|Image 1: "Fasting? Man, everyone knows that this makes you fat and miserable - gimme that frickin' Big Mac I need to keep my metabolic rate elevated!" |
Digging into the metabolic and endocrine effects of "fasting"
|Illustration 1: Click here to read up on the previous three installments on (1) Calorie Expenditure; (2) Fat gain; (3) Performance decreases|
An important qualification we have to make, when we are trying to get to the nitty gritty of intermittent fasting is a clear-cut distinction between "not being eating constantly" and being in a "fasted state". After all, the actual fasting period begins with the "postabsorptive period", which, in turn, does not start before all of the nutrients ingested from the last meal have either been absorbed or passed your intestines undigested. Depending on the meal composition, this process can take anywhere between 3-4h and 7-8h, which - in view of the longer digestion time of proteins and fats, supports the idea that longer intermittent fasts would require higher amounts of proteins + fats (we will get back to that in one of the next installments)...According to Maughan et al. (Maughan. 2010) the "early phase of fasting" comprises roughly 24h and is characterized by sufficient glycogen supply from the liver (you will be familiar with this concept from the previous installments of the Intermittent Thoughts on Intermittent Fasting series), with the liver releasing about 4g of glucose per hour in the initial phase of fasting. In oder to spare the precious glycogen stores (Maughan estimates the average liver glycogen stores with only 44g/kg liver tissue, or about 60g for an average human liver) an upregulation in fatty acid oxidation takes place even in this early stages of fasting (Cahill. 1966). Consequently the concentration of circulating free fatty acids and glycerol (both released from white adipose tissue) in the blood increases and fatty acids and glycerol become available as a potential alternate fuel source for muscle and substrate for glyconeogenesis in the liver.
|Figure 1: Effects of 8 days of fasting on glucose, free fatty acid, glycerol, insulin and growth hormone (secondary axis) levels in six perfectly healthy subjects from the Cahill study (Cahill. 1966)|
[...] that involves mobilisation [sic] of fat stores and hepatic gluconeogenesis is regulated by changes in the hormonal environment, including a reduction in the plasma insulin concentration and increased circulating concentrations of glucagon, catecholamines, growth hormone, thyroid-stimulating hormone and corticosteroids.Of these changes, the decrease in serum insulin levels (in the Cahill study about -40-50%) facilitates, while the increases in circulating catecholamines, glucagon, growth hormone, thyroid-stimulating hormone and corticosteroids trigger the release of fat from adipose tissue and promote hepatic gluconeogenesis.
Alexander. 1964) and have also been implicated in the etiology of the "euthyroid sick syndrome" (De Groot. 1999). It does yet appear to be a uniquely beneficial characteristic of intermittent fasting that despite gradual increases in TSH, as they were observed by Sajid et al. in their 1991 study on the effects of Ramadan fasting on thyroid hormone profile, "[t]here was no significant change in T3 and T4 levels" (Sajid. 1991) with fasting periods below 24h. A study on the effects of Ramadan fasting on thyroid function in 28 healthy male subjects by Sulimani that was conducted back in 1987, yet published (in English) only 5 years ago, corroborates these results (Sulimani. 2006):GH, thyroid, cortisol... "What about testosterone? And other sex hormones?" I knew you would ask that. Unfortunately the data on testosterone levels and related hormones is relatively inconclusive. While Ghaderi and Khameneh report that testosterone levels were "significantly greater than baseline one (p=0.007, p=0.025 respectively)" (Ghaderi. 2006) in 32 single men (age 24-26) and Shahabi et al. found no effects of Ramadan fasting on hormone secretion in women (Shababi. 2010), Mesbahzadeh et al. state in a short communication that "[t]estosterone level was lower, significantly so for the 20th and 28th of the month (P < 0.05)" (Mesbahzadeh. 2005). Other studies report shifts in the circadian rhythm of cortisol and testosterone release, which could partly explain differences, if before and after levels were measured only once and at the same time of the day - the complicated shift in circadian pattern is yet a topic for another installment of the Intermittent Thoughts on Intermittent Fasting series ;-)
[...] there was no significant change in the results of the thyroid function tests done before and at the end of Ramadan. The values respectively for plasma T4, T3, free T4 and TSH before and after Ramadan were 7.0±1.08 μg% and 7.1±1.34 μg%; 1.1±0.17 ng/ml and 1.1±17 ng/ml; 1.1±0.21 ng/dL and 1.1±0.15 ng/dL; 1.7±0.62 mu/ml and 1.4±0.81 mu/ml; P>0.1 for all comparisons.And in a more recent study on the effects of religious fasting on elite athletes (15 male judo player), intermittent fasting even increased "the mean blood level of thyroid-stimulating hormone and free thyroxine [...] significantly" (Chaouachi. 2009). In view of these results, it is unlikely that a decrease in thyroid function could become a sticking point for someone who wants to improve his body composition on an intermittent fast.
