How does diet and lifestyle drive chronic disease?
By Isabelle Sadler and Shireen Kassam
The alarming rise in disease rates, including type 2 diabetes, cardiovascular diseases and many cancers, can partly be attributed to changing lifestyle habits and dietary patterns. Our lives are becoming increasingly sedentary and our diets increasingly high in animal-based and highly processed foods while being low in fruits, vegetables, nuts, and whole grains.
Most chronic diseases share similar pathogenic mechanisms, even though their manifestations may differ. The key driver is low-grade chronic inflammation. Inflammation is the body’s response to tissue damage, and usually it is a protective process. However, when the body becomes overwhelmed, inflammation can lead to damage of normal tissues, resulting in chronic disease. Diet and lifestyle choices can either promote or prevent this kind of inflammation.
Below, we look at the main mechanisms that link diet to chronic disease.
1) Oxidative stress
Oxidation is a normal process in the body, referring to the loss of electrons by a molecule, atom or ion. The opposite reaction, the gain of an electron, is called reduction. These processes are usually in balance and play a crucial role in normal cellular metabolism. An imbalance between oxidation and reduction can give rise to reactive oxygen species (ROS). ROS are a normal byproduct of cellular metabolism, but during times of “stress” their levels can rise dramatically, resulting in tissue damage through oxidative stress.
Oxidative stress can damage proteins, DNA and cell membranes. Stressors that increase ROS levels include cigarette smoking, medication, pesticides, radiation, and our diet choices. The body requires antioxidants to counter these damaging ROS. Studies have shown that people eating predominantly plant-based diets have higher levels of antioxidants in the body than omnivores, including various polyphenols, vitamin C, and vitamin E.
Plant foods contain hundreds of antioxidant compounds and have vastly higher antioxidant content than animal-derived foods. Some compounds within animal-derived foods, such as haem iron (found in haemoglobin and myoglobin in meat), are pro-oxidants that create oxidative stress and can contribute to cellular damage. Haem iron is also a catalyst for ROS formation, causing significant damage to DNA and increasing inflammation and protein damage. There is evidence from observational studies to suggest that high dietary haem intake from animal meat consumption increases the risk for adverse health effects including type 2 diabetes, gestational diabetes, cardiovascular, and some cancers.
Advanced glycation end products (AGEs) are a group of compounds that induce oxidative stress and increase inflammation. They are formed by a spontaneous chemical reaction between an amino acid (protein) and a monosaccharide (glucose). AGEs accumulate over time, and the body’s process for clearing them is slow. The long-term consumption of AGEs results in the production of pro-inflammatory molecules, increases inflammatory markers, and leads to immune activation. They have also been shown to cause cellular damage and insulin resistance, worsening endothelial function and organ health, and have been implicated in the pathogenesis of a number of chronic diseases, including type 2 diabetes, kidney failure, cancer and neurodegenerative and cardiovascular diseases.
Some AGEs are produced in the body every day, but diet is the biggest contributor to AGE formation, along with tobacco products. AGEs from food are generated more readily from protein-rich foods, when cooking at high temperatures, for longer periods, and with dry-heat cooking. Lower amounts form when moisture is present. A 2010 study that categorised AGE levels across 549 foods found animal-derived foods that are high in fat and protein are highest in AGEs and also prone to new AGE formation during cooking. The highest levels were observed in beef and cheeses followed by poultry, pork, fish, and eggs. Fried and processed foods also generate high levels of AGEs. In contrast foods such as vegetables, fruits, whole grains, and milk contain relatively few AGEs, even after cooking. AGE formation is also increased by altered glucose metabolism, that is, high blood sugar, insulin resistance and diabetes.
2) Gut dysbiosis
The gut microbiome is made up of trillions of microorganisms living in the gut. We understand most about the bacteria there, but viruses, fungi and protozoa are present too. The gut microbiota ferment indigestible substrates, including dietary fibre, and produce short-chain fatty acids (SCFAs) such as butyrate, propionate and acetate. SCFAs are signalling molecules required for the integrity of the gut lining, the gut’s immune system, reducing colonic pH and protecting against pathogens, and are thought to have a direct anti-inflammatory effect in the gut. A healthy gut microbiome is characterised by richness and high microbial diversity with a wide range of species present, whereas dysbiosis is defined by an imbalance of the bacterial species in the gut. This imbalance is linked to metabolic dysfunction, which contributes to the development of various chronic diseases.
