comments:
With homozygous C677T, the primary supplement to use is B2. Here is a general C677T protocol: For homozygous C677T specifically: 10-100mg supplemental B2 The C677T variant causes reducing binding of MTHFR to its cofactor, riboflavin. Studies have shown that for homozygous C677T simply adding supplemental vitamin B2 may increase the concentration of riboflavin sufficiently to restore most or all of the binding success, thereby restoring most/all MTHFR function. So a 10-100mg B2 supplement may restore much of the MTHFR function, thereby reducing the needed amount of extra choline/TMG (or high-dose folate if going that route). The R5P form of B2 may possibly be preferable. (E.g., Thorne R5P 36mg) 550-600mg of choline, preferably from food 550mg is the baseline adult Adequate Intake Choline sources include such foods as meat, eggs, liver, lecithin, nuts, some legumes, and vegetables such as crucifers. 750mg of trimethylglycine (TMG aka betaine) I.e., one 750mg capsule Choline is converted to TMG for methylation use, so TMG reduces need for even more choline. 400-800mcg of folate, preferably from food Folinic acid or methylfolate can also be used, as needed and as tolerated. Target serum folate levels are 15+ ng/mL (34+ nmol/L). 2.4-10mcg B12, preferably from food Past history of B12 deficiency, malabsorption issues, etc., may suggest that supplemental B12, in the form of hydroxocobalamin, adenosylcobalamin, or methylcobalamin may be prudent. Target serum B12 levels are 500-950 pg/mL (~370-700 pmol/L). (Optional) 3-15g of creatine monohydrate or creatine HCL The body uses ~40% of methylation output, SAM, just to produce creatine. So supplementing creatine can free up a lot of SAM for other uses. Low vitamin A, iron, and/or glycine can cause the built-in methyl buffer system to not work properly, which can make overmethylation (rising anxiety, irritability, insomnia, etc.) from methylation-related supplements much more likely. Beta carotene is not vitamin A and some people genetically have poor conversion of beta carotene to real vitamin A (retinol). A food app like Cronometer is helpful for tracking nutrients in your diet.
Do you have bloodwork for B12 and folate? Here is a general protocol for homozygous C677T. The B2 is key to correcting the C677T, and choline/TMG is as important for pregnancy as folate. For homozygous C677T specifically: 10-100mg supplemental B2 The C677T variant causes reducing binding of MTHFR to its cofactor, riboflavin. Studies have shown that for homozygous C677T simply adding supplemental vitamin B2 may increase the concentration of riboflavin sufficiently to restore most or all of the binding success, thereby restoring most/all MTHFR function. So a 10-100mg B2 supplement may restore much of the MTHFR function, thereby reducing the needed amount of extra choline/TMG (or high-dose folate if going that route). The R5P form of B2 may possibly be preferable. (E.g., Thorne R5P 36mg) 550-600mg of choline, preferably from food 550mg is the baseline adult Adequate Intake Choline sources include such foods as meat, eggs, liver, lecithin, nuts, some legumes, and vegetables such as crucifers. 750mg of trimethylglycine (TMG aka betaine) I.e., one 750mg capsule Choline is converted to TMG for methylation use, so TMG reduces need for even more choline. 400-800mcg of folate, preferably from food Folinic acid or methylfolate can also be used, as needed and as tolerated. Target serum folate levels are 15+ ng/mL (34+ nmol/L). 2.4-10mcg B12, preferably from food Past history of B12 deficiency, malabsorption issues, etc., may suggest that supplemental B12, in the form of hydroxocobalamin, adenosylcobalamin, or methylcobalamin may be prudent. Target serum B12 levels are 500-950 pg/mL (~370-700 pmol/L). (Optional) 3-15g of creatine monohydrate or creatine HCL The body uses ~40% of methylation output, SAM, just to produce creatine. So supplementing creatine can free up a lot of SAM for other uses. Low vitamin A, iron, and/or glycine can cause the built-in methyl buffer system to not work properly, which can make overmethylation (rising anxiety, irritability, insomnia, etc.) from methylation-related supplements much more likely. Beta carotene is not vitamin A and some people genetically have poor conversion of beta carotene to real vitamin A (retinol). A food app like Cronometer is helpful for tracking nutrients in your diet.
