<\/p>\n
Research on the benefits of fasting in humans, in the form of clinical intervention studies, is still early in development.\u00a0Animal studies<\/a><\/span>, however, have consistently demonstrated that caloric restriction and fasting increases lifespan. The main mechanism for this is a reduction of nutrient-sensing pathways. In other words, eating much less or going for long periods without food could make us live longer. It appears that dietary restriction improves longevity by improving mitochondrial function, increasing autophagy, and reducing inflammation. Autophagy is the process by which your body cleans out debris and recycles damaged cell components.<\/span><\/p>\n <\/p>\n The ketogenic diet mimics a fasting state, without the need for caloric restriction. We have seen that cutting out carbohydrates significantly reduces glucose levels, and, therefore, insulin levels. Insulin is sensitive to carbohydrates, or a carb-protein combination.<\/span><\/p>\n However, insulin is not the only nutrient sensor. There are others, like mTOR (mechanistic Target of Rapamycin) and AMPK (5′ Adenosine Monophosphate-activated Protein Kinase). These, together with insulin, are the three main nutrient sensors in the human body. A ketogenic diet may have little impact on insulin, but it will still activate mTOR and AMPK.<\/span><\/p>\n <\/p>\n mTOR controls cell growth, repair, and metabolism in response to nutrients, growth factors and cellular energy. It is mostly sensitive to protein. We know that virtually all cancers are associated with mTOR activation and that when mTOR is\u00a0suppressed, growth is inhibited and maintenance and repair are stimulated. This is clearly favourable in the cancer setting, because we want to prioritise maintenance and repair of cells, over growth.<\/span><\/p>\n The fact that amino acids (from protein) are the most potent stimulators of mTOR raises a problem. Just as reducing glucose intake reduces stimulation of insulin, should we be restricting protein intake to reduce mTOR stimulation?<\/span><\/p>\n There are no essential sugars. This means that there is no absolute requirement to consume carbohydrates. However, there are 9 \u2018essential\u2019 amino acids that cannot be made by the body. This means that they must come from food. Furthermore, there are \u2018conditional\u2019 amino acids that are usually not essential, except in times of illness and stress.<\/span><\/p>\n <\/p>\n Protein is incredibly important. Twenty percent of the human body is made up of protein. A large proportion of our cells, muscles, and tissue is made up of amino acids, which have a multitude of roles, including giving cells their structure. They play a key role in the transport and the storage of nutrients. They are essential for healing wounds and repairing tissue, especially in the muscles, bones, skin, and hair, as well as for the removal of all kinds of waste produced during metabolism.<\/span><\/p>\n It is well known that if an individual restricts protein, they develop low bone density (osteoporosis), and low muscle mass (sarcopenia) leading to weakness, and an increased risk of falls and bone fractures.<\/span><\/p><\/blockquote>\n Current evidence indicates intakes in the range of at least 1.2 to 1.6g\/(kg\/day) of high-quality (animal-based) protein is a more ideal target for achieving optimal health outcomes in adults. This is in sharp contrast to 0.8 grams\/kg\/day – which is typical of \u2018official\u2019 guidelines for protein intake. 0.8g\/kg was determined to be the amount of protein that would keep most people in nitrogen balance, i.e., rebuilding as much tissue as they were breaking down.\u00a0\u00a0While this might be OK in healthy people, it is not nearly sufficient if one is trying to build muscle, or if they are recovering from major surgery\/trauma, and they need to rebuild skin, bones, and connective tissue.<\/span><\/p>\n <\/p>\n Animal Based Protein is Remarkably Bioavailable INSULEAN<\/p><\/div>\n <\/p>\n In addition, very few of these nitrogen-balance studies were performed in older individuals, further supporting the notion that 0.8g\/kg\/day is a wholly inappropriate figure for establishing recommendations. The totality of the available evidence suggests that despite persistent beliefs to the contrary, there is no evidence-based link between higher protein diets and kidney disease or adverse bone health. In fact, insufficient dietary protein intakes may be a more severe problem than protein excess in the elderly<\/span><\/a>.