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Don Gordon

Unlocking the Secrets of Longevity The 5 Pillars of Fasting for a Revitalized Life

Fasting appears to be the new health trend these days due to an increased level of research supporting numerous health and weight loss benefits associated with restricting food intake. However, increasingly research is emerging that paints a more holistic picture when considering Longevity & Lifespan. Additionally, as practitioners we become conscious of the significant role that personalisation, gender and lifestyle must play. Our relationship with the foods we eat, when we eat them, or conversely abstain, can have dramatic consequences on our whole holistic ecosystem. Seasonality and elemental cycles can also impact our circadian rhythm, not just our metabolic and hormonal physiology, but also our neurology and emotional wellbeing.


New research is uncovering the multi-systemic benefits of fasting, revealing how specific approaches to fasting can positively impact the body's key functions and support long-term health. These breakthroughs are being implemented as first-line treatments for reversing metabolic disorders, particularly in the US, where registered dietitian coaching plays a vital role.

At the heart of this movement are the 5 pillars of fasting, which focus on improving metabolic health, enhancing energy levels, and preventing chronic diseases. These principles are already being integrated into programs like Healthspan Coaching, built around Longevity Nutrition and currently used by L-Nutra Health to support individuals with Type 2 Diabetes. While not yet available in the UK, this science-backed approach holds immense promise for transforming mainstream health interventions in the near future.

By incorporating these five pillars into your lifestyle, you can revitalize your life, enhance your wellbeing, and take proactive steps towards preventing conditions like diabetes, cardiovascular disease, and obesity—unlocking the secrets to a longer, healthier life. 


The Five key areas that are influenced by certain types of fasting are already well documented in human studies – these include;

1.       Reduction of Oxidative Stress

Emerging research points towards certain forms of fasting triggering various beneficial processes in the body. One of which is the lowering of oxidative stress, which can damage cells and increase risk factors for aging 1

 

2.       Promoting stem cell regeneration

Fasting has been shown to stimulate the production of new stem cells, which can aid in tissue repair and rejuvenation 2.

Fasting has been shown to stimulate the production of new stem cells, which can significantly aid in tissue repair and rejuvenation. Studies indicate that fasting triggers a metabolic switch in stem cells, enhancing their regenerative capacity by breaking down fatty acids instead of glucose1. This process not only helps in repairing tissues but also rejuvenates aged stem cells, restoring their youthful function 2. The benefits for anti-aging are substantial, as improved stem cell function can combat age-related diseases, enhance immune response, and promote overall cellular health 3. Thus, fasting offers a promising approach to maintaining vitality and longevity


3.       Biological Age and Healthspan

Prolonged fasting (PF) promotes stress resistance, although effects on longevity are still poorly understood. Alternating PF and nutrient-rich medium extended yeast lifespan independently of established pro-longevity genes. Periodic cycles of the fasting mimicking diet revealed a protection of normal cells while killing damaged cells including cancer and autoimmune cells, a reduction of inflammation, promotion of multi-system regeneration and longevity extension.  Furthermore, three FMD cycles were associated with a decrease of 2.5 years in median biological age, independent of weight loss. Nearly identical findings resulted from a second clinical study (NCT04150159). Together these results provide initial support for beneficial effects of the FMD on multiple cardiometabolic risk factors and biomarkers of biological age. biomarkers of biological age 3 .


4.       Autophagy

Autophagy is a cellular process that recycles damaged components, promoting rejuvenation and extending healthspan. By clearing out cellular debris and toxic proteins, autophagy enhances cellular function, reduces oxidative stress, and supports longevity. Prolonged fasting more than 2 days activates autophagy. Fasting has also shown to enhance insulin sensitivity, reduce inflammation, and lower the risk of chronic diseases 4.

 


5.       Microbiome and Gut Health

Hidden within your body lies a bustling metropolis of microscopic inhabitants collectively known as your microbiome. These tiny microorganisms significantly outnumber your own human cells and play a crucial role in maintaining overall health. But why is your microbiome so important? A healthy microbiome acts as a guardian of your well-being, with changes in its composition potentially enhancing or impairing metabolic and immune functions.

