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Morning Sickness might be eliminated by Vitamin D

Hyperemesis Gravidarum is a severe form of Morning Sickness
Thalidomide was used as a treatment for morning sickness, among many other things.

Hyperemesis Gravidarum 40% more likely if low vitamin D - Dec 2023

Vitamin D and hyperemesis gravidarum: A mendelian randomization study
J Gynecol Obstet Hum Reprod. 2023 Dec;52(10):102678. doi: 10.1016/j.jogoh.2023.102678
Fang Hu 1

Background: The causality between vitamin D and hyperemesis gravidarum remains unknown. Our aim was to investigate the causal effect of vitamin D on hyperemesis gravidarum using the two-sample Mendelian randomization method.

Methods: Independent single nucleotide polymorphisms significantly associated with serum 25-hydroxyvitamin D levels served as instrumental variables. The corresponding effect estimates for hyperemesis gravidarum were obtained from the Finngen Biobank. For Mendelian randomization analysis, inverse variance weighting was used as the primary method. We also used weighted median, MR-Egger regression, simple mode, and weighted mode as complementary methods to inverse variance weighting. The MR-Egger intercept test, Cochran's Q test, and "leave-one-out" sensitivity analysis were performed to assess the horizontal pleiotropy, heterogeneity, and stability of the causal association between 25-hydroxyvitamin D levels and hyperemesis gravidarum.

Results: We found that an increase in 25-hydroxyvitamin D level was associated with a lower risk of hyperemesis gravidarum odds ratio (OR): 0.568, 95 % CI: 0.403-0.800, p = 0.001. The result demonstrates the causal relationship between 25-hydroxyvitamin D level and the risk of hyperemesis gravidarum in the European population.

Conclusions: The large Mendelian randomization analysis suggests that vitamin D may be causally associated with risk of hyperemesis gravidarum.

Introduction
Hyperemesis gravidarum (HG) is severe nausea and vomiting in pregnancy. Between 0.3 %- 3 % of all pregnant women suffer from HG 1. Worldwide, prevalence rates are higher in women of Asian and Middle Eastern ethnicities, as high as about 10 % in a study of a Chinese population 2. HG can be complicated by dehydration, electrolyte disturbances, poor nutritional intake, weight loss, and requires hospitalization in most cases 3. In addition to the negative effects on maternal, physical, and psychological well-being, HG can impair fetal growth and have negative consequences for the health of the offspring.

Vitamin D, a fat-soluble vitamin, is the collective name for cholecalciferol and ergocalciferol 4. 25-Hydroxyvitamin D (25OHD) is the main form of vitamin D in the human bloodstream and is often used as an indicator for evaluating the nutritional status of vitamin D. Therefore, in this work, we focus on serum 25OHD levels. Evidence is accumulating that vitamin D deficiency increases the risk of adverse perinatal outcomes 5. There are preliminary studies suggesting that vitamin D levels were lower in women with hyperemesis gravidarum compared to others 6. Vitamin D is an immunomodulator that may play a crucial role in the development of hyperemesis gravidarum. Therefore, vitamin D is thought to play a crucial role in controlling the inflammatory status associated with hyperemesis gravidarum.

Because of the special nature of pregnancy, randomization clinical trials researches (RCTs) are limited. In the absence of RCTs, Mendelian randomization (MR) design is an important strategy for causal inference. MR uses genetic variants as proxies for an exposure to predict its causal association with an outcome. This method skillfully exploits the genetic variation's distributive randomness while successfully avoiding confounding biases 7.

Overall, the relationship between vitamin D levels and the risk of HG is still not clear, and further studies are need. In this study, we focused on exploring the causal relationship between serum 25OHD level and the occurrence of HG, which may have significant clinical potential.

Section snippets
Study design
MR is a method for determining the causal relationship between the phenotype of exposure and the outcome by using genetic variants for exposure as instrument variables (IV) 8. This method could use the publicly available dataset from large-sample genome-wide association studies (GWAS) for both “exposures” and “outcomes” and address the common drawbacks of observational studies. To obtain reliable causal relationships, MR studies must meet the assumptions of relevance assumptions (IVs are….

