Local and Systemic Therapies for Breast Cancer Patients: Reducing Short-term Symptoms with the Methods of Integrative Medicine.

With improved prognosis due to advances in the diagnosis and therapy of breast cancer, physicians and therapists now focus on aspects such as quality of life and the management of side effects from breast cancer treatment. Therapy- and disease-related side effects often reduce the patient's quality of life and can place a further burden on patients, with non-compliance or discontinuation of therapy a potential consequence. Study data have shown that therapy- and disease-related side effects can be reduced using the methods of integrative medicine. Reported benefits include improving patients' wellbeing and quality of life, reducing stress, and improving patients' mood, sleeping patterns and capacity to cope with disease. Examining the impact of integrative medicine on the side effects of cancer treatment would be beyond the scope of this review. This article therefore looks at short-term side effects of cancer treatment which are usually temporary and occur during or after local and systemic therapy. The focus is on mind-body medicine, acupuncture and classic naturopathic treatments developed by Sebastian Kneipp as complementary therapies. The latter includes hydrotherapy, phytotherapy, nutritional therapy, exercise therapy and a balanced lifestyle.

Systematic review of complementary and alternative medicine treatments in inflammatory bowel diseases.

OBJECTIVE: We performed a systematic review for Complementary and Alternative Medicine [CAM] as defined by the National Institute of Health in Inflammatory Bowel Disease [IBD], ie Crohn's disease [CD] and ulcerative colitis [UC], with the exception of dietary and nutritional supplements, and manipulative therapies. METHODS: A computerized search of databases [Cochrane Library, Pubmed/Medline, PsychINFO, and Scopus] through March 2014 was performed. We screened the reference sections of original studies and systematic reviews in English language for CAM in IBD, CD and UC. Randomized controlled trials [RCT] and controlled trials [CT] were referred and assessed using the Cochrane risk of bias tool. RESULTS: A total of: 26 RCT and 3 CT for herbal medicine, eg aloe-vera gel, andrographis paniculata, artemisia absinthium, barley foodstuff, boswellia serrata, cannabis, curcumin, evening primrose oil, Myrrhinil intest®, plantago ovata, silymarin, sophora, tormentil, wheatgrass-juice and wormwood; 1 RCT for trichuris suis ovata; 7 RCT for mind/body interventions such as lifestyle modification, hypnotherapy, relaxation training and mindfulness; and 2 RCT in acupuncture; were found. Risk of bias was quite heterogeneous. Best evidence was found for herbal therapy, ie plantago ovata and curcumin in UC maintenance therapy, wormwood in CD, mind/body therapy and self-intervention in UC, and acupuncture in UC and CD. CONCLUSIONS: Complementary and alternative therapies might be effective for the treatment of inflammatory bowel diseases; however, given the low number of trials and the heterogeneous methodological quality of trials, further in-depth research is necessary.

Randomised clinical trial: a herbal preparation of myrrh, chamomile and coffee charcoal compared with mesalazine in maintaining remission in ulcerative colitis--a double-blind, double-dummy study.

BACKGROUND: The herbal treatment with myrrh, dry extract of chamomile flowers and coffee charcoal has anti-inflammatory and antidiarrhoeal potential and might benefit patients with UC. Aminosalicylates are used as standard treatment for maintaining remission in ulcerative colitis (UC). AIM: To compare the efficacy of the two treatments in maintaining remission in patients with ulcerative colitis. METHODS: We performed a randomised, double-blind, double-dummy study over a 12-month period in patients with UC. Primary endpoint was non-inferiority of the herbal preparation as defined by mean Clinical Colitis Activity Index (CAI-Rachmilewitz). Secondary endpoints were relapse rates, safety profile, relapse-free times, endoscopic activity and faecal biomarkers. RESULTS: A total of 96 patients (51 female) with inactive UC were included. Mean CAI demonstrated no significant difference between the two treatment groups in the intention-to-treat (P = 0.121) or per-protocol (P = 0.251) analysis. Relapse rates in total were 22/49 patients (45%) in the mesalazine treatment group and 25/47 patients (53%) in the herbal treatment group (P = 0.540). Safety profile and tolerability were good and no significant differences were shown in relapse-free time, endoscopy and faecal biomarkers. CONCLUSIONS: The herbal preparation of myrrh, chamomile extract and coffee charcoal is well tolerated and shows a good safety profile. We found first evidence for a potential efficacy non-inferior to the gold standard therapy mesalazine, which merits further study of its clinical usefulness in maintenance therapy of patients with ulcerative colitis. EudraCT-Number 2007-007928-18.

