Cephalic Response Research Articles

Biomedical gastronomy in the interventions of smell and taste disorders in ‘altered eating’

Biomedical gastronomy in the interventions of smell and taste disorders in ‘altered eating’

Biological Prescience: The Role of Anticipation in Organismal Processes.

Anticipation is the act of using information about the past and present to make predictions about future scenarios. As a concept, it is predominantly associated with the psychology of the human mind; however, there is accumulating evidence that diverse taxa without complex neural systems, and even biochemical networks themselves, can respond to perceived future conditions. Although anticipatory processes, such as circadian rhythms, stress priming, and cephalic responses, have been extensively studied over the last three centuries, newer research on anticipatory genetic networks in microbial species shows that anticipatory processes are widespread, evolutionarily old, and not simply reserved for neurological complex organisms. Overall, data suggest that anticipatory responses represent a unique type of biological processes that can be distinguished based on their organizational properties and mechanisms. Unfortunately, an empirically based biologically explicit framework for describing anticipatory processes does not currently exist. This review attempts to fill this void by discussing the existing examples of anticipatory processes in non-cognitive organisms, providing potential criteria for defining anticipatory processes, as well as their putative mechanisms, and drawing attention to the often-overlooked role of anticipation in the evolution of physiological systems. Ultimately, a case is made for incorporating an anticipatory framework into the existing physiological paradigm to advance our understanding of complex biological processes.

Nitroglycerine triggers triptan-responsive cranial allodynia and trigeminal neuronal hypersensitivity.

Cranial allodynia associated with spontaneous migraine is reported as either responsive to triptan treatment or to be predictive of lack of triptan efficacy. These conflicting results suggest that a single mechanism mediating the underlying neurophysiology of migraine symptoms is unlikely. The lack of a translational approach to study cranial allodynia reported in migraine patients is a limitation in dissecting potential mechanisms. Our objective was to study triptan-responsive cranial allodynia in migraine patients, and to develop an approach to studying its neural basis in the laboratory. Using nitroglycerine to trigger migraine attacks, we investigated whether cranial allodynia could be triggered experimentally, observing its response to treatment. Preclinically, we examined the cephalic response properties of central trigeminocervical neurons using extracellular recording techniques, determining changes to ongoing firing and somatosensory cranial-evoked sensitivity, in response to nitroglycerine followed by triptan treatment. Cranial allodynia was triggered alongside migraine-like headache in nearly half of subjects. Those who reported cranial allodynia accompanying their spontaneous migraine attacks were significantly more likely to have symptoms triggered than those that did not. Patients responded to treatment with aspirin or sumatriptan. Preclinically, nitroglycerine caused an increase in ongoing firing and hypersensitivity to intracranial-dural and extracranial-cutaneous (noxious and innocuous) somatosensory stimulation, reflecting signatures of central sensitization potentially mediating throbbing headache and cranial allodynia. These responses were aborted by a triptan. These data suggest that nitroglycerine can be used as an effective and reliable method to trigger cranial allodynia in subjects during evoked migraine, and the symptom is responsive to abortive triptan treatments. Preclinically, nitroglycerine activates the underlying neural mechanism of cephalic migraine symptoms, central sensitization, also predicting the clinical outcome to triptans. This supports a biological rationale that several mechanisms can mediate the underlying neurophysiology of migraine symptoms, with nitrergic-induced changes reflecting one that is relevant to spontaneous migraine in many migraineurs, whose symptoms of cranial allodynia are responsive to triptan treatment. This approach translates directly to responses in animals and is therefore a relevant platform to study migraine pathophysiology, and for use in migraine drug discovery.

Sham Feeding with Bacon Does Not Alter Transit Time or Complete Examination Rate During Small Bowel Capsule Endoscopy.

