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Obesity

Weight gain and cancer

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Weight gain leading to obesity can be a cause of cancer and a consequence of cancer treatments so this chapter addresses both these issues. A recent study reported that over 60% patients with early cancer who had undergone cancer treatments gain a significant amount of weight.

Across the World, obesity has tripled in the last thirty years. In 2018, in the UK, over a quarter of the population were obese (Body mass index of 30 kg/m²) and over 60% were overweight (BMI 25-30 kg/m²). A report from the World Health Organisation (WHO) estimates that by 2030, the percentage obesity rate in the UK would be 40% and in Ireland and Wales, over 50%. The USA, Greece, UK and Australia have the highest obesity figures. Japan, Norway, Korea and Switzerland have the lowest obesity figures. Being curvy is regarded as attractive by many individuals and a sign of prosperity in many cultures. However, the reality is, as the table below summarises, obesity causes many day-to-day problems and is linked to numerous medical conditions. What’s more, the UK’s National Institute of Clinical Excellence (NICE) estimated that obesity currently costs the UK £5.1 billion in lost production and medical management.  More worryingly they project by 2050 this would rise to £50 billion/year unless this epidemic was addressed by government and society.

In terms of cancer, being obese more than doubles the lifetime risk of hormone-related cancers such as breast and uterus but also over 20 other non-hormone related cancers particularly bowel, kidney and oesophagus. Overweight women also have an increased risk of breast cancer irrespective of their daily saturated fat intake. Obese men are 33% more likely to die of cancer compared to those of a normal weight and obese women have a staggering 55% increased risk of dying from cancer compared to those of a normal weight. Associations of fat distribution in the body, and outcomes after cancer treatments, have been substantially observed for bowel cancer but also for breast and prostate cancer, with the improvement in survival being a result of decreased cancer deaths as well as reduced deaths from all causes.

What are the causes of weight gain after cancer?

Obesity doesn't happen overnight but develops gradually over time, as a result of environmental, genetic, lifestyle and dietary choices. The fundamental  cause is the consumption of calories in excess of the body’s needs for metabolism and level of physical activity. An average physically active man needs about 2,500 calories a day to maintain a healthy weight, and an average physically active woman needs about 2,000 calories a day. This amount can be easy to reach especially with types of calorie-rich food. For example, eating a large takeaway hamburger, fries and a milkshake can total 1,500 calories – and that's just one meal. After cancer, there may be tendency to snack between meals or comfort eat. Someone people are also told not to worry about weight gain by well-meaning but doctors and nurses but this is not good advice as people who had previously controlled their weight would very rapidly pack on extra pounds, which would then be very difficult to lose.

In western societies, numerous surveys have revealed that the vast majority aren't physically active enough, so most of the calories people consume end up being stored in the body as fat. The Department of Health recommends that adults do at least two-and-a-half hours of moderate-intensity aerobic activity, such as cycling or fast walking, every week. This doesn’t need to be done all in one go, but can be broken down into smaller periods. For example, you could exercise for 30 minutes a day for five days a week or even 10 minute bouts spread through the day. The trouble is, if you're obese and trying to lose weight, you have to eat < 2500 calories a day and exercise > 2.5 hours / weeks to start burning up stored up energy stores.  What’s more, this has to be sustained for many months and even years to have any long-term benefit. These factors are still an issue after cancer but are compounded by several issues with add further to burden for the patient who is contemplating an exercise programme:

Disability is common after cancer either sustained from the disease itself, or the treatments. Some of disabilities can be overcome with retraining and support such as exercising with a stoma. The peripheral neuropathy which can occur after some chemotherapy interfering with the ability to walk or jog.

Fatigue is now one of the most prominent and distressing side effects after most treatments. Especially if associated with a low mood, prolonged fatigue can have a considerable demotivating influence on the decision to exercise.

Chemotherapy tends to cause some mild nausea, which many patients report gets worse on an empty stomach, resulting in regular snacking. With modern anti-sickness medications, unlike in the past, nausea is seldom enough to stop people eating, apart from the first few days. Many oncology units and information materials, however, still encourage patients to eat more as a throw-back to days when vomiting and weight loss was ‘normal’. 

