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Amp Relay Questions

Taste and Smell in Cancer

The Cooking with Cancer Concept:

Taste and Smell in Cancer

Luis F. Pineda, M.D., M.S.H.A

Taste and Smell in Cancer

Introduction

With the aging process and prolongation of life, cancer is, and will continue to be, a major health issue. One of many, not the least important, yet critical problems, is the ability of patients with cancer to support normal nutrition.

Basic assumptions are that cancer, a state of abnormal cellular behavior, imposes a catabolic state on the individual.

Documented further by recent technological development of the PET scan, we are able to obtain images of cancer cell locations on the basis of the incorporation of radioactively labeled glucose as the result of their hyperactive metabolism. If the individual is unable to keep up to the demand on the basis of incorporation or intake of nutrients, then malnutrition and weight loss ensues. There is a possible participation of endogenously released cytokines such as Interleukins or a tumor necrosis factor.

Additionally, the cancer treatment modalities of today are causes of substantial changes to taste, smell, and appetite by either psychological trauma, neurochemical changes or inflammatory cytolytic damage to the mouth, nose, or gastrointestinal tract. Things are further worsened by cancer therapy complications, including infection, nausea, and vomiting.

Palliative modalities of pain control, use of narcotic pain medications such as codeine, morphine and analogs, which directly affect the central nervous system (limbic system), affect the function of the gastrointestinal tract causing severe constipation, nausea and vomiting. Most culinary literature available addresses these issues by attempting to minimize the smell of preparation, the temperature, and color. By this, I mean, historically it was recommended to consume white, cold, and non smelly foods versus hot, red, and smelly foods. By garnishing and coloring the food we can now impact the taste and intake and create appeal.

Most nutritional literature available addresses these issues by the drastic use of involuntary nutrition such as total parenteral nutrition or TPN, tube feeding via gastrointestinal infusion through nasogastric or percutaneous endoscopicly placed gastric tube (PEG). All of these are unappealing and excessively expensive interventions. The use of high calorie oral supplements such as puddings, bars, and boosters have failed despite their easy availability. This failure is due to patient intolerance, mostly because of the high carbohydrate content, which makes the products excessively sweet.

Appetite stimulants such as Marinol® (tetrahydrocannabinol) or Megace® (megastrol) have the disadvantage of causing mental status changes and sedation. They are exceedingly expensive, or in the case of Megace, there is an inability to use it in cases of hormone dependent cancers (ex. prostate cancer – a very common cancer in adult males). There is also the potential for abnormal blood clotting which is already heightened in cancer.

The management of cancer induced taste alteration should be aimed at maintaining optimal nutrition (Brodie 1998), but above all, quality of life.

Taste

Flavor is a complex mixture of sensory inputs (Smith 2001). Its components are gustation (taste), olfaction (smell, perhaps more important than credited), and tactile (mechanics of chewing). Traditionally described qualities of taste are sourness, sweetness, bitterness, and saltiness. Some others may exist, notably Umami, (Japanese translation “delicious”). This is most elicited by glutamate, an enhancer of taste commercially available as monosodium glutamate or MSG. In 1908, Ikeda from Japan, recognized it as the tasting chemical component of the brown algae soup Kombu. This Umami concept was developed by Chaudhari and Roper from the University of Miami in 1998. Loosely implying a “meaty” taste, this concept is still not widely accepted.

Most recent research has documented Umami receptors mediated via mGluR4 glutamate receptor, as well as mT2R8 denatonium receptors located in the mouth, glutamate related and cyclic AMP conducted via calcium channels. Sodium glutamate is a food enhancer that is very similar in taste to common cooking salt and definitely enhances the pleasantness of food by at least 50% or better at appropriate culinary levels (Yamaguchi, 1984). The main concern has been the flatulence and abdominal discomfort sometimes associated with it. It is blamed for obesity in oriental people and occasionally allergic reactions. Nonetheless, the significantly lesser amount of Sodium content when compared with regular cooking salt (65% less) has a potentially significant impact in hypertension management and can be a great benefit.

For years it was believed the tongue was the source of taste receptors, all selectively located by geography and specificity (i.e. sweetness located at the tip or sourness to the side).