During capsule endoscopy (CE) studies, the complete examination rate (CER) can be increased by prolonging capsule battery life or reducing gastric transit time (GTT) and/or small bowel transit time (SBTT). However, despite enhanced battery life, 10% of studies remain incomplete. Previously studied interventions to reduce SBTT and enhance CER have produced conflicting results. We hypothesize that this may be a consequence of an insufficiently potent stimulus of small bowel motility. To examine whether potent stimulation of the cephalic response of digestion during small bowel CE reduces GTT and/or SBTT and thus increases the CER. A single-blind randomized trial was performed to evaluate the effect of bacon sham feeding on GTT, SBTT and CER. Baseline characteristics were similar between 63 sham fed patients and 59 controls. The median GTT was 17min (9-65) in the bacon group and 25min (14-55) in the control group. The median SBTT was 199min (119-316) and 222min (151-287), respectively. Cox proportional hazards model demonstrated no significant difference between groups for GTT (rate ratio 1.03, 95% CI 0.71-1.51, P=0.87) or SBTT (rate ratio 1.02, 95% CI 0.70-1.49, P=0.93). Although the taste of bacon was considered favorably by 72% of participants, taste did not correlate with GTT (ρ=0.03, P=0.83) or SBTT (ρ=-0.115, P=0.33). The CER was 91 and 95% in the bacon and control groups, respectively (P=0.35). Bacon sham feeding has no effect on GTT, SBTT or CER and cannot be recommended in clinical practice.

Non-Nutritive Sweeteners and Their Contradictory Effect on the Control of Energetic and Glycemic Homeostasis

Non-nutritive sweeteners (NNSs) gained attention as dietary tools that provide a free sweet taste of energy to foods. However, its health benefits have been questioned. The aim of this review is to present and discuss the effects of NNSs on energy and glycemic homeostasis, as well as the mechanisms involved. Recent studies in animals and humans have shown that consumption of NNSs appears to have a negative effect on the energy and glycemic homeostasis, promoting body weight gain, insulin resistance, and hyperglycemia. The hypotheses proposed to explain these effects are changes in the perception of taste sweet and weakening of the cephalic response, interaction of NNSs with sweet-taste receptors in the intestinal tract, and changes in intestinal microbiota. However, the determinants of energy and glucose homeostasis are diverse, which may explain in part the unclear effects evidenced in many studies. Therefore, other studies are important to clarify the conflicts between the safety of NNSs and metabolic disorders. J Endocrinol Metab. 2018;8(6):119-125 doi: https://doi.org/10.14740/jem547

Non-Nutritive Sweeteners and Their Contradictory Effect on the Control of Energetic and Glycemic Homeostasis

Non-nutritive sweeteners (NNSs) gained attention as dietary tools that provide a free sweet taste of energy to foods. However, its health benefits have been questioned. The aim of this review is to present and discuss the effects of NNSs on energy and glycemic homeostasis, as well as the mechanisms involved. Recent studies in animals and humans have shown that consumption of NNSs appears to have a negative effect on the energy and glycemic homeostasis, promoting body weight gain, insulin resistance, and hyperglycemia. The hypotheses proposed to explain these effects are changes in the perception of taste sweet and weakening of the cephalic response, interaction of NNSs with sweet-taste receptors in the intestinal tract, and changes in intestinal microbiota. However, the determinants of energy and glucose homeostasis are diverse, which may explain in part the unclear effects evidenced in many studies. Therefore, other studies are important to clarify the conflicts between the safety of NNSs and metabolic disorders. J Endocrinol Metab. 2018;8(6):119-125 doi: https://doi.org/10.14740/jem547

Bitters: Time for a New Paradigm.

