As oestrogen/progesterone are insulin sensitizing hormones, a reduction in these hormones can increase insulin resistance which may contribute to the metabolic dysregulation and symptoms of menopause. This section includes studies that support potential benefits of a TCR approach to help manage areas of common concern during menopause, primarily as a means of reducing glycaemic variability and insulin resistance.
Insulin resistance, weight gain and cardiovascular disease
Therapeutic carbohydrate reduction is one way to combat insulin resistance, weight gain, and inflammation – risk factors for CVD. Insulin resistance also contributes to platelet dysfunction and clotting risk.
- Mozaffarian D, Rimm EB, Herrington DM. Dietary fats, carbohydrate, and progression of coronary atherosclerosis in postmenopausal women. Am J Clin Nutr. 2004;80(5):1175-1184. doi:10.1093/ajcn/80.5.1175
- Blomquist C, Chorell E, Ryberg M, et al. Decreased lipogenesis-promoting factors in adipose tissue in postmenopausal women with overweight on a Paleolithic-type diet. Eur J Nutr. 2018;57(8):2877-2886. doi:10.1007/s00394-017-1558-0
- McPhee JC, Zinn C, Smith M. Exploring the acceptability of, and adherence to a carbohydrate-restricted diet as self-reported by women aged 40-55 years. J Holistic Performance NutritionTM. doi: 10.26712/230120181 PDF
- Segal-Isaacson C, Johnson S, Tomuta V, Cowell B, Stein DT. A Randomized Trial Comparing Low-Fat and Low-Carbohydrate Diets Matched for Energy and Protein. Obesity Research. 2004;12(S11):130S-140S. doi:10.1038/oby.2004.278
- Nickols-Richardson, S.M. et al. (2005) ‘Perceived hunger is lower and weight loss is greater in overweight premenopausal women consuming a low-carbohydrate/high-protein vs high-carbohydrate/low-fat diet’, Journal of the American Dietetic Association, 105(9), pp. 1433–1437. doi:10.1016/j.jada.2005.06.025.
- Simpson, S.J., Raubenheimer, D., Black, K.I., Conigrave, A.D., n.d. Weight gain during the menopause transition: Evidence for a mechanism dependent on protein leverage. BJOG: An International Journal of Obstetrics & Gynaecology n/a. doi.org/10.1111/1471-0528.17290
For more on this see CVD, obesity, and insulin resistance sections.
Glycaemic variability, insulin resistance and hot flashes
In addition to reducing hyperinsulinaemia, a TCR approach reduces glycaemic variability – keeping blood sugars more stable and can successfully reduce abdominal adiposity.
- Dormire SL. The Potential Role of Glucose Transport Changes in Hot Flash Physiology: A Hypothesis. Biol Res Nurs. 2009;10(3):241-247. doi:10.1177/1099800408324558
- Dormire S, Howharn C. The Effect of Dietary Intake on Hot Flashes in Menopausal Women. J Obstet Gynecol Neonatal Nurs. 2007;36(3):255-262. doi:10.1111/j.1552-6909.2007.00142.x
Namgoung, S. et al.
(2022) ‘Metabolically healthy and unhealthy obesity and risk of vasomotor symptoms in premenopausal women: cross-sectional and cohort studies’, BJOG: an international journal of obstetrics and gynaecology
- Huang W-Y, Chang C-C, Chen D-R, Kor C-T, Chen T-Y, Wu H-M. Circulating leptin and adiponectin are associated with insulin resistance in healthy postmenopausal women with hot flashes. PLoS One. 2017;12(4). doi:10.1371/journal.pone.0176430
- Thurston RC, Sowers MR, Sutton-Tyrrell K, et al. Abdominal adiposity and hot flashes among midlife women. Menopause. 2008;15(3):429-434. doi:10.1097/gme.0b013e31815879cf
Sleep has a bidirectional effect on metabolic health. Poor sleep patterns, such as shift work, can increase insulin resistance and increase the risk of developing metabolic syndrome. Increasing insulin resistance via other mechanisms, like changes in hormones, can reduce melatonin (inverse relationship) and affect sleep.