Arthritis affects over 55% of men and women on hormone therapies. An increase in a level of join stiffness is often at a level which limits their ability to exercise. In fact, a study from Bedford presented at the international cancer conference reported that arthritis was the barrier to exercise for men with prostate cancer or women with breast cancer who had started hormones.

Steroids are usually given with chemotherapy drugs. They encourage a strong appetite and tend to cause increased fat deposition. They also cause wakefulness at night and when they are stopped they cause withdrawal fatigue.

Underactivity of the  thyroid can be caused by radiotherapy to the neck can lead to damage to the thyroid. Some chemotherapy regimens can also damage the thyroid. If you have radiotherapy to the neck you should receive regular thyroid function tests and any deficiencies corrected with thyroxine. After chemotherapy, if the fatigue is marked and associated with weight gain, feeling cold and dry skin then you should ask for a thyroid function test from your hospital team or GP.

Hormone therapies such as tamoxifen, aromatase inhibitors and the testosterone-reducing drugs including zoladex can also cause weight gain. These drugs are now often recommended for 10 years after initial surgery.

Obesity affects cancer outcomes

The National Surgical Adjuvant Breast and Bowel Project (NSABP) evaluated 4,310 patients who had successfully been treated for breast and bowel cancer and showed that obese patients with colon cancer had worse overall survival than normal weight patients, due to both greater recurrence risk and non-cancer deaths. On a cautionary note however, patients who were very underweight (Body Mass Index <19 kg/m²) also had a worse outcome. Another study from Cedars-Sinai Medical centre in Los Angeles, evaluated 1069 men treated with prostate cancer who had either received surgery or radiotherapy. The cure rate for either was the same but overall obese men had a significantly higher rate of early disease recurrence.

A study in 2009 evaluated the lifestyle habits of 365 women with Estrogen Receptor positive (ER+ve). Women who were obese or consumed more than 7 alcoholic beverages a week, or smoked had double the risk of developing a new breast cancer on the opposite side. A further analysis of 5204 registered nurses within the Nurses’ Health Study reported that high BMI at diagnosis correlated with an overall worse survival but a correlation with breast cancer relapse was only seen in non-smokers. Of more clinical relevance was that weight gain of more than 0.5kg/m² at 1 year correlated both with overall survival and breast cancer specific survival. This effect was strongest in women who gained the most weight (>2kg/m²).

Why is obesity harmful?

The underlying biochemical and physical mechanisms of the harm linked to obesity are multifactorial and influenced by other lifestyle and genetic factors. The most dangerous situation is called sarcopenic obesity which is the combination of muscle wasting with obesity. This can affect people at any stage in the cancer journey but particularly those in the later more advanced stages. The European consensus on the definition of sarcopenic obesity is a BMI greater than 30 kg/m² combined with low skeletal muscle mass, low grip strength and slow gait speed. People with sarcopenic obesity have particularly high levels of chronic inflammation and reduced immunity. They have higher risks of cancer, poorer surgical outcomes and more complications such as infection and blood clots. They also have poor tolerance to chemotherapy leading to dose delays and dose reduction. Ultimately, this will lead to worsening of both short and long term cancer outcomes. Scientist are still discovering ways obesity and sarcopenic obesity influences the expression of genes which promote cancer but the most likely mechanism can be summarised into the following direct and indirect categories:

Direct mechanisms:

• Oestrogen higher / Progesterone lower

• Insulin resistance / Insulin-like growth factor receptor (IGF-1)

• Higher leptin / lower adiponectin

•  Chronic inflammation / poor immunity

Indirect mechanisms:

