Nutrition in Pathogenesis of Uterine Fibroids: Comparison
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Please note this is a comparison between Version 2 by Mona Zou and Version 1 by Jarosław Wojciech Krzyżanowski.

Uterine fibroids are common benign tumors in women. They pose significant public health concerns due to their prevalence and impact on women's quality of life. This paper investigates various dietary components and their potential roles in the pathogenesis and symptomatology of uterine fibroids.

  • leiomyoma
  • nutrients
  • diet
  • vitamins

1. Introduction

Uterine fibroids (UF), also known as leiomyomas, are benign tumors originating from smooth muscle tissue of the uterus. They consist of a large amount of extracellular substance containing fibronectin, collagen and proteoglycans. Fibroids are surrounded by a pseudocapsule, which includes compressed collagen, muscle fibers, blood vessels and neurofibers. Their prevalence increases with age, peaking in the fourth and fifth decades of life. It is influenced by factors such as ethnicity, family history, and hormonal exposure. Being estrogen-dependent tumors, their occurrence before menarche is rare and their size generally decreases after the menopause. Accurately determining the prevalence of fibroids in the population is challenging, as a significant number remain asymptomatic and remain undiagnosed. Depending on the population, studies indicate that 5.4% to 77% of patients have fibroids. In about 30% of cases leiomyomas are symptomatic. Risk factors for UF include age, low parity, early menarche, diabetes, obesity, polycystic ovary syndrome (PCOS) and African ethnicity [1]. A number of factors may explain increased incidence of UF in black women, including higher serum estrogen levels and a higher risk of being overweight or obese compared to white women. In addition, differences in gene expression, higher exposure to chronic stress, poor diet, frequent use of hair straighteners as well as environmental and occupational exposures might also affect the occurrence of UF [2,3,4][2][3][4].
In the last century, the most common cause of death shifted from infectious or communicable diseases to chronic, non-communicable diseases. These include, among others, obesity, cerebrovascular disease, cancer and diabetes mellitus. Diet plays a crucial role in the prevention and development of many of these diseases. Adopting healthy eating not only extends life but also enhances the quality of those additional years [12][5]. The effect of diet on uterine fibroids has been a subject of speculation for many years. However, the lack of high-quality research prevents drawing definitive conclusions [13][6]. Most studies on nutrition and uterine fibroids concentrate on dietary components such as vegetables, fruits, carotenoids, soy-derived products or vitamin D and their impact on the prevalence of UFs. Some research has also explored the impact of other vitamins, cereal, dairy, green tea or environmental pollutants.

2. Vegetables and Fruits

Several studies indicate a correlation between a diet rich in vegetables and fruits and the risk for uterine fibroids. Phytochemicals, which are compounds found in plants, possess disease-preventive properties and also contribute to plant color. Phytochemicals are abundant in fruits, vegetables, grains, beans, nuts and seeds. Phytochemicals include, among others, flavonoids, carotenoids and polyphenols. These compounds are known for their ability to regulate cell proliferation, inflammation, fibrosis, apoptosis and angiogenesis [34][7]. In an in vitro study on leyomyoma cells, methanolic extract of two strawberry strains rich in phytochemicals Romina (R) and Alba (A), as well as Romina anthocyanin (RA) extract, were administered for 48 h. UF cells treated with R and RA exhibited significant decreases in collagen, fibronectin, activin A and versican expression. RA was also the most efficient in inducing apoptosis of UF cells [35][8]. In the Black Women’s Health Study (BWHS) including 59,000 African American women, 6627 were diagnosed with uterine fibroids. Based on the information obtained from patients, an inverse correlation was found between more servings of vegetables and fruits, including citrus, per day and the occurrence of fibroids. However, no significant relationship was observed between the intake of vitamins C, E, folic acid, carotenoids or fiber and uterine leiomyomas [16][9]. In a prospective cohort study by Davis et al., it was concluded that participants with the highest intake of fruits had a lower risk of uterine fibroids than those consuming the least amount of fruits, also suggesting an inverse correlation between amount of pesticide residues on vegetables and fruits and the prevalence of uterine fibroids [17][10]. A Chinese study investigating the influence of a vegetarian diet on the prevalence of fibroids found that consumption of broccoli, cabbage, tomato, Chinese cabbage and apple significantly reduced the prevalence of leiomyomas [18][11]. Similar results regarding vegetable and fruit intake were achieved in other studies conducted on the Chinese population [8,19][12][13]. Given these research outcomes, as well as the overall positive health impact of eating more vegetables and fruits, it is sensible to advise patients at risk or with uterine fibroids to increase their intake of these nutrients.