In plant-based medical systems, bitter tasting plants play a key role in managing dyspepsia. Yet when it comes to defining their mechanism of activity, herbalists and pharmacologists are split between two theories: one involves cephalic elicited vagal responses while the other comprises purely local responses. Recent studies indicate that bitters elicit a range of cephalic responses which alter postprandial gastric phase haemodynamics. Caffeine and regular coffee (Coffea arabica semen, L.) increase heart rate whereas gentian (Gentiana lutea radix, L.) and wormwood (Artemisia absinthium herba L.) increase tonus in the vascular resistance vessels. Following meals increased cardiac activity acts to support postprandial hyperaemia and maintain systemic blood pressure. The increased vascular tonus acts in parallel with the increased cardiac activity and in normal adults this additional pressor effect results in a reduced cardiac workload. The vascular response is a sympathetic reflex, evident after 5 minutes and dose dependent. Thus gentian and wormwood elicit cephalic responses which facilitate rather than stimulate digestive activity when postprandial hyperaemia is inadequate. Encapsulated caffeine elicits cardiovascular responses indicating that gastrointestinal bitter receptors are functionally active in humans. However, neither encapsulated gentian nor wormwood elicited cardiovascular responses during the gastric phase. These findings provide the platform for a new evidence-based paradigm.

Alcohol and plasma triglycerides

This study reviews recent developments concerning the effects of alcohol on plasma triglycerides. The focus will be on population, intervention and metabolic studies with respect to alcohol and plasma triglycerides. Alcohol consumption and fat ingestion are closely associated and stimulated by each other via hypothalamic signals and by an elevated cephalic response. A J-shaped relationship between alcohol intake and plasma triglycerides has been described. A normal body weight, polyphenols in red wine and specific polymorphisms of the apolipoprotein A-V and apolipoprotein C-III genes may protect against alcohol-associated hypertriglyceridemia. In contrast, obesity exaggerates alcohol-associated hypertriglyceridemia and therefore the risk of pancreatitis. High alcohol intake remains harmful since it is associated with elevated plasma triglycerides, but also with cardiovascular disease, alcoholic fatty liver disease and the development of pancreatitis. Alcohol-induced hypertriglyceridemia is due to increased very-low-density lipoprotein secretion, impaired lipolysis and increased free fatty acid fluxes from adipose tissue to the liver. However, light to moderate alcohol consumption may be associated with decreased plasma triglycerides, probably determined by the type of alcoholic beverage consumed, genetic polymorphisms and lifestyle factors. Nevertheless, patients should be advised to reduce or stop alcohol consumption in case of hypertriglyceridemia.

Functionality of Fatty Acid Chemoreception: A Potential Factor in the Development of Obesity?

Excess dietary fat consumption is recognized as a strong contributing factor in the development of overweight and obesity. Understanding why some individuals are better than others at regulating fat intake will become increasingly important and emerging associative evidence implicates attenuated fatty acid sensing in both the oral cavity and gastrointestinal (GI) tract in the development of obesity. Functional implications of impaired fatty acid chemoreception include diminished activation of the gustatory system, the cephalic response and satiety. This review will focus on knowledge from animal and human studies supporting the existence of oral fatty acid chemoreception including putative oral detection mechanisms, and how sensitivity to fatty acids is associated with fat consumption and fatty food preference.

Expecting to Eat: Glucagon-Like Peptide-1 and the Anticipation of Meals

We have known for more than a century that the sight, smell, and taste of food can provoke a number of physiological responses referred to as cephalic because they are initiated by the central nervous system (CNS) and not by direct gastrointestinal contact with food (1,2,3). These responses can be elicited by previously arbitrary cues that have become associated with the presentation of food, including sounds or time of day (4). In this sense, cephalic phase responses are a physiological manifestation of an animal’s prediction that food is on the way. Cephalic insulin and pancreatic polypeptide responses have been among the most well studied, and such food-anticipatory secretions are observed in multiple species, including humans (3,5,6). A variety of evidence suggests that the function of these cephalic responses is to better prepare the organism to handle the influx of nutrients about to occur (7). Several studies support the idea that these cephalic responses are indeed required for an animal to be fully capable of ingesting large meals; in their absence, intake is reduced (8,9). In this issue, Vahl et al. (10) reported that we can now add glucagon-like peptide (GLP)-1 to the list. Using rats maintained on a highly restrictive meal-feeding schedule, which tends to exaggerate meal-anticipatory responses, they identified a robust premeal rise in plasma GLP-1 levels. Moreover, they showed that intake during that scheduled meal was reduced by blockade of GLP-1 receptors during the premeal period.

