The role of fat-soluble vitamins in hormone balance  

Hormones play a significant role in our health and while it’s natural for them to change during certain life stages, if they are out of balance, they can cause a variety of symptoms and conditions. When we experience hormonal problems, it is our body’s way of letting us know that something is amiss.

Unfortunately for many of us, we’ve just come to accept that they are a part of life. However, these symptoms aren’t normal, nor should they be an inevitable part of life.

In fact, there are various ways to promote hormone balance and reduce or eliminate some of the associated symptoms of an imbalance. Our nutrient status, for instance, is incredibly important and for the purpose of this blog we will take a look at the role fat-soluble vitamins play in our hormonal health.

The Endocrine System

The human endocrine system is composed of:

• endocrine glands (hypothalamus, pituitary, pineal, parathyroid, thyroid, adrenal, pancreas, ovaries, testes etc.)
• hormones (chemical messengers) which are produced by the endocrine glands (adrenaline, insulin, cortisol, thyroid hormones, oestrogen, progesterone and testosterone etc.)
• hormone receptors, without which the message transported by the hormone would not be recognised by the target cell

Our body uses hormones for two types of communication:

1. Between two endocrine glands
2. Between an endocrine gland and a target organ

We have around fifty known hormones which vary in their structure and action, and which regulate many processes such as metabolism, sexual function, mood, growth and development, reproduction and the sleep-wake cycle.

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Imbalances 

Our endocrine system is complex and there are many factors that can contribute to a hormonal imbalance. These include being overweight, chronic stress, poor sleep, sedentary lifestyle, western diet, and nutritional deficiencies. Imbalances may be responsible for a variety of undesirable symptoms from weight gain and mood swings to blood sugar problems and skin eruptions. Other signs that may be indicative of a hormonal imbalance include:

• low libido
• heavy and painful periods
• fertility problems
• depression
• hair loss
• PMS
• Osteoporosis
• Metabolic Syndrome
• sleep difficulties

Fat-soluble vitamins

The fat-soluble vitamins  A, D, E and K are required for a range of physiological functions and deficiencies have been associated with many symptoms. Fat-soluble vitamins are absorbed along with fats in the diet and are stored in the body’s fatty tissue and in the liver.

The role that the fat-soluble vitamins play is complex and wide-reaching and will extend far beyond the scope of this blog but below are some examples of how they can relate to our hormonal health.

Vitamin D 

Inadequate vitamin D status is common in the UK with many of us likely to have insufficient levels. Vitamin D is synthesised by sunlight and is found in foods such as liver, eggs, fortified foods and oily fish. However, many of us have limited sun exposure and few foods naturally contain enough vitamin D to meet adequate levels. For most people, the best way to get enough vitamin D is by taking a supplement.

Vitamin D affects hormones both directly and indirectly and is considered to be a hormone itself. Our knowledge of the spectrum of vitamin D mediated effects has expanded in recent years and it is now recognized as a versatile signalling molecule rather than being solely a regulator of bone health and calcium homeostasis.¹ Vitamin D exerts its biological actions through vitamin D receptors and hence plays its role through the regulation of gene expression in places where its receptors exist, such as the endocrine system.² Research suggests that vitamin D can influence several different hormones in the body.

Insulin

Low levels of vitamin D have been associated with insulin resistance and increased diabetes risk.³ The important role that it plays is likely mediated by an effect on beta cell function, insulin sensitivity and systemic inflammation.

Vitamin D may have a beneficial effect on insulin action:⁴

• directly, by stimulating the expression of insulin receptors, thereby enhancing insulin responsiveness for glucose transport
• indirectly, via its role in regulating extracellular calcium, which is essential for insulin-mediated intracellular processes in insulin-responsive tissues
• Vitamin D can also down regulate activation of NF-kB which is an important regulator of genes encoding the pro-inflammatory cytokines implicated in insulin resistance

Insulin resistance is a hallmark of polycystic ovary syndrome (PCOS), one of the most common endocrine disorders that affects women of reproductive age.⁵ It is also closely associated with metabolic syndrome and obesity.

Reproduction/Fertility

The presence of vitamin D receptors in the ovary, uterus, placenta, and the testis suggest a regulatory role for vitamin D in reproductive physiology.⁶ As well as influencing local effect on both the endometrium and the testes, vitamin D also has an influence over steroid hormones, namely oestrogen and testosterone. It is involved in many reproductive processes including steroidogenesis, spermatogenesis, and acrosome reaction and research links vitamin D deficiency with hypogonadism and decreased fertility in men. In women, there is evidence for its role in PCOS, endometriosis, in vitro fertilization, ovarian reserve and pregnancy outcomes.⁷

Thyroid

The thyroid gland is one of the largest endocrine glands with many roles for homeostatic control, including growth, energy expenditure, and metabolism.⁸ Symptoms related to imbalances include tiredness, sensitivity to the cold/heat, weight gain/loss and mood disorders. A recent systematic review and meta-analysis found that that vitamin D deficiency was significantly associated with hypothyroidism, autoimmune thyroid disease, and Hashimoto’s thyroiditis.^9-11

Parathyroid (PTH)

PTH and Vitamin D form a tightly controlled feedback cycle – PTH being a major stimulator of vitamin D synthesis in the kidney, while vitamin D exerts negative feedback on PTH secretion.¹² Vitamin D deficiency is associated with hyperparathyroidism – this drives the leaching of calcium from bone into blood and can be a major contributor to reduced bone density, osteoporosis and osteopenia.