3. Dairy

Dairy is raw or processed food products made from milk. Dairy products contain many minerals and vitamins, including calcium, magnesium and vitamin D, which may be responsible for their effects in inhibiting tumorigenesis and inflammation [20][14]. Wise et al. in a prospective study on black women, observed that a higher diary intake reduces the risk of uterine fibroids [21][15]. Orta et al. concluded that consumption of yogurt and higher calcium intake reduced the risk of fibroids. However, the effect of dairy products in general on the occurrence of fibroids was unclear [20][14]. In contrast, a prospective cohort study on Chinese population by Gao et al. indicated that increased consumption of milk and soybean elevated the risk of uterine fibroids. It is important to note, however, that this study did not distinguish between milk and soybean consumption [22][16]. Given the limited data available, further research is needed to clarify the effect of dairy products on uterine fibroids.

4. Soybean

Soybean and soy-derived foods are key source of protein for many people across the world [36][17]. Rich in daidzein and genistein, soybeans contain isoflavones, which are nonsteroidal phenolic plant compounds and are among the most estrogenic substances. These isoflavones belong to the group of phytoestrogens with structural similarities to 17β-estradiol [37][18]. It was hypothesized that high consumption of foods containing soy protein may have an influence on the endocrine system, as well as on the prevalence and growth of fibroids. However, the existing data on this topic remain limited [36][17]. Two studies have investigated the correlation between urinary isoflavone levels and the risk of uterine fibroids. In the first study, patients with UF exhibited elevated urine enterolactone levels, but there was no observed association between urinary genistein, daidzein, equol (a metabolic product of intestinal bacteria), total isoflavones or phytoestrogens and uterine fibroids [24][19]. Conversely, in a recent study on US women, Yang et al. identified a positive association between the concentration of isoflavone metabolites in urine and uterine fibroids, with equol demonstrating the most significant effect [9][20]. Qin et al. performed a meta-analysis to evaluate the influence of soy-derived products on the prevalence of uterine fibroids. This analysis encompassed studies on both the consumption of soy products in infants as well as in adult women. Based on infant studies, soy formula was found to increase the risk of fibroids by 35%. Among adults, consumption of large amounts of soy products was linked to a 92% increase in the UF risk [38][21]. It is worth noting, however, that this relationship was not the same in all studies. Upson et al. found that although the prevalence of uterine fibroids did not increase in women fed with soy formula during their infancy, the diameter of fibroids was on average 32% higher in these patients [23][22]. Similarly, Wise et al. concluded with no correlation between soy intake and UF risk [21][15].

