TRE or intermittent fasting (IF) has gained substantial ground in both the fitness and health spheres since the turn of the 21st century, with purported benefits initially drawing much scepticism. Fitness aficionados scoffed at the idea of skipping but one bi-hourly scheduled meal for fear of hindering muscular growth potential and stalling the metabolism. However, lower meal frequency appears to have a noticeably superior effect on diet-induced thermogenesis (i.e. what most people think of when they claim to “speed up metabolism” with smaller, more frequent meals).
Scientific research continues to cast an overwhelmingly positive light on this practice. In fact, I would go as far as deeming TRE the finest anti-ageing doctor that exists. Usually use of the word ‘panacea’ by health professionals would elicit a due sense of dubiety in me, but periodic abstinence from food is one exception I will allow. Until the research contradicts that line of thought anyway, which won’t happen but must be said given this is a body of research whose surface has barely been probed.
It is extraordinary how something as inherently passive as food abstinence can be an elixir of health.
Ironically, I first implemented fasting in 2013 for a rationale perhaps least supported by the science to date, which was to directly increase my testosterone levels. I employed a flexible 16/8 hour fasting/eating window religiously for 3 years during which time I gained ~25kg of lean weight. My testosterone improved too, but this was because I replaced daily running with progressive resistance training 3-4 days a week while eating a calorie surplus.
The science mostly demonstrates small but insignificant reductions in testosterone levels amongst male participants, but a definitive answer to IF’s effects on testosterone won’t be elucidated for some time. This question needs to be investigated in the context of strength training participants over at least a medium to longer term study method. There is a dearth of the latter at present.
Indirectly, however, my provisional understanding is that habitual TRE does improve the androgen profile of males over time by virtue of other improved markers which will be explored below.
Awareness of IF as a tool to promote diet adherence is widespread in the fitness community, pioneered by Ori Hofmekler (The Warrior Diet) and Martin Berkhan (The Leangains Method) originally. Of course, it makes sense that limiting oneself to a certain timeframe in which food can be consumed should translate to less daily calories when compared with ad-libitum feeding. In other words, a calorie deficit and thus weight loss becomes more achievable.
I don’t need to necessarily lose more weight, though. So what compels me to fast 18+ hours most days?
8 weeks into resumption of daily fasting, albeit this time for longer bouts and with a few fundamental changes, both physical and non-physical benefits have already manifested. My skin has improved, waist circumference has lessened by 2 inches, greater perceived clarity of thought and working memory, improved digestion and satiety… and most profoundly, a deep sense of Zen that grows in accordance with extent of time in the fasting state.
“Yeah, that’s great, but N = 1”.
Let’s synthesise the main findings from recent scientific literature.
Cognition and Brain-Derived Neutrophic Factor (BDNF)
Brain-derived neurotrophic factor (BDNF) is a secretory growth factor that supports the survival of existing neurons and promotes synaptogenesis and differentiation of new neurons (Park and Poo, 2013).
BDNF is crucial in the context of our mental capacity and cognition and dysregulation of BDNF is associated with the onset of several neurodegenerative diseases, including Alzheimer’s Disease. It is something we can never have too much of.
Mammalian food deprivation and fasting consistently demonstrates reduction in size of most organs, except the brain and the testes. Quite to the contrary, IF enhances brain function via upregulation of BDNF and its associated increase in neurogenesis (growth of new brain tissue, pathways).
Exercise has this effect too, but fasting appears to be even more powerful as a driver of BDNF. Short and intense bouts of exercise during the fasting phase appears to be highest yield.
Ad-libitum eating downregulates BDNF which is known to accelerate brain dysfunction as we age.
Other pros of elevating BDNF include:
- Neuronal resistance to brain injury and tissue damage (an area pertinent to TBI victims especially)
- May modulate depressive symptoms like anti-depressant medication (successful intervention with the latter increasing blood levels of BDNF)
- Regulation of appetite and circadian rhythm, crucial to counter overeating
- Helps with re-myelination of nerves after nerve-related injuries
- Aids in glucose metabolism
- Helps with control of the cardiovascular and gastrointestinal systems
Visceral Fat and Metabolic Disease
As mentioned above, IF can shrink fatty organ tissue. This phenomenon can even take place when subjects consume the same calories (‘iso-caloric’) as the control subjects and maintain overall body weight.
