Every one has a doctor in him; we just have to help him in his work. The natural healing force within each one of us is the greatest force in getting well. To eat when you are sick, is to feed your sickness. – Hippocrates
With the rise in the incidence of themetabolic syndrome and its complications, autoimmune conditions, and cancer we are facing a health crisis of epic proportions globally.
The environment and our diets have changed markedly over the last two centuries, and it has been suggested that the increase in these conditions reflects the inability of our bodies to adjust to these changes. This concept is known as “evolutionary mismatch”. (1)
The purpose of this article is to introduce a potential solution for this mismatch: fasting.
There are three essentials forms of fasting:
- Dietary restriction (the type of macro- and micronutrients consumed)
- Caloric restriction (how much is consumed)
- Time restricted eating (when food is consumed)
The “standard Australian diet” mindset for many of our patients is rather maladaptive – consume as much as you want (no caloric restriction), of anything you want (no dietary restriction), whenever you want (no time restriction).
To make sense of what has led to the current situation, we need to appreciate our evolutionary journey as human beings.
The concept of agriculture was only born about 10,000 years ago – prior to that, human existence was largely based on a diet rich in protein and animal fat with some access to plants (tubers, edible leaves) and seasonal fruits. These palaeolithic/neolithic hunter-gatherer societies did not consume frequent meals and the concept of “feast and famine” in settings of sparse food source distribution truly applied. (2)
In this plentiful age, we battle with excess energy consumption, wherein highly processed carbohydrate-based foods consumed frequently lead to hyperinsulinemia and insulin resistance. Ultimately, “excess energy” is locked away as fat and our ability to access or burn this stored energy is strictly limited.
Insulin, at its core, is a storage hormone – it signals to the body to “switch off” lipolysis and “switch on” lipogenesis.
Refined carbohydrates tend to be nutrient poor which can cause the body to “call for more food” frequently during the day in an attempt to reach its requirements for essential nutrients (protein, essential fatty acids, vitamins and minerals). The levels of circulating insulin are very different between the modern man and his ancestors – thus the concept of evolutionary mismatch. We are currently facing the challenges of “a space-age diet but a stone-age body”. (3)
The human body is a “hybrid vehicle” – it can run on two forms of fuel: fat and glucose. (4)
The average non-obese human stores about 15,000g of fat yet only consumes about 40g (0.2% of body storage capacity) daily in a standard Western diet. Alternatively, the body can only store about 450g of glycogen (stored glucose) at any given point yet current diets contain about 250-450g (up to 100% of body storage capacity) of carbohydrates daily. This excessive carbohydrate load stimulates an excessive insulin response and creates an almost constant physiological environment of fat-storage.
In addition, we no longer have the activity levels that we used to have from an evolutionary perspective, or even prior to the industrial revolution. Herein lies, the modern-day energy crisis.
Fasting may provide a solution to this crisis, by helping us tap into stored energy. (5)
During periods of fasting, triglycerides are broken down in to fatty acids and glycerol which are used for energy. The liver converts fatty acids into ketone bodies, which provide a source of energy for the body.
In the past, it was believed that we require at least 130g of carbohydrate daily to supply adequate glucose for bodily functions, especially in terms of providing energy to the brain.
However, this is not physiologically accurate, given that ketone bodies can efficiently supply the brain, muscle and almost all the tissues of the body with adequate energy.
In a highly fed state, in particular with carbohydrate-rich meals, circulating ketone levels are always negligible or undetectable (0.0-0.1mmol/L) meaning that no fat is being burnt. In a fasted state, ketone levels begin to rise as our glycogen supply is exhausted.
In humans, they rise within 8 to 12 hours after the onset of fasting. With glycogen-depleting, high-intensity exercises such as sprinting – the ketone levels can rise much more quickly.
Ketone bodies are not just an energy source, they perform a wide range of functions in the body. Ketones are signalling molecules, they regulate the expression of proteins involved in ageing and health, and they act positively on brain-derived neurotrophic factor (with promising effects shown in neurodegenerative conditions). (6)
Greater periods of fasting with subsequent ketogenesis have been linked to several beneficial immediate effects including increased mitochondrial stress resistance, antioxidant defences, DNA repair and autophagy and decreased insulin.
