This is an excerpt from the upcoming 2nd Edition of It Starts with the Egg (expected in late February 2019)
Vitamin D and Miscarriage
Vitamin D appears to be particularly important for preventing miscarriage. That was the finding of several clinical studies published in 2018, which reported that women who had adequate vitamin D levels before they became pregnant had a significantly lower risk of miscarriage.[i] In one of the studies, conducted by the National Institutes of Health, women who had sufficient preconception vitamin D levels were 10% more likely to become pregnant and 15% more likely to give birth, compared to those with insufficient levels. In this study, the cut-off value characterized as “sufficient” was 30 nanograms per milliliter (ng/ml), yet the preferred level is likely higher. Each 10 ng/ml increase in preconception vitamin D was associated with a 12% lower risk of pregnancy loss.
Separate research has also shown a clear link between vitamin D levels and the immune factors often involved in recurrent miscarriage, such as natural killer cells and markers of systemic inflammation.[ii] Women with higher vitamin D levels are less likely to have these immune abnormalities. This suggests that supplementing with vitamin D could be particularly helpful if you have a history of miscarriage caused by immune factors.
Optimal Vitamin D Levels
Vitamin D deficiencies are surprisingly common, particularly in cooler climates. By some estimates, as much as 36% of the U.S. population is deficient, even with the most conservative cut-off value.[iii] There is actually a great deal of controversy over exactly what level of vitamin D counts as a deficiency. Conventionally, 20 ng/ml has been the minimum recommended level, but that is based on preserving bone health.
As mentioned above, the recent miscarriage studies indicate that 30 ng/ml (75 nmol/l) should be considered the bare minimum. Up to 80% of women have vitamin D levels below this point.[iv] New research indicates that an even higher level is preferred to balance the immune system and allow optimal development of the placenta.[v] As discussed in detail in my upcoming pregnancy book (www.itstartswiththeegg.com/sequel), the latest studies show that the optimal vitamin D level is likely at least 40 ng/mL (100 nmol/L).
Vitamin D Cut-off Levels for Fertility and Miscarriage Prevention
Deficient: below 20 ng/ml (50 nmol/l)
Insufficient: 20 –30 ng/ml (50–75 nmol/l)
Sufficient: at least 30 ngl/ml (75 nmol/l)
Optimal: at least 40 ng/mL (100 nmol/L).
Supplementing with Vitamin D
Unless you live in a tropical climate and get significant daily sun exposure, it is highly likely that your vitamin D level is too low and you will need to supplement. The necessary dose depends on just how deficient you are and how high you are aiming, so it is best to have your level tested and seek your doctors advice on the appropriate dose in your case. If your doctor is reluctant to run the test, it is likely best to assume you have a mild deficiency and supplement accordingly.
For most women 2000 IU per day will eventually raise the vitamin D level to the normal range, but a higher dose is likely needed to raise levels more quickly, and to reach the optimal amount for fertility and pregnancy.
The Endocrine Society recommends that all adults that are vitamin D deficient should be treated with 6000 to 10000 IU of vitamin D per day in the short term (typically two weeks), followed by a lower ongoing maintenance dose. The standard maintenance dose is typically 2000 IU, yet that is aimed at maintaining “normal” levels, not the higher levels that are optimal for fertility and pregnancy.
Studies indicate that most women need approximately 4000 IU per day to maintain vitamin D levels above 40 ng/mL (100 nmol/L). Depending on genetics and sun exposure, you may require more or less. If your current level is already between 30 and 40 ng/mL, you may only need to add an additional 2000 IU per day. On the other hand, some people will need at least 5000 IU per day.
Supplementing with a higher dose of vitamin D is likely to be particularly helpful for those with conditions associated with inflammation or autoimmunity, such as as thyroid disease, endometriosis, or a history of recurrent miscarriage. In these cases it is likely best to err on the side of a higher dose while trying to conceive. (For example 10,000 IU per day for two weeks, then 5000 IU per day as a maintenance dosage.) Dr. Amy Myers, physician and author of The Autoimmune Solution, recommends a target level of 60-90 ng/mL for those with thyroid conditions or other autoimmune diseases.
