A review of the week’s plant-based nutrition news 4th July 2021
This week has a cancer theme as I am preparing for my talk for the International Conference on Nutrition in Medicine. I summarise the main headline messages from my talk.
At least 40% OF CANCER CASES COULD BE PREVENTED BY ADOPTING A HEALTHY DIET AND LIFESTYLE
Cancer prevention recommendations are done in my view. I doubt the advice will change in the coming 5–10 years. I believe the evidence supporting these recommendations will only be strengthened by a better understanding of the underlying mechanisms involved. The recommendations are summarised in an excellent guideline from the American Cancer Society and highlights are shown in the table below. In the US, the combination of excess body weight, alcohol intake, poor diet, and physical inactivity account for the highest proportion of all cancer cases in women and is second only to tobacco smoking in men. These 4 combined risk factors also account for the second highest proportion of cancer deaths in both men and women. When it comes to diet, the international consensus is to focus on eating fruits, vegetables, whole grains, beans, nuts and seeds as these are the only foods that have been associated with cancer prevention.
MEAT CONSUMPTION IS ASSOCIATED WITH AN INCREASED RISK OF CANCER
This study shows once again that red meat consumption is implicated in cancer development. The study analysed data from 474 996 participants (54% women) in the UK Biobank study, followed for 7 years. Participants were aged 37–73 years and cancer-free at baseline. The results show that a 50g/day higher intake of red meat was associated with a 22% increased risk of colorectal cancer and a 20g/day higher intake of processed meat was associated with a 18% increased risk. 70 g/day higher red and processed meat intake combined was associated with a 32% greater risk of colorectal cancer and a 40% greater risk of colon cancer. Although the association was less robust, red meat consumption was shown to increase the risk of prostate cancer by 18%. The data also suggested an increased risk of breast cancer (10–14%) and endometrial cancer (30–48%) with higher intakes of meat, but these associations were attenuated after adjustment for BMI, suggesting overweight/obesity are likely to be causing the association. In addition, a 20% increase in risk of cancer of the lymphatic and haematopoietic tissue was found with poultry intake, although the results did not hold true after correcting for multiple testing. So once again — moderation is not the answer. 70g of processed meat is equivalent to 2 slices of bacon or 1.5 sausages.
MECHANISMS BY WHICH MEAT CAUSES CANCER OUR BETTER UNDERSTOOD
This is a really important study. We have known for several years that processed and unprocessed red meat increases the risk of cancer, particularly bowel cancer, but the actual mechanism has been less certain, with many theories proposed.
In this study, DNA was analysed from matched normal and colorectal tumour tissues from 900 patients with colorectal cancer who had participated in one of three prospective cohort studies from the US, the Nurses’ Health Studies and the Health Professionals Follow-Up Study. All participants had previously provided information on their diet, lifestyle, and other factors over the course of several years prior to their colorectal cancer diagnoses.
DNA sequencing data showed different mutation signatures in the different tissues. One particular mutation signature found in the colorectal cancer tissue is associated with alkylation of DNA, indicating a type of DNA damage. This particular alkylating signature was associated with high intakes (more than 150g per day) of processed and red meat prior to the diagnosis of colorectal cancer. However, other dietary factors such as poultry and fish consumption, and lifestyle factors such as body mass index, alcohol, smoking and physical activity was not associated with this alkylating signature. The tumours that displayed the alkylating DNA signature were more likely to have mutations in genes associated with driving the development of colorectal cancer. In addition, this higher levels of alkylating damage was associated with a 47% greater risk of dying from colorectal compared to patients with lower levels of damage.
The lead author was quoted by the American Association for Cancer research to say ‘Our study identified for the first time an alkylating mutational signature in colon cells and linked it to red meat consumption and cancer driver mutations. Our data further support red meat intake as a risk factor for colorectal cancer and also provide opportunities to prevent, detect, and treat this disease.’
WHICH FOODS ARE BEST FOR CANCER PREVENTION?
I don’t like to focus on individual foods but prefer to emphasise the benefits of variety within a plant-based diet. Variety and abundance are some of the joys of a plant-based diet. However, if I had to choose, mushrooms and soya would be in my top 10.
