Overview of the Cephalic Phase Response

Ph ysiological responses to eating episodes are divided into three phases, referring to the part o f the digestive system being stimulated by food: namely the cephalic, gastric and intestinal phases. Th e cephalic phase relates to pre-absorptive effects w h ile gastric and intestinal phases relate to post-ingestion effects o f fo od intake (G iduck et al., 1987, Zafra et al., 2006).

Th e cephalic phase response is initiated by food-related sensory stimuli including the thought, sight, smell, taste and chew ing o f food, and occurs before and during the first moments o f an eating episode (Feldm an and Richardson, 1986, T e ff, 2000). These

effects arise from vagal cholinergic signalling and have been shown to initiate a variety o f autonomic and endocrine responses linked to digestion, absorption and m etabolism (summarised in Table 1.13).

T able 1.13. O verview o f the main physiological responses triggered durin g the cephalic phase. Adapted from (Robertson, 2009), (Zafra et al., 2006) and (P o w e r and

Schulkin, 2008)

Site Response(s) Cephalic Function(s)

Oral cavity f salivation •Lubricate food, start starch & fat digestion (amylase & ligual lipase in saliva), dissolve food particles to be transported to taste buds

Stomach t gastric acid secretion t gastric motility t gastrin levels

f pre-prandial ghrelin levels

t leptin mucosal secretion

• Hydrolysis & breakdown o f food

• tgastric emptying rate -> regulate food passage • Stimulate gastric acid secretion

•R ise stimulates appetite. H owever postprandial suppression rapidly follows (i.e. inhibit appetite) • M a y inhibit CHO absorption, promote small peptide

absorption, reduce appetite

Small t intestinal motility • Regulate food passage

intestine _{t absorption water, glucose}

t motilin

• Feed-forward mechanism •Stimulate intestinal motility

Large t intestinal motility •Regulate food passage

intestine _{t neurotensin • Unknown}

Pancreas t insulin release • Anticipatory metabolic role

f digestive enzymes ©Digest protein, CHO, fat

t bicarbonate secretion • Neutralise stomach acid

t glucagon release ©Unknown. M ay t postprandial thermogenesis & or

prevent C PIR induced hypoglycaemia

t PP release • Cephalic phase role unknown

Liver t V L D L levels • Cephalic phase role unknown 1 N E F A levels (suppressed by

C PIR )

•M a y enhance glucose metabolism in insulin sensitive tissues

Adipose Tissue

t L P L expression (stimulated by C PIR )

•Probably in preparation for imminently incoming nutrients

Vasculature t intestinal blood flow •Probably in preparation for imminently incoming nutrients

t cardiac output, heart rate •Cephalic phase role unknown

Other t cephalic phase thermogenesis

• M a y arise from actions o f cephalic phase hormones (e.g. insulin, glucagon)

The cephalic response is thought to be a “ feed-forw ard” effect “ prim ing” the G IT and m etabolic processes in preparation fo r im m inently incoming nutrients (Robertson, 2009, Zafra et al., 2006). Cephalic initiated responses are more rapid in onset, shorter-lived and low er in magnitude than gastric and intestinal phase responses (Robertson, 2009, Zafra et al., 2006).

Th e concept o f cephalic phase responses were first introduced in the classical experiments o f P avlov, w ho documented anticipatory salivary and gastric secretions occurring in response to the sight and sm ell fo o d or even just the expectation o f feeding in dogs (P a vlo v, 1902).

Experim entally, sham feeding and m odified sham feeding (M S F ) are the most com m only used methods to investigate cephalic phase responses. In early sham feeding experiments, animals w ere fitted with a gastric or oesophageal fistulae allow in g fo o d to be eaten but not absorbed from the small intestine. These studies have provided much evidence regarding cephalic phase processes, how ever this m odel does not allow researchers to differentiate between responses arising from receptors in the mouth, or further down in the oesophagus or stomach (Robertson, 2009, Zafra et al., 2006).

Th e M S F (or “ chew-and-spit” ) technique, which involves chew ing and tasting but not sw allow ing food, was developed to investigate cephalic phase responses in humans (Richardson et al., 1977). Th e M S F technique allows researchers to selectively investigate oral vagal activity, avoiding pharyngeal and oesophageal receptors (Robertson, 2009). H o w e v e r as fo o d is not sw allowed the influence o f cephalic responses on subsequent nutrient handling is not so clear (T e ff, 2000). T o overcom e this, M S F is often coupled with intragastric nutrient delivery or intravenous glucose (T e ff, 2000, LeBlanc, 2000).

Saliva is the first cephalic secretion and is secreted into the oral cavity both prior to eating in response to visual and olfactory stimuli and also once fo o d is being tasted and chew ed (Giduck et al., 1987, Robertson, 2009), with taste and chew ing inducing higher secretion levels (Mattes, 1997). Indeed, as demonstrated by P a vlo v, salivary output increases even at the mere thought o f fo o d (P a vlo v, 1902), and favourite foods are often described as being “ mouth watering” (Mattes, 2000). The quantity o f saliva produced in anticipation o f a meal has been found to be correlated with hunger ratings and the rated palatability o f the fo o d (W o o le y and W o o le y , 1973).

Saliva acts as a lubricant and protects the oral mucosa during chewing, aiding mastication, bolus formation and sw allow ing. In addition, saliva contains enzymes such as amylase and lingual lipase fo r initial digestion o f starch and fats respectively (Mattes, 2000, Pedersen et al., 2002). O f importance, saliva acts as a solute so nutrients are dissolved allow ing them to be transported to taste buds to stimulate taste receptor cells, thereby facilitating taste perception (Pedersen et al., 2002).

Taste is important in identifying potentially harmful and toxic compounds and, in addition to mastication and sw allow ing, is the main stimulant o f salivary production (Pedersen et al., 2002, Mattes, 2000). Th e type o f gustatory stimulus influences saliva volum e and composition, with a sour/acidic (e.g. lem on ju ice) or bitter (e.g. quinine) taste potently stimulating salivary flo w and a sour/acidic taste increasing protein levels in saliva (Davenport, 1982, Robertson, 2009). Increased salivary flo w in response to bitter or acidic tastes m ay have evolved as a protective mechanism to dilute or clear potential toxins, irritants or other dangerous substances from the mouth (Robertson, 2009, Mattes, 2000).