Protein is a vital macronutrient essential for numerous bodily functions, including tissue repair, growth, and development. While adequate protein intake is crucial for overall health, concerns have been raised regarding the potential association between high-protein diets and cancer risk. This article aims to provide a comprehensive overview of the current evidence, exploring the complexities of this relationship and addressing common misconceptions.
The Claim: Plant-Based Diets and Reduced Cancer Risk
It is often claimed that a plant-based diet, with minimal or no animal protein, is the optimal approach to lowering cancer risk. This claim stems from concerns about several factors associated with animal products.
Concerns Regarding Animal Protein
Several potential issues are raised regarding animal protein consumption and its impact on cancer risk:
- Fat and Cholesterol Content: The fat content, particularly the cholesterol content, of animal foods is a primary concern.
- Heme Iron: Red meat, liver, and processed meats are high in heme iron, which has been implicated in increased cancer risk. For example, among over 60,000 women in the Swedish Mammography Cohort, a modest elevation in risk for endometrial cancer was shown with those with the highest intake of heme iron, especially from consuming liver.
- Choline Content: Eggs, liver, red meat, and milk are rich in choline. Choline is converted to trimethylamine oxide in the liver, potentially increasing inflammation in the body.
- Industrialized Husbandry Practices: The quality of animal food is affected by industrialized husbandry practices. Pesticides used on feed, medications, or hormones given to animals can leave toxic residues in the meat we consume.
- Grain-Based Diets for Animals: Meat from animals fed grain-based diets may possess inflammation-producing properties. Grass-based diets produce beef with higher contents of omega-3s and CLA and higher levels of antioxidants, as noted in a 2010 Nutrition Journal review.
Cooking Methods
Cooking methods are a crucial factor contributing to the concern with meat and cancer. Carcinogenic by-products are produced through high-heat cooking.
Examining the Evidence: Types of Studies
Before delving into specific research findings, it's essential to acknowledge the limitations of studies in this area:
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- Pre-clinical Animal Model Studies: Results from these studies may not translate to human populations.
- Epidemiological Studies: These studies cannot definitively prove cause and effect.
Specific Cancers and Dietary Factors
Bladder Cancer
The pooled results of 10 cohort studies and 11 case-control studies indicate that overall meat intake was not related to risk of bladder cancer. However, those with the highest intake of red and processed meats were at a 17% or 10% increased risk, respectively.
Endometrial Cancer
Among over 60,000 women in the Swedish Mammography Cohort, a modest elevation in risk for endometrial cancer was shown with those with the highest intake of heme iron, especially from consuming liver. There was no statistically significant association observed for intakes of other red or processed meats.
Gastric Cancer
Salted meat seems to increase the risk of gastric cancer, as high salt intake damages mucosa within the stomach and increases the risk for H. pylori infection. The heme iron content of red meat may also be implicated for an increased risk of stomach cancer as heme iron is a growth factor for H. pylori.
Oral Cancer
There is an increased risk of oral cancer with increasing processed meat intake.
Pancreatic Cancer
The by-products of high-heat cooking have shown an association with an increased risk of pancreatic cancer. Reviewing data from a large prospective cohort study (over 12,000 people) showed that total dietary fat intake, specifically saturated fat from red meat and dairy products, was associated with increased risk for pancreatic cancer.
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Prostate Cancer
The results of a meta-analysis showed increased prostate cancer risk with high intake of dairy foods; 14 oz/day total dairy, 7 oz/day milk, 3.5 oz/day yogurt, 1.75 oz cheese. One set of authors hypothesize that this is because of dairy’s IGF-1 content, which promotes proliferation of cancer cells and inhibits apoptosis of prostate cells. They also speculate that it could be due to dairy’s high calcium intake interfering with vitamin D levels. However, another set of authors believe that it’s dairy’s high phosphate content, rather than the calcium content, that reduces systemic serum vitamin D levels.
Gastrointestinal Cancers
A 2014 meta-analysis published findings from 37 case-control studies and 7 cohort studies supporting the association between egg consumption and increased risk for GI cancers; with a stronger correlation for colon cancer and in Western populations.
Bladder Cancer
Another recent case control study showed a connection between dietary cholesterol intake and risk of bladder cancer. Cholesterol is converted in the liver to primary bile acids, which are then converted in the gut by bacterial flora into secondary bile acids. The concern is that these bile acids produce reactive oxygen species, NF-kB activation, DNA damage, and increase cellular resistance to apoptosis.
Dairy Products: A Complex Relationship
The research is mixed around gastric cancer. A 2015 meta-analysis of 17 case-control and 6 cohort studies showed protective effects with the highest total dairy intake and hypothesized that it may be due to the anti-cancer properties of vitamin D and calcium or probiotic-rich dairy foods (like yogurt and kefir), which interfere with H. pylori colonization, or even the phospholipid content increasing cellular renewal. Another meta-analysis showed that dairy products were unlikely to be strongly protective against gastric cancer but didn’t increase risk. And yet another meta-analysis showed a non-significant increased risk of gastric cancer with dairy intake.