We already know mushrooms are a very healthy food. They are low in calories yet packed with nutrients, including phytochemicals (alkaloids, phenolic acids, flavonoids, carotenoids), fibre, selenium, vitamins (e.g., niacin, thiamin, riboflavin, ascorbic acid, and vitamins B and D) and important antioxidants ergothioneine and glutathione that are thought to play a significant role in the prevention of cancer.
So how good are mushroom for cancer prevention? This study brought together data from 17 observational studies, including 19,732 cases of cancer. Most of the studies were from Asian countries. The results showed that compared to those eating the least (less than once a week), those eating the most mushrooms (more than 5 times a week) had a 44% reduced risk of cancer, with benefits for breast cancer being most apparent.
I always like to highlight the benefits of soya in my talks as there are still so many myths that persist. There is no doubt that the consumption of minimally processed soya foods is healthy and can reduce the risk of a number of chronic conditions. This huge analysis of all the human data on soya consumption, which includes 114 meta-analyses and systematic reviews reported a significant reduction in the risk of a number of cancers, including ovarian (48% reduction), gastric (37%), prostate (29%), breast (13%), colorectal (24%), endometrial (19%) and lung (17%). Not only that, soya consumption is beneficially for heart health with soya protein lowering LDL-cholesterol levels. Soya also has benefits for bone and kidney health, prevention of type 2 diabetes and for menopausal symptoms in women.
CHRONIC HEALTH CONDITIONS INCREASE THE RISK OF CANCER
This does not get enough attention in my view. Chronic conditions, such as cardiovascular disease, type 2 diabetes, renal failure and autoimmune conditions, increase the risk of cancer. Most chronic diseases arise from a combination of inflammation, insulin resistance, dyslipidaemia and dysbiosis (abnormal gut microbiome). Cancer is also driven by these same mechanisms, which is why diseases cluster in the same individuals. A study from Taiwan following more than 400,000 participants for nearly 9 years found that around a third of the risk of dying from cancer was due to underlying chronic health conditions, with a further third from unhealthy lifestyle habits.
This paper examines the association between type 2 diabetes and cancer risk. in the Nurses’ Health Study and the Health Professionals Follow-up Study, a cohort of almost 200,000 participants from the US followed for over 30 years. The results showed that participants with a new diagnosis of type 2 diabetes during the follow-up period had a significantly increased risk of developing cancer, particularly, colorectal, lung, pancreas, oesophageal, liver, thyroid, breast, and endometrial cancers. This risk was increased in the first 8 years following diagnosis of type 2 diabetes but not after this. Overall, there was a 21% increased risk of total cancer, 28% increased risk of obesity-related cancer, and 25% increased risk of diabetes-related cancer comparing participants with and without diabetes.
Some participants had data available on C-peptide and HBA1c levels. C-peptide levels are a marker of endogenous insulin levels, which was elevated in the first 8 years following diagnosis of type 2 diabetes and then tended to fall (as the pancreas became unable to produce insulin). HBA1c levels remained stable over a 15 year period. These data suggest that higher insulin levels may be driving the increased risk of cancer rather than higher glucose levels per se. The results are consistent with those that show patients with type 1 diabetes are not at increased risk of cancer as their insulin levels are low/absent. In addition, other studies have shown higher circulating insulin levels are associated with an increased risk of cancer.
LIFESTYLE TRUMPS GENETICS EVERY TIME
Colorectal cancer (CRC) is the third commonest cancer and 4th leading cause of cancer death globally with the burden expected to increase by 60% to more than 2.2 million new cases and 1.1 million cancer deaths by 2030. Yet around more than 50% of cases could be prevented by addressing common risk factors: eating too little fibre, red and processed meat consumption, obesity, tobacco smoking and alcohol consumption. There are of course some individuals who have a higher genetic risk of CRC and this study assesses the impact of healthy lifestyle factors in people with different levels of genetic risk.