Communication

Cell-cell communication mediated by gap junctional channels is an important homeostatic control mechanism for regulating cell growth and differentiation. Gap junctions form channels between neighbouring cells – their function is primarily defined by their ability to pass small signalling molecules, metabolites, and electrical stimuli directly between these cells. The core proteins of these channels are the connexins, and vitamin D has been shown to enhance the expression and subsequent assembly into gap junctions. Research implies that connexin signalling may also be involved between selected endocrine cells.^13,14

Vitamin A 

Vitamin A plays a well-established role in vision and immune health but is also intricately involved in our hormone health. The two main forms of vitamin A are preformed vitamin A (from animal products, fortified foods, and supplements) and provitamin A carotenoids (such as beta-carotene) that are converted to retinol and are found in many plant foods.

Thyroid

One of the most critical roles of vitamin A in human health is its effect on thyroid function,^1,2 Vitamin A is required for the activation of thyroid hormone receptors and insufficient levels may depress thyroid function.¹

Vitamin A helps to regulate^2-6

• thyroid gland metabolism
• the synthesis of thyroid hormone
• the peripheral function of thyroid hormone
• the secretion of thyroid stimulating hormone (TSH) by the pituitary

Insulin

In recent years, evidence has demonstrated that vitamin A regulates metabolic pathways implicated in the pathogenesis of obesity and diabetes. Researchers have found that vitamin A may be crucial to the insulin-secreting function of beta cells and discovered that insulin cells have a cell surface expressed receptor for vitamin A. In one study, vitamin A levels, were significantly lower in patients with metabolic syndrome than those without.^3-7

Reproduction/Fertility

Vitamin is A is important for fertility and for foetal development and is essential for both male and female sex hormone production. It is a critical factor for the formation of the gonads in men and one of the consequences of deficiency is infertility.⁸ In Leydig cells (the primary source of testosterone or androgens in males) as well as ovarian cells, vitamin A stimulates steroid hormone synthesis. Vitamin A is also essential for the maintenance of the male genital tract and spermatogenesis. Recent studies show that vitamin A participates in a signalling mechanism to initiate meiosis in the female gonad during embryogenesis, and in the male gonad postnatally.⁹

Vitamin E 

Vitamin E is a group of eight fat-soluble compounds that include four tocopherols and four tocotrienols. It is found in plant-based oils, fruit, vegetables, nut and seeds and is well-known for its balancing effects on hormones. It has been indicated in high oestrogen/low progesterone, PCOS, hypothyroidism, endometriosis and high/low cortisol.

Menstrual cycle

It has been demonstrated that vitamin status and inflammatory mechanisms are often related to menstrual cycle abnormalities. In one study, supplemental vitamin E (with vitamin D) was an effective solution for PMS.¹ A further study showed that serum vitamin E was inversely associated with PMS and primary dysmenorrhea.² Furthermore, girls with long bleeding periods had lower concentrations of serum vitamin E compared to those who reported a normal period duration. Vitamin E may also help to alleviate menstrual pain and cramping.^1,2

Endometriosis

In a randomised controlled trial, the intake of vitamin C and vitamin E supplements effectively reduced dysmenorrhea severity and improved dyspareunia and severity of pelvic pain in endometriosis.³

Insulin

Observational studies have revealed that higher serum vitamin E concentrations and increased vitamin E intake are associated with beneficial effects on glycaemic control in type 2 diabetes.⁴ Furthermore, in a recent meta-analysis of randomised controlled trials, vitamin E supplementation improved glucose, lipid, and androgenic-related biomarkers in women with PCOS.⁴ A further systematic review showed that vitamin E positively affected metabolic and hormonal parameters in women with PCOS.⁵

Vitamin K

There are two forms of vitamin K:

• K1 (phylloquinone) – found in plant foods (leafy greens)

• K2 (menaquinone) – found in animal foods, fermented foods and is also manufactured by gut bacteria

Insulin

A recent systematic review found that vitamin K plays an important role in the prevention and control of type 2 diabetes, which may be related to the improvement of insulin metabolism and blood glucose level.¹

