Understanding the ProLon® Fasting Mimicking Diet
Fasting is associated with numerous health benefits; from weight loss to longevity. There are many different types of fasting methods, such as intermittent fasting. The fasting mimicking diet allows you to experience the benefits of traditional fasting without depriving your body of food. The main difference of the FMD is that instead of completely eliminating all food for several days or even weeks, you only restrict your calorie intake for five days out of the month.
While anyone can follow the FMD on their own, the ProLon® fasting mimicking diet offers a 5-day meal program which has been individually packed and labeled for each day and it serves the foods you need for the FMD in precise quantities and combinations. The meal program is made up of ready-to-eat or easy-to-prepare, plant-based foods, including bars, soups, snacks, supplements, a drink concentrate, and teas. The products are scientifically formulated and great tasting. Before starting the ProLon® fasting mimicking diet, 5-day meal program, please make sure to talk to a healthcare professional to find out if the FMD is right for you. The purpose of the research study below is to demonstrate the molecular mechanisms and clinical applications of fasting in the FMD.
Fasting: Molecular Mechanisms and Clinical Applications
Fasting has been practiced for millennia, but only
In humans, fasting is achieved by ingesting no or minimal amounts of food and caloric beverages for periods that typically range from 12 hours to three weeks. Many religious groups incorporate periods of fasting into their rituals including Muslims who fast from dawn until dusk during the month of Ramadan, and Christians, Jews, Buddhists and Hindus who traditionally fast on designated days of the week or calendar year. In many clinics, patients are now monitored by physicians while undergoing water only or very low calorie (less than 200 kcal/day) fasting periods lasting from 1 week or longer for weight management, and for disease prevention and treatment. Fasting is distinct from caloric restriction (CR) in which the daily caloric intake is reduced chronically by 20–40%, but meal frequency is maintained. Starvation is instead a chronic nutritional insufficiency that is commonly used as a substitute for the word fasting, particularly in lower eukaryotes, but that is also used to define extreme forms of fasting, which can result in degeneration and death. We now know that fasting results in ketogenesis, promotes potent changes in metabolic pathways and cellular processes such as stress resistance, lipolysis and autophagy, and can have medical applications that in some cases are as effective as those of approved drugs such as the dampening of seizures and seizure-associated brain damage and the amelioration of rheumatoid arthritis (Bruce-Keller et al., 1999; Hartman et al., 2012; Muller et al., 2001). As detailed in the remainder of this article, findings from well-controlled investigations in experimental animals, and emerging findings from human
Lessons from Simple O
The remarkable effects of the typical 20–40% CR on aging and diseases in mice and rats are often viewed as responses evolved in mammals to adapt to periods of limited availability of food (Fontana and Klein, 2007; Fontana et al., 2010; Masoro, 2005; Weindruch and Walford, 1988). However, the cellular and molecular mechanisms responsible for the protective effects of CR have likely evolved billions of years earlier in prokaryotes attempting to survive in an environment largely or completely devoid of energy sources while avoiding age-dependent damage that could compromise fitness. In fact, E. coli switched from a
In the yeast S. cerevisiae, switching cells from standard growth medium to water also causes a consistent 2-fold chronological lifespan extension as well as a major increase in the resistance to multiple stresses (Figure 1B) (Longo et al., 1997; Longo et al., 2012). The mechanisms of food deprivation-dependent lifespan extension involve the down-regulation of the amino acid response Tor-S6K (Sch9) pathway as well as of the
Another major model organism in which fasting extends lifespan is the nematode C.
In flies, most studies indicate that intermittent food deprivation does not affect lifespan (Grandison et al., 2009). However, food reduction or food dilution have been consistently shown to extend Drosophila longevity (Piper and Partridge, 2007) suggesting that flies can benefit from dietary restriction but may be sensitive to even short starvation periods.
Together these results indicate that food deprivation can result in pro-longevity effects in a wide variety of organisms, but also underline that different organisms have different responses to fasting.
