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Nutrition and Impacts on Hormone Signaling

Specific nutrients, dietary patterns, and overall nutrition may play either beneficial or detrimental roles in hormonal balance. Nutrition intake patterns, such as fasting and excess calories, and foods with a higher glycemic load are known to impact circulating levels of certain hormones. For example, thyroid hormone regulation is influenced by the state of the body, from fed to starved,1 and adequate intake and availability of the nutrients selenium, iodine, and iron contribute to healthy levels and functioning of thyroid hormones.2,3 In addition, the steroid hormone cortisol regulates a wide range of body processes. While cortisol itself has an appetite-stimulating effect,4,5 extremes in nutrition intake, from overeating to starvation,6-8 as well as intake of specific nutrients, such as fish oil,9 may impact cortisol production and secretion.

While understanding nutrition’s potential impact on hormone levels is important, another puzzle piece to consider is nutrition’s potential impact on hormone sensitivity.

Do dietary factors impact cell sensitivity to hormonal signals, meaning how strongly they respond to the hormone message? Specifically, are tissues and cells more resistant or more sensitive to hormones based on specific nutrients, dietary patterns, or overall nutrition?

Understanding potential nutrition-hormone relationships, including hormone signaling sensitivity, is a key part of the Functional Medicine approach to hormonal dysfunction. When multiple hormones work together at fluctuating levels within a fluctuating environment, this creates a web of interconnection where many factors may impact the hormonal balance. Adding to the complexity, this hormonal web can vary from one patient to the next, depending on presentation, which may create a potential challenge for assessment and intervention. In the following video, IFM educator Joel Evans, MD, IFMCP, discusses an anchoring concept and effective tool used in Functional Medicine to address a patient’s hormonal imbalance

As part of Functional Medicine’s root-cause approach to hormonal dysfunction, Joel Evans, MD, IFMCP, highlights the sensitivity component of the IFM mnemonic “PTSD.”

Nutrition may influence tissue or cellular sensitivity to hormone signals in different ways: by direct or indirect paths and based on dietary patterns or specific nutrients. Identifying potential connections between cellular sensitivity to the hormone signal and nutrition may highlight additional points of leverage where therapeutic intervention may help restore balance.

Direct Nutritional Impacts on Hormone Signaling Sensitivity

Dietary patterns and composition may impact tissue sensitivity to at least some hormones. Studies have suggested an upregulation of cortisol release with a Western-pattern diet that includes increased amounts of refined carbohydrates and saturated fats and decreased amounts of fiber.6,10 Diet composition has also been suggested to influence pancreatic beta cell responsiveness and subsequent insulin sensitivity.11,12 A small study, within the context of a weight-maintaining diet for women with polycystic ovary syndrome (PCOS), indicated that with a modest carbohydrate reduction, a decrease in beta cell response and an increase in insulin sensitivity could be induced.12

Leptin is an appetite hormone released from fat cells in adipose tissue, and different foods may potentially increase or decrease leptin sensitivity. Anti-inflammatory diets, such as a fish diet, rich in polyunsaturated fatty acids, have been shown to improve leptin sensitivity,13 while increased amounts of saturated fatty acids have been found to induce leptin resistance by interrupting leptin signaling after chronic overstimulation of the leptin receptor.14 Further, an overall decrease in tissue sensitivity to leptin may lead to the development of obesity and the cyclic effect of “leptin-induced leptin resistance.”15

Indirect Nutritional Impact on Hormone Signaling Sensitivity

Cellular sensitivity to hormonal signals may be influenced by a patient’s physiological state, including systemic inflammation, amount of visceral fat, lifecycle stage, and the level of glucose intolerance.16-18 Nutrition may indirectly influence hormone signaling sensitivity in a manner that is dependent on these states. For example, intake of excess nutrients, such as high dietary fat, may lead to an increase in mitochondrial-generated reactive oxygen species (ROS). In turn, the chronic elevation of ROS can lead to impaired insulin sensitivity.19-21 Another indirect pathway involves the role of nutritional signals, such as leptin, in the modulation of thyroid hormones.22 Dietary patterns potentially influence leptin sensitivity and levels,13,14 and any resulting drops in leptin signaling may ultimately influence thyroid hormone secretion, though the precise regulatory relationship is still unclear.23

Clinical Applications

Determining the underlying cause of a hormonal imbalance or dysfunction may be challenging, depending on the individual patient and presentation. Understanding a cell’s sensitivity to hormonal signaling and what may be influencing any impaired signal reception is an important consideration for a subsequent intervention. Cellular sensitivity is S in IFM’s “PTSD” mnemonic, which is used in the general assessment of hormone dysfunction and helps determine if the dysfunction is related to hormone production, hormone transport, signaling sensitivity, or to an issue with detoxification. This Functional Medicine approach also helps identify points of leverage where physicians can apply individualized interventions to help restore hormonal balance. Learn more about Functional Medicine’s root-cause approach to hormonal dysfunction at the Hormone Advanced Practice Module.

