Metabolic Health and the Menopause

Globally, the proportion of older adults is growing. With life expectancy dramatically increased, there are currently more people over the age of 65 than under the age of 5.  There are a number of age-related health conditions that are impacted by what we eat (several have been discussed in our Healthy Ageing Science Splash), but here, we are going to have a closer look at the interplay between our diet and the changes that occur during menopause.  We will also discuss concepts that would help empower women to take control of the change and set-up their health for the next phase of their lives.

Menopause is clinically diagnosed when a woman has not menstruated for twelve months and marks the end of a woman’s reproductive years.  It typically occurs between the ages of 45 and 55 and is characterised by a decline in the production of hormones such as oestrogen and progesterone, resulting in the cessation of menstruation.  The decline and ultimately end of hormone production affects many biological systems, with physical impacts on metabolic health, weight, musculoskeletal system, genitourinary tract, skin condition, sexual function, and the central nervous system¹.  The physiological causes for these effects are multiple and complex, but they are not solely caused by oestrogen deficiency.

During menopause, there is a material change to both morphology and the amount of adipose tissue.  As oestrogen levels decline, there is a shift from a predominantly oestrogenic state to an androgenic state as the ratio of oestrogen:testosterone changes, with the ovaries continuing to produce androgens for several years after oestrogen production stops².  This affects several other hormones (gonadotropin, sex-hormone binding globulin) which further exacerbates the androgenic state.  The increase in bioavailable testosterone induces visceral fat accumulation, and at the same time there are elevated levels of follicle-stimulating hormone (FSH), which induces adipose tissue to further increase lipid accumulation in the fat cells and decreases serum adiponectin levels.  This chain of events leads to changes in body composition (including loss of lean body mass), fat accumulation and redistribution of adipose tissue in the abdominal area in menopausal women^{1, 3}.

With these hormonal changes promoting weight gain and fat accumulation, it is not surprising that there is also a change in blood lipid profiles, with an increase in total cholesterol, LDL cholesterol and apolipoprotein B, leading to further elevated cardiometabolic risk.  A recent cohort study, the ZOE PREDICT study, explored this further by examining the impact of postprandial metabolism on health and metabolic risk in menopausal women.

The ZOE PREDICT study investigated the effects of foods on postprandial responses in women in the UK and US (366 premenopausal, 55 perimenopausal, 206 postmenopausal).  The study measured cardiometabolic blood parameters in both the fasting and postprandial period, as well as examining time-in-range (measured using Continuous Glucose Monitors) and gut microbiome data³.  Postmenopausal women had higher fasting glucose, HbA1c, and inflammatory markers (6%, 5%, 4% increase respectively) compared with premenopausal women.  The postprandial period glucose and insulin responses were higher (42% and 4% increase respectively), and time-in-range was more poorly controlled in postmenopausal women compared with premenopausal women³.

The study also conducted a mediation analysis to identify associations between the menopausal state and metabolic health risks (visceral fat, inflammation, glycaemia) and found that diet and gut health were associated and in part mediated these risks.  Glycaemic control (time-in-range and glycaemic variability) was worse in menopausal women compared with pre-menopause, and using age-matching, the authors determined the differences were not just due to age, but rather attributable to the menopausal changes³.

Most people spend the majority of their day in the postprandial phase, and postprandial hyperglycaemia and hyperlipidaemia are known independent risk factors for cardiovascular diseases⁴.  Considering the additional cardiometabolic risks that are associated with menopause, and that these risks are exacerbated by glucose excursions, it is important that women in the peri- and post-menopausal phases actively maintain their glucose levels within a normal, healthy range^{5, 6}.

One of the most bothersome symptoms during menopause are hot flashes.  They can happen at day or night and are experienced by up to 80% of women.  At least half of women experience them for more than seven years, and they can have a strong impact on sleep, mood, and cognitive function.  In the past, hot flashes were thought to only have a negative impact on quality of life, but an ever-increasing number of large clinical trials and epidemiological studies have shown links between hot flashes and cardiovascular risk^{7, 8}.

Insulin resistance is considered a risk factor for cardiovascular disease, and recently it has been shown that both hot flashes and night sweats are also strongly associated with insulin resistance⁸. Women who experience more severe hot flashes typically have higher glucose and insulin levels⁹, while diet modifications that increase the consumption of fruit, vegetable and whole grains, result in a decrease in hot flash frequency¹⁰.

Sharp spikes and drops in our blood glucose levels can lead to insulin resistance, and so keeping our glucose levels within a healthy range and improving insulin sensitivity may be an effective strategy to mitigate hot flashes. This can be achieved through diet modification or the use of supplements that help support healthy blood sugar levels and a healthy insulin response.