Adaptive Responses to Fasting in M
In most mammals, the liver serves as the main reservoir of glucose, which is stored in the form of glycogen. In humans, depending upon their level of physical activity, 12 to 24 hours of fasting typically results in a 20% or greater decrease in serum glucose and depletion of the hepatic glycogen, accompanied by a switch to a metabolic
Fasting and the Brain
In mammals, severe CR/food deprivation results in a decrease in the size of most organs except the brain, and the testicles in male mice (Weindruch and Sohal, 1997). From an evolutionary
Particularly interesting with regards to adaptive responses of the brain to limited food availability during human evolution is
Hunger is an adaptive response to food deprivation that involves sensory, cognitive and neuroendocrine changes which motivate and enable food seeking behaviors. It has been proposed that hunger-related neuronal networks, neuropeptides
Fasting, Aging, and Disease in Rodent M
Different Fasting Methods and Aging
The major differences between IF and PF in mice are the length and the frequency of the fast cycles. IF cycles usually last 24 hours and are one to a few days apart, whereas PF cycles last 2 or more days and are at least 1 week apart, which is necessary for mice to regain their normal weight. One difference in the molecular changes caused by different fasting regimes is the effect on a variety of growth factors and metabolic markers, with IF causing more frequent but less pronounced changes than PF. It will be important to determine how the frequency of specific changes such as the lowering of IGF-1 and glucose affect cellular protection, diseases
Fasting and C
Fasting can have positive effects
In the treatment of cancer, fasting has been shown to have more consistent and positive effects. PF for 2–3 days was shown to protect mice from a variety of chemotherapy drugs, an effect called differential stress resistance (DSR) to reflect the inability of cancer cells to become protected based on the role of oncogenes in negatively regulating stress resistance, thus rendering cancer cells, by definition, unable to become protected in response to fasting conditions (Figure 5) (Raffaghello et al., 2008). PF also causes a major sensitization of various cancer cells to chemo-treatment, since it fosters an extreme environment in combination with the stress conditions caused by chemotherapy. In contrast to the protected state entered by normal cells during fasting, cancer cells are unable to adapt, a phenomenon called differential stress sensitization (DSS), based on the notion that most mutations are deleterious and that the many mutations accumulated in cancer cells promote growth under standard conditions but render them much less effective in adapting to extreme environments (Lee et al., 2012). In mouse models of metastatic tumors, combinations of fasting and chemotherapy that cause DSR and DSS, result in 20 to 60% cancer-free survival compared to the same levels of chemotherapy or fasting alone, which are not sufficient to cause any cancer-free survival (Lee et al., 2012; Shi et al., 2012). Thus, the idea that cancer could be treated with weeks of fasting alone, made popular decades ago,
Fasting and N
Compared to ad libitum-fed controls, rats and mice maintained on an IF diet exhibit less neuronal dysfunction and degeneration, and fewer clinical symptoms in models of Alzheimer’s disease (AD), Parkinson’s disease (PD) and Huntington’s disease (HD). These models include transgenic mice expressing mutant human genes that cause dominantly inherited AD (amyloid precursor protein and presenilin-1) and frontotemporal lobe dementia (Tau) (Halagappa et al., 2007), PD (α-synuclein) (Griffioen et al., 2012) and HD (huntingtin) (Duan et al., 2003), as well as neurotoxin-based models pertinent to AD, PD and HD (Bruce-Keller et al., 1999; Duan and Mattson, 1999). Animals on an IF diet also fare better than ad libitum-fed controls after acute injury including severe epileptic seizures, stroke, and traumatic brain and spinal cord injuries (Arumugam et al., 2010; Bruce-Keller et al., 1999; Plunet et al., 2008).