The fact is that all the mouth, not only the tongue, possesses 72 receptors that are capable of responding to different stimuli regardless of the quality and nature. An example is the following salt receptor

diagram. It highlights the importance of the electrolyte channels and the electrical nature of the transmission.

Recent studies have described more specific receptors for tasting sensations and further research continues.

Taste buds, receptors and conductors will respond to a sensation in particular, but to all sensations to a certain degree. So, the receptor for sweet will respond to mostly sweet taste, but to bitter, sour, and salty to a lesser degree (Wickham 1999). The locations of the receptors are the tongue, soft palate, glossopalatine arch, and the posterior portion of the pharynx. Most taste receptors are located on the tongue. They are located within the papillae projection giving the tongue its velvety appearance. Several geographical areas on the tongue are identified. As shown, the tip is rich in mushroom like taste buds. The taste buds on the back of the tongue are flat circumvallates distributed in an inverted V. The taste buds on the lateral portion of the tongue are foliates. The filiform lack tasting receptors, yet provide tactile sensations. The concept of the geographic tongue (sweet, hot, salty) is no longer sustainable as each receptor is capable of reacting to more than one kind of stimuli 73 at a time. They are not unique to a given taste, nor are they geographically distributed as previously thought.

The taste buds contain about 50 to 100 taste cells. They are arranged in an onion shaped fashion with small microvilli poking through the opening at the top (taste pore).  The vehicle for taste is the saliva (Schiffman 1994). Tastants, or food chemicals dissolved in saliva, contact the receptors via the pore, activating the chemical G-protein (gustducin and transducin) receptors (ion channels) that transform into electrical impulses that are then sent to the brain.

The process of depolarization activates the receptors. The inside and outside of the cells are in constant electrical balance. In the case of taste receptors, they are negatively charged inside. The contact with the stimulating agent tends to neutralize or turn the inside positive. This creates a cascade of electrical current, which gets passed through the nerve line, the end of which releases a chemical neurotransmitter to communicate in relay to the next nerve cell until it arrives at its destination in the brain.

As the receptor, nerve line, relay points, and end stations are electrically activated they become unable to respond to another stimuli (taste) until delivery, and then become depolarized again. This is called the refractile or recovery phase. The impulses from the taste are then transmitted to the cerebrum via cranial nerves V, VII, IX, and X (Bender 1999).

 

Chorda tympani (CT) are the primary innervation pathway for the anterior tongue receptors in addition to providing the taste receptors structural and functional fitness (McCluskey 2002). Surgical alteration of the tongue leads to loss of sweet and salty receptors.  Surgery of the palate can alter sour and bitter receptors (Grant 2000). The final receptor, thought to be the parietal operculum near the Rolando’s fissure, is now believed to be mostly located in the insula (This 2005).

The likelihood is that there is not a single taste center in the brain, but it is likely the electrical interaction of many areas allowing the brain to construct a global sensation.

Smell

Smell has played a very special role in the natural evolution of animals, especially the mammals. Many of them are nocturnal and they had to depend on olfactory guidance to detect food, avoid predators, recognize territories, social groups, and even sexual contact (McGee 1984).

 

The human olfactory area is approximately 16 square centimeters as compared with almost 150 square centimeters in dogs. S mell and taste cannot be separated. “Smell and taste form a single sense, of which the mouth is the laboratory and the nose is the chimney. To be more specific, of which, one serves for the tasting of actual bodies and the other for the savoring of their gases” (Brillat-Savarin 1994).

Little has been known about smell until recent years.  Researchers have earned two major Noble prizes in physiology and medicine (Linda Buck and Richard Axel 2004) by defining the olfactory receptor protein as shown.

This system still depends on receptor activation, transmission of electrical impulses via cyclic AMP (amino mono phosphate), and electric exchange interaction with sodium exchange.

Often misunderstood, the act of smelling does not happen exclusively by inhaling aromas via the nose, but rather by a pheromontal action. This mixture of combined saliva, product, and evaporation penetrates the back of the nose via the back soft palate and activates the smell receptors.