• Difficultly exercising e.g. breathlessness, arthritis

• Low mood

• Abnormal gut microflora

• Lower Vitamin D

Oestrogen and progesterone levels:
Adiposity influences the production and availability of the body’s sex hormones including oestrogen, androgens and progesterone. In post-menopausal women oestrogen is made in the peripheral body fat whilst in pre-menopausal women it is produced primarily in the ovaries. So irrespective of their daily saturated fat intake, overweight post-menopausal women have higher levels of the female sex hormone oestrogen. This may explain a higher risk of breast and endometrial cancer for overweight post-menopausal women but not for pre-menopausal women. Compared to women with pre-menopausal ‘normal’ weight, obese women in particular have reduced serum progesterone. There is a significant body of evidence demonstrating that progesterone plays a protective role i.e. preventing or slowing cancer progression, particularly in the ovaries. Progesterone increases in pregnancy, which may be why women who have had children have a lower incidence of breast and ovarian cancer. In post-menopausal women who are not overweight the evidence is less clear. The risk of breast cancer, in one large study from Sweden, was actually higher in women taking HRT containing progesterone and oestrogen than those containing oestrogen alone. On the other hand, another study of post-menopausal women with breast cancer from Boston, USA, no such correlation was found with progesterone. It may well be therefore, that the protective effect of progesterone is greater in pre-menopausal women.  

Insulin and Insulin-like growth factor receptor (IGF-1);
The increased risk of cancer, or its rate of progression, is not just hormone related. We know this because overweight women have a worse prognosis after cancer, regardless of whether their cancers were sensitive to oestrogen (ER positive) or not (ER negative). One mechanism for a non-hormone-related increased risk of cancer progression is via IGF-1, which is higher in overweight people.  Higher levels have also been associated with breast, ovary and prostate cancer. This protein, also higher in sedentary individuals, has been shown to promote cancer cell division (encouraging proliferation), to inhibit apoptosis (cells not dying when they should) and encouraging cancer cells to spread. Fortunately, this cancer-promoting protein level drops in the blood stream if individuals lose weight or exercise.

Leptin and adiponectin:
Leptin is a multifunctional neuro-endocrine hormone generated primarily from fat cells so overweight, particularly post-menopausal women, have higher  levels. Leptin is known to promote breast cancer directly and independently, as well as through involvement with the oestrogen and insulin signalling pathways, via enhanced angiogenesis (new blood vessel formation) and cell proliferation, which explains the links between higher levels of leptin, adiposity and hormone-related cancers such as breast and uterus.

Conversely, serum concentration of another adipokine cytokine, called adiponectin, is lower in people who are overweight. It is also lower in patients who have developed breast and prostate cancer because, unlike leptin which is pro-inflammatory, it has significant anti-inflammatory properties. Furthermore, adiponectin also suppresses inactivation of nitric oxide which dose-dependently reduces platelet aggregation. Tumour cell-induced platelet aggregation correlates with metastatic potential (spread of cancer cells) by ‘cloaking’ tumour cells with adherent platelets, protecting them from NK-cell mediated killing.  A number of studies have shown that weight reduction resulted in lowering platelet aggregation, lower leptin levels and increasing adipokine levels – clearly a good thing.  

Chronic inflammation:
As mentioned in part one, there are multiple factors for activation of markers of inflammation among individuals who are overweight.  Inflammatory markers such as C-reactive protein, TNF and IL-6 are significantly higher in obese people. One study involving biopsies of rectal mucosa showed that that overweight individuals had also increased mucosal concentrations which reduced following lifestyle interventions. There are some theories for these associations. Excessive intake of calories over the body’s need leads to metabolic syndrome which evokes an inflammatory stress reaction. Fat cell hypertrophy, facilitates cell rupture, which evokes the accumulation of macrophages in visceral fat (The fat overspill theory). Inability of adipose tissue development to engulf incoming fat leads to deposition in other organs, mainly in the liver, with further consequences on insulin resistance. The oxidative stress which accompanies over feeding, particularly when there is excessive ingestion of fat and/or other macronutrients without concomitant ingestion of polyphenol rich foods, may contribute to the inflammation attributed to obesity. Obesity also leads to an increased risk of chronic infections such as those of the urinary tract or candida in the skin folds. - lifestyle tips to reduce inflammation

