Combating malnutrition and cachexia is a core challenge in oncology. Protein is an important building block for our bodies and is especially important for cancer patients because cancer treatment can be hard on the body. To limit muscle mass loss, the use of proteins in cancer is encouraged by experts in the field.
The Role of Protein in Cancer Patients
Cancer treatment can cause unwanted weight loss due to a decrease in muscle mass. This can make you frail and less responsive to treatment. When you’re going through cancer treatment, it can be hard to get enough protein sometimes.
The prevalence of malnutrition among patients with cancer is about 20% and can reach more than 70% depending on patient age, cancer type, and cancer stage. Both ESPEN and ESMO recommend implementing appropriate nutritional support in cancer. They reported many clinical or methodological concerns which prevented drawn definite conclusion.
Protein Intake Recommendations
Protein needs vary from person to person. To calculate how much protein you need based on your weight, divide your weight in pounds by 2.2 to convert to kilograms. The average healthy person requires about 0.8 grams of protein per kilogram of body weight for maintenance. It's best to spread out your protein throughout the day. Aim to consume around 25 to 30 grams of protein at a time, so your body has time to use it.
The Debate Around High-Protein Diets
The use of proteins in cancer is still debated due to their antagonist effects. Indeed, a high protein intake could preserve lean body mass but may promote tumour growth, whereas a low‐protein diet could reduce tumour size but without addressing cachexia.
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From a mechanistic point of view, there is a strong rationale to increase the protein intake of patients. While this approach could be beneficial for the patient, it could also be beneficial for the tumour: if increased dietary protein intakes induce an increased protein synthesis in the tumour, via the same mTOR signalling, it could thereby promote tumour growth. However, adopting this dietary strategy could have harmful consequences for patients, by worsening their undernutrition and cachexia status.
Research on Protein Intake and Cancer
To date, to the best of our knowledge, the impact of the amount of protein ingested in both muscle wasting and tumour growth has never been evaluated in a realistic research model involving cancer and chemotherapy. To addresses this gap, researchers evaluated the influence of different protein diets on muscle wasting, tumour growth and immune system response in a tumour‐bearing rat model undergoing chemotherapy. The objective of this work was to gain a firm understanding of the effect of protein intake in oncology and determine the optimal dose of protein that would reduce cancer cachexia to minimum while minimizing tumour growth.
Experimental Setup
Seventy-eight female Fischer 344 rats (10-12 weeks old, 130-160 g) were housed for the 8‐day acclimatization period at six per cage in a temperature‐controlled facility (22 ± 2°C) on a 12 h light/dark cycle. This preclinical model involving tumour and treatment (i.e chemotherapy) is a realistic one. Interestingly, it is closer to malnutrition observed in cancer patients.
Seventy ‘cancer + chemotherapy’ rats (‘C + C’ rats) were injected with Ward colon tumour. The other rats constituted the healthy control group without tumour or chemotherapy (‘Ctrl’, n = 8). As tumour growth is heterogeneous, each C + C rat group was composed of 14 rats. Tumour volume was measured every day in three dimensions with a calliper to determine length (L, cm), width (W, cm) and height (H, cm).
After a 1‐week acclimatization period (D‐14), 70 11‐week-old female fisher rats received tumour injection (C + C rats). One week later (D‐7), all the animals (n = 78) received the normal‐protein diet. Then, after 13 days of tumour growth (D‐2), the rats received either the normal‐protein diet (NP16%, n = 14) or a low‐protein diet with 8% protein (LP8%, n = 14), a low‐protein diet with 12% protein (LP12%, n = 14), a high‐protein diet with 24% protein (HP24%, n = 14) or a high‐protein diet with 32% protein (HP32%, n = 14).
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Two days later, the first chemotherapy cycle was initiated: irinotecan (CPT‐11; 50 mg/kg; dark grey arrow) at D0 and 5‐fluorouracil (5‐FU; 50 mg/kg; light grey arrow) at D1. One week later, the rats received the second cycle of chemotherapy (CPT‐11 at D7 and 5‐FU at D8). The tumour was treated with a combination of irinotecan (7‐ethyl‐10‐[4‐(1‐piperidino)‐1‐piperidino]carbonyloxy‐camptothecin; CPT‐11) and five fluorouracil (5‐FU) solutions.
After 12 days of tumour growth, when they had reached approximatively 1 cm3, the C + C rats were divided into five groups according to body weight and tumour size, to ensure homogeneity in the five groups at that time of the study. The Ctrl group and one C + C group (‘NP16%’, n = 14) still received the normal‐protein diet, which contained 16% protein. Two C + C groups received a ‘low‐protein’ diet with either 8% protein (‘LP8%’, n = 14), that is, 50% of the protein content of the normal‐protein diet, or 12% protein (‘LP12%’, n = 14), that is, 75% of the protein content of the normal‐protein diet. The last two groups received a ‘high‐protein’ diet with either 24% protein (‘HP24%’, n = 14), that is, 150% of the protein content of the normal‐protein diet, or 32% protein (‘HP32%’, n = 14), that is, 200% of the protein content of the normal‐protein diet. All the diets were available ad libitum.