Research has shown that prolonged fasting programs can benefit the microbiome by fostering the growth of beneficial microbes. In mice studies modelling irritable bowel disease (IBD), fasting-mimicking diet (FMD) cycles reduced intestinal inflammation, increased the number of stem cells, stimulated protective gut microbes, and even reversed intestinal damage caused by IBD 5. These exciting discoveries have led to the development of daily pre- and probiotic supplements like ProLon™' L-Biome, designed to mimic the microbiome of fasting. 

 


Aging skin is a natural part of life, but it doesn’t mean we can’t feel incredible in our own skin as we age. A recent study found remarkable results from three monthly cycles of FMD on the skin. Participants on the FMD experienced a significant increase in skin hydration and smoother skin texture compared to those not on the diet. Just one cycle of the FMD resulted in a 25% increase in skin hydration, with three monthly cycles resulting in a 35% increase. Participants also reported significant improvements in skin texture, smoothness, hydration, and skin tone evenness, along with other skin improvements on post-FMD surveys. Beyond the visible changes, many participants reported improvements in happiness, confidence, and a sense of empowerment to take control of their health 6.



 

Types of fasting protocols

There are many different types of fasting methods including intermittent fasting (IF), time restricted fasting (TRF), and water-based fasting. For example, a 16:8 intermittent fast involves a 16 hour fast followed by an 8 hour period when you consume all of your daily calories. Other popular variations include 13:11, 18:16, and 20:4. More prolonged fasting may include water only for three days or more, and the increasingly popular fasting mimicking diets (FMD), which involves fasting with food for five days. Aside from religious and spiritual significance, fasting has been used by physicians throughout the millennia as a therapy for numerous health conditions. Research is increasingly observing that the biological systems in the body involved with digestion and creating energy may be directed towards metabolic rest, resulting in the body administering cellular repair and rejuvenation.


The emergence of fasting mimicking diets (FMDs)

We now know that fasting can result in ketogenesis, which can promote potent changes in metabolic pathways and cellular processes, such as stress resistance and autophagy, but how much more is there to the story? The emerging popularity of the fasting mimicking dieting (FMD) approach has been developed after 25 years of clinical research by Professor Valter Longo, who is considered a worldwide leading expert on lifespan and longevity. This ‘pretend’ fast appears to have all the health benefits of water fasting, but without the hardships or safety concerns.

The popular ProLon FMD approach consists of between 34 and 54 per cent of normal adult daily calorie intake, with the macronutrient ratio made up of 9-10 per cent protein, 56 per cent fat and 34 per cent carbohydrate, the five days of the programme are split into:

• Day 1 – 1,090 calories (9 per cent protein)

• Days 2 to 5 – 725 calories (10 per cent protein)


What Happens During The Fasting Mimicking Diet Programme Journey?

The journey may last 7 days including a prep day at the beginning and transition day at the end.


Fig.1 ProLon FMD Journey.  The journey may last 7 days including a prep day at the beginning and transition day at the end


The focus of the ProLon FMD includes a certain balance of nutrients, so that it does not feel like a fast, but still conveys the same health benefits. The FMD places less stress on the body than complete water fasting, supplying most of the carbs in the form of vegetables, meaning a strong focus on phytonutrients, along with a reduction in calories. Recent studies have suggested that fasting triggers the downregulation of nutrient sensing pathways, which brings about adaptive cellular responses, reducing oxidative damage and inflammation, as well as improving energy metabolism 7. That said, this experience may vary across individuals based upon health history.

FMD research has been shown to inhibit nutrient sensing pathways like Protein kinase alpha (PKA), Insulin Like Growth Factor (IGF-1), and Mammalian Target of Rapamycin (mTOR) which reduces cellular growth signals, promoting autophagy and stress resistance. This process rejuvenates cells, enhances metabolic health, and extends healthspan by delaying age-related diseases and improving overall cellular function 7.