When a glucose-based metabolic framework is switched to become ketone-based, longer term adaptations also occur, including increased insulin sensitivity, increased heart rate variability, improved lipid metabolism, favourable gut microbiota, reduced abdominal fat, reduced inflammation and blood pressure. All of these contribute to immune, metabolic and cardiovascular resilience and may reduce the likelihood or defer the onset of clinical disease. (7)
Elevated ketones, low circulating insulin and stable blood glucose levels are common characteristics of normal human physiology enabled by intermittent fasting and real-food diets.
In modern society, the idea that we need three to five meals a day is deeply embedded in society’s culture and most of us believe that “breakfast is the most important meal of the day” with highly processed grains and cereals forming the base of many children’s diets.
But where is the evidence for this? Powerful marketing forces support the idea that “the human body must be nourished frequently” to achieve a state of optimal health. From a practical standpoint, this is often a difficult conversation to have with a patient to challenge the ingrained perception that frequent meals are important.
Firstly, it helps to establish mutual acknowledgement that diet is adversely impacting the patient’s life through the manifestation of metabolic syndrome be it obesity, hypertension, dyslipidaemia or type 2 diabetes for example.
It can then be useful to present the concept of “evolutionary mismatch” and how the rise of agriculture with the industrial revolution changed the pattern of how the modern human eats.
To introduce the concept of fasting consider using statements such as:
- The medicine-centric model assumes that disease in humans is simply due to “bad luck” rather than an unfavourable environment. The model which heals with environmental modification (diet, exercise, and recognition of impulse behaviours) is a powerful and economically more viable option as we hurtle into the new era of healthcare.
- The human brain is a hybrid engine capable of running on a glucose supply and ketones (breakdown product of fat). The modern diet is almost devoid of the fat we need to produce ketones, we are less active thus we do not tap into our fat stores and regular carbohydrate-rich meals without fasting means fat cannot be liberated from storage.
- Low-calorie, low-fat diets to combat obesity and metabolic syndrome have been largely unsuccessful – large bodies of literature show that these diets are difficult to maintain. The “calories in” need to be less than the “calories out” model fails to understand that this is largely a hormonal disease from hypersecretion of insulin. (8)
- Encouraging the consumption of nutrient-dense whole foods – If the human body’s energy was a fire, “logs of wood” are analogous to protein and dietary fat – they burn for a long time satiety). Carbohydrates on the other hand is like “kindling”, burns quickly and needs constant replenishing (snacking). Therefore, long periods of fasting to liberate stored fat and then nourishing the body with nutrient-dense meals is a sustainable method of eating.
- The advice to load or refuel with carbohydrates to those trying to lose weight for health reasons is based on debatable science. To allow for maximal fat store utilisation it is best to keep the hormone insulin dormant by not eating at all post-workout. In this way, the cycle of fat burning continues. Therefore, a lot of low carbohydrate diets are termed “fast mimicking” diets – because dietary fats and protein do not spike the insulin as much as carbohydrates do. (9)
- Switching to an intermittent fasting regimen, many people will experience hunger, irritability, and a reduced ability to concentrate during periods of food restriction. However, these initial side effects usually disappear within one month, and patients should be advised of this fact. (10, 11)
There are several methods of fasting.
- Time restricted eating – the goal is to achieve a calorie free fast of 16 to 18 hours per day in a 24-hour window
- Other types of fasting – often known as “5:2 fasts” – the goal is achieved through two low calorie (500 calories) fasts of 24 hours out of seven days. This could be further extended to select one to two days of 24 to 48 hours of a calorie-free fast during the week
It is important to develop a framework for prescribing the fasting regimen which is suitable to the individual patient.
This involves sufficient education, including the basic scientific rationale, benefits, and having a multidisciplinary approach to implementation, including the engagement of dieticians, nurses, and relevant health care providers.
Ongoing engagement and follow up as well as monitoring of key objective markers such as weight, waist: height ratio, blood pressure, blood sugar and relevant serum metabolic panel markers is important to provide feedback to patients and their health care providers.