Growth hormone - major or minor player in the beneficial effects of intermittent fasting?
|Figure 3. Blood Glucose, Insulin, Hematocrit, GH, IGF-1 and IGFBP-3 in rugby players at rest and after HIIT training on a an cycle ergometer on week 1 and week 4 of Ramadan fasting relative to baseline (data calculated based on Bouhlel. 2008)|
[...] Ramadan is an intermittent fast, and the severity of food restriction and dehydration may therefore be insufficient to induce changes in the GH/IGF-1 axis. (Bouhlel. 2008)As the data in figure 3 goes to show, even after 4 weeks of intermittent fasting, GH levels at rest were elevated by "only" 40%; an elevation, which, due the cyclic nature of growth hormone secretion, does not even reach a p-value (probability that it is not plain statistical coincidence) of p < 0.05 and must thus be considered statistically non-significant. In view of the fact that the exercise induced rise in GH was blunted during the fast (ca. -30% compared to pre-Ramadan values), the absence of accompanying increases in IGF-1 and the slight increase in IGF-binding-protein-3 (which is still believed to make it impossible for IGF to bind to the receptor to do its anabolic magic, cf. Elgin. 1987) at rest, it is altogether unlikely that intermittent fasters would see benefits from increases in growth hormone that go beyond the previously mentioned shift towards a muscle sparing and fat-burning.
|Figure 4: Changes in body composition (left) as a consequence of 4 weeks of Ramadan fasting at the given (self-selected) macronutrient amounts (right) in rugby players (data calculated based on Bouhlel. 2008)|
[t]his shows that 1 week of Ramadan fasting is not long enough to induce changes in body composition, and that the decrease in body mass seen at this stage is likely related to a reduction in body fluids. Fat had been lost by the end of Ramadan, but lean tissue was still preserved.In this context it is also worth mentioning that dehydration blunts the release of growth hormone, you would see on a fitness oriented (vs. a religious) intermittent fast, where sufficient hydration obviously is of paramount importance and the consumption of calorie-free beverages is mandatory, even during the fasting period. Now, with the established body-recompositioning effect of growth hormone (e.g. Meinhard. 2010) in mind, we may safely assume that evn adequate fluid consumption alone could have had beneficial effects on the changes in body composition Bouhlel et al. observed in their study.
IF and exercise a dynamic duo for the perseverance of muscle mass on a diet
As far as the reasons for the perseverance of muscle mass is concerned Bouhlel et al. highlight the importance of the "continuation of a substantial training regimen during Ramadan" [my emphasis], which obviously countered the protein-catabolic effect of fasting (I'd rather say malnutrition, because a -28% in energy intake is pretty substantial for high level athletes) that has been observed in more or less related studies in the sedentary population.
|Image 3: Diet and exercise are key components of body recompositioning.|
Exercise did prevent the increase in the rate of total protein degradation caused by food restriction, which may have important implications in weight reduction diets.And indeed, any type of fast (even an intermittent one) that is intended to improve body composition makes little sense without the exercise component.
Physiologic increases in plasma FFA levels cause insulin resistance in both diabetic and nondiabetic subjects by producing several metabolic defects: (1) FFA inhibit insulin-stimulated glucose uptake at the level of glucose transport or phosphorylation (or both); (2) FFA inhibit insulin-stimulated glycogen synthesis; and (3) FFA inhibit insulin-stimulated glucose oxidation.[...] FFA probably also cause hepatic insulin resistance, which results in increased rates of endogenous glucose production in relationship to the prevailing degree of hyperinsulinemia. (Boden. 2001)The obvious question, now, is: Would intermittent fasting have similarly detrimental effects on insulin sensitivity? After all, fasting is stressing and we have previously identified the increase in free fatty acids as a consequence of fasting induced metabolic adaptations that will allow your body to feed preferentially on fat, instead of carbs. It thus seems to be reasonable to assume that intermittent fasting would predispose its practitioners to insulin resistance.
It should be noted that the temporary insulin resistance actually is a fundamental and important mechanism by which intermittent fasting works its fat burning, muscle sparing magic. In fact, the combination of increased free fatty acids and the ensuing decrease in glucose uptake by skeletal muscle in the initial phase of fasting (and intermittent fasting does not go beyond this initial phase) have been shown to ramp up uncoupling proteins and thus fatty acid oxidation in slow-twitch oxidative muscles (Samec. 1998) and thusly set the scene for improvements in body composition, as long as you are in a caloric deficit (read more on the significance of total caloric intake in future episodes of this series).While data from the Cahill study, where 8 days of fasting reduced the coefficient of glucose disappearance from 2.1%/min to 0.63%/min (-70%), would support this idea, further research reveals that this is another case, where "normal" fasting with its prolonged periods of food abstinence differs fundamentally from its "intermittent" incarnation with fasting periods of 12-24h, of which a group of Danish scientists were able to show that it "increases insulin-mediated glucose uptake rates" (Halberg. 2005).
The Halberg study did however use an alternate-day fasting regimen (for my thoughts on alternate-day vs. intermittent fasting cf. part II of this series), which is obviously characterized by ~50% longer fasting periods. Similar data (cf. figure 5) does yet come from another Ramadan fasting study (12-16h fasting), in which 55 subjects with metabolic syndrome crammed their habitual caloric intake (this is an important difference to most of the other Ramadan studies, where mostly healthy participants automatically decreased their calorie intake !) into the two meals this kind of religious fasting allows for.
|Figure 5: Changes in waist circumference, BMI, HDL, triglycerides, fasting glucose, QUICKI (quantitative insulin sensitivity check index) and 1/HOMA-IR after non-calorie-restricted (not even unconsciously) Ramadan fasting in 55 subjects with metabolic syndrome (data adapted from Shariatpanahi. 2008)|
In view of the fact that I have already spent the major part of this precious day-off thinking, researching and blogging about Intermittent Fasting, I will yet postpone any further elaborations on the health benefits of (intermittent) fasting and the subsequent analysis of what happens when you finally "break the fast" to the next installments of this series. In the mean time, I hope you got some new points to think about and repeat my invitation to post your comments, questions and suggestions as to where this series should be heading on Facebook, Twitter or in the comments area of this page.