insights

Nutrition and Impacts on Hormone Signaling

cooking food kitchen cutting cook hands man male knife preparation fresh preparing hand table salad concept - stock image
Read Time: 4 Minutes

Specific nutrients, dietary patterns, and overall nutrition may play either beneficial or detrimental roles in hormonal balance. Various nutrition intake patterns, from fasting to excess calories, as well as 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, IIFM Chief of Medical Affairs Joel Evans, MD, IFMCP, discusses an anchoring concept and effective tool used in functional medicine to address a patient’s hormonal imbalance.

(Video Time: 3 minutes) As part of functional medicine’s root-cause approach to hormonal dysfunction, IFM Chief of Medical Affairs 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 nutrition and cellular sensitivity to the hormone signal 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 positively influence pancreatic beta cell responsiveness and subsequent insulin sensitivity.11-15 A 2021 clinical trial randomized 32 morbidly obese patients who were on a waiting list for bariatric surgery into either a low-calorie diet group (30% carbohydrates, 30% protein, 40% lipids) or a Mediterranean diet group (55% carbohydrates, 15% protein, 30% lipids). After four weeks of treatment in addition to two sessions of behavioral dietary counseling, researchers found that while the diets did not affect fasting plasma glucose, both dietary approaches were similarly effective in improving insulin resistance and enhancing beta cell glucose sensitivity.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 the Mediterranean diet and others that are rich in plant-based foods and healthy fats, have been shown to decrease leptin levels and improve leptin sensitivity16,17 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.18 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.”19

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.20-22 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 may potentially lead to impaired insulin sensitivity.23-26 Another indirect pathway involves the role of nutritional signals, such as leptin, in the modulation of thyroid hormones.27 Dietary patterns potentially influence leptin sensitivity and levels,16-18 and any resulting drops in leptin signaling may ultimately influence thyroid hormone secretion, though the precise regulatory relationship is still unclear.28,29

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 the 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>

Related Articles

Assessing the Cortisol Curve

Testosterone Deficiency

Menopause and Nutrition

Chronic Stress and Hormone Disruption 

Balancing Thyroid Hormones Naturally

References

  1. Flier JS, Harris M, Hollenberg AN. Leptin, nutrition, and the thyroid: the why, the wherefore, and the wiring. J Clin Invest. 2000;105(7):859-861. doi:10.1172/JCI9725
  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):173-189. 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.  Tricò D, Moriconi D, Berta R, et al. Effects of low-carbohydrate versus Mediterranean diets on weight loss, glucose metabolism, insulin kinetics and β-cell function in morbidly obese individuals. Nutrients. 2021;13(4):1345. doi:10.3390/nu13041345
  13.  Galié S, García-Gavilán J, Papandreou C, et al. Effects of Mediterranean diet on plasma metabolites and their relationship with insulin resistance and gut microbiota composition in a crossover randomized clinical trial. Clin Nutr. 2021;40(6):3798-3806. doi:10.1016/j.clnu.2021.04.028
  14.  Kawaguchi T, Charlton M, Kawaguchi A, et al. Effects of Mediterranean diet in patients with nonalcoholic fatty liver disease: a systematic review, meta-analysis, and meta-regression analysis of randomized controlled trials. Semin Liver Dis. 2021;41(3):225-234. doi:10.1055/s-0041-1723751
  15.  Tettamanzi F, Bagnardi V, Louca P, et al. A high protein diet is more effective in improving insulin resistance and glycemic variability compared to a Mediterranean diet—a cross-over controlled inpatient dietary study. Nutrients. 2021;13(12):4380. doi:10.3390/nu13124380
  16.  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
  17.  Dinu M, Colombini B, Pagliai G, et al. Effects of a dietary intervention with Mediterranean and vegetarian diets on hormones that influence energy balance: results from the CARDIVEG study. Int J Food Sci Nutr. 2020;71(3):362-369. doi:10.1080/09637486.2019.1658723
  18.  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
  19.  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
  20.  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
  21.  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
  22.  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
  23.  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
  24.  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
  25.  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
  26.  Montgomery MK, Turner N. Mitochondrial dysfunction and insulin resistance: an update. Endocr Connect. 2015;4(1):R1-R15. doi:10.1530/EC-14-0092
  27.  Mullur R, Liu YY, Brent GA. Thyroid hormone regulation of metabolism. Physiol Rev. 2014;94(2):355-382. doi:10.1152/physrev.00030.2013
  28.  Witkowska-Sadek E, Kucharska A, Ruminska M, Pyrza B. Thyroid dysfunction in obese and overweight children. Endokrynol Pol. 2017;68(1):54-60. doi:10.5603/EP.2017.0007
  29.  Yu H, Li Q, Zhang M, et al. Decreased leptin is associated with alterations in thyroid-stimulating hormone levels after Roux-en-Y gastric bypass surgery in obese euthyroid patients with type 2 diabetes. Obes Facts. 2019;12(3):272-280. doi:10.1159/000499385

Related Insights