See the slow COMT section of this post. Here is a general protocol for homozygous C677T: For homozygous C677T specifically: 10-100mg supplemental B2 The C677T variant causes reducing binding of MTHFR to its cofactor, riboflavin. Studies have shown that for homozygous C677T simply adding supplemental vitamin B2 may increase the concentration of riboflavin sufficiently to restore most or all of the binding success, thereby restoring most/all MTHFR function. So a 10-100mg B2 supplement may restore much of the MTHFR function, thereby reducing the needed amount of extra choline/TMG (or high-dose folate if going that route). The R5P form of B2 may possibly be preferable. (E.g., Thorne R5P 36mg) 550-600mg of choline, preferably from food 550mg is the baseline adult Adequate Intake Choline sources include such foods as meat, eggs, liver, lecithin, nuts, some legumes, and vegetables such as crucifers. 750mg of trimethylglycine (TMG aka betaine) I.e., one 750mg capsule Choline is converted to TMG for methylation use, so TMG reduces need for even more choline. 400-800mcg of folate, preferably from food Folinic acid or methylfolate can also be used, as needed and as tolerated. Target serum folate levels are 15+ ng/mL (34+ nmol/L). 2.4-10mcg B12, preferably from food Past history of B12 deficiency, malabsorption issues, etc., may suggest that supplemental B12, in the form of hydroxocobalamin, adenosylcobalamin, or methylcobalamin may be prudent. Target serum B12 levels are 500-950 pg/mL (~370-700 pmol/L). (Optional) 3-15g of creatine monohydrate or creatine HCL The body uses ~40% of methylation output, SAM, just to produce creatine. So supplementing creatine can free up a lot of SAM for other uses. Low vitamin A, iron, and/or glycine can cause the built-in methyl buffer system to not work properly, which can make overmethylation (rising anxiety, irritability, insomnia, etc.) from methylation-related supplements much more likely. Beta carotene is not vitamin A and some people genetically have poor conversion of beta carotene to real vitamin A (retinol). A food app like Cronometer is helpful for tracking nutrients in your diet.
Here is a general protocol applicable to homozygous C677T. For homozygous C677T specifically: 10-100mg supplemental B2 The C677T variant causes reducing binding of MTHFR to its cofactor, riboflavin. Studies have shown that for homozygous C677T simply adding supplemental vitamin B2 may increase the concentration of riboflavin sufficiently to restore most or all of the binding success, thereby restoring most/all MTHFR function. So a 10-100mg B2 supplement may restore much of the MTHFR function, thereby reducing the needed amount of extra choline/TMG (or high-dose folate if going that route). The R5P form of B2 may possibly be preferable. (E.g., Thorne R5P 36mg) 550-600mg of choline, preferably from food 550mg is the baseline adult Adequate Intake Choline sources include such foods as meat, eggs, liver, lecithin, nuts, some legumes, and vegetables such as crucifers. 750mg of trimethylglycine (TMG aka betaine) I.e., one 750mg capsule Choline is converted to TMG for methylation use, so TMG reduces need for even more choline. 400-800mcg of folate, preferably from food Folinic acid or methylfolate can also be used, as needed and as tolerated. Target serum folate levels are 15+ ng/mL (34+ nmol/L). 2.4-10mcg B12, preferably from food Past history of B12 deficiency, malabsorption issues, etc., may suggest that supplemental B12, in the form of hydroxocobalamin, adenosylcobalamin, or methylcobalamin may be prudent. Target serum B12 levels are 500-950 pg/mL (~370-700 pmol/L). (Optional) 3-15g of creatine monohydrate or creatine HCL The body uses ~40% of methylation output, SAM, just to produce creatine. So supplementing creatine can free up a lot of SAM for other uses. Low vitamin A, iron, and/or glycine can cause the built-in methyl buffer system to not work properly, which can make overmethylation (rising anxiety, irritability, insomnia, etc.) from methylation-related supplements much more likely. Beta carotene is not vitamin A and some people genetically have poor conversion of beta carotene to real vitamin A (retinol). A food app like Cronometer is helpful for tracking nutrients in your diet.
Here is a general protocol for homozygous C677T. This variant reduces methylfolate production by ~75% but fortunately it usually responds well to a small dose of vitamin B2. The other elements of the protocol are to keep the rest of the methylation system working well: For homozygous C677T specifically: 10-100mg supplemental B2 The C677T variant causes reducing binding of MTHFR to its cofactor, riboflavin. Studies have shown that for homozygous C677T simply adding supplemental vitamin B2 may increase the concentration of riboflavin sufficiently to restore most or all of the binding success, thereby restoring most/all MTHFR function. So a 10-100mg B2 supplement may restore much of the MTHFR function, thereby reducing the needed amount of extra choline/TMG (or high-dose folate if going that route). The R5P form of B2 may possibly be preferable. (E.g., Thorne R5P 36mg) 550-600mg of choline, preferably from food 550mg is the baseline adult Adequate Intake Choline sources include such foods as meat, eggs, liver, lecithin, nuts, some legumes, and vegetables such as crucifers. 750mg of trimethylglycine (TMG aka betaine) I.e., one 750mg capsule Choline is converted to TMG for methylation use, so TMG reduces need for even more choline. 400-800mcg of folate, preferably from food Folinic acid or methylfolate can also be used, as needed and as tolerated. Target serum folate levels are 15+ ng/mL (34+ nmol/L). 2.4-10mcg B12, preferably from food Past history of B12 deficiency, malabsorption issues, etc., may suggest that supplemental B12, in the form of hydroxocobalamin, adenosylcobalamin, or methylcobalamin may be prudent. Target serum B12 levels are 500-950 pg/mL (~370-700 pmol/L). (Optional) 3-15g of creatine monohydrate or creatine HCL The body uses ~40% of methylation output, SAM, just to produce creatine. So supplementing creatine can free up a lot of SAM for other uses. Low vitamin A, iron, and/or glycine can cause the built-in methyl buffer system to not work properly, which can make overmethylation (rising anxiety, irritability, insomnia, etc.) from methylation-related supplements much more likely. Beta carotene is not vitamin A and some people genetically have poor conversion of beta carotene to real vitamin A (retinol). A food app like Cronometer is helpful for tracking nutrients in your diet.