The addition of monosodium glutamate and inosine monophosphate-5 to high-protein meals: effects on satiety, and energy and macronutrient intakes

In a fed and orally stimulated state, whether the addition of monosodium glutamate (MSG) (alone or in combination with inosine monophosphate-5 (IMP-5)) to a high-protein (HP) meal leads to early satiety and a difference in energy intake at a second course was investigated. Ten men and twelve women consumed, in random order, a first-course meal consisting of: (1) water (control); (2) a HP meal with 0.6% MSG and 0.25% IMP-5; (3) a HP meal with no additives; (4) a HP meal with MSG only; (5) a sham-fed meal 2 (oral-stimulation). Appetite perceptions, plasma concentrations of glucagon-like peptide 1 (GLP-1), glucose and insulin, and energy intake at a buffet (i.e. a second course) were measured before and after each condition. Changes in appetite, and in GLP-1, glucose and insulin, were similar for the three fed HP conditions and all were greater (post hoc all P < 0.01) than the control and sham conditions. Energy intake was not different following the HP+MSG+IMP (1.86 (SEM 0.3) MJ) as compared with the HP+MSG-only (2.24 (SEM 0.28) MJ) condition (P = 0.08), or for the HP+MSG+IMP compared with the HP no-additives condition (1.60 (SEM 0.29) MJ) (P = 0.21). Following the HP+MSG-only condition, 0.64 (SEM 0.20) MJ more energy was consumed compared with the HP no-additives condition (P = 0.005). We conclude that the addition of MSG to a HP meal does not influence perceptions of satiety and it may increase energy intake at a second course. Cephalic responses after the sham condition were of similar magnitude to the control and therefore just tasting food is not enough to influence appetite and energy intake.

The growing case for an immunological component to irritable bowel syndrome

It is now generally accepted that irritable bowel syndrome (IBS) is a multifactorial condition with a variety of mechanisms being involved in its pathogenesis. In addition to psychological influences, which have probably been somewhat over-rated in the past, abnormalities of motility, visceral sensation as well as the central processing of noxious stimuli have been demonstrated [1]. The condition undoubtedly runs in families suggesting a genetic component and there is increasing evidence for the presence of low-grade inflammation in the gastrointestinal mucosa of at least a proportion of individuals. Dietary factors are also important and it is common for patients to complain that their symptoms are particularly troublesome following a meal. As a consequence they frequently conclude that they must have some form of dietary allergy, they certainly want to discuss the role of food in their condition and usually ask for a diet sheet. In addition, patients are now often seeking, finding and spending a lot of money on commercially available allergy tests of extremely questionable validity.

Dietary Synergies in Appetite Control: Distal Gastrointestinal Tract

AbstractWOODS, STEPHEN C. Dietary synergies in appetite control: distal gastrointestinal tract.

Satiety and substrate mobilization after oral fat stimulation

The aim of the study was to provoke cephalic and metabolic responses by oral fat stimulation with different high-fat meals in the postprandial state. A randomized parallel design was executed with three groups of subjects (twenty-six women and ten men; twelve subjects per group). Oral fat stimulation was achieved by the modified sham feeding (MSF) technique. Five hours after a high-fat breakfast, the subjects were given one of three test meals in random order: a high-fat lunch, water or the same lunch as the MSF. The main fat sources in the high-fat lunch and MSF were olive oil, linoleic oil and oleic oil. For 3 h after the test meal, blood samples were taken for analysis of metabolite, and visual analogue scales of appetite profile were completed. A cephalic response appeared to be achieved by MSF in that we observed a relative increase in insulin and glucose; this response lasted up until 90 min, indicating possible vagal stimulation. NEFA increased significantly after MSF compared with water ingestion in the case of olive oil (P<0.0001) and linoleic oil (P<0.05), but not with oleic oil. MSF provoked a significantly higher increase in triacylglycerol and glycerol levels compared with water ingestion in the case of linoleic oil (P<0.05). Satiety was significantly increased in the eating condition and in the MSF condition (P<0.0002, all oils) compared with water ingestion. We conclude that cephalic and perhaps vagal stimulation by different fats increased the concentrations of the metabolites and stimulated satiety, with linoleic oil showing the strongest response.