The human sense of smell depends on the functioning of cranial nerve I or the olfactory nerve, for qualitative odor sensations such as the smell of roses, lemon or grass and the ophthalmic and maxillary portions of cranial nerve V the trigeminal nerve for somatic sensory overtones of odorants such as warmth, coolness, sharpness, and irritation.

 

The olfactory neuroepithelium is located over the cribiform plate, the superior septum and a segment of the superior turbinate and is rich in smell receptors.

As in the case of taste, odors attach to and dissolve within the covering mucus layer to obtain contact with the receptors (Doty R.L. Bromley, S.M. 1997). Taste, smell, and other impulses will make their way via nerve conduction to the brain where the ultimate arrangement of impulses gets coded for the final perception.

Thermal and Mechanical Receptors

Other minor receptors include:

• Mechanical: tactile sensing of texture (crunchy, soft, hard,

dry, wet)

• Thermal: temperature sensation

All of this is aided by mastication, the mechanical dismembering of the food bolus into smaller particles capable of being mixed with saliva, and the carrying of particles to contact the taste receptors via fluid or smell receptors via gases (pheromontal). The process of mastication reduces the size of the particles to be swallowed and mixes the saliva to bind all together in a safe bolus. This mixes the food for better exposure to digestive enzymes.

Most people will chew about twenty times before swallowing; however, under normal circumstances the more likable the food the longer the mastication as a source of pleasure. The slower and longer the mastication, the more opportunity for odorants, which are volatile molecules, to travel up to the smell receptors via the back of the mouth. This is relevant for the chewing gum industry.

Enhancers

Peppers are used in many cultures as a flavor enhancer. Capsaicin, the active substance in peppers, increases the blood flow to the mouth and activates VRI receptors, a membrane channel protein, which exchanges calcium in and out of the cells. Capsaicin has four different subunits, which located in different sites of the mouth, count for the different effect in flavor by different kinds of peppers.  Being fat soluble and heat sensitive improves the taste for fatty foods.  Peppers are, if nothing else, taste enhancers. Their physiological function is based on three principles.

 

• An overwhelming inducer of blood supply to the mouth (please

note to yourself what happens when exposed to a minimal amount of

peppers on your lips) that causes an increased production of saliva,

a vehicle to the distribution of elements of flavor in the mouth, and

rapid heart rate with an increase in bronchial secretions and indices

perspiration (cooling effect).

• They are depolarizers of the electrical charges to the taste and smell

receptors.

• They are a direct stimulant of the brain via pain sensory pathways.

This is done by reducing the availability of substance P and

increasing levels of prostaglandins, both crucial elements of the

inflammatory human response.

 

All these enhance the brain capacityy for taste and smell. Thismakes the act of eating more pleasurable.

Well known to other cultures, such as Latin America (jalapeno, ancho), India (sanaam, dundicut), and China (tien tsin pepper), the use of chilli peppers is intrinsically part of the culture.

Chilli peppers, originally from Latin America, were used by Maya, Inca and Aztecs. Chilli peppers were taken to the old world by Christopher Columbus as a substitute to the better-known peppers.  The medicinal effects were recognized early on by pre-Columbian Mayan. They prepared chillatolli, maize flour mixed with chilli, for all kinds of respiratory ailments. The Aztec would use the direct fruit for toothache pain control. Tukano Indians in Colombia used it for the treatment of hangovers and Mayans and Aztecs as infection control for open wounds.

The assumption that peppers are an anti-cancer chemical is less important. They are otherwise well recognized as a pain controller and widely used in the United States of America as a localized anti-arthritis medicine. Peppers are not just “hot” they are used as flavor enhancers, for example Paprika.

They are all graded in the intensity of the heat according to the Scoville Heat Unit System (Wilbur L. Scoville 1912). This scale is human rated so consequently, this is subjective and liable to human error. The scale establishes pungency by dilution and testing. In essence, they attempt to document the number of dilution times in a neutral liquid where a normal human being can no longer detect the bite. The most scientific measurement is a high performance liquid chromatography which extracts and measures capsaicinoid chemicals.