Here is a protocol for homozygous C677T. The primary components are B2, choline, TMG. Excess B12 and folate will have minimal benefit. Regarding slow MAO-A, see the MAO-A section of this post. For homozygous C677T specifically: 10-100mg supplemental B2 The C677T variant causes reducing binding of MTHFR to its cofactor, riboflavin. Studies have shown that for homozygous C677T simply adding supplemental vitamin B2 may increase the concentration of riboflavin sufficiently to restore most or all of the binding success, thereby restoring most/all MTHFR function. So a 10-100mg B2 supplement may restore much of the MTHFR function, thereby reducing the needed amount of extra choline/TMG (or high-dose folate if going that route). The R5P form of B2 may possibly be preferable. (E.g., Thorne R5P 36mg) 550-600mg of choline, preferably from food 550mg is the baseline adult Adequate Intake Choline sources include such foods as meat, eggs, liver, lecithin, nuts, some legumes, and vegetables such as crucifers. 750mg of trimethylglycine (TMG aka betaine) I.e., one 750mg capsule Choline is converted to TMG for methylation use, so TMG reduces need for even more choline. 400-800mcg of folate, preferably from food Folinic acid or methylfolate can also be used, as needed and as tolerated. Target serum folate levels are 15+ ng/mL (34+ nmol/L). 2.4-10mcg B12, preferably from food Past history of B12 deficiency, malabsorption issues, etc., may suggest that supplemental B12, in the form of hydroxocobalamin, adenosylcobalamin, or methylcobalamin may be prudent. Target serum B12 levels are 500-950 pg/mL (~370-700 pmol/L). (Optional) 3-15g of creatine monohydrate or creatine HCL The body uses ~40% of methylation output, SAM, just to produce creatine. So supplementing creatine can free up a lot of SAM for other uses. Low vitamin A, iron, and/or glycine can cause the built-in methyl buffer system to not work properly, which can make overmethylation (rising anxiety, irritability, insomnia, etc.) from methylation-related supplements much more likely. Beta carotene is not vitamin A and some people genetically have poor conversion of beta carotene to real vitamin A (retinol). A food app like Cronometer is helpful for tracking nutrients in your diet.
You have homozygous C677T MTHFR, homozygous SLC19A1, and heterozygous MTHFD1 which together result in ~89% reduction in methylfolate production, which impairs methylation. A small excess of vitamin B2 can partially or completely correct the C677T, but the MTHFD1 and SLC19A1 still leave you with ~57% reduction. The body tries to compensate for the methylation impairment in the folate-dependent methylation pathway by placing a greater demand on the choline-dependent methylation pathway. This increases the amount of choline + TMG needed to support this extra demand. A homozygous PEMT (5465G>A) will also increase this demand. Here is a general protocol. You may need to add supplements starting with very low doses and increment up slowly if your methylation is indeed that impaired. Getting bloodwork for B12 (serum and MMA) and folate (serum and RBC folate) would be helpful. For homozygous C677T specifically: 10-100mg supplemental B2 The C677T variant causes reducing binding of MTHFR to its cofactor, riboflavin. Studies have shown that for homozygous C677T simply adding supplemental vitamin B2 may increase the concentration of riboflavin sufficiently to restore most or all of the binding success, thereby restoring most/all MTHFR function. So a 10-100mg B2 supplement may restore much of the MTHFR function, thereby reducing the needed amount of extra choline/TMG (or high-dose folate if going that route). The R5P form of B2 may possibly be preferable. (E.g., Thorne R5P 36mg) 550-600mg of choline, preferably from food 550mg is the baseline adult Adequate Intake Choline sources include such foods as meat, eggs, liver, lecithin, nuts, some legumes, and vegetables such as crucifers. 750mg of trimethylglycine (TMG aka betaine) I.e., one 750mg capsule Choline is converted to TMG for methylation use, so TMG reduces need for even more choline. 400-800mcg of folate, preferably from food Folinic acid or methylfolate can also be used, as needed and as tolerated. Target serum folate levels are 15+ ng/mL (34+ nmol/L). 2.4-10mcg B12, preferably from food Past history of B12 deficiency, malabsorption issues, etc., may suggest that supplemental B12, in the form of hydroxocobalamin, adenosylcobalamin, or methylcobalamin may be prudent. Target serum B12 levels are 500-950 pg/mL (~370-700 pmol/L). (Optional) 3-15g of creatine monohydrate or creatine HCL The body uses ~40% of methylation output, SAM, just to produce creatine. So supplementing creatine can free up a lot of SAM for other uses. Low vitamin A, iron, and/or glycine can cause the built-in methyl buffer system to not work properly, which can make overmethylation (rising anxiety, irritability, insomnia, etc.) from methylation-related supplements much more likely. Beta carotene is not vitamin A and some people genetically have poor conversion of beta carotene to real vitamin A (retinol). A food app like Cronometer is helpful for tracking nutrients in your diet.