 Fig 2. Clinical Study Results - Brandhorst et al 2017


As shown in Figure 2, it also appears that a calorific restrictive practice (with limited protein intake) may confer a multi stress resistance, and even stimulate transient stem cell-based regeneration 8. The benefits of fasting protocols have been shown by some research to normalise elevated biomarkers for type 2 diabetes, asthma, obesity, high blood pressure and inflammation 9. It also has the potential to prolong lifespan by reprogramming metabolic and stress resistance pathways. Some of these biomarkers (especially inflammation and reverse immunosuppression ) may have longer term benefits for healthspan, although further research needs to be done. One scientific review focussed on protein restriction, which leads to the lowering of intracellular amino acid levels, reducing mammalian target of rapamycin (mTOR) activity and stimulating autophagy, two key processes involved in ageing and cancer 10.


Promising as it looks, randomised clinical trials in larger human population groups are needed to establish the long term metabolic and clinical effects of protein restriction in humans. Professor Longo believes that post-fasting stem cell activation drives the health and longevity benefits of the FMD. He states “During the re-feeding, the stem cells are turned on and… they rebuild the cells and systems and organs that have been reduced in size and cell number during the fasting,” he said. Additionally, with this prolonged 48 to 120 hour fasting period, insulin-like growth factor-1 (IGF-1) and protein kinase (PKA) signalling are shown to have a crucial role in regulating hematopoietic stem cell protection, self-renewal, and regeneration 9. Because a FMD contains food, lean body mass has been shown to be preserved after three cycles, which is not the case with water based fasting.

 

Muscle Mass and Performance

While weight loss can improve overall health, the type of weight lost is key. Many diets result in the loss of both fat and valuable lean muscle mass. (Nardon et al., 2022) (Wei & et al., 2017). But why is muscle mass so important? Muscle is your body's engine, playing multiple roles that are vital to your well-being. It supports a higher metabolic rate, helping maintain weight loss, safeguards your strength, enhances immune function, and even reduces the risk of insulin resistance and type 2 diabetes. (Ravussin et al., 1988) (Willoughby et al., 2018) (LeBrasseur et al., 2011) (Shao et al., 2021). 

Unlike most diets, the FMD (Fasting Mimicking Diet) focuses on preserving muscle mass while promoting fat loss. Research shows that adults following the FMD experience a reduction in BMI without losing muscle volume or neuromuscular performance. (Nardon et al., 2022). These findings are significant, whether you're aiming to boost performance or maintain strength during dietary changes.


Female Fasting & personalisation

The paradigm of fasting and some recent media articles are expressing concerns around the application of varying fasting methods being detrimental for women. However, some research suggests that fasting with 100% consistency might not be universally applicable.

For men, whose biology naturally maintains a consistent output of male hormones, a regular fasting schedule could work well. But for females, the story is different. The female body experiences hormonal fluctuations each month, and different hormones require different nutrients. Therefore, any fasting plan should align with the dominant hormone to achieve optimal results.

Key hormones include oestrogen (high after menstruation) and progesterone (high during the luteal phase). These hormonal shifts influence nutrient requirements and metabolic responses and should therefore be addressed appropriately.


Intermittent Fasting and Hormones:

Evidence from randomized trials suggests that intermittent fasting does not significantly affect circulating concentrations of oestrogen, testosterone, sex hormone binding globulin (SHBG), gonadotropins, or prolactin in women over a 1-year period 11.

However, more research is needed, especially in postmenopausal individuals with obesity 2.

Adapting Fasting to Hormonal Phases:

After Menstruation (Follicular Phase): Oestrogen levels are high. Carbohydrates are not essential during this time, making it an ideal period for fasting. During the Luteal Phase (Progesterone High): Progesterone dominance may lead to PMS symptoms. Fasting during this phase could disrupt well-being.


Adapting any fasting approach should take account of your hormonal fluctuations if you have no cycle then using the lunar cycle may be useful. As always the key is to listen to your body and adjust as needed. Some studies have found a potential link between the lunar phases and menstrual cycles, suggesting that more women menstruate during the new moon or full moon. However, these studies often have small sample sizes and varying methodologies. You can find out your moon birth sign through lunarium or online calculator app.


Positive Outcomes for Women:

When aligned with hormonal cycles, intermittent fasting can help some women improve overall well-being through shedding old habits and metabolic flexibility leading to enhanced energy levels and focus.

