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How the 5:2 Diet Delivers Health and Longevity Gains. Mosley, Fontana and the Latest Science.

Updated: Jul 10

5:2 Diet Singapore

Intermittent fasting continues to gain attention as a flexible and potentially sustainable approach to weight management and metabolic health. Among its various forms, the 5:2 diet remains one of the most popular. It offers an appealing simplicity: eat normally for five days and limit calories sharply for two. But how effective is it, really, for weight loss and health? And what are the true origins of this diet popularised by the recently departed Michael Mosley?


As ever, please talk to your doctor or medical practitioner most familiar with your medical history before implementing any changes in diet, exercise or lifestyle, especially if you are under treatment. Links to all studies at bottom of page.

The Origins and Evolution of the 5:2 Diet


The 5:2 approach became widely known after British journalist Michael Mosley’s 2012 BBC Horizon documentary, Eat, Fast and Live Longer. Inspired by emerging research on calorie restriction and longevity, Mosley explored fasting's effects on health, eventually popularising the 5:2 format in his bestselling book The Fast Diet. The diet involves eating normally for five days a week and restricting calorie intake to about 500 to 600 calories on two non-consecutive days.


A key influence was Dr Luigi Fontana, a physician-scientist internationally recognised for his work on nutrition, ageing and metabolic health. Fontana’s research consistently emphasised that any fasting regimen - including the 5:2 - should be paired with a high-quality, nutrient-rich diet on non-fasting days - no 'junk'. The fasting days themselves should be limited to purely non-starchy vegetables, dressed with a tablespoon of olive oil, lemon juice or vinegar at lunch or dinner. No animal protein, fruit or grains.


The goal is not just to lose weight, but to support long-term metabolic health, reduce disease risk, and promote longevity. This eating practice, according to Fontana, shuts down the insulin/IGF-1/m-TOR pathway that modulates aging and the development of cancer. It acts both as a beneficial mild stressor (hormesis) and promotes BDNF, a protein that supports nerve cell development.


Key Terms:


  • Insulin is a hormone that helps cells absorb glucose from the blood for energy or storage. It also sends growth signals to cells.


  • IGF-1 (Insulin-like Growth Factor 1) is a hormone similar to insulin. It mainly promotes cell growth and survival, especially during childhood but it remains active throughout life.


  • mTOR (mechanistic Target of Rapamycin) is a key protein that controls cell growth, protein synthesis and metabolism. It acts like a 'growth switch' inside cells, responding to signals from insulin, IGF-1, nutrients and energy availability.


The insulin/IGF-1/mTOR pathway is a network of signals in which insulin and IGF-1 activate mTOR, promoting cell growth, protein synthesis and reproduction. While this pathway is essential for development, recovery and metabolic function, chronic activation - especially in nutrient-rich environments - can accelerate ageing by keeping cells in a continuous growth mode and increase cancer risk by promoting unchecked cell division and reducing autophagy. In contrast, down regulating this pathway through caloric or protein restriction, physical activity or compounds like rapamycin has been associated with longevity and reduced disease risk in various species.


Unfortunately, the public often interprets the 5:2 diet as a licence to eat freely (normally) on the five unrestricted days, undermining its potential to support long-term health rather than weight alone. Fontana’s dietary advice stresses plant-based, whole-food meals and limits ultra-processed foods and excess protein intake.

What the Science Shows


The caloric restriction found in the 5:2 diet has weight loss benefits in its own right. A 2025 meta-analysis in the International Journal of Endocrinology, focusing solely on the 5:2 diet, showed impressive results. In people with overweight or obesity, it reduced BMI, body fat percentage, waist circumference and LDL cholesterol. It also improved insulin sensitivity (measured by HOMA-IR) and systolic blood pressure, although effects on fasting glucose and long-term blood sugar control were less pronounced.


A 2022 meta-analysis in Obesity Reviews found that while all forms of intermittent fasting resulted in weight loss similar to traditional calorie restriction, alternate day fasting (a regimen consists of a fasting day, alternated with a day when participants can eat as desired) was slightly more effective. Unfortunately this eating practice is hard to maintain and the benefits appear to dwindle in the long-term. The 5:2 diet showed moderate success - reducing body weight by 1.7% to 7.97% in short- to mid-term trials.


For those who carry too much weight, weight loss or rather - fat loss - is inherently healthy. So what's not to enjoy with results like these?

A Closer Look at How Diet Quality Impacts Outcomes


A revealing insight comes from a 2023 a randomised controlled trial ('When a Calorie Is Not a Calorie") led by Dr Luigi Fontana, published in Aging Biology. The goal of this study was to see how intermittent fasting (IF) and the weight loss it causes might affect inflammation, metabolism, and biological processes related to healthy aging.


The study used a "vegetable fasting-mimicking" protocol - essentially fasting days with unlimited non-starchy vegetables and olive oil - intended to minimise calorie intake while ensuring nutritional value. On the non-fasting days, participants were advised to maintain their usual diet. This design allowed researchers to observe the effects of fasting alone, without changes in overall diet quality. In this six-month the researchers found that, even though participants lost about 8% of their body weight with IF, it did not reduce inflammation in the body - measured by markers like C-reactive protein. This is different from what is seen with chronic daily calorie restriction (the common form of dieting for weight loss), which can lower inflammation.