\u201d <\/span><\/p>\n There is no evidence-based link between higher protein diets and kidney disease or adverse bone health.<\/span><\/p><\/blockquote>\n It is reasonable to assume that we need to keep amino acids, and growth factors like IGF-1 (which are stimulated by protein) low, so as to suppress mTOR. However, mTOR and IGF-1 are not necessarily \u2018bad\u2019. Neither is insulin. We need these important hormones for thousands of normal biological processes. However, like insulin, we do not need to have persistently raised levels of these nutrient signalling molecules. What we need to do is keep them pulsatile. We do this not by keeping dietary protein intake as low as possible, but by including regular time-restricted eating (intermittent fasting) and block fasting (fasting for a day or more) into our dietary patterns.<\/span><\/p>\n <\/p>\n AMPK is activated in response to a shortage of energy (ATP) from carbohydrates, protein, and fat. When ATP is low, AMPK goes up. AMPK stimulates the creation of new mitochondria and regulates their metabolic function.\u00a0AMPK signalling is interesting because it is a known target for treating the metabolic syndrome and type-2 diabetes. Metformin, a widely used anti-diabetic drug stimulates AMPK.<\/span><\/p>\n Recently AMPK is emerging<\/a> <\/span>as a target for cancer prevention and treatment. AMPK activity opposes tumour development and progression in part by regulating inflammation and metabolism. This explains the recent resurgence of interest in Metformin as a potential anti-cancer therapy.<\/span><\/p>\n <\/p>\n Ketogenic diets lower insulin, but will still activate mTOR and AMPK. In animal studies, fasting lowers insulin, IGF-1, and MTOR, while increasing AMPK. These are the most important nutrient sensors in humans, but there are many more nutrient sensors, and likely more yet to be discovered. We can wait until all these discoveries and human studies are complete, or we could start advising people to fast regularly.<\/span><\/p>\n Fasting is an ideal intervention to influence nutrient-sensing pathways, which, as we have discussed, can optimise mitochondrial health. Fasting is far from a new idea. Cultures all over the world have adopted fasting for reasons relating to \u2018purification\u2019 of the body and mind. This has been an established practice for thousands of years. We also know that our early ancestors must have cycled between periods of fasting – during food scarcity, and periods of feasting. The human body is exquisitely well adapted to storing energy in form of glycogen (glucose chains) and fat. These adaptations enabled us to survive and thrive irrespective of the prevailing environment.<\/span><\/p>\n \u00a0\u201cThe best of all medicines is resting and fasting” Benjamin Franklin<\/span><\/p><\/blockquote>\n Fasting (not eating) can target and eliminate cancer cells through multiple mechanisms. This dietary intervention is anti-angiogenic (prevents growth of new blood vessels), anti-inflammatory, and pro-apoptotic (encourages cell death). Fasting also stimulates mitophagy<\/span><\/a>, the process of destroying old, dysfunctional mitochondria.\u00a0In addition, by increasing AMPK, and suppressing mTOR, fasting stimulates the growth of new mitochondria, keeping them in a \u2018youthful\u2019 state.<\/span><\/p>\n Jason Fung, MD, is the preeminent authority on fasting. His book, \u2018The Complete Guide to Fasting\u2019\u2019<\/a><\/span>, is packed with useful information and practical tips to help you incorporate regular fasting into your lifestyle. It is well worth a read.<\/span><\/p>\nNutrient Sensors<\/strong><\/span><\/h3>\n
mTOR<\/strong><\/span><\/h4>\n
mTOR and Protein<\/strong><\/span><\/h4>\n
![\"mTOR](\"http:\/\/insulean.co.uk\/wp-content\/uploads\/2019\/02\/Protein.jpg\")
AMPK<\/strong><\/span><\/h4>\n
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Starving Cancer – Fasting<\/strong><\/span><\/h3>\n