Several interrelated cellular mechanisms contribute to the beneficial effects of IF on the nervous system including reduced accumulation of oxidatively damaged molecules, improved cellular bioenergetics, enhanced neurotrophic factor signaling, and reduced inflammation (Mattson, 2012a). The latter neuroprotective mechanisms are supported by studies showing that IF diets boost levels of antioxidant defenses, neurotrophic factors (BDNF and FGF2) and protein chaperones (HSP-70 and GRP-78), and reduce levels of
Fasting and the Metabolic S
Metabolic syndrome (MS), defined as abdominal adiposity, combined with insulin resistance, elevated triglycerides and/or hypertension, greatly increases the risk of cardiovascular disease, diabetes, stroke
Multiple hormonal changes that typify MS in humans a
The ProLon® fasting mimicking diet is a 5-day meal program consisting of scientifically developed and clinically tested, natural ingredients which “trick” the human body into a fasting mode. The FMD is low in carbohydrates as well as proteins and it’s high in fats. The ProLon® fasting mimicking diet promotes a variety of healthy benefits, including weight loss and decreased abdominal fat, all while preserving lead body mass, improved energy levels, softer and healthier looking skin, as well as overall health and wellness.Dr. Alex Jimenez D.C., C.C.S.T. Insight
The FMDcan promote longevity.
Fasting, Aging, and Disease in H
Fasting and Factors Implicated in Aging
Clinical and epidemiological data are consistent
Among the major effects of fasting relevant to aging and diseases
IF can be achieved in with a minimal decrease in overall calorie intake if the refeeding period in which subjects overeat is considered. Thus, fasting cycles provide a much more feasible strategy to achieve the beneficial effects of CR, and possibly stronger effects, without the burden of chronic underfeeding and some of the potentially adverse effects associated with weight loss or very low BMIs. In fact, subjects who are moderately overweight (BMI of 25–30) in later life can have reduced overall mortality risk compared to subjects of normal weight (Flegal et al., 2013). Although these results may be affected by the presence of many existing or developing pathologies in the low weight control group, they underline the necessity to differentiate between young individuals and elderly individuals who may use CR or fasting to reduce weight or delay aging. Although extreme dietary interventions during old age may continue to protect from age-related diseases, they could have detrimental effects on the immune system and the ability to respond to certain infectious diseases, wounds and other challenges (Kristan, 2008; Reed et al., 1996). However, IF or PF designed to avoid weight loss and maximize nourishment have the potential to have beneficial effects on infectious diseases, wounds
Fasting and C
Fasting has the potential for applications in both cancer prevention and treatment. Although no human data are available on the effect of IF or PF in cancer prevention, their effect on reducing IGF-1, insulin and glucose levels, and increasing IGFBP1 and ketone body levels could generate a protective environment that reduces DNA damage and carcinogenesis, while at the same time creating hostile conditions for tumor and pre-cancerous cells (Figure 5). In fact, elevated circulating IGF-1 is associated with increased risk of developing certain cancers (Chan et al., 2000; Giovannucci et al., 2000) and individuals with severe IGF-1deficiency caused by growth hormone receptor deficiency, rarely develop cancer (Guevara-Aguirre et al., 2011; Shevah and Laron, 2007; Steuerman et al., 2011). Furthermore, the serum from these IGF-1deficient subjects protected human epithelial cells from oxidative stress-induced DNA damage. Furthermore, once their DNA became damaged, cells were more likely to undergo programmed cell death (Guevara-Aguirre et al., 2011). Thus, fasting may protect from cancer by reducing cellular and DNA damage but also by enhancing the death of pre-cancerous cells.
In a preliminary study of 10 subjects with a variety of malignancies, the combination of chemotherapy with fasting resulted in a decrease in a range of self-reported common side effects caused by chemotherapy compared to the same subjects receiving chemotherapy while on a standard diet (Safdie et al., 2009). The effect of fasting on chemotherapy toxicity and cancer progression is now being tested in clinical trials in both Europe and the US (0S-08-9, 0S-10-3).
