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Can vitamin D deficiency cause recurrent miscarriage?

Reviewed by | Last updated Aug 9, 2020 | 1 comment

Allison Schaaf - Miscarriage Hope Desk

Hi, my name is Allison Schaaf, my own fertility journey, including 5 miscarriages, inspired me to create this website to help YOU navigate your own fertility journey.

Here are my main takeaways I would share with you as a friend:

  • Knowing your vitamin D levels is your first step to understanding if it might be impacting you fertility!
  • Low vitamin D might indicate an auto-immune condition or metabolic issues

Of course, I also recommend you do your own research! That is why I have coordinated these articles with the nitty-gritty details and links to research so you can best decide what works best for you, read on for more! And don’t miss my Action Steps at the bottom of the article!

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Table of Contents

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What is vitamin D?

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How vitamin D is processed and used in the body

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How vitamin D may prevent miscarriage

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How to know if you are vitamin D deficient

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Factors affecting vitamin D & your vitamin D levels

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Getting enough vitamin D – Sun or Supplement?

You may think of vitamin D as important for bone health, but it has many other important roles throughout the body. Vitamin D deficiency during pregnancy is linked to adverse outcomes, including preeclampsia, insulin resistance, gestational diabetes, increased risk of infections, preterm labor, and recurrent miscarriage. 1234 Unfortunately, vitamin D deficiency remains a widespread but unaddressed problem that may affect up to 50% of pregnant women. 5

However, simply supplementing with vitamin D does not always solve the problem. This article will cover how vitamin D is important for pregnancy, how vitamin D problems may contribute to recurrent pregnancy loss, and what you can do about it.

What is vitamin D?

Vitamin D is a fat-soluble vitamin that also functions as a hormone. It has a steroid backbone similar to the stress hormone cortisol, and sex hormones estrogen and testosterone. Your body can synthesize vitamin D when your skin is exposed to the Ultraviolet B (UVB) ray in sunlight, so it is called “the Sunshine Vitamin.” However, you can also get vitamin D from food and supplements. There are two main forms of vitamin D, including D2 and D3.

Food sources of vitamin D3 include:

  • Free-range eggs and fatty meats
  • Liver
  • Cod liver oil
  • Dairy products such as butter, cream, and cheese
  • Fatty fish, such as salmon and mackerel
  • Foods fortified with vitamin D, including dairy products, orange juice, soy milk, and breakfast cereals

Mushrooms that have been irradiated with UVB or the sun are good sources of plant-based vitamin D2. Vitamin D2 is easier to produce than D3, so you may also find it in dietary supplements and fortified foods. However, because vitamin D3 is better because it is twice as potent as vitamin D2. 67

How vitamin D is processed and used in the body

How vitamin D is processed and activated in the body
How vitamin D is processed and activated in the body; DBP = vitamin D-binding protein. 8

Ingested vitamin D3 and vitamin D produced in the skin is converted into 25-hydroxyvitamin D (25(OH)D) in the liver. 25(OH)D is the circulating form of vitamin D that is most often tested in vitamin D lab tests, although it is not the active form of vitamin D.

The kidneys activate 25(OH)D into the active vitamin D called 1,25-dihydroxyvitamin D, also called calcitriol and 1,25(OH)2D, using the mitochondrial enzyme CYP27B1. Here, the enzyme CYP24A1 inactivates 1,25(OH)2D to keep the active vitamin D within the narrow range.

Some other tissues can uptake and activate 25(OH)D, including decidua (thick mucus membranes that line the uterus during pregnancy) and placental tissues. 9

1,25(OH)2D activates vitamin D receptor (VDR), which combines with a vitamin A receptor called retinoid X receptor (RXR). VDR works with RXR to turn on vitamin D’s target genes, such as genes for antimicrobial peptides, bone matrix proteins, and immune system balance. 1011

How vitamin D may prevent miscarriage

Although it is best known for bone building and calcium absorption, vitamin D has many other important roles in the body, especially during pregnancy. Clinical studies have clearly shown that preconception healthy vitamin D levels improve the odds of pregnancy and live births.  A large US National Institute of Health study showed that among women who became pregnant, each 10 ng/mL increase in preconception vitamin D level was associated with a 12% lowered risk of miscarriages. 12 In addition, vitamin D deficiency is associated with first-trimester miscarriage. 13 Here are the important roles of vitamin D in pregnancy.

