Vitamin D in preconception, pregnancy, and postpartum

Vitamin D is a secosteroid hormone with numerous functions throughout the body. It’s needed for bone metabolism via the regulation of calcium and phosphorus, modulation of the immune system (1), and acts as an epigenetic modifier (2).

Because vitamin D regulates many body systems, it’s critical during pregnancy, preconception, and postpartum. Vitamin D insufficiency and deficiency are exceedingly common in the general population, and nearly 50% of people worldwide have vitamin D deficiency (<50 nmol/L or <20ng/mL) (3).

Amazingly, a 2022 Australian study observed that 66% of women had insufficient vitamin D during preconception (4).

In this blog, I’ll cover the topic of vitamin D during preconception, pregnancy, and postpartum, including:

The roles of vitamin D during these critical periods
Optimal vitamin D levels during pregnancy
The importance of vitamin D cofactors, vitamin K2, and magnesium
Food sources of D, K2, and magnesium that can be easily incorporated into your patient’s diet

What role does vitamin D play during preconception?

In females, vitamin D is extraordinarily important for preconception and pregnancy. Many studies show that women with sufficient vitamin D status have better fertility and pregnancy outcomes (5, 6).

Vitamin D receptors are found in the cytoplasm of cells and in the ovaries, uterus, placenta, and testes, as well as the hypothalamus and pituitary. The critical need for vitamin D in the reproductive organs foreshadows its importance for both sperm and egg health (5).

During pregnancy, the placenta highly depends on vitamin D (7, 8). The placenta metabolizes vitamin D and releases the active metabolites into the fetal and maternal circulation. Additionally, vitamin D influences the expression of proteins and messenger RNA in the placenta (8).

With this knowledge, it makes sense that more vitamin D is needed during pregnancy. In my pregnancy-specific blood work class, I teach you how to interpret your patients’ vitamin D results in preconception, by trimester of pregnancy, and postpartum (9).

In males, vitamin D plays a role in testosterone production and helps regulate testicular calcium channels, essential for sperm motility. Sufficient vitamin D status in men before conception is associated with improved fertility and pregnancy outcomes (10).

It is common to overlook the importance of male nutrient status on pregnancy outcomes. However, male factors affect epigenetic changes that influence pregnancy outcomes and the health of the fetus and infant.

More specifically, male nutritional and hormonal health can affect not only his fertility and the ability of the couple to conceive but also the course of the pregnancy, whether the pregnancy is going to be viable, and the chances of congenital disabilities and other epigenetic issues that can have a positive or negative impact on the lifelong health outcomes of the offspring.

With this in mind, I recommend that the male partner take his health into account during the preconception period. This may include a functional health consultation, lab work (including vitamin D), and adapting a plan to address nutrient deficiencies and optimize metabolic health.

What is the role of vitamin D during pregnancy?

During pregnancy, intestinal calcium and phosphate absorption double due to the increased production of calcitriol (1,25-dihydroxy vitamin D), the active form of vitamin D (11).

Optimal vitamin D levels are associated with decreased risk of gestational diabetes (12), preeclampsia (13), and immune imbalances (14).

Let’s take a quick look at some of these connections in detail to better understand the importance of vitamin D during pregnancy.

Low vitamin D levels are linked to an increased risk of gestational diabetes (12, 15).

Vitamin D is negatively associated with insulin resistance in pregnant women (16) and the general population (17).

Xu et al. (2022) suggested that one of the beneficial effects of vitamin D on insulin signaling may be due to the role vitamin D plays in regulating inflammation.

“This may be because vitamin D3 can effectively inhibit the occurrence of inflammation, and inflammation is the main factor inducing insulin resistance. Vitamin D3 can inhibit the occurrence of inflammatory reaction by up-regulating MAP kinase, regulating NF-kB signaling pathway, regulating cytokine level and prostaglandin pathway, and then achieve the purpose of reducing insulin resistance” (17).

Vitamin D and preeclampsia

Vitamin D deficiency and insufficiency are linked to an increased risk of preeclampsia (13, 18), and vitamin D supplementation may be an effective strategy for preventing preeclampsia (19).

