July 31, 2019

expert reaction to study looking at dietary methionine restriction and tumour growth in mice

A study, published in Nature, reports that dietary  restriction of the amino acid methionine, can reduce tumour growth and improve the outcome of chemotherapy and radiation treatments in mice.

Prof Justin Stebbing, NIHR Research Professor of Cancer Medicine and Medical Oncology, Imperial College London, said:

“It’s now well known that nutrition exerts considerable effects on health and wellness, as well as helping maintain a healthy weight.  Dietary interventions are commonly used to treat diseases such as diabetes often in conjunction with medicines. It’s now thought to have an important role in cancer as well.

“This paper shows that dietary restriction of the essential amino acid methionine influences cancer outcome, but only in mice.  They showed how this happens and elegantly describe some beautiful science, even showing that a methionine-restrictive diet in 6 healthy volunteers can reduce methionine levels in the body.  But, we just don’t have any human data to even suggest it might be a useful anti-cancer strategy, either alone or in conjunction with drugs that we know are effective.

“But research like this can lead to studies in people, based on an understanding of basic science.  How dietary interventions influence cancer, its response treatment, and interacts with those treatments such as drugs or radiation is likely to be really important in years to come.”

Prof Paul Pharoah, Professor of Cancer Epidemiology, University of Cambridge, said:

“Yet again this is a study in mice that has almost no implications for treatment of cancer in humans.

“The authors have reported that a diet low in methionine inhibits tumour growth in mice.  This may or may not apply in humans and so before drawing any conclusions about the potential for dietary restriction as an approach to treating cancer, human studies are needed.

“The sample size is small – they had 14 mice (7 with dietary restriction and 7 without), and the type of stats analysis used may not have been suitable.  They used a parametric test which is not appropriate for such small sample sizes.  The smallest P-value you could get for a rank test with 7 in each group is 0.00058, whereas they report P = 5.71 x 10-12, which doesn’t quite make sense to me.”

Prof Tom Sanders, Professor emeritus of Nutrition and Dietetics, King’s College London, said:

“This study is based on experiments in mice and a small uncontrolled trial in six healthy subjects.  Methionine is an essential amino required for growth but it is also involved in some other metabolic reactions which transfer methyl groups between molecules including DNA.  Methylation of DNA can switch genes either on or off.  This study suggests that restricting the intake of methionine might have effects on tumour growth in some types of cancer in mice.  Methionine is found in most proteins e.g. in meat, fish and eggs and the level is quite high in wheat.  The proteins in legumes and in dried milk are low in methionine compared to other protein rich foods.

“Cancer at different sites has different metabolic effects – some cancers result in metabolic changes that cause weight loss (e.g. pancreatic cancer) whereas others (breast cancer) have little effect on weight.  Furthermore, appetite may be affected by some cancers resulting in protein-energy malnutrition (cachexia).  Several previous studies have examined the effect of protein supplementation patients with cancer and found no effect on survival.

“There is no evidence from this study to suggest that following a vegan diet will help patients with cancer.  Furthermore, a previous observational study¹ found that breast cancer patients given advice to follow a vegan diet had a poorer outcome than those on conventional treatment.”

1 Bagenal FS, Easton DF, Harris E, Chilvers CE, McElwain TJ. Survival of patients with breast cancer attending Bristol Cancer Help Centre. Lancet. 1990 Sep 8;336(8715): 606-10.

Prof Karen Vousden, Cancer Research UK’s chief scientist, said:

“One day doctors might be able to provide cancer patients with a carefully controlled diet designed to improve their treatment, and research into this is ongoing.  This study provides an interesting example of how limiting the amount of the amino acid methionine in food given to mice improves the response of some cancers to certain types of chemotherapy or radiation therapy.  The next step for this research will be to carry out clinical trials to see if these dietary restrictions have the same ability to improve the response to cancer treatments in people.”

Dr Elizabeth Lund, Independent Consultant in Nutrition and Gastrointestinal Health, said:

“The authors have reported a possible benefit in mice with tumours of restricting the intake of methionine.  The idea that dietary methionine could play a role in some elements of cancer biology is not new as studies on just a few patients (11) have previously been undertaken in France and published in 2010¹, although they had some difficulties.

“The idea that diet may interact with chemo or radiation therapy is very intriguing, but it is important to remember that most of this study was carried out in mice.  Also it is interesting that dietary methionine restriction in the absence of chemo or radiation therapy had no effect on mouse tumour size in this short-term study.  The human data showing parallels in healthy men in relation to changes in various biochemicals in the blood means it would be well worth investigating these ideas further, although the French scientists that tried previously had limited success.”