1. Promotes immune balance

During pregnancy, the immune system adapts in order to avoid rejecting the fetus, but also to maintain the ability to fight off infections effectively. These include the shift from Th1 (autoimmune, antiviral, and anti-bacterial) to Th2 (allergic and antiparasitic), and Th17 (autoimmune) to regulatory T cells, which induces immune tolerance. 14 This immune shift explains why many women with preexisting autoimmune conditions experience remission during their pregnancies, whereas allergic diseases often worsen during pregnancies. In addition, vitamin D increases certain immune responses and may overall reduce infection rate during pregnancy and in neonates. 15

Many women with recurrent pregnancy loss suffer from autoimmune conditions or have ongoing autoimmune pathology that prevents or reverses these immune adaptations. 161718 Along with increased autoimmunity, many of these women have abnormal vitamin D function in their uterine and pregnancy tissues. 19

Vitamin D promotes immune balance by stimulating regulatory T cells, and reduces excessive Th1 and Th17 activity. 20 Sensibly, vitamin D deficiency and abnormal vitamin D metabolism are linked to many autoimmune diseases. 21

Vitamin D may be important for necessary immunological changes during pregnancy, which is why vitamin D deficiency is linked to adverse pregnancy outcomes. 22 Also, the deficiency may worsen autoimmune diseases that lead to miscarriage, such as antiphospholipid syndrome. 23 However, the benefit of vitamin D supplementation in autoimmune disease and pregnancy is debated, as some experts suspect that low 25(OH)D levels could be a symptom of autoimmunity. 2425

2. Promotes metabolic health

Pregnancy is a metabolic stressor, which explains why preexisting metabolic disorders, such as obesity, diabetes, and polycystic ovarian syndrome often lead to infertility. In addition, insulin resistance during pregnancy often leads to adverse outcomes, such as gestational diabetes, preeclampsia, and hypertension. 26 Vitamin D deficiency may contribute to obesity, insulin resistance, and cardiovascular disease. 2728

In women with gestational diabetes, supplementation with vitamin D may improve insulin sensitivity and metabolic markers, including triglycerides and cholesterol. 29 By promoting metabolic health, vitamin D supports a healthy pregnancy and reduces the risk of complications.

3. Supports fetal development

Vitamin D is so important for fetal development and pregnancy that the pregnancy tissue has its own built-in vitamin D transport and processing systems. 3031 First, vitamin D helps with calcium absorption and metabolism, which are essential for the development of bones and many other tissues. 32 Second, vitamin D controls many key processes in pregnancy. In early pregnancy, 1,25(OH)2D helps prepare the endometrium (innermost cell lining of the uterus) for implantation. 33 1,25(OH)2D also promotes correct cell division and controls the production of pregnancy hormones such as hCG, estradiol, and progesterone. 34

How to know if you are vitamin D deficient

The best way to know your vitamin D levels is to use a blood test. Tests for both 25(OH)D and 1,25(OH)2D are commercially available, although 25(OH)D levels are typically more stable and thus more commonly tested to screen for vitamin D deficiencies. 