Fasting and N
Our current understanding of the impact of IF on the nervous system and cognitive functions is largely inferred from animal studies (see above). Interventional studies to determine the impact of fasting on brain function and neurodegenerative disease processes are lacking.
After 3–4 month, CR improved cognitive function (verbal memory) in overweight women (Kretsch et al., 1997) and in elderly subjects (Witte et al., 2009). Similarly, when subjects with mild cognitive impairment were maintained for 1 month on a low glycemic diet, they exhibited improved delayed visual memory, cerebrospinal fluid biomarkers of Aβ metabolism and brain bioenergetics (Bayer-Carter et al., 2011). Studies in which cognitive function, regional brain volumes, neural network activity, and biochemical analyses of cerebrospinal fluid are measured in human subjects before and during an extended period of IF should clarify the impact of IF on human brain structure and function.
and H ypertension
In humans, one of the best demonstrations of the beneficial effects of long-term fasting lasting one to 3 weeks is in the treatment of rheumatoid arthritis (RA). In agreement with the results in rodents, there is little doubt that during the period of fasting both inflammation and pain are reduced in RA patients (Muller et al., 2001). However, after the normal diet is resumed, inflammation returns unless the fasting period is followed by a vegetarian diet (Kjeldsen-Kragh et al., 1991), a combination therapy that has beneficial effects lasting for two years or longer (Kjeldsen-Kragh et al., 1994). The validity of this approach is supported by four differently controlled studies, including two randomized trials (Muller et al., 2001). Therefore, fasting combined with a vegetarian diet and possibly with other modified diets provides beneficial effects in the treatment of RA. Alternate day IF also resulted in significant reductions in serum TNFα and ceramides in asthma patients during a 2 month period (Johnson et al., 2007). The latter study further showed that markers of oxidative stress often associated with inflammation (protein and lipid oxidation) were significantly reduced in response to IF. Thus, for many patients able and willing to endure long-term fasting and to permanently modify their diet, fasting cycles would have the potential to not only augment but also replace existing medical treatments.
Water only and other forms of long-term fasting have also been documented to have potent effects on hypertension. An average of 13 days of water only fasting resulted in the achievement of
For both hypertension and
Fasting and the Metabolic S
Periodic fasting can reverse multiple features of the metabolic syndrome in humans: it enhances insulin sensitivity, stimulates lipolysis and reduces blood pressure. Body fat and blood pressure were reduced and glucose metabolism improved in obese subjects in response to an alternate day modified fast (Klempel et al., 2013; Varady et al., 2009). Overweight subjects maintained for 6 months on a
Conclusions and Recommendations
Based on the existing evidence from animal and human studies described, we conclude that there is great potential for lifestyles that incorporate periodic fasting during adult life to promote optimal health and reduce the risk of many chronic diseases, particularly for those who are overweight and sedentary. Animal studies have documented robust and replicable effects of fasting on health indicators including greater insulin sensitivity, and reduced levels of blood pressure, body fat, IGF-I, insulin, glucose, atherogenic lipids and inflammation. Fasting regimens can ameliorate disease processes and improve functional outcome in animal models of disorders that include myocardial infarction, diabetes, stroke, AD and PD. One general mechanism of action of fasting is that it triggers adaptive cellular stress responses, which result in an enhanced ability to cope with more severe stress and counteract disease processes. In addition, by protecting cells from DNA damage, suppressing cell growth and enhancing apoptosis of damaged cells, fasting could retard and/ or prevent the formation and growth of cancers.