5. Green Tea Extracts

Green tea is one of the most popular beverages in the world. It originated in China, spread all over the world and, currently, it is one of the most popular beverages [39][23]. Green tea is made from the Camellia sinensis plant. It contains significant amounts of catechins like epigallocatechin gallate (EGCG), epigallocatechin and epicatechin gallate, with EGCG being the main antioxidant. It has anti-angiogenic and anti-proliferative effects. EGCG has been studied as a potential treatment option for many diseases, including those affecting the female reproductive system. Several studies have assessed its impact on UFs both in vitro and in vivo. EGCG has an apoptosis-promoting effect in both cell lines and animal models, which resulted in a reduction in the number and size of the observed fibroids [40][24]. Cyclin D1, a protein involved in cell-cycle progression, Was shown to be increased in UF cells. However, EGCG has been found to reduce these levels. EGCG also appears to inhibit the production of collagen and fibronectin in UF cells [41][25]. In a study by Roshdy et al., patients received 800 mg of green tea extract (45% EGCG), resulting in a significant reduction in symptoms and the size of UF compared to the placebo group [25][26]. In a subsequent 6-month observational study by Biro et al., participants taking EGCG-enriched green tea extract capsules (390 mg EGCG daily) reported significant improvement in their physical quality of life. However, no significant change in myoma size and number was detected [26][27]. In another study on women of reproductive age, no drug-induced liver injury was found during one-month-long therapy with 720 mg ECGC daily [42][28]. If the preliminary results are confirmed, EGCG may be a viable treatment option for uterine fibroids.

6. Vitamins

Vitamins are essential dietary components that are not synthesized in the human body, or are synthesized in quantities insufficient to maintain health. The daily requirements of most vitamins have been well established. Their deficiency leads to the development of various diseases, including scurvy, anemia, pellagra and osteoporosis [47,48,49][29][30][31]. The most widely studied vitamin in the context of uterine fibroids is vitamin D.

6.1. Vitamin D

Vitamin D is a group of steroid compounds including calciferol-D1, ergocalciferol-D2 and cholecalciferol-D3. It is involved in cell cycle regulation, cell differentiation and calcium–phosphate balance [50][32]. Produced in the human body through exposure to sunlight, it can also be sourced from the diet and supplements. The nutrients containing the most vitamin D include fatty fish and fortified foods. Small quantities of vitamin D can be found in foods such as cheese, egg yolks or beef liver [39][23]. Vitamin D seems to inhibit the proliferation of fibroid cells, while its deficiency may induce inflammation within the myometrium [20][14]. Through its nuclear receptor (vitamin D receptor—VDR) and activation of tyrosine kinase, it affects various signaling pathways. Immunohistochemistry studies showed reduced amounts of VDRs in fibroids compared to the myometrium surrounding the UF and reduced amounts of VDRs in the vicinity of the fibroid compared to the normal myometrium [51][33]. CYP24A1 is responsible for coding 24-hydroxylase, a vitamin D3-catabolizing-enzyme. Its expression in fibroids is higher than in normal myometrium and it leads to relative hypovitaminosis D inside the UF [52][34]. Meanwhile, data presented by Ali et al. showed that vitamin D3 treatment mitigates pathogenic DNA damage and may explain the beneficial effects of vitamin D3 in studies on rats and human UF cells and patients [53][35]. Ciebiera et al. found that serum vitamin D levels are significantly lower in patients with UF. The authors concluded that vitamin D deficiency may be a risk factor for UF [27][36]. Similar results were achieved in the Chinese population [28][37]. In a recent study by Harmon et al., 25-hydroxyvitamin D concentrations in blood serum above 20 ng/mL were associated with reduction in UF growth, while concentrations above 30 ng/mL were associated with decreased incidence of UF [30][38]. In a 12-month follow-up, patients receiving Vitamin D supplementation experienced a decrease in the UF volume. In addition, patients in this group required fewer surgical interventions [29][39]. In a study by Grandi et al., significant reduction in the size of UF was observed after three months of combined treatment with vitamin D 50 µg, EGCG 300 mg and Vitamin B6 10 mg [54][40]. In conclusion, given the prevalence of Vitamin D deficiency around the world [55][41] and the health benefits of its supplementation, in the future, vitamin D may be considered as a method of preventing or slowing down the development of uterine fibroids. However, randomized trials are still needed to determine the precise effect of vitamin D on the pathogenesis, prevalence and size of uterine fibroids. Determining the appropriate dose and target serum vitamin D level in patients with uterine fibroids also requires further research.