Tumour‐bearing and healthy control rats were housed in individual cages in order to perform food intake measurement. As explained above, Ward colon tumour‐bearing rats were fed with isocaloric diets with low protein diet with 8% (LP8% group) or 12% (LP12% group) of caloric intake from protein, with standard diet with 16% (NP16% group) of proteins, or with high protein diet with 24% (HP24% group) or 32% (HP32% group) of proteins. Two days after, they received one cycle of chemotherapy, consisting of an injection of CPT‐11 (50 mg/kg) followed by 5‐fluorouracil (50 mg/kg) the day after, and a second cycle 1 week after. One healthy control group (n = 8) were fed a 16% protein diet.
Measurements and Analysis
On day 9, the rats were euthanized and organs were weighed. Body composition was determined and protein content and protein synthesis (SUnSET method) were measured in the muscle, liver, intestine, and tumour. After euthanasia, plasma was deproteinized with 10% (w/v) sulfosalicylic acid and centrifuged (10,600 g for 10 min at 4°C). Frozen tibialis, liver, tumour, jejunal and ileal mucosa were homogenized in 10 volumes of ice‐cold 10% trichloroacetic acid with 0.5 mmol/L EDTA. Frozen tibialis, liver, tumour, jejunal and ileal mucosa were homogenized at 4°C in extraction buffer using a ball extractor (30 Hz for 2 × 1 min at 4°C). Extracted proteins were loaded onto a SDS-polyacrylamide gel electrophoresis (15%) and transferred onto a nitrocellulose membrane. Proteins were revealed by staining the membrane with Ponceau S dye. mTOR pathway activation was analysed with the phosphorylated form of 4E‐BP1 on serine 65. The SUnSETmethod is a new technique to measure relative protein synthesis which has been compared with classical tracers' methods.
The organs (spleen, Peyer's patches and tumour) were crushed using a syringe plunger, or chopped with scissors before being filtered through a sieve. The cell suspensions obtained were washed with complete RPMI1640 medium containing 10% FBS and 1% antibiotics (except the spleen cells which were washed in complete RPMI1640 medium without FBS) then centrifuged at 600 g for 5 min at 4°C. The pellets, including spleen cells, were suspended in 5 mL of complete medium. Cells were washed twice in PBS‐10%FBS and then fixed in 1× FACS lysing buffer. After two washes in PBS, 250 μL aliquots of the samples were kept for 48 h at 4°C in the dark before analysis in a FACS BD‐LSRII flow cytometer using BD FACSDiva 6.3.1 software for data acquisition and Diva software for analysis.
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Results
Cancer and chemotherapy led to a decrease in body weight characterized by a decrease of both fat mass (−56 ± 3%, P < 0.05) and fat‐free mass (−8 ± 1%, P < 0.05). Surprisingly, there was no effect of protein diet on body composition, muscle or tumour parameters (weight, protein content, or protein synthesis) but a high cumulative protein intake was positively associated with a high relative body weight and high fat‐free mass. From D0 to D9, food intakes were similar in all C + C groups, as illustrated by cumulative food intake, and lower than the Ctrl group. All the C + C groups showed a second substantial decrease after the second cycle of chemotherapy.
Conclusion from the Research
Using a realistic model of cancer and chemotherapy, researchers demonstrated for the first time that protein intake did not positively or negatively modulate tumour growth. Moreover, their results suggested that a high cumulative protein intake was able to improve moderately nutritional status in chemotherapy treated cancer rodents.
Food Sources of Protein
There are a variety of options to ensure you’re receiving enough protein with each meal.
- Chicken: Fully cooked chicken is a great source of protein.
- Fish: Salmon, shrimp and cold-water fish are great sources of protein. Salmon is an especially good choice because it contains Omega-3 fatty acids, which are important for brain and heart health. The average salmon filet is about 3.5 to 4 ounces and can contain 20 to 25 grams of protein.
- Nut Butters: Almond butter and peanut butter make for easy, healthy snacks when paired with fruit or yogurt bowls. Nut butters like almond butter and peanut butter are good sources of protein and often contain 6 to 8 grams of protein per serving (2 tablespoons).
- Eggs: Whether you like them scrambled or hard-boiled, eggs can be a good source of protein in the morning or on the go.
- Greek Yogurt: Greek yogurt is a great base for smoothies, or it can be enjoyed alone or with fruit and/or nuts.
- Protein Shakes: Protein shakes can be enjoyed ready to drink from the store, homemade or a mix of both. Ready-to-drink protein shakes are a great option if you are on the go, or you can use them as a base for a homemade protein shake.
- Plant-based Protein Powders: These often contain pea protein and brown rice, which must be used in combination for you to receive all of the amino acids.