Appetite, I Hardly Know Her (Pt. 2)

Before diving into this article, I suggest you read my primary research article published in “Geriatric Nursing,” and Pt. 1 of this series. Pt. 1 of this series gave a brief overview of the primary research I conducted, and Pt. 2 will give a brief overview of the biochemical implications (which was the basis of my Honors dissertation).

Considering that appetite is associated with both food intake and nutritional status, and that food intake and nutritional status are associated with function, focus must be placed on understanding the appetite regulation changes associated with aging. This will lead to the creation of proper intervention strategies to combat the anorexia of aging and its negative health outcomes. However, the creation of effective and efficient intervention strategies is difficult due to the multi factorial etiology of the anorexia of aging.

A brief mind-map of the etiology of the anorexia of aging. Figure was altered from its original format found in reference #9

Thus, for my Honors dissertation, I decided to focus on a biochemical approach to appetite regulation, and dig into why we tend to lose our appetite as we age, thereby resulting in the anorexia of aging.

Again, I am not going to go too deep into the weeds here, I am more than happy to share my very-technical thesis with you if you’d like. Instead, I will give you the 10,000 foot view of appetite regulation (a highly highly highly complex process that I even barely scratch the surface of in my thesis).

A great place to start is with a proper definition of appetite. I think of appetite as a drive to fulfill bodily desire through hunger, satiety, and satiation. Hunger promotes nutrient consumption, feelings of satiation (fullness) encourage meal termination, and satiety provides a feeling of fullness that persists in between bouts of hunger and satiation (1).

We can then distill appetite regulation into two complimentary pathways: 1)Homeostatic hunger, and 2) hedonistic hunger (I touched on both of these concepts in a previous article). As a brief recap, homeostatic hunger is driven by the internal and metabolic signals to maintain energy balance, whereas, hedonistic hunger is driven by environmental signals based on reward and desire to consume palatable food for pleasure rather than for metabolic maintenance (2–5). For the purposes of this article, I am primarily focusing on homeostatic hunger

Today, it is evident that homeostatic appetite is highly complex in the sense that a signaling pathway occurs between the digestive system, the endocrine system, the brain, and sensory nerves to modulate hunger, satiation, and satiety. However, homeostatic appetite can more simplistically be imagined as a system which is controlled by two complementary pathways. These pathways are effectively thought of as the anorectic pathway which functions by suppressing appetite (RED LIGHT), and the orexigenic pathway which functions by de-supressing appetite (GREEN LIGHT). These complementary pathways are centralized in the arcuate nucleus (ARC) of the hypothalamus and project to similar regions of the brain such as the lateral hypothalamus and paraventricular nucleus (6).

Within the ARC exists two distinct subsets of neurons. The first subset, referred to as AgRP-ARC neurons, express agouti-related peptide (AgRP), neuropeptide Y (NPY), and GABA (These are all neurotransmitters that have many downstream effects). This subset of neurons in the ARC modulate the orexigenic pathway and predominately function through inhibiting the anorectic pathway, thereby de-suppressing appetite (7). The second subset of neurons in the ARC, referred to as POMC-ARC neurons, express the peptide neurotransmitter pro-opiomelanocortin (POMC) and cocaine-amphetamine-regulated transcript (CART; again more neurotransmitters). This subset of neurons in the ARC modulates the anorectic pathway and functions primarily by activating neuronal networks that suppress feeding (6). The subsequent activation and inhibition of these distinct ARC neuronal populations are controlled by physiological signals that fluctuate with the body’s energy levels. The peptide hormone leptin (released from fat cells) is the main controller of the anorectic pathway, whereas ghrelin (released from A-like endocrine cells in the gut) is the main controller of the orexigenic pathway (8).

Ghrelin and leptin serve as the main controllers of the orexigenic and anorectic pathways respectively. The orexigenic pathway in the ARC (AgRP neurons) are stimulated by ghrelin. The anorectic pathway in the ARC (POMC neurons) are stimulated by leptin. Activation of the anorectic pathway suppresses appetite, whereas, activation of the orexigenic pathway de-supresses appetite through second-order neurons. This figure is from reference #9

Now that is really as far as I want to get into the weeds with the biochemistry (if you want the full picture, reach out to me at Adam.Plotkin49@gmail.com, and I can send you my Honors Thesis).

I know what I just threw at you was a lot, so here is a nice flow chart to help put your troubles at ease :)

Now appetite regulation is highly complex (and I cover a lot of the biochemistry in my thesis) but here is a simplistic way to look at things:

When ghrelin levels are high, ghrelin will stimulate the AgRP neurons causing a downstream effects which stimulates your appetite. When these AgRP neurons are stimulated, they also are able to inhibit the POMC neurons, thereby “removing the brakes” and further stimulating appetite. Whereas, when leptin levels are high, leptin will bind to POMC neurons, resulting in downstream effects that suppresses your appetite. Leptin also binds to AgRP neurons, but rather than stimulating these neurons, it inhibits them, thereby further suppressing our appetite.

So leptin and ghrelin can be thought of as Yin and Yang, as they try to balance our homeostatic appetite

Now there are a ton of other hormones and factors at play here, but if we stick with this simplistic view, we can start to see how appetite changes with age, thereby resulting in the anorexia of aging (see Pt. 1). In my Honors Thesis I discuss several factors that impact appetite as we age, but for the sake of this article, let’s talk about 3 key alterations: 1) chemo sensory, 2) gastrointestinal tract, and 3) gut-hormone secretion

I will briefly discuss these factors below(if you want the excruciating details, please let me know).

