Other dietary exposures

Elements of the diet

Carbohydrates, fats and proteins are macronutrients that supply energy and are essential for tissue structure and function as well as physical and mental growth and development. These macronutrients can be subdivided into monosaccharides (such as glucose) and polysaccharides (such as starch) for carbohydrates; saturated, unsaturated and trans fatty acids for fats; and amino acids for proteins.

These constituent parts have different metabolic, physiological and biochemical effects, alone or in combination. Glycaemic index and glycaemic load are terms used to characterise foods and diets based on their effects on blood glucose levels.

A series of substances that do not supply energy have been identified as also being vital to life, typically in small amounts: these are vitamins, minerals and trace elements. As well as being contained in foods, these micronutrients are also available as supplements (usually in pill or powder form), and some are consumed in doses far in excess of what could be absorbed from food in any typical diet.

The evidence shows that, in general, the greater the glycaemic load in a person’s diet, the higher the risk of endometrial cancer. For high-dose beta-carotene supplements and calcium supplements, conclusions can be drawn only for the doses that were investigated.

Recommendations

Our Cancer Prevention Recommendations – for preventing cancer in general – include maintaining a healthy weight, being physically active and eating a healthy diet. It is best to eat a healthy diet rather than rely on dietary supplements to protect against cancer.

What are vitamins?

Vitamins are organic molecules, which may be fat or water soluble, that are needed for metabolism but most cannot be made in the body and so must be supplied in the diet. They each have specific functions in the body.

Vitamins A (retinol), D, E and K are fat soluble and can only be digested, absorbed and transported in conjunction with fats. They are found in liver, egg yolk and oily fish, and in the fat in milk and dairy products, animal fats and vegetable oils. Fat-soluble vitamins are stored in the liver and in body fat stores. For this reason, they do not need to be consumed every day. Partly for the same reason, continuous high intakes, especially of retinol and vitamin D, can lead to excess accumulation and toxicity.

Vitamin C and the B vitamins are water soluble. The B group includes thiamin (vitamin B1), riboflavin (B2), niacin (B3), pantothenic acid (B5), pyridoxine (B6), biotin (B7), folate (B9) and cobalamin (B12). Excess amounts of water-soluble vitamins are generally not toxic because they are excreted in the urine rather than stored in the body. This also means that they generally have to be consumed more frequently than fat-soluble vitamins. Foods of plant origin are important sources of water-soluble vitamins: for example, grains, vegetables, fruit, some roots and tubers and pulses. They can be destroyed by heat or exposure to the air, or lost by leaching during cooking, for instance when vegetables are boiled.

Mechanisms

Healthy dietary patterns and cancers of the mouth, pharynx and larynx

Healthy dietary patterns characterised by higher consumption of fruit and vegetables and reflecting lower consumption of alcohol as well as red and processed meats have been shown to be protective for cancers of the mouth, pharynx and larynx. It is likely that multiple individual components of healthy dietary patterns contribute to a potential impact on development of cancers of the mouth, pharynx and larynx, either with additive or interactive effects on pathways involved in oral carcinogenesis.

Further development of statistical and bioinformatics approaches to examining dietary patterns in prospective cohort studies and oral cancer risk, particularly in those at higher risk due to tobacco smoking and infections, will provide greater insight into key relationships. There are currently no human clinical intervention trials evaluating healthy dietary patterns and the risk of cancers of the mouth, pharynx and larynx.

Glycaemic load and endometrial cancer

The major proposed mechanisms by which the intake of foods with higher glycaemic load could affect endometrial cancer risk relate to elevated postprandial glucose and insulin levels, and subsequent development of insulin resistance, diabetes and obesity – all factors that are associated with endometrial cancer development.

Foods and drinks containing fructose and pancreatic cancer

Fructose is metabolised largely in the liver. Higher fructose intake may promote the development of non-alcoholic fatty liver disease and a cancer-promotive environment. Fructose has also been shown to enhance insulin resistance, inflammation and production of reactive oxygen species.

Foods containing saturated fatty acids and pancreatic cancer

Higher consumption of saturated fatty acids may be pro-inflammatory and promote the development of insulin resistance, both of which are proposed mechanisms for pancreatic cancer development. An in vitro study on the HPAF line of pancreatic cancer cells shows a growth-promoting effect of saturated fatty acids, but there is little additional supporting data.