SCOVILLE HEAT UNITS SCALE

The following is a list of chiles, put into a scale to show the relative pungency levels and their Scoville Heat Units.*

Name Pod Type Species Scoville Units

Orange Habanero Habanero C. chinense 210,000

Red Habanero Habanero C. chinense 150,000

Tabasco Tabasco C. frutescens 120,000

Tepin Tepin C annuum 75,000

Chiltepin Tepin C. annuum 70,000

Thai Hot A sain C. annuum 60,000

Jalapeno M Jalapeno C. annuum 25,000

Long Slim Cayenne Cayenne C. annuum 23,000

Mitla Jalapeno C annuum 22,000

Santa Fe Grande Hungarian C. annuum 21,000

Aji Escabeche A ji C. baccatum 17,000

Long Thick

Cayenne Cayenne C. annuum 8,500

Cayenne Cayenne C. annuum 8,000

Pasilla Pasilla C. annuum 5,500

Primavera Jalapeno C. annuum 5,000

Sandia N ew Mexican C. annuum 5,000

NuMex Joe E. Parker N ew Mexican C. annuum 4,500

Serrano S errano C. annuum 4,000

Mulato A ncho C. annuum 1,000

Bell Bell C. annuum 0

 

Capsaicin

Chemical Structure of is the most widely recognized chemically active ingredient in chilli peppers. Contrary to popular belief, the heat is not located in the seeds, but in the placenta, which are little sacs located in the inner wall of the fruit. When opening the fruit they tend to splash into the seeds since they are very fragile and easy to rupture.  Capsaicin binds directly to the receptors in tasting but can be unbound by casein, a protein obtained from milk, beans, nuts, and chocolate that is used as a moderator of pungency.

To date, there are fourteen different capsaicins namedcapsaicinoids. Each one has a quite unique and characteristic property on the nature of the bite, the location in the mouth that gets activated, and the duration of its action.

• Nordyhydrocapsaicin gives a mellow warming effect, rapidly on

and off, mostly at the front of the mouth and the palate.

• By comparison, dihydrocapsaicin is more potent and affects the

middle of the mouth and palate.

• Homohydrocapsaicin is a harsh, sharp irritant, with a slow onset

but a longer duration at the throat and back of the tongue.

Likewise, heating of the tip of the tongue produces a sweet taste,

while cooling elicits a sour sensation.

Taste and Smell Behavior

 

Most flavor preferences and aversions are learned. There is an innate liking to sweetness perhaps associated with common eating of fruits, and a disliking to bitterness that is mostly associated with poisonous and bitter alkaloids. Social customs, opportunities, and private associations with pleasant and painful moments are imprinted from early childhood. This has been experimentally exemplified in well-known studies such as the case of Pavlov and his experiences with dogs. There are repeated reports of food “cravings” rich in needed fundamental electrolytes or nutritional items. For example, water and salt in dehydration, water and carbohydrates in cases of Diabetes Mellitus, and pregnancy cravings.

Preabsorptive Satiety refers to the point in time when a sense of fulfillment of eating arises. Several mechanisms are believed 82 associated with this since the actual biochemical satisfactions of need cannot be corroborated, so pressure receptors in the wall of the stomach, chemical receptors in the wall of the intestine, or downgraded affinity of the tasting receptors via blood glucose has been sited (this could be nonetheless overridden by cultural pressures, for example obesity in the USA). It is unclear why someone becomesfull after a meal or why a given desired food intake becomes sickening when taken in excess.

Pathophysiology

The life span of a taste cell is approximately ten days. Because of this rapid proliferation, they become highly susceptible to cellular destruction during chemotherapy (Strohl 1984). In cancer patients in general, there is a higher taste threshold as a result of a decrease in the number of taste buds (Stubbs 1989)

Cytokines are proteins manufactured by the body. They influence the cellular behavior by inducing specific cellular functions. Cancer drives up the production of them (Interleukins, tumor necrosis factor).

They are known for lowering the threshold for bitter sensations(Davidson 1998).

Radiation therapy to the head and neck area is known to cause alteration of taste: initially at 20Gy (the unit of measurement in radiation) you experience alteration of taste. This increases 50% at 30Gy and Becomes permanent at 60Gy (Madeya 1996). Radiation directly reduces the number of taste buds and damages the 83 microvilli of the cells. Initially this impairs the bitter and salty sensations and later to a lesser degree the sweet taste (Mossman K.1978).