- Kravitz HM, Kazlauskaite R, Joffe H. Sleep, Health, and Metabolism in Midlife Women and Menopause: Food for Thought. Obstet Gynecol Clin North Am. 2018;45(4):679-694. doi:10.1016/j.ogc.2018.07.008
- Gangwisch JE, Hale L, St-Onge M-P, et al. High glycemic index and glycemic load diets as risk factors for insomnia: analyses from the Women’s Health Initiative. Am J Clin Nutr. 2020;111(2):429-439. doi:10.1093/ajcn/nqz275
- Siegmann MJ, Athinarayanan SJ, Hallberg SJ, et al. Improvement in patient-reported sleep in type 2 diabetes and prediabetes participants receiving a continuous care intervention with nutritional ketosis. Sleep Medicine. 2019;55:92-99. doi:10.1016/j.sleep.2018.12.014
- Tavakoli A, Mirzababaei A, Mirzaei K. Association between low carbohydrate diet (LCD) and sleep quality by mediating role of inflammatory factors in women with overweight and obesity: A cross-sectional study. Food Science & Nutrition. n/a(n/a). doi:10.1002/fsn3.2584
For more on this, see section on sleep.
Brain glucose hypometabolism and cognitive decline
‘The peri-menopausal transition is a tipping point for female brain aging. From the metabolic perspective, the process begins with decline in glucose metabolism and increase in insulin resistance, followed by a compensatory mechanism to use fatty acids and ketone bodies as an auxiliary fuel source’ Wang et al
TCR reduces brain insulin resistance and inflammation. If carbohydrate intake is sufficiently reduced ketone bodies can provide an alternative fuel source for the brain, further supporting cognitive function.
- Cunnane SC, Trushina E, Morland C, et al. Brain energy rescue: an emerging therapeutic concept for neurodegenerative disorders of ageing. Nat Rev Drug Discov. 2020;19(9):609-633. doi:10.1038/s41573-020-0072-x
- Yang H, Shan W, Zhu F, Wu J, Wang Q. Ketone Bodies in Neurological Diseases: Focus on Neuroprotection and Underlying Mechanisms. Front Neurol. 2019;10. doi:10.3389/fneur.2019.00585
- Mishra, A. et al. (2021) ‘A Tale of Two Systems: Lessons Learned from Female Mid-Life Aging with Implications for Alzheimer’s Prevention & Treatment’, Ageing Research Reviews, p. 101542. doi:10.1016/j.arr.2021.101542.
- Phillips MCL, Deprez LM, Mortimer GMN, et al. Randomized crossover trial of a modified ketogenic diet in Alzheimer’s disease. Alzheimer’s Research & Therapy. 2021;13(1):51. doi:10.1186/s13195-021-00783-x
- Taylor MK, Sullivan DK, Mahnken JD, Burns JM, Swerdlow RH. Feasibility and efficacy data from a ketogenic diet intervention in Alzheimer’s disease. Alzheimers Dement (N Y). 2017;4:28-36. doi:10.1016/j.trci.2017.11.002
For more on this, see section on Neurodegeneration.
Insulin resistance and mental health
This is an emerging area. See the section on Mental Health for the full collection.