[Aspects of traditional Indian medicine (Ayurveda) in urology]. / Aspekte der traditionellen indischen Medizin (Ayurveda) in der Urologie.

Ayurveda is from a global viewpoint the oldest and the most employed traditional form of medicine in India. The difference to western medicine is that this form of medicine is based on experience, empirical evidence and intuition accumulated over thousands of years and passed down through generations orally as well as by sketches. Ayurveda is not only concerned with the physical but also with the spiritual aspects of the body and according to this doctrine most diseases result from psychological and pathological alterations in the body. Ultimately, the definition of health according to Ayurveda is an equilibrium between the physical, mental and spiritual components. Ayurvedic medicine is used within the framework of the treatment of urolithiasis for diuresis, for litholysis, as an analgetic for spasms and with an antimicrobial function.

Impact of stimulation dose and personality on autonomic and psychological effects induced by acupuncture.

Acupuncture has been shown to exhibit distinct effects on the autonomic nervous system. We tested whether the autonomic and psychological response to acupuncture depends on the stimulation dose and the personality of the treated subjects. 52 healthy subjects were randomized to receive either low dose (one needle at point Hegu bilaterally) or high dose (additional 4 needles at non-acupoints bilaterally) acupuncture stimulation after stratification according to their personality to "reduce" or "augment" incoming stimuli. Outcomes were changes of electrodermal activity (EDA), high frequency component of heart rate variability, heart rate, mean arterial blood pressure, respiration rate and subjective parameters for psychological well being and perceived intensity of needling. Electrodermal activity increased during needle insertion and decreased under baseline when subjects were resting with the needles in the body for 20 min. The initial EDA increase was significantly (GEE ANCOVA p<0.001) more pronounced during high dose stimulation and independent of personality. All other physiological parameters did not show any significant group effect. Strong stimulated augmenters perceived acupuncture most painful and increased with their psychological activation after the acupuncture session in contrast to the other groups, which showed a decrease of activation in the pre-post comparison (overall group effect p=0.032). The data indicate that during needle insertion high dose acupuncture stimulation leads to a higher increase of sympathetic nerve activity than low dose stimulation independent of personality. After needle insertion subjects who tend to augment incoming stimuli might show a lack of psychological relaxation when receiving high dose stimulation.

[Impressive picture of a melanosis coli after chronic anthraquinone laxative use--is there an increased risk for colorectal cancer?].

We report the case of a 74-year-old female with an extreme picture of melanosis coli of the whole colon after chronic use of anthraquinone laxatives for the treatment of constipation over many decades. Endoscopic work-up revealed an impressive deep black pigmentation of the whole colon mucosa which could be verified by histopathology as a widespread lipofuscin granulation. In addition, various adenomas but no colorectal carcinoma could be detected. The term melanosis coli describes a brown or black pigmentation of the colonic mucosa. Induction of melanosis coli by anthraquinone laxatives and their derivatives can be regarded as verified. The question if melanosis coli predisposes for colorectal neoplasia is discussed controversially. Based on the current literature, an association of melanosis coli between colorectal adenomas, but not colorectal carcinomas, is under discussion but the mechanisms to effect the development of colorectal neoplasia are not completely understood. Considering our case and the current scientific backround, we conclude that due to pharmaceutical side effects of anthraquinone derivatives such as electrolytic shift and water loss in addition to the risk of developing melanosis coli, anthraquinone laxatives should not be used for long-term therapy of constipation.

A functional GNAS promoter polymorphism is associated with altered weight loss during short-term fasting.

In mice, heterozygous knockout of the stimulatory G protein Gas results in obesity which suggests a key role of Gas in body weight regulation. We have recently identified a functional G(-1211)A promoter polymorphism in the human GNAS gene encoding Gas, the GG genotype being associated with increased promoter activity and lipolysis in vitro and increased weight loss capacity in vivo. The present study aimed to independently confirm these results. We genotyped 87 subjects who underwent a 7-day modified fast for the GNAS polymorphism and recorded weight, hunger, and mood. While both mood and hunger were not dependent on genotype, GNAS genotypes were significantly associated with weight loss (GG: -5.0 +/- 1.5 kg, n = 28; AG: -4.2 +/- 1.1 kg, n = 50; AA: -3.2 +/- 1.2, n = 9; p = 0.0003). The present study reconfirms our earlier reported findings and suggests that GNAS genotypes also influence weight loss during short-term fasting. related to a low vascular density (CD31 expression) in CDC.