Foods containing retinol and lung cancer

Retinoid molecules possess an antiproliferative effect at the cellular level via growth arrest signalling, promotion of differentiation and induction of apoptosis. Retinoic acid has also been shown to downregulate markers of cell proliferation such as hTERT (human telomerase reverse transcriptase) and cyclins D1 and 3, markers of DNA damage such as 8-oxo dGuo, and growth factors such as epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF), potentially inhibiting tumour growth, angiogenesis and metastasis.

Retinoids are also hypothesised to modulate additional targets such as reactive oxygen species, mitochondrial permeability, lipoxygenase, cyclooxygenase-2 (Cox-2), nuclear factor-kB, ubiquitination, tumour necrosis factor-α, c-Myc, Ap-1 and cell surface death receptors.

Vitamin D and colorectal cancer

Underlying mechanisms for an association of vitamin D with colorectal cancer risk have been mostly studied in in vitro and experimental models, and there are limited data in humans. These studies suggest a role for circulating vitamin D, through its active form 1α,25-dihydroxyvitamin D3[1,25(OH)2D3], in control of cell growth, by reducing cell proliferation and promoting differentiation and apoptosis.

Other purported mechanisms of vitamin D action pertain to improved innate and adaptive immune function, inhibition of angiogenesis, reduced inflammation and regulation of microRNA expression with higher vitamin D status.

Low plasma alpha-tocopherol concentrations and prostate cancer

Alpha-tocopherol is believed to be the most biologically active isomer of vitamin E, with anti-oxidative properties. Alpha-tocopherol has also been shown to favourably modulate immune function, induce cellular apoptosis and lower concentrations of circulating testosterone.

Low plasma selenium concentrations and prostate cancer

Experimental evidence suggests selenium induces apoptosis and inhibits cell proliferation in tumour cell lines. In addition, selenium availability has been shown to regulate the activity of glutathione peroxidase, an enzyme which protects the cell from peroxide damage.

Beta-carotene and lung cancer

A number of human studies and meta-analyses have shown that higher circulating levels of carotenoids including β-carotene, lycopene and β-cryptoxanthin are associated with lower risk of lung cancer. Further, evidence from both animal and laboratory studies have shown that carotenoids can block certain carcinogenic processes and inhibit tumour cell growth. Some proposed mechanisms for these actions include:

1. functioning as an antioxidant
2. acting as a precursor for retinoic acid
3. enhancing immunologic function
4. inducing of carcinogen-metabolising enzymes
5. inhibiting of cell proliferation and inducing of apoptosis

High-dose beta-carotene supplements and lung cancer, in people who smoke/used to smoke tobacco

High-dose beta-carotene supplements in humans were shown to increase the risk of lung cancer among people who smoke in two out of three intervention trials. These findings contrast with epidemiologic studies on dietary-derived beta-carotene and circulating beta-carotene levels which generally report a decreased risk of lung cancer.

The mechanisms underlying the effect of beta-carotene supplementation on lung cancer risk are likely complex and not fully understood. It has been hypothesised that carotenoids can also display pro-oxidant activity, and animal model studies have demonstrated that administration of high-dose beta-carotene leads to the initiation of lung neoplasia in the presence of tobacco smoke.

High-dose beta-carotene in the smoke-exposed animals was also found to yield a number of transient oxidative metabolites and upregulation of cytochrome P450 enzymes that may result in the destruction of retinoic acid, diminished retinoid signalling and enhanced cell proliferation. In addition, specific beta-carotene metabolites facilitate the binding of smoke-derived carcinogens to DNA.

Overall, it appears that the dose of beta-carotene is critical with respect to the risk of lung cancer and likely explains the apparent paradoxical elevation of lung cancer incidence among people who smoke and who take high-dose beta-carotene supplements.

Calcium supplements and colorectal cancer

A long-standing mechanism proposed for calcium and its potential activity against colorectal cancer development is the ability of calcium to bind unconjugated bile acids and free fatty acids, diminishing their toxic effects on the colorectum. More recent cell culture studies suggest that it may also reduce cancer cell proliferation and promote cell differentiation, likely by influencing different cell-signalling pathways.

Multivitamin supplements and colorectal cancer

Multivitamin supplements consist of a combination of several or in some instances many vitamins, making it challenging to determine the specific active ingredient. Numerous vitamins contained in multivitamin supplements have been shown to capture free radicals and reactive oxygen species and to prevent lipid peroxidation.

> Our Recommendation is Don’t use supplements for cancer prevention