“Indeed, vitamin D deficiency is associated with a relatively large number of risk factors for endothelial dysfunction and vascular health impairment. On the other side, adequate vitamin D intake might help with the maintenance of the calcium homeostasis – which is inversely related to blood pressure levels–or may directly suppress the proliferation of the vascular smooth muscle cells. Furthermore, vitamin D might be a powerful endocrine suppressor of renin biosynthesis and could regulate the renin–angiotensin system, which plays a critical role in blood pressure control. Finally, vitamin D could also modulate the synthesis of adipokines related to endothelial and vascular health” 20.

There are many risk factors for preeclampsia beyond vitamin D deficiency. If you’re at risk of preeclampsia, there are effective science-backed strategies to reduce your risk and symptom severity.

Vitamin D and immune modulation during pregnancy

During pregnancy, the maternal immune system suppresses the Th1 response and favors a Th2 and Treg (tolerance) response. This immunological change is a natural occurrence that protects the developing fetus from the maternal immune system.

Vitamin D is critical for healthy immune function (21) and may play a role in this immune shift during pregnancy (22).

“Firstly, vitamin D plays an important role in modulation of the T-cell subsets. Vitamin D inhibits the release of certain cytokines, including IL-2, IL-12, and IFN-γ, thus impeding Th1 differentiation. Vitamin D has also showed activity against IL-17, therefore diminishing pro-inflammatory innate activation.91 Moreover, vitamin D increases the production of Treg cells, and IL-4 secretion, promoting the shift to Th2 predominance and enhancing fetomaternal tolerance” (22).

Dysregulation of T-cell balance during pregnancy has been associated with difficulty conceiving, recurrent pregnancy loss, and preeclampsia. This may be one reason why vitamin D deficiency elevates the risk of pregnancy complications (1).

The vitamin D/autoimmune connection

Vitamin D deficiency has been linked to several autoimmune diseases, including Hashimoto’s thyroiditis, lupus, and rheumatoid arthritis (1). Because of the role of T-cell dysregulation on autoimmunity (many autoimmune diseases involve an overactive Th1 response) and the role of vitamin D on T-cell regulation, vitamin D should be considered for pregnant women with a history of autoimmunity.

Fascinatingly, maternal vitamin D status appears to influence not only the health of the infant but also their risk of autoimmunity later in life (1).

For instance, a 2016 study observed that adults born to mothers with vitamin D deficiency (<30 nmol/L) had a nearly 2-fold increased risk of multiple sclerosis when compared to adults born to mothers with sufficient vitamin D (23).

Vitamin D supplementation during pregnancy

While studies show that 4,000 IU a day of vitamin D is generally safe and effective in pregnancy (24, 25), testing individual levels allows for properly individualized supplementation because there have been cases of infants with hypervitaminosis D or hypercalcemia at birth born to mothers who supplemented at this level (26, 27).

Some practitioners like to measure both the 25(OH)D, which is the inactive form or storage form, and the active form (1,25 [OH]2 D), and some have a practice of looking at the ratio of these two forms of vitamin D depending on the patient’s presentation.

It’s important to avoid excessively low levels (by far the most common scenario) and excessively high ones (quite unusual).

The Vitamin D Council considers 40 ng/mL (100 nmol/L) the minimum for vitamin D sufficiency and anything greater than 150 ng/mL (375 nmol/L) toxic.

I’ve only had two clients (one pregnant, one a male client with hypercalcemia) in the entire eleven years I’ve been in practice who have tested positive for excessively high vitamin D at the start of our working together. I’ve never had a client following my suggestions for vitamin D supplementation test above optimal levels.

It’s important to calculate vitamin D intake from all supplements and recalculate intake every time the patient changes supplements, including their prenatal multi—high-quality prenatals range from 1,000 to 4,000 IUs in a daily dose.

Testing is important because signs and symptoms of excess and deficiency could be mistaken for run-of-the-mill pregnancy symptoms.

