Stethoscopes, statins, and stents were the tools of my first 25 years of practice. After completing training in cardiology and interventional practice at the University of Michigan, University of Texas Southwestern and the Mid-America Heart Institute (with the late but great Geoffrey Hartzler, MD), I had a personal practice of eating plant-based. I would teach nutrition to patients but never thought that an equally powerful tool could be to teach them not eat (or to eat a diet of reduced calories created to activate cellular regeneration). Indeed, fasting is a powerful tool for all cardiology practices and one I use in my office successfully. Fasting may surpass traditional cardiovascular therapeutics as path to preventive health for both cardiologists and their patients.
What is Fasting?
There’s a lot of misconception around what “fasting” actually means. The common definition of fasting is the abstinence from all or some kinds of food or drink, but the biological definition is actually the switch from burning glucose (sugar) for energy to burning fatty acids and ketones, typically induced by mild stress to the body. Scientific studies indicate that true biological fasting occurs about 48 hours after the last meal. This is important to note because many of the benefits of a fast require the body to reach a biological fasting state.
Fasting induces a protective response against future stressors and fasting for a few days in a row actually triggers the body to reduce inflammation and remove and replace damaged and dysfunctional cells. You may recognize this as the process of autophagy, centered in the lysosomes of cells, and the topic for the awarding of the Nobel Prize in Medicine in 2016. For example, mice live longer, healthier lives if their diets are restricted or if they are fasting. The incredible part is that this mechanism, which is to say this process, is conserved in humans too. Decades of research have been dedicated to this one mechanism: the nutrient sensing pathways. Regenerative pathways are similar in various animal models including humans.
What Happens During Fasting?
When we stop eating food, the body starts to utilize energy stores to fuel itself. The body can pull from three different kinds of materials to create energy:
• protein (muscle mass)
• carbohydrates (glycogen storage)
• lipid (fat mass)
All three of these materials provide energy for the body, but at different rates and through different pathways. The body only has a small amount of glycogen (essentially stored sugar) that it can pull from. Once this has been depleted, it moves right on over to protein and lipid. However, it is more efficient to use lipid (or fat mass) than protein because there is a lot more energy in fat mass than in muscle mass. So, for the most part, the body will begin to burn fat once all of the carbohydrate has been depleted. At this moment when the body is burning fat, we believe the body is truly in the fasting state; this is just around 48 hours after the last meal. The way we see the body burning fat is actually through the unique molecules called a ketone bodies. As fat burning increases, ketone bodies appear in the blood and urine and can be easily confirmed with test strips.” If the body is left in “ketosis”, a form of starvation, then the body will eventually become malnourished. The role of periodic fasting and ketosis is a path that provides balance for benefit versus risk.
What Are the Types of Fasting?
The fasting state can be induced by total absence of eating or a specific and tested combination and quantity of macro- and micronutrients that produce similar responses to a water fast but permit some nutrition (fasting mimicking diets or FMD described below). There is more than one way to fast, but there is only one that has been shown to induce rejuvenation and regeneration, the FMD.
Time Restricted Feeding (TRF)
TRF is a form of intake restriction, specifically focused on the when and how long eating occurs rather than macronutrients. This type of fasting is based off of the theory that our ancestors likely fed during daylight with limited resources and fasted during the night. Interestingly, this is controlled by what we call the circadian system. The circadian system oscillates every ~24 hours in a rhythm that enables organisms to respond to the light-dark cycle, which coincides with food accessibility. Today, this system has been disrupted due to long work hours, artificial light exposure, and haphazard eating behavior. To get back control of this system, we can mimic the natural circadian pattern by restricting feeding to a certain period of time.
As far as benefits of fasting and TRF specifically, preclinical trials have been positive, but clinical trials are inconsistent.