Certainly, around the menopause research is scanty. The exact mechanisms here are still unclear, but some research has observed that women had a more severe response to calorie restriction or fasting due to negative impacts on several hormones, including gonadotropin releasing hormone and luteinising hormone, both of which are required to be in balance for proper reproductive function 12.


Dr. Mindy Pelz emphasizes the importance of tailoring fasting methods to women at various life stages and the significance of focusing on specific aspects of the hormonal hierarchy, as well as the timing and duration of fasts according to the female cycle, as detailed in her informative books 'The Menopause Reset' and 'Fast Like a Girl'.

She further explains the concept that calories are not the main concern, but rather the impact of hormones such as thyroid hormones, cortisol, insulin, leptin, growth hormone, and Oestrogen.



Functional integrative practitioners, including Dr. Mindy, Mark Hyman, and Dr. Gemma Newman (The Plant Doctor), emphasize the significance of evaluating biomarkers such as gut integrity, acid-base balance, hormonal status, dietary intolerances, and allergies as part of a comprehensive nutritional health screening. Additionally, it is crucial to consider holistic lifestyle factors like stress, sleep, exercise, menarche, and perimenopausal status.


In conclusion

While it’s impossible to account for every variable and scenario, practitioners should use sensitivity and care when making any recommendations around appropriate methods of fasting, with evidence-based considerations that respect bio-individuality cultural nuance, as well as training protocols. So, it's important to appreciate some methods of fasting for certain groups, such people with a history of eating disorders, diagnosed metabolic disorders, pregnant women, as well as female athletes should be a no go!  IF you are looking for support around fasting to support metabolic health longevity and healthspan you can connect here.



ProLon – Fasting Mimicking Diet – 5 Day Fast with Food - Total Body reset with cellular rejuvenation through autophagy

 

This article is intended for educational purposes and does not substitute professional medical advice. Always consult a medical healthcare provider for guidance on medical conditions.

 


References

1.       Wei M, Brandhorst S, Shelehchi M, Mirzaei H, Cheng CW, Budniak J, Groshen S, Mack WJ, Guen E, Di Biase S, Cohen P, Morgan TE, Dorff T, Hong K, Michalsen A, Laviano A, Longo VD. Fasting-mimicking diet and markers/risk factors for aging, diabetes, cancer, and cardiovascular disease. Sci Transl Med. 2017 Feb 15;9(377):eaai 8700. doi: 10.1126/scitranslmed.aai 8700. PMID: 28202779; PMCID: PMC6816332.

2.       Cheng CW, Adams GB, Perin L, Wei M, Zhou X, Lam BS, Da Sacco S, Mirisola M, Quinn DI, Dorff TB, Kopchick JJ, Longo VD. Prolonged fasting reduces IGF-1/PKA to promote hematopoietic-stem-cell-based regeneration and reverse immunosuppression. Cell Stem Cell. 2014 Jun 5;14(6):810-23. doi: 10.1016/j.stem.2014.04.014. Erratum in: Cell Stem Cell. 2016 Feb 4;18(2):291-2. PMID: 24905167; PMCID: PMC4102383.

3.       Brandhorst S, Levine ME, Wei M, Shelehchi M, Morgan TE, Nayak KS, Dorff T, Hong K, Crimmins EM, Cohen P, Longo VD. Fasting-mimicking diet causes hepatic and blood markers changes indicating reduced biological age and disease risk. Nat Commun. 2024 Feb 20;15(1):1309. doi: 10.1038/s41467-024-45260-9. PMID: 38378685; PMCID: PMC10879164.

4.       Wei M, Brandhorst S, Shelehchi M, Mirzaei H, Cheng CW, Budniak J, Groshen S, Mack WJ, Guen E, Di Biase S, Cohen P, Morgan TE, Dorff T, Hong K, Michalsen A, Laviano A, Longo VD. Fasting-mimicking diet and markers/risk factors for aging, diabetes, cancer, and cardiovascular disease. Sci Transl Med. 2017 Feb 15;9(377):eaai 8700. doi: 10.1126/scitranslmed.aai 8700. PMID: 28202779; PMCID: PMC6816332.