Visceral fat, the fat that suffuses our vital organs, is far more dangerous to our health than subcutaneous fat (beneath the skin). An individual with who is moderately overweight with the latter can be healthy, but visceral fat is never absolutely benign.
Metabolic disease such as Type II Diabetes Mellitus (T2DM) is at an unprecedented high in developed countries and we know that adiposity of the liver, both alcohol-induced and non-alcoholic fatty liver (NAFLD), is a significant predisposing risk factor to such.
At this point in time there is a far greater volume of studies looking at fasting’s effect on mice with fatty liver, though human studies of this nature are still continuing to grow in number. Regardless, fasting windows of 18+ hours promote glycogenolysis and subsequent lipolysis of the diseased liver in NALFD patients.
Insulin resistance is a hallmark of NAFLD and T2DM, so improving the state of our liver with TRE may restore the efficiency with which we metabolise glucose and even reverse these diseases over time.
With the exception of a true ketogenic diet, eating ad-libitum or ‘around the clock’ as we are so socially conditioned to do induces chronically elevated blood glucose levels. This is a key mechanism in the development of insulin receptor resistance that eventually manifests as T2DM.
Anti-ageing
Many advocates of IF label it the bona fide fountain of youth for its cellular cleansing mechanism known as ‘autophagy’. Autophagy is essentially the degradation of old cells and proliferation of new cells. By preventing the toxic accumulation of damaged protein and organelles, particularly mitochondria, autophagy limits oxidative stress, chronic tissue damage, and oncogenic signaling, which suppresses cancer initiation.
Protein oxidation, on the other hand, appears to accelerate the ageing process by nullifying the autophagic compounds responsible for its life extension benefits. But we should all be acutely aware of how important protein intake AND quality is from the viewpoint of performance, anti-fragility, and muscular development.
Perhaps it is the fact that the traditional Okinawan diet comprised a mere 10% of protein that this blue zone boasts such a lofty life expectancy. Similarly, vegetarianism and veganism may be correlated with longer lifespan not by virtue of less saturated fat and cholesterol; rather, it is likely the naturally lower intake of protein.
What’s the fun in living longer if you’re skinny, weak and lack sex drive?
My advice is not to eschew protein, or consciously limit it, but to incorporate generous amount of high quality protein (in the vicinity of 2-3x bodyweight in kg) in your daily fasting regime.
In doing so, muscle retention is at least encouraged and consideration for longevity is exercised.
Improved Heart Rate Variability (HRV)
I mentioned to my friend recently how I have come to identify a perceptible state of zen the deeper I go into a fast, which at first didn’t make sense to me given cortisol (the major stress hormone) expectedly rises during this time.
So I dived into the science.
Periodic fasting reduces systolic blood pressure, heart rate; and increases HRV. HRV is a less commonly known biomarker that denotes the variation of timespan from one heart beat to the next one, i.e. from R- to R-wave in the electrocardiogram (ECG) of “normal to normal beats”. A healthy amount of HRV helps us transition between parasympathetic (‘rest and digest’) and sympathetic (‘fight or flight’) nervous states.
Patients with major depressive disorder (MDD) and anxiety demonstrate remarkably lower levels of HRV. Conversely, we see rises in HRV with laughter and meditative exercise like yoga.
In short, IF seems to have a powerful influence on our mood and perception of stress.
TRE > Caloric Restriction Alone
Given the limited time window one has to eat when employing an IF protocol, caloric restriction (CR) and thus weight loss is almost inevitable. However, the studies that do examine pure CR compared with IF alone suggest comparable improvements in health biomarkers.
When the IF group isn’t in a calorie deficit, the time-contingent abstinence elicits notable gains in insulin sensitivity, cellular processing and beiging of white adipose tissue. These positive changes can elapse despite nil to minimal subcutaneous fat loss.
So even if you’re not concerned with body weight or physique changes, in which calorie counting is necessary to quantify and monitor progress, simply abbreviating your eating window will bolster your health.
Practical Application
There are many iterations of TRE and, though the 5:2 method in which only 2 days of the week sees drastic calorie reduction has gained traction in recent years, I prefer a more consistent and substantial fast.
My first implementation of IF closely resembled the 16:8 Leangains Method formulated by Berkhan, and during this time I would tend to push the eating window far into the PM.