Faecal S100A12 as a non-invasive marker distinguishing inflammatory bowel disease from irritable bowel syndrome.

OBJECTIVE: S100A12 is a pro-inflammatory protein that is secreted by granulocytes. S100A12 serum levels increase during inflammatory bowel disease (IBD). We performed the first study analysing faecal S100A12 in adults with signs of intestinal inflammation. METHODS: Faecal S100A12 was determined by ELISA in faecal specimens of 171 consecutive patients and 24 healthy controls. Patients either suffered from infectious gastroenteritis confirmed by stool analysis (65 bacterial, 23 viral) or underwent endoscopic and histological investigation (32 with Crohn's disease, 27 with ulcerative colitis, and 24 with irritable bowel syndrome; IBS). Intestinal S100A12 expression was analysed in biopsies obtained from all patients. Faecal calprotectin was used as an additional non-invasive surrogate marker. RESULTS: Faecal S100A12 was significantly higher in patients with active IBD (2.45 +/- 1.15 mg/kg) compared with healthy controls (0.006 +/- 0.03 mg/kg; p<0.001) or patients with IBS (0.05 +/- 0.11 mg/kg; p<0.001). Faecal S100A12 distinguished active IBD from healthy controls with a sensitivity of 86% and a specificity of 100%. We also found excellent sensitivity of 86% and specificity of 96% for distinguishing IBD from IBS. Faecal S100A12 was also elevated in bacterial enteritis but not in viral gastroenteritis. Faecal S100A12 correlated better with intestinal inflammation than faecal calprotectin or other biomarkers. CONCLUSIONS: Faecal S100A12 is a novel non-invasive marker distinguishing IBD from IBS or healthy individuals with a high sensitivity and specificity. Furthermore, S100A12 reflects inflammatory activity of chronic IBD. As a marker for neutrophil activation, faecal S100A12 may significantly improve our arsenal of non-invasive biomarkers of intestinal inflammation.

Disturbed in vitro adrenergic modulation of cytokine production in inflammatory bowel diseases in remission.

OBJECTIVE: Psychological stress has been implicated in the pathophysiology of both inflammatory and functional gastrointestinal (GI) diseases. The goal of this study was to address neuroendocrine modulation of cytokine production by peripheral blood cells in GI diseases. METHODS: We analyzed the in vitro effects of the beta-adrenergic agonist terbutaline and the glucocorticoid agonist dexamethasone on TNF-alpha and IL-10 production by LPS-stimulated monocytes in whole cell blood cultures in patients with inflammatory bowel diseases in remission (N=10), diarrhoea-predominant irritable bowel syndrome (IBS, N=12), patients with a recent gastroenteritis (post-infectious group, N=10), and healthy controls (N=15). RESULTS: In response to terbutaline, there was a significant increase in IL-10 production (concentration effect: p<0.05), which was diminished in IBD (group effect: p<0.01), comparable in IBS and controls, but enhanced in the post-infectious group (group x concentration effect: p<0.05). In contrast, terbutaline resulted in a concentration-dependent suppression of TNF-alpha production, which was comparable in all groups. Dexamethasone suppressed TNF-alpha production in a dose-dependent manner in all groups, but this effect was significantly more pronounced in post-infectious subjects (group effect: p<0.05). CONCLUSIONS: In IBD, disturbed adrenergic regulation of IL-10 could be part of the mechanism(s) underlying the modulation of disease activity by psychological stress. Diarrhoea-predominant IBS was not associated with altered adrenergic or glucocorticoid regulation of cytokine production by peripheral blood cells, whereas a recent history of gastroenteritis was associated with disturbed neuroendocrine modulation of cytokine production, which may play role in the pathophysiology of post-infectious IBS.

[Stress management in the treatment of essential arterial hypertension]. / Stressmanagement. Entspannung für Hypertoniker-- aktiv oder meditativ.