However, studies of fasting regimens have not been performed in children, the very old and underweight individuals, and it is possible that IF and PF would be harmful to these populations. Fasting periods lasting longer than 24 hours and particularly those lasting 3 or more days should be done under the supervision of a physician and preferably in a clinic. IF- and PF-based approaches towards combating the current epidemics of overweight, diabetes and related diseases should be pursued in human research studies and medical treatment plans. Several variations of potential ‘fasting prescriptions’ that have been adopted for overweight subjects revolve around the common theme of abstaining from food and caloric beverages for at least 12 – 24 hours on one or more days each week or month, depending on the length, combined with regular exercise. For those who are overweight, physicians could ask their patients to choose a fasting-based intervention that they believe they could comply with based upon their daily and weekly schedules. Examples include the ‘5:2’ IF diet (Harvie et al., 2011), the alternate day modified fasting diet (Johnson et al., 2007; Varady et al., 2009), a 4–5 day fast or low calorie but high nourishment fasting mimicking diets once every 1–3 months followed by the skipping of one major meal every day if needed (V. Longo, clinical trial in progress). One of the concerns with unbalanced alternating diets such as those in which low calorie intake is only observed for 2 days a week are the potential effects on circadian rhythm and the endocrine and gastrointestinal systems, which are known to be influenced by eating habits. During the first 4 – 6 weeks of implementation of the fasting regimen, a physician or registered dietitian should be in regular contact with the patient to monitor their progress and to provide advice and supervision.
Fasting regimens could also be tailored for specific diseases as stand-alone or adjunct therapies. Results of initial trials of IF (fasting 2 days per week or every other day) in human subjects suggest that there is a critical transition period of 3 – 6 weeks during which time the brain and body adapt to the new eating pattern and mood is enhanced (Harvie et al., 2011; Johnson et al., 2007). Though speculative, it is likely that during the latter transition period brain neurochemistry changes so that the ‘addiction’ to regular consumption of food throughout the day is overcome. Notably, the various fasting approaches are likely to have limited efficacy particularly on aging and conditions other than obesity unless combined with diets such as the moderate calorie intake and mostly plant-based Mediterranean or Okinawa low protein diets (0.8 g protein/Kg of body weight), consistently associated with health and longevity.
In the future, it will be important to combine epidemiological data, studies of long-lived populations and their diets, results from model organisms connecting specific dietary components to pro-aging and pro-disease factors, with data from studies on fasting regimens in humans, to design large clinical studies that integrate fasting with diets recognized as protective and enjoyable. A better understanding of the molecular mechanisms by which fasting affects various cell types and organ systems should lead to the development of novel prophylactic and therapeutic interventions for a wide range of disorders.
Take Home Message
The fasting mimicking diet provides the same benefits of traditional fasting by restricting your calorie intake for five days out of the month instead of completely eliminating all food for several days or even weeks. The ProLon® fasting mimicking diet offers a 5-day meal program which has been individually packed and labeled in precise quantities and combinations for each day. Although the research study above has demonstrated the health benefits of fasting, please make sure to talk to a healthcare professional before starting the ProLon® fasting mimicking diet, 5-day meal program to find out if the FMD, or any other diet, is right for you.
The published, final edited form of the research study referenced above was made available in the NIH Public Access Author Manuscript on PMC February 4, 2015. The scope of our information is limited to chiropractic, spinal health issues, and functional medicine topics. To further discuss the subject matter, please feel free to ask Dr. Alex Jimenez or contact us at 915-850-0900 .
Curated by Dr. Alex Jimenez
Referenced from: Nih.gov
Additional Topic Discussion: Acute Back Pain
Back pain is one of the most prevalent causes of disability and missed days at work worldwide. Back pain attributes to the second most common reason for doctor office visits, outnumbered only by upper-respiratory infections. Approximately 80 percent of the population will experience back pain at least once throughout their life. Your spine is a complex structure made up of bones, joints, ligaments, and muscles, among other soft tissues. Injuries and/or aggravated conditions, such as herniated discs, can eventually lead to symptoms of back pain. Sports injuries or automobile accident injuries are often the most frequent cause of back pain, however, sometimes the simplest of movements can have painful results. Fortunately, alternative treatment options, such as chiropractic care, can help ease back pain through the use of spinal adjustments and manual manipulations, ultimately improving pain relief.
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