Dietary choices affect the health of the gut microbiota, partly because they rely predominantly on fibre from whole plant foods. Plant-based diets can increase bacterial diversity and promote the generation of SCFAs. Diets lacking in plant-derived fibre, as is the case for most Western-style diet patterns, are known to reduce SCFA production and increase production of secondary bile acids, which are formed by gut bacteria acting on primary bile acids from the liver. Secondary bile acids can damage gut cells, increase gut permeability, and are implicated in the development of gastrointestinal cancers. Diets high in saturated fat may also negatively affect microbiota richness and diversity, and can increase gut permeability, allowing inflammatory substances such as bacteria and lipopolysaccharides (bacterial endotoxins) into the circulation, which contributes to inflammation. An unhealthy gut microbiome also results in lower levels of incretin hormones, a group of gut hormones released after eating that lower blood glucose and support the effects of insulin. In people with type 2 diabetes, this incretin effect is reduced or absent.
3) Lipotoxicity / dyslipidaemia
An unhealthy diet that provides more calories than the body needs, especially from saturated fat and highly processed foods, can drive excess fat accumulation. While weight gain is often most visible as subcutaneous fat stored beneath the skin, fat stored around the organs (visceral fat) and within tissues where it would not normally be stored (ectopic fat) is particularly harmful to health.
Body fat, or adipose tissue, is considered a metabolically active endocrine organ, secreting signalling molecules that regulate metabolism, inflammation, and immunity. As adipose tissue expands, fat cells become larger and/or increase in number, which can place stress on the cells, disrupt their normal function, and activate inflammatory pathways.
When excess fat accumulates in the liver, skeletal muscle, heart and pancreas, it can cause these organs to become dysfunctional and lead to metabolic disease. For instance, high levels of visceral fat are strongly associated with insulin resistance, an important predictor of type two diabetes risk. In the pancreas, fat infiltration can damage cells to the point where they can no longer produce enough insulin.
In obesity, this can contribute to low-grade chronic inflammation and impaired immune cell function, leading to systemic metabolic dysregulation. This increases the risk of developing obesity-related metabolic disorders such as type 2 diabetes, cardiovascular disease, and metabolic dysfunction-associated steatotic liver disease.
Importantly, you don’t have to be overweight, or carry much excess subcutaneous fat, to have excess visceral or ectopic fat. This is one reason people of normal weight or BMI can still develop type 2 diabetes when exposed to a Western-style lifestyle and diet.
4) Protein source
Protein has become a rather revered macronutrient, but more isn’t necessarily better, and the source and quality of protein matters more than the quantity.
Studies have shown that higher intake of protein from animal sources is associated with increased risk of mortality, cardiovascular disease and cancer, whereas intake of plant protein has been associated with a lower risk of these diseases. This has been demonstrated across various large cohorts, including the Nurses’ Health Study, the Health Professionals Follow-up Study, the Adventist Health Study, and a large prospective cohort study conducted in Japan. In a 2021 cohort study, substituting 5% energy of animal protein with plant protein was associated with between a 9%-19% lower risk of all‐cause mortality, 13%-30% lower risk of CVD mortality, and 3%-32% lower risk of dementia mortality.
There are several reasons animal protein is a less healthy choice: it’s typically packaged with cholesterol and saturated fat, and it has a higher content of sulphur-containing and branched-chain amino acids compared with plant-derived protein – both linked to a higher risk of chronic disease. Red meat also increases trimethylamine-N-oxide (TMAO) in the body, which may underlie the association with cardiovascular disease. As previously mentioned, animal proteins contain higher amounts of AGEs, especially when cooked. Cooking animal protein at high temperatures may also lead to the production of heterocyclic amines (HAAs), which are thought to increase cancer risk in humans.
Can a plant-based diet help prevent and reverse these diseases?
Oxidative stress, gut dysbiosis and lipotoxicity all feed into chronic low-grade inflammation, which in turn drives chronic disease. LDL-cholesterol, elevated largely by the saturated fat content of a Western diet, is a further underlying cause of atherosclerosis on top of these mechanisms.
A whole-food, plant-based diet is best described as an anti-inflammatory diet, working against each of the mechanisms above. Individuals following a predominantly whole foods, plant-based diet can have lower levels of inflammatory markers, less evidence of oxidative stress (see also), lower levels of AGE’s, higher fibre intake leading to a healthier gut microbiome with higher SCFA levels, and are less likely to be overweight.
To learn more about plant-based diets for the prevention of chronic diseases, you can visit our article pages that cover:
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