LEARN MORE ABOUT RE-ESTABLISHING HORMONAL BALANCE>

For more information on hormone balance and nutritional interventions, please read the following IFM-authored articles:

Assessing the Cortisol Curve

Testosterone Deficiency

Menopause and Nutrition

Chronic Stress and Hormone Disruption 

References

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  2. Köhrle J. Selenium and the thyroid. Curr Opin Endocrinol Diabetes Obes. 2015;22(5):392-401. doi:10.1097/01.med.0000433066.24541.88.
  3. Guastamacchia E, Giagulli VA, Licchelli B, Triggiani V. Selenium and iodine in autoimmune thyroiditis. Endocr Metab Immune Disord Drug Targets. 2015;15(4):288-292. doi:10.2174/1871530315666150619094242.
  4. Takeda E, Terao J, Nakaya Y, et al. Stress control and human nutrition. J Med Invest. 2004;51(3-4):139-145. doi:10.2152/jmi.51.139.
  5. Yau YHC, Potenza MN. Stress and eating behaviors. Minerva Endocrinol. 2013;38(3):255-267.
  6. Vicennati V, Pasqui F, Cavazza C, et al. Cortisol, energy intake, and food frequency in overweight/obese women. Nutrition. 2011;27(6):677-680. doi:10.1016/j.nut.2010.07.016.
  7. Douyon L, Schteingart, DE. Effect of obesity and starvation on thyroid hormone, growth hormone and cortisol secretion. Endocrinol Metab Clin North Am. 2002;31(1):173-179. doi:10.1016/s0889-8529(01)00023-8.
  8. Nakamura Y, Walker BR, Ikuta T. Systematic review and meta-analysis reveals acutely elevated plasma cortisol following fasting but not less severe calorie restriction. Stress. 2016;19(2):151-157. doi:10.3109/10253890.2015.1121984.
  9. Noreen EE, Sass MJ, Crowe ML, Pabon VA, Brandauer J, Averill LK. Effects of supplemental fish oil on resting metabolic rate, body composition, and salivary cortisol in healthy adults. J Int Soc Sports Nutr. 2010;7:31. doi:10.1186/1550-2783-7-31.
  10. Pistollato F, Cano SS, Elio I, Vergara MM, Giampieri F, Battino M. Associations between sleep, cortisol regulation, and diet: possible implications for the risk of Alzheimer disease. Adv Nutr. 2016;7(4):679-689. doi:10.3945/an.115.011775.
  11. Silvestris E, Lovero D, Palmirotta R. Nutrition and female fertility: an interdependent correlation. Front Endocrinol. 2019;10:346. doi:10.3389/fendo.2019.00346.
  12. Gower BA, Chandler-Laney PC, Ovalle F, et al. Favourable metabolic effects of a eucaloric lower-carbohydrate diet in women with PCOS. Clin Endocrinol. 2013;79(4):550-557. doi:10.1111/cen.12175.
  13. Winnicki M, Somers VK, Accurso V, et al. Fish-rich diet, leptin, and body mass. Circulation. 2002;106(3):289-291. doi:10.1161/01.cir.0000025241.01418.4d.
  14. Engin A. Diet-induced obesity and the mechanism of leptin resistance. Adv Exp Med Biol. 2017;960:381-397. doi:10.1007/978-3-319-48382-5_16.
  15. Gruzdeva O, Borodkina D, Uchasova E, Dyleva Y, Barbarash O. Leptin resistance: underlying mechanisms and diagnosis. Diabetes Metab Syndro Obes. 2019;12:191-198. doi:10.2147/DMSO.S182406.
  16. Burhans MS, Hagman DK, Kuzma JN, Schmidt KA, Kratz M. Contribution of adipose tissue inflammation to the development of type 2 diabetes mellitus. Compr Physiol. 2018;9(1):1-58. doi:10.1002/cphy.c170040.
  17. Weiss G, Skurnick JH, Goldsmith LT, Santoro NF, Park SJ. Menopause and hypothalamic-pituitary sensitivity to estrogen. JAMA. 2004;292(24):2991-2996. doi:10.1001/jama.292.24.2991.
  18. Andrews RC, Herlihy O, Livingstone DEW, Andrew R, Walker B. Abnormal cortisol metabolism and tissue sensitivity to cortisol in patients with glucose intolerance. J Clin Endocrinol Metab. 2002;87(12):5587-5593. doi:10.1210/jc.2002-020048.
  19. Wellen KE, Thompson CB. Cellular metabolic stress: considering how cells respond to nutrient excess. Molecular Cell. 2010;40(2):323-332. doi:10.1016/j.molcel.2010.10.004.
  20. Anderson EJ, Lustig ME, Boyle KE, et al. Mitochondrial H2O2 emission and cellular redox state link excess fat intake to insulin resistance in both rodents and humans. J Clin Invest. 2009;119(3):573-581. doi:10.1172/JCI37048.
  21. Loh K, Deng H, Fukushima A, et al. Reactive oxygen species enhance insulin sensitivity. Cell Metab. 2009;10(4):260-272. doi:10.1016/j.cmet.2009.08.009.
  22. Mullur R, Liu YY, Brent GA. Thyroid hormone regulation of metabolism. Physiol Rev. 2014;94(2):355-382. doi:10.1152/physrev.00030.2013.
  23. Witkowska-Sedek E, Kucharska A, Ruminska M, Pyrzak B. Thyroid dysfunction in obese and overweight children. Endkrynol Pol. 2017;68(1):54-60. doi:10.5603/EP.2017.0007.

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