6.2. Vitamin C

Ascorbic acid, a water-soluble vitamin, was first synthesized in 1923. Its presence in the diet is essential for the physiological functioning of the human body. Vitamin C is involved in the synthesis and metabolism of folic acid, tyrosine and tryptophan. It accelerates the hydroxylation of glycine, lysine and proline by keeping the active center of metal ions in a reduced state. The main sources of vitamin C are fruits and vegetables. Its concentration in food of animal origin is low. A deficiency in vitamin C leads to anemia, infections, scurvy and other health issues. Additionally, some research suggests that ascorbic acid may also influence both male and female infertility [56][42]. Two randomized studies investigated the effect of administering two grams of ascorbic acid on perioperative blood loss during myomectomy. In a study by Lee et al., vitamin C had no impact on blood loss during laparoscopic myomectomy. Conversely, in a study by Pourmatroud et al., blood loss during abdominal myomectomy was significantly reduced in the group receiving ascorbic acid [57,58][43][44]. Currently, the available data on the effects of vitamin C on fibroids are insufficient to draw any conclusions.

6.3. Vitamin A

Vitamin A, a fat-soluble compound, owes its broad effects in metabolic processes to its β-ionone ring and isoprenoid chain. Food provides vitamin A in the form of retinols and carotenoids. Retinols are typically found in foods of animal origin, while the main sources of carotenoids are vegetables and fruits. Vitamin A is stored in hepatocytes in the ester form and is de-esterified as needed. Retinoid acid is a biologically active form of vitamin A. By binding to nuclear receptors, it enables transcription [59][45]. Initially, in a BWHS study, Wise et al. concluded that animal-derived vitamin A seems to be inversely associated with uterine fibroids risk in black women [16][9]. However, in a subsequent study on black women, no association was identified between the intake of lycopene or other carotenoids and UF incidence [31][46]. Furthermore, Martin et al. demonstrated that women with medium to high levels of vitamin A are at increased risk of uterine fibroids, compared to those with low concentrations of vitamin A [32][47].