Vitamin D reference range

CategoryInstitute of Medicine, General Population 35Endocrine Society Population at Risk 36
ng/mLnmol/L or nMng/mLnmol/L or nM
Deficiency<12<30<20<50
Insufficiency12–2030 – 5020–2950 – 75
Sufficiency20–3050 – 7530–10075 – 250
No added benefit30–5075 – 125
Possible harm>50>125>100>250

Vitamin D optimal ranges during pregnancy

Optimal vitamin D levels is debated. Vitamin D levels between 30 – 40 ng/mL or 75 – 100 nmoL/L are associated with healthy pregnancy and live birth, and lowest all-cause mortality in the general population. 3738 Some doctors may recommend at least 40 ng/mL to account for potential technical variabilities between labs. 39 A study that examines vitamin D metabolites also suggests that over 40 ng/mL may be more optimal for pregnant women. 40

Clinical studies have found that approximately 45% of women with recurrent pregnancy loss are deficient in vitamin D. 4142 Therefore, low blood vitamin D may be a contributor but not the sole cause of the miscarriages. 

Can you have too high vitamin D?

Excessive vitamin D is associated with increased all-cause mortality and is typically not beneficial. 43 However, vitamin D toxicity is rare and typically only happens after prolonged consumption of very high doses (>10,000 IU) given normal absorption. Excess vitamin D function can be diagnosed when there is elevated 25(OH)D, along with elevated calcium and possibly phosphate levels. 44 However, high 25(OH)D may not always lead to vitamin D toxicity. 

Factors affecting your vitamin D levels

Risk factors for vitamin D deficiency 45

  • Darker skin complexion
  • Air pollution
  • Latitude or being further away from the equator, such as in the Scandinavians 
  • Regular sunscreen use
  • Obesity
  • Extensive clothing covering skin
  • Aging
  • Malabsorption syndromes, such as cystic fibrosis, irritable bowel syndrome, short bowel syndrome, liver disease, and bariatric surgery
  • Poor digestion
  • Compromised fat digestion and absorption, such as not having a gallbladder
  • Kidney and liver diseases
  • Medications such as anticonvulsants, spironolactone, clotrimazole, rifampin corticosteroid drugs may prevent absorption or increase vitamin D breakdown
  • Chronic inflammation

Influence of skin pigmentation (darkness) on the risk of burns and skin cancers. Darker complexions, such as those found in people with African, Indian, or aboriginal ascents, may increase the risk of vitamin D deficiency. Image source: 46

Getting enough vitamin D – Sun or Supplement?

Humans evolved near the equator before migrating north. In addition, our ancestors spent much more time outdoors than most of us currently do now. Our skin produces vitamin D upon exposure to ultraviolet B (UVB) radiation, which is an invisible light present in sunlight. 47

Also, keep in mind that full-spectrum sunlight contains other wavelengths than UVB, including visible light, infrared, UVA, and UVC (at high elevation). Full-spectrum sunlight affects your biology beyond increasing vitamin D levels, such as increasing nitric oxide, entraining our circadian rhythm, increasing regulatory T cells, boosting mood, and increasing anti-inflammatory and antioxidant enzymes. 4849 Therefore, sun exposure is more beneficial than vitamin D supplementation. 50 However, it may be tricky to reach healthy vitamin D levels from the sun alone, especially if you live far away from the equator, have long winters, or have a dark complexion. 

Caucasians with type II skin (tans minimally) in the southern US states (Latitude ~40 degrees) may be able to obtain sufficient vitamin D by spending 15 minutes in the sun with face, arms, and legs exposed 2 – 3 times a week between May – October. 5152

Benefits of sun exposure

Risks of sun exposure

Is sun exposure dangerous?

For decades, we have been advised to avoid the sun and use sunscreen to protect ourselves from skin cancer. However, more recent studies suggest that the health benefits of sun exposure without sunburn may exceed the risk. 65 Paradoxically, vitamin D deficiency increases the risk of melanoma and people with indoor occupations are more likely to develop skin cancers than those who work outdoors. 6667 However, indoor tanning significantly increases the risk of skin cancers. 68