My more recent regime differs in a few ways with the most notable changes being a shorter and earlier eating window. However, some flexibility is always necessary to foster sustainability so it is in this regard that I will simply try to eat the bulk of calories in the middle of the day.
At present, I aim to consume 1-2 big meals and perhaps a snack within a 4-7 hour window, minimising food intake within a few hours of bed time. The primary reason for the latter is that elevated insulin can interfere with melatonin production and consequently diminish sleep quality. It is still a relatively grey area of research but a plausible hypothesis that has been verified by several papers.
The ‘ideal’ eating window, in light of recent literature, seems to be in the AM but this can be impractical for social reasons. Striving to eat within the middle of the day to early evening strikes a sensible compromise. A few alcoholic drinks prior to bed won’t impact insulin significantly and can actually improve insulin sensitivity in the medium to long term, so this doesn’t pose a concern. Choose alcoholic beverages lower in sugar content (spirits ftw) where possible, of course.
Consider self-experimenting by pushing your usual breakfast back by 2 hours and eating an earlier dinner at, say, 5.30pm. Prolong breakfast by an hour each week as a means to gradually habituate.
References
Aksungar, F. B., Sarikaya, M., Coskun, A., Serteser, M., & Unsal, I. (2017). Comparison of Intermittent Fasting Versus Caloric Restriction in Obese Subjects: A Two Year Follow-Up. J Nutr Health Aging, 21(6), 681-685. doi:10.1007/s12603-016-0786-y
Anton, S. D., Moehl, K., Donahoo, W. T., Marosi, K., Lee, S. A., Mainous III, A. G., . . . Mattson, M. P. (2018). Flipping the metabolic switch: understanding and applying the health benefits of fasting. Obesity, 26(2), 254-268.
Dolgoff-Kaspar, R., Baldwin, A., Johnson, S., Edling, N., & Sethi, G. K. (2012). Effect of laughter on mood and heart rate variability in patients awaiting organ transplantation: a pilot study. Altern Ther Health Med, 18(4), 53-58.
Horne, B. D., Muhlestein, J. B., & Anderson, J. L. (2015). Health effects of intermittent fasting: hormesis or harm? A systematic review. The American journal of clinical nutrition, 102(2), 464-470.
Lee, C., & Longo, V. (2016). Dietary restriction with and without caloric restriction for healthy aging. F1000Research, 5.
Levine, M. E., Suarez, J. A., Brandhorst, S., Balasubramanian, P., Cheng, C.-W., Madia, F., . . . Wan, J. (2014). Low protein intake is associated with a major reduction in IGF-1, cancer, and overall mortality in the 65 and younger but not older population. Cell metabolism, 19(3), 407-417.
Longo, V. D., & Mattson, M. P. (2014). Fasting: molecular mechanisms and clinical applications. Cell metabolism, 19(2), 181-192.
Marosi, K., & Mattson, M. P. (2014). BDNF mediates adaptive brain and body responses to energetic challenges. Trends in Endocrinology & Metabolism, 25(2), 89-98.
Mattson, M. P., Longo, V. D., & Harvie, M. (2017). Impact of intermittent fasting on health and disease processes. Ageing Research Reviews, 39, 46-58.
Nicoll, R., & Henein, M. Y. (2018). Caloric Restriction and Its Effect on Blood Pressure, Heart Rate Variability and Arterial Stiffness and Dilatation: A Review of the Evidence. International journal of molecular sciences, 19(3), 751.
Schrieks, I. C., Heil, A. L., Hendriks, H. F., Mukamal, K. J., & Beulens, J. W. (2015). The effect of alcohol consumption on insulin sensitivity and glycemic status: a systematic review and meta-analysis of intervention studies. Diabetes Care, 38(4), 723-732.
Wan, R., Weigand, L. A., Bateman, R., Griffioen, K., Mendelowitz, D., & Mattson, M. P. (2014). Evidence that BDNF regulates heart rate by a mechanism involving increased brainstem parasympathetic neuron excitability. Journal of Neurochemistry, 129(4), 573-580. doi:doi:10.1111/jnc.12656
Young, H. A., & Benton, D. (2018). Heart-rate variability: a biomarker to study the influence of nutrition on physiological and psychological health? Behavioural pharmacology, 29(2-), 140.
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