Preclinical:
• Reduction in body weight, total cholesterol, triglycerides, glucose, insulin, inflammatory markers, insulin resistance
Clinical:
• Fat mass decreases, muscle mass retention, IGF-1 decreases, adiponectin increases, total leptin decreases (when adjusted for fat mass, this did not change)
• Decreased body weight (inconsistent), triglycerides, glucose, LDL
Intermittent Fasting on Alternating Days
Intermittent fasting is not a precise term as it can involve a 24-hour abstinence from food which many not trigger “biological fasting” and glycogen depletion. Alternate day fasting is a form of fasting where the individual will fast for an interval of time, usually 24 hours, and then eat normally the next day. Another popular example of this is known as the “5:2” diet, where the individual restricts calories for 2 days, consecutive or not, and then eats normally for the remaining 5 days of the week.
For the most part, the preclinical trials have shown positive results, but clinical trials have been mixed.
Preclinical
• Reduction in body weight, glucose, insulin, inflammation, myocardial tissue damage, and leptin; elevation of adiponectin levels
Clinical
• Maintenance of healthy levels of blood glucose
• Increased metabolism of fatty acids and ketones
• Lower adherence rates compared to daily caloric restriction
• No comparable difference between alternative day fasting versus daily caloric restriction regarding: weight loss, fat mass loss, blood pressure, cholesterol, insulin sensitivity, inflammation
Periodic Fasting
Periodic fasting is fasting for an extended period of time and then returning to a baseline diet. Most commonly, this can be from 4 to 7 days. The overarching goal of periodic fasting is to induce the stress of fasting onto the body for a period of time in order to activate the stress resistant mechanisms in the body to combat future stressors. An example of a periodic fast would be either a water fast for 5 days or a fasting mimicking (FMD) for 5 days.
As far as the preclinical trials go, the results are promising. The same can be said for the clinical trials.
Preclinical
• Extend lifespan, induce stress resistance, and promote visceral fat loss
• Induce stem cell proliferation
• Promote cellular regeneration and rejuvenation
• Improve cognitive performance
Clinical
• Maintain healthy levels of glucose, triglycerides, LDL, total cholesterol, diastolic blood pressure, insulin-like growth factor-1, and insulin
- Promote weight loss (specifically visceral adiposity) while preventing lean body mass loss
The Basics of the Fasting Mimicking Diet in Cardiology Practices
In my experience, the easiest program to offer the health benefits of fasting to patients in a cardiology practice is also the one based in the most science. I have used the the FMDknown as Prolon in my practice for over 2 years in hundreds of patients. Prolon is the result of several decades of work by Dr. Valter Longo and his team at the University of South California. Dr. Longo is recognized as a leading expert on longevity and has done extensive research describing the basic biochemical pathways by which cells age. His book, The Longevity Diet, is an international best seller and I highly recommend that you read it. All of Dr. Longo’s proceeds from his book and the Prolon program are donated to research and a charitable foundation.
The FMD program was patented by Dr. Longo after years of experimenting with specific nutrients, called nutritechnology. The diet in humans provides 1,100 on the first day and then 800 calories for four more days. The 5-day program is packaged in an attractive box that is simple to use by patients (and health care professionals too). The nutrients that comprise the meals are the key and include plant-based whole foods like nuts, olives, teas, and soup mixes. They are all packaged in the box to provide an all-in-one FMD program. The macronutrients provided are about 60 percent of calories from fat, 10 percent from protein, and about 30 percent from carbohydrate. During the five days of FMD, vigorous exercise and alcohol are avoided. Coffee is limited to zero or one cup a day.
In the first year that I made the FMD available in my clinic, I completed 6 cycles of the program as I found that I enjoyed the program. I found it simple, tasty, and filling. It was plant-based and, gluten-free, and non-GMO. I often was a bit hungry on day one — despite it was the day with the most calories — but felt energized and clear of mind on days two through five. There was a sense of freedom from not wasting time considering what I was going to eat and I spent not money at coffee shops, restaurants, or grocery stores. All of the food I ate was in the box and I needed only hot water for the teas and soups. I slept well, worked efficiently, and was satiated. I lost 5 or more pounds each time I did the plan without being “hangry” or tired. The weight loss has been maintained. I also enjoyed a drop in my systolic blood pressure of over 20 mmHg with the Prolon FMD. My plantar fasciitis and a nagging pain in my right shoulder resolved during this year. Dozens of my patients have had similar results.