Instrumental variable selection
Independent SNPs were selected from the GWAS dataset, which were associated with the 25OHD serum level at the genome-wide significance level (p < 5 × 10−8) and the low level of linkage disequilibrium (LD) (r2 < 0.001) were related. Removing the following SNPs because they are palindromic and have intermediate allele frequencies: rs10127775, rs5112. The genes in which they occur were queried in Pubmed, and the genes of SNPs that do not belong to a specific gene were defined as NULL. The….

Discussion
The Mendelian randomization study performed an analysis of the causal relationship between vitamin D and HG based on GWAS summary datasets generated by many different consortia including 441,291 individuals using multiple SNPs as instrumental variables. Our results showed a causal relationship between serum 25OHD level and the occurrence of HG…..

A previous research showed that vitamin D levels were lower in women with hyperemesis gravidarum compared to other women although it did not reach….

Conclusion
In the MR study, we found that decreases in serum 25OHD levels were associated with a higher risk of HG, which is consistent with previous studies describing a critical biological role of vitamin D in the development of HG. However, because of the limited availability of evidence from clinical studies, further clinical studies are needed to investigate the benefits of vitamin D for the prevention and treatment of HG…..

Acknowledgments
Data in the European population on serum 25OHD levels are available through the United Kingdom Biobank and data analysis is available through the GWAS database. We thank these researchers for their selfless sharing. Data in the European population on excessive vomiting in pregnancy are available through the GWAS database, we would like to thank the participants and investigators of the FinnGen study.

4 of the references
  • M.S. Fejzo et al. High prevalence of severe nausea and vomiting of pregnancy and hyperemesis gravidarum among relatives of affected individuals Eur J Obstetric Gynecol Reproduct Biol (2008)
  • E. Kan et al. Evaluation of relationship between inflammatory markers and hyperemesis gravidarum in patients admitted to emergency department – Am J Emerg Med (2020)
  • S. Yılmaz et al. – Do vitamin D and high-sensitivity-C reactive protein levels differ in patients with hyperemesis gravidarum? A preliminary study – Turk J Obstet Gynecol – (2016)
  • K. Maslin, C. Dean (2021)- Nutritional consequences and management of hyperemesis gravidarum: a narrative review - Nutrition Research Reviews, 35

Yes, morning sickness is associated with low vitamin D levels. Several studies have indicated that vitamin D deficiency may play a role in the etiopathogenesis of nausea and vomiting during pregnancy (NVP), commonly referred to as morning sickness.

Is morning sickness associated with low vitamin D (Perplexity AI April 2024 said yes)

  1. Role of Vitamin D in Nausea and Vomiting of Pregnancy: Research has shown that vitamin D has immunomodulatory and anti-inflammatory properties, which are significant during pregnancy. A study highlighted that pregnant women with morning sickness had a higher risk of vitamin D deficiency compared to those without morning sickness. It was found that there was a significant decrease in serum vitamin D3 levels in patients with NVP compared to control groups1.
  2. Clinical Observations and Recommendations: The study from Thi-Qar, Iraq, included clinical observations that supported the association between lower levels of vitamin D and increased severity of morning sickness. This study was among the first to classify the effects of various vitamins and elements on women experiencing NVP1.
  3. Vitamin D Deficiency and Dietary Intake: Another study emphasized the importance of proper nutritional status before and during pregnancy to prevent NVP. It noted that low consumption of vitamin D-rich foods and supplements before pregnancy was associated with vitamin D deficiency, which could exacerbate morning sickness2.
  4. General Findings on Vitamin D in Pregnancy: General medical advice and research also support the notion that vitamin D plays a crucial role in pregnancy, affecting not just the mother's health but also the child's development. Vitamin D helps in the absorption and metabolism of calcium and phosphorus, which are vital for bone health and development11.

In conclusion, while vitamin D deficiency is not the sole cause of morning sickness, it is associated with an increased risk and severity of NVP. Pregnant women are advised to monitor their vitamin D levels and consider appropriate supplementation, as recommended by healthcare providers, to potentially alleviate the symptoms of morning sickness1  2   11.