References

  1. Szkodziak, P.; Pyra, K.; Szkodziak, F.; Krzyżanowski, J.; Czuczwar, P.; Woźniak, S.; Jargiełło, T.; Paszkowski, T. The Lublin Protocol of the Uterine Arteries Embolization in the Treatment of Symptomatic Uterine Fibroids. J. Vis. Exp. 2020, 163, e61530.
  2. Katon, J.G.; Plowden, T.C.; Marsh, E.E. Racial Disparities in Uterine Fibroids and Endometriosis: A Systematic Review and Application of Social, Structural, and Political Context. Fertil. Steril. 2023, 119, 355–363.
  3. Marsh, E.E.; Shaw, N.D.; Klingman, K.M.; Tiamfook-Morgan, T.O.; Yialamas, M.A.; Sluss, P.M.; Hall, J.E. Estrogen Levels Are Higher across the Menstrual Cycle in African-American Women Compared with Caucasian Women. J. Clin. Endocrinol. Metab. 2011, 96, 3199–3206.
  4. Jackson, C.L.; Szklo, M.; Yeh, H.-C.; Wang, N.-Y.; Dray-Spira, R.; Thorpe, R.; Brancati, F.L. Black-White Disparities in Overweight and Obesity Trends by Educational Attainment in the United States, 1997–2008. J. Obes. 2013, 2013, 140743.
  5. Neuhouser, M.L. The Importance of Healthy Dietary Patterns in Chronic Disease Prevention. Nutr. Res. 2019, 70, 3–6.
  6. Chiaffarino, F. Diet and Uterine Myomas. Obstet. Gynecol. 1999, 94, 395–398.
  7. Islam, M.S.; Segars, J.H.; Castellucci, M.; Ciarmela, P. Dietary Phytochemicals for Possible Preventive and Therapeutic Option of Uterine Fibroids: Signaling Pathways as Target. Pharmacol. Rep. 2017, 69, 57–70.
  8. Giampieri, F.; Islam, M.S.; Greco, S.; Gasparrini, M.; Forbes Hernandez, T.Y.; Delli Carpini, G.; Giannubilo, S.R.; Ciavattini, A.; Mezzetti, B.; Mazzoni, L.; et al. Romina: A Powerful Strawberry with in Vitro Efficacy against Uterine Leiomyoma Cells. J. Cell Physiol. 2019, 234, 7622–7633.
  9. Wise, L.A.; Radin, R.G.; Palmer, J.R.; Kumanyika, S.K.; Boggs, D.A.; Rosenberg, L. Intake of Fruit, Vegetables, and Carotenoids in Relation to Risk of Uterine Leiomyomata. Am. J. Clin. Nutr. 2011, 94, 1620–1631.
  10. Davis, C.P.; Garzia, N.A.; Cushing-Haugen, K.; Terry, K.L.; Chiu, Y.-H.; Sandoval-Insausti, H.; Chavarro, J.E.; Missmer, S.A.; Harris, H.R. Fruit and Vegetable Consumption, Pesticide Residue Intake from Consumption of Fruits and Vegetables, and Risk of Uterine Fibroids. F S Sci. 2023, 4, 90–99.
  11. Shen, Y.; Wu, Y.; Lu, Q.; Ren, M. Vegetarian Diet and Reduced Uterine Fibroids Risk: A Case-Control Study in Nanjing, China. J. Obstet. Gynaecol. Res. 2016, 42, 87–94.
  12. Zhou, M.; Zhai, Y.; Wang, C.; Liu, T.; Tian, S. Association of Dietary Diversity with Uterine Fibroids among Urban Premenopausal Women in Shijiazhuang, China: A Cross-Sectional Study. Asia Pac. J. Clin. Nutr. 2020, 29, 771–781.
  13. He, Y.; Zeng, Q.; Dong, S.; Qin, L.; Li, G.; Wang, P. Associations between Uterine Fibroids and Lifestyles Including Diet, Physical Activity and Stress: A Case-Control Study in China. Asia Pac. J. Clin. Nutr. 2013, 22, 109–117.
  14. Orta, O.R.; Terry, K.L.; Missmer, S.A.; Harris, H.R. Dairy and Related Nutrient Intake and Risk of Uterine Leiomyoma: A Prospective Cohort Study. Hum. Reprod. 2020, 35, 453–463.
  15. Wise, L.A.; Radin, R.G.; Palmer, J.R.; Kumanyika, S.K.; Rosenberg, L. A Prospective Study of Dairy Intake and Risk of Uterine Leiomyomata. Am. J. Epidemiol. 2010, 171, 221–232.
