Obesity has moved from a disease of the developed world to become a global issue. According to the World Health Organization (WHO), there are 1.9 billion overweight adults worldwide, 650 million of which are obese. Obesity increases our susceptibility to a variety of illnesses as the body becomes overworked and under-supported. These illnesses include heart disease, type 2 diabetes (T2DM) and musculoskeletal problems. Most recently, researchers are discovering the impact obesity has on cancer.
A notable clinical study published by the Journal of the National Cancer Institute (JNCI), confirmed the connection between obesity and cancer, with data demonstrating that with each five kilograms gained in weight, the risk of developing colon cancer increases by six percent.  However, it is important to note that studies which show statistical links between one condition and another are often flawed due to lack of proof for causality. In other words, a statistical association can be identified, but without a tested hypothesis to demonstrate a mechanism whereby the first leads to the second, the study is not really informative. Therefore, if we are to believe that obesity itself increases our risk of cancer, then we should propose how it might happen, and in order to do so, we need to understand how cancer develops in the first place.
Beginning at birth, our body produces, renews and replenishes cells which constitute it. As we age, our existing cells die, diminishing the need for creating more cells and increasing the need for replenishing dead cells. It is important to note that as new cells are created, each cell can develop a mutation in its DNA, which happens all the time. However, most often when cell mutations occur, our immune system kicks in and kills any harmful cells before they can grow. In fact, our immune system which is divided into two arms, the adaptive and the innate, and the Natural Killer (NK) cells of the innate immune system conduct constant immune surveillance, patrolling the body for harmful cells and killing them before they can grow. Sometimes, NK cells fail to identify and kill the mutated cells developing in the body, allowing the harmful cells to grow without control. These cells can develop into a tumor mass and lead to clinical cancer.
Going back to the link between obesity and cancer, we could form a simple hypothesis that people suffering from obesity simply have more cells constituting their body and thus have a higher statistical chance of developing a cancerous cell. Alas, this conclusion is too simplistic since people who are tall have more cells than people who are short, and yet there is no higher risk of cancer with respect to height. However, we know that when the immune system is compromised, the immune surveillance process is suppressed, putting us at greater risk of infection and cancer. Could the link between obesity and increased cancer risk be due to an immunosuppressive effect of obesity? What is the evidence?
Obesity: The Overworked Workforce
Obesity is a complex disease, but among its features is the creation of a state of chronic inflammation. While acute inflammation is a beneficial immune response that signals the immune system to activate and fight infection, chronic inflammation is not part of the body’s healing process. In fact, chronic inflammation creates a state of constant, low grade immune activation which ultimately leads to immune dysfunction due to exhaustion. Think of the chronically stimulated immune system as the “boy who cried wolf” – the immune cells are simply too exhausted to respond to a real threat when it occurs. Similarly, obese patients have exhausted the resources of their immune system, including NK cell function, leaving them vulnerable to developing diseases such as cancer.
Some evidence that chronic inflammation leads to immune suppression is that patients who are obese are known to be at greater risk of dying during an outbreak of influenza, due to their relatively poor immunity. In an experimental study, researchers showed that low NK cell function seen in obese rats improved after they were put on a regimented meal plan, whereas rats that were allowed to eat without restrictions had reduced NK cell function. In searching for causation of this effect, the scientists discovered that high concentrations of leptin, a hormone that affects hunger by decreasing our appetite, reduces NK cell function. The more you eat, the more leptin is produced in order to make you feel satiated and stop you from eating further.
However, in patients with obesity, although leptin continues to be released in response to eating, the hormone imbalances of the patient render them insensitive to its effect. In other words, they eat but do not feel satiated, leading to a build-up of leptin that suppresses their NK cell function and impairs their immune surveillance. On the flip side, this research demonstrated that if patients with obesity were to go on a regimented meal plan, they could decrease leptin levels and increase NK cell function, to protect them from developing cancer and infection.
Fasting and Cancer
Beyond reducing the presence of leptin in the body to increase NK cell activity, fasting can give the body time to repair itself. A study of intermittent fasting demonstrated that periods of energy restriction can help the body’s natural remodeling process which removes damaged cells; presumably because damaged cells require more energy to survive than healthy cells. Much ado has been made of the Mediterranean Diet and its relatively low fat content. However, one aspect of Mediterranean living is the regimented meal plan of breakfast, lunch and dinner with virtually no “snacking”. Perhaps it is the periods of minor hunger during each day which enhance endogenous cell repair mechanisms.
There have been many diets which restrict eating for periods of time that have demonstrated positive effects on the immune system, among them, the 5:2 diet has shown many merits. The diet calls for five days of normal eating interspersed with two days of limited calorie intake, ultimately leading to decreased leptin levels, increasing NK cell function and boosting immune surveillance. A laboratory study of the effect of a 5:2 type diet showed that it reduced Insulin Growth Factor-1 (IGF-1) levels in the blood, which led to enhanced bone marrow production of the white blood cells (including NK cells) that fight infection and cancer.  Whilst doctors have shown that good NK cell function is linked to a lower risk of cancer, no study has been reported showing a direct link between intermittent fasting and the ability of NK cells to kill cancer cells. So be sure to watch this space closely.
At this point in time, there have been numerous areas of cancer prevention that have been addressed, recommended and validated. We can find many studies that support the premise that if obesity increases the risk of cancer development, diet might serve as a preventative measure to reduce our chances of disease. While scientists are still studying the effect of intermittent fasting on our immune responses, its impact on NK cell activity is encouraging. More generally, now that we understand that our bodies need time to self-renew, and periods of energy intake restriction aid that process, the premise of dieting is the right one.
We can help our body protect us from cancer, and it all starts with how often we grab a bite.
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Last Editorial Review: February 20, 2019
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