The study used data from 346,297 participants in the UK Biobank cohort. Healthy lifestyle scores (HLSs) were constructed using 8 lifestyle factors, according to the American Cancer Society guidelines, and were categorized into unhealthy, intermediate, and healthy groups. These lifestyle factors were BMI (kg/m2), waist-to-hip ratio (WHR), physical activity, sedentary time, processed and red meat intake, vegetable and fruit intake, alcohol consumption, and tobacco smoking. A polygenic risk score (PRS) was created using 95 genetic risk variants. During the 5.8 years of follow-up there were 2066 new cases of CRC.
The results showed that a high HLS was associated with a significantly lower risk of CRC and there was a dose effect. In addition, the reduction in risk was greater in those with a higher PRS. This risk reduction was in the order of 30–50%. The greatest individual risk factors were higher WHR, consumption of red and processed meat, alcohol consumption and tobacco smoking.
Once again, your genes are not your destiny. We talk about personalised medicine for cancer treatment, but the authors conclude that we need to ‘establish personalized preventive strategies for cancer prevention’. These same healthy lifestyle factors are just as important after a diagnosis of CRC as they can help increase the length of remission and survival following treatment.
I will be coming down strong on alcohol consumption
When it comes to alcohol consumption, many doctors have a blind spot. Consumption is socially acceptable and pleasurable for most. Nonetheless, it is important to be honest with the scientific data. Unfortunately alcohol consumption does increase the risk of cancer. This is through a number of mechanisms. Acetaldehyde, the main metabolite of alcohol, disrupts DNA synthesis and repair. Ethanol induces oxidative stress through increased production of reactive oxygen species, which also damage DNA. Alcohol may also act as a solvent such that it is easier for dietary or environmental carcinogens to penetrate cells and interfere with DNA repair mechanisms. Those consuming the most may also have diets that are lacking in essential nutrients, such as folate, making tissues more susceptible to carcinogenic effects of alcohol. Of course, like with most toxins, there is a dose effect and there may be a sweet spot where a certain level of alcohol consumption is acceptable to most whilst accepting a very small increase in cancer risk.
This study determined the current burden of alcohol-associated cancer risk in the US down to the state level between 2013–2016. Overall, it was estimated that 4.8% of cancer cases among adults aged ≥30 years could be attributed to alcohol consumption with a slightly higher risk in women (5%) than men (4.7%). The range was as low as 2.2% and as high as 7.7% based on the state. Nationally, alcohol consumption accounted for 75,199 cancer cases and 18,947 cancer deaths annually.
Alcohol consumption accounted for 49.8% (n=91,017) of oral cavity/pharyngeal cancers and 30.1 % (n=14,899) of laryngeal cancers. Alcohol consumption also accounted for an estimated 12.1% of female breast cancers, equating to an estimated 115,794 cases. Additionally, 11.1% (n=62,766) of colorectal, 10.5% (n=11,124) of liver, and 7.7 % (n=5146) of oesophageal cancers could be attributed to alcohol consumption. In most states, ≥45% of oral cavity/pharyngeal cancers and ≥25% of laryngeal cancers were attributable to alcohol consumption.
Current guidelines for cancer prevention already state ‘do not consume alcohol’. The authors of this paper state ‘Healthcare providers and public health practitioners can educate the community to expand the currently limited awareness of the cancer-related risks of alcohol consumption’. Fortunately, cancer risk declines with increasing years of cessation from alcohol consumption.
THE HEALTH OF OUR GUT MICROBIOME IS IMPORTANT TO HOW WE RESPOND TO CERTAIN ANTI-CANCER TREATMENTS
It’s becoming clear that a healthy gut microbiome can not only reduce the risk of developing cancer but may help to improve cancer outcomes in those receiving treatment for cancer. In this study, 52 patients with solid tumour treated with immunotherapy had measurements performed of short chain fatty acids (SCFA) in plasma and faeces. Diet information was also analysed. With a median follow up of 2 years, higher levels of SCFAs were associated with a longer remission. High fibre foods, including green vegetables, cabbage, and mushrooms, were associated with higher concentrations of faecal SCFAs. High frequency of mushroom intake was associated with a better response to treatment. SCFA’s are produced by healthy gut bacteria and integral to maintaining a healthy gut lining, reducing inflammation and maintaining a healthy immune system both in the gut and the rest of the body.
