Fullscript Academy

Fullscript has partnered with Dr. Lara Zakaria, PharmD, CNS, IFMCP, to provide the following protocol to better support individuals taking oral contraceptives. 

This protocol was designed to address common oral contraceptive-induced nutrient depletions. Beyond drug-induced depletions, it offers additional considerations when treating menstruating individuals, such as supporting healthy iron levels, elimination pathways, hormone metabolism, and microbiomes.

Multivitamin/multimineral including folate, zinc, selenium, vitamin C, vitamin A, vitamin E, and B complex

Minimum of 400 mcg folate, 100 mcg selenium, 15 mg zinc, and 500 mg vitamin C

Studies suggest that oral contraceptives might lead to nutrient depletions, which can lead to nutritional imbalances. A well-absorbed multivitamin and multimineral supplement can help us close those gaps and ensure a balance of key minerals and B vitamins, especially folate, necessary for optimal metabolic health and hormone balance. 

• A 2013 review suggests supplementing with B vitamins, vitamin C, selenium, magnesium, and zinc to help reduce the risk of nutrient depletion-related conditions associated with the use of oral contraceptive pills (OCPs): anemia, leukopenia, thrombocytopenia, thromboembolism, low serotonin levels, headaches, muscle spasms, osteoporosis, and increased blood pressure. (Prescott et al., 2018) 
• The authors of a second review elaborate that individuals consuming diets low in nutrients or with malabsorption conditions are especially vulnerable to nutrient deficiencies brought on by OCPs and may benefit from proper supplementation. (Palmery et al., 2013)

200–400 mg daily

In studies analyzing drug-induced nutrient depletions due to OCPs, magnesium is a well-documented deficiency. Because of its importance in multiple biochemical reactions in the body, supplementing magnesium can be important. Magnesium is associated with improved blood sugar balance, mood, sleep, hormone, and neurotransmitter balance.

• The review authors emphasize the importance of maintaining adequate levels of magnesium, which research finds to be depleted in individuals taking OCPs. (Palmery et al., 2013)
• Authors of the review note the mechanisms associated with OCP-induced nutrient depletions include malabsorption, increased excretion, decreased protein binding, and altered metabolism, warranting regular assessment and supplementation, including magnesium. (Prescott et al., 2018)

Prebiotics fiber blend

4–8 g daily

A balanced microbiome is a key foundational health consideration for gut health, hormone balance, and mood. Metabolizing oral contraceptives requires a diverse and robust microbiome. 

Prebiotic fibers have been shown to be an effective and sustainable way to improve microbiome balance. Studies show that there is a dose-dependent relationship between certain prebiotic fibers like xylooligosaccharides (XOS), fructooligosaccharide (FOS), and galactooligosaccharides (GOS) with improving short-chain fatty acid (SCFA) production, especially butyric acid and lowering beta-glucuronidase—key compounds associated with improved gastrointestinal health and hormonal balance.

• A 2019 prospective study found that trimethylamine N-oxide (TMAO) and its precursors were elevated in patients with polycystic ovarian syndrome (PCOS) taking OCPs compared to participants without PCOS taking OCPs. This study suggests that OCP use may alter the microbiome of patients with PCOS, increasing the production of TMAO, a well-known cardiometabolic risk factor. (Eyupoglu et al., 2019)
• Probiotics and prebiotics have been shown to possess antioxidant, anti-inflammatory, antiplatelet, antilipidemic, and TMAO-lowering properties. The authors of the study conclude that restoring the health of the gut microbiota may help reduce the risk of cardiovascular disease in the general population. (Oniszczuk et al., 2021) Although research is still in the early stages, probiotics and prebiotics supplementation may help reduce the risk of cardiometabolic disease in individuals taking OCPs.
• Prebiotics have been shown to support overall microbiome diversity and the production of SCFAs. Bifidobacterium, Faecalibacterium, and Akkermansia are especially responsive to prebiotic supplementation, as seen by the increased production of total SCFA levels, butyrate in particular, as well as improvement in beta-glucuronidase. (Bedu-Ferrari et al., 2022)(Vinelli et al., 2022)
• A prospective randomized controlled trial (RCT) found that supplementation with 10 g per day of FOS positively impacted the production of microbiome strains associated with butyrate production. (Tandon et al., 2019)

Support nutrient deficiencies associated with oral contraceptives with the evidence-based ingredients in this protocol. 

Iron bisglycinate

25–30 mg, every other day

Iron is an important mineral necessary for multiple physiological functions including thyroid function and the production of hemoglobin, energy, and neurotransmitters like dopamine. Women are at increased risk of iron deficiency anemia (IDA), which can lead to symptoms like fatigue, weakness, dizziness, headaches, brittle nails, hair loss, and increased susceptibility to infections.

Along with signs and symptoms, laboratory testing can help identify iron deficiency and correct it with proper supplementation. Bisglycinate formulations may enhance absorption and reduce the risk of common side effects like stomach upset, nausea, and constipation. Every-other-day dosing is associated with improved iron repletion and a reduced risk of side effects through the regulation of hepcidin, a protein that controls iron absorption.

• Ferrous bisglycinate, has been demonstrated to have higher bioavailability and absorption and lower side effects and tolerability issues compared to conventional iron salts, including ferrous sulfate and ferrous fumarate. (Coplin et al., 1991)(Szarfarc et al., 2001) 
• A 2013 review suggests supplementing with iron to help reduce the risk of OCP-related IDA. Monitoring and treating IDA with supplemental or dietary iron should always be personalized. (Prescott et al., 2018) 
• A cross-over study examining the absorption rate of supplemental iron found that, compared to daily dosing, alternate-day dosing significantly increased fractional iron absorption (FIA) but did not increase hepcidin expression. The study suggests that alternate-day dosing may be especially helpful when treating individuals with IDA due to hepatic hepcidin expression. (Stoffel et al., 2020)

Ashwagandha (Withania somnifera)

500 mg daily

Ashwagandha is known for its adaptogenic properties, assisting in managing stress by regulating cortisol levels. It can benefit individuals facing stress-related issues and support hormonal balance, particularly in conditions like hypothyroidism and PCOS by potentially regulating hormone levels via multiple mechanisms.

This adaptogenic herb has been shown in studies to help improve mood, reduce anxiety, and boost energy, focus, and resilience.

• A systematic review, including 12 studies, found that supplemental ashwagandha was superior to placebo in improving athletic performance, endurance, and mental health, including anxiety. (Bonilla et al., 2021) 
• A trial examining the impact of 225 mg per day or 400 mg per day of ashwagandha demonstrated a statistically significant improvement in cognitive abilities, cortisol levels, and self-reported mood, stress, food cravings, and anxiety. (Remenapp et al., 2021)