Between 60 and 90% of patients consult their family doctor for stress-associated complaints. Not infrequently, a considerable number of these patients already have elevated blood pressure. The positive effect on high blood pressure of relaxation techniques has been confirmed in various studies. Accordingly, stress management should now have a permanent place in effective antihypertensive treatment. Appropriate relaxation techniques include, for example, autogenic training, progressive muscle relaxation, visualization and breathing exercises, chi gong and yoga. These practices are incorporated in various lifestyle programs. They act in different ways, and can be offered to the patient in accordance with his/her individual wishes.

[Glycotoxins and cellular dysfunction. A new mechanism for understanding the preventive effects of lifestyle modifications]. / Glykotoxine und Zellaktivierung: Neuere Erklärungsmodelle zum Mechanismus präventiv wirksamer Lebensstilmodifikationen.

Recently the AGE-RAGE interaction was identified as a potential mechanism underlying chronic and inflammatory diseases like atherosclerosis, diabetes mellitus and kidney disease. Advanced glycation end products (AGEs) are the derivatives of glucose-protein or glucose-lipid reactions and are mainly generated from the diet (depending on intensity of heating, cooking time and oxygenation). Binding of AGEs or other ligands to the AGE receptor (RAGE) results in cellular activation, i.e. increased expression of inflammatory mediators and oxidative stress. Diet-derived AGEs thus induce deleterious effects on tissues and the cardiovascular system. Recent research also found that other lifestyle factors are associated with pronounced inflammatory activation, e.g. psychosocial stress and smoking. In addition, each intake of meals is associated with proinflammatory cellular changes. The AGE-RAGE model and investigations of the underlying cellular mechanisms thus may lead to a better understanding of the health benefits of diets (Mediterranean diet, uncooked vegetarian diets), caloric restriction and intermittent fasting. The clinical impact of low-AGE diets and fasting and the interaction between stress and food intake should be further investigated in controlled trials.

[Acupuncture: quo vadis?]. / Akupunktur -- quo vadis? Zur aktuellen Diskussion um Wirksamkeit und "Punktspezifität" der Nadeltherapie.

On the current discussion about efficacy and "point-specificity" of the needle therapy To improve the evidence base for acupuncture in pain treatment the German health insurance initiated the so called "Acupuncture randomised trials (ART)" and "German Acupuncture Trials" (GERAC) with a sample size of 300 (ART) and 1000 (GERAC) patients, providing a new dimension in acupuncture research. These studies have yielded data, which indicate that acupuncture is effective in the treatment of migraine, tension type headache, osteoarthritis of the knee and chronic low back pain. For the two latter indications acupuncture showed an even higher therapeutic response rate than conventional standard treatment. In migraine acupuncture showed an effect comparable to pharmacological treatment. The studies moreover indicate that the relevance of point-specific effects may have been overestimated concerning some indications. This article discusses the results of ART and GERAC, based on differentiating the mechanisms of action in acupuncture therapy. It is shown that the current data neither support the postulate of a "no-matter-where acupuncture" nor the irrefutability of the theorems of Chinese Medicine. Future studies will have to determine more precisely the mechanism by which the therapeutic effect of acupuncture is mediated. Furthermore, it will be necessary to find out more clearly in what diseases the location of needling represents the crucial part of the treatment and in what diseases rather different factors, like the intensity of stimulation or the doctor-patient interaction, are more relevant for the therapeutic effect. Research into acupuncture is still at the beginning. For this reason it should be avoided to draw premature and untenable conclusions from the current data.

Mediterranean diet has no effect on markers of inflammation and metabolic risk factors in patients with coronary artery disease.

OBJECTIVE: Mediterranean diet is associated with decreased levels of inflammatory markers and metabolic risk factors in epidemiologic studies and recent trials on patients with metabolic syndrome. Given the recent improvements in medical treatments, it is unclear if such beneficial effects are also present in patients with coronary artery disease (CAD). We therefore investigated the effect of Mediterranean diet on markers of inflammation and metabolic risk factors in patients with treated CAD. DESIGN: Randomized, controlled trial. SUBJECTS: A total of 101 patients (59.4+/-8.6 years, 23% female) with established and treated CAD (80% statins). INTERVENTIONS: Participants were assigned to a Mediterranean diet group (MG; n=48) with a 1-year program of 100 h of education, or to a written advice-only group (AG; n=53). Before and after intervention, we measured serum high-sensitivity C-reactive protein (hs-CRP), fibrinogen, fasting insulin, homocysteine, serum lipids and plasma fatty acids. RESULTS: The Mediterranean diet program increased the intakes of fish, fruits/vegetables and moderately of canola/olive oil and increased plasma concentrations of long-chain n-3 polyunsaturated fatty acids in the MG. Median hs-CRP and mean fibrinogen, homocysteine, fasting insulin, triglycerides and serum cholesterols remained unchanged in both groups. CONCLUSIONS: Adoption of a Mediterranean diet by patients with medically treated CAD has no effect on markers of inflammation and metabolic risk factors. SPONSORSHIP: Alfried Krupp Foundation, Essen, Germany.

