The truth about Intermittent Fasting for women over 40, Part 2: Autophagy, cortisol, and the sign it isn't working for you
5min read
In this second part I'm looking at what's actually known about intermittent fasting for women in perimenopause and menopause: the claims around autophagy and longevity, what cortisol has to do with it, and how to tell when fasting isn't working for you.
You'll find part one here, where I covered weight management, muscle preservation, and metabolism.
If you read nothing else, read this
One thing worth knowing: If you're on a GLP-1 medication, such as semaglutide (Ozempic, Wegovy) or the dual GLP-1/GIP medication tirzepatide (Mounjaro, Zepbound), think twice before adding fasting on top, and talk to your prescriber first. These medications already suppress appetite enough to cause malnutrition, in some cases.
One thing to ponder: What's your overall stress load right now, and how much room do you actually have to take on more?
One thing to experiment with: Instead of removing a meal or trying to manage calories and macros, try adding more fruit and vegetables to your meals, slow down while you eat, and notice how you feel.
What autophagy actually is
Autophagy is your body's ongoing way of clearing out damaged or worn-out parts of cells. It's running at a low level all the time, not just when you fast. What changes with fasting or exercise is the rate of this process, not whether it happens at all. Two switches drive this: AMPK senses when the body's energy is low and turns autophagy up directly, while mTOR normally holds it back and switches off when food is scarce, releasing that brake [1]. Fasting engages both. Exercise turns AMPK on too, through the energy demand of working muscle [2].
Human studies have found markers of increased autophagy activity after both fasting and exercise [2][3]. The strongest human evidence used a proper measure of the process itself, not just gene activity, and it came from one intensive protocol, three near-fasting days a week, not a daily pattern that one can typically manage [4]. The fasting-mimicking diet, a structured 5-day very-low-calorie plan followed monthly, has shown real benefits in a randomised trial, including better insulin sensitivity, less fat in the liver, and markers of slower biological ageing, independent of weight loss [5].
Whether fasting longer or more often increases the autophagy benefit further, it hasn't actually been tested.
Cortisol, stress, and fasting
You'll often hear that stress and cortisol cause "meno belly." The evidence for that is weaker than its reputation, and it's worth its own piece, which I'll write separately. The short version: declining oestrogen is the best-supported driver of where fat sits in midlife [6][7]. Cortisol is associated with central fat, but association isn't causation [8]. Chronic stress does matter, mostly through changes you can see, disrupted sleep, increased cravings, less movement [9].
What's relevant here is more nuanced. Does fasting raise cortisol, and does that matter?
Restriction itself is a stressor
Postmenopausal women who deliberately limited their food to manage weight had higher cortisol than women who didn't, even though their weight, exercise, and reported stress were the same [10]. The restriction itself seemed to be the difference.
That's worth knowing, but cortisol isn't really the point. Restriction is one more demand on a system that may already be stretched. If your sleep is poor, your stress is high, and you're training hard, a fasting window is one more thing to manage.
Whether fasting suits you depends on your stress levels, your sleep, and your recovery. If your stress is manageable and your sleep is good, it may be worth trying fasting. But if it starts to affect your sleep, or you find yourself more preoccupied with food and cravings, or your workouts suffer and your energy and mood begin to fluctuate, then it's worth rethinking this pattern of eating and how much restriction you've taken on.
GLP-1 medications and fasting
If you're on semaglutide (Ozempic, Wegovy) or tirzepatide (Mounjaro, Zepbound, which acts on both the GLP-1 and GIP receptors), combining either with fasting needs real caution. These medications suppress appetite as their actual mechanism, not as a side effect, which means hunger isn't a reliable signal that something's wrong.
This isn't theoretical. One study found people on GLP-1 medications were over six times more likely to show signs of malnutrition before surgery than people not taking them [11]. In a study of more than 450,000 people on these medications, 22 percent developed a nutritional deficiency within a year, most often vitamin D [12]. And people managing treatment without nutrition guidance often cut their intake further than they realise [13].
Watch for fatigue, hair thinning, low energy, or trouble concentrating. And talk to your prescriber before adding fasting on top, however little appetite you have.
The sign it isn’t working for you
Food restriction doesn't just affect how the body works, it can change how someone relates to food itself. The classic demonstration is the Minnesota Starvation Experiment, where 36 men followed a semi-starvation diet for six months, roughly half their previous intake, and lost about a quarter of their body weight. Many became preoccupied with food, dreaming about it, talking about it constantly, collecting recipes [14].
That preoccupation doesn't stay contained. Periods of restriction are often followed by periods of eating more than you meant to, and the cycle tends to repeat.
This kind of preoccupation tends to show up more in women with a longer history of dieting. The pattern seems easier to trigger once it's been triggered before. Women without that history often find fasting unremarkable.