Fasting can be a simple, cost-effective and effective means to help with a range of disease states. The effect of fasting appears to be independent of weight/adipocyte loss itself. An understanding of the basic science is essential when engaging with patients and having a framework to incorporate fasting patterns into lifestyle is crucial.
Further study is needed into the optimal type of fast for individual disease states and patient types. In addition, improved ways to monitor outcomes are still in development.
WHAT TO EAT WHILE FASTING
It may seem like a paradoxical concept, but what to eat while fasting is extremely important for not only for the success of the fast (i.e., one’s ability to go for a period of time without eating) but for optimising health and wellbeing long-term.
Healthcare professionals recommending fasting should emphasise the importance of prioritising nutrient-dense whole foods at meal times.
Humans have certain requirements for essential proteins, fatty acids, vitamins and minerals. (12)
If we don’t consume enough of these nutrients, over time we risk deficiencies which can be associated with serious health conditions.For example, low magnesium levels are associated with insulin resistance and type 2 diabetes (13), likely due to the essential role that magnesium plays in the efficient signalling of insulin (14).
It is recommended that patients wishing to undertake intermittent fasting speak to a dietitian or nutritionist for advice about their individual requirements for macro- and micronutrients.
In brief, prioritising nutrient-dense foods such as meat, fish, eggs, dairy, nuts, seeds and vegetables is an effective adjunctive strategy to intermittent fasting.
- Richards, M. A brief review of the archaeological evidence for Palaeolithic and Neolithic subsistence. Eur J Clin Nutr 56, 1270–1278 (2002). https://doi.org/10.1038/sj.ejcn.1601646
- Cordain L, Eaton SB, Sebastian A, Mann N, Lindeberg S, Watkins BA, O’Keefe JH, Brand-Miller J. Origins and evolution of the Western diet: health implications for the 21st century. Am J Clin Nutr 2005;81:341–54
- Masharani, U., Sherchan, P., Schloetter, M. et al. Metabolic and physiologic effects from consuming a hunter-gatherer (Paleolithic)-type diet in type 2 diabetes. Eur J Clin Nutr 69, 944–948 (2015). https://doi.org/10.1038/ejcn.2015.39
- Randle PJ, Garland PB, Hales CN & Newsholme EA The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet 1, 785–789 (1963).
- Early Time-Restricted Feeding Improves 24-Hour Glucose Levels and Affects Markers of the Circadian Clock, Aging, and Autophagy in Humans Humaira Jamshed, Robbie A. Beyl, Deborah L. Della Manna, Eddy S. Yang, Eric Ravussin, Courtney M. Peterson Nutrients. 2019 Jun; 11(6): 1234. Published online 2019 May 30. doi: 10.3390/nu11061234
- Arnold SE, Arvanitakis Z, Macauley-Rambach SL, et al. Brain insulin resistance in type 2 diabetes and Alzheimer disease: concepts and conundrums. Nat Rev Neurol 2018; 14: 168-81.
- Effects of Intermittent Fasting on Health, Aging, and Disease. Rafael de Cabo, Ph.D., and Mark P. Mattson, Ph.D.. n engl j med 381;26 nejm.org December 26, 2019
- Zatterale F, Longo M, Naderi J, et al. Chronic Adipose Tissue Inflammation Linking Obesity to Insulin Resistance and Type 2 Diabetes. Front Physiol. 2020;10:1607. Published 2020 Jan 29. doi:10.3389/fphys.2019.01607
- Velingkaar N, Mezhnina V, Poe A, Makwana K, Tulsian R, Kondratov RV. Reduced caloric intake and periodic fasting independently contribute to metabolic effects of caloric restriction. Aging Cell. 2020;19(4):e13138. doi:10.1111/acel.1313
- Harvie MN, Pegington M, Mattson MP, et al. The effects of intermittent or continuous energy restriction on weight loss and metabolic disease risk markers: a randomized trial in young overweight women. Int J Obes (Lond) 2011; 35: 714-27.
- Harvie M, Wright C, Pegington M, et al. The effect of intermittent energy and carbohydrate restriction v. daily energy restriction on weight loss and metabolic disease risk markers in overweight women. Br J Nutr 2013; 110: 1534-47.