5.       Rangan P, Choi I, Wei M, Navarrete G, Guen E, Brandhorst S, Enyati N, Pasia G, Maesincee D, Ocon V, Abdulridha M, Longo VD. Fasting-Mimicking Diet Modulates Microbiota and Promotes Intestinal Regeneration to Reduce Inflammatory Bowel Disease Pathology. Cell Rep. 2019 Mar 5;26(10):2704-2719.e6. doi: 10.1016/j.celrep.2019.02.019. PMID: 30840892; PMCID: PMC6528490.

7.       Brandhorst S, Choi IY, Wei M, Cheng CW, Sedrakyan S, Navarrete G, Dubeau L, Yap LP, Park R, Vinciguerra M, Di Biase S, Mirzaei H, Mirisola MG, Childress P, Ji L, Groshen S, Penna F, Odetti P, Perin L, Conti PS, Ikeno Y, Kennedy BK, Cohen P, Morgan TE, Dorff TB, Longo VD. A Periodic Diet that Mimics Fasting Promotes Multi-System Regeneration, Enhanced Cognitive Performance, and Healthspan. Cell Metab. 2015 Jul 7;22(1):86-99. doi: 10.1016/j.cmet.2015.05.012. Epub 2015 Jun 18. PMID: 26094889; PMCID: PMC4509734.

8.       Wei M, Brandhorst S, Shelehchi M, Mirzaei H, Cheng CW, Budniak J, Groshen S, Mack WJ, Guen E, Di BiaseS, Cohen P, Morgan TE, Dorff T, Hong K, MichalsenA, LavianoA, Longo VD. Fasting-mimicking diet and markers/risk factors for aging, diabetes, cancer, and cardiovascular disease. Sci TranslMed. 2017;9(377). doi: 10.1126/scitranslmed.aai8700. PubMed PMID: 28202779.

9.       Cheng CW, Adams GB, Perin L, Wei M, Zhou X, Lam BS, Da Sacco S, Mirisola M, Quinn DI, Dorff TB, Kopchick JJ, Longo VD. Prolonged fasting reduces IGF-1/PKA to promote hematopoietic-stem-cell-based regeneration and reverse immunosuppression. Cell Stem Cell. 2014 Jun 5;14(6):810-23. doi: 10.1016/j.stem.2014.04.014. Erratum in: Cell Stem Cell. 2016 Feb 4;18(2):291-2. PMID: 24905167; PMCID: PMC4102383.

10.   Danna Wang, Jin Ye, Renjie Shi, Beita Zhao, Zhigang Liu, Wei Lin, Xuebo Liu, Dietary protein and amino acid restriction: Roles in metabolic health and aging-related diseases, Free Radical Biology and Medicine, Volume 178, 2022, Pages 226-242, ISSN 0891-5849, https://doi.org/10.1016/j.freeradbiomed.2021.12.009.

11.   Marques P, Skorupskaite K, Rozario KS, Anderson RA, George JT. Physiology of GnRH and Gonadotropin Secretion. 2022 Jan 5. In: Feingold KR, Anawalt B, Blackman MR, Boyce A, Chrousos G, Corpas E, de Herder WW, Dhatariya K, Dungan K, Hofland J, Kalra S, Kaltsas G, Kapoor N, Koch C, Kopp P, Korbonits M, Kovacs CS, Kuohung W, Laferrère B, Levy M, McGee EA, McLachlan R, New M, Purnell J, Sahay R, Shah AS, Singer F, Sperling MA, Stratakis CA, Trence DL, Wilson DP, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000–. PMID: 25905297.

12.   Varady, K.A., Lin, S., Oddo, V.M. et al. Debunking the myths of intermittent fasting. Nat Rev Endocrinol 20, 503–504 (2024). https://doi.org/10.1038/s41574-024-01009-4


ABOUT THE AUTHOR

DONALD GORDON BSc (Hons)NS, FHT is a degree qualified nutrition practitioner from the Centre of Nutrition and Lifestyle Management (CNELM). He has extensive knowledge in a wide range of holistic disciplines fasting and wellness longevity, and is a published author and researcher Connect with Don through Instagram @functionalnutritiondon and dongordon.co.uk

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