Chemotherapy, on the other hand, lowers the threshold for bitter tastes and increases it for the sweet tastes (Madeya 1996). Many patients complain about a metallic taste. The main offending agents are Nitrogen Mustard, Cisplatin, Cyclophosphamide, and Doxorubicin.  Repeated adverse reaction to chemotherapy has been known to develop into a behaviorally adverse reaction by the patient according to Pavlov’s mechanism (Bender 1999).

 

Damage by chemotherapy:

Mucositis

Damage by Infections:

Herpes Zoster Infection

Damage by Radiation Therapy:

Osteonecrosis

 

Does it make any difference?  Beyond the issue of pure quality of life and the enjoyment of eating, would nutrition make any difference? For most anyone, including medical or neophytes, the answer is yes. Usually, this question is not primarily addressed and sometimes priority is the second or third tier in nutritional importance.

 

Food for thought:

• The fundamentals are misunderstood in importance.

• The Positron Emitting Tomography (PET scan), the up-to-date technological tool in oncology, precisely depends on the cellular utilization of glucose by cancer cells.

• In 1998 a double blind, random study with a small sample, showed that administration of zinc sulfate three to four times per day restored not only the acuity of taste but also slowed the worsening of taste alterations and taste bud anatomy (Ripamonti 1998).

• Monosodium Glutamate, commonly used in oriental food, is becoming a good candidate as a “flavor enhancer”, not only because of its salty taste but it stimulates Umami, the latest recognized taste, triggering release of glucagons and insulin (This 2005).

Alcohol and Health

The relationship between alcohol and health has been long-lived and controversial. For years medical schools have taught students the serious adverse effects including alcoholism and its social consequences, as well as the more physical impacts including liver cirrhosis and fetal alcohol syndrome.

For moderate drinkers, indications show a mortality rate 16% lower than the 28% seen in non-drinkers (Boffetta, Fuchs). The National Institute on Alcohol Abuse and Alcoholism has established the greatest longevity with the consumption of one to two drinks per day (Ellison 1993). A drink is defined as a five-ounce glass of wine, one ounce of hard alcohol or one can of beer.

The most protective effect is on the cardiovascular and circulatory systems by increasing levels of HDL (high density lipoprotein) or the good cholesterol, decreasing thrombosis, reducing fibrinogen, increasing fibrinolysis and reducing arterial spasm during stress (Paassilta 1998).

 

Moderate alcohol consumers suffer a lesser number of heart attacks and arteriosclerosis. They have a lower risk for dementias including Alzheimer’s disease (Mukamal 2003), and there is a lower incidence for metabolic syndrome (Matthew 2004). They all seem associated with the presence of resveratrol, a phytoalexin chemical found in the skin of the red grapes used in the production of red wines.

For our purposes, alcohol seems to have an enhancing property to appetite and taste, interestingly enough, by enhancing the sense of smell.

Food Chemistry

What healthy people like:

• Taste of fat (concept of marveling)

• Taste of sugar (concept of caramelizing)

Recommendations:

• Because of the described metallic taste, use plastic utensils

(Stubbs 1989).

• Patients should eat small and frequent meals throughout

the day (Sherry 2002).

• Chilled or frozen foods are more acceptable than warm food

(Brodie 1998).

• Mouth care is of crucial importance (Sherry 2002).

• Provide rapid shifting tastes:

1. By enhancing receptors activities (chilli pepper).

2. By cleansing of receptors

a. (ginger/pickles)

3. By use of sauces of the nature of coulis

(fruit based sauce with no fat)

• Portions should be small.

• Presentation should be simple and colorful.

• Drink a glass of red wine before a meal. (Alcoholic beverages

are used as an appetite stimulant.)

Disclaimer

This paper is not intended to be a scientific presentation in as much as a compilation of information and ideas in the attempt to improve quality and perhaps quantity of the lives of patients afflicted by cancer.

The hope is to provide a simple, superlative, and better quality of life to patients afflicted with cancer.

Personal Statement

My quest in taste and smell in patients afflicted with cancer has been accomplished with the help of God and those patients for whom this manuscript is dedicated and intended.

http://www.cookingwithcancer.org

 

Bibliography

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