By Gabi Giacomin
When I was a teenager I begged my mum let me take Roacutane. I cried so much after the Dermatologist said I didn’t need it, that he gave it to me. He said it was so safe he would give it to his own children. I was so happy my skin would be perfect, and I took it for around 6 months until my skin started burning and feeling weird. Then I stopped.
Roacutane is a brand name for Isotretinoin, a retinoid derivative of Vitamin A. It reduces the skin’s production of natural oil which reduces bacteria in the skin that thrive on sebum, thus reducing acne.
Isotretinoin is linked to birth defects if taken during pregnancy, can cause depression and suicidal thoughts, elevated liver enzymes (liver stress) anemia and life threatening skin reactions which require immediate medical attention.
Isotretinoin is used in the beauty industry today to enhance the effects of facial peeling.
Today, many precautions are taken to reduce the negative side effects of Roacutane such as taking contraceptives, regular dermatological check ups, shorter prescription times and and taking a supplement of Folate and B12.
What I discovered recently was that Isotretinoin is a folate antagonist and now that I understand I am homozygous for MTHFR where does that leave me? Most likely very deficient in folate and B12 for most of my adult life.
This was the only drug i have taken as an adult. But what if I took the pill?
Older research (1982) claims the pill reduced serum levels of folate, B6 and B12. More recent research (2011) suggests the pill now contains lower levels of Oestrogen and only reduces serum levels of B6. It goes on to say that if a woman gets pregnant while on the pill or soon after coming off she will be deficient during pregnancy. Vitamin B6 is used in the methylation cycle to convert Folate to methylfolate, the active form, which then combines with Vitamin B12 to make Methionine and drive the methylation cycle. It also converts Homocysteine to cysteine in the transsulfuration pathway. In other words, its important if you want to have children.
What about antacids?
Antacids reduce folate in small amounts but its only an issue if you take them long term.
Nitrous Oxide? a Vitamin B12 antagonist, reducing methylation and increasing homocysteine values.
So what now? I will take precautions not to expose my daughters to drug medication unnecessarily. Or at least take a good multivitamin to compensate for the loss of vitamins.
Below I have listed all the folate reducing drugs I know of, however there may be more. If you or your children have an MTHFR mutation, I strongly suggest you get your folate and Vitamin B12 levels checked to see if you are deficient and supplement. There are several good multivitamins around which contain the active forms of folate and Vitamin B12 such as Thorne’s Basic Multi 2/ Day.
Information allows us to make better choices as parents and adults for ourselves and our children and its important to understand the side effects.
Antacids (digestive aid)
Alka-Seltzer.Milk of Magnesia.Alternagel, Amphojel.Gaviscon, Gelusil, Maalox, Mylanta, Rolaids.
Pepto-Bismol.TumsBuscopanDe-gasEnoQuick ezeRennieZantac
Effect of antacid and H2 receptor antagonists on the intestinal absorption of folic acid.
https://www.ncbi.nlm.nih.gov/pubmed/2902178
“Although the effects of these drugs on reducing folic acid absorption were relatively small, such reductions could become clinically significant in chronic antacid or H2 receptor antagonist use or intensive antacid or H2 receptor antagonist use by individuals eating diets that are marginal in folate content.”
Isotretinoin (acne)
Roacutane
Decreased Vitamin B12 and Folic Acid Concentrations in Acne Patients After Isotretinoin Therapy: A Controlled Study
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4248518/
“Vitamin B12/folic acid treatment should be given under medical surveillance before and during isotretinoin therapy. Supplementation of these vitamins should be recommended in cases of their deficiency, so as to decrease the risks of neuropsychiatric and occlusive vascular diseases.”
Cholestyramine (cholesterol)
PrevaliteQuestran
The effect of cholestyramine on intestinal absorption.
https://www.ncbi.nlm.nih.gov/pubmed/1168607
“Cholestyramine in a mean dosage of 0-6 g/kg/day has been given to 18 children with familial hypercholesterolaemia for between one and two and a half years. With prolonged treatment folate deficiency occurred, as evidenced by a fall in the mean serum folate concentration from 7-7 ng/ml before treatment to 4-4 ng/ml for patients on treatment for over one year; a corresponding lowering of red cell folate was also seen. “
Cholestipol (cholesterol)
CHolestid
In vitro binding of various biological substances by two hypocholesterolaemic resins. Cholestyramine and colestipol.
https://www.ncbi.nlm.nih.gov/pubmed/40578
“The ability of cholestyramine and colestipol, two hypocholesterolaemic resins, to bind in vitro several compounds such as vitamin B12, vitamin B12-intrinsic factor complex, folic acid, iron citrate and calcium chloride was investigated. Both resins bound to a high extent vitamin B12-intrinsic factor complex, folic acid and iron citrate; in addition, cholestyramine also caused appreciable binding of calcium.”
Methotrexate (rheumatoid arthritis)
Otrexup™, Rasuvo®, Rheumatrex® and Trexall™ or other names MTX, Amethopterin, and Methotrexate Sodium when referring to the generic drug name Methotrexate.
Methotrexate is an anti-cancer (“antineoplastic” or “cytotoxic”) chemotherapy drug.