1 Durando et al. Oncology 2010;78:205–209. https://doi.org/10.1159/000313700

Dr Duane Mellor, Registered Dietitian and Senior Teaching Fellow, Aston Medical School, Aston University, said:

On this study:

“This is an interesting mechanistic and proof of concept study which provides evidence that reducing dietary methionine levels can lower levels of this essential amino acid in the circulation.  It also provides some data to support the idea that methionine restriction may improve management outcomes of colon cancer models in mice.  It does not provide any evidence that limiting methionine intake in humans is of direct benefit to individuals currently being treated with colon cancer.

On methionine in general:

“Methionine is an essential amino acid, meaning as humans we need to obtain it from the food we eat as our bodies cannot make it.  It is found often in animal based foods, which also happen to be good sources of protein such as meat, fish and dairy produce.  Previous studies have shown that lower methionine intakes and higher folic acid intakes are associated with lower rates of colon cancer.  Together the evidence has been used to support a theory that, as both folic acid and methionine are involved in one-carbon metabolism which is key for DNA synthesis, reducing this could help slow down the development and growth of new cancer cells.  This does not however mean that cutting out all animal foods and going vegan is the best way to prevent cancer.  In fact there are potential consequences to that, as methionine is also a key building block for glutathione, an antioxidant our body makes itself, that can reduce damage to our cells from free radicals, compounds that are also linked to cancer.  So, it’s not as simple as all the effects of methionine being negative with respect to cancer risk.  Consistently studies on diet have found that it is almost never the answer to cut out one type of food or restrict one nutrient – it is about eating a dietary pattern that includes both plant and animal derived foods, e.g. vegetables, fruits, nuts, seeds and pulses along with lean meat, fish and dairy according to personal preferences in a way that is balanced, culturally acceptable and enjoyable to the individual.

“It is key that interesting and novel research like this is acknowledged for how it increases our understanding of how biology works, but also it should be clear it is not saying one diet or way of eating is best.  In general, to prevent diseases like cancer or to maximise health, the answer is not to restrict one nutrient or to have larger amounts of a nutrient or food.  Instead, the best way to enjoy health through foods is to enjoy eating a wide variety of foods.  The science of nutrition is consistent on the evidence that there is no one perfect diet for humans, and restrictions or high intakes of any one food or nutrient is not the answer.”

* ‘Dietary methionine influences therapy in mouse cancer models and alters human metabolism’ by Xia Gao et al. was published in Nature at 18:00 UK time on Wednesday 31 July 2019. 

DOI: 10.1038/s41586-019-1437-3

Declared interests

Prof Paul Pharoah: “I have no conflict of interest.”

Prof Tom Sanders: “Honorary Nutritional Director of HEART UK.  Scientific Governor of the British Nutrition Foundation.  He is now emeritus but when he was doing research at King’s College London, the following applied: Tom does not hold any grants or have any consultancies with companies involved in the production or marketing of sugar-sweetened drinks.  In reference to previous funding to Tom’s institution: £4.5 million was donated to King’s College London by Tate & Lyle in 2006; this funding finished in 2011.  This money was given to the College and was in recognition of the discovery of the artificial sweetener sucralose by Prof Hough at the Queen Elizabeth College (QEC), which merged with King’s College London.  The Tate & Lyle grant paid for the Clinical Research Centre at St Thomas’ that is run by the Guy’s & St Thomas’ Trust, it was not used to fund research on sugar.  Tate & Lyle sold their sugar interests to American Sugar so the brand Tate & Lyle still exists but it is no longer linked to the company Tate & Lyle PLC, which gave the money to King’s College London in 2006.  Tom also used to work for Ajinomoto on aspartame about 8 years ago.  Tom was a member of the FAO/WHO Joint Expert Committee that recommended that trans fatty acids be removed from the human food chain.  Tom has previously acted as a member of the Global Dairy Platform Scientific Advisory Panel and Tom is a member of the Programme Advisory Committee of the Malaysian Palm Oil Board.  In the past Tom has acted as a consultant to Archer Daniel Midland Company and received honoraria for meetings sponsored by Unilever PLC.  Tom’s research on fats was funded by Public Health England/Food Standards Agency.”

Dr Elizabeth Lund: “No conflicts of interest.  Previously research leader at Institute of Food Research in Norwich.”

Dr Duane Mellor: “I am Nutrition Expert for Healthy For Men magazine (independently edited and managed for Holland and Barrett).  I have receive honoraria speaking for pharmaceutical companies in relation to nutritional management of cardiovascular disease and diabetes.”

None others received.