  16. Gao, M.; Wang, H. Frequent Milk and Soybean Consumption Are High Risks for Uterine Leiomyoma. Medicine 2018, 97, e12009.
  17. Belobrajdic, D.P.; James-Martin, G.; Jones, D.; Tran, C.D. Soy and Gastrointestinal Health: A Review. Nutrients 2023, 15, 1959.
  18. Křížová, L.; Dadáková, K.; Kašparovská, J.; Kašparovský, T. Isoflavones. Molecules 2019, 24, 1076.
  19. Simon, G.A.; Fletcher, H.M.; Golden, K.; McFarlane-Anderson, N.D. Urinary Isoflavone and Lignan Phytoestrogen Levels and Risk of Uterine Fibroid in Jamaican Women. Maturitas 2015, 82, 170–175.
  20. Yang, F.; Chen, Y. Urinary Phytoestrogens and the Risk of Uterine Leiomyomata in US Women. BMC Womens Health 2023, 23, 261.
  21. Qin, H.; Lin, Z.; Vásquez, E.; Luan, X.; Guo, F.; Xu, L. High Soy Isoflavone or Soy-Based Food Intake during Infancy and in Adulthood Is Associated with an Increased Risk of Uterine Fibroids in Premenopausal Women: A Meta-Analysis. Nutr. Res. 2019, 71, 30–42.
  22. Upson, K.; Harmon, Q.E.; Baird, D.D. Soy-Based Infant Formula Feeding and Ultrasound-Detected Uterine Fibroids among Young African-American Women with No Prior Clinical Diagnosis of Fibroids. Environ. Health Perspect. 2016, 124, 769–775.
  23. Ciebiera, M.; Łukaszuk, K.; Męczekalski, B.; Ciebiera, M.; Wojtyła, C.; Słabuszewska-Jóźwiak, A.; Jakiel, G. Alternative Oral Agents in Prophylaxis and Therapy of Uterine Fibroids—An Up-to-Date Review. Int. J. Mol. Sci. 2017, 18, 2586.
  24. Hazimeh, D.; Massoud, G.; Parish, M.; Singh, B.; Segars, J.; Islam, M.S. Green Tea and Benign Gynecologic Disorders: A New Trick for An Old Beverage? Nutrients 2023, 15, 1439.
  25. Islam, M.S.; Parish, M.; Brennan, J.T.; Winer, B.L.; Segars, J.H. Targeting Fibrotic Signaling Pathways by EGCG as a Therapeutic Strategy for Uterine Fibroids. Sci. Rep. 2023, 13, 8492.
  26. Roshdy, E.; Rajaratnam, V.; Maitra, S.; Sabry, M.; Ait Allah, A.S.; Al-Hendy, A. Treatment of Symptomatic Uterine Fibroids with Green Tea Extract: A Pilot Randomized Controlled Clinical Study. Int. J. Womens Health 2013, 5, 477–486.
  27. Biro, R.; Richter, R.; Ortiz, M.; Sehouli, J.; David, M. Effects of Epigallocatechin Gallate-Enriched Green Tea Extract Capsules in Uterine Myomas: Results of an Observational Study. Arch. Gynecol. Obstet. 2021, 303, 1235–1243.
  28. Siblini, H.; Al-Hendy, A.; Segars, J.; González, F.; Taylor, H.S.; Singh, B.; Flaminia, A.; Flores, V.A.; Christman, G.M.; Huang, H.; et al. Assessing the Hepatic Safety of Epigallocatechin Gallate (EGCG) in Reproductive-Aged Women. Nutrients 2023, 15, 320.
  29. Dresen, E.; Lee, Z.; Hill, A.; Notz, Q.; Patel, J.J.; Stoppe, C. History of Scurvy and Use of Vitamin C in Critical Illness: A Narrative Review. Nutr. Clin. Pract. 2023, 38, 46–54.
  30. Tardy, A.-L.; Pouteau, E.; Marquez, D.; Yilmaz, C.; Scholey, A. Vitamins and Minerals for Energy, Fatigue and Cognition: A Narrative Review of the Biochemical and Clinical Evidence. Nutrients 2020, 12, 228.
  31. Badawy, A.A.-B. Pellagra and Alcoholism: A Biochemical Perspective. Alcohol. Alcohol. 2014, 49, 238–250.
  32. Ciebiera, M.; Włodarczyk, M.; Ciebiera, M.; Zaręba, K.; Łukaszuk, K.; Jakiel, G. Vitamin D and Uterine Fibroids—Review of the Literature and Novel Concepts. Int. J. Mol. Sci. 2018, 19, 2051.