The main concern with taking too much vitamin D is raising blood calcium levels, since vitamin D improves calcium absorption from food. Yet the Mayo Clinic advises that this problem has been reported with 60,000 IU per day for several months. In a study of patients with multiple sclerosis, 20,000 IU per day for 12 weeks reduced inflammatory immune cells without causing a significant rise in calcium levels.[vi]
Based on this study and other current evidence, it appears that high blood calcium levels are unlikely at just 5000 IU per day. Even so, it may still be prudent to lower your dairy intake and occasionally check your blood calcium levels if you are taking this dose long-term. (Adding a vitamin K2 supplement can also help to direct any excess calcium into strengthening bones, rather than forming calcium deposits in blood vessels, but it is best to keep this low, such as 45 mcg)
To obtain the most benefit from a vitamin D supplement, it is best to choose Vitamin D3 formulated in oil-based drops or an oil-based soft gel capsule, rather than a solid tablet, and to take it with a meal containing some fat. These measures significantly improve the absorption of vitamin D because it is a fat-soluble vitamin.
The brand is not particularly important, but good-quality options include:
NOW Vitamin D-3 2000 IU (can take 2 to reach 4000IU)
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[i] Masbou, A. K., Kramer, Y., Taveras, D., McCulloh, D. H., & Grifo, J. A. (2018). Vitamin D deficiency at time of frozen embryo transfer is associated with increased miscarriage rate but does not impact folliculogenesis. Fertility and Sterility, 109(3), e37-e38.
Mumford, S. L., Garbose, R. A., Kim, K., Kissell, K., Kuhr, D. L., Omosigho, U. R., … & Plowden, T. C. (2018). Association of preconception serum 25-hydroxyvitamin D concentrations with livebirth and pregnancy loss: a prospective cohort study. The Lancet Diabetes & Endocrinology.
[ii] Ota, K., Dambaeva, S., Han, A. R., Beaman, K., Gilman-Sachs, A., & Kwak-Kim, J. (2013). Vitamin D deficiency may be a risk factor for recurrent pregnancy losses by increasing cellular immunity and autoimmunity. Human reproduction, 29(2), 208-219.
Chen, X., Yin, B., Lian, R. C., Zhang, T., Zhang, H. Z., Diao, L. H., … & Zeng, Y. (2016). Modulatory effects of vitamin D on peripheral cellular immunity in patients with recurrent miscarriage. American Journal of Reproductive Immunology, 76(6), 432-438.
[iii] Looker AC, Pfeiffer CM, Lacher DA, Schleicher RL, Picciano MF, Yetley EA. Serum 25-hydroxyvitamin D status of the US population: 1988-1994 compared with 2000-2004. Am J Clin Nutr. 2008 Dec;88(6):1519-27 (“Looker 2008”);
Nesby-O’Dell S, Scanlon KS, Cogswell ME, Gillespie C, Hollis BW, Looker AC, Allen C, Doughertly C, Gunter EW, Bowman BA. Hypovitaminosis D prevalence and determinants among African American and white women of reproductive age: third National Health and Nutrition Examination Survey, 1988-1994. Am J Clin Nutr. 2002 Jul;76(1):187-92
[iv] Ginde, A. A., Sullivan, A. F., Mansbach, J. M., & Camargo Jr, C. A. (2010). Vitamin D insufficiency in pregnant and nonpregnant women of childbearing age in the United States. American journal of obstetrics and gynecology, 202(5), 436-e1.
Haq, A., Svobodová, J., Imran, S., Stanford, C., & Razzaque, M. S. (2016). Vitamin D deficiency: A single centre analysis of patients from 136 countries. The Journal of steroid biochemistry and molecular biology, 164, 209-213.
[v] Hollis, B. W., & Wagner, C. L. (2017). New insights into the vitamin D requirements during pregnancy. Bone research, 5, 17030.
[vi] Smolders, J., Peelen, E., Thewissen, M., Tervaert, J. W. C., Menheere, P., Hupperts, R., & Damoiseaux, J. (2010). Safety and T cell modulating effects of high dose vitamin D3 supplementation in multiple sclerosis. PLoS One, 5(12), e15235.
[vii] Grossmann RE, Tangpricha V. Evaluation of vehicle substances on vitamin D bioavailability: a systematic review. Mol Nutr Food Res. 2010 Aug;54(8):1055-61;
Raimundo FV, Faulhaber GA, Menegatti PK, Marques Lda S, Furlanetto TW. Effect of High- versus Low-Fat Meal on Serum 25-Hydroxyvitamin D Levels after a Single Oral Dose of Vitamin D: A Single-Blind, Parallel, Randomized Trial. Int J Endocrinol. 2011;2011:809069.