Effects of modified sham feeding on ghrelin levels in healthy human subjects.

The mechanisms involved in the preprandial rise and postprandial fall of circulating ghrelin levels are as yet unknown. Many hormonal and metabolic responses to nutrient intake begin during the cephalic or preabsorptive phase and are mostly mediated by the autonomous nervous system. The aim of the present study was to investigate the effects of the cephalic phase on ghrelin response to feeding in human subjects. The modified sham feeding (MSF), a well established technique in which nutrients are smelled, chewed, and tasted, but not swallowed, was used. Sixteen healthy volunteers (seven men and nine women; mean age +/- sd: 31 +/- 8 yr; body mass index, 22 +/- 3 kg/m(2)) were studied after overnight fasting. Seven of them received a standardized mixed meal, and nine underwent MSF. Blood samples for ghrelin, insulin, and glucose were taken at time -30, 0, 15, 30, 45, 60, 120 min during both tests. Pancreatic polypeptide determinations were evaluated at all times as markers of vagal activity only during MSF. Ghrelin levels significantly increased from time -30 to 0 min before the two tests, then significantly decreased: after the real feeding from 933 +/- 479 pg/ml (277 +/- 142 pmol/liter) to 455 +/- 185 pg/ml (135 +/- 55 pmol/liter; P < 0.05), and after the sham feeding from 917 +/- 313 pg/ml (272 +/- 93 pmol/liter) to 519 +/- 261 pg/ml (154 +/- 77 pmol/liter; P < 0.05). There were no significant differences between the patterns of the responses as evaluated by ANOVA (P = 0.863). As expected after MSF, plasma pancreatic polypeptide concentrations promptly increased from 58 +/- 29 pg/ml (14 +/- 7 pmol/liter) to 113 +/- 38 pg/ml (27 +/- 9 pmol/liter) at 15 min (P < 0.01). Both insulin and glucose levels increased during the actual mixed meal, whereas they were not significantly modified by MSF. In conclusion, circulating ghrelin concentrations are decreased by sham feeding as they are by real feeding in humans. These findings underline the importance of the cephalic response to nutrient intake, i.e. the role of vagal activity, in the control of ghrelin secretion.

Prolonged effects of modified sham feeding on energy substrate mobilization

Vagal stimulation in response to nutrients is reported to elicit an array of digestive and endocrine responses, including an alteration in postprandial lipid metabolism. The objective of this study was to assess whether neural stimulation could alter hormone and substrate metabolism during the late postprandial phase, with implications for body fat mobilization. Vagal stimulation was achieved by using the modified sham feeding (MSF) technique, in which nutrients are chewed and tasted but not swallowed. Ten healthy subjects were studied on 3 separate occasions, 4 wk apart. Five hours after a high-fat breakfast (56 g fat), the subjects were given 1 of 3 test meals allocated in random order: water, a lunch containing a modest amount of fat (38 g), or MSF (38 g fat). Blood was collected for 3 h poststimulus for hormone and metabolite analyses. Plasma insulin and pancreatic polypeptide concentrations peaked at 250% and 209% of baseline concentrations within 15 min of MSF. The plasma glucose concentration increased significantly (P = 0.038) in parallel with the changes observed in the plasma insulin concentration. The nonesterified fatty acid concentration was significantly suppressed (P: = 0.006); maximum suppression occurred at a mean time of 114 min after MSF. This fall in nonesterified fatty acid was accompanied by a fall in the plasma glucagon concentration from 122 to 85 pmol/L (P = 0.018) at a mean time of 113 min after MSF. Effects on substrate metabolism after MSF in the postprandial state differ from those usually reported in the postabsorptive state. The effects of MSF were prolonged beyond the period of the cephalic response and these may be relevant for longer-term metabolic regulation.