While weight and fat mass improved, the results suggested that diet quality on non-fasting days plays a pivotal role in whether intermittent fasting translates into deeper metabolic benefits.

They also found that IF led to a small improvement in how the body handles insulin, but it wasn’t a big or very meaningful change. Other recent studies on similar types of fasting have shown the same thing - little to no effect on inflammation or insulin sensitivity.


Interestingly, early results from the study also showed that the amount of weight someone lost on IF was strongly linked to changes in certain cellular pathways related to aging. But surprisingly, losing too much weight might negatively affect some important processes, like those involved in cell cleaning and growth.


Fontana’s team hypothesised that participants' typical Western diets on their five 'normal' days might have counteracted the longevity benefits of fasting. High protein intake, in particular, may overstimulate the mTOR pathway - linked to ageing and chronic disease - even when caloric intake is reduced.


This backs Fontana’s long-held position: intermittent fasting works best when paired with a nutrient-dense, plant-forward diet, as described in his book, The Path to Longevity. Without this, weight loss alone may not achieve the same anti-inflammatory or longevity-enhancing effects seen in controlled studies of calorie restriction.

Practical Insights and Pitfalls


  • Eat well on "off" days: Fontana’s findings challenge the common assumption that one can eat anything on the five non-fasting days. For meaningful health gains, these days should focus on whole grains, legumes, vegetables, fruits, nuts and healthy fats - mirroring Mediterranean-style diets.


  • Fast with care: Caloric intake on fasting days should be limited to around 500–600 kcal, ideally through non-starchy vegetable only meals, cooked in a little olive oil or steam fried. Simple salads, soups and smoothies can work well.


    Non-starchy vegetables are low in calories and carbohydrates, making them ideal for supporting weight management and blood sugar control. They’re rich in fibre, water, vitamins and antioxidants, helping to promote satiety without significantly increasing energy intake.


    Common examples include leafy greens like spinach, kale, and rocket; cruciferous vegetables such as broccoli, cauliflower and cabbage; as well as capsicum (bell peppers), tomatoes, courgettes, cucumbers, mushrooms, asparagus and green beans.


    These vegetables typically contain fewer than 5 grams of carbohydrate per 100g, most of which is fibre, making them a nutrient-dense foundation for any healthy eating plan.


  • Watch for muscle loss: Include resistance exercise and adequate protein on non-fasting days to protect lean muscle.

Final Thoughts


The 5:2 diet continues to be a promising strategy for managing weight and improving some metabolic health indicators. But the latest evidence - especially from Dr Fontana’s trial - makes clear that not all calories are equal. The benefits of fasting are amplified, not replaced, by what we eat in between.


Notably, and worth repeating, it was Dr. Fontana's original research that led Mosley to popularise his version of the 5:2 diet. It is, however, Fontana’s version of the diet remains the gold standard: fasting is only part of the picture. How we eat on the other five days matters just as much. And what happens when one comes off the diet, eating normally will simply put the weight back on. Another reason to be mindful of what one eats on the 'off-days'.


A key question when dieting for weight loss is what happens when the goal is achieved? What eating practice is then followed? Changing to a healthier eating pattern, with a whole food emphasis, requires permanent change for most people: new habits and skills that need to be learnt until they become a natural and enjoyable part of daily life.


Changing health for the better is about progress, not perfection, and even small changes can have a powerful and positive effect on health. For most people, improving health is about finding motivation and prioritising self-care - with an ultimate goal of taking action. If you want to take effective and targeted steps that fit into your unique lifestyle and circumstances, The Whole Health Practice is here to help.


Whether your interest is healthspan and longevity, to beat chronic illness or to enhance your mental health and well-being, our consultations and programs deliver results that are tailored to your needs.

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Related Studies


Wu C, Chen B, Yu J, Zhang Q, Piao C. Effect of the 5:2 Diet on Weight Loss and Cardiovascular Disease Risk Factors in Overweight and/or Obesity: A Systematic Review and Meta-Analysis. Int J Endocrinol. 2025 Feb 24;2025:6658512. doi: 10.1155/ije/6658512. PMID: 40041761; PMCID: PMC11876533.


Cagigas ML, Twigg SM, Fontana L. Ten tips for promoting cardiometabolic health and slowing cardiovascular aging. Eur Heart J. 2024 Apr 1;45(13):1094-1097. doi: 10.1093/eurheartj/ehad853. PMID: 38206047.


Guo L, Xi Y, Jin W, et al. A 5:2 Intermittent Fasting Meal Replacement Diet and Glycemic Control for Adults With Diabetes: The EARLY Randomized Clinical Trial. JAMA Netw Open. 2024;7(6):e2416786. doi:10.1001/jamanetworkopen.2024.16786



Elortegui Pascual P, Rolands MR, Eldridge AL, Kassis A, Mainardi F, Lê KA, Karagounis LG, Gut P, Varady KA. A meta-analysis comparing the effectiveness of alternate day fasting, the 5:2 diet, and time-restricted eating for weight loss. Obesity (Silver Spring). 2023 Feb;31 Suppl 1(Suppl 1):9-21. doi: 10.1002/oby.23568. Epub 2022 Nov 8. Erratum in: Obesity (Silver Spring). 2025 Feb 20. doi: 10.1002/oby.24266. PMID: 36349432; PMCID: PMC10098946.


