October 20, 2021

expert reaction to study looking at diet and tumour growth in mice

A study published in Nature looks at diet influence on tumour growth in mice.

Dr George Poulogiannis, Leader of the Signalling and Cancer Metabolism Team, The Institute of Cancer Research, London, said:

“This is an intriguing study with carefully selected experiments which support the notion that dietary interventions in some tumour contexts may inhibit tumour growth by altering tumour lipid availability.

“There is increasing evidence in the literature that cancers are hooked on fat, and that low glycaemic diets can inhibit tumour growth and increase therapy response.  However, in all instances the data should be interpreted with caution, as given the multifactorial and multigenic nature of cancer, the effects of dietary restriction are also likely to depend on the individual cancer subtype or the diet being used.

“For example, evidence suggests that a ketogenic diet alone may accelerate disease progression in a model of acute myeloid leukaemia and tumours which rely on specific signalling pathways do not respond to dietary restriction or a fat free diet.  This suggests that tumour responses to specific diets and restrictions depend on the individual genetics of a patient’s tumour, which can vary hugely, even for the same type of cancer.

“The experimental aspects of the study were carried out in mice, and warrant further validation in a clinical setting to evaluate the impact of dietary interventions on patient outcomes.  The part of the study that involved patients only looked at associations between diets and survival in patients diagnosed with pancreatic cancer.  This type of study has limitations and cannot tease out cause and effect meaning many other factors could influence a patient’s survival.

“Last but not least, the distinct effects of these diets on systemic metabolism indicate that further studies are needed to provide guidance on how dietary interventions can improve the care of patients with cancer, and under no circumstances patients should feel like they need to eat less because of this.  A healthy nutritional intake is important at maintaining a strong immune system and improving cancer treatment tolerance.”

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

“This paper reports on a study aimed at understanding how a low calorie diet (caloric restriction) and a ketogenic diet in mice results in a reduction in pancreatic tumour growth.  The findings suggest that a low calorie diet limits growth by affecting the levels of fats within the tumours.  However, these findings are from a mouse model in which pancreatic tumours are implanted under the skin of the mice.  While these findings are intriguing, the findings from animal models such as these often do not translate to humans.  Consequently the relevance of these findings to pancreatic tumours in humans – that develop and grow in the pancreas – is simply speculative.  The authors suggest that their findings are supported by an analysis of survival in individuals with pancreatic cancer.  However, this component of the study is described very briefly so that it cannot be properly evaluated.  It thus does not provide meaningful evidence that a calorie restriction diet would be of any value in people with pancreatic cancer.”

Prof Gunter Kuhnle, Professor of Nutrition and Food Science, University of Reading, said:

“This is a study that primarily investigates the effect of different diets in mice and it is impossible to translate these results directly into humans.  The diets used in the animal experiments where different from what humans would normally eat – for example, we get about 30% of our energy from fat, whereas the control diet contained only 17%.  The authors conducted a wide range of analysis to explore underlying pathways and molecular mechanisms, and these results are likely useful in further research but need to be interpreted with caution.

“In order to investigate whether their findings can be translated to humans, the authors conducted a small epidemiological study in two well characterised cohorts.  They used self-reported dietary data and classified study participants according to their dietary patterns.  In contrast to the press release, the results do not support any particular dietary pattern.  The only modest reduction in risk was observed for people consuming a higher amount of plant-based fat, but the study does not provide any information on the actual amount of fat consumed.

“In summary, this is a well conducted study, mainly in mice, that provides further information on potential mechanisms linking diet with disease, but it is not easily possible to translate these results into recommendations for the public.”

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

“This is an interesting study comparing work in animals looking at how different diets affect how two particular types of cancer cells lead to tumours in mice.  It is important to consider that the tumours were from cells added under the skin of mice and not cancers which are linked to and developed in the actual organs.  So, although the research mentions pancreatic and lung cancer, these were the type of cell cancers which grew under the skin of mice.  It did this to test the idea that higher levels of insulin and glucose might by linked to increased tumour growth.  It did not look at initial risk of cancer, which might have different dietary risk factors in mice, but more importantly humans.

“The study found a low glycaemic index diet, achieved by giving the mouse less calories lowered insulin and glucose (sugar levels) resulted in a smaller tumour, this did not happen with a ketogenic diet, which was expected to have a similar effect, but did not reduce glucose levels as might have been expected.  This was done to test what is known as the Walberg hypothesis, that some types of cancer cell grow better in a test tube with more glucose, however there is also the reverse Walberg hypothesis, where other types of cancer cell do better with ketones (broken down fats) as their source of fuel.  Overall this study suggested in mice that less calories reduced the size of the cancer.  This was partly looked at by considering humans that survived pancreatic cancer, this suggested a prudent diet may be linked to better survival.  But this was only an association with respect to their human data and not in any way causal.  The authors do point out applying this type of diet to human health is difficult as it can be hard to follow, and with a number of people with pancreatic as well as other cancers being malnourished it would be potentially harmful to restrict their calorie intake in any way, and they may actually need more calories to help them to get through the treatment and avoid the risk of malnutrition.

“Overall, this is an interesting study, looking at the mechanisms of tumour growth, but it only looked at two types of cancer cell and not actually how the cancer develops within an organ or tissue.  Also as it is largely based on a mouse experiments it is difficult to apply the findings to humans.  Although a review of cases of survivors of pancreatic cancer were looked at, the risk of a low glycaemic and calorie diet in people with cancer in terms of wasting and malnutrition possibly outweighs any benefits.”

‘Low glycaemic diets alter lipid metabolism to influence tumour growth’ by Evan C. Lien et al. was published in Nature at 16:00 UK time on Wednesday 20 October 2021.

DOI: 10.1038/s41586-021-04049-2

Declared interests

Dr George Poulogiannis: “No conflicts of interest.”

Prof Paul Pharoah: “I have no conflicts of interest to declare.”

Prof Gunter Kuhnle: “I have no interest to declare.”

Dr Duane Mellor: “No conflicts of interest to declare.”