Reducose® is an example of an ingredient that can help.  It is a proprietary mulberry leaf extract that has been shown across nine human clinical trials to significantly reduce postprandial glucose and insulin levels already in a normal, healthy range.  Reducose®, inhibits the digestive enzymes that break down carbohydrates and prevents their absorption into the body.  Clinical trials have shown that Reducose® lowers glucose and insulin spikes after eating by more than 40%¹¹.  It is well tolerated with no difference in frequency or severity of gastrointestinal symptoms compared with a placebo¹². The undigested carbohydrates continue to travel through the GI tract, where they stimulate GLP-1¹³, and an unpublished pilot study has shown that Reducose® improves blood lipid profile, lowering LDL and total cholesterol by 11% and 14% respectively.  These undigested nutrients ultimately reach the microbiome, where they are fermented to short chain fatty acids, which have further metabolic health benefits.  These effects will contribute to improved time-in-range, better glycaemic control, lower insulin spikes and improved insulin sensitivity, and long-term use may lead to weight loss; all of which would contribute to maintaining metabolic health and may help lower the frequency and severity of hot flashes in menopausal women.

Reducose®’s small dose of only 200mg-250mg, allows for great flexibility when combining it with other functional ingredients that may be beneficial for women going through menopause.  Reducose® is stable, water soluble, and easy to formulate into a range of dietary supplement dosage forms including tablets, capsules, powders, gummies, stick-packs, fast melts as well as in different food applications such as baked goods and beverages.

The changes that occur in a woman during menopause not only have physical effects but may have psychosocial impacts as well.  There are many things a woman can do to take back control during menopause and using products containing Reducose® can be part of a management plan that helps empower women to manage their health and wellbeing.

References

1. Jeong HG, Park H. Metabolic Disorders in Menopause. Metabolites. 2022;12(10).
2. Janssen I, Powell LH, Jasielec MS, Kazlauskaite R. Covariation of change in bioavailable testosterone and adiposity in midlife women. Obesity (Silver Spring). 2015;23(2):488-94.
3. Bermingham KM, Linenberg I, Hall WL, Kade K, Franks PW, Davies R, et al. Menopause is associated with postprandial metabolism, metabolic health and lifestyle: The ZOE PREDICT study. EBioMedicine. 2022;85:104303.
4. Wajchenberg BL. Postprandial glycemia and cardiovascular disease in diabetes mellitus. Arq Bras Endocrinol Metabol. 2007;51(2):212-21.
5. Cho YA, Kim J, Cho ER, Shin A. Dietary patterns and the prevalence of metabolic syndrome in Korean women. Nutr Metab Cardiovasc Dis. 2011;21(11):893-900.
6. Millen BE, Pencina MJ, Kimokoti RW, Zhu L, Meigs JB, Ordovas JM, et al. Nutritional risk and the metabolic syndrome in women: opportunities for preventive intervention from the Framingham Nutrition Study. Am J Clin Nutr. 2006;84(2):434-41.
7. Szmuilowicz ED, Manson JE, Rossouw JE, Howard BV, Margolis KL, Greep NC, et al. Vasomotor symptoms and cardiovascular events in postmenopausal women. Menopause. 2011;18(6):603-10.
8. Thurston RC, El Khoudary SR, Sutton-Tyrrell K, Crandall CJ, Sternfeld B, Joffe H, et al. Vasomotor symptoms and insulin resistance in the study of women’s health across the nation. J Clin Endocrinol Metab. 2012;97(10):3487-94.
9. Huang WY, Chang CC, Chen DR, Kor CT, Chen TY, Wu HM. Circulating leptin and adiponectin are associated with insulin resistance in healthy postmenopausal women with hot flashes. PLoS One. 2017;12(4):e0176430.
10. Kroenke CH, Caan BJ, Stefanick ML, Anderson G, Brzyski R, Johnson KC, et al. Effects of a dietary intervention and weight change on vasomotor symptoms in the Women’s Health Initiative. Menopause. 2012;19(9):980-8.
11. Thondre PS, Lightowler H, Ahlstrom L, Gallagher A. Mulberry leaf extract improves glycaemic response and insulaemic response to sucrose in healthy subjects: results of a randomized, double blind, placebo-controlled study. Nutr Metab (Lond). 2021;18(1):41.
12. Lown M, Fuller R, Lightowler H, Fraser A, Gallagher A, Stuart B, et al. Mulberry-extract improves glucose tolerance and decreases insulin concentrations in normoglycaemic adults: Results of a randomised double-blind placebo-controlled study. PLoS One. 2017;12(2):e0172239.
13. Mafauzy M, Zagury RL, Bhaskaran K, Neutel J, Yusof BNM, Yeo L, et al. A Randomized, Placebo-Controlled Crossover Study to Evaluate Postprandial Glucometabolic Effects of Mulberry Leaf Extract, Vitamin D, Chromium, and Fiber in People with Type 2 Diabetes. Diabetes Ther. 2023;14:749-66.