Researchers have now taken the next step and tried to improve the health of patients’ gut microbiome using faecal microbiota transplants. My question is, why not try a fibre-rich, plant-based diet!
CANCER TREATMENTS CAN INCREASE THE RISK OF OTHER CHRONIC ILLNESSES
Unfortunately all cancer treatments have side effects, but these side-effects can be reduced by maintaining a healthy diet and lifestyle. This systematic review and meta-analysis included 6,962 patients with breast cancer treated with tamoxifen and 975 patients not treated with tamoxifen. The data show that tamoxifen increases the risk of non-alcoholic fatty liver disease, with a prevalence of 40% in women taking tamoxifen. This was a 3 times increased risk compared to patients with breast cancer not taking tamoxifen. The main risk factors identified were greater body mass index and high cholesterol levels suggesting that a healthy diet and lifestyle are important after a cancer diagnosis to reduce side effects of anti-cancer medications. This is just one example of long-term side-effects of cancer treatments. The more common side-effects of cancer treatment are cardiovascular disease and second cancers making diet and lifestyle habits even more important.
A HEALTHY DIET AFTER CANCER TREATMENT CAN ALSO MAKE A BIG DIFFERENCE
The good news is that even after a diagnosis of cancer, a healthy diet can improve your chances of survival. This paper reports data from the Women’s Health Initiative study, which included 48,835 postmenopausal women, aged 50–79 years. Participants were randomly assigned to a low-fat diet intervention with increased consumption of fruits, vegetables and whole grain, or their usual diet. Even though a low fat diet of <20% calories from fat was not achieved by the participants in the intervention group, the study showed that those who developed breast cancer and ate more fruits, vegetables and whole grains lived longer after the diagnosis. The authors conclude ‘Adoption of a low-fat dietary pattern associated with increased vegetable, fruit, and grain intake, demonstrably achievable by many, may reduce the risk of death as a result of breast cancer in postmenopausal women’.
We already know that the risk of a second cancer is further increased in those who have already had a diagnosis of cancer. This is in part due the cancer treatments we use. However, it seems lifestyle factors are also important for prevention of second cancers.
This study examined the the risk of and mortality from second primary cancers among 1.5 million adult cancer survivors between 1992 and 2017 in the US. Compared with the general population, adult cancer survivors had a higher risk of developing a second primary cancer (11% increased risk in men and 10% in women) and an even higher risk of dying after such a diagnosis is made (45% in men and 33% in women). The risk of developing a second primary cancer among adult cancer survivors increased between 1975 to 1989 and 2000 to 2015 suggesting that environmental and lifestyle factors are having a greater impact over time.
Although it is accepted that some of this increased risk is due to underlying genetic predisposition and the cancer treatments received, the results suggest that most of this excess risk is due to host factors (aging, immunity) and to lifestyle risk factors (eg, smoking, obesity, alcohol, infection) shared by the first and subsequent cancers. Four common smoking-related cancers (lung, urinary bladder, oral cavity/pharynx, and oesophagus) accounted for 26% to 45% of the total second primary cancer incidence and mortality and 4 common obesity-related cancers (colorectal, pancreas, uterus, and liver) accounted for 22% to 26% of the total second primary cancer incidence and mortality. Lung cancer alone comprising a third of the mortality from all second primary cancers. Alcohol-related second cancers were also increased in those with alcohol-related primary cancers.
Although these are many limitations to this retrospective analysis, the take home message is a reminder of the importance of encouraging a healthy lifestyle in cancer survivors as well as in previvors (those who are at high risk of cancer but have not yet been diagnosed). This includes, avoidance of tobacco and alcohol and promoting healthy eating and regular exercise. There is still a big piece of work needed in effective public health messaging as less than 50% of people in the UK and US are even aware of the impact of lifestyle choices on cancer risk.
Hope to see you all at the conference!
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