Exercise:
It is physically more difficult to exercise if overweight or obese. The lower mood demotivates even the best intentions for starting an exercise programme. Low self-esteem and body image issues may be a barrier to joining a gym or exercise class. A local trial, presented in Adelaide Australia in 2017,  asked over 800 participants what symptoms they were troubled with after cancer treatments. Over 55% of participants said arthritis was a problem which often stopped them exercising satisfactorily. - tips to increase exercise levels

Gut microflora:
Overweight individuals tend to have a sub-optimal microbiota which can affect immune regulation.  Research is underway to establish whether it’s the abnormal gut flora which causes obesity (the leaky gut theory) or the obesity which causes the altered microbiota. In the meantime, anecdotal cases report the finding of weight loss with a good probiotic supplement.

Vitamin D levels:
A number of studies have reported a link between obesity and vitamin D deficiency but the most notable was the Genetic Investigation of Anthropometric Traits (GIANT) study which evaluated 123,864 people.  Researchers found that there was a direct correlation between higher BMI and lower Vitamin D blood levels, independent of any genetic factors. The authors hypothesised that as vitamin D is stored in fatty tissue, obese people store more vitamin D in their fat, and have less vitamin D circulating in their blood. In addition, obese people are likely to have suboptimal sun exposure as they are less likely to exercise in the sunshine and when they do venture outside they are more likely to cover up due to body image issues. The mechanism by which vitamin D3 influences cancer is thought to be due to calcitriol’s effect on cellular proliferation, differentiation and apoptosis (natural cell death). The vitamin D receptor is highly expressed in epithelial cells known to be at risk of carcinogenesis, such as the breast, skin and prostate. Higher vitamin D levels are associated with lower colorectal, breast and prostate cancer mortality. Sunlight exposure, independent of vitamin D levels, has been linked to a lower incidence of prostate and bowel cancer. - Tips to increase vitamin D

Low mood:
As well as being distressing, low mood and depression have been linked to a reduce survival following cancer treatments. Of note, a large prospective cohort study from California reported that 4.6% of 41,000 men who were clinically depressed after prostate cancer diagnosis, had a 25% reduction in disease specific survival compared to non-depressed men. Low mood contributes to an unhealthy oxidative and inflammatory status and reduces the incentive change to more healthy behaviours such as eating less and being more active). There may also be some direct biochemical effect linked with leptin as demonstrated in a laboratory experiment. Mice with cancer where spilt into two groups. One group had a normal cage the other had a five-star version with more room, more toys and gadgets –  everything a happy mouse could dream. The tumours in the happy mice group grew significantly slower and these mice also had significantly lower leptin levels. Several studies have linked obesity with low self-esteem, lower mood status and subclinical depression. - Tips to improve mood

Tips to lose weight

It is hard enough to lose weight at the best of times, but it is even harder after cancer, both physically and emotionally. Although it is rarely talked about at the start of medical treatments, awareness of the risk of weight gain and its causes is imperative because weight gain can be avoided. Several studies of interventional strategies confirm prevention of weight gain after starting hormones, for example, is readily achievable in most cases but few oncology units in the UK offer organised weight gain prevention programmes. Once weight has been assimilated it’s much harder to lose. Fat is a very efficient energy source so weight reduction programmes would have to continue for several months in order to make any difference to the body store. Unfortunately, this means there will be times when you will feel hungry. Faddy diets may seem initially successful but they seldom lead to a sustained long-term change of behaviour, which is what is required; there really is no easy short cut! Once the weight has been lost, the energy intake then has to match the energy requirement, so even then you cannot relax and start overeating again. Many people develop strategies and tricks which suit their individual needs and situations but here are areas to concentrate on with an explanation of why and how they may work best:

Exercise:
In terms of weight loss (rather than prevention) it is often quoted that exercise has no impact but that is simply not quite rue. Several interventional studies show that interventional exercise programmes have a significant impact but it’s fairly small and requires a lot of effort. For example, the ENERGY Study involving 690 women with breast cancer from, reported that those randomised to a group-based exercise intervention had a 6% reduction in weight as opposed to a 1.5% reduction for those women randomised to standard care. Likewise, the American Society of Sports Medicine meta-analysis of many interventions concluded that weight reduction, resulted in a10% reduction in weight if >150-250 min moderate exercise / week was maintained for over 6 months but if participants did <150 mins / week there was no change in weight. A combination of resistance and endurance exercises seem to be most effective but the important thing is that it is sustained and combined with calories reduction and even fasting. Ideally, try to do some of the exercise first thing in the morning, before breakfast, even if only for 20 mins. This means the stomach is empty so the body has to use energy from stores in the liver and fat tissues. It also extends the period of overnight fasting which, as highlighted in the section below, also significantly helps weight loss and prevents diabetes.

Extra benefits of exercise for overweight people: Regular physical activity is particularly beneficial for overweight or obese individuals even though it is much harder to sustain regular levels. Even before weight reduction, oestrogen and leptin levels decrease and adiponectin levels increase. Exercise also mitigates many of the adverse risks of obesity particular thrombo-embolism, indigestions and low mood. Also the positive biochemical changes which occur when exercising, counter-balance the negative factors caused by obesity, particularly raised levels of IGF, increased insulin resistance and also blood markers of chronic inflammation.

Reduce high calorific foods:
It sounds obvious but being overweight means you have eaten more than the body’s energy requirements on most days of the week. Caloric requirements change on a daily basis so on days in which you are physically active you can eat more but on sedentary days it’s vital to eat much less. Fast food outlets generally offer foods high in unhealthy fat and sugar yet people often regard then as a snack between meals. Sometimes, it is not also clear which foods are high in calories but the usual culprits include cakes, biscuits, muffins, pasties, pies, fatty chips, crisps, pakoras, samosas and bhajis. Alcohol contains a lot of calories, and also stimulates the appetite. We have all had the urge to go for a curry on the way back from the pub or raid the fridge after getting home. People who drink heavily are often overweight unless they smoke.  Dinning out may be a danger zone as often you are offered and tempted by three courses. 

Reduce processed sugar:
Quenching your thirst with sugary drinks, including soft fizzy drinks and processed fruit juices, is not a good idea. They have a lot of calories, but they not satiating (don’t fill you up) and their high glycaemic index means there will be peaks and troughs in your blood sugar levels making you hungry again an hour later. This usually result in needing a snack and ultimately a high total caloric intake. Many low calorie ready meals have removed the fat and added more processed sugars which may induce you to go on snacking - read more about the dangers of processed sugar.

Eat a high proportion of whole foods:
Breaking down foods reduces the need for chewing and foods are absorbed quicker. Chewing send signals to the brain that you are eating a substantial meal so more likely to fill you up compared to liquid meals. Wholes foods have more bulk and fibre making them slower to eat and more satiating without increasing the calorie content as because fibre is not absorbed into the body. A good example, is whole, wild rice which has the same amount of calories as plain white rice but most people would eat much less as because it also includes the germ and husk. Both of these add to the bulk the taste and overall nutritional value of the rice. Likewise, whole grain bread is considerably less likely to contribute to weight gain than highly processed while bread and also contains vitamins, and soluble fibre which acts as prebiotics, supporting healthy gut bacteria. Both processed rice and bread (starchy foods) have high glycaemic indices which means they are best avoided in order to ensure blood insulin and blood sugar levels remain level and your anti-inflammatory state is maintained.

Enhance the gut flora:
As mentioned above, overweight and certainly obese individuals tend to have a suboptimal microbiota. It has not been established whether it’s the abnormal gut flora which causes obesity or if the obesity triggers the altered bacterial growth. One theory is the abnormal bacteria contributes to a state of chronic inflammation, fatigue, and low mood. Thus stimulating the body to reabsorb more fats and discourages exercise which leads to obesity. Until that is proved, taking some of the advice for gut health, including a good probiotic supplement, may be beneficial.  Including in your diet fermented foods such as live unsweetened yogurt, miso, kimchi, kombucha, kefir or sauerkraut will all help to induce good gut health.