Folate supplementation and methotrexate treatment in rheumatoid arthritis: a review
https://academic.oup.com/rheumatology/article/43/3/267/1774685
“MTX inhibits the enzyme dihydrofolate reductase, thereby depleting the pool of reduced folates, which act as donors of 1-carbon moieties in the formation of metabolic intermediates, including purines, deoxythymidylate monophosphate and methionine, and producing a state of effective folate deficiency [1].”
Nitrous oxide (anaesthetic)
Entonox
Effect of nitrous oxide on plasma homocysteine and folate in patients undergoing major surgery
https://academic.oup.com/bja/article/100/6/780/302965
“Nitrous oxide (N2O) oxidizes the cobalt atom on vitamin B12, leading to inhibition of the enzyme methionine synthetase.1–5 Because methionine synthetase is required for folate and DNA synthesis, prolonged or repeated exposure to N2O can lead to megaloblastic anaemia and subacute degeneration of the spinal cord.6–11”
Theophylline (asthma medication)
ElixophyllinNorphylPhyllocontinQuibron-TQuibron-TSRTheo-24TheoCapTheochron
Theo-DurTheo-TimeTruxophyllinUniphylNuelin syrup
Effect of caffeine, theophylline and nicotine on d-glucose and folate transport in rat jejunal brush border membrane vesicles
https://www.sciencedirect.com/science/article/pii/0020711X82901598
Cyclosporin A (immune suppressant)
Cicloral, Neoral and. Sandimmun)
Protective effect of folic acid on cyclosporine‐induced bone loss in rats
https://onlinelibrary.wiley.com/doi/full/10.1111/j.1432-2277.2011.01375.x
“In our experimental model, cyclosporine increased serum homocysteine levels and decreased bone volume and density. Folic acid may have a preventive role against bone loss in rats treated with cyclosporine.”
Metformin (diabetes)
Diabex®, Diaformin®, Formet®, Metforbell®, Glucohexal®, Glucomet®, Glucophage®, Genrx metformin®, Genepharm metformin®. METFORMIN ER : Diabex®,Diaformin XR®, Metex XR
Adverse effect of metformin therapy on serum vitamin B12 and folate: short-term treatment causes disadvantages?
https://www.ncbi.nlm.nih.gov/pubmed/23751310
“Recent observational studies, however, have demonstrated that long-term metformin therapy increases the probability of vitamin B12 and folate deficiency, and might contribute to the progression of diabetic peripheral neuropathy.”
Phenytoin (seizure)
DilantinInfatab
Phenytoin-folic acid: a review.
https://www.ncbi.nlm.nih.gov/pubmed/6370643
“Folate deficiency resulting from long-term phenytoin therapy is a common occurrence, but progression of the deficiency to a megaloblastic anemia is rare. “
Carbamezipine (anti convulsant)
Tegretol, teril
Sandoz
The effects of carbamazepine and valproate on folate metabolism in man.
https://www.ncbi.nlm.nih.gov/pubmed/6430017
These findings are interpreted as an inhibition of intestinal folic acid absorption caused by the antiepileptic therapy.
Oral contraceptives
Alesse, Apri, Aranelle, Aviane, Enpresse, Estrostep, Lessina, Levlen, Levlite, Levora, Loestrin, Mircette, Natazia, Nordette, Lo/Orval, Ortho-Novum, Ortho Tri-Cyclen, Yasmin and Yaz.
Oral contraceptives: effect of folate and vitamin B12 metabolism.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1862844/
Women who use oral contraceptives have impaired folate metabolism as shown by slightly but significantly lower levels of folate in the serum and the erythrocytes and an increased urinary excretion of formiminoglutamic acid. The vitamin B12 level in their serum is also significantly lower than that of control groups.
Antimalarials
malarone, aralen, mefloquine, qualaqine, primaquine, coartem
Folate metabolism as a source of molecular targets for antimalarials.
https://www.ncbi.nlm.nih.gov/pubmed/17661690
Dihydrofolate reductase inhibitors have been used as antimalarials over the past few decades, often in combination with dihydropteroate synthase inhibitors.
Trimethoprim (antibacterial)
Bactrim, Septra
The Effect of Trimethoprim on Serum Folate Levels in Humans: A Randomized, Double-Blind, Placebo-Controlled Trial.
https://www.ncbi.nlm.nih.gov/pubmed/26566149
In conclusion, we found that a daily dose of 400 mg trimethoprim for 7 days significantly lowered serum folate levels in healthy study participants.
Sulfazalazine (rheumatoid arthritis)
Azulfidine
Inhibition of Folate Enzymes by Sulfasalazine
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC372530/
These results are interpreted to indicate that sulfasalazine interferes with a folate recognition site which is common to these enzymes and to the intestinal transport system. Sulfasalazine, therefore, has certain properties of an antifolate drug.
Triamterine (hypertension)
Maxzide and Dyazide.
Competitive inhibition of folic acid absorption in rat jejunum by triamterene.
https://www.ncbi.nlm.nih.gov/pubmed/3760669
In an in vivo intestinal loop method, triamterene inhibited the intestinal absorption of folic acid in a dose-dependent fashion, with 50% inhibition of systemic absorption occurring at a luminal concentration of 0.01 mmol/L of triamterene.
