT, mutation positions:
1. Val108/158Met
2. Ala52/102Thr
Presence of 1 and/or 2 SNPs
effects enzyme activity in
degradation of substances.
Supplementation: SAMe
(S-adenosyl- methionine)
Methyl Detox
Profile
Homocysteine:
Monitoring and
maintaining progress of
personalized treatment
Supplementation :
(Recommended, if blood
levels are still elevated after
personalized treatment):
1. Vitamin B6
2. L-Cysteine
3. L-Glycine
4. L-Glutamic acid
Methyl Detox
Profile
Sample Results
Methyl Detox
Profile
Sample Results
Methyl Detox Profile
Sample Results
Methyl Detox Profile
Sample Results
Methyl Detox
Profile
Sample Results
Methyl Detox
Profile
Sample Results
Methyl Detox Profile
Sample Results
Methyl Detox Profile
Sample Results
Understanding Methylation, Gene Regulation and the MethylDetox Profile
Methyl Detox
Profile
Q&A
Pre-Webinar Survey Questions
• What would be a ‘red flag’ for a practitioner to prompt the ordering of the
Methyl Detox Profile?
• How do you know when someone is under or over methylating?
• Does someone with a SNP require lifelong supplementation?
• How does the SAD vs. Paleo diet affect this?
• How does one decide which methylating supplement to use?
• How do I specifically use the MTHFR results on pharmacogenomics
testing to help mental health patients?
www.cellsciencesystems.com | info@alcat.com | 800-872-5228
Thank you for
joining us

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Understanding Methylation, Gene Regulation and the MethylDetox Profile

  • 1. Understanding Methylation, Gene Regulation and the Methyl Detox Profile
  • 2. As Always… Tonight’s discussion does not take into consideration your patient’s medical history, drug/supplement interactions and/or allergies/sensitivities. It is the responsibility of the practitioner to determine appropriate supplement and dosing choices for each patient.
  • 3. About the Commentators Amy Pieczarka, RD,LDN,CCN,CDE Director of Nutrition Services PreviMedica Andrew W. Campbell, M.D. Medical Advisor Cell Science Systems
  • 4. About the Speaker • Friedrich Schiller Universitaet – Heidelberg, Germany • Institut National de La Recherche Agronomique - France • Krankenhaus Harlaching -Germany Dr. Dino Celeda holds a Ph.D in Biology specialized in Human Genetics from the Ruprecht Karls Universitaet, Heidelberg, Germany. He completed his training and held positions at many renowned institutions including: Dr. Celeda has authored numerous publications in the field of Human Genetics. Included in his experience are Senior R&D, Scientific Advisor, Director of Genetic Testing and Director of Science positions. Dr. rer. nat. Dino Celeda (Ph.D) Scientific Officer
  • 5. Objectives Identifythemostimportantgenesinvolvedinthemethionine/ homocysteinecycle: • their mutations (SNPs), controlling methionine/homocysteine cycle. • their impact on homocysteine levels. Personalizedinterventionaccordingtothegenetictestresult: • Targeted nutrition • Targeted supplementation • Monitoring of individual progress by measuring homocysteine levels in the blood
  • 7. Genetic Polymorphism (SNP) A SNP can lead to a change in protein sequence and thus influence the 3-D conformation. In the example here, the SNP disrupts hemoglobin formation and causes sickle cell anemia.
  • 8. Functional Genetic Test Results The individual’s functional genetic test results are shown on a level of functionality and/or expression of the corresponding enzyme. • homozygous positive, -;-, both alleles from both parents show mutation. Reduced function/expression. • heterozygous +;-, one allele from one parent shows mutation, the other allele shows the normal, wild-type. 50% of the genes are normal • homozygous negative +;+, both alleles from both parents have no mutation and show the normal, wild type. 100% of the genes are normal.
  • 9. Genomic Insights TM – TEST Individual’s current status: testing of relevant SNPs and corresponding metabolic markers in blood – TARGET Targeted intervention: personalized, specific supplementation according to individual results of relevant of SNPs, and corresponding metabolic markers in blood – MONITOR Individual progress: monitoring and maintaining the progress of personalized, specific supplementation with measurement of metabolic markers in blood Applying Functional Genetics for targeted intervention by personalized, specific supplementation
  • 10. Genomic Insights TM Importance of personalized targeted nutrition Overload of Supplements can impact metabolic process and lead to side effects. Individual Genetic SNPs may require personalized supplementation of specific vitamins, minerals, trace elements and /or amino acids for the maintenance and optimization of metabolic processes. Side Effects can influence a variety of functions in the organism like immune responses (reduced NK- cytotoxicity).
  • 11. Genes in the Methionine/Homocysteine Cycle • MTHFR (Methylenetetrahydrofolate reductase) C677T and A1298C mutations in the MTHFR gene are known to cause a diminished methylation capacity, by a reduction in 5-MethylTHF synthesis. • Methionine synthase (MS) MS is encoded by the 5-methyltetrahydrofolate-homocysteine-methyltransferase gene (MTR). Its task is to generate methionine from homocysteine by using methylcobalamin (methylated vitamin B12) obtained when 5-MethylTHF donates its methyl group to vitamin B12. The mutation at position C3518T in the gene is described with a reduced activity of the resulting enzyme. • COMT (Catechol-O-Methyltransferase) COMT is responsible for the transfer of the methyl group from SAMe to specific substances (e.g. catecholamines) for removal. COMT is also involved in drug metabolism/clearance, neurotransmitter regulation, gene expression as well as in the detoxification of a variety of environmental toxins. The mutations at position G472A (Val108/158Met) and G304A (Ala52/102Thr) are described with a reduced activity of the resulting enzyme.
  • 12. Treatment Monitoring • Homocysteine Measurement of homocysteine levels in serum for monitoring and maintaining treatment progress.
  • 14. Methyl Detox Profile MTHFR, mutation positions: 1. C677T 2. A1298C Presence of 1 and/or 2 SNPs effects enzyme activity in biosynthesis of 5-MethylTHF Supplementation: 5-MethylTHF
  • 15. Methyl Detox Profile 5-MethylTHF: methyl donor for methylcobalamin
  • 17. Methyl Detox Profile MTR, mutation position: c.3518C>T, methylcobalamin-deficiency (cblG) (Mutation Pro1173Leu). Presence affects enzyme activity in biosynthesis of methionine. Supplementation: Methylcobalamin
  • 18. Methyl Detox Profile SAM-e (S-Adenosyl-methionine): Methyl donor for degradation of specific substances by COMT.
  • 19. Methyl Detox Profile COMT, mutation positions: 1. Val108/158Met 2. Ala52/102Thr Presence of 1 and/or 2 SNPs effects enzyme activity in degradation of substances. Supplementation: SAMe (S-adenosyl- methionine)
  • 20. Methyl Detox Profile Homocysteine: Monitoring and maintaining progress of personalized treatment Supplementation : (Recommended, if blood levels are still elevated after personalized treatment): 1. Vitamin B6 2. L-Cysteine 3. L-Glycine 4. L-Glutamic acid
  • 31. Pre-Webinar Survey Questions • What would be a ‘red flag’ for a practitioner to prompt the ordering of the Methyl Detox Profile? • How do you know when someone is under or over methylating? • Does someone with a SNP require lifelong supplementation? • How does the SAD vs. Paleo diet affect this? • How does one decide which methylating supplement to use? • How do I specifically use the MTHFR results on pharmacogenomics testing to help mental health patients?
  • 32. www.cellsciencesystems.com | info@alcat.com | 800-872-5228 Thank you for joining us