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“Even though COCs (combined oral contraceptives) are among the most prescribed drugs, with more than 100 million users worldwide, various side effects may occur during their assumption, most of which may correlate to nutritional deficiency of vitamins and minerals.”1

This excerpt is taken from the introduction to a 2022 Review on ‘Counteracting side effects of combined oral contraceptives through the administration of specific micronutrients’, and published in the European Review for Medical and Pharmacological Sciences. It speaks volumes on the potential for COCs to deplete essential nutrients. And since COCs are ‘among the most prescribed drugs, with more than 100 million users worldwide’, it also highlights the need for women to have easy access to accurate information on nutrient intakes and depletions with COCs, to enable informed health decisions. This is a complex topic; the full breadth of which we can’t cover in this article. We can however make a good start by reviewing 5 essential nutrients that are commonly depleted by the pill. Read on to find out more.


Folate is a water-soluble vitamin that has critical roles to play in DNA synthesis and cell division. It’s no accident that it sits right at the top of this list. Shortly after the introduction of oral contraceptives, studies appeared to suggest their consumption might reduce blood folate levels.2-6 The hormonal content of oral contraceptives was however much higher in the 1960s and 70s when these initial studies were carried out, which has raised the question of how relevant these results still are today? A more recent systematic review and meta-analysis answered this question and concluded, “because of the reduction in blood folate concentrations associated with the use of oral contraceptives, it is crtical for women of childbearing age to continue folate supplementation during oral contraceptive use.”7

Folate is particularly important during the early stages of pregnancy and folate supplementation during this time is associated with a reduced risk of neural tube defects (NTDs), congenital heart defects and orofacial clefts.8

In recognition of the importance of folate for women during reproductive years and the potential folate-depleting effects of oral contraceptives, a product fortified with folate was made available in 2012 in some markets to help reduce the risk of NTDs in a pregnancy conceived during use or shortly after discontinuation of oral contraceptive products.9,10

There is also some evidence that oral contraceptives may increase the rate of progression of cervical dysplasia to cervical cancer, and that folate may slow or reverse this dysplasia.11,12

It is crucial that women of child-bearing age pay particular attention to their folate status and this is especially important if they are taking COCs.  You will find folate in foods such as leafy green vegetables.  You can also take folate in supplements. Many supplements contain the synthetic form of folic acid which needs to be converted to the more active form of 5- methyltetrahydrofolate (5-MTHF) in the body.  There is however a fairly common genetic variant which may reduce the ability to make this conversion.  Supplementing directly with the body-ready form of 5-methyltetrahydrofolate (5-MTHF) by-passes the need for this conversion and may be a more effective choice.

Vitamin B12

Several studies have found low levels of vitamin B12 in women using oral contraceptives, compared to non-users.13-23 There is a close relationship between folate and vitamin B12 metabolism in the body, however it is still not well understood how oral contraceptives may cause low vitamin B12. As with low folate levels, low maternal B12 status is also considered to be an independent risk factor for neural tube defects (NTDs).24

In addition to its protective role in pregnancy, vitamin B12 is involved in over 100 daily functions; it helps the blood to carry oxygen and is essential for healthy nerves, DNA synthesis, fatty acid synthesis and energy production. Our vitamin B12 levels depend directly on dietary intake from food or dietary supplements. It is found in rich supply in animal products and can’t be reliably supplied by a plant-based diet.

A recent systematic review found that combined oral contraceptives deplete vitamin B1225 and supports the view that vitamin supplements may be helpful in women taking these oral contraceptives.26

Vitamin E

Vitamin E is well known for its diverse and crucial effects on health – as an important antioxidant, for skin health, immune function and to protect cardiovascular health too. It is a fat-soluble vitamin and is incorporated into fat-rich cell membranes where it helps to provide essential protection against oxidative damage.

Research has shown that oral contraceptives increase markers of oxidative stress and decrease blood levels of vitamin E. 27-29 Research has also found an increase in blood clotting activity in combined oral contraceptive users, which may be linked to reduced levels of alpha-tocopherol found in these subjects. Supplementation with vitamin E may help to reduce platelet over-activity.30-33

Many people are unaware that the term vitamin E actually refers to a group of compounds which include several different tocopherols and tocotrienols. It is important therefore to choose a supplement that reflects this natural mix.


In a 2022 review of micronutrients and oral contraceptives, the authors wrote, “mineral status appears frequently affected in women taking hormonal therapies, especially for what concerns magnesium, zinc and selenium levels.”1 In fact, research shows that poor magnesium levels are common among women taking COCs and many studies have shown lower serum magnesium levels in oral contraceptive users compared to both non users and women taking other forms of contraception.34-40

This is particularly concerning when you consider that the body has widespread needs for magnesium and the average Western diet is already unlikely to provide enough. And this is especially true when coupled with a fast-paced 21st century lifestyle - characterised by poor sleep, high intensity exercise and chronic stress – all factors which may further deplete magnesium.

When magnesium depletion occurs, it alters the calcium: magnesium ratio; “the resulting altered calcium: magnesium ratio influences processes of blood coagulation, increasing the risk of venous thrombosis, as described in a meta-analysis of 26 observational studies.”1,41-42

It seems reasonable therefore for women taking combined oral contraceptives to consider supplementing with additional magnesium. Magnesium glycinate is a calming and relaxing supplement form which is generally well tolerated and may be particularly helpful.

Vitamin B6

Many micronutrients work together and it is crucial to consider these inter relationships, as well as the context or ‘bigger picture’, when choosing to supplement. Vitamin B6 has important roles as a co-factor in many enzymatic reactions including supporting the conversion of an amino acid called tryptophan into the ‘happy’ neurotransmitter serotonin, supporting energy production and working together with nutrients such as folate and vitamin B12 to support methylation processes and DNA synthesis.43 Vitamin B6 may also be involved in modulating magnesium levels and has similar effects to vitamin E in reducing breast pain.44-46 In a large cross-sectional study involving 3362 adults, researchers found inadequate intake of vitamin B6 was related to an increased risk of anxiety and depression in women.47

Pyridoxal-5-phosphate is an active form of vitamin B6 which has been found to be reduced in oral contraceptive users compared to non-users.48,49 This demonstrates the likelihood of reduced levels of B6 in women taking combined oral contraceptives. Studies have also shown that daily supplementation with vitamin B6 reduces common side effects of oral contraceptives.50-52

Vitamin B6 can be supplemented in the active form of pyridoxal-5-phosphate and may be an important consideration for women taking combined oral contraceptives.

So what supplements should I consider while taking the combined oral contraceptive pill?

Research clearly demonstrates that combined oral contraceptives have the potential to
deplete many essential nutrients. Here we have highlighted just a few, and sadly there are many more. It seems reasonable to recommend therefore, on the back of even just the evidence presented here, that women taking combined oral contraceptives may benefit from supplementing their diets with a daily multivitamin and mineral supplement. Selecting a high quality daily multivitamin and mineral supplement that provides essential nutrients in active forms seems a worthwhile investment in both immediate and long term health.

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