Stop snacking:
Contrary to popular opinion, humans will not become extinct if we do not constantly eat. Hunger has become an unacceptable sensation in Western societies but it should be embraced as because this is when the weight starts falling off. The fall in blood sugar triggers the break-down of glycogen in the liver and fats to fatty acids and glycerol for energy. Instead of grazing throughout the day, its best to have a meal then allow it to digest completely and pass through the gut. This also allows the digestive mechanisms and stomach acids to rest before the next meal. If you do feel distressing hungry pangs then drinking a glass of water, going for a brief walk to take your mind off food or if this fails having a small handful of unsalted tree nuts will help.

Fasting to lose weight: 
One interesting laboratory experiment highlighted the benefits of fasting in which a healthy colony of mice was split into two groups and kept in a safe, comfortable, stimulating and warm environment. The only difference between them was that one group had as much food as they wanted at all time, and the other group had their food withdrawn for a few days every fortnight. The group that endured a modest degree of regular fasting maintained a normal weight and lived almost twice as long as the others. It is not clear how this relates to humans, but it is fair to say most of us would not tolerate missing a meal let alone going without food for more than a day. Maybe the fasting practices in some religions are based on a fundamental wish to improve the health of their followers, rather than a penance to demonstrate their faith. More information on energy restrictive diets such as the Atkins and Ketogenic diet

Several diets advocate intermittent fasting in humans but despite the popularity in the media they are not particularly practical or sustainable for most people. The 5:2 is the most widely broadcast. That’s five days of normal eating, with little thought to calorie control and a desert for pudding if that’s what you want. Then, on the other two days, calorie intake is reduced to 500 calories for women and 600 calories for men. Since you are only fasting for two days of your choice each week, and eating normally on the other five days, there is always something to look forward to on the near horizon.

The most sustainable way of fasting is to extending the gaps between meals and avoiding snacks is the most practical way of introducing gentle fasting on a daily basis. The best evidence of sensible effective fasting comes from a study published in the prestigious medical journal JAMA in 2016 which evaluated a large cohort of overweight women who completed their initial treatments. They discovered that initially overweight women who tended to early dinners or late breakfast leaving 13 hours between the meals (without intermediate snacking) lost significantly more weight but also had lower levels of glycated Hb (HbA1c - a marker of glucose control over time) and lower chronic inflammatory markers. What’s more, after 5 years there was a 36% lower risk of breast cancer recurrence in the overnight fasting women.

Tips to loose help you achieve a healthy weight - summary

• Avoid ‘faddy’ diets because keeping off the lost weight may be harder to achieve

• Go for a walk or do some exercise before breakfast

• Extend the interval between the evening meal and breakfast to 13 hour

• Don’t worry about feeling hungry and drink plenty of water (avoid sugary drinks)

• Distract yourself from thinking about food – get up and take a walk  

• Avoid processed food (unhealthy fat, sugar, high GI foods)

• Eat less of food cooked in fat and most vegetable oils e.g. deep-fried batter, chips, crisps.

• Avoid pastries and pies.

• Avoid biscuits and cakes. 

• Avoid muffins which have more fat than a bacon sandwich!

• Trim the excess fat off meat

• It is better to stew, boil or broil rather than grilling, roasting or frying

• Eat less meat and more oily fish 

• Eat a large ‘rainbow-of-colours’ which are fibre and polyphenol rich such as fresh salad with every meal

• Reduce alcohol intake (alcohol is liquid sugar)  

• Try not to eat 3 hours before bedtime and aim for around 8 hours of sleep

• Try not to snack between meals, especially sweet snacks

• Avoid food between breakfast and lunch or lunch to your evening meal

•   Increase exercise levels (see exercise section)  

• Eat mainly plants.  

• Eat real, minimally processed, food if possible (which is recognisable)

• Consider having no more than 2 meals a day with no snacking in between meals  

• Don’t eat in front of the TV or computer screen  

• Take a break and eat your meal with family or friends round a table.  

• Try to make your meals yourself from scratch – you know what’s in them!