Chemo sensory: Alterations in chemo sensory detection of food plays a role in the suppression of appetite in the elderly population, thereby resulting in decreased food intake (10). The decreased craving to consume palatable and variable foods demonstrated in the elderly population is linked to a decline in taste and smell perception that accompanies the aging process (11). The decline in taste and smell perception in the elderly population is often enhanced by prescription drug interactions that may impact taste and smell perception (11). As of 2017, more than 350 drugs have been reported to impact the sense of taste and smell, (12). Additionally, according to the most recent National Nursing Home Survey taken in 2004, approximately 40% of residents living in a United States nursing home qualified as receiving nine or more medications (13). Therefore, residents in nursing homes are highly susceptible to detrimental drug-drug interactions that could alter chemo sensory pathways.

Gastrointestinal Tract: Modifications in the gastrointestinal tract play a role in decreased food intake in the elderly population (10). Elderly individuals require a longer period to digest the same nutrients as a younger individual, in which the extra distension placed on the antral stomach (portion of stomach that holds broken-down nutrients) is directly related to sensations of satiation (14–16). This delayed gastric emptying is typically a result of three overarching factors: 1) gastroparesis due to damage of the vagus nerve (disease in which the stomach cannot empty itself of food in a normal fashion), 2) increased antral distention, and 3) reduction in nitric oxide (a vasodilator that aids in the digestion process).

Gut Hormone Secretion: Modifications in the secretion of key anorectic and orexigenic gut hormones due to the normal aging process results in the suppression of appetite in elderly individuals. For instance, plasma ghrelin levels decrease during the normal aging process (10). This age-related decline in plasma ghrelin concentrations is in part due to the progressive deterioration of human gastric mucosa throughout the normal aging process (17). In contrast to plasma ghrelin decreasing with age, plasma leptin concentrations increase with age (18). The elevated leptin levels in elderly individuals are attributed to the secretion of leptin in concentrations proportional to fat mass (19–21). Thereby, as body-fat increases, so too does the secretion of leptin from adipocytes (fat cells). And of course, as we all know, the process of aging is linked with a continual increase in body fat mass and a loss of fat free mass (22). And here is the kicker: adults residing in Western societies on average experience a two-fold increase in body fat in between 20 and 60 years of age (23, 24).

So, what do we do with this information? Well in my article I make several propositions (some of which are covered below, but others have been omitted) that were specifically formulated for residents in a nursing home. I am happy to announce that after the publication of this research, and a presentation to the Board of Directors at this facility, they have implemented several of the practices Dr. Kovach and I recommended, and food intake has increased across the board.

Of course, these strategies can most definitely be implemented by any elderly community-dwelling citizen as well:

CNA= Certified Nursing Assistant (depending on the floor of the nursing home, the day of the week, and the meal, the number of CNA’s per meal varied widely, and it definitely was evident in the food intake of the residents).

Most of these are self-explanatory.

A “Feel Better Menu” was proposed because comorbid illness was associated with food intake. Therefore, if someone was ill, it would reflect in their food intake. Thus, I proposed a “Feel Better Menu” to include foods that have been associated with symptom relief and other benefits when ill. For example, chicken soup demonstrates a mild anti-inflammatory effect and is a great source of electrolytes and fluids (25), garlic can stimulate the immune system (26), and ginger is a known gastrointestinal and nausea remedy (27).

But there was one more piece of the puzzle that was left unsolved. To take a brief paragraph from my paper:

“Poor appetite was highly prevalent in our sample, which indicates a high number of residents who are at risk of 5% weight loss and may explain why the majority of our sample was either malnourished or at risk of being malnourished. Our sample had a much higher prevalence of poor appetite than previously described in the literature regarding geriatric inpatients (28). Our study included only people with dementia who may face many more food intake difficulties than older adults without dementia, thereby serving as a possible explanation for the high number of residents who are at risk of weight loss. In addition, our sample was taken from a single facility that follows kosher food practices. Kosher dietary laws are restrictive through the prohibition of certain foods and of mixing meat and milk (29). Residents may have trouble adjusting to new food practices such as a prescribed heart healthy diet, or not getting the food to which they are culturally accustomed. There are over 95 documented kosher-practicing assisted living facilities in the United States (30). This study suggests that future research is needed to determine if receiving a new prescribed diet or a diet that is culturally different for the recipient is associated with a higher rate of declined food intake or weight loss.”

There is a well-known “Anorexia of Aging Hierarchy” that is laid out in the literature. Previous research has demonstrated that community-dwelling elderly citizens are the least susceptible to significant weight loss with age, elderly residing in nursing homes are more susceptible, and elderly citizens residing in nursing homes who are diagnosed with dementia are the most susceptible. Yet, my study has uncovered a fourth layer to this hierarchy: Elderly individuals with dementia who reside in a nursing home with some form of dietary restrictions. Therefore, extra precaution must be taken, and based on my findings, I suggest we start by flagging residents with early signs of appetite fluctuations.

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Post-Baccalaureate research assistant in the Molecular and Clinical Nutrition Lab at the National Institutes of Health