Intestinal motility.

This review covers the recent advances that have been made in intestinal motility. Failure to stimulate the cephalic response when enteral tube feeding via the nasogastric route is important in contributing to enteral tube feeding related diarrhoea, which cannot be initially overcome by the use of fibre containing feeds. Dysfunction of the nervous system and visceral hypersensitivity appear to be important in contributing to the symptoms associated with irritable bowel syndrome.

Interactions between postprandial thermogenesis, sensory stimulation of feeding, and hunger.

An early thermogenic response has been described following the ingestion of palatable food. This study was designed to investigate the possible relationship between this so-called cephalic response, the sensory stimulation of feeding, and the declining feeling of hunger as the meal progresses. O2 consumption, carbohydrate and lipid oxidation, as well as ratings of hunger were measured in four experimental situations in which the subjects, after overnight fast, ate either two small caramel cakes at one time or the same amount of calories divided in eight portions that were eaten at 10-min intervals. The third experiment, the sham-feeding experiment, was similar to the last one except that the food was spit out instead of being swallowed after being chewed. A control experiment was added in which no food was given but during which the subject mimicked the act of chewing as was done in the preceding experiment. A small increase in O2 consumed was observed in the control experiment. After the one-meal experiment, the increase was larger for the first 90 min and declined thereafter. During the first 40 min of the sham-feeding experiment, O2 consumption increased more than when the eight meals were eaten, indicating that during this period the sensory stimulation per se is responsible for the cephalic thermic response to food. At 90 min, the ratings of hunger were diminished not only in the eight meals experiment but in the eight sham meals experiment as well, showing the role of sensory stimulation in the control of hunger. These results indicate a possible causal relationship between the cephalic thermogenesis, the control of hunger, and the prandial sensory stimulations.

Effect of guar gum on insulinogenic and thermogenic response to glucose

A 300 ml glucose solution (300 calories) was ingested by nine healthy subjects following a 14 hour fast. On a second occasion the subjects took the same glucose solution to which was added 9 g of guar gum. Before and during 180 minutes following feeding oxygen consumption, respiratory quotient, and plasma glucose, insulin, C-peptide and catecholamine levels were measured. During the first thirty minutes after the meal, the thermogenic response was not affected by guar gum. This early cephalic response seem to be related to the in creased catecholamine secretion rather than to the meal composition. During the 30 to 180 minute postprandial period a significant diminution in the thermogenic response was observed when guar gum was fed with the glucose solution and this effect paralleled the marked reduction in insulin secretion as well as in the respiratory quotient increase.

A comparison of the effects of atropine on real-feeding and sham-feeding of sucrose in rats

In Experiment 1 the influence of atropine methyl nitrate on the sham-feeding response of adult female rats to sucrose solution was determined. Atropine (1 or 5 mg/kg) reliability suppressed the sham-intake of sucrose when the drug was administered 30 or 0 min prior to, or 17 min after the start of the feeding session. The suppressive effect was less, however, when the drug was administered 30 min before testing compared to the other two injection-test conditions. In Experiment 2 atropine failed to reliably decrease the real-feeding of a sucrose solution whether it was injected 30, 15, or 0 min prior to testing. These results were replicated in Experiment 3; atropine (0 min injection-test interval) reduced the sham-intake but not the real-intake of a sucrose solution. However, atropine decreased the rate of feeding under both real- and sham-feeding conditions. The fact that atropine reduced feeding rate but not meal size in the real-feeding condition was attributed to the drug's lack of effect on postingestive satiety. The present findings along with other recent results indicate that (1) the injection-test interval is a potentially important variable in studies involving atropine; (2) results obtained with sham-feeding animals do not always generalize to real-feeding animals; and (3) cholinergically-mediated cephalic responses are of questionable importance in the control of meal size.