As mentioned, a report on yet another mechanism (the latest of several) whereby CR makes for a happy brain:
increasing ghrelin levels, through subcutaneous injections or calorie restriction, produced anxiolytic- and antidepressant-like responses in the elevated plus maze and forced swim test.(1)
Having seen numerous previous reports of "anxiolytic- and antidepressant-like responses" to CR, I wasn't surprised by the
effect, but I was surprised by the
mechanism: the increase in
ghrelin -- a neurohormone whose best-researched effects are precisely the inducement of hunger itself.
Certainly, however, this is one mechanism amongst several. Notably, because of its role in regulating energy balance (2), levels of the neurotrophic factor
brain-derived neurotrophic factor (BDNF), are increased by CR; this is not only a mechanism whereby CR enhances neurogenesis and protects neurons from neurotoxic insult,(3) but is also known to be a central mood regulator, whose levels are boosted by all major classes of antidepressant:
Stress is known to precipitate or exacerbate depression in susceptible individuals (Gold and Chrousos, 2002). Moreover, depressed patients show atrophy in several brain regions, including the hippocampus, frontal cortex, and amygdala (McEwen, 2001). These anatomical changes caused by stress are paralleled by reductions in BDNF expression (Duman and Monteggia, 2006). On the other hand, chronic administration of antidepressant treatments from different classes have been reported to commonly increase the expression of BDNF mRNA in the hippocampus (Coppell et al., 2003; Dias et al., 2003; Fujimaki et al., 2000; Molteni et al., 2005; Nibuya et al., 1995; Nibuya et al., 1996). Changes in BDNF expression emerge from chronic antidepressant treatment and parallel the time course of clinical response to these drugs. This could indicate that antidepressants regulate BDNF to oppose the effects of chronic stress and may be critical for therapeutic recovery ...
Chronic (21 days), but not acute (1 day), treatment with the tricyclic antidepressant (TCA) desipramine (10 mg/kg), the selective serotonin reuptake inhibitor (SSRI) fluoxetine (10 mg/kg), and the monoamine oxidase inhibitor (MAOI) phenelzine (10 mg/kg) increased BDNF protein levels in the frontal cortex (10-30%), but not in the hippocampus, amygdala, olfactory bulb, and brain stem. [Note that CR increases BDNF in the hippocampus (3) -MR]. ...
The frontal cortex is also sensitive to effects of stress and antidepressant treatments and is likely to be involved in depression. In postmortem studies of depressed patients, cellular and morphological changes reported in cortical brain regions include reductions in the number of glia and neuronal size of cortical structures (Cotter et al., 2001; Ongur et al., 1998; Rajkowska and Miguel-Hildalgo, 2007). In rodents, chronic stress decreases cell proliferation and the production of glia in the cerebral cortex, and this effect was reversed by chronic fluoxetine treatment (Banasr et al., 2007). Moreover, chronic antidepressant treatments elevate BDNF mRNA in the frontal cortex (Nibuya et al., 1995). These findings favor the existence of decreased cortical neurotrophic support in depression, and suggest that the increased levels of BDNF in the frontal cortex following chronic antidepressant treatment could be important in reversing pathogenic deficits in this region. The promotion of hippocampal neurogenesis by chronic antidepressant treatments might also be linked to the ability of these drugs to increase BDNF protein levels in the frontal cortex. Increased levels of BDNF could influence hippocampal function by direct connections from the frontal cortex to the hippocampus (Zhong et al., 2006), or by a network of indirect connections to hippocampal afferents (Fuchs et al., 2006).
Moreover, animal studies have found that CR has many positive effects on brain function, including reducing anxiety (5); indeed, it's long been observed that many anorexics maintain their (misguided, malnourished, and self-destructive) reduction in Caloric intake in part because it relieves their anxiety symptoms (6). Similarly, in overweight humans undergoing weight loss, contrary to 'fat acceptance' dogma:
numerous studies conducted during the past 25 years have reported reductions in symptoms of depression and anxiety or, at minimum, no worsening in affect in obese patients treated by behavior modification combined with moderate caloric restriction,47-50 severe caloric restriction,24,47,50-51 or use of weight loss medications.40,52-53 ...
Although most studies evaluating psychological changes with weight loss are from those who participated in clinical studies, recent information is available from 629 women and 155 men in the National Weight Control Registry, a registry of individuals who have lost at least 13.6 kg (mean, 30.0 kg) and who maintained a required minimum weight loss of greater than 13.6 kg for more than 1 year (mean, 6 years).60 Almost half of the individuals in this sample report having lost weight on their own, without a formal weight loss program, and the remainder lost their weight in a variety of weight loss programs. Both groups reported using diet and exercise to lose weight. Registry participants completed a variety of measures of mood, distress, restraint, disinhibition, binge eating, and purging.61 Distress and depression levels were similar to those of community-based samples, as were rates of binge eating and purging. Levels of restraint and disinhibition were similar to those in patients recently treated for obesity and differed from those of eating disordered samples. Although this is not a random sample of all long-term weight maintainers, and hence is subject to selection bias, the results provide reassurance that many individuals who have lost and maintained weight through a variety of methods do not experience significant psychological distress or eating disordered behaviors.