Osteocalcin

There are many vitamin K-dependent proteins, one of which is a hormone called osteocalcin, produced by osteoblasts. This is needed to bind calcium into the matrix of the bone. Without Vitamin K2 as a cofactor, the body cannot direct calcium to the bones where it’s needed. Instead, the calcium resides in soft tissues potentially contributing to osteoporosis or atherosclerosis.²

Ensuring adequate intake of the fat-soluble vitamins is important for hormone balance. As fat-soluble vitamins are stored in the body for long periods of time, they may pose a greater risk for toxicity than water-soluble vitamins when consumed in excess, so it is important to be mindful of this. However, it is thought that vitamin D deficiency affects a large percentage of the population and that dietary intakes of vitamin K2 among the general population are also inadequate.² Furthermore, those with a poor diet, a low-fat diet, digestive disorders or with conditions that impair fat absorption (pancreatitis, coeliac disease etc) may be at an increased risk of insufficient intake.

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If you have questions regarding the topics that have been raised, or any other health matters, please do contact our team of Nutritional Therapists.

nutrition@cytoplan.co.uk
01684 310099

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References:

Vitamin D

1. Blomberg Jensen, M. (2012) “Vitamin D metabolism, sex hormones, and male reproductive function,” Reproduction, 144(2), pp. 135–152. Available at: https://doi.org/10.1530/REP-12-0064.
2. Ławnicka H, Galant-Gdula A, Motylewska E, Komorowski J, Świętosławski J, Stępień H. Estimation of vitamin D status in patients with secondary and primary hypothyroidism of different etiology. Neuroendocrinol Lett. 2017;38(8):565-74.
3. Talaei, A., Mohamadi, M. and Adgi, Z. (2013) “The effect of vitamin D on insulin resistance in patients with type 2 diabetes,” Diabetology and Metabolic Syndrome, 5(1), pp. 1–5. Available at: https://doi.org/10.1186/1758-5996-5-8/COMMENTS.
4. Pittas, A.G. et al. (2007) “The Role of Vitamin D and Calcium in type 2 diabetes. A systematic Review and Meta-Analysis,” The Journal of clinical endocrinology and metabolism, 92(6), p. 2017. Available at: https://doi.org/10.1210/JC.2007-0298.
5. Chu, C., Tsuprykov, O., Chen, X., Elitok, S., Krämer, B. K., & Hocher, B. (2021). Relationship Between Vitamin D and Hormones Important for Human Fertility in Reproductive-Aged Women. Frontiers in endocrinology, 12, 666687. https://doi.org/10.3389/fendo.2021.666687
6. Luk, J. et al. (2012) “Relevance of vitamin D in reproduction,” Human Reproduction (Oxford, England), 27(10), p. 3015. Available at: https://doi.org/10.1093/HUMREP/DES248.
7. Nandi, A. et al. (2016) “Is there a role for vitamin D in human reproduction?,” Hormone Molecular Biology and Clinical Investigation, 25(1), pp. 15–28. Available at: https://doi.org/10.1515/HMBCI-2015-0051/ASSET/GRAPHIC/J_HMBCI-2015-0051_FIG_003.JPG.
8. Feng M, Li H, Chen SF, Li WF, Zhang FB. Polymorphisms in the vitamin D receptor gene and risk of autoimmune thyroid diseases: a meta-analysis. Endocrine. 2013;43(2):318–26. https://doi.org/10.1007/s12020-012-9812-y
9. The Role of Vitamin D Deficiency in Thyroid Disorders
   https://chriskresser.com/the-role-of-vitamin-d-deficiency-in-thyroid-disorders/
10. Taheriniya, S., Arab, A., Hadi, A. et al.Vitamin D and thyroid disorders: a systematic review and Meta-analysis of observational studies. BMC Endocr Disord 21, 171 (2021). https://doi.org/10.1186/s12902-021-00831-5
11. Cantorna MT, Yu S, Bruce D. The paradoxical effects of vitamin D on type 1 mediated immunity. Mol Aspects Med. 2008;29(6):369-375. doi:10.1016/j.mam.2008.04.004
12. Khundmiri SJ, Murray RD, Lederer E. PTH and Vitamin D. Compr Physiol. 2016 Mar 15;6(2):561-601. doi: 10.1002/cphy.c140071. PMID: 27065162.
13. Kelsey, L. et al. (2014) “Vitamin D3 Regulates the Formation and Degradation of Gap Junctions in Androgen-Responsive Human Prostate Cancer Cells,” PLoS ONE, 9(9), p. 106437. Available at: https://doi.org/10.1371/JOURNAL.PONE.0106437.
14. Potolicchio, I. et al. (2012) “Connexin-dependent signaling in neuro-hormonal systems,” Biochimica et Biophysica Acta (BBA) – Biomembranes, 1818(8), pp. 1919–1936. Available at: https://doi.org/10.1016/J.BBAMEM.2011.09.022.