Are national quality standards for traditional Chinese herbal medicine sufficient? Current governmental regulations for traditional Chinese herbal medicine in certain Western countries and China as the Eastern origin country.

Traditional Chinese herbal Medicine (TCHM) has been gaining interest and acceptance world wide. TCHM provides on the one side promising perspective of scientific interest and on the other side possible health risks if TCHM drugs are not controlled with respect to quality standards or if practitioners for TCHM are not well trained. This paper outlines an introduction to the scientific aspects and potential risks of TCHM therapy followed by a brief, exploratory overview of the current status of TCHM regulations in certain Western countries like the USA, United Kingdom, Germany, Australia and in China as the Eastern origin country of TCHM. Legal foundations to establish quality and safety standards for TCHM crude drugs and ready-made formulas exist in some countries on a local basis but in practice are poorly enforced, where this products have no drug status. In addition practitioners treating patients with TCHM should be well versed in the pharmacology, side effects, and interactions of these substances with Western medicines and should be certified on a regular basis.

[Effects of nutritional factors on haemostasis]. / Einfluss von Ernährungsparametern auf die Hämostase.

Among all exogenic factors nutrition has a most relevant impact on the haemostatic system and related cardiovascular and thrombotic disease. Whereas obesity and high-caloric diet are associated with negative changes of mostly all parameters of haemostasis, fibrinolysis and platelet reactivity, weight reduction and lifestyle modification induce respective beneficial effects. Recent studies demonstrate large evidence for the beneficial effects of a mediterranean diet in thrombotic diseases not mediated by cholesterol or weight reduction. The principal sources of fat within this diet, olive oil and omega-3 polyunsaturated fatty acids from fatty fish, nuts, seeds, and vegetables show a variety of beneficial effects on the haemostatic system in experimental and observational studies. Furthermore, for an increasing number of substances such as plant-based polyphenols and for moderate alcohol consumption attenuation of coagulation and platelet reactivity have been demonstrated. In the clinical context, mediterranean diet may exert its beneficial effects through synergistic action on haemostasis, endothelial function and vascular inflammation.

[Acupuncture in the treatment of pain--hypothesis to adaptive effects]. / Akupunktur in der Schmerztherapie -- Hypothese zu adaptiven Prozessen.

A basic principle in conventional pain therapy is that the treatment should be tailored to the pathological mechanism of the disease. This is based on the knowledge of the effector mechanisms of the applied treatment modalities. Although for acupuncture the mode of action still remains elusive in many parts, evidence about its mechanisms in pain treatment is growing. A better understanding of the hypalgesic effects of acupuncture might lead to a more differentiated and mechanism guided application. The aim of this article is to evaluate the scientific data about the neurobiological mechanisms of acupuncture in the treatment of pain. Data are critically evaluated regarding their relevance for clinical practice. Possible mechanisms are differentiated in local and systemic effects and the question of point specificity is discussed. Additionally a comprehensive hypothesis is set up for the long-term effects of acupuncture in the treatment of chronic pain. In this context acupuncture is considered as a mode of repetitive, nociceptive stimulation, which induces adaptive processes on different physiological levels leading to an improved ability of the nociceptive system to cope with painful stimuli.

[Health-related control belief and quality of life in chronically ill patients after a behavioral intervention in an integrative medicine clinic--an observational study]. / Gesundheitsbezogene Kontrollüberzeugung und Lebensqualität bei chronisch Kranken nach stationärer Behandlung mit Integrativer Medizin - eine Beobachtungsstudie.