If fasting leaves you constantly thinking about food, that's worth paying attention to. It's a sign to discuss with a coach or healthcare provider, not something to push through alone.
In summary
Autophagy runs in your body all the time. Fasting and exercise both seem to turn up its activity, but the evidence is limited, and more fasting hasn't been shown to result in more benefit.
Declining oestrogen is the best-supported driver of midlife belly fat. Cortisol is associated with it but isn't a proven direct cause, and sleep, nutrition, and muscle preservation matter at least as much.
Restriction itself raises cortisol. It also changes how you think about food, and may result in overeating. Whether fasting suits you depends on your stress levels and quality of sleep.
Combining fasting with a GLP-1 medication needs real caution. Hunger won't warn you reliably to recognise your body’s needs, so watch for fatigue and hair loss, and work with a coach or nutritionist to make sure you cover your nutrition needs.
If you want help working out what's worth your effort and what isn't, book a free discovery call. It's a friendly conversation. You'll leave clearer on what actually drives results in midlife, whether or not we work together.
References
[1] Lu C, He C. Autophagy: nutrient and energy mobilization in need. Current Biology. 2022. PMID: 35728554. https://pmc.ncbi.nlm.nih.gov/articles/PMC9652773/
[2] Brandt N, Gunnarsson TP, Bangsbo J, Pilegaard H. Exercise and exercise training-induced increase in autophagy markers in human skeletal muscle. Physiological Reports. 2018;6(7):e13651. https://pmc.ncbi.nlm.nih.gov/articles/PMC5889490/
[3] Jamshed H, Beyl RA, Della Manna DL, Yang ES, Ravussin E, Peterson CM. Early time-restricted feeding improves 24-hour glucose levels and affects markers of the circadian clock, aging, and autophagy in humans. Nutrients. 2019;11(6):1234.
[4] Bensalem J, Teong XT, Hattersley KJ, et al. Intermittent time-restricted eating may increase autophagic flux in humans: an exploratory analysis. Journal of Physiology. 2025;603(10):3019-3032. https://pubmed.ncbi.nlm.nih.gov/40345145/
[5] Wei M, Brandhorst S, et al. Fasting-mimicking diet and markers/risk factors for aging, diabetes, cancer, and cardiovascular disease. Science Translational Medicine. 2017;9(377):eaai8700.
[6] Grub J, Süss H, Willi J, Ehlert U. Steroid Hormone Secretion Over the Course of the Perimenopause: Findings From the Swiss Perimenopause Study. Frontiers in Global Women's Health. 2021;2:774308. PMID: 34970652; PMCID: PMC8712488.
[7] Pedersen SB, Kristensen K, Hermann PA, Katzenellenbogen JA, Richelsen B. Estrogen controls lipolysis by up-regulating α2A-adrenergic receptors directly in human adipose tissue through the estrogen receptor α. Journal of Clinical Endocrinology and Metabolism. 2004;89(4):1869-1878.
[8] Epel ES, McEwen B, Seeman T, Matthews K, Castellazzo G, Brownell KD, Bell J, Ickovics JR. Stress and body shape: stress-induced cortisol secretion is consistently greater among women with central fat. Psychosomatic Medicine. 2000;62(5):623-632.
[9] Migala J. What is "cortisol belly"? How stress leads to abdominal fat, and how to reduce it. Everyday Health. Published 18 August 2025. Medically reviewed by Sean Hashmi, MD. https://www.everydayhealth.com/mental-health/what-is-cortisol-belly/
[10] Rideout CA, Linden W, Barr SI. High cognitive dietary restraint is associated with increased cortisol excretion in postmenopausal women. Journal of Gerontology: Series A. 2006;61(6):628-633. https://academic.oup.com/biomedgerontology/article/61/6/628/589490
[11] Jodoin Z, Young WH, Sheikh D, et al. Malnutrition is common in patients utilizing glucagon-like peptide-1 agonists prior to total joint arthroplasty. Arthroplasty Today. 2025.
[12] Butsch WS, Sulo S, et al. Nutritional deficiencies and muscle loss in adults with type 2 diabetes using GLP-1 receptor agonists. Obesity Pillars. 2025;15:100186.
[13] Mogna-Peláez P, Guasch-Ferré M. Avoiding malnutrition in the era of GLP-1 medications: emerging evidence and opportunities for integrated nutrition care. The Journal of Nutrition. 2026; In Press, Journal Pre-proof, 101684. https://www.sciencedirect.com/science/article/pii/S0022316626003330
[14] Kalm LM, Semba RD. They starved so that others be better fed: remembering Ancel Keys and the Minnesota Experiment. Journal of Nutrition. 2005;135(6):1347-1352.