Morning Sickness associated with smoking (smoking reduces Vitamin D levels) Dec 2017

Link found between morning sickness, smoking and healthy pregnancies
URL

A link between the ‘old wives’ tale that morning sickness may indicate a healthy pregnancy, and the reason smoking is so detrimental has been found, according to a review published in the Journal of Molecular Endocrinology. The article discusses the importance of the hormone endokinin for healthy pregnancies, its role in causing morning sickness, and how its normal function may be adversely affected by smoking, leading to poor outcomes in pregnancy.

Successful and effective implantation of the placenta is essential for a healthy pregnancy but how this is achieved remains to be firmly established. In particular, the role of peptide hormones and the placenta in causing morning sickness is unclear. In this article, Professor Philip Lowry and Dr Russell Woods from the University of Reading review the critical roles that peptide hormones have in ensuring successful implantation of the placenta, discuss how endokinin can indirectly lead to the development of morning sickness symptoms, and how its normal hormone function can be impaired by smoking.

Endokinin is a peptide hormone found throughout the body that can affect blood supply to organs locally. Placental endokinin, even at low levels, appears to be capable of improving local blood flow, which is a key factor for ensuring successful implantation. Endokinin also acts on the brain to induce nausea and vomiting. This is why drugs that block the actions of endokinin in the brain are often used to treat nausea associated with chemotherapy. Furthermore, recent data indicates that tobacco smoke also influences lung endokinin levels.

Since hormones like endokinin are transported in the blood, they can also affect functions in other parts of the body and this is the basis of the link between morning sickness, pregnancy and smoking. Increases in endokinin levels during pregnancy that ensure good placental blood flow can also overspill and activate the brain areas that cause morning sickness symptoms. Similarly, the nausea experienced by non-smokers on inhaling tobacco smoke may be due to raised levels of endokinin in the lungs also activating those brain areas. Given that smoking during pregnancy is well known to lead to poor placental implantation, this suggests that impaired endokinin activity may be involved.

Prof Lowry suggests, “It is feasible that the regular release of lung endokinin into a mother’s blood from smoking adversely affects the normal local response to placental endokinin, which is needed to ensure a healthy pregnancy.”

Prof Lowry cautions, “There may be a temptation to use endokinin blocking drugs to treat morning sickness during pregnancy but these findings suggest that such drugs could affect the health of the pregnancy and must be avoided.”

Prof Lowry concludes, “I hope that this article will give some psychological relief to pregnant women suffering from morning sickness, but will also persuade smokers who are intending to have a baby to kick the habit well beforehand.”

VitaminDWiki - Pregnancy category contains

923 items in Pregnancy category

 - see also

VitaminDWiki – Healthy pregnancies need lots of vitamin D contains

Most were taking 2,000 to 7,000 IU daily for >50% of pregnancy
   Click on hyperlinks for details

Problem
Vit. D
Reduces		Evidence
0. Chance of not conceiving3.4 times Observe
1. Miscarriage 2.5 times Observe
2. Pre-eclampsia 3.6 timesRCT
3. Gestational Diabetes 3 times RCT
4. Good 2nd trimester sleep quality 3.5 times Observe
5. Premature birth 2 times RCT
6. C-section - unplanned 1.6 timesObserve
     Stillbirth - OMEGA-3 4 timesRCT - Omega-3
7. Depression AFTER pregnancy 1.4 times RCT
8. Small for Gestational Age 1.6 times meta-analysis
9. Infant height, weight, head size
     within normal limits		 RCT
10. Childhood Wheezing 1.3 times RCT
11. Additional child is Autistic 4 times Intervention
12.Young adult Multiple Sclerosis 1.9 timesObserve
13. Preeclampsia in young adult 3.5 timesRCT
14. Good motor skills @ age 31.4 times Observe
15. Childhood Mite allergy 5 times RCT
16. Childhood Respiratory Tract visits 2.5 times RCT

RCT = Randomized Controlled Trial

Morning Sickness might be eliminated by Vitamin D        
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