BACKGROUND: In 1999 the Clinic for Internal Medicine and Integrative Medicine was founded in Essen as a regular part of the German inpatient health care system. Integrative medicine (standard internal medicine, evidence-based complementary and alternative medicine combined with intensified lifestyle modification) aims to help patients with chronic illness to cope with their condition more effectively and to achieve a health-promoting lifestyle. Techniques include cognitive restructuring, the elicitation of the relaxation response, and lifestyle education. The goal is to increase health-related quality of life (QoL) as well as control beliefs and to reduce morbidity in later life. AIM: To demonstrate changes in quality of life, lifestyle, and control beliefs after a two-week hospital stay. METHODS: Uncontrolled prospective observational study with 557 consecutive hospital patients. Outcome parameters were quality of life (SF36), control beliefs (GKU), and daily health-related behavior (nutrition, physical activity, relaxation) on admission, at discharge, as well as 3 and 6 months after discharge. RESULTS: Weekly physical activity increases by 29%, consumption of not recommendable foods decreases by 18%. The majority of patients (57%) engage in relaxation exercises 6 months after discharge (on admission 23%). The physical sum scale (SF36) increases from 33.9 (95% KI 32.5-35.3) on admission to 37.3 (35.8-38.9) 6 months after discharge, the mental sum scale from 41.2 (39.5-42.9) to 45.1 (43.5-46.7). The ratio internal/external control belief rises from 1.17 (95% KI 1.11-1.24) to 1.32 (1.24-1.40). Pretherapeutic ratio internal/external control belief and its increase are associated with rises in QoL. CONCLUSIONS: After integrative medicine treatment a lasting increase in QoL and lifestyle changes can be achieved. Reinforcement of internal control beliefs and own competence is possible and enhances outcomes in chronically ill patients.

Changes of cerebrovascular response to visual stimulation in migraineurs after repetitive sessions of somatosensory stimulation (acupuncture): a pilot study.

OBJECTIVES: To evaluate the effect of repetitive somatosensory stimulation (acupuncture) on cerebrovascular response in migraineurs by functional transcranial Doppler. METHODS: Changes of cerebral blood flow velocity in the right posterior and left middle cerebral arteries were measured by functional transcranial Doppler during visual stimulation (flickering light over 57 seconds) in 10 migraineurs before and after 10 acupuncture sessions. The same stimulation paradigm was performed in 10 control subjects. Cerebral blood flow velocity data were analyzed with a previously validated technique based on automated stimulus-related averaging. To evaluate the clinical effect of the treatment, a headache diary monitored the frequency and intensity of the migraine attacks. A positive treatment effect was defined as a reduction of at least 50% in the attack frequency or the mean headache intensity (or both). RESULTS: Before treatment, migraineurs showed overshooting cerebral blood flow velocity changes at the beginning and at the end of the stimulation and a delayed decline to baseline compared with control subjects. After treatment, this response pattern was significantly diminished (P

Effects of short-term modified fasting on sleep patterns and daytime vigilance in non-obese subjects: results of a pilot study.

BACKGROUND: Periodically repeated short-term fasting is a frequently practised tradition worldwide. Empirical reports suggest that during fasting periods the quality of sleep and daytime performance are improved. The effects of a home-based 1-week modified fasting on sleep patterns and daytime vigilance and performance were analysed in 15 healthy non-obese volunteers. METHODS: Sleep was measured by polysomnography before and after a 7-day fasting period; sleep inventories with assessment of daytime performance were collected throughout the observation period. Blood samples and urine were drawn at the beginning and at the end of fasting. RESULTS: 13 subjects (12 females, 1 male; age 41.2 +/- 13.4 years; BMI 23.9 +/- 4.2 kg/m(2)) completed the fasting period; weight decreased from 66.5 +/- 11.7 kg to 63 +/- 11.9 kg. Compared to baseline, a significant decrease in arousals, a decrease in periodic leg movements (PLM) and a non-significant increase in REM sleep were observed at the end of fasting. Subjective sleep ratings showed a fasting-induced increase in global quality of sleep, daytime concentration, vigour and emotional balance. Clinical laboratory tests showed a decrease in serum magnesium; urinary melatonin excretion decreased moderately. CONCLUSION: This open pilot study demonstrates that along with a decrease in sleep arousals a 1-week fasting period promotes the quality of sleep and daytime performance in non-obese subjects. The observed decrease in PLM might point to a nutritional modification of brain dopaminergic functions. In terms of evolutionary development, an improved daytime performance during periods of food deprivation could have been beneficial for the success in search for food.