  33. Markowska, A.; Kurzawa, P.; Bednarek, W.; Gryboś, A.; Mardas, M.; Krzyżaniak, M.; Majewski, J.; Markowska, J.; Gryboś, M.; Żurawski, J. Immunohistochemical Expression of Vitamin D Receptor in Uterine Fibroids. Nutrients 2022, 14, 3371.
  34. Othman, E.R.; Ahmed, E.; Sayed, A.A.; Hussein, M.; Abdelaal, I.I.; Fetih, A.N.; Abou-Taleb, H.A.; Yousef, A.-E.A. Human Uterine Leiomyoma Contains Low Levels of 1, 25 Dihdroxyvitamin D3, and Shows Dysregulated Expression of Vitamin D Metabolizing Enzymes. Eur. J. Obstet. Gynecol. Reprod. Biol. 2018, 229, 117–122.
  35. Ali, M.; Shahin, S.M.; Sabri, N.A.; Al-Hendy, A.; Yang, Q. Hypovitaminosis D Exacerbates the DNA Damage Load in Human Uterine Fibroids, Which Is Ameliorated by Vitamin D3 Treatment. Acta Pharmacol. Sin. 2019, 40, 957–970.
  36. Ciebiera, M.; Włodarczyk, M.; Słabuszewska-Jóźwiak, A.; Nowicka, G.; Jakiel, G. Influence of Vitamin D and Transforming Growth Factor Β3 Serum Concentrations, Obesity, and Family History on the Risk for Uterine Fibroids. Fertil. Steril. 2016, 106, 1787–1792.
  37. Li, S.; Chen, B.; Sheng, B.; Wang, J.; Zhu, X. The Associations between Serum Vitamin D, Calcium and Uterine Fibroids in Chinese Women: A Case-Controlled Study. Int. J. Med. Res. 2020, 48, 030006052092349.
  38. Harmon, Q.E.; Patchel, S.A.; Denslow, S.; LaPorte, F.; Cooper, T.; Wise, L.A.; Wegienka, G.; Baird, D.D. Vitamin D and Uterine Fibroid Growth, Incidence, and Loss: A Prospective Ultrasound Study. Fertil. Steril. 2022, 118, 1127–1136.
  39. Ciavattini, A.; Delli Carpini, G.; Serri, M.; Vignini, A.; Sabbatinelli, J.; Tozzi, A.; Aggiusti, A.; Clemente, N. Hypovitaminosis D and “Small Burden” Uterine Fibroids. Medicine 2016, 95, e5698.
  40. Grandi, G.; Del Savio, M.C.; Melotti, C.; Feliciello, L.; Facchinetti, F. Vitamin D and Green Tea Extracts for the Treatment of Uterine Fibroids in Late Reproductive Life: A Pilot, Prospective, Daily-Diary Based Study. Gynecol. Endocrinol. 2022, 38, 63–67.
  41. Lips, P.; de Jongh, R.T.; van Schoor, N.M. Trends in Vitamin Status Around the World. JBMR Plus 2021, 5, e10585.
  42. Chambial, S.; Dwivedi, S.; Shukla, K.K.; John, P.J.; Sharma, P. Vitamin C in Disease Prevention and Cure: An Overview. Indian J. Clin. Biochem. 2013, 28, 314–328.
  43. Pourmatroud, E.; Hormozi, L.; Hemadi, M.; Golshahi, R. Intravenous Ascorbic Acid (Vitamin C) Administration in Myomectomy: A Prospective, Randomized, Clinical Trial. Arch. Gynecol. Obstet. 2012, 285, 111–115.
  44. Lee, B.; Kim, K.; Cho, H.Y.; Yang, E.J.; Suh, D.H.; No, J.H.; Lee, J.R.; Hwang, J.W.; Do, S.H.; Kim, Y.B. Effect of Intravenous Ascorbic Acid Infusion on Blood Loss during Laparoscopic Myomectomy: A Randomized, Double-Blind, Placebo-Controlled Trial. Eur. J. Obstet. Gynecol. Reprod. Biol. 2016, 199, 187–191.
  45. Chapman, M.S. Vitamin A: History, Current Uses, and Controversies. Semin. Cutan. Med. Surg. 2012, 31, 11–16.
  46. Wise, L.A.; Wesselink, A.K.; Bethea, T.N.; Brasky, T.M.; Wegienka, G.; Harmon, Q.; Block, T.; Baird, D.D. Intake of Lycopene and Other Carotenoids and Incidence of Uterine Leiomyomata: A Prospective Ultrasound Study. J. Acad. Nutr. Diet. 2021, 121, 92–104.
  47. Martin, C.L.; Huber, L.R.B.; Thompson, M.E.; Racine, E.F. Serum Micronutrient Concentrations and Risk of Uterine Fibroids. J. Womens Health 2011, 20, 915–922.
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