- Jeremiah OJ, Cousins G, Boland F, Kirby BP, Ryan BK. Evaluation of the effect of insulin sensitivity-enhancing lifestyle- and dietary-related adjuncts on antidepressant treatment response: A systematic review and meta-analysis. Heliyon. 2020;6(9):e04845. doi:10.1016/j.heliyon.2020.e04845
- Firth J, Gangwisch JE, Borisini A, Wootton RE, Mayer EA. Food and mood: how do diet and nutrition affect mental wellbeing? BMJ. 2020;369. doi:10.1136/bmj.m2382
- Setayesh L, Ebrahimi R, Pooyan S, Yarizadeh H, Rashidbeygi E, Badrooj N, et al. The possible mediatory role of adipokines in the association between low carbohydrate diet and depressive symptoms among overweight and obese women. PloS one. 2021;16(9). doi:10.1371/journal.pone.0257275
Insulin resistance and bone turnover
Diet quality affects bone markers and metabolic syndrome is associated with reduced bone mineral density therefore addressing metabolic health through diet may have a valid role in protection from osteoporosis.
- Hu T, Yao L, Bazzano L. Effects of a 12-month Low-Carbohydrate Diet vs. a Low-Fat Diet on Bone Mineral Density: A Randomized Controlled Trial. The FASEB Journal. 2016;30(S1):678.12-678.12. doi:10.1096/fasebj.30.1_supplement.678.12
- Campillo-Sánchez F, Usategui-Martín R, Ruiz -de Temiño Á, et al. Relationship between Insulin Resistance (HOMA-IR), Trabecular Bone Score (TBS), and Three-Dimensional Dual-Energy X-ray Absorptiometry (3D-DXA) in Non-Diabetic Postmenopausal Women. Journal of Clinical Medicine. 2020;9(6):1732. doi:10.3390/jcm9061732
- Sharma DK, Anderson PH, Morris HA, Clifton PM. Visceral Fat Is a Negative Determinant of Bone Health in Obese Postmenopausal Women. International Journal of Environmental Research and Public Health. 2020;17(11):3996. doi:10.3390/ijerph17113996
- Cooper ID, Brookler KH, Crofts CAP. Rethinking Fragility Fractures in Type 2 Diabetes: The Link between Hyperinsulinaemia and Osteofragilitas. Biomedicines. 2021;9(9):1165. doi:10.3390/biomedicines9091165
- Salas R, Tijerina A, Cardona M, et al. Association between Bone Mineral Density and Metabolic Syndrome among Reproductive, Menopausal Transition, and Postmenopausal Women. Journal of Clinical Medicine. 2021;10(21):4819. doi:10.3390/jcm1021481
- Hunt HB, Miller NA, Hemmerling KJ, et al. Bone tissue composition in post-menopausal women varies with glycemic control from normal glucose tolerance to type 2 diabetes mellitus. Journal of Bone and Mineral Research. 2020;n/a(n/a). doi:10.1002/jbmr.4186 ABSTRACT
- Crivelli M, Chain A, da Silva ITF, Waked AM, Bezerra FF. Association of Visceral and Subcutaneous Fat Mass With Bone Density and Vertebral Fractures in Women With Severe Obesity. Journal of Clinical Densitometry. Published online October 16, 2020. doi:10.1016/j.jocd.2020.10.005 ABSTRACT
For more on this, see section on bone health.
Breast Cancer and Insulin Resistance
Multiple factors contribute to increased risk of breast cancer – the presence of insulin resistance/metabolic syndrome is known to impact risk and prognosis. For more on this, see section on cancer.
- Dong S, Wang Z, Shen K, Chen X. Metabolic Syndrome and Breast Cancer: Prevalence, Treatment Response, and Prognosis. Front Oncol. 2021;11. doi:10.3389/fonc.2021.629666
- Kundaktepe BP, Durmus S, Cengiz M, et al. The Significance of Insulin Resistance in Nondiabetic Breast Cancer Patients. Journal of Endocrinology and Metabolism. 2021;11(2):42-48. doi:10.14740/jem.v11i2.729
- Maiello M, Cecere A, Ciccone MM, Palmiero P. Metabolic syndrome and breast cancer: a dangerous association for postmenopausal women. A postmenopausal women prevention study. Acta Bio Medica : Atenei Parmensis. 2021;92(4). doi:10.23750/abm.v92i4.11335