Vitamin A

1. Vitamin A: Underappreciated Role in Thyroid Health | Designs for Health. (n.d.). Retrieved July 28, 2022, from https://blog.designsforhealth.com/vitamin-a-underappreciated-role-in-thyroid-health-0
2. Haugen, B.R. (2004) “The Effect of Vitamin A, Retinoids and Retinoid Receptors on the Hypothalamic-Pituitary-Thyroid Axis,” pp. 149–163. Available at: https://doi.org/10.1007/978-1-4020-7852-1_10
3. Brossaud, J., Pallet, V., & Corcuff, J. B. (2017). Vitamin A, endocrine tissues and hormones: interplay and interactions. Endocrine connections, 6(7), R121–R130. https://doi.org/10.1530/EC-17-0101
4. Zimmermann MB. Interactions of vitamin A and iodine deficiencies: effects on the pituitary-thyroid axis. Int J Vitam Nutr Res.(2007) 77:236–40. doi: 10.1024/0300-9831.77.3.236
5. Wolf G. The regulation of the thyroid-stimulating hormone of the anterior pituitary gland by thyroid hormone and by 9-cis-retinoic acid. Nutr Rev. (2002) 60:374–7. doi: 10.1301/00296640260385919
6. Trasino, S. E., & Gudas, L. J. (2015). Vitamin A: a missing link in diabetes? Diabetes Management (London, England), 5(5), 359. https://doi.org/10.2217/DMT.15.30
7. Amisten, S. et al. (2017) “Anti-diabetic action of all-trans retinoic acid and the orphan G protein coupled receptor GPRC5C in pancreatic β-cells,” Endocrine Journal, 64(3), pp. 325–338. Available at: https://doi.org/10.1507/ENDOCRJ.EJ16-0338.
8. Brossaud, J., Pallet, V. and Corcuff, J.B. (2017) “Vitamin A, endocrine tissues and hormones: interplay and interactions,” Endocrine connections, 6(7), pp. R121–R130. Available at: https://doi.org/10.1530/EC-17-0101.
9. Clagett-Dame, M. and Knutson, D. (2011) “Vitamin A in Reproduction and Development,” Nutrients, 3(4), p. 385. Available at: https://doi.org/10.3390/NU3040385.

Vitamin E

1. Dadkhah, H., Ebrahimi, E. and Fathizadeh, N. (2016) “Evaluating the effects of vitamin D and vitamin E supplement on premenstrual syndrome: A randomized, double-blind, controlled trial,” Iranian journal of nursing and midwifery research, 21(2), pp. 159–164. Available at: https://doi.org/10.4103/1735-9066.178237.
2. Bahrami, A. et al. (2020) “Menstrual problems in adolescence: relationship to serum vitamins A and E, and systemic inflammation,” Archives of gynecology and obstetrics, 301(1), pp. 189–197. Available at: https://doi.org/10.1007/S00404-019-05343-1.
3. Amini, L. et al. (2021) “The Effect of Combined Vitamin C and Vitamin E Supplementation on Oxidative Stress Markers in Women with Endometriosis: A Randomized, Triple-Blind Placebo-Controlled Clinical Trial,” Pain research & management, 2021. Available at: https://doi.org/10.1155/2021/5529741.
4. Xu, R. et al. (2014) “Influence of Vitamin E Supplementation on Glycaemic Control: A Meta-Analysis of Randomised Controlled Trials,” PLoS ONE, 9(4), p. 95008. Available at: https://doi.org/10.1371/JOURNAL.PONE.0095008.
5. Yalle-Vásquez, S. et al. (2022) “Vitamin E supplementation improves testosterone, glucose- and lipid-related metabolism in women with polycystic ovary syndrome: a meta-analysis of randomized clinical trials,” Gynecological Endocrinology [Preprint]. Available at: https://doi.org/10.1080/09513590.2022.2079629.
6. Tefagh, G. et al. (2022) “Effect of vitamin E supplementation on cardiometabolic risk factors, inflammatory and oxidative markers and hormonal functions in PCOS (polycystic ovary syndrome): a systematic review and meta-analysis,” Scientific reports, 12(1). Available at: https://doi.org/10.1038/S41598-022-09082-3.

Vitamin K

1. Cao, A.L. et al. (2020) “[Research progress of relationship between vitamin K and type 2 diabetes],” Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine], 54(5), pp. 555–562. Available at: https://doi.org/10.3760/CMA.J.CN112150-20190520-00407.
2. Vermeer, C. (2012) “Vitamin K: The effect on health beyond coagulation – An overview,” Food and Nutrition Research, 56. Available at: https://doi.org/10.3402/FNR.V56I0.5329.

Last updated on 10th August 2022 by cytoffice