Optimal vitamin D levels during preconception, pregnancy, and postpartum

My initial bias as a practitioner was against vitamin D supplementation, and I was skeptical of the recommendations of the Vitamin D Council, which seemed too high to me at the time.

However, over the years, I’ve worked with many clients who have autoimmune issues and other complex health problems. I’ve also read numerous research studies on vitamin D and have implemented what I learned from those studies in my practice. Based on my experience and the research, I believe that following the Vitamin D Council’s recommendations can lead to optimal health outcomes for both pregnant and non-pregnant individuals.

40 ng/mL (100 nmol/L) is the bare minimum that many consider optimal during preconception, pregnancy, and postpartum (24).

If someone is taking 4,000 IU per day of vitamin D and has levels of at least 40 ng/mL, I consider that acceptable if they aren’t demonstrating a high risk for autoimmune conditions, infections, and postpartum depression, in which case we might consider the possibility of taking a somewhat higher dose, contingent on approval by their medical team.

Additionally, if someone is taking 4,000 IU per day and has a level of up to 80 ng/dL, I consider that to be optimal as well (consistent with the sufficient ranges of the vitamin D Council, which are 40-80 ng/mL).

Conversely, if someone is taking 4,000 IU per day and has levels that are above the upper level of the high-normal threshold of 100 ng/mL set by the Vitamin D Council, I would suggest that the person decrease their intake of vitamin D and retest levels after about eight weeks to ensure they are in the optimal range.

While not much is known conclusively about the impact of excess vitamin D levels during pregnancy, there is a concern for fetal and neonatal hypercalcemia. The studies are really mixed, so we can’t be sure that there is a substantial risk of symptomatic neonatal hypercalcemia versus transitory high calcium levels in the blood with no symptoms. Sometimes, these hypercalcemias are just found incidentally, not because the baby is actually having symptoms.

The role of vitamin D during postpartum and lactation

During postpartum and lactation, maintaining optimal levels of vitamin D is protective against postpartum depression (28), postpartum anxiety (29), and postpartum thyroiditis (30).

For example, Wang et al. (2018) observed that women with vitamin D levels less than 20 ng/mL (50 nmol/L) had 2.67 times the risk of PPD (31).

Click here to learn more about nutrients and postpartum depression.

It’s important to note that vitamin D status during pregnancy also affects postpartum outcomes, just as preconception D status affects pregnancy outcomes. Vitamin D status during pregnancy is correlated with postpartum depression and anxiety risk (32, 33), as well as postpartum thyroid function (34).

Although only a handful of studies have examined the connection between vitamin D and postpartum thyroiditis, there is abundant evidence regarding the importance of optimal vitamin D for thyroid health and autoimmune thyroid disease (35).

“…the latest studies have shown that VitD levels ≥50 ng/mL (125 nmol/L) reduce the risk of hypothyroidism by up to 30%. Therefore, the administration of high doses of VitD in patients with hypothyroidism rapidly improved thyroid function. It has been proven that VitD supplementation can also prevent the development of thyroid diseases. Moreover, in their meta-analysis and systematic review, Wang et al. have proved that VitD supplementation significantly reduces anti-TPO and anti-Tg levels. These results have been confirmed by Koehler et al., and this was especially true of the level of anti-TPO antibodies ” (35).

When and how often should you test vitamin D?

It’s ideal to test vitamin D levels about every six months and more often in special situations. More frequent testing may also benefit patients with above-optimal vitamin D levels.

I have my clients run a vitamin D panel twice a year. It doesn’t matter when, but once your patient gets in the groove of things, have them consistently retest about every six months.

Two easy reminders to help your patients know when to get their vitamin D checked are to test around the summer and winter solstice or during the time change in the spring and fall.

Important cofactors for vitamin D metabolism: magnesium and vitamin K2

Magnesium, the essential mineral responsible for hundreds of enzymatic functions in the body, maintains a delicate balance with vitamin D and is crucial for maintaining optimal vitamin D levels.