There was no association between dairy intake and pancreatic cancer risk observed in a pooled analysis of 14 cohort studies. Although as mentioned above under “Red Meats”, the dietary fat content of dairy foods has shown some association of increased risk for pancreatic cancer.
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Processed Meats and N-Nitroso Compounds (NOCs)
The by-products of processing have also shown associations with several other cancers. N-nitroso compounds (NOCs) also seem to be particularly problematic as they have been shown to reach the pancreas via the blood stream.
Umbrella Review of Systematic Reviews
A recent umbrella review of systematic reviews (SRs) examined the association between protein intake and cancer risk. This review, conducted according to a pre-specified protocol (PROSPERO: CRD42018082395), analyzed SRs published before January 22, 2024. The methodological quality and outcome-specific certainty of the evidence were assessed using modified versions of AMSTAR 2 and NutriGrade, respectively.
Key Findings of the Umbrella Review
- No Association with Specific Cancers: Higher total protein intake was not associated with the risks of breast, prostate, colorectal, ovarian, or pancreatic cancer incidence.
- Methodological Quality: The methodological quality of the included SRs varied, ranging from critically low (kidney cancer) to high (colorectal cancer).
- Outcome-Specific Certainty: The outcome-specific certainty of the evidence ranged from very low (pancreatic, ovarian, and prostate cancer) to low (colorectal, ovarian, prostate, and breast cancer).
- Animal vs. Plant Protein: Animal and plant protein intakes were not associated with cancer risks, with certainty ranging from low (breast and prostate cancer) to very low (pancreatic and prostate cancer).
- Overall Evidence: The evidence for the lack of an association between protein intake and colorectal cancer risk and breast cancer risk was rated as possible.
Methods of the Umbrella Review
The umbrella review followed a rigorous methodology, including:
- Literature Search: A systematic search was conducted in PubMed, Embase, and the Cochrane Database of Systematic Reviews for SRs published between July 1, 2009, and January 22, 2024.
- Literature Selection: Studies were included if they were SRs evaluating the association between protein intake (total, animal-derived, plant-derived, from supplements) and cancer in the general adult population.
- Data Extraction: Data on study characteristics, exposures, outcomes, and effect estimates were extracted from each included SR.
- Methodological Quality Assessment: The AMSTAR 2 tool was used to assess the methodological quality of the SRs.
- Outcome-Specific Certainty Assessment: The NutriGrade scoring tool was used to rate the outcome-specific certainty of evidence.
- Overall Certainty Assessment: The overall certainty of evidence was rated based on methodological quality, outcome-specific certainty, biological plausibility, and consistency of results.
Contradictory Evidence: A Case-Control Study in Iran
Conflicting results exist in various studies. High-protein diets have been linked to an increased risk of respiratory tract and renal cell cancer but a decreased risk of prostate cancer. However, there is no clear link between high protein diet and the incidence or mortality of BC. Studies have suggested that a higher intake of protein can improve the survival rate in individuals with BC. However, a long observational study has highlighted that the source of protein consumed is a more crucial factor in determining the incidence of BC than the overall amount of protein consumed. Notably, increased consumption of animal-based proteins may lead to a heightened risk of BC up to 20%.
A hospital-based case-control study conducted in Iran explored the relationship between high protein diet scores and odds of breast cancer in Iranian adults.
Methods of the Iranian study
- Study Population: The study included 134 newly diagnosed women with breast cancer and 267 controls.
- Dietary Assessment: Dietary intake was assessed using a validated food frequency questionnaire.
- High Protein Diet Scores: High protein diet scores were defined based on the percentage of energy intake from protein, fat, and carbohydrates.
- Statistical Analysis: Logistic regression models were used to determine the odds ratios (OR) and 95% confidence intervals (CI) of breast cancer across tertiles of high protein diet scores.
Key Findings of the Iranian study
- Lower Odds of Breast Cancer: Individuals in the highest tertile of high-protein-low-CHO and fat diet score and high-protein and CHO-low-fat diet had lower odds of BC compared to those in the lowest tertile.
- No Significant Association: No significant association was found between high-protein and fat-low-CHO diet and BC risk.
Limitations of the Iranian study
- Case-Control Design: The case-control design limits the ability to establish causality.
- Dietary Assessment: Dietary intake was assessed using a food frequency questionnaire, which is subject to recall bias.
- Confounding Factors: Although the study adjusted for several potential confounding factors, residual confounding may still be present.
Despite these limitations, the Iranian study provides valuable insights into the complex relationship between high protein diets and breast cancer risk.
Additional Research
Washington University and Alvin J. Siteman Cancer Center are conducting studies to investigate the impact of protein intake on cancer. One study targets men with prostate cancer to see whether lowering daily protein intake slows tumor growth before surgery. A second study involves post-surgical patients who continue to have elevated PSA levels. Half are asked to eat a diet with about 10 percent of total calories from protein. The others are asked to continue to eat a typical American high-protein diet.