Most findings indicate that obese adults who lose weight are likely to experience modest improvements in mood or, at minimum, no worsening in affect. Before weight loss, eg, obese individuals typically score in the nondepressed range on the Beck Depression Inventory.62 With weight loss, they report even fewer symptoms of dysphoria.(7)
So I was a bit puzzled to read this assertion:
I would like to see some discussion on the possibility of depression among CR practitioners. It would be a *serious* side effect, and certainly seems at least as likely as your folic acid hypothesis.
I couldn't see what basis he could have for such a statement, and indeed I knew of a fair body of evidence supporting the idea that CR
improves mood. Now I see one source of misunderstanding:
I bet if you believe in the philosophy of calorie restriction, there is a good chance you may be happier restricting calories. Though I have seen studies to the contrary.
"... the classic study on calorie restriction, involving 20 healthy young men who cut their food intake in half for six months, found many negative effects, including "marked signs of depression and irritability." The subjects "were despondent, had very low energy and had lost the initiative to do things. When allowed to eat again, they in--dulged in binge eating." They did lose weight--almost a quarter of their body weight--but, Wadden says, "it's hard to argue for [calorie restriction] in the absence of definitive data." from http://www.newsweek....6?tid=relatedcl
Ah: the famous Ancel Keys "Minnesota Semistarvation study". Well, firstly, that
wasn't "to the contrary": despite the Newsweek characterization of this as 'calorie restriction', these folks
didn't " believe in the philosophy of calorie restriction", but were conscientious objectors who chose being subjected to a medical experiment on the effects of starvation over going to war or to prison. They did apparently believe in the value of the experiment as such, and favored it over shooting people or being mixed in with murderers and petty thieves, but were certainly not practicing voluntary CR. Moreover, their diets were very poor, and the level of energy deficit and the suddenness of its imposition were quite extreme. I'd feel pretty miserable too if I were locked up, half of my food taken away over a period of a few weeks, and was starved for EFAs and protein; I don't think it's reasonable to take this as evidence about the likely effects of volutary,
properly-performed, life-extending CR in humans. And, from the previously-cited review:
Concerns about a "dieting depression" can be traced to 2 early studies, the first by Keys and colleagues,14 ... The second study45 found that 54% of obese patients, who were treated in a nutrition clinic, reported (retrospectively) that they had experienced symptoms of weakness, nervousness, irritability, fatigue, or nausea at some time when previously trying to lose weight. These individuals did not report symptoms of depression, although the report of the findings was titled the "Dieting Depression." The title derived from observations of a second group of 25 individuals who were treated at an inpatient unit for both their psychiatric complications and obesity. Other early studies, reviewed by Stunkard and Rush,46 also reported negative emotional responses to dieting.
In contrast to these early findings, numerous studies conducted during the past 25 years have reported reductions in symptoms of depression and anxiety or, at minimum, no worsening in affect ... Several factors seem to explain the discrepancy between the early and later findings. Studies in the 1950s and 1960s were based primarily on patients who were undergoing psychodynamic psychotherapy and, thus, were likely to have had significant emotional disturbance before weight loss.54-55 By contrast, more recent behavioral studies included obese individuals who volunteered specifically for weight reduction; most were known to be free of significant depression.56 In addition, most patients in recent studies received group support and cognitive behavioral therapy, each of which might favorably affect mood.54-55 Differences in methods used to assess mood, and the frequency of assessment, might further explain the discrepancies between the early and later studies.54
I also seem to recall a study on monkeys indicating that they became more irritable from calorie restriction
I don't believe there's any such data.
This is great news, if true. For those who practice calorie restriction, are you happier now than before CR?
Yes, I am; moreover,
anecdotally, there have been many reports on the
CR Society discussion forums and personal conversation indicate substantial CR-induced relief from anxiety and bipolar disorder. In fact, many CR practitioners (myself included) experience remarkable
euphoria during the first few months of CR, and enjoy the coursing, streaming sensation of a cleaned-up metabolism thereafter, every cell humming with a near-mystical sense of a 'life force.'
Fortunately, we have more rigorous evidence than anecdotes, however. Although on the border between true CR and 'mere' healthy weight loss (because the subjects were high-normal or overweight to begin with and didn't lose weight into a range that was beyond their personal or a population norm, we now have a controlled study of 6 months of human "Calorie restriction" of a sort, in the form of the
CALERIE study; it now reports:
During CALERIE Phase I, the Medical Outcomes Study Short-Form 36 Health Survey (SF-36) was used to measure [quality of life], and the Beck Depression Inventory II and depression scale of the MAEDS [Multidimensional Assessment of Eating Disorder Symptoms ] were used to measure mood. Our results indicate that depressed mood, measured by the BDI-II, did not change during the trial. Additionally, in the CR group, scores on the MAEDS depression subscale decreased at three and six months in comparison to baseline. These results indicate that CR had no negative effect on mood during this trial and, in fact, symptoms of depressed mood, measured with the MAEDS, decreased in the CR group.
The SF-36 was used to test the effects of CR on two components of QOL - physical functioning and vitality. All dieting groups, but not the control group, had improved physical functioning during the trial. For the CR group, physical functioning was significantly improved from baseline to month three and baseline to month six. CR had no significant effect on vitality. (8)
I suspect that better-quality
diets, with fewer grain products and more vegetables, total fat, omega-3 and short-chain omega-6 fatty acids, and vegetarian protein, would have yielded better results.
-Michael
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Edited by Michael, 01 September 2008 - 01:57 AM.