The Science Behind Prolon FMD
What is so special about the FMD? After years of experimenting with FMD in animal models and showing its benefits on metabolism and lifespan, Dr. Longo’s team analyzed the effects of FMD in a human clinical trial that was reported in early 2017. One hundred healthy subjects participated in this study; half of them followed the Prolon FMD program for five days a month for three months. The other half ate their usual diet for 3 months and then were offered Prolon. Profound differences were seen in terms of weight loss, visceral fat loss, drops in blood pressure, blood sugar, blood cholesterol, and markers of inflammation in the FMD group.
Even more profound over the 3 months were the reductions of insulin-like growth factor 1 (IGF-1) — which is a biomarker for cancer growth — and increases in stem cell production, a marker for regeneration of cells. In fact, the Prolon FMD program is a program that promotes stem cell-based regeneration, unique amongst various fasting programs. It has received the first patent in the US for promoting a longer healthspan.
How FMD Works in My Office
I advise my patients that if they want to achieve the published results for clinical and regenerative benefits they will need to do three cycles of FMD over 3 months. The manufacturer has developed a smart-phone app to guide patients through the program that is available at no cost and has also introduced a complementary coaching program during patient’s fasting program. I have found these add-ons to reduce the number of questions from patients and to increase their success.
I view the Prolon FMD as one of the greatest examples of translating years of peer-reviewed science into a plan that almost anyone can adopt and benefit from. Patients struggling with excess weight, inflammation, hypertension, hyperglycemia, and accelerated aging can be considered for the program. Some patients should not do the Prolon FMD such as those that are underweight, on insulin or multiple medications for diabetes, that are underweight, or are of advanced age or frailty. I carry some of the Prolon boxes in my office to demonstrate the program during a clinic visit. A convenient and customized online store has been added to my practice website and permits an easy route for patients to order or re-order the program without a need for inventory. In my opinion, fasting in general, and the ProlonFMD is one of the most important advances of the decade for in a cardiology practice. Specialists in cardiology should consider using the program themselves. In addition to stethoscopes, statins and stents, we can add soups and teas to the cardiology therapeutic toolbox.
References
• Brandhorst et al., A Periodic Diet that Mimics Fasting Promotes Multi-System Regeneration, Enhanced Cognitive Performance, and Healthspan, Cell Metabolism (2015), http://dx.doi.org/10.1016/j.cmet.2015.05.012
• Longo VD, Panda S. Fasting, circadian rhythms, and time restricted feeding in healthy lifespan. Cell metabolism. 2016;23(6):1048–1059. doi:10.1016/j.cmet.2016.06.001.
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• Moro T, Tinsley G, Bianco A, et al. Effects of eight weeks of time-restricted feeding (16/8) on basal metabolism, maximal strength, body composition, inflammation, and cardiovascular risk factors in resistance-trained males. Journal of Translational Medicine. 2016;14:290. doi:10.1186/s12967–016–1044–0.
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• Johnson, J.B., Summer, W., Cutler, R.G., Martin, B., Hyun, D.H., Dixit, V.D., Pearson,M., Nassar, M., Telljohann, R., Maudsley, S., Carlson, O., John, S., Laub, D.R., Mattson, M.P., 2007. Alternate day calorie restriction improves clinical findings and reduces markers of oxidative stress and inflammation in overweight adults with moderate asthma. Free Radic. Biol. Med. 42, 665–674.
• 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.
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• 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). pii: eaai8700. doi: 10.1126/scitranslmed.aai8700.
• Prolon Patent: https://patents.google.com/patent/US20150004280
• Prolon Healthspan Patent: https://medium.com/@Kahn642/the-first-u-s-patent-for-the-reversal-of-aging-the-prolon-fasting-mimicking-diet-b5eab5586052