Considerations when getting vitamin D from the sun

  1. UVB light penetrates the atmosphere poorly, so the further you are from the equator, the less UVB light you get. 
  2. UVB does not penetrate glass, so you cannot get vitamin D from exposure to sunlight indoors.
  3. Sunscreens with SPF15 may reduce vitamin D3 production by 99%. 69
  4. When an adult is exposed to the sun in a bathing suit until the skin turns pink, the amount of vitamin D produced is equivalent to 10,000 – 25,000 IU of supplementation. 70 However, sun exposure does not result in toxic levels of vitamin D. 
  5. Individual responses to sun exposure on 25(OH)D may vary based on risk factors of vitamin D deficiency listed above.
  6. To prevent sunburn, acclimatize to the sun by gradually increasing the dose, especially if you are fair-skinned. Start from 5 minutes before 11 AM and after 3 PM, and gradually work up your exposure by a few minutes until just before you burn or your vitamin D levels are above 40 ng/mL.
  7. Skin products that contain vitamin A (retinol or retin A) and vitamin C or acidic peels make your skin more vulnerable to aging and burning from UV exposure.

Vitamin D supplementation

In the 1960s, vitamin D supplementation during pregnancy was mistakenly associated with aortic stenosis syndrome and developmental abnormalities. 7172 As a result, the dosage recommendations for vitamin D supplementation have been kept very low at 200 – 400 IU for decades. However, recent clinical trials have shown that doses up to 4000 IU are safe and may be required to achieve healthy levels in pregnant women. 7374

Based on a 2019 systematic review of clinical trials involving over 7,000 women, vitamin D supplementation during pregnancy may reduce the risk of preeclampsia, preterm birth, postpartum bleeding, and low birth weight. Vitamin D supplementation may increase infant length or circumference at birth. Adverse effects were rare and inconsistently reported, including mild hypercalcemia. 75 However, vitamin D supplementation alone may not be adequate treatments for miscarriage or pregnancy complications. 

Test, don’t guess. Individual response to sun exposure and vitamin D supplementation may vary, so it is important to test for blood 25(OH)D levels and adjust accordingly. If your physician prescribes very high doses of vitamin D (>10000 IU/day) to treat your vitamin D deficiency, serum calcium and vitamin D should be checked within a month since the start of the protocol and again every three months. 7677 For seasonal maintenance at lower doses or with regular sun exposure, consider checking every 2 – 3 months. Because serum 25(OH)D has a half-life of 15 days, 78 it may not be useful to check vitamin D levels more frequently than every few months. 

Supplements/actions that may work well with vitamin D

Conclusion

Vitamin D deficiency may play a role in recurrent miscarriages. Correcting vitamin D deficiency is important for both overall health and healthy pregnancy. Many studies have also demonstrated that abnormal vitamin D function leads to elevated inflammation that contributes to recurrent pregnancy losses. 84 Up to 4,000 IU of vitamin D supplementation is generally safe in pregnancy. 8586

However, clinically, it is unclear whether vitamin D supplements should be recommended as a treatment for recurrent pregnancy loss and spontaneous abortion. 87 Possibly, this is because these conditions are often multifactorial and cannot be addressed with vitamin D supplementation alone. Also, some forms of abnormal vitamin D function, such as decreased VDR or increased vitamin D breakdown in the placenta, may not resolve with vitamin D supplementation. 

Next Steps to Consider

  • Get your Vitamin D levels tested seasonally as well as every few months during pregnancy
  • If you have low Vitamin D levels, talk with your doctor to see if this could be signaling an auto-immune or metabolic condition
  • Also consider regular sun exposure and supplementation to help improve vitamin D levels if needed

References[+]

1 Comment

  1. Lisa

    Thank you so much for this information. I am low in Vitamin D (right at 20) and have been supplementing. After reading this, I realize I’m not supplementing enough and it may be beneficial to incorporate Magnesium to help absorb it. Not only this, but I never knew not having a galbladder played a factor in low vitamin D. I have had two miscarriages and I am trying everything I can to learn about what I need to fix before I even feel comfortable trying again. Thank you for this information and your podcast.

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