3 ms·

Ensure they are getting adequate folate, noting that normal blood levels may not indicate functional sufficiency [1][2]: "Folate deficiencies may lead to an in

Ensure they are getting adequate folate, noting that normal blood levels may not indicate functional sufficiency [1][2]: "Folate deficiencies may lead to an increased risk of depression and poorer antidepressant treatment outcomes..." "...deficiencies may be caused by improper absorption and utilization, often due to genetic polymorphisms." "Supplementation with the active form of folate, (methylfolate), which is more readily absorbed, may be effective in the prevention and treatment of both depression and dementia." "...(methylfolate) indicated efficacy as adjunctive therapy or monotherapy in reducing depressive symptoms in patients with normal and low folate levels..." [1] https://www.ncbi.nlm.nih.gov/pubmed/19909688 https://www.ncbi.nlm.nih.gov/pubmed/19909688 [2] https://www.ncbi.nlm.nih.gov/pubmed/17900207 https://www.ncbi.nlm.nih.gov/pubmed/17900207

ridgeguy 8y ago
Yes. There is a subset of patients with depression who have either of two different genetic polymorphisms for methyeneltetrahydrofolate reductase. This may be causally linked to their depression. [1] Supplementing diet with a modified form of folate appears to diminish depression in patients with these particular polymorphisms. My understanding is that this is still a matter of controversy. [1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1810582/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1810582/
- mendelsd 8y ago
  A few interesting things to note on this topic: 1) Prevalence of MTHFR gene variants you refer to is very high, e.g. 10%/50% for homo/heterozygous C677T SNP [1] (with frequencies varying substantially between ethnic groups). 2) Effects tend to be stronger with two copies of a variant (homozygous), but a single copy (heterozygous) may still be a concern, e.g. for C677T: "Individuals with the 677TT genotype, have approximately 30% the MTHFR enzyme activity of those with the 677CC genotype, whereas heterozygotes 677CT have around 65% of enzymatic activity" [2] 3) It seems odd to me that pharmacological dosages of folate are getting prescribed (I mean, it's a nutrient so why take it in doses that exceed the nutritional range?): "The most active form of folate has recently been approved in the United States as a prescription medical food for depressed patients with folate deficiency. Doses are usually 7.5 to 15 mg/d". [3] "Another concern is that folate doses > 800 μg/d can result in high levels of unmetabolized serum folic acid, reducing the amount of brain l-methylfolate and leading to decreased monoamines, an outcome that potentially increases the risk of or exacerbates depression." [3] Folate RDA is 400-800 μg/d depending on pregnancy status [4] [1] https://www.ncbi.nlm.nih.gov/pubmed/28847029 https://www.ncbi.nlm.nih.gov/pubmed/28847029 [2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3078648/#R6 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3078648/#R6 [3] https://www.ncbi.nlm.nih.gov/pubmed/19909688 https://www.ncbi.nlm.nih.gov/pubmed/19909688 [4] https://www.mayoclinic.org/drugs-supplements-folate/art-20364625 https://www.mayoclinic.org/drugs-supplements-folate/art-2036...

ridgeguy 8y ago

Yes. There is a subset of patients with depression who have either of two different genetic polymorphisms for methyeneltetrahydrofolate reductase. This may be causally linked to their depression. [1] Supplementing diet with a modified form of folate appears to diminish depression in patients with these particular polymorphisms. My understanding is that this is still a matter of controversy. [1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1810582/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1810582/

mendelsd 8y ago
A few interesting things to note on this topic: 1) Prevalence of MTHFR gene variants you refer to is very high, e.g. 10%/50% for homo/heterozygous C677T SNP [1] (with frequencies varying substantially between ethnic groups). 2) Effects tend to be stronger with two copies of a variant (homozygous), but a single copy (heterozygous) may still be a concern, e.g. for C677T: "Individuals with the 677TT genotype, have approximately 30% the MTHFR enzyme activity of those with the 677CC genotype, whereas heterozygotes 677CT have around 65% of enzymatic activity" [2] 3) It seems odd to me that pharmacological dosages of folate are getting prescribed (I mean, it's a nutrient so why take it in doses that exceed the nutritional range?): "The most active form of folate has recently been approved in the United States as a prescription medical food for depressed patients with folate deficiency. Doses are usually 7.5 to 15 mg/d". [3] "Another concern is that folate doses > 800 μg/d can result in high levels of unmetabolized serum folic acid, reducing the amount of brain l-methylfolate and leading to decreased monoamines, an outcome that potentially increases the risk of or exacerbates depression." [3] Folate RDA is 400-800 μg/d depending on pregnancy status [4] [1] https://www.ncbi.nlm.nih.gov/pubmed/28847029 https://www.ncbi.nlm.nih.gov/pubmed/28847029 [2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3078648/#R6 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3078648/#R6 [3] https://www.ncbi.nlm.nih.gov/pubmed/19909688 https://www.ncbi.nlm.nih.gov/pubmed/19909688 [4] https://www.mayoclinic.org/drugs-supplements-folate/art-20364625 https://www.mayoclinic.org/drugs-supplements-folate/art-2036...