Another thing worth looking into is your MTHFR status. If you have this mutation (and just under 50% of us do), then you can have problem processing folate and it can also affect B12. There are other genetic mutations that can affect B12 absorption as well. If you add metformin on top of those, it could potentially cause all sorts of issues.
Anyone who has this mutation do much better taking (more expensive admittedly) methylated versions of the B12 and folate, namely methylcobalamin and L-5-Methyltetrahydrofolate.
I'm paying more attention to this now that I've received my genome results and discovered I have one of the MTHFR mutations.
A quote from Dr Rhonda Patrick's nutrigenomics paper:
"Folate and MTHFR:
Folate (vitamin B9) serves two very important functions: 1). It serves as a precursor to make the DNA nucleotide thymine, which means it is essential to many new cells in the body, whether we are talking about the gut or the brain. 2). It serves as a precursor to make methyl groups, which are molecules that play a very important role in epigenetics. These methyl groups also play a very important role in converting homocysteine back into the amino acid methionine, which requires vitamin B12 as a cofactor.
There are a cluster of polymorphisms in the folate metabolism pathway. These specific polymorphisms are in the gene 5,10methylenetetrahydrofolate reductase, known as MTHFR , which converts 5,10methylenetetrahydrofolate into 5methylfolate and uses riboflavin as a cofactor. 5methylfolate is needed to make those methyl molecules that regulate epigenetics and to convert homocysteine into methionine. This means that while people with MTHFR polymorphisms can make new DNA from dietary folate (or supplemental folic acid), they do not efficiently produce methyl groups and subsequently can have higher than normal homocysteine levels. High homocysteine is associated with a host of vascular diseases including coronary artery disease, stroke, and dementia. While this cluster of polymorphisms effects a pretty large number of people, studies have shown that supplementing with L5MTHF (also known as 5methylfolate), methylcobalamin (vitamin B12), and riboflavin are able to circumvent these shortcomings, and bring down homocysteine in these populations. For example, individuals homozygous for MTHFR (rs1801133 (T;T)) that supplemented with 480 micrograms of Lmethyltetrahydrofolate for 4 weeks lowered their homocysteine levels by 15%.
The following are the cluster of polymorphisms and their corresponding loss of function:
● rs1801133 (C;T or T;C) ~40% of the population are heterozygous for one polymorphism which results in a 40% decrease in functional efficiency of MTHFR.
● rs1801133 (C;T or T;C) and rs1801131 (A;C or or C;A or C;C) ~20% of the population has two separate polymorphisms in the MTHFR gene which results in a 70% decrease in functional efficiency of MTHFR.
● rs1801133 (T;T) ~10% are homozygous for one polymorphism which results in 80-90% reduced functional efficiency of MTHFR.”
Another mutation discussed in the same paper:
"Vitamin B12 and FUT2
There are very common variations in the FUT2 gene that either decrease or increase vitamin B12 absorption. In those cases where poor vitamin B12 absorption occurs, sublingual vitamin B12 has been shown to bypass the malabsorption issue."