Longo VD, Anderson RM. Nutrition, longevity and disease: From molecular mechanisms to interventions. Cell. 2022 Apr 28;185(9):1455-1470. doi: 10.1016/j.cell.2022.04.002. PMID: 35487190; PMCID: PMC9089818.


Arciero PJ, Arciero KM, Poe M, Mohr AE, Ives SJ, Arciero A, Boyce M, Zhang J, Haas M, Valdez E, Corbet D, Judd K, Smith A, Furlong O, Wahler M, Gumpricht E. Intermittent fasting two days versus one day per week, matched for total energy intake and expenditure, increases weight loss in overweight/obese men and women. Nutr J. 2022 Jun 4;21(1):36. doi: 10.1186/s12937-022-00790-0. PMID: 35658959; PMCID: PMC9166203.


Kang J, Shi X, Fu J, Li H, Ma E, Chen W. Effects of an Intermittent Fasting 5:2 Plus Program on Body Weight in Chinese Adults with Overweight or Obesity: A Pilot Study. Nutrients. 2022 Nov 9;14(22):4734. doi: 10.3390/nu14224734. PMID: 36432420; PMCID: PMC9698935.


Most J, Tosti V, Redman LM, Fontana L. Calorie restriction in humans: An update. Ageing Res Rev. 2017 Oct;39:36-45. doi: 10.1016/j.arr.2016.08.005. Epub 2016 Aug 17. PMID: 27544442; PMCID: PMC5315691.


Trepanowski JF, Kroeger CM, Barnosky A, Klempel MC, Bhutani S, Hoddy KK, Gabel K, Freels S, Rigdon J, Rood J, Ravussin E, Varady KA. Effect of Alternate-Day Fasting on Weight Loss, Weight Maintenance, and Cardioprotection Among Metabolically Healthy Obese Adults: A Randomized Clinical Trial. JAMA Intern Med. 2017 Jul 1;177(7):930-938. doi: 10.1001/jamainternmed.2017.0936. PMID: 28459931; PMCID: PMC5680777.


Ravussin E, Redman LM, Rochon J, Das SK, Fontana L, Kraus WE, Romashkan S, Williamson DA, Meydani SN, Villareal DT, Smith SR, Stein RI, Scott TM, Stewart TM, Saltzman E, Klein S, Bhapkar M, Martin CK, Gilhooly CH, Holloszy JO, Hadley EC, Roberts SB; CALERIE Study Group. A 2-Year Randomized Controlled Trial of Human Caloric Restriction: Feasibility and Effects on Predictors of Health Span and Longevity. J Gerontol A Biol Sci Med Sci. 2015 Sep;70(9):1097-104. doi: 10.1093/gerona/glv057. Epub 2015 Jul 17. Erratum in: J Gerontol A Biol Sci Med Sci. 2016 Jun;71(6):839-40. doi: 10.1093/gerona/glw056. PMID: 26187233; PMCID: PMC4841173.


Levine ME, Suarez JA, Brandhorst S, Balasubramanian P, Cheng CW, Madia F, Fontana L, Mirisola MG, Guevara-Aguirre J, Wan J, Passarino G, Kennedy BK, Wei M, Cohen P, Crimmins EM, Longo VD. Low protein intake is associated with a major reduction in IGF-1, cancer, and overall mortality in the 65 and younger but not older population. Cell Metab. 2014 Mar 4;19(3):407-17. doi: 10.1016/j.cmet.2014.02.006. PMID: 24606898; PMCID: PMC3988204.


Kennedy BK, Lamming DW. The Mechanistic Target of Rapamycin: The Grand ConducTOR of Metabolism and Aging. Cell Metab. 2016 Jun 14;23(6):990-1003. doi: 10.1016/j.cmet.2016.05.009. PMID: 27304501; PMCID: PMC4910876.


Fontana L, Partridge L, Longo VD. Extending healthy life span--from yeast to humans. Science. 2010 Apr 16;328(5976):321-6. doi: 10.1126/science.1172539. PMID: 20395504; PMCID: PMC3607354.


Fontana L, Villareal DT, Weiss EP, Racette SB, Steger-May K, Klein S, Holloszy JO; Washington University School of Medicine CALERIE Group. Calorie restriction or exercise: effects on coronary heart disease risk factors. A randomized, controlled trial. Am J Physiol Endocrinol Metab. 2007 Jul;293(1):E197-202. doi: 10.1152/ajpendo.00102.2007. Epub 2007 Mar 27. PMID: 17389710.


Renehan AG, Zwahlen M, Minder C, O'Dwyer ST, Shalet SM, Egger M. Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis. Lancet. 2004 Apr 24;363(9418):1346-53. doi: 10.1016/S0140-6736(04)16044-3. PMID: 15110491.


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