Modern diets are severely deficient in magnesium, and it’s estimated that around 75% of the population consumes a diet deficient in magnesium and that 50% of women of reproductive age do not consume enough magnesium to meet their basic needs (36).

Magnesium deficiency leads to lower levels of the active form of vitamin D

(36), and a higher magnesium intake protects against vitamin D deficiency and the risk of mortality due to deficiency (37).

Vitamin K2 and D have a synergistic relationship that appears essential for cardiovascular health, particularly when supplementing with vitamin D (38).

Vitamin K2 is also necessary for calcium metabolism, and vitamin D plays a part in bone health. Supplementing with vitamin K2 and D has been shown to improve bone mineral density more than vitamin D alone (39).

Some researchers have suggested that vitamin D toxicity may result from vitamin K deficiency caused by high vitamin D levels (38, 40).

According to Ballegooijen et al. (2017),

“A large group of people uses both vitamin D and calcium for the prevention of falls and fractures. Given the fact that 25(OH)D is converted to 1,25(OH)D, vitamin D supplementation stimulates the production of 1,25(OH)D. This means that long-term vitamin D supplementation could promote the production of large amounts of vitamin K-dependent proteins, which remain inactive because there is not enough vitamin K to carboxylate. We propose a new hypothesis that if vitamin D concentrations are constantly high, there might not be enough vitamin K for activation of vitamin K-dependent proteins. Consequently, excess vitamin D diminishes the ability of vitamin K-dependent proteins to function properly, to stimulate bone mineralization, and to inhibit soft tissue calcification.

Increased calcium intake by itself may not be problematic as long as there is a steady state between optimal vitamin D and vitamin K concentrations. The disbalance between vitamin D and vitamin K promotes an environment in which excess calcium will be deposited into our vascular tissue instead of bone” (38).

Chris Masterjohn (2007) has hypothesized that vitamin A can mediate the delicate balance between D and K2, protecting against vitamin D toxicity by reducing vitamin K-dependent proteins (40).

Each cofactor demonstrates a fascinating connection between the vital micronutrients often found in isolated form in the supplement aisle. We must only supplement with an isolated vitamin such as vitamin D if we know the individual status of other micronutrients such as magnesium and K2.

In my practice, I generally have clients on a prenatal or multi with K2, magnesium, and vitamin A. They may take additional vitamin D beyond what’s in their multi, but I am not giving the additional D in the form of a combination D/K2 supplement. I also suggest foods rich in D, magnesium, A and K2..

Use this link to get the most evidence-based and up-to-date information on choosing the perfect prenatal for your patients.

For many, vitamin A and magnesium are easier to get through foods than vitamin D and K2. Sunlight is the best way to raise vitamin D levels outside of supplementation; however, this can be difficult during cold months.

Food sources of vitamin D:

Fatty fish
Cod liver oil
Egg yolks
Beef liver

Food sources of vitamin K2:

Natto (fermented soybeans)
Beef liver
Beef
Grass-fed butter and cream
Hard cheeses

Food sources of magnesium:

Pumpkin seeds
Chia seeds
Almonds
Cashews
Leafy greens
Legumes and whole grains
Soy milk
Skin-on potato

Food sources of vitamin A:

Beef liver
Cod liver oil
Sweet potato, carrots, pumpkin, cantaloupe, spinach, and other red and orange plant foods provide vitamin A as provitamin A or beta-carotene. Beta carotene must be converted into the active form of vitamin A called preformed A (retinol). The conversion rate varies between individuals due to genetic influences. Animal foods like those listed above are good sources of preformed A.

References

1)https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883724/

2)https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4010791/

3)https://www.frontiersin.org/articles/10.3389/fnut.2023.1070808/full

4)https://www.sciencedirect.com/science/article/pii/S2772598722000022

5) https://pubmed.ncbi.nlm.nih.gov/30322097/

6) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5545066/

7) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2993775/

8) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8903835

9) https://pubmed.ncbi.nlm.nih.gov/30322097

10)https://pubmed.ncbi.nlm.nih.gov/31